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The integrity of the actively transcribed genome against helix‐distorting DNA lesions relies on a multilayered cellular response that enhances Transcription‐Coupled Nucleotide Excision Repair (TC‐NER). When defective, TC‐NER is causatively associated with Cockayne‐Syndrome (CS), a rare severe human progeroid disorder. Although the presence of unresolved transcription‐blocking lesions is considered a driver of the aging process, the molecular features of the transcription‐driven response to genotoxic stress in CS‐B cells remain largely unknown. Here, an in‐depth view of the transcriptional and associated chromatin dynamics that occur in CS‐B cells illuminates the role of CSB therein. By employing high‐throughput genome‐wide approaches, we observed that absence of a functional CSB protein results in a delay in transcription progression, more positioned +1 nucleosomes, and less dynamic chromatin structure, compared to normal cells. We found that early after exposure to UV, CS‐B cells released RNA polymerase II (RNAPII) from promoter‐proximal pause sites into elongation. However, the magnitude of this response and the progression of RNAPII were reduced compared to normal counterparts. Notably, we detected increased post‐UV retainment of unprocessed nascent RNA transcripts and chromatin‐associated elongating RNAPII molecules. Contrary to the prevailing models, we found that transcription initiation is operational in CS‐B fibroblasts early after UV and that chromatin accessibility showed a marginal increase. Our study provides robust evidence for the role of CSB in shaping the transcription and chromatin landscape both in homeostasis and in response to genotoxic insults, which is independent of its known role in TC‐NER, and which may underlie major aspects of the CS phenotype. [ABSTRACT FROM AUTHOR]

We present results of the Near-Earth objects Lunar Impacts and Optical TrAnsients (NELIOTA) campaign for lunar impact flashes observed with the 1.2 m Kryoneri telescope. From August 2019 to August 2023, we report 113 validated and 70 suspected flashes. For the validated flashes, we calculate the physical parameters (masses, radii) of the corresponding projectiles, the temperatures developed during the impacts, and the expected crater sizes. For the multiframe flashes, we present light curves and thermal evolution plots. Using the whole sample of NELIOTA that encompasses 192 validated flashes in total from 2017, the statistics of the physical parameters of the meteoroids, the peak temperatures of the impacts, and the expected crater sizes has been updated. Using this large sample, empirical relations correlating the luminous energies per photometric band were derived and used to roughly estimate the parameters of 92 suspected flashes of the NELIOTA archive. For a typical value of the luminous efficiency, we found that the majority (>75%) of the impacting meteoroids have masses between 1 and 200 g, radii between 0.5 and 3 cm and produced craters up to 3.5 m. 85% of the peak temperatures of the impacts range between 2000 and 4500 K. Statistics regarding the magnitude decline and the cooling rates of the multiframe flashes are also presented. The recalculation of the appearance frequency of meteoroids (lying within the aforementioned ranges of physical parameters) on the Moon yields that the total lunar surface is bombarded with 7.4 sporadic meteoroids per hour and up to 12.6 meteoroids per hour when the Earth-Moon system passes through a strong meteoroid stream. By extrapolating these rates on Earth, the respective rates for various distances from its surface are calculated and used to estimate the probability of an impact of a meteoroid with a hypothetical infrastructure on the Moon, or with a satellite orbiting Earth for various impact surfaces and duration times of the missions. [ABSTRACT FROM AUTHOR]

How can a post-Christian, secular audience understand the devoutly Christian, sacred music of Johann Sebastian Bach's St. Matthew Passion ? This article addresses this question with reference to the hermeneutics of Hans-Georg Gadamer and Hans Blumenberg. Their confrontation reveals broad implications for the theory of humanistic interpretation at large. Gadamer celebrates Bach as a 'classical' touchstone of Western culture whom we may productively interpret through a 'fusion of horizons'. Blumenberg, by contrast, cautions that our relation to Bach's Passion is fractured because it is impossible to 'pace off the horizon'. Blumenberg emphasizes the first-person experience of the diminution of historical meaning, a position this article calls 'shattered hermeneutics'. The article concludes that Blumenberg's interpretation of Bach and his critique of Gadamer thereby usefully and plausibly deepen and radicalize hermeneutics. [ABSTRACT FROM AUTHOR]

The article focuses on the critique of contemporary political philosophy's emphasis on activity. It highlighting the coercive control and optimization of human behavior in various aspects like social media usage, productivity culture & responses to global issues like climate change; how philosophers Giorgio Agamben and Michael Oakeshott propose a withdrawal from this dominant concept of activity; and advocating for a mode of spiritual peace and freedom that fosters open.

Purpose: Vigorous physical activity may acutely trigger the onset of an acute coronary syndrome especially in sedentary persons with established cardiovascular risk factors such as arterial hypertension. The rupture of an inflamed coronary plaque and the activation of the coagulation cascade are the main underlying mechanisms. The present study aimed to determine the effect of acute exercise on the inflammatory and thrombotic response in patients with arterial hypertension as compared to normotensive peers.After excluding patients with any inflammatory or/and coronary artery disease, a total of 60 non-treated hypertensive patients and 65 normotensive individuals underwent a maximal treadmill exercise testing. Βlood samples were drawn at rest and immediately after peak exercise. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cell (WBC), interleukin-6 (IL-6), and total fibrinogen (TF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity, were measured.All biomarkers increased with exercise, except PAI-1, which decreased (P < 0.05 for the change between resting and peak exercise for all biomarkers). Αfter adjusting for relevant confounders (duration of exercise, metabolic equivalents, systolic BP, and rate-pressure product achieved at peak exercise), the normotensive group had less marked (P < 0.05) exercise-induced changes than the hypertensive group in hsCRP (7.7 vs. 8.6%), SAA (5.6 vs. 11.9%), WBC (45.0 vs. 51.7%), and PAI-1 (−17.3 vs. -20.1%) and a similar (P = NS) change in IL-6 (23.8 vs. 23.0%) and TF (8.5 vs. 8.5%).In conclusion, the acute exercise-induced inflammatory and thrombotic response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. Possible clinical implications of this finding merit further examination.Methods: Vigorous physical activity may acutely trigger the onset of an acute coronary syndrome especially in sedentary persons with established cardiovascular risk factors such as arterial hypertension. The rupture of an inflamed coronary plaque and the activation of the coagulation cascade are the main underlying mechanisms. The present study aimed to determine the effect of acute exercise on the inflammatory and thrombotic response in patients with arterial hypertension as compared to normotensive peers.After excluding patients with any inflammatory or/and coronary artery disease, a total of 60 non-treated hypertensive patients and 65 normotensive individuals underwent a maximal treadmill exercise testing. Βlood samples were drawn at rest and immediately after peak exercise. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cell (WBC), interleukin-6 (IL-6), and total fibrinogen (TF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity, were measured.All biomarkers increased with exercise, except PAI-1, which decreased (P < 0.05 for the change between resting and peak exercise for all biomarkers). Αfter adjusting for relevant confounders (duration of exercise, metabolic equivalents, systolic BP, and rate-pressure product achieved at peak exercise), the normotensive group had less marked (P < 0.05) exercise-induced changes than the hypertensive group in hsCRP (7.7 vs. 8.6%), SAA (5.6 vs. 11.9%), WBC (45.0 vs. 51.7%), and PAI-1 (−17.3 vs. -20.1%) and a similar (P = NS) change in IL-6 (23.8 vs. 23.0%) and TF (8.5 vs. 8.5%).In conclusion, the acute exercise-induced inflammatory and thrombotic response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. Possible clinical implications of this finding merit further examination.Results: Vigorous physical activity may acutely trigger the onset of an acute coronary syndrome especially in sedentary persons with established cardiovascular risk factors such as arterial hypertension. The rupture of an inflamed coronary plaque and the activation of the coagulation cascade are the main underlying mechanisms. The present study aimed to determine the effect of acute exercise on the inflammatory and thrombotic response in patients with arterial hypertension as compared to normotensive peers.After excluding patients with any inflammatory or/and coronary artery disease, a total of 60 non-treated hypertensive patients and 65 normotensive individuals underwent a maximal treadmill exercise testing. Βlood samples were drawn at rest and immediately after peak exercise. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cell (WBC), interleukin-6 (IL-6), and total fibrinogen (TF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity, were measured.All biomarkers increased with exercise, except PAI-1, which decreased (P < 0.05 for the change between resting and peak exercise for all biomarkers). Αfter adjusting for relevant confounders (duration of exercise, metabolic equivalents, systolic BP, and rate-pressure product achieved at peak exercise), the normotensive group had less marked (P < 0.05) exercise-induced changes than the hypertensive group in hsCRP (7.7 vs. 8.6%), SAA (5.6 vs. 11.9%), WBC (45.0 vs. 51.7%), and PAI-1 (−17.3 vs. -20.1%) and a similar (P = NS) change in IL-6 (23.8 vs. 23.0%) and TF (8.5 vs. 8.5%).In conclusion, the acute exercise-induced inflammatory and thrombotic response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. Possible clinical implications of this finding merit further examination.Conclusion: Vigorous physical activity may acutely trigger the onset of an acute coronary syndrome especially in sedentary persons with established cardiovascular risk factors such as arterial hypertension. The rupture of an inflamed coronary plaque and the activation of the coagulation cascade are the main underlying mechanisms. The present study aimed to determine the effect of acute exercise on the inflammatory and thrombotic response in patients with arterial hypertension as compared to normotensive peers.After excluding patients with any inflammatory or/and coronary artery disease, a total of 60 non-treated hypertensive patients and 65 normotensive individuals underwent a maximal treadmill exercise testing. Βlood samples were drawn at rest and immediately after peak exercise. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cell (WBC), interleukin-6 (IL-6), and total fibrinogen (TF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity, were measured.All biomarkers increased with exercise, except PAI-1, which decreased (P < 0.05 for the change between resting and peak exercise for all biomarkers). Αfter adjusting for relevant confounders (duration of exercise, metabolic equivalents, systolic BP, and rate-pressure product achieved at peak exercise), the normotensive group had less marked (P < 0.05) exercise-induced changes than the hypertensive group in hsCRP (7.7 vs. 8.6%), SAA (5.6 vs. 11.9%), WBC (45.0 vs. 51.7%), and PAI-1 (−17.3 vs. -20.1%) and a similar (P = NS) change in IL-6 (23.8 vs. 23.0%) and TF (8.5 vs. 8.5%).In conclusion, the acute exercise-induced inflammatory and thrombotic response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. Possible clinical implications of this finding merit further examination. [ABSTRACT FROM AUTHOR]

We examine the problem of uncovering communities in complex real-world networks whose elements and their respective associations manifest as streams of data. Community detection is applied in emerging computational environments and concerns critical applications in diverse areas including social computing, web analysis, IoT and biology. Despite the already expended related research efforts, the task of revealing the community structure of massive and rapidly-evolving networks remains very challenging. More specifically, there is an emerging need for online approaches that ingest graph data as a stream. In this paper, we propose a streaming-graph community-detection algorithm that expands seed-sets of nodes to communities. We consider an online setting and process a stream of edges while aiming to form communities on-the-fly using partial knowledge of the graph structure. We use space-efficient structures to maintain very limited information regarding the nodes of the graph and the sought communities, so as to effectively process large scale networks. In addition to our novel streaming approach, we develop a technique that increases the accuracy of our algorithm considerably and additionally propose a new clustering algorithm that allows for automatically deriving the size of the communities we seek to detect. Using ground-truth communities for a wide range of large real-word and synthetic networks, our experimental evaluation shows that our approach does achieve accuracy comparable, and oftentimes better, to the state-of-the-art non-streaming community detection algorithms. More importantly, we attain significant improvements in both execution time and memory requirements. [ABSTRACT FROM AUTHOR]

We investigate how an inquiry-oriented, dynamic, open-source calculus textbook shaped one college instructor's planning. We rely on Dietiker et al.'s [(2018). Research commentary: Curricular noticing: A framework to describe teachers' interactions with curriculum materials. Journal for Research in Mathematics Education, 49(5), 521–532. ] curriculum noticing framework to situate the instructor's actions during lesson planning using data from surveys, logs and interviews. The instructor's planning practices are characterized by intense use of the textbook, including creating additional curricular material related to its content. Our observations suggest that the textbook supported and influenced the instructor in implementing his inquiry-oriented visions and goals while planning his lessons. We conclude by suggesting further investigation of how textbooks shape undergraduate mathematics education and the textbooks' role in shaping undergraduate mathematics planning practices. [ABSTRACT FROM AUTHOR]

This study opts to investigate the thus far ill-defined intra-hemispheric topography, morphology, and connectivity of the extrapyramidal fibers that originate from the frontoparietal cortex and project to the tegmental area and to explore structural correlations to the pyramidal pathway. To this end, twenty normal adult, formalin-fixed cerebral hemispheres were studied through the fiber micro-dissection technique. Stepwise and in-tandem medial to lateral and lateral to medial dissections were carried out in all specimens. The cortical termination of the fibers under investigation was carefully defined, and their entry zone at the tegmental area was meticulously recorded. We consistently identified the corticotegmental tract (CTT) as a distinct fiber pathway lying in the white matter of the genu and posterior limb of the internal capsule and travelling medial to the corticospinal tract (CST) and lateral to the thalamic radiations. The CTT exhibits a fan-shaped configuration and can be classified into three discrete segments: a rostral one receiving fibers from BA8 (pre-SMA, frontal eye fields, dorsal prefrontal cortex), a middle one arising from areas BA4 and BA6 (primary motor cortex and premotor cortex), and a caudal one stemming from areas BA1/2/3 (somatosensory cortex). The anatomical location, configuration, trajectory, and axonal connectivity of this tract are attuned to the descending component of the extrapyramidal system, and therefore, it is believed to be implicated in locomotion, postural control, motor inhibition, and motor modification. Our results provide further support on the emerging concept of a dynamic, parallel, and delocalized theory for complex human motor behavior. [ABSTRACT FROM AUTHOR]

Recent studies advocate a connectivity pattern wider than previously believed of the uncinate fasciculus that extends to the ventrolateral and dorsolateral prefrontal cortices. These new percepts on the connectivity of the tract suggest a more expansive role for the uncinate fasciculus. Our aim was to shed light on this controversy through fiber dissections. Twenty normal adult human formalin-fixed cerebral hemispheres were used. Focused dissections on the insular, orbitofrontal, ventromedial, ventrolateral, and dorsolateral prefrontal areas were performed to record the topography of the frontal terminations of the uncinate fasciculus. Three discrete fiber layers were consistently disclosed: the first layer was recorded to terminate at the posterior orbital gyrus and pars orbitalis, the second layer at the posterior two thirds of the gyrus rectus, and the last layer at the posterior one third of the paraolfactory gyrus. The insular apex was documented as a crucial landmark regarding the topographic differentiation of the uncinate and occipitofrontal fasciculi (i.e., fibers that travel ventrally belong to the uncinate fasciculus whereas those traveling dorsally are occipitofrontal fibers). The frontal terminations of the uncinate fasciculus were consistently documented to project to the posterior orbitofrontal area. The area of the insular apex is introduced for the first time as a crucial surface landmark to effectively distinguish the stems of the uncinate and occipitofrontal fasciculi. This finding could refine the spatial resolution of awake subcortical mapping, especially for insular lesions, and improve the accuracy of in vivo diffusion tensor imaging protocols. [ABSTRACT FROM AUTHOR]

Summary: Lupus miliaris disseminatus faciei (LMDF) is a chronic inflammatory dermatosis of unknown aetiology, most often seen in young adults. Although many treatments for LMDF exist, treatment guidelines have not been developed, and response to therapy is generally unpredictable. We present the results of transcriptomic analysis of LMDF lesional skin, which revealed a variety of differentially expressed genes linking LMDF to alterations in innate and adaptive T helper 1 immunity. Immunohistochemical analysis was also performed, identifying similar changes in T‐cell immune responses. Given evidence for increased tumour necrosis factor (TNF) pathway activity, our patient, who had previously been refractory to multiple treatments, was initiated on TNF inhibitor therapy with excellent response. This characterization of the LMDF immune response may lead to improved treatment of this condition. [ABSTRACT FROM AUTHOR]

The prevalence of arterial hypertension is high in patients with diabetes mellitus (DM). When DM and hypertension coexist, they constitute a dual cardiovascular threat and should be adequately controlled. Novel antihyperglycemic agents, including sodium-glucose co-transporter 2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 (DPP-4) inhibitors, have recently been used in the treatment of DM. Beyond their glucose-lowering effects, these drugs have shown beneficial pleiotropic cardiovascular effects, including lowering of arterial blood pressure (BP), as acknowledged in the 2019 European Society of Cardiology/European Association for the Study of Diabetes guidelines on diabetes, prediabetes, and cardiovascular diseases. The purpose of this review was to summarize the available information on the BP-reducing effects of these new glucose-lowering drug classes and provide a brief report on underlying pathophysiological mechanisms. We also compare the three drug classes (SGLT-2 inhibitors, GLP-1 RAs, and DPP-4 inhibitors) in terms of their BP-lowering effect and show that the greater BP reduction seems to be achieved with SGLT-2 inhibitors, whereas DPP-4 inhibitors have probably the mildest antihypertensive effect. [ABSTRACT FROM AUTHOR]

Background/Objectives: The characteristics of patients experiencing recurrent Mycoplasma pneumoniae–induced rash and mucositis (MIRM) are not well understood. We aimed to characterize patients with recurrent disease by comparing the demographics, skin and mucosal involvement, seasonality, and treatment to those with single episodes (isolated MIRM). Methods: This retrospective case series screened all patients seen by our dermatology inpatient consult service from September 2014 to March 2020. Cases were selected based on laboratory and clinical criteria that confirmed a diagnosis of MIRM. Results: We identified 13 patients with MIRM: 5 who experienced recurrence (38%) and 8 with isolated, single episodes without recurrence. Mean age was 13.6 years for initial episodes in the recurrent patients compared to 11.7 in patients with isolated episodes. All 5 recurrent MIRM patients were male (compared with 75% of isolated MIRM patients) and predominantly Black (60%, compared with 25%). Most episodes overall (isolated and recurrent) occurred from the months of October to February. Recurrences after initial MIRM episode had less severe skin and mucosal findings, often involving only one mucous membrane, less frequent need for hospital admission, and shorter duration of hospital stay. Prophylactic treatments and treatments beyond supportive care were of unclear value. Conclusions: Some characteristics of MIRM differ between patients with recurrent and isolated disease. Clinicians should be aware of the potential for recurrence, which occurred in 38% of our cohort. Although recurrences after initial MIRM episode tended to be less severe, there is still potential for prolonged hospitalizations with recurrent episodes. More evidence is needed regarding effective preventive and treatment regimens in patients with recurrent MIRM. [ABSTRACT FROM AUTHOR]

The present work contains light curve, spectroscopic, and asteroseismic analyses for KIC 04851217 and KIC 10686876. These systems are detached eclipsing binaries hosting a pulsating component of δ Scuti type and have been observed with the unprecedented accuracy of the Kepler space telescope. Using ground-based spectroscopic observations, the spectral types of the primary components of the systems were estimated as A6V and A5V for KIC 04851217 and KIC 10686876, respectively, with an uncertainty of one subclass. The present spectral classification, together with literature radial velocity curves, were used to model the light curves of the systems and, therefore, to calculate the absolute parameters of their components with a higher degree of certainty. The photometric data were analysed using standard eclipsing binary modeling techniques, while their residuals were further analysed using Fourier transformation techniques to extract the pulsation frequencies of their host δ Scuti stars. The oscillation modes of the independent frequencies were identified using theoretical models of δ Scuti stars. The distances of the systems were calculated using the relation between the luminosity and the pulsation period for δ Scuti stars. Here, the physical and the oscillation properties of the pulsating components of these systems are discussed and compared with others of the same type. Moreover, using all the currently known cases of δ Scuti stars in detached binaries, updated correlations between orbital and dominant pulsation periods and between log g and pulsation periods are derived. It can concluded that the proximity of the companion plays significant role in the evolution of the pulsational frequencies. [ABSTRACT FROM AUTHOR]

The objectives of this study were to compare variable rate and uniform fertilizer applications in apple (Malus domestica Borkh.) and its effect on production and economic return. In the study, 59.6% and 63.4% less fertilizer were applied in the variable rate treatments (VRT) in 2011 and 2012, respectively, with less than 4% difference in yield. Soil properties did not significantly affect yield and fruit quality. The VRT fertilizer cost was reduced by 2.3% and 7.6% in 2011 and 2012, respectively, and fruit quality was not significantly affected. Assessing yield to calculate fertilizer demand suggests variable rate fertilizer inputs can potentially increase the profitability of an apple orchard. [ABSTRACT FROM AUTHOR]

The objectives of this study were to compare variable rate and uniform fertilizer applications in apple (Malus domestica Borkh.) and its effect on production and economic return. In the study, 59.6% and 63.4% less fertilizer were applied in the variable rate treatments (VRT) in 2011 and 2012, respectively, with less than 4% difference in yield. Soil properties did not significantly affect yield and fruit quality. The VRT fertilizer cost was reduced by 2.3% and 7.6% in 2011 and 2012, respectively, and fruit quality was not significantly affected. Assessing yield to calculate fertilizer demand suggests variable rate fertilizer inputs can potentially increase the profitability of an apple orchard. [ABSTRACT FROM AUTHOR]

We have combined photometric and spectroscopic observations of two very close eclipsing binary systems, ST Centauri and V775 Centauri, to determine their evolutionary state from calculations of masses and radii and other properties. Spectral types were determined and radial velocities calculated from spectra obtained with the Australian National University's 2.3 m telescope and Wide Field Spectrograph. The spectral type of the ST Cen primary component is F8 IV and the secondary is F8-8.5 IV. The ST Cen mean masses and radii of 1.40 ± 0.05 M ⊙ and 1.38 ± 0.10 M ⊙ and 2.2 ± 0.1 R ⊙ and 2.13 ± 0.08 R ⊙ for the primary and secondary components respectively, indicate that they are close to terminal age on the Main Sequence. Although the spectra of V775 Cen appeared to be single lined, the broadening function method enabled us to determine the radial velocities of the faint secondary component as well as those of the primary star. The mean masses and radii of the V775 Cen components are 1.65 ± 0.31 M ⊙ and 0.72 ± 0.29 M ⊙ and 1.68 ± 0.11 R ⊙ and 1.24 ± 0.08 R ⊙ for components 1 and 2 respectively. Our data show that V775 Cen is a close Algol binary system, with a secondary component that has evolved beyond terminal age Main Sequence, has filled its inner critical equipotential surface and is transferring mass to the primary star. The masses and radii of both components of V775 Cen are smaller than those of other Algol binary systems. Although the primary component of V775 Cen is on the Main Sequence, its spectral type is F0/F1 class IV. Both systems displayed episodes of photospheric and chromospheric activity. This was evident in the H α lines of ST Cen and the Na I D lines of the components in both systems. Narrow Na I D lines between those of the binary components suggest that circumbinary gas is present. [ABSTRACT FROM AUTHOR]

This article considers the limitations, but also the insights, of Gadamerian hermeneutics for understanding and responding to the crisis precipitated by the Covid-19 pandemic. Our point of departure is the experience of deep disagreements amid the pandemic, and our primary example is ongoing debates in the United States about wearing masks. We argue that, during this dire situation, interpersonal mutual understanding is insufficient for resolving such bitter disputes. Rather, following Gadamer's account of our dialogical experience with an artwork, we suggest that our encounter with the virus gives rise to new ways of seeing and experiencing ourselves and the world. Further, we draw on Gadamer's account of the fusion of horizons to show how even competing perspectives on wearing masks arise within a shared space of meaning created by the virus. These insights provide hope for an improved model of political dialogue in the world of Covid-19. [ABSTRACT FROM AUTHOR]

A production level implementation of the high-spin open-shell (spin unrestricted) single reference coupled pair, quadratic configuration interaction and coupled cluster methods with up to doubly excited determinants in the framework of the local pair natural orbital (LPNO) concept is reported. This work is an extension of the closed-shell LPNO methods developed earlier [F. Neese, F. Wennmohs, and A. Hansen, J. Chem. Phys. 130, 114108 (2009); F. Neese, A. Hansen, and D. G. Liakos, J. Chem. Phys. 131, 064103 (2009)]. The internal space is spanned by localized orbitals, while the external space for each electron pair is represented by a truncated PNO expansion. The laborious integral transformation associated with the large number of PNOs becomes feasible through the extensive use of density fitting (resolution of the identity (RI)) techniques. Technical complications arising for the open-shell case and the use of quasi-restricted orbitals for the construction of the reference determinant are discussed in detail. As in the closed-shell case, only three cutoff parameters control the average number of PNOs per electron pair, the size of the significant pair list, and the number of contributing auxiliary basis functions per PNO. The chosen threshold default values ensure robustness and the results of the parent canonical methods are reproduced to high accuracy. Comprehensive numerical tests on absolute and relative energies as well as timings consistently show that the outstanding performance of the LPNO methods carries over to the open-shell case with minor modifications. Finally, hyperfine couplings calculated with the variational LPNO-CEPA/1 method, for which a well-defined expectation value type density exists, indicate the great potential of the LPNO approach for the efficient calculation of molecular properties. [ABSTRACT FROM AUTHOR]

Background The controlled attenuation parameter (CAP) enables the noninvasive assessment of liver steatosis. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of CAP for identifying liver steatosis in patients at risk for metabolic dysfunctionassociated steatotic liver disease (MASLD), using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. Method We searched Medline, Embase, Cochrane Library and gray literature sources up to March 2024. We defined MASLD as MRI-PDFF =5%. We also assessed the accuracy of CAP for identifying patients with MRI-PDFF =10%. We calculated pooled sensitivity and specificity estimates using hierarchical random-effects models. We assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool, and the certainty in meta-analysis estimates using the Grading of Recommendations Assessment, Development and Evaluation framework. Results We included 8 studies with 1116 participants. The prevalence of MASLD ranged from 65.2-93.9%. Pooled sensitivity and specificity of CAP for MRI-PDFF =5% were 0.84 (95% confidence interval [CI] 0.79-0.88) and 0.77 (95%CI 0.68-0.84), respectively, with an area under the receiver operating characteristic curve (AUROC) of 0.88. The pooled sensitivity and specificity for MRI-PDFF =10% were 0.83 (95%CI 0.80-0.87) and 0.72 (95%CI 0.59-0.82), with an AUROC of 0.85. The certainty in our estimates was low to very low because of the high risk of bias, inconsistency and imprecision. Conclusions CAP has acceptable diagnostic accuracy for both MRI-PDFF =5% and MRI-PDFF =10%. Adequately powered and rigorously conducted diagnostic accuracy studies are warranted to establish the optimal CAP thresholds. [ABSTRACT FROM AUTHOR]

Source Citation: Bajaj HS, Aberle J, Davies M, et al. Once-weekly insulin icodec with dosing guide app versus once-daily basal insulin analogues in insulin-naive type 2 diabetes (ONWARDS 5): a randomized trial. Ann Intern Med. 2023;176:1476-1485. 37748181 Clinical Impact Ratings: GIM/FP/GP: Endocrinology: [ABSTRACT FROM AUTHOR]

Martin Heidegger's critique of modernity, and his vision of what may come after it, constitutes a sustained argument across the arc of his career. Does Hans-Georg Gadamer follow Heidegger's path of making possible "another beginning" after the modern age? In this article, I show that, in contrast to Heidegger, Gadamer cultivates modernity's hidden resources. We can gain insight into Gadamer's difference from Heidegger on this fundamental point with reference to his ambivalence toward and departure from two of Heidegger's touchstones for postmodernity, namely, Friedrich Nietzsche and Friedrich Hölderlin. We can appreciate and motivate Gadamer's proposal to rehabilitate modernity by juxtaposing his rootedness in Wilhelm Dilthey and Rainer Maria Rilke with Heidegger's corresponding interest in Nietzsche and Hölderlin. This difference in influences and conceptual starting points demonstrates Heidegger and Gadamer's competing approaches to the modern age, a contrast that I concretize through a close reading of Gadamer's choice of a poem by Rilke as the epigraph to Truth and Method [ABSTRACT FROM AUTHOR]

Aims: To assess the effect of liraglutide on 24‐hour ambulatory blood pressure and heart rate in patients with hypertension (pre‐ and stage 1 hypertension) and inadequately controlled Type 2 diabetes (glycated haemoglobin 7%–10% [53‐86 mmol/mol]). Materials and methods: Eligible patients for this investigator‐initiated, parallel‐group, randomized, double‐blind trial were on stable background antihyperglycaemic therapy excluding insulin, glucagon‐like peptide‐1 receptor agonists and dipeptidyl‐peptidase‐4 inhibitors. Participants were centrally randomized in a 1:1 ratio to daily liraglutide 0.6 mg, titrated to 1.2 mg after the first week, or placebo for 5 weeks. The primary outcome was change in 24‐hour ambulatory systolic blood pressure (SBP), and secondary outcomes included change in ambulatory diastolic blood pressure (DBP) and heart rate. We also assessed renal sodium handling. Results: Of 87 patients assessed for eligibility, 62 (66.1% men) with a mean age of 60.2 years were randomized to liraglutide (n = 31) or placebo (n = 31). All participants received background therapy with metformin, whilst 35.5% were treated concomitantly with sulphonylureas and 14.5% with pioglitazone. Compared with placebo, liraglutide reduced 24‐hour SBP by −5.73 mm Hg (95% confidence interval [CI] –9.81 to −1.65) and had a neutral effect on 24‐hour DBP (mean difference − 1.42 mm Hg; 95% CI –4.25 to 1.40), whilst increasing 24‐hour heart rate by 6.16 beats/min (95% CI 3.25 to 9.07). Findings were consistent for daytime and night‐time measurements. Liraglutide did not increase urine sodium excretion. Conclusion: Based on 24‐hour ambulatory measurements, short‐term treatment with liraglutide had a favourable effect on SBP whilst increasing heart rate. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma (SCC) is the second most common cutaneous malignancy in the United States, with increased frequency in immunosuppressed individuals or those exposed to ultraviolet radiation.1 Overall, 2% to 5% of SCCs spread to lymph nodes or more distant sites.1 Surgical excision remains the "gold standard", though depending on patients' comorbidities, topical, intralesional (IL), or radiation therapy may also be appropriate.1 In this report, we describe a case of SCC of the scalp treated with repeated, extensive measures resulting in a poor outcome. IL 5-FU, intralesional fluorouracil 50 mg/mL gl Over the next 2 months, she underwent weekly intralesional fluorouracil (IL 5-FU) treatments without improvement (Figure 2B). Despite these comorbidities, the patient received aggressive treatments for her SCC including radiation therapy, intralesional chemotherapy, and multiple surgeries ultimately resulting in a necrosed and exposed calvarium. [Extracted from the article]

Angiogenesis is a key enabling feature of mammalian embryonic development and tumor progression, which provides oxygen and nutrients that are required for vessel growth and tumor cell growth, respectively. Hypoxia is a driver of this phenomenon and is considered to be one of the most potent initiators of angiogenesis both in vitro and in vivo through stabilization of the transcription factors, hypoxia‐inducible factor‐1 and ‐2 (HIF‐1 and HIF‐2). Although these proteins are highly homologous, emerging evidence suggests that they have unique transcriptional targets and differential impact on angiogenesis. Although HIF‐1α is the best known and widely described isoform, recent studies suggest that HIF‐2α is a critical regulator of physiological and pathophysiological angiogenesis and, at least, the similiarly important as HIF‐1α. Indeed, HIF‐2α has been shown to regulate multiple aspects of angiogenesis, including cell proliferation, migration, maturation of blood vessels, and metastasis. In this review, we focus on recent insights into HIF‐2α expression, activation, and function under hypoxic and nonhypoxic conditions. We also summarize the current knowledge on the crosstalk between HIF‐2 and angiogenesis, describing reported phenotypical changes of HIF‐2α genetic models and HIF‐2 target genes implicated in angiogenesis. Finally, we provide a survey of recent pharmacologic strategies to specifically target HIF‐2 activity. Hypoxia‐inducible factor (HIF)‐2α has been shown to regulate multiple aspects of angiogenesis, including cell proliferation, migration, maturation of blood vessels, and metastasis. In this review, we focus on recent insights into HIF‐2α expression, activation, and function under hypoxic and nonhypoxic conditions. We also summarize the current knowledge on the crosstalk between HIF‐2 and angiogenesis, describing reported phenotypical changes of HIF‐2α genetic models and HIF‐2 target genes implicated in angiogenesis. Finally, we provide a survey of recent pharmacologic strategies to specifically target HIF‐2 activity. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The method creating cellulose acetate - essential oils nanocapsules was optimized. • No surfactant was needed for the formation of nanocapsules. • The nanocapsules have antimicrobial activity against 3 bacteria and a yeast strain. • The nanocapsules prevent microbial colonization and biofilm development. Abstract This study aimed to obtain bioactive nanosystems by combining cellulose acetate with three selected essential oils (EOs) to create spherical nanocapsules (NCs) using the solvent/anti-solvent technique. The biological activity of the obtained NCs was promoted by the use of some antimicrobial EOs: Peppermint, Cinnamon and lemongrass which were grafted on the cellulose acetate molecules. Due to their chemistry, such as long hydrocarbon tails and heads with functional groups these EOs were playing also the role of surfactant-like substance facilitating the formation of NCs. A dispersion of NCs was obtained in water and various spectroscopy techniques used to examine their size, morphology and chemistry. Dynamic light scattering calculate the size of the NCs whereas scanning electron microscopy showed their morphology. Fluorescent microscopy and Raman spectroscopy proved the attachment of the EOs in the cellulose acetate molecules. The antimicrobial activity of the obtained nanomaterials was tested against four microbial strains (bacteria: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli , and a yeast strain of Candida albicans). The obtained results demonstrated that such NCs can be used in a variety of applications including medical, pharmaceutical recipients and in household products for treating or preventing microbial colonization and biofilm development. [ABSTRACT FROM AUTHOR]

A multitude of contemporary applications heavily involve graph data whose size appears to be ever–increasing. This trend shows no signs of subsiding and has caused the emergence of a number of distributed graph processing systems including Pregel, Apache Giraph, and GraphX . However, the unprecedented scale now reached by real-world graphs hardens the task of graph processing due to excessive memory demands even for distributed environments. By and large, such contemporary graph processing systems employ ineffective in-memory representations of adjacency lists. Therefore, memory usage patterns emerge as a primary concern in distributed graph processing. We seek to address this challenge by exploiting empirically-observed properties demonstrated by graphs generated by human activity. In this paper, we propose 1) three compressed adjacency list representations that can be applied to any distributed graph processing system, 2) a variable-byte encoded representation of out-edge weights for space-efficient support of weighted graphs, and 3) a tree-based compact out-edge representation that allows for efficient mutations on the graph elements. We experiment with publicly-available graphs whose size reaches two-billion edges and report our findings in terms of both space-efficiency and execution time. Our suggested compact representations do reduce respective memory requirements for accommodating the graph elements up–to 5 times if compared with state-of-the-art methods. At the same time, our memory-optimized methods retain the efficiency of uncompressed structures and enable the execution of algorithms for large scale graphs in settings where contemporary alternative structures fail due to memory errors. [ABSTRACT FROM AUTHOR]

Background: Initiation of antihypertensive therapy with a two-drug fixed-dose combination (FDC) in a single tablet may be recommended in patients at high risk of cardiovascular events to improve adherence and effectiveness. Preferred combinations include an angiotensin-converting enzyme inhibitor with a dihydropyridine calcium antagonist. Objective: This study assessed adherence to and the safety, tolerance, and effectiveness of the perindopril/amlodipine FDC in Greek patients with hypertension and stable coronary artery disease (CAD) over a 4-month period. Methods: A total of 1907 patients with hypertension and CAD (59.1% males) who had recently (≤2 weeks) commenced treatment with the perindopril/amlodipine FDC (5/5, 5/10, 10/5, or 10/10 mg) were studied at baseline and at 1 and 4 months. Adherence to treatment was assessed with the Morisky Medication-taking Adherence Scale (MMAS). Results: Seven patients (0.4%) did not attend the scheduled visits. In total, 1607 (84.6%) patients received a constant treatment dose throughout the study. High adherence (MMAS score = 0) was reported by 1592 (83.6%), 1628 (85.7%), and 1477 (77.7%) patients at the second and the third visit and at both visits, respectively. Adverse reactions were reported by only 13 (0.7%) patients, were all minor, and did not result in treatment discontinuation. Office blood pressure (BP) was significantly decreased at the third visit (130.8 ± 8.4/78.2 ± 6.4 mmHg) compared with baseline (156.5 ± 15.0/89.9 ± 9.6 mmHg; p < 0.001), regardless of previous antihypertensive treatment. Patients with grade 1, 2, and 3 hypertension at baseline showed a reduction in BP of 19.3/9.4, 31.5/13.5, and 47.8/22.2 mmHg, respectively ( p < 0.001). Uncontrolled hypertension (≥140/90 mmHg) was notably reduced from 90.3% at baseline to 18.5% at the third visit. Conclusions: The perindopril/amlodipine FDC is characterized by high adherence and effectiveness, regardless of previous treatment. Degree of BP reduction was related to baseline BP levels. Clinical trials registration number (Protocol Number): IC4 - 05985 - 011 - GRC. [ABSTRACT FROM AUTHOR]

Tissue hypoxia affects gene expression through the hypoxia-inducible transcription factors, HIF-1 and HIF-2, in both physiological and pathological angiogenesis. Angiogenesis is a complex response of endothelial cells integrating cell proliferation, migration, tube formation, and their interaction with the extracellular matrix through integrin receptors. In this report, we studied the effect of hypoxia on the angiogenic functions of human microvascular endothelial cells (HMEC-1) as well as on expression of the angiogenic integrins ανβ3, ανβ5, and α5β1. Exposure of HMEC-1 to hypoxia (1% O2) or to DMOG, a prolyl-4-hydroxylase inhibitor, caused significant reduction to their proliferation rate, whereas their migration ability toward laminin-1 or collagen IV and capillary-like tube formation were significantly enhanced. In addition, αv, β1, β3, and β5 integrins expression was increased under hypoxia in HMEC-1, while α5 integrin was not affected. Both HIF-1 and HIF-2 protein expression and transcriptional activity were induced under hypoxia in HMEC-1. The knockdown of either HIF-1α or HIF-2α inhibited integrin β3 hypoxic stimulation, suggesting a HIF-dependent induction of β3 integrin in HMEC-1. Taken together, our results indicate that hypoxia transcriptionally up-regulates angiogenic integrins in microvascular endothelial cells along with promoting migration and tube formation of HMEC-1. [ABSTRACT FROM AUTHOR]

The method of electrospinning was used to create nanofibers made of cellulose acetate (CA) and essential oils (EOs). CA polymer at 15% w/v was dissolved in acetone and then 1% or 5% v/v of EOs was added to the polymer solution. The utilized essential oils were rosemary and oregano oils. Then, the CA/EOs in acetone solution were electrospun, creating micro/nanofibers, approximately 700-1500 nm in diameter. Raman spectroscopy was used to detect the attachment of the EOs in the CA electrospun fibers (ESFs). Scanning electron microscopy was used to study the morphology, topography and dimensions of the ESFs. The formed CA/EOs ESFs are found to have good antimicrobial properties against three common microbial species, frequently found in difficult to treat infections: Bacteria species Staphylococcus aureus, Escherichia coli and the yeast Candida albicans. ESFs with 5% v/v oregano oil with respect to the initial solution, showed the best antimicrobial and anti-biofilm effects due to the potency of this EO against bacteria and fungi, especially for Escherichia coli and Candida albicans. This work describes an effective and simple method to prepare CA/EOs ESFs and opens up many new applications of micro/nanofibers such as improved antimicrobial wound dressings, anti-biofilm surfaces, sensors and packaging alternatives. [ABSTRACT FROM AUTHOR]

The catalogue contains 199 confirmed cases of binary systems containing at least one pulsating component of δ Sct type. The sample is divided into subgroups in order to describe the properties and characteristics of the δ Sct-type stars in binaries according to their Roche geometry. Demographics describing quantitatively our knowledge for these systems as well as the distributions of their pulsating components in the mass--radius, colour--magnitude, and evolutionary status--temperature diagrams are presented and discussed. It is shown that a threshold of ~13 d of the orbital period regarding the influence of binarity on the pulsations is established. Finally, the correlations between the pulsation periods and the orbital periods, evolutionary status, and companion's gravity influence are updated based on the largest sample to date. [ABSTRACT FROM AUTHOR]

Crop irrigation which results in high water use efficiencies typically uses science-based irrigation scheduling tools to determine irrigation application timing and quantities. Although a large variety of sensors are available for measuring soil moisture status, there are a few easy-to-use irrigation scheduling tools which provide a yes/no irrigation decision or recommend how much water should be applied to return the soil profile to an optimal soil moisture condition. The work described here developed a method which uses soil water tension data from soil moisture sensors and the van Genuchten model to provide irrigation scheduling recommendations. The strength of the method is that it can use data readily available from USDA-NRCS soil surveys to predict soil water retention curves and calculate the volumetric water content and soil water tension of a soil at field capacity. Those parameters are then used to translate measured soil water tension into irrigation recommendations which are specific to the soil moisture status of the soil. The method was validated by comparing its results to other published methods and with continuous soil water tension data with multiple wetting and drying cycles from six fields in southern Georgia, USA. Finally, the model was incorporated into a web-based irrigation scheduling tool and used in conjunction with a wireless soil moisture sensing system to schedule irrigation in a large commercial field during 2015. By the van Genuchten model, we used about two thirds of the irrigation water and produced about the same yields as a commonly used yes/no irrigation decision tool. The presented method can be used to build resiliency to climate variability because it provides growers with data which they can use to make informed decisions about managing their water resources. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the role of urine α1 -microglobulin as a marker of hypertension-induced renal damage compared with estimated glomerular filtration rate, (eGFR), urine albumin, and urine albumin-to-creatinine ratio (ACR). Its response on different blood pressure (BP)-lowering drugs was also studied. Sixty never-treated hypertensive patients (65.0% men, 46.9 years, BP 141.4/94.0 mm Hg) were randomized to an irbesartan (an angiotensin receptor blocker [ARB]) or a diltiazem (a nondihydropyridine calcium channel blocker [CCB])-based regimen. Patients with diabetes or established cardiovascular, renal, or liver disease were excluded. Blood samples and 24-hour urine were analyzed at baseline and 6 months after pharmaceutical BP normalization. Serum creatinine was measured and eGFR was calculated. Urine albumin, creatinine, and α1 -microglobulin were measured and ACR was calculated. Minor changes (P=not significant [NS]) in eGFR were noted during follow-up in both groups (from 111.0 mL/min/1.73 m2 to 108.4 mL/min/1.73 m2 in the ARB group and from 111.3 mL/min/1.73 m2 to 114.0 mL/min/1.73 m2 in the CCB group). Twenty-four-hour urine indices were all significantly improved (P<.01) in the ARB group (albumin from 19.4 mg/L to 8.2 mg/L, ACR from 21.5 mg/g to 10.0 mg/g, α1 -microglobulin from 5.06 mg/L to 3.64 mg/L) but not (P=NS) in the CCB group (albumin from 15.6 mg/L to 13.9 mg/L, ACR from 17.6 mg/g to 17.1 mg/g, α1 -microglobulin from 4.94 mg/L to 4.79 mg/L). These differences between groups remained significant (P<.05) after adjusting for office heart rate and BP. α1 -Microglobulin was significantly correlated (P<.05) with albumin and ACR both at baseline (r=0.283 and 0.299, respectively) and at the end of follow-up (r=0.432 and 0.465, respectively) but not (P=NS) with eGFR. It was also significantly related (P<.05) to cardiovascular risk scores (Framingham and HeartScore) both at baseline (r=0.264 and 0.436, respectively) and at the end of follow-up (r=0.308 and 0.472, respectively). Urine α1 -microglobulin emerges as a potentially usable marker of hypertension-induced renal impairment. Its excretion rate and its response to treatment appears similar to that of albumin. Irbesartan but not diltiazem seems to be associated with reduced excretion of α1 -microglobulin in urine. [ABSTRACT FROM AUTHOR]

Polylactic acid was combined with lemongrass essential oil (EO) to produce functional nanocapsules (NCs). The obtained polylactic acid nanoparticles showed antimicrobial activity both with and without the presence of lemongrass oil; however, the presence of EO improved the activity of the NCs. The presence of lemongrass assisted the formation of well-separated NCs and also provided enhanced antimicrobial properties, since lemongrass is known for its antimicrobial character. Fluorescence microscopy was used to optically observe the nanoparticles and NCs and revealed the attachment of lemongrass oil with the polylactic acid NCs. Dynamic light scattering was used to determine their size. UV absorption was used to determine the exact amount of lemongrass oil found in the polylactic acid--lemongrass oil NCs, which was important for understanding the minimum inhibitory concentration for the antimicrobial experiments. A series of clinically important microbial species were used in the study and the obtained NCs proved to have very good antimicrobial properties against all tested strains. Such NCs can be used for the design of ecological strategies, based on natural alternatives, which may be efficient against severe infections, including those that involve resistant pathogens and biofilms or those with difficult to reach localization. [ABSTRACT FROM AUTHOR]

The goal of this work was to develop an easy-to-use and engaging irrigation scheduling tool for cotton which operates on a smartphone platform. The model which drives the Cotton SmartIrrigation App (Cotton App) is an interactive ET-based soil water balance model. The Cotton App uses meteorological data from weather station networks, soil parameters, crop phenology, crop coefficients, and irrigation applications to estimate root zone soil water deficits (RZSWD) in terms of percent as well as of inches of water. The Cotton App sends notifications to the user when the RZSWD exceeds 40%, when phenological changes occur, and when rain is recorded at the nearest weather station. It operates on both iOS and Android operating systems and was released during March 2014. The soil water balance model was calibrated and validated during 2012 and 2013 using data from replicated plot experiments and commercial fields. The Cotton App was evaluated in field trials for three years and performed well when compared to other irrigation scheduling tools. Its geographical footprint is currently limited to the states of Georgia and Florida, United States, because it is enabled to use meteorological data only from weather station networks in these states. A new version is currently under development which will use national gridded meteorological data sets and allow the Cotton App to be used in most cotton growing areas of the United States. [ABSTRACT FROM AUTHOR]

Nanocapsules and nanoparticles play an essential role in the delivery of pharmaceutical agents in modern era, since they can be delivered in specific tissues and cells. Natural polymers, such as cellulose acetate, are becoming very important due to their availability, biocompatibility, absence of toxicity and biodegradability. In parallel, essential oils are having continuous growth in biomedical applications due to the inherent active compounds that they contain. A characteristic example is lemongrass oil that has exceptional antimicrobial properties. In this work, nanocapsules of cellulose acetate with lemongrass oil were developed with the solvent/anti-solvent method with resulting diameter tailored between 95 and 185 nm. Various physico-chemical and surface analysis techniques were employed to investigate the formation of the nanocapsules. These all-natural nanocapsules found to well bioadhere to mucous membranes and to have very good antimicrobial properties at little concentrations against Escherichia coli and Staphylococcus aureus . [ABSTRACT FROM AUTHOR]

The topology and evolution of three-dimensional flow past a cylinder of slenderness ratio SR=1 mounted in a wind tunnel is examined for 0.1≤Re≤325 (based on the diameter of the cylinder) where steady-state solutions have been obtained. Direct numerical simulations were computed using an in-house parallel finite element code. The three-dimensional theory of separation is used to analyze and interpret the flow phenomena. Results indicate that symmetry breaking occurs at Re=1, while the first prominent structure is a horseshoe vortex downstream from the cylinder. At Re=150, two foci are observed, indicating the formation of two tornadolike vortices downstream. Concurrently, another horseshoe vortex is formed upstream from the cylinder. For higher Reynolds numbers, the flow downstream is segmented to upper and lower parts, whereas the topology of the flow on the solid boundaries remains unaltered. Pressure distributions show that pressure, the key physical parameter in the flow, decreases everywhere except immediately upstream from the cylinder. In addition, creation of critical points from saddle-node-type bifurcations occur when the streamwise component of the pressure gradient changes sign. Finally, at Re=325, an additional horseshoe vortex is formed at the wake of the cylinder. In all computations, an absence of critical points was observed on the free end of the cylinder. [ABSTRACT FROM AUTHOR]

A constantly growing amount of high-quality information resides in databases and is guarded behind forms that users fill out and submit. The Hidden Web comprises all these information sources that conventional web crawlers are incapable of discovering. In order to excavate and make available meaningful data from the Hidden Web, previous work has focused on developing query generation techniques that aim at downloading all the content of a given Hidden Web site with the minimum cost. However, there are circumstances where only a specific part of such a site might be of interest. For example, a politics portal should not have to waste bandwidth or processing power to retrieve sports articles just because they are residing in databases also containing documents relevant to politics. In cases like this one, we need to make the best use of our resources in downloading only the portion of the Hidden Web site that we are interested in. We investigate how we can build a focused Hidden Web crawler that can autonomously extract topic-specific pages from the Hidden Web by searching only the subset that is related to the corresponding area. In this regard, we present an approach that progresses iteratively and analyzes the returned results in order to extract terms that capture the essence of the topic we are interested in. We propose a number of different crawling policies and we experimentally evaluate them with data from four popular sites. Our approach is able to download most of the content in search in all cases, using a significantly smaller number of queries compared to existing approaches. [ABSTRACT FROM AUTHOR]

Cellulose acetate (CA) nanoparticles were combined with two antimicrobial agents, namely lemongrass (LG) essential oil and Cu-ferrite nanoparticles. The preparation method of CA nanocapsules (NCs), with the two antimicrobial agents, was based on the nanoprecipitation method using the solvent/anti-solvent technique. Several physical and chemical analyses were performed to characterize the resulting NCs and to study their formation mechanism. The size of the combined antimicrobial NCs was found to be ca. 220 nm. The presence of Cu-ferrites enhanced the attachment of LG essential oil into the CA matrix. The magnetic properties of the combined construct were weak, due to the shielding of Cu-ferrites from the polymeric matrix, making them available for drug delivery applications where spontaneous magnetization effects should be avoided. The antimicrobial properties of the NCs were significantly enhanced with respect to CA/LG only. This work opens novel routes for the development of organic/inorganic nanoparticles with exceptional antimicrobial activities. [ABSTRACT FROM AUTHOR]

The recovery of melanoidin and betaine from aqueous solutions was investigated by sorption onto anion and cation exchange resin, respectively. The effect of pH and temperature was studied in single component batch experiments. The data followed the Langmuir–Freundlich model. Desorption of solutes from the resins is feasible by employing KOH. The effect of contact time and initial solute concentration was studied in two component batch consecutive sorption experiments. The kinetic data followed the pseudo-second order kinetic model and equilibrium followed the Langmuir–Freundlich model. Two successive cycles of sorption–desorption were realized for the two component system in two consecutive fixed beds. The breakthrough curves were fitted to Thomas dynamic model. [ABSTRACT FROM AUTHOR]

[Display omitted] • Disposal of five NSAIDs compounds mixture from aqueous matrices with adsorption process. • Preparation of three new orange peels-activated carbon materials by pyrolysis method. • Completed adsorbents characterisation and adsorption performance. • Equilibrium, kinetic and thermodynamic parameters were established. • Application of inexpensive biomass waste for environmental reason. In recent years, bio-based carbons derived from environmentally friendly biomass materials have received considerable attention because of their abundance, easy processability, tunable surface properties and relatively low cost. Herein, a simple, less hazardous and low-cost method for the synthesis of ultrahigh surface area activated carbon material was proposed using orange peels as a carbon source. Within this context, three different biosorbents were synthesized: activated carbon samples derived from orange peels after activation with (i) phosphoric acid by pyrolysis at 450 °C (ORPs-H 3 PO 4 (450)) and (ii) at 650 °C (ORPs-H 3 PO 4 (650)), as well as (iii) after activation with potassium hydroxide at 450 °C (ORPs-KOH(450)). Characterisation and morphology of all materials has been conducted using various characterization techniques as FTIR, BET and SEM. The adsorption capacity was evaluated in a multi-component fashion for a mixture of five NSAIDs, namely diclofenac (DCF), ibuprofen (IBF), ketoprofen (KPF), salicylic acid (SAL) and paracetamol (PAR). The evaluation of the adsorption was achieved by investigating several variables like the effect of the solution's pH, of contact time (kinetic modelling) and of the initial pharmaceuticals' concentration. Acidic pH (pH = 2) appeared to be the optimal pH value while the pseudo-second order kinetic model and the Langmuir model demonstrate better fitting to the adsorption kinetics and isotherms respectively. Increase of temperature from 25 to 35 °C appears to have a positive effect on the adsorption capacity and the negative values of ΔG0 indicated that all target pharmaceuticals were adsorbed spontaneously to the synthesized biosorbents. Aqueous eluents with different pH values were used to accomplish desorption while pH = 6 appears to the optimum pH value for the desorption of the target pollutants. [ABSTRACT FROM AUTHOR]

Intrarenal hemodynamics depend on blood pressure (BP), heart rate (HR), and smoking. Although BP levels have been associated with kidney function, the effect of HR levels, BP, and HR variability on renal function are less well clarified. This cross-sectional study sought to determine the association of 24-hour BP and HR variability with kidney function in hypertensive patients, stratified by smoking. The study comprised 9600 nondiabetic, never-treated hypertensive individuals without evident renal impairment examined from 1985 to 2014 (aged 53.3±13.4 years, 55.3% males). The 24-hour systolic BP (SBP) and HR variability were estimated via their coefficient of variation (CV =standard deviation×100/mean value) derived from ambulatory recording. The CV SBP-to-CV HR ratio (CV R) was used as a marker of the interplay between 24-hour SBP and HR variability. Renal function was estimated via 24-hour urine creatinine clearance (CrCl), estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), and 24-hour urine α1 -microglobulin. After adjustment for age, sex, and smoking, CV SBP was found to be weakly correlated to eGFR (r=-0.017, P=.1) and somewhat more strongly to CrCl, ACR, and α1 -microglobulin (r=-0.032, 0.072, and 0.065; P=.002, <.001 and <.001, respectively). CV HR was much better related to renal function, with stronger adjusted correlations to CrCl, eGFR, ACR, and α1 -microglobulin (r=0.185, 0.134, -0.306, -0.247; all P<.001, respectively). CV R also showed equally good adjusted correlations (r=-0.175, -0.125, 0.336, 0.262; all P<.001, respectively). Most adjusted correlations for CV HR and CV R were even better in smokers (r=0.213, 0.158, -0.332, -0.272 and -0.183, -0.118, 0.351, 0.275, respectively; all P<.001). CV HR and CV R emerge as better related to kidney function than CV SBP, especially in smokers. The correlation of CV HR and CV SBP to renal function is inverse to each other. ACR and α1 -microglobulin are better related to variability indices than CrCl and eGFR. However, causal relations cannot be proved. [ABSTRACT FROM AUTHOR]

Aim To assess the efficacy and safety of recently approved once-weekly glucagon-like peptide 1 receptor agonists ( GLP-1 RAs) in patients with type 2 diabetes. Methods We conducted a systematic review and meta-analysis of randomized controlled trials comparing any GLP-1 RA licensed for once-weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched Medline, Embase, the Cochrane Library and grey literature for articles published up to December 2014 and extracted data in duplicate. Results In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin ( HbA1c) concentration was −0.66% [six studies; 95% confidence interval ( CI) −1.14 to −0.19; I2 = 88%] with albiglutide, and −1.18% (seven studies; 95% CI −1.34 to −1.02; I2 = 65%) with dulaglutide. Based on data from placebo-controlled trials, we did not detect statistically significant weight-sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once-weekly GLP-1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c-lowering (mean differences −0.40%; 95% CI −0.66 to −0.14; I2 = 85%, −0.44%; 95% CI −0.58 to −0.29; I2 = 40% and −0.28; 95% CI −0.45 to −0.10; I2 = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions. Conclusions Given their dosing scheme and overall efficacy and safety profile, once-weekly GLP-1 RAs are a convenient therapeutic option for use as add-on to metformin. [ABSTRACT FROM AUTHOR]

Objective White matter fiber dissection is an important method in acquiring a thorough neuroanatomic knowledge for surgical practice. Previous studies have definitely improved our understanding of intrinsic brain anatomy and emphasized on the significance of this technique in modern neurosurgery. However, current literature lacks a complete and concentrated laboratory guide about the entire dissection procedure. Hence, our primary objective is to introduce a detailed laboratory manual for cerebral white matter dissection by highlighting consecutive dissection steps, and to stress important technical comments facilitating this complex procedure. Methods Twenty adult, formalin-fixed cerebral hemispheres were included in the study. Ten specimens were dissected in the lateromedial and 10 in the mediolateral direction, respectively, using the fiber dissection technique and the microscope. Results Eleven and 8 consecutive and distinctive dissection steps are recommended for the lateromedial and mediolateral dissection procedures, respectively. Photographs highlighting various anatomic landmarks accompany every step. Technical recommendations, facilitating the dissection process, are also indicated. Conclusions The fiber dissection technique, although complex and time consuming, offers a three-dimensional knowledge of intrinsic brain anatomy and architecture, thus improving both the quality of microneurosurgery and the patient's standard of care. The present anatomic study provides a thorough dissection manual to those who study brain anatomy using this technique. [ABSTRACT FROM AUTHOR]

What is known and objective: Aspirin is an important drug in acute coronary syndromes (ACS) and percutaneous coronary interventions (PCI). However, its use is contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency (risk for haemolytic anaemia). We report the management of 2 patients with class II G6PD deficiency and non-ST-segment elevation ACS (NSTE-ACS). Case description: The two patients were safely and efficiently treated with dual antiplatelet treatment (DAPT, aspirin plus ticagrelor) and PCI using new-generation drug-eluting stent (DES) despite G6PD deficiency. What is new and conclusion: NSTE-ACS management with DAPT and DES is probably safe and effective in class II G6PD-deficient patients. [ABSTRACT FROM AUTHOR]

Amyloid-β protein precursor (AβPP) metabolism and the accumulation of its derivative amyloid-β (Aβ) peptide in senile plaques have been considered key players in the development of Alzheimer's disease (AD). However, the mechanisms underlying the generation and the deposition of Aβ are not clear but emphasis has been given in the role of AβPP protein interactions that regulate its processing and offer a means to manipulate Aβ production. We have previously shown that AβPP interacts with members of the Homer protein family, which leads to inhibition of Aβ generation. Herein, we studied the structural parameters of AβPP/Homer3 interaction by analyzing the sequences and domains that play a role in the formation of the complex. We found that the cytoplasmic tail of AβPP is necessary for the interaction. Regarding Homer3, we report that both the EVH1 protein interacting domain and the polymerization coiled coil domain are essential for the complex assembly. Importantly, phosphorylation of Homers at certain serine residues seems to enhance the interaction with AβPP, possibly underlying our recent work suggesting that calcium signaling also regulates the interaction. Our results show that the regulation of AβPP/Homer3 interaction might be critical in the context of Alzheimer's disease pathology as a novel target for regulating AβPP function and metabolism. [ABSTRACT FROM AUTHOR]

This is a review article aiming to make focus on the changes made in the European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines for the management of arterial hypertension with some criticism for each element discussed in the text. Given that in the real world clinical practice physicians would hardly spend the time needed for studying the 77 pages manuscript of the recently released 2013 ESH/ESC hypertension guidelines, the present review summarizes all the significant updates (along with their clinical implications) compared to the 2007 ESH/ESC hypertension guidelines and the 2009 reappraisal document. [ABSTRACT FROM AUTHOR]

Amyloid-β protein precursor (AβPP) metabolism and the accumulation of its derivative amyloid-β (Aβ) peptide in senile plaques have been considered key players in the development of Alzheimer's disease (AD). However, the mechanisms underlying the generation and the deposition of Aβ are not clear but emphasis has been given in the role of AβPP protein interactions that regulate its processing and offer a means to manipulate Aβ production. We have previously shown that AβPP interacts with members of the Homer protein family, which leads to inhibition of Aβ generation. Herein, we studied the structural parameters of AβPP/Homer3 interaction by analyzing the sequences and domains that play a role in the formation of the complex. We found that the cytoplasmic tail of AβPP is necessary for the interaction. Regarding Homer3, we report that both the EVH1 protein interacting domain and the polymerization coiled coil domain are essential for the complex assembly. Importantly, phosphorylation of Homers at certain serine residues seems to enhance the interaction with AβPP, possibly underlying our recent work suggesting that calcium signaling also regulates the interaction. Our results show that the regulation of AβPP/Homer3 interaction might be critical in the context of Alzheimer's disease pathology as a novel target for regulating AβPP function and metabolism. [ABSTRACT FROM AUTHOR]

The coupled cluster method with single-, double-, and perturbative triple excitations [CCSD(T)] is considered to be one of the most reliable quantum chemistry theories. However, the steep scaling of CCSD(T) has limited its application to small or medium-sized systems for a long time. In our previous work, the linear scaling domain based local pair natural orbital CCSD variant (DLPNO-CCSD) has been developed for closed-shell and open-shell. However, it is known from extensive benchmark studies that triple-excitation contributions are important to reach chemical accuracy. In the present work, two linear scaling (T) approximations for open-shell DLPNO-CCSD are implemented and compared: (a) an algorithm based on the semicanonical approximation, in which off-diagonal Fock matrix elements in the occupied space are neglected [referred to as DLPNO-(T0)]; and (b) an improved algorithm in which the triples amplitudes are computed iteratively [referred to as DLPNO-(T)]. This work is based on the previous open-shell DLPNO-CCSD algorithm [M. Saitow et al., J. Chem. Phys. 146, 164105 (2017)] as well as the iterative (T) correction for closed-shell systems [Y. Guo et al., J. Chem. Phys. 148, 011101 (2018)]. Our results show that the new open-shell perturbative corrections, DLPNO-(T0/T), can predict accurate absolute and relative correlation energies relative to the canonical reference calculations with the same basis set. The absolute energies from DLPNO-(T) are significantly more accurate than those of DLPNO-(T0). The additional computational effort of DLPNO-(T) relative to DLPNO-(T0) is a factor of 4 on average. We report calculations on systems with more than 4000 basis functions. [ABSTRACT FROM AUTHOR]