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Uncovering the material dissipation mechanisms of two-dimensional materials is essential for their implementation in advanced devices. While graphene resonators are highly attractive due to their high operational frequency and excellent durability, they dissipate a considerable amount of energy due to significant material dissipation associated with atomic friction manifested by the relative slipping of atomic layers. We mitigate the atomic friction by changing the atomic composition of the devices through the insertion of boron and nitride atoms that create polar interlayer bonds and, therefore, also reduce the energy dissipation. As a case study, we built boron carbonitride (BCN) foam cantilever devices and studied their frequency responses compared to those of their graphene counterparts. Indeed, we show that inserting boron and nitride atoms into the lattice improves the interlayer interactions and, thus, reduces the interlayer atomic friction. In addition, the air dissipation of BCN is also lower than that of graphene. Therefore, we pave the path for the development of BCN devices with tunable dissipation. [ABSTRACT FROM AUTHOR]

The chemotherapy regimen capecitabine/temozolomide (CAPTEM) is routinely used in neuroendocrine tumors (NET), with antitumor activity particularly demonstrated in pancreatic or high-grade neuroendocrine neoplasms (NEN). However, different dosing regimens are used, and the optimal schedule remains to be defined. This single-center retrospective analysis assessed the efficacy and safety of CAPTEM in patients with NEN using a schedule starting both compounds simultaneously (temozolomide on days 1-5 and capecitabine on days 1-14 of a 28-day cycle) rather than sequentially. The primary parameters of interest were response rates, progression-free survival (PFS), and toxicities following this treatment regimen, hereinafter referred to as TEMCAP. The study population comprised 40 patients, half of whom (n = 20) had pancreatic NEN, and 9 patients (22.5%) had pulmonary or thymic NETs. The most common histology was NET G3 (n = 15, 37.5%), and 8 patients (20.0%) had a neuroendocrine carcinoma (NEC). Most patients (77.5%) had at least one prior systemic therapy, and 16 patients (40.0%) prior chemotherapy. The median number of TEMCAP cycles was 6 (range 1-16). Median PFS for the highly heterogeneous population was 13.3 months, while the median overall survival was 31.9 months. In total, 14/36 patients (38.9%) exhibited a partial response, and the disease control rate was 75.0%. The safety profile of TEMCAP (at a below-target mean temozolomide dose of 118.85 mg/m2) in our cohort was remarkably good with no toxicities of grade 3 or 4. Taken together, the results of this analysis further support the use of temozolomide/capecitabine in NEN and prompt further assessment of our modified TEMCAP schedule. [ABSTRACT FROM AUTHOR]

Fluorescence microscopy has witnessed many clever innovations in the last two decades, leading to new methods such as structured illumination and super-resolution microscopies. The attainable resolution in biological samples is, however, ultimately limited by residual motion within the sample or in the microscope setup. Thus, such experiments are typically performed on chemically fixed samples. Cryogenic light microscopy (Cryo-LM) has been investigated as an alternative, drawing on various preservation techniques developed for cryogenic electron microscopy (Cryo-EM). Moreover, this approach offers a powerful platform for correlative microscopy. Another key advantage of Cryo-LM is the strong reduction in photobleaching at low temperatures, facilitating the collection of orders of magnitude more photons from a single fluorophore. This results in much higher localization precision, leading to Angstrom resolution. In this review, we discuss the general development and progress of Cryo-LM with an emphasis on its application in harnessing structural information on proteins and protein complexes. [ABSTRACT FROM AUTHOR]

There are differences in the features of nursing, in light of the transformations that took place, such as the tasks of clinic nurses in contrast to hospital nurses. This is also mirrored in the tasks of the 20th century nurse in comparison to the nurse of the 21st century; the standards of nursing are essentially the same but have been streamlined over the years with the introduction of various supporting technologies into the world of nursing. This article reviews the role of the nurse and its evolution over time and explores the differences between the nursing profession in the past, present, and future. [ABSTRACT FROM AUTHOR]

Protein motions occur on multiple time and distance scales. Large-scale motions of protein tertiary-structure elements, i.e., domains, are particularly intriguing as they are essential for the catalytic activity of many enzymes and for the functional cycles of protein machines and motors. Theoretical estimates suggest that domain motions should be very fast, occurring on the nanosecond or microsecond time scales. Indeed, free-energy barriers for domain motions are likely to involve salt bridges, which can break in microseconds. Experimental methods that can directly probe domain motions on fast time scales have appeared only in recent years. This Perspective discusses briefly some of these techniques, including nuclear magnetic resonance and single-molecule fluorescence spectroscopies. We introduce a few recent studies that demonstrate ultrafast domain motions and discuss their potential roles. Particularly surprising is the observation of tertiary-structure element dynamics that are much faster than the functional cycles in some protein machines. These swift motions can be rationalized on a case-by-case basis. For example, fast domain closure in multi-substrate enzymes may be utilized to optimize relative substrate orientation. Whether a large mismatch in time scales of conformational dynamics vs functional cycles is a general design principle in proteins remains to be determined. [ABSTRACT FROM AUTHOR]

It has been recently shown that in some proteins, tertiary‐structure dynamics occur surprisingly fast, that is on the microsecond or sub‐millisecond time scales. In this State of the Art Review, we discuss how such ultrafast domain motions relate to the function of caseinolytic peptidase B (ClpB), a AAA+ disaggregation machine. ClpB is a large hexameric protein that collaborates with cellular chaperone machinery to rescue protein chains from aggregates. We used single‐molecule FRET spectroscopy to capture the dynamics of essential structural elements within this machine. It was found that the middle domain of ClpB, known to act as its activator, toggles between two states much faster than the overall activity cycle of the protein, suggesting a novel mode of continuous, tunable switching. Motions of the N‐terminal domain were observed to restrict the conformational space of the M domain in the absence of a substrate protein, thereby preventing it from tilting and spuriously activating ClpB. Finally, microsecond dynamics of pore loops responsible for substrate pulling through ClpB's central channel, together with their response to specific perturbations, point to a Brownian‐ratchet mechanism for protein translocation. Based on our findings, we propose a two‐time‐scale model for the activity of ClpB, in which fast conformational dynamics affect slower functional steps, determined by ATP hydrolysis time. Future work on this and other proteins is likely to shed further light on the role of ultrafast dynamics on protein function. [ABSTRACT FROM AUTHOR]

Summary Statement: We propose to add some aspects that are of great complementary importance to broaden the kin recognition, discrimination and selection framework in plants and that need to be considered in future studies. [ABSTRACT FROM AUTHOR]

Tissue-specific transcription factors (TFs) control the transcriptome through an association with noncoding regulatory regions (cistromes). Identifying the combination of TFs that dictate specific cell fate, their specific cistromes and examining their involvement in complex human traits remain a major challenge. Here, we focus on the retinal pigmented epithelium (RPE), an essential lineage for retinal development and function and the primary tissue affected in age-related macular degeneration (AMD), a leading cause of blindness. By combining mechanistic findings in stem-cell-derived human RPE, in vivo functional studies in mice and global transcriptomic and proteomic analyses, we revealed that the key developmental TFs LHX2 and OTX2 function together in transcriptional module containing LDB1 and SWI/SNF (BAF) to regulate the RPE transcriptome. Importantly, the intersection between the identified LHX2-OTX2 cistrome with published expression quantitative trait loci, ATAC-seq data from human RPE, and AMD genome-wide association study (GWAS) data, followed by functional validation using a reporter assay, revealed a causal genetic variant that affects AMD risk by altering TRPM1 expression in the RPE through modulation of LHX2 transcriptional activity on its promoter. Taken together, the reported cistrome of LHX2 and OTX2, the identified downstream genes and interacting co-factors reveal the RPE transcription module and uncover a causal regulatory risk single-nucleotide polymorphism (SNP) in the multifactorial common blinding disease AMD. This study reveals that the transcription factors LHX2 and OTX2 function together in a transcriptional module containing LDB1 and SWI/SNF to regulate the retinal pigmented epithelium differentiation program; a causal regulatory risk SNP contributes to age-related macular degeneration by altering the binding of LHX2-OTX2 to the TRPM1 promoter. [ABSTRACT FROM AUTHOR]

Cryogenic optical localization in three dimensions (COLD) was recently shown to resolve up to four binding sites on a single protein. However, because COLD relies on intensity fluctuations that result from the blinking behavior of fluorophores, it is limited to cases where individual emitters show different brightness. This significantly lowers the measurement yield. To extend the number of resolved sites as well as the measurement yield, we employ partial labeling and combine it with polarization encoding in order to identify single fluorophores during their stochastic blinking. We then use a particle classification scheme to identify and resolve heterogenous subsets and combine them to reconstruct the three-dimensional arrangement of large molecular complexes. We showcase this method (polarCOLD) by resolving the trimer arrangement of proliferating cell nuclear antigen (PCNA) and six different sites of the hexamer protein Caseinolytic Peptidase B (ClpB) of Thermus thermophilus in its quaternary structure, both with Angstrom resolution. The combination of polarCOLD and single-particle cryogenic electron microscopy (cryoEM) promises to provide crucial insight into intrinsic heterogeneities of biomolecular structures. Furthermore, our approach is fully compatible with fluorescent protein labeling and can, thus, be used in a wide range of studies in cell and membrane biology. [ABSTRACT FROM AUTHOR]

The Black poplar is a pioneer tree species occurring along many river courses across Europe. Seedlings establish at very high density and experience various stresses (e.g., hydric, mechanical). In a previous study conducted in 2017 on the same population we described the fine-scale genetic structure (FSGS) of three age cohorts (5, 10 and > 20 years old) and found a significant SGS in the younger cohort. In this study, we aim to determine the FSGS in Black poplar cohorts of one-year-old seedlings, which is the most informative about seed dispersal. We used microsatellite markers to explore the FSGS of four different patches of Back poplar seedlings from two riverbanks in the Val d'Allier National Natural Reserve (France). We found a high genetic diversity and detected no FSGS in any of the four sampled seedlings patches. The absence of SGS at the seedling stage suggests that in this natural population, seeds from different mother trees are widely dispersed, well mixed and are deposited homogeneously on the various germination sites available over few kilometres. [ABSTRACT FROM AUTHOR]

Abnormal liver blood tests and liver tumor burden are known prognostic factors in neuroendocrine neoplasms (NEN). However, the relationship between biochemical liver parameters and hepatic tumor load is largely unknown in NEN and in high‐grade NEN (G3) specifically. The primary objective of this study was to correlate the biochemical parameters and liver tumor volume of patients with neuroendocrine tumors grade 3 (NET G3) or neuroendocrine carcinomas (NEC). We wanted to investigate whether patients with NET G3 with extensive liver involvement had less severely elevated laboratory liver parameters than NEC patients. In total, 46 patients with NEN were included, 31 had NEC and 15 NET G3. All patients had distant metastatic disease, with liver metastases being the most common (n = 39). Both laboratory results and semiautomatic volumetric measurements of liver tumor burden were obtainable for 34 patients at baseline and 26 patients at follow‐up. Alkaline phosphatase (AP), gamma‐GT (gGT), and lactate dehydrogenase (LDH) increased significantly between the two time periods (p <.01). In a regression model, liver tumor burden significantly affected several blood parameters, for example, increasing AP, gGT, LDH, and aspartate aminotransferase (ASAT) by a factor of 1.02–1.04 per unit increase (1% tumor burden; all p <.001). AP, gGT, and LDH were significantly lower in NET G3 (factor of 0.43–0.68) than in NEC. Here, we found that liver chemistries changed over the NEN disease course, correlated with hepatic tumor burden, and differed by histologic subtype. The current data can potentially guide treatment decisions, for example, with regard to integration of liver‐directed therapies. [ABSTRACT FROM AUTHOR]

Evaluation of genetic biodiversity for micronutrients is crucial for breeding high-quality crops and addressing the negative impacts of mineral deficiencies. The objectives of this research were to assess genetic variation and the relationship between grain Fe and Zn levels and agronomic traits in a diverse collection of wheat varieties. Additionally, the study aimed to determine the correlation between microsatellite markers (SSR) and micronutrient quantities. A total of 42 genotypes (Iranian commercial cultivars, landraces, and Afghan and Swiss varieties) were evaluated over a two-year period. Fe and Zn levels were measured using two semi quantitative staining assays and atomic absorption spectrophotometry (AAS) facility. Semi-quantitative staining methods and AAS showed high correlations for micronutrient contents. Landraces exhibited higher Fe (63.79 mg/kg) and Zn (44.76 mg/kg) but lower grain yield compared with commercial cultivars. Heritability estimates ranged 53%-79.43%, suggesting that genetic variance played a higher contribution in the phenotypic variation of traits than environmental factors. Notably, Fe content displayed significant correlations with days to maturity. Canonical correlation analysis (CCA) revealed that Zn content was correlated with four agronomic traits. Evaluation of genetic diversity using SSR markers demonstrated high genetic variation among the genotypes tested. The analysis of polymorphism information content (PIC) indicated that SSR primers had an average PIC of 0.75, with the Xgwm192 primer exhibiting higher PIC than others. Several SSR markers revealed association with micronutrient content that can be used in marker-assisted selection (MAS) programs aimed at selection of high micronutrient genotypes. In conclusion, the findings underscored the substantial genetic diversity present in micronutrient levels among global wheat genotypes, the potential of landraces for micronutrients biofortification of wheat cultivars through cross hybridization, the utility of staining methods for screening high/low micronutrient genotypes, and use of microsatellite markers for marker-assisted breeding aiming to micronutrient improvement in breeding programs. [ABSTRACT FROM AUTHOR]

Aquaculture conditions expose fish to internal and environmental stressors that increase their susceptibility to morbidity and mortality. The brain accumulates stress signals and processes them according to the intensity, frequency duration and type of stress, recruiting several brain functions to activate the autonomic or limbic system. Triggering the autonomic system causes the rapid release of catecholamines, such as adrenaline and noradrenaline, into circulation from chromaffin cells in the head kidney. Catecholamines trigger blood cells to release proinflammatory and regulatory cytokines to cope with acute stress. Activation of the limbic axis stimulates the dorsolateral and dorsomedial pallium to process emotions, memory, behaviour and the activation of preoptic nucleus‐pituitary gland‐interrenal cells in the head kidney, releasing glucocorticoids, such as cortisol to the bloodstream. Glucocorticoids cause downregulation of various immune system functions depending on the duration, intensity and type of chronic stress. As stress persists, most immune functions, with the exception of cytotoxic functions, overcome these effects and return to homeostasis. The deterioration of cytotoxic functions during chronic stress appears to be responsible for increased morbidity and mortality. [ABSTRACT FROM AUTHOR]

This paper explores, locates, and reviews the mentions made by Lacan in the course of his teaching about the so-called "passions of being". As this is a first approach that constitutes a more extensive investigation, it was considered to initially locate the mentions accompanied by the effects carried out by tracking. Firstly, the problem of passions for the psychoanalytic clinic is introduced. Then, the tracking we previously mentioned is arranged, contextualizing the references, and marking similarities and differences, in the process of generating a dialectical movement between them. The final section sets forth the conclusions and subsequent lines of work. [ABSTRACT FROM AUTHOR]

The thermodynamics of protein folding in bulk solution have been thoroughly investigated for decades. By contrast, measurements of protein substrate stability inside the GroEL/ES chaperonin cage have not been reported. Such measurements require stable encapsulation, that is no escape of the substrate into bulk solution during experiments, and a way to perturb protein stability without affecting the chaperonin system itself. Here, by establishing such conditions, we show that protein stability in the chaperonin cage is reduced dramatically by more than 5 kcal mol-1 compared to that in bulk solution. Given that steric confinement alone is stabilizing, our results indicate that hydrophobic and/or electrostatic effects in the cavity are strongly destabilizing. Our findings are consistent with the iterative annealing mechanism of action proposed for the chaperonin GroEL. [ABSTRACT FROM AUTHOR]

This paper demonstrates the relationship between acoustic emission (AE) method parameters and loaded pneumatic cylinders. The cylinders in our experiment were loaded gradually by different weights in a vertical direction. The effect of the defect occurs when the cylinder is loaded at the retreat and progress strokes. This defect affects the relationship between the applied load and the recorded signal of the sensors. The signals of the acoustic emission were recorded from the progress and retreat strokes and then analysed. The time delay is calculated between the digital input and the initiation of movement, and the time of the stroke. The energy and root mean square of the acoustic emission compare between the distinctive different responses in damaged and undamaged pneumatic cylinders, with and without loading. The energy and RMS were calculated for each cylinder with gradual loading. The results of the test showed approximate linear relationship between the RMS and loading. This paper is a continuation of a previous article and the extension of my work to find distinctive differences that determine whether the cylinder is damaged or undamaged. [ABSTRACT FROM AUTHOR]

• Abscission of date palm fruitlets and fruits occur throughout development. • Two abscission peaks occur specifically at 25–45 and 80–100 days after pollination. • Ethrel treatment induces abscission while auxin delays abscission in vitro. • A specific zone at the fruit base is activated both at early and late fruit drops. 'Medjoul' is a large semidry date cultivar that is marketed as a special elite product. Fruit size and quality are determined by fruit load, which is dependent on the level of fruit set, fruitlet thinning protocols and natural drop. Currently there is no information on the process of natural fruit abscission in date palms and specifically not on abscission of 'Medjoul'. In the present study abscission levels were characterized through fruit development in vivo and in vitro. Fruit abscise throughout development. During two stages, at an 'Early fruitlet drop' and a 'June drop' (at 25–45 and 80–100 days after pollination respectively), specifically high rates of abscission were observed. The level of fruit set and the fruit load affects these two peaks respectively. Ethrel treatment, an ethylene releasing chemical, significantly induced fruitlet drop while Auxin (2,4-D) treatment reduced the rate of natural fruit drop in vitro , especially during the developmental stages with high natural abscission. A specific abscission zone located at the base of the fruit, just between the calyx and spikelet was detected. Following Ethrel treatment, breaks and cracks in this tissue were detected. This data will enable better understanding of fruitlet and fruit abscission in date palm, which is extremely important for a high quality production of 'Medjoul' dates. [ABSTRACT FROM AUTHOR]

This paper focuses on the development of an efficient new diagnostic procedure for checking the function of pneumatic cylinders using acoustic emission. This diagnostic procedure is able to detect distinctive differences that determine whether the cylinder is damaged or undamaged. Moreover, the paper aims to find the diagnostic criteria that can be used to evaluate the pneumatic cylinder and detect defects. In this study, acoustic emission testing of several undamaged cylinders is carried out before artificial defects are created in each one. The signals from the progress and retreat strokes are recorded and analysed according to many parameters. The root mean square is normalised and the different responses of damaged and undamaged pneumatic cylinders are recognised by the time delay of the strokes. The differences are identified by comparing the maximum root mean square from sensor A and the maximum root mean square from sensor B for one cycle in the retreat stroke. The damaged and undamaged cylinders are distinguished using the difference in energy values present in the signals of the two sensors in the retreat stroke. The final evaluation of the cylinder is determined by calculating the total value of the root mean square. This paper is a continuation of a prior article and the extension of that work. [ABSTRACT FROM AUTHOR]

Peripheral nerve sheath tumors (PNSTs) account for ~ 5% of soft tissue neoplasms and are responsible for a wide spectrum of morbidities ranging from localized neuropathy to fulminant metastatic spread and death. MR imaging represents the gold standard for identification of these neoplasms, however, current anatomic MR imaging markers do not reliably detect or differentiate benign and malignant lesions, and therefore, biopsy or excision is required for definitive diagnosis. Diffusion-weighted MR imaging (DWI) serves as a useful tool in the evaluation and management of PNSTs by providing functional information regarding the degree of diffusion, while diffusion tensor imaging (DTI) aids in determining the directional information of predominant diffusion and has been shown to be particularly useful for pre-operative planning of these tumors by delineating healthy and pathologic fascicles. The article focuses on these important neurogenic lesions, highlighting the current utility of diffusion MR imaging and future directions including computerized radiomic analysis. KEY POINTS: • Anatomic MRI is moderately accurate in differentiating benign from malignant PNST. • Diffusion tensor imaging facilitates pre-operative planning of PNSTs by depicting neuropathy and tractography. • Radiomics will likely augment current observer-based diagnostic criteria for PNSTs. [ABSTRACT FROM AUTHOR]

This paper describes the methodology of combining experimental measurements with mathematical–physics analyses in the investigation of flow in the aperture and nozzle. The aperture and nozzle separate the differentially pumped chamber from the specimen chamber in an environmental scanning electron microscope (ESEM). Experimental measurements are provided by temperature and pressure sensors that meet the demanding conditions of cryogenic temperature zones and low pressures. This aperture maintains the required pressure difference between the chambers. Since it separates the large pressure gradient, critical flow occurs on it and supersonic gas flow with the characteristic properties of critical flow in the state variables occurs behind it. As a primary electron beam passes through the differential pumped chamber and the given aperture, the aperture is equipped with a nozzle. The shape of the nozzle strongly influences the character of the supersonic flow. The course of state variables is also strongly influenced by this shape; thus, it affects the number of collisions the primary beam's electrons have with gas molecules, and so the resulting image. This paper describes experimental measurements made using sensors under laboratory conditions in a specially created experimental chamber. Then, validation using mathematical–physical analysis in the Ansys Fluent system is described. [ABSTRACT FROM AUTHOR]

The article deals with the decision of the European Court of Justice (ECJ) regarding the recognition of a medical professional training in another member state. In the specific case, a person who had completed a three-year basic medical training was unable to provide a certificate for the unrestricted practice of medicine in the United Kingdom. The ECJ ruled that the authorities of a member state must take into account the diplomas, examination certificates, and experience of the applicant in order to ensure adequate comparability with national requirements. However, the article emphasizes that informally acquired competencies do not have to be included in the examination. It is discussed whether informal qualifications can be recognized if they are converted into a formal proof through a formal assessment. [Extracted from the article]

Hybrid semiconductor-metallic nanostructures play an important role in a wide range of applications and are key components in photocatalysis. Here we reveal that the nature of a nanojunction formed between a semiconductor nanorod and metal nanoparticle is sensitive to the size of the metal component. This is reflected in the activity toward hydrogen production, emission quantum yields, and the efficiency of charge separation which is determined by transient absorption spectroscopy. A set of Ni decorated CdSe@CdS nanorods with different tip size were examined, and an optimal metal domain size of 5.2 nm was obtained. Remarkably, charge separation time constants were found to be nonvariant with metal tip size. It is proposed that electron transfer mechanism encompasses two consecutive but separate processes: slow charge migration along the rod toward the interface, followed by fast interface crossing of the electron from the semiconductor into the metal phase. The first migration step dominates the time constant for the charge separation process and is not affected by the metal size. The efficiency of charge separation on the other hand was found to be sensitive to metal size. It is suggested that Coulomb blockade charging energy and a size-dependent Schottky barrier contribute to the metal size effect on charge transfer probability across the semiconductor-metal nanojunction. These two opposing trends result in an optimal metal size domain for the cocatalyst. This work is expected to benefit a broad range of applications utilizing semiconductor-metal nanocomposites. [ABSTRACT FROM AUTHOR]

Normal vision depends on the retinal pigmented epithelium (RPE), a metabolic cell layer that is vital to the development and function of the adjacent retinal photoreceptors. The LIM‐homeodomain transcription factor Lhx2 is important key factor for generation of the progenitors of both RPE and retina during early stages of eye development and is also essential for the generation of different stem cells giving rise to multiple types of organs. The purpose of this project is to understand the gene regulatory network (GRN) and the cis‐regulatory sequences bound by Lhx2/LHX2 in mouse and human in the developing and mature retinal pigment epithelium (RPE) of mammals. The methods include functional studies in vivo using Cre/loxP and knockdown approaches in RPE derived from human embryonic stem cells (hES‐RPE). The functional studies are combined with analyses of the global molecular changes, by identifying and characterizing cis‐regulatory regions bound by the complex and the impact of the mutation on gene expression and tissue differentiation. The results reveal essential role for Lhx2 in maintaining RPE fate in the embryonic optic cup and in differentiated hES‐RPE. Lhx2 seems to function as direct regulator of tissue specific transcription factors as well as cytoskeletal and cell adhesion genes. Conclusions: the GRN and the cis regulatory sequences identified provide novel insight on the activity of an important developmental regulator in controlling RPE differentiation, morphology and function in mice and humans. [ABSTRACT FROM AUTHOR]

This paper gives an overview of the common experiments performed in identifying the possible usage of acoustic emission (AE) in selected areas of monitoring life processes of living organisms. The paper accumulates and partially comments the results of experiments where AE method has been applied to evaluation of response of transpiratory flow responses in various species in different parts of day. The second part is focused on deepening knowledge of diagnostics and evaluation of the influence of natural conditions to the growth of maize. The final part of the paper deals with a continuous monitoring of honey bee (Apis mellifera) colony. Overall colony activity was monitored and data was recorded to describe development of the bee colony. [ABSTRACT FROM AUTHOR]

The aim of this review is to investigate whether changes in olfactory bulb volume relate to changes in specific olfactory functions. We studied currently available peer-reviewed articles on the volume of the human olfactory bulb that also included a psychophysical measure of olfactory function. In the present review, we observed a very clear and consistent correlation between general olfactory function and olfactory bulb (OB) volume. We were not able to find a clear relationship between a specific smell component and OB volume, even when analyzing pathologic conditions separately. In some cases, changes were observed for different subtests, but these changes did not significantly correlate with OB volume or had only a borderline correlation. In other cases, we found contradictory data. Several factors may contribute to the difficulties in finding correlations with the different components of smell: (1) the OB volume may be influenced by information from olfactory receptor neurons (bottom-up effect), information from central nervous system (top-down effect) and by direct damage; (2) most pathologic conditions affect more than one area of the olfactory pathway; (3) small sample sizes of hyposmic subjects were used. We believe that it is necessary to do further studies with larger numbers of subjects to answer the currently investigated question. [ABSTRACT FROM AUTHOR]

The role of a clinical nurse specialist in oncology varies greatly between healthcare systems, and implementing this healthcare role with its multifaceted and co-existing responsibilities may prove challenging. While already integrated into healthcare systems and services in several European countries, Asia, Canada, and the United States, other countries are just beginning to develop clinical nursing specialties. The current study aims to provide healthcare policymakers with up-to-date evidence that focuses on the diverse modes of oncology clinical nurse specialist role implementation across several healthcare systems and pertinent implementation challenges as described in the literature. A rapid evidence assessment was carried out in order to provide policymakers with a rigorous review in a condensed timescale. Initially, only items in the English language were included, and "grey literature" was excluded. We searched PubMed between 1 January 2022 and 28 February 2022 and two independent scholars reviewed items. Based on 64 papers, both non-scientific and papers that met the initial criteria of the rapid review, we describe the modes of implementation of the oncology clinical nurse specialist in the United States, Canada, United Kingdom, Japan, Brazil and Australia. Barriers to implementation include conflicts around role boundaries, skepticism and lack of organizational support, as well as fears that oncology clinical nurse specialists will "encroach" on doctors' powers. In contrast, an oncology clinical nurse specialist is found to be universally more accessible to patients and their families and can help physicians deal with difficult workloads, among other advantages. Conclusions: This role offers a myriad of gains for cancer patients, oncology physicians, and the healthcare system. The literature demonstrates that it is a necessary role, albeit one that brings specific implementation challenges. [ABSTRACT FROM AUTHOR]

In vivo studies questioned the ability of Langerhans cells (LCs) to mediate CD8+ T cell priming. To address this issue, we used intradermal immunization with plasmid DNA, a system in which activation of CD8+ T cells depends on delayed kinetics of Ag presentation. We found that dendritic cells (DCs) located in the skin at the time of immunization have limited ability to activate CD8+ T cells. This activity was mediated by a second generation of DCs that differentiated in the skin several days after immunization, as well as by lymph node-resident DCs. Intriguingly, CD8+ T cell responses were not affected following treatment with clodronate liposomes, immunization of CCR22/2 mice, or local neutralization of CCL20. This suggests that local, rather than blood-derived, DC precursors mediate CD8+ T cell priming. Analysis of DC differentiation in the immunized skin revealed a gradual increase in the number of CD11c+ cells, which reached their maximum 2 wk after immunization. A similar differentiation kinetics was observed for LCs, with the majority of differentiating LCs proliferating in situ from epidermal precursors. By using B6/Langerin-diphtheria toxin receptor chimeric mice and LC ablation, we demonstrated that epidermal LCs were crucial for the elicitation of CD8+ T cell responses in vivo. Furthermore, LCs isolated from lymph nodes 2 wk after immunization contained the immunization plasmid and directly activated Ag-specific CD8+ T cells ex vivo. Thus, these results indicate that second-generation Ag-expressing LCs differentiating from epidermal precursors directly prime CD8+ T cells and are essential for optimal cellular immune responses following immunization with plasmid DNA. [ABSTRACT FROM AUTHOR]

Abstract: Cluster flight is a term used for describing multiple satellites that are being held within pre-defined minimum and maximum distances for long time intervals, possibly the entire mission. This technology is required for a myriad of space architectures and missions, including disaggregated space architectures. Whereas the literature is abundant with works on control laws for satellite formation flying, there are only a handful of works on control of cluster flight. The purpose of the current work is to develop a cluster flight control algorithm, which is able to keep the satellites of the cluster within pre-specified minimum and maximum distances, while utilizing small amounts of propellant. The newly developed algorithm relies on the natural inter-satellite distance dynamics. The algorithm incorporates realistic mission constraints, such as constant-magnitude thrust, and is implemented in feedback form, steering the mean elements to judiciously selected reference values. Simulations indicate that a few tens of grams of propellent are sufficient for operating a cluster flight mission in excess of 1 year, using low specific-impulse thrusters. [Copyright &y& Elsevier]

Authors present an overview of the contemporary applications of acoustic emission method for the diagnosis of non-standard operating conditions of machines with rotating parts. The main attention is focused on operational diagnostics of axial and radial bearings. In part are reviewed also options of supplementary use of the AE method for the diagnosis of damage of gears and real gearboxes. This overview of published results is confronted with the practical experiences gained during the implementation of several projects at Laboratory of Acoustic Emission of the Institute of Machine and Industrial Design in Brno University of Technology. [ABSTRACT FROM AUTHOR]

The Tn antigen (GalNAcα- O-Ser/Thr) is a well-established tumor-associated marker which represents a good target for the design of anti-tumor vaccines. Several studies have established that the binding of some anti-Tn antibodies could be affected by the density of Tn determinant or/and by the amino acid residues neighboring O-glycosylation sites. In the present study, using synthetic Tn-based vaccines, we have generated a panel of anti-Tn monoclonal antibodies. Analysis of their binding to various synthetic glycopeptides, modifying the amino acid carrier of the GalNAc(*) (Ser* vs Thr*), showed subtle differences in their fine specificities. We found that the recognition of these glycopeptides by some of these MAbs was strongly affected by the Tn backbone, such as a S*S*S* specific MAb (15G9) which failed to recognize a S*T*T* or a T*T*T* structure. Different binding patterns of these antibodies were also observed in FACS and Western blot analysis using three human cancer cell lines (MCF-7, LS174T and Jurkat). Importantly, an immunohistochemical analysis of human tumors (72 breast cancer and 44 colon cancer) showed the existence of different recognition profiles among the five antibodies evaluated, demonstrating that the aglyconic part of the Tn structure (Ser vs Thr) plays a key role in the anti-Tn specificity for breast and colon cancer detection. This new structural feature of the Tn antigen could be of important clinical value, notably due to the increasing interest of this antigen in anticancer vaccine design as well as for the development of anti-Tn antibodies for in vivo diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Memory CD8+ T lymphocytes play a central role in protective immunity. In attempt to increase the frequencies of memory CD8+ T cells, repeated immunizations with viral vectors are regularly explored. Lentivectors have emerged as a powerful vaccine modality with relatively low pre-existing and anti-vector immunity, thus, thought to be ideal for boosting memory T cells. Nevertheless, we found that lentivectors elicited diminished secondary T-cell responses that did not exceed those obtained by priming. This was not due to the presence of anti-vector immunity, as limited secondary responses were also observed following heterologous prime-boost immunizations. By dissecting the mechanisms involved in this process, we demonstrate that lentivectors trigger exceptionally slow kinetics of antigen expression, while optimal activation of lentivector-induced T cells relays on durable expression of the antigen. These qualities hamper secondary responses, since lentivector-encoded antigen is rapidly cleared by primary cytotoxic T cells that limit its presentation by dendritic cells. Indeed, blocking antigen clearance by cytotoxic T cells via FTY720 treatment, fully restored antigen presentation. Taken together, while low antigen expression is expected during secondary immunization with any vaccine vector, our results reveal that the intrinsic delayed expression kinetics of lentiviral-encoded antigen, further dampens secondary CD8+ T-cell expansion. [ABSTRACT FROM AUTHOR]

An interview with Ken Salazar, U.S. Department of Interior Secretary is presented. When ask to describe the role of his agency in the promotion of Latino culture, Salazar mentions that his role is to preserve the country's natural resources and its heritage. Salazar also defended having a National Museum of the American Latino saying that such establishment is important as the country is at the critical point of its history. He also cites the different sites that his office manages.

An interview with women activist Teresa Ulloa Ziáurriz is presented. When asked about how she started as an advocate against human trafficking, Ziáurriz mentions that she started working as a lawyer for union trades when she was asked to help two young girls who were gang raped. Ziáurriz also discusses on how they could prevent human trafficking. She also mentions on how the governments can help in the transformation of the society and in the treatment of women in general.

Objective To assess the frequency of the D1152H mutation in the CFTR gene in normal individuals, in cystic fibrosis (CF) patients and in the setting of prenatal diagnosis. Setting A database analysis of sequential screening results seen at the Sheba Medical Center, Israel, between 2001 and 2010. Methods We retrospectively analyzed the frequency of D1152H in a large cohort of healthy individuals who were screened as part of a routine prenatal care programme, in individuals referred due to CF-related symptoms and in the setting of prenatal diagnosis. Results We found one asymptomatic homozygous female and 195 D1152H carriers among 49,940 healthy individuals screened, establishing a carrier rate of 1:255 for this mutation. We detected D1152H in nine of 103 individuals referred due to CF-related symptoms. Four suffered from respiratory symptoms and five from congenital bilateral absence of the vas deferens (CBAVD). During this period D1152H was detected in three pregnancies, two of which were aborted. Conclusion The increased frequency of D1152H in individuals referred due to CF-related symptoms compared with healthy individuals included in the CF carrier screening programme (P < 0.001) clearly indicates that it is a disease-causing mutation. [ABSTRACT FROM AUTHOR]

Abstract: We isolated and characterized a mango (Mangifera indica L.) cDNA homolog of the ethylene receptor gene ERS1, designated MiERS1. Genomic Southern blot analysis suggested the existence of a second gene with homology to MiERS1. Spatial and temporal expression patterns of MiERS1 were first studied during fruitlet drop and compared with those of a previously identified MiETR1 gene that encodes an ETR1-type ethylene receptor. Experiments were conducted on developing fruitlet explants in which fruitlet abscission was induced by ethephon treatment. Northern analysis revealed a notable increase in MiERS1 mRNA levels in the fruitlet’s activated abscission zone within 24 h of ethephon application, followed by a decreasing pattern 48 h post-treatment. A transient, albeit lesser, increase in MiERS1 mRNA levels was also observed in treated fruitlet seed and mesocarp tissues. In contrast, in the abscission zone, accumulation of MiETR1 transcript remained unchanged; a temporal increase in MiETR1 transcript level was observed in the fruitlet mesocarp, whereas in the seed, MiETR1 expression had already dropped by 24 h. Expression profiles of MiERS1 and MiETR1 were then studied during fruit ripening. In agreement with a previous study and coinciding with the climacteric rise in ethylene production, RNA blot analysis revealed that during fruit ripening, MiETR1 mRNA level increases in both mesocarp and seed tissues. Unexpectedly, however, in those same tissues, MiERS1 transcript accumulation was barely detected. Collectively, our data highlight MiERS1’s possible specific function in regulating fruitlet abscission rather than fruit ripening. [Copyright &y& Elsevier]

Abstract: TP53 plays a pivotal role in the process of DNA repair and apoptosis. In 10–20% of patients with chronic lymphocytic leukemia (CLL), the TP53 pathway is affected. In this study, we analyzed the TP53 mutation status in 2435 consecutive CLL samples, including 1287 diagnostic samples and 1148 samples during follow-up, using FASAY (Functional Analysis of Separated Alleles in Yeast) and direct sequencing. In a cohort of 1287 diagnostic CLL samples, we identified 237 cases with TP53 variants, including mutations, temperature-sensitive variants, deletions, insertions and aberrant splicing variants (18.4%). In 1148 follow-up samples, no TP53 clonal evolution was observed. [Copyright &y& Elsevier]

Although oral dendritic cells (DCs) were shown to induce cell-mediated immunity, the identity and function of the various oral DC subsets involved in this process is unclear. In this study, we examined the mechanisms used by DCs of the buccal mucosa and of the lining mucosa to elicit immunity. After plasmid DNA immunization, buccally immunized mice generated robust local and systemic CD8+ T cell responses, whereas lower responses were seen by lining immunization. A delayed Ag presentation was monitored in vivo in both groups; yet, a more efficient presentation was mediated by buccal-derived DCs. Restricting transgene expression to CD11c+ cells resulted in diminished CD8+ T cell responses in both oral tissues, suggesting that immune induction is mediated mainly by cross-presentation. We then identified, in addition to the previously characterized Langerhans cells (LCs) and interstitial dendritic cells (iDCs), a third DC subset expressing the CD103+ molecule, which represents an uncharacterized subset of oral iDCs expressing the langerin receptor (Ln+ iDCs). Using Langerin-DTR mice, we demonstrated that whereas LCs and Ln+ iDCs were dispensable for T cell induction in lining-immunized mice, LCs were essential for optimal CD8+ T cell priming in the buccal mucosa. Buccal LCs, however, failed to directly present Ag to CD8+ T cells, an activity that was mediated by buccal iDCs and Ln+ iDCs. Taken together, our findings suggest that the mechanisms engaged by oral DCs to prime T cells vary between oral mucosal tissues, thus emphasizing the complexity of the oral immune network. Furthermore, we found a novel regulatory role for buccal LCs in potentiating CD8+ T cell responses. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Auditory processing disorder (APD) is typically characterised by difficulties in ‘listening’, particularly to speech in a noisy environment, despite normal peripheral function. In school-age children, APD has attracted considerable interest because of suspicions that it may lead to learning difficulties, especially affecting language and literacy. Here, we evaluated auditory and cognitive abilities in a group of children referred for an auditory evaluation on the grounds of a suspected auditory processing disorder (susAPD), and in age-matched children who were typically developing, in order to determine the extent to which any deficits in cognitive abilities could be related to auditory deficits. Methods: A battery of auditory and cognitive tests was applied to 20 susAPD school-age children, all reported as having listening/hearing problems but performing within normal limits for standard audiometric assessments. Also tested was a group of 28 age-matched controls. The auditory tasks consisted of two simple same/different discrimination tasks, one using speech, and one nonspeech. The cognitive evaluation comprised a vocabulary test, a test of grammar and four non-verbal IQ measures. Symptoms of Attention Deficit Hyperactivity Disorder (ADHD) were assessed in the susAPD group through a standardised questionnaire. Results: A significant proportion of susAPD children appeared to display genuine auditory deficits evidenced by poor performance on at least one of the auditory tasks, although about 1/3 had no detectable deficit. Children in the susAPD group scored consistently lower than the controls on cognitive measures that were both verbal (vocabulary and grammar) and non-verbal. Strikingly, susAPD children with relatively good auditory performance did not differ in cognitive ability from susAPD children with poor auditory performance. Similarly, within-group correlations between auditory and cognitive measures were weak or non-existent. Measures of ADHD did not correlate with any aspect of auditory or cognitive performance. Conclusions: Although children suspected of having APD do show, on average, poorer performance on a number of auditory tasks, the presence or absence of an auditory deficit appears to have little impact on the development of the verbal and non-verbal skills tested here. [Copyright &y& Elsevier]

This contribution treats the evaluation of degradation processes appearing during the cyclic loading of the samples from Al alloys EN AW-2017/T4 and EN AW-6082/T6. Two NDT methods have been applied in this case, namely the acoustic emission (AE) and the X-ray diffraction used to detect the microstructural changes in the material during the fatigue damages as well as to report the microcracks appearing afterwards. These measurements have been completed with reports of changes to the loading (resonance) frequency coming from fatigue loading equipment. Moreover, the article describes the records of AE signal coming from a newly developed AE analyser. The main advantage of this analyser (compared with current AE measuring systems) is continuous sampling and full recording of the entire AE signals. The AE detects the changes in the material during the damage accumulation. It is a problem to identify such changes. The structure monitoring by means of X-ray diffraction assists in identifying the AE sources. The results imply a correlation between the AE signal changes and the changes of so-called mosaic blocks of crystal structure detected by means of X-ray diffraction. [ABSTRACT FROM AUTHOR]

The reduction of a series of α-cyanostilbenes with Sml2 was studied in THF in the presence of various proton donors. No reaction occurred in the presence of the alcohols TFE, i-PrOH and t-BuOH. In the presence of MeOH, water and ethylene glycol the reactions occurred; however in the presence of water and ethylene glycol they were too fast for kinetic determinations (τ½ < 1 ms). Reactions with MeOH were first order in Sml2 and first order in the substrate. The order in MeOH varies as a function of its concentration and the plot of log k vs log [MeOH] is sigmoidal. Comparison of the kinetic isotope effect and the incorporation isotope effect suggests that, counterintuitively, protonation of the radical anion takes place on the carbon β to the cyano group. It is concluded that proton donors that form complexes with Sml2 expand the range of substrates that can be reduced by Sml2. This is due to their proximity to the radical anion as it is formed. This short-lived radical anion cannot be efficiently trapped by a proton donor from the bulk medium. A protocol is herein suggested as to when proton donors which complex to Sml2, e.g. MeOH, water and ethyleneglycol should be used, and when it is recommended to use noncomplexing proton donors, e.g. TFE, i-PrOH and t-BuOH, to induce reaction. [ABSTRACT FROM AUTHOR]

A simple device to check the machine output in rotational mode is described. Integral and instantaneous beam output in absolute dose can be measured and analyzed in a very simple manner. A method to correlate the results with the value obtained during the machine calibration in static beam and the reference value used by the treatment planning system for dose calculation in rotation beam is also described. Using this method and device, the daily output can be performed in rotational conditions which are closer to the treatment conditions. Measurement results using this device show differences in the beam output between static and rotational delivery which have to be considered carefully during the calibration process. [ABSTRACT FROM AUTHOR]

The objective of this research was to evaluate the effects of 2 levels of raw milk Somatic cell count (SCC) on the composition of Prato cheese and on the microbiological and sensory changes of Prato cheese throughout ripening. Two groups of dairy cows were selected to obtain low-SCC (<200,000 cells/mL) and high-SCC (>700,000 cells/mL) milks, which were used to manufacture 2 vats of cheese. The pasteurized milk was evaluated according to the pH, total solids, fat, total protein, lactose, standard plate count, coliforms at 45°C, and Salmonella spp. The cheese composition was evaluated 2 d after manufacture. Lactic acid bacteria, psychrotrophic bacteria, and yeast and mold counts were carried out after 3, 9, 16, 32, and 51 d of storage. Salmonella spp., Listeria monocytogenes, and coagulase-positive Staphylococcus counts were carried out after 3, 32, and 51 d of storage. A 2 x 5 factorial design with 4 replications was performed. Sensory evaluation of the cheeses from low- and high-SCC milks was carried out for overall acceptance by using a 9-point hedonic scale after 8, 22, 35, 50, and 63 d of storage. The somatic cell levels used did not affect the total protein and salt:moisture contents of the cheeses. The pH and moisture content were higher and the clotting time was longer for cheeses from high-SCC milk. Both cheeses presented the absence of Salmonella spp. and L. monocytogenes, and the coagulase-positive Staphylococcus count was below 1 x 10² cfu/g throughout the storage time. The lactic acid bacteria count decreased significantly during the storage time for the cheeses from both low- and high-SCC milks, but at a faster rate for the cheese from high-SCC milk. Cheeses from high-SCC milk presented lower psychrotrophic bacteria counts and higher yeast and mold counts than cheeses from low-SCC milk. Cheeses from low-SCC milk showed better overall acceptance by the consumers. The lower overall acceptance of the cheeses from high-SCC milk may be associated with texture and flavor defects, probably caused by the higher proteolysis of these cheeses. [ABSTRACT FROM AUTHOR]

A cocrystal of gabapentin and oxalic acid has been prepared employing a strategy based on a hydrogen-bonded synthon described by the graph set notation R 42(8). High throughput techniques and solvent drop grinding were used along with traditional crystallization methods, including crystallization in aqueous solutions at various pH. A number of new solid forms have been detected. The cocrystal of gabapentin and oxalic acid was fully characterized including single crystal structure analysis, which revealed the R 42(8) synthon. [ABSTRACT FROM AUTHOR]

The objective of this research was to evaluate the effect of 2 levels of somatic cell counts (SCC) in raw milk on Prato cheese composition, protein and fat recovery, cheese yield, and ripening. A 2 x 6 factorial design with 3 replications was performed in this study: 2 levels of SCC and 6 levels of storage time. Initially, 2 groups of dairy cows were selected to obtain low (<200,000 cells/ mL) and high (>600,000 cells/mL) SCC in milks that were used to manufacture 2 vats of cheese: 1) low SCC and 2) high SCC. Milk, whey, and cheese compositions were evaluated; clotting time was measured; and cheese yield, protein recovery, and fat recovery were calculated. The cheeses were evaluated after 5, 12, 19, 26, 33, and 40 d of ripening according to pH, moisture, pH 4.6 soluble nitrogen, 12% trichloroacetic acid soluble nitrogen as a percentage of total nitrogen, and firmness. High-SCC milk presented significantly higher total protein and nonprotein nitrogen and lower true protein and casein concentrations than did low-SCC milk, indicating an increased whey protein content and a higher level of proteolysis. Although the pH of the milk was not affected by the somatic cell level, the cheese obtained from high-SCC milk presented significantly higher pH values during manufacture and a higher clotting time. No significant differences in cheese yield and protein recovery were observed for these levels of milk somatic cells. The cheese from high-SCC milk was higher in moisture and had a higher level of proteolysis during ripening, which could compromise the typical sensory quality of the product. [ABSTRACT FROM AUTHOR]

Usher syndrome is both genetically and phenotypically heterogeneous. Traditionally, the condition has been classified into three clinical types, differentiated by the severity and progression of the hearing impairment and by the presence or absence of vestibular symptoms. Recent advances in molecular genetics have enabled researchers to study the phenotypic expression in confirmed molecular groups of Usher. In response to the expansion of clinical and genetic information on Usher, we report an up to date review of the different clinical forms of Usher in known molecular groups and use the emerging evidence to appraise the diagnostic utility of the traditional classification of Usher. Our findings undermine the traditional view that the clinical types of Usher have distinct genetic causes. The pleiotropic effects of some of the major causes of Usher lead to considerable overlap between the different clinical types, with very little evidence for phenotypic-genotypic correlations. The novel synthesis emerging from this review suggests more productive approaches to the diagnosis of Usher in hearing-impaired children which would provide more accurate prognostic information to families. [ABSTRACT FROM AUTHOR]