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Background Aims Materials and Methods Results Conclusions Preterm birth (PTB) is a major pregnancy complication. There is evidence that a short cervical length in mid‐pregnancy may predict women at increased risk of PTB.To evaluate the utility of population‐based, transabdominal cervical length (TACL) measurement screening in mid‐pregnancy for PTB prediction in women.A transabdominal approach was initially performed, with a transvaginal (TVCL) approach offered when the TACL was <35 mm, could not be accurately measured, or the pregnancy had risk factors for PTB. TACL was compared to the directly related TVCL, when both were performed at the same assessment. Women with risk factors of PTB were included when they had both TACL and TVCL measurements performed at the same visit.Data were provided for 9355 singleton pregnancies from 13 participating imaging centres. A transabdominal approach was used in 9006 (96.3%), including 682 (7.3%) TVCL combined with TACL. There were 349 (3.7%) women who had TVCL only. The median TACL was longer (40 mm) than the TVCL (38 mm). In 682 paired TACL and TVCL measurements, TACL <35 mm correctly identified 96.2% of pregnancies with TVCL <25 mm, compared with 65.4% of cases when using a TACL <30 mm. A TVCL <25 mm occurred in 59 (0.6%) women. A TACL <35 mm was associated with birth <37 weeks of gestation in 12.1% of women and birth <32 weeks of gestation in 3.9%.Universal TACL is a feasible option for population screening of cervical length in a low‐risk population, progressing to TVCL if the TACL is <35 mm or the cervix cannot be transabdominally accurately measured. [ABSTRACT FROM AUTHOR]

This article introduces a new evidence‐based clinical practice guideline (CPG) for sonographers; Ultrasound assessment of the gravid cervix to assess for risk of spontaneous preterm birth (sPTB). The purpose of this new CPG is to provide evidence‐based guidance for sonographers in Australia and New Zealand when making decisions on how and when they should sonographically assess the cervix in the gravid patient. Clinical questions relevant to the sonographic assessment of the gravid cervix were developed to inform the CPG. The primary sources to answer the clinical questions were relevant, existing CPGs. Recommendations in these existing CPGs were appraised for the level of evidence on which they were based and adapted for use in the new CPG. New recommendations were adapted from 19 existing CPGs rated as being based on best evidence and were applicable to three specific patient groups, each at different risk for sPTB. 'How to Guidance', statements about safety, acceptability, feasibility of ultrasound techniques, sonographer training and supplementary material were also developed using information from existing CPGs, relevant literature and the clinical experience of clinical guideline group members. The CPG recommendations, 'how to guides' and areas of future research are presented in this article. The full guideline and its supplementary materials are available at https://www.sonographers.org/resources-tools/clinical-guidance. [ABSTRACT FROM AUTHOR]

Block polyethers comprised of poly(propylene oxide) (PPO) and poly(ethylene oxide) (PEG or PEO) segments form the basis of ABA‐type PEO‐b‐PPO‐b‐PEO poloxamer materials. The inverse architecture with an internal hydrophilic PEO segment flanked by hydrophobic blocks can be difficult to prepare with control of architecture by use of traditional anionic polymerization. These oxyanionic polymerizations are plagued by chain‐transfer‐to‐monomer side reactions that occur with substituted epoxides such as propylene oxide (PO). Herein, we report a new method for the preparation of block polymers through a controlled polymerization involving a N‐Al Lewis adduct catalyst and an aluminum alkoxide macroinitiator. The Lewis pair catalyst was able to chain‐extend commercial PEO macroinitiators to prepare di‐, tri‐, and pentablock polyethers with low dispersity and reasonable monomer tolerance. Chain extension was confirmed using size exclusion chromatography and diffusion ordered nuclear magnetic resonance spectroscopy. The resulting block polymers were additionally analyzed with small‐angle X‐ray scattering to correlate the morphology to molecular architecture. [ABSTRACT FROM AUTHOR]

Neuronal maturation is the phase during which neurons acquire their final characteristics in terms of morphology, electrical activity, and metabolism. However, little is known about the metabolic pathways governing neuronal maturation. Here, we investigate the contribution of the main metabolic pathways, namely glucose, glutamine, and fatty acid oxidation, during the maturation of primary rat hippocampal neurons. Blunting glucose oxidation through the genetic and chemical inhibition of the mitochondrial pyruvate transporter reveals that this protein is critical for the production of glutamate, which is required for neuronal arborization, proper dendritic elongation, and spine formation. Glutamate supplementation in the early phase of differentiation restores morphological defects and synaptic function in mitochondrial pyruvate transporter-inhibited cells. Furthermore, the selective activation of metabotropic glutamate receptors restores the impairment of neuronal differentiation due to the reduced generation of glucose-derived glutamate and rescues synaptic local translation. Fatty acid oxidation does not impact neuronal maturation. Whereas glutamine metabolism is important for mitochondria, it is not for endogenous glutamate production. Our results provide insights into the role of glucose-derived glutamate as a key player in neuronal terminal differentiation. Synopsis: Glucose oxidation sustains glutamate production and the terminal differentiation of neurons. Blunting glucose oxidation affects glutamate levels, neuronal maturation in terms of morphology and synaptic activity, and impairs protein synthesis. Genetic and chemical inhibition of the mitochondrial pyruvate transporter reduces glutamate levels, and impairs neuronal complexity, synaptogenesis, and synaptic transmission. The combination of a reduction in glutamate levels and altered mitochondrial function upon inhibition of glucose oxidation decreases the energy-demanding process of protein translation. The activation of group I metabotropic glutamate receptors rescues dendritic architecture, spine morphology defects, and restores local translation of synaptic proteins. Glucose oxidation sustains glutamate production and the terminal differentiation of neurons. Blunting glucose oxidation affects glutamate levels, neuronal maturation in terms of morphology and synaptic activity, and impairs protein synthesis. [ABSTRACT FROM AUTHOR]

This article presents a study on folliculitis decalvans (FD) and frontal fibrosing alopecia (FFA) in women. The study found that FD is a rare condition characterized by hair loss, pustules, and crusts on the scalp, and it has a significant psychosocial impact. The etiology of FD remains unclear, but Staphylococcus aureus and the host's immune response may play a role. The study also found that FFA primarily affects women, with common symptoms including erythema, pruritus, pustules, and pain. The study suggested that autoimmune factors and environmental triggers may contribute to the development of FD. Dermatologists should be aware of the unique characteristics of FD in women for early diagnosis and appropriate treatment. [Extracted from the article]

In this paper a modeling method is validated at multiple scales for the seismic performance of multiblock tower structure (MTS). MTS are a proposed concept for large‐capacity gravitational energy storage that will enable renewable energy sources. The structure modeled is a tower of 7144 nominally identical blocks arranged in a 38‐layered annular pattern with no adhesive mechanisms between the blocks or the blocks and the foundation. The level set discrete element method is used to model the dynamics of the tower structure experiencing a ground motion. Experimental determination of each model parameter is shown from the use of individual blocks before construction. Close comparisons to experimental results are shown for the dynamic motion of the tower over a full ground motion time history for multiple scales, materials and ground motions. When the tower was brought to failure, the two ground motions used produced distinct failure modes of the tower showing both a peeling and buckling behavior. Both the effect of the friction coefficient and unequal block heights are investigated. Friction coefficient has a noticeable effect on the amplitude of motion of the tower while the unevenness of the block heights affects mostly the structural speed. [ABSTRACT FROM AUTHOR]

Summary: Astra, deployed in 2018, was the first petascale supercomputer to utilize processors based on the ARM instruction set. The system was also the first under Sandia's Vanguard program which seeks to provide an evaluation vehicle for novel technologies that with refinement could be utilized in demanding, large‐scale HPC environments. In addition to ARM, several other important first‐of‐a‐kind developments were used in the machine, including new approaches to cooling the datacenter and machine. This article documents our experiences building a power measurement and control infrastructure for Astra. While this is often beyond the control of users today, the accurate measurement, cataloging, and evaluation of power, as our experiences show, is critical to the successful deployment of a large‐scale platform. While such systems exist in part for other architectures, Astra required new development to support the novel Marvell ThunderX2 processor used in compute nodes. In addition to documenting the measurement of power during system bring up and for subsequent on‐going routine use, we present results associated with controlling the power usage of the processor, an area which is becoming of progressively greater interest as data centers and supercomputing sites look to improve compute/energy efficiency and find additional sources for full system optimization. [ABSTRACT FROM AUTHOR]

The paper presents the VEGA Online web service, which includes a set of freely available tools deriving from the development of the VEGA suite of programs. In detail, the paper is focused on two tools: the VEGA Web Edition (WE) and the Score tool. The former is a versatile file format converter including relevant features for 2D/3D conversion, for surface mapping and for editing/preparing input files. The Score application allows rescoring docking poses and in particular includes the MLP Interactions Scores (MLPInS) for describing hydrophobic interactions. To the best of our knowledge, this web service is the only available resource by which one can calculate both the virtual log P of a given input molecule according to the MLP approach plus the corresponding MLP surface. [ABSTRACT FROM AUTHOR]

Gyrate atrophy of choroid and retina (GACR) is a chorioretinal degeneration caused by pathogenic variants in the gene encoding ornithine aminotransferase (OAT), an enzyme mainly expressed in liver. Affected patients have increased ornithine concentrations in blood and other body fluids and develop progressive constriction of vision fields leading to blindness. Current therapies are unsatisfactory and better treatments are highly needed. In two mouse models of OAT deficiency that recapitulates biochemical and retinal changes of GACR, we investigated the efficacy of an intravenously injected serotype 8 adeno‐associated (AAV8) vector expressing OAT under the control of a hepatocyte‐specific promoter. Following injections, OAT‐deficient mice showed reductions of ornithine concentrations in blood and eye cups compared with control mice injected with a vector expressing green fluorescent protein. AAV‐injected mice showed improved electroretinogram response and partial restoration of retinal structure up to one‐year post‐injection. In summary, hepatic OAT expression by AAV8 vector was effective at correction of hyperornithinemia and improved function and structure of the retina. In conclusion, this study provides proof‐of‐concept of efficacy of liver‐directed AAV‐mediated gene therapy of GACR. Synopsis: Deficiency of ornithine aminotransferase (OAT) results in increased plasma ornithine concentrations and retinal toxicity, especially in the retinal pigment epithelium (RPE). This study investigated liver‐directed gene transfer for OAT deficiency. Intravenous injections of AAV8 vector delivering OAT gene to hepatocytes reduced ornithine concentrations in plasma and eye.The treatment improved function and structure of the retina. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted in Lusaka, Zambia, on severe cutaneous adverse reactions (SCARs). SCARs are rare and poorly understood, especially in African settings. The study aimed to describe the socio-demographic, clinical, and laboratory characteristics of SCAR patients in Zambia. The study found that SCAR primarily affects young females, with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) being the most common forms. The study also identified certain HLA haplotypes that may be associated with SCAR. Overall, the study provides valuable insights into SCAR in the Zambian population. [Extracted from the article]

Genetic and nongenetic factors are involved in the pathogenesis of immune‐mediated inflammatory diseases (IMIDs). The best‐known genetic factor for susceptibility to IMIDs is the human leukocyte antigen (HLA). The aim of the present study was to evaluate the association of HLA class II genes with the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) in the Paraguayan population. We included 254 patients with IMIDs (101 SLE, 103 RA, and 50 SSc) and 50 healthy controls. The haplotypes of five genes corresponding to HLA class II genes and their relationship to the IMIDs studied were determined. Note that 84.6% were women, with a mean age of 43.4 ± 14 years. Among the associated HLA alleles, we found the previously identified risk factors in other populations like HLA‐DRB1*03:01 and HLA‐DRB1*14:02 for RA, as well as new ones not previously identified, such as DPA1*02:01 for SLE and, DB1*02:01 for RA and SSc. In the genetic association analysis, already known associations have been replicated, and unpublished associations have been identified in Paraguayan patients with IMIDs. This is the first genetic association study in Paraguayan patients with IMIDs. [ABSTRACT FROM AUTHOR]

This article, titled "OP16.03: First trimester ultrasound markers for the prediction of adverse pregnancy outcomes in monochorionic diamniotic pregnancies," explores the role of intertwin discordance of Crown–rump length (CRL) and nuchal translucency (NT) in predicting Twin–twin transfusion syndrome (TTTS) or selective growth restriction (sIUGR) in monochorionic diamniotic (MCDA) twin pregnancies. The study analyzed data from 183 MCDA pregnancies and found that NT discordance ≥20% was associated with a higher incidence of TTTS, while CRL discordance ≥10% was associated with a higher incidence of sIUGR. However, the predictive value of these markers was found to be low. [Extracted from the article]

Background: Routine cervical length (CL) measurement at the mid‐pregnancy ultrasound is a central recommendation of the Western Australian Preterm Birth Prevention Initiative (Initiative). Aim: To evaluate the perceptions and changes in practice of Western Australian obstetric care providers regarding routine CL screening for preterm birth (PTB) prevention following the Initiative introduction. Methods: Two self‐administered questionnaires were completed by providers from a range of practices. The first was during site visits with the Initiative Outreach team in 2015–2016. The questionnaire was re‐issued in 2021 via online dissemination. Participant demographic data and opinions on CL screening for PTB prevention were collected. Results: Two hundred and fourteen providers participated in 2015–2016 and 109 in 2021. In both surveys, providers were more likely to discuss transvaginal CL screening with high‐risk women (48.1%, 76.1%; P < 0.001) compared with low‐risk (7.5%, 18.3%; P = 0.002) and the importance of CL screening (13.5%, 40.4%; P < 0.001), in 2015–2016 and 2021, respectively. Responses relating to CL screening, including what constitutes a short cervix on ultrasound were varied. A transabdominal CL <35 mm was classified as short by 46.2% and 37.6% and <25 mm on transvaginal ultrasound by 49.1% and 64.2%, in the respective surveys. Most providers ceased progesterone (68.6%, 75.2%) at >28 weeks gestation. Conclusions: Providers focused on women with overt PTB risk factors, rather than a universal CL screening approach. Although there was improvement between the surveys, the definition of what constitutes a short cervix on ultrasound and how to treat and monitor women with a short CL remained varied. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to evaluate the effectiveness of interventions through Physical Education (PE) exercises on bone mineral content (BMC) and density (BMD) of children and adolescents. The research was conducted using the online electronic databases PubMed, Science Direct, Web of Science and Scopus (March 2021). The analysis was restricted to school-based studies that examined the effect of PE interventions on BMC and BMD in schoolchildren (<18 years old). Standardised mean differences (SMD) with 95% confidence interval (CI) and random-effects models were calculated. The heterogeneity and inconsistency of the studies were estimated using Cochran's Q-statistic and I2, respectively. Twenty-two studies with 2,556 participants were selected. PE interventions were associated with a significant increase in BMC (SMD = 1.348; 95% CI, 1.053–1.643) and BMD (SMD = 0.640; 95% CI, 0.417–0.862). Femoral neck subgroup analysis indicate an increase in BMC for boys (SMD = 1.527; 95% CI, 0.990–2.065) and girls (SMD = 1.27; 95% CI, 0.782–1.767), and in BMD for boys (SMD = 0.518; 95% CI, 0.064–0.972) and girls (SMD = 0.817; 95% CI, 0.349–1.284). Finally, increases are reported in the lumbar spine BMC for boys (SMD = 1.860; 95% CI, 1.018–2.700) and girls (SMD = 1.275; 95% CI, 0.782–1.767). This meta-analysis provides insights into the effectiveness of interventions aimed at including physical exercise in PE on bone mass, suggesting that increasing the proportion of curriculum time allocated to PE may improve students' BMD and BMC, especially in the femoral neck and lumbar spine. [ABSTRACT FROM AUTHOR]

Purpose: The Western Australian Preterm Birth Prevention Initiative recommends a transabdominal cervical length (TACL) measurement at the mid‐pregnancy ultrasound to screen low‐risk women for preterm birth risk. In view of this recommendation, we assessed the inter‐observer consistency of TACL screening in mid‐pregnancy. Methods: Routinely collected mid‐pregnancy TACL ultrasound images were graded from 0 to 4 according to the anatomical landmarks identified by a single expert. A random selection of 10 images of each grade were disseminated in an electronic survey to determine inter‐ and intra‐observer variations in the classification of the cervical image. Results: A total of 244 participants graded 50 TACL images. Six participants repeated the grading. Overall agreement to the exact initial grade for all images was 49.6%, highest for images at both ends of the spectrum (83% Grade 0 and 70.4% for Grade 4). Overall agreement to the initial diagnostic Grades 3 and 4 was 75.3% (95% CI 74.5–76.0%) and was higher when the maternal bladder was empty. There was moderate inter‐rater agreement (κ = 0.42) for Grades 3 and 4 (diagnostic) or Grades 1 and 2 (non‐diagnostic). The intra‐rater agreement was fair to good (κ = 0.59, 95% CI 0.49–0.70) for those who repeated the assessment (including the expert grader). Conclusions: Sonographic CL screening is considered an important tool for the identification of women at high risk of preterm birth. Image classification of TACL performed poorly compared with previous studies assessing transvaginal cervical length. Improved reliability and measurement consistency may be achieved through high levels of quality assurance, ongoing training and image audit. [ABSTRACT FROM AUTHOR]

Memristors, Flash, and related nonvolatile analog device technologies offer in‐memory computing structures operating in the analog domain, such as accelerating linear matrix operations in array structures. These take advantage of analog tunability and large dynamic range. At the other side, content addressable memories (CAM) are fast digital lookup tables which effectively perform nonlinear Boolean logic and return a digital match/mismatch value. Recently, nonvolatile analog CAMs have been presented merging analog storage and analog search operations with digital match/mismatch output. However, CAM blocks cannot easily be inserted within a larger adaptive system due to the challenges of training and learning with binary outputs. Here, a missing link between analog crossbar arrays and CAMs, namely a differentiable content addressable memory (dCAM), is presented. Utilizing nonvolatile memories that act as a "soft" memory with analog outputs, dCAM enables learning and fine‐tuning of the memory operation and performance. Four applications are quantitatively evaluated to highlight the capabilities: improved data pattern storage, improved robustness to noise and variability, reduced energy and latency performance, and an application to solving Boolean satisfiability optimization problems. The use of dCAM is envisioned as a core building block of fully differentiable computing systems employing multiple types of analog compute operations and memories. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the applicability of four existing fetal growth charts to a local tertiary hospital obstetric population. Method: Four existing fetal growth charts (the Raine study reference charts, INTERGROWTH‐21st charts, World Health Organization (WHO) fetal growth study charts and Australasian Society for Ultrasound in Medicine (ASUM) endorsed Campbell Westerway charts were compared using data from 11651 singleton pregnancy ultrasound scans at King Edward Memorial Hospital (KEMH). The 3rd, 10th, 50th 90th and 97th percentile curves for abdominal circumference (AC) biometry for the KEMH data were calculated and the four primary correlation parameters from fitted 3rd order polynomials (a, b, c and d) were used to generate like‐for‐like comparisons for all charts. Results: The overall comparisons showed a significant variation with different growth charts, giving different percentiles for the same fetal AC measurement. INTERGROWTH‐21st percentile curves tended to fall below those of other charts for AC measurements. Both the Raine Study charts and ASUM charts were the charts of closest overall fit to the local data. Conclusion: Our data show the Raine Study charts are the most appropriate for our population compared with the other three charts assessed suggesting the 'one size fits all' model may not be appropriate. However, additional analysis of biometry measurements, primarily AC, is needed to address the deficiency of data at 14‐18 weeks gestation which exists for the Raine Study data. A reasonable alternative may be to adopt the WHO charts with local calibration (including the 14 ‐ 18 week gestation period). [ABSTRACT FROM AUTHOR]

Antibiotic resistance is a major threat to global public health. β‐lactamases, which catalyze breakdown of β‐lactam antibiotics, are a principal cause. Metallo β‐lactamases (MBLs) represent a particular challenge because they hydrolyze almost all β‐lactams and to date no MBL inhibitor has been approved for clinical use. Molecular simulations can aid drug discovery, for example, predicting inhibitor complexes, but empirical molecular mechanics (MM) methods often perform poorly for metalloproteins. Here we present a multiscale approach to model thiol inhibitor binding to IMP‐1, a clinically important MBL containing two catalytic zinc ions, and predict the binding mode of a 2‐mercaptomethyl thiazolidine (MMTZ) inhibitor. Inhibitors were first docked into the IMP‐1 active site, testing different docking programs and scoring functions on multiple crystal structures. Complexes were then subjected to molecular dynamics (MD) simulations and subsequently refined through QM/MM optimization with a density functional theory (DFT) method, B3LYP/6‐31G(d), increasing the accuracy of the method with successive steps. This workflow was tested on two IMP‐1:MMTZ complexes, for which it reproduced crystallographically observed binding, and applied to predict the binding mode of a third MMTZ inhibitor for which a complex structure was crystallographically intractable. We also tested a 12‐6‐4 nonbonded interaction model in MD simulations and optimization with a SCC‐DFTB QM/MM approach. The results show the limitations of empirical models for treating these systems and indicate the need for higher level calculations, for example, DFT/MM, for reliable structural predictions. This study demonstrates a reliable computational pipeline that can be applied to inhibitor design for MBLs and other zinc‐metalloenzyme systems. [ABSTRACT FROM AUTHOR]

Background: The Western Australian Preterm Birth Prevention Initiative was officially launched in November 2014. It demonstrated an initial decrease in the preterm birth rate in Western Australia. One of the key points of this initiative is the routine ultrasound measurement of the cervical length in mid‐pregnancy. Aim: The aim of this study was to evaluate the perceptions and attitudes of Western Australian women regarding transvaginal cervical length (TVCL) screening for preterm birth prevention. Materials and methods: Self‐administered questionnaires were completed by pregnant women before and after their mid‐trimester obstetric ultrasound. Maternal demographical and medical data were collected in addition to opinions of TVCL screening. Results: A total of 598 women participated with the maternal age range representative of the Western Australian obstetric population. There was a high rate of acceptance of TVCL imaging, with 2% of the 149 women declining a transvaginal ultrasound (TVU) offered in this study, 1.5% refusing a TVU in the past and 5.7% reporting that they would have a concern in having a TVU in the future. Women stated that they either had declined TVCL in the past (11%) or would decline in the future (30.7%) as they wanted to discuss the procedure with their clinician first, had been advised not to have a TVU by their clinician (11% in the past and 47.7% in the future) or felt uncomfortable with the operator (22% at a previous TVU and 34.4% in the future). Conclusion: Pregnant women participating in this study had a high acceptance of TVCL screening for preterm birth prevention. [ABSTRACT FROM AUTHOR]

Introduction: Factors influencing malignant arrhythmia onset are not fully understood. We explored the circadian periodicity of ventricular arrhythmias (VAs) in patients with implantable cardioverter and cardiac resynchronization defibrillators (ICD/CRT‐D). Methods: Time, morphology (monomorphic/polymorphic), and mode of termination (anti‐tachycardia pacing [ATP] or shock) of VAs stored in a database of remote monitoring data were adjudicated. Episodes were grouped in six 4‐h timeslots from 00:00 to 24:00. Circadian distributions and adjusted marginal odds ratios (ORs), with 95% confidence interval (CI), were analyzed using mixed‐effect models and logit generalized estimating equations, respectively, to account for within‐subject correlation of multiple episodes. Results: Among 1303 VA episodes from 446 patients (63% ICD and 37% CRT‐D), 120 (9%) self‐extinguished, and 842 (65%) were terminated by ATP, 343 (26%) by shock. VAs clustered from 08:00 to 16:00 with 44% of episodes, as compared with 22% from 00:00 to 08:00 (p <.001) and 34% from 16:00 to 24:00 (p =.005). Episodes were more likely to be polymorphic at night with an adjusted marginal OR of 1.66 (CI, 1.15–2.40; p =.007) at 00:00–04:00 versus other timeslots. Episodes were less likely to be terminated by ATP in the 00:00–04:00 (success‐to‐failure ratio, 0.67; CI, 0.46–0.98; p =.039) and 08:00–12:00 (0.70; CI, 0.51–0.96; p =.02) timeslots, and most likely to be terminated by ATP between 12:00 and 16:00 (success‐to‐failure ratio 1.42; CI, 1.06–1.91; p =.02). Conclusion: VAs did not distribute uniformly over the 24 h, with a majority of episodes occurring from 08:00 to 16:00. Nocturnal episodes were more likely to be polymorphic. The efficacy of ATP depended on the time of delivery. [ABSTRACT FROM AUTHOR]

Background: No data exist on the ability of the novel Rhythmia 3‐D mapping system to minimize fluoroscopy exposure during transcatheter ablation of arrhythmias. We report data on the feasibility and safety of a minimal fluoroscopic approach using this system in supraventricular tachycardia (SVT) procedures. Methods: Consecutive patients were enrolled in the CHARISMA registry at 12 centers. All right‐sided procedures performed with the Rhythmia mapping system were analyzed. The acquired electroanatomic information was used to reconstruct 3‐D cardiac geometry; fluoroscopic confirmation was used whenever deemed necessary. Results: Three hundred twenty‐five patients (mean age = 56 ± 17 years, 57% male) were included: 152 atrioventricular nodal reentrant tachycardia, 116 atrial flutter, 41 and 16 right‐sided accessory pathway and atrial tachycardia, respectively. Overall, 27 481 s of fluoroscopy were used (84.6 ± 224 s per procedure, equivalent effective dose = 1.1 ± 3.7 mSv per patient). One hundred ninety‐two procedures (59.1%) were completed without the use of fluoroscopy (zero fluoroscopy, ZF). In multivariate analysis, the presence of a fellow in training (OR = 0.15, 95% CI: 0.05–0.46; p =.0008), radiofrequency application (0.99, 0.99–1.00; p =.0002), and mapping times (0.99, 0.99–1.00; p =.042) were all inversely associated with ZF approach. Acute procedural success was achieved in 97.8% of the cases (98.4 vs. 97% in the ZF vs. non‐ZF group; p =.4503). During a mean of 290.7 ± 169.6 days follow‐up, no major adverse events were reported, and recurrence of the primary arrhythmia was 2.5% (2.1 vs. 3% in the ZF vs. non‐ZF group; p =.7206). Conclusions: The Rhythmia mapping system permits transcatheter ablation of right‐sided SVT with minimal fluoroscopy exposure. Even more, in most cases, the system enables a ZF approach, without affecting safety and efficacy. [ABSTRACT FROM AUTHOR]

Motion detection is a primary visual function, crucial for the survival of animals in nature. Direction‐selective (DS) neurons can be found in multiple locations in the visual neural system, both in the retina and in the visual cortex. For instance, the DS ganglion cell in the retina provides a real‐time response to moving objects, which is much faster than the image recognition executed in the visual cortex. Such in‐retina biological signal processing capability is enabled by the spatiotemporal correlation within different receptive fields of the DS ganglion cells. Taking inspiration from the biological DS ganglion cells in the retina, the motion detection is demonstrated in an artificial neural network made of volatile resistive switching devices with short‐term memory effects. The motion detection arises from the spatiotemporal correlation between the adjacent excitatory and inhibitory receptive fields with short‐term memory synapses, closely resembling the physiological response of DS ganglion cells in the retina. The work supports real‐time neuromorphic processing of sensor data by exploiting the unique physics of innovative memory devices. [ABSTRACT FROM AUTHOR]

Metabolism is the set of life‐sustaining reactions in organisms. These biochemical reactions are organized in metabolic pathways, in which one metabolite is converted through a series of steps catalyzed by enzymes in another chemical compound. Metabolic reactions are categorized as catabolic, the breaking down of metabolites to produce energy, and/or anabolic, the synthesis of compounds that consume energy. The balance between catabolism of the preferential fuel substrate and anabolism defines the overall metabolism of a cell or tissue. Metabolomics is a powerful tool to gain new insights contributing to the identification of complex molecular mechanisms in the field of biomedical research, both basic and translational. The enormous potential of this kind of analyses consists of two key aspects: (i) the possibility of performing so‐called targeted and untargeted experiments through which it is feasible to verify or formulate a hypothesis, respectively, and (ii) the opportunity to run either steady‐state analyses to have snapshots of the metabolome at a given time under different experimental conditions or dynamic analyses through the use of labeled tracers. In this review, we will highlight the most important practical (e.g., different sample extraction approaches) and conceptual steps to consider for metabolomic analysis, describing also the main application contexts in which it is used. In addition, we will provide some insights into the most innovative approaches and progress in the field of data analysis and processing, highlighting how this part is essential for the proper extrapolation and interpretation of data. [ABSTRACT FROM AUTHOR]

This work proposed a novel method to elucidate the controls of As mobility in complex aquifers based on an unsupervised machine learning algorithm, Self‐Organizing Map (SOM), and process‐based geochemical modeling. The approach is tested in the shallow aquifers of the Venetian Alluvial Plain (VAP) near Venice, Italy, where As concentrations seasonally and locally exceed recommended drinking water limits. SOM was fed using information from two geochemical surveys on eight VAP boreholes, and continuous reading of hourly groundwater head levels and weekly geochemical analyses from three VAP boreholes between mid‐October 2017 and end of January 2018. The SOM analysis is consistent with redox‐controlled dissolution‐precipitation hydrous ferric oxides (HFOs) as a key control of As mobility in the aquifer. Dissolved As is positively correlated to Fe and NHþ 4 and negatively to the oxidizing‐reducing potential (ORP). Negative correlation between As and groundwater head levels suggests a redox control by rainfall‐driven recharge, which adds oxidants to the aquifer while progressively attenuating As. This mechanism is tested using process‐based geochemical modeling, which simulates different transport modalities of oxidants entering the aquifer. Starting from reducing aquifer conditions, the model reproduces correctly the observed ORP and the trends in As and Fe, when the function describing the occurrence of oxidizing events scales according to the temporal occurrence of rainfall events. Heterogeneity can strongly control the local‐scale effectiveness of recharge as a natural As attenuating factor, requiring a different model analysis to be properly assessed and to be developed in a follow‐up study. [ABSTRACT FROM AUTHOR]

Acting as artificial synapses, two‐terminal memristive devices are considered fundamental building blocks for the realization of artificial neural networks. Current memristive crossbar architectures demonstrate the implementation of neuromorphic computing paradigms, although they are unable to emulate typical features of biological neural networks such as high connectivity, adaptability through reconnection and rewiring, and long‐range spatio‐temporal correlation. Herein, self‐organizing memristive random nanowire (NW) networks with functional connectivity able to display homo‐ and heterosynaptic plasticity is reported thanks to the mutual electrochemical interaction among memristive NWs and NW junctions. In particular, it is shown that rewiring and reweighting effects observed in single NWs and single NW junctions, respectively, are responsible for structural plasticity of the network under electrical stimulation. Such biologically inspired systems allow a low‐cost realization of neural networks that can learn and adapt when subjected to multiple external stimuli, emulating the experience‐dependent synaptic plasticity that shape the connectivity and functionalities of the nervous system that can be exploited for hardware implementation of unconventional computing paradigms. [ABSTRACT FROM AUTHOR]

In‐memory computing with cross‐point resistive memory arrays has gained enormous attention to accelerate the matrix‐vector multiplication in the computation of data‐centric applications. By combining a cross‐point array and feedback amplifiers, it is possible to compute matrix eigenvectors in one step without algorithmic iterations. Herein, time complexity of the eigenvector computation is investigated, based on the feedback analysis of the cross‐point circuit. The results show that the computing time of the circuit is determined by the mismatch degree of the eigenvalues implemented in the circuit, which controls the rising speed of output voltages. For a dataset of random matrices, the time for computing the dominant eigenvector in the circuit is constant for various matrix sizes; namely, the time complexity is O(1). The O(1) time complexity is also supported by simulations of PageRank of real‐world datasets. This work paves the way for fast, energy‐efficient accelerators for eigenvector computation in a wide range of practical applications. [ABSTRACT FROM AUTHOR]

With the rise in artificial intelligence (AI), computing systems are facing new challenges related to the large amount of data and the increasing burden of communication between the memory and the processing unit. In‐memory computing (IMC) appears as a promising approach to suppress the memory bottleneck and enable higher parallelism of data processing, thanks to the memory array architecture. As a result, IMC shows a better throughput and lower energy consumption with respect to the conventional digital approach, not only for typical AI tasks, but also for general‐purpose problems such as constraint satisfaction problems (CSPs) and linear algebra. Herein, an overview of IMC is provided in terms of memory devices and circuit architectures. First, the memory device technologies adopted for IMC are summarized, focusing on both charge‐based memories and emerging devices relying on electrically induced material modification at the chemical or physical level. Then, the computational memory programming and the corresponding device nonidealities are described with reference to offline and online training of IMC circuits. Finally, array architectures for computing are reviewed, including typical architectures for neural network accelerators, content addressable memory (CAM), and novel circuit topologies for general‐purpose computing with low complexity. [ABSTRACT FROM AUTHOR]

The metabolic transition from anaerobic glycolysis and fatty acid β‐oxidation to glycolysis coupled to oxidative phosphorylation is a key process for the transition of quiescent neural stem cells to proliferative neural progenitor cells. However, a full characterization of the metabolic shift and the involvement of mitochondria during the last step of neurogenesis, from neuroblasts to neuron maturation, is still elusive. Here, we describe a model of neuroblasts, Neuro2a cells, with impaired differentiation capacity due to mitochondrial dysfunction. Using a detailed biochemical characterization consisting of steady‐state metabolomics and metabolic flux analysis, we find increased fatty acid β‐oxidation as a peculiar feature of neuroblasts with altered mitochondria. The consequent metabolic switch favors neuroblast proliferation at the expense of neuron maturation. [ABSTRACT FROM AUTHOR]

There is an urgent need to understand and predict how extreme precipitation events (EPEs) will change at high latitudes, both for local climate change adaptation plans and risk mitigation and as a potential proxy "anticipating" the impact of climate change elsewhere in the world. This paper illustrates that a combination of non‐stationary modelling approaches can be adopted to evaluate trends in EPEs under uncertainty. A large database of daily rainfall events from 281 sparsely distributed weather stations in Finland between 1961 and 2016 was analysed. Among the tested methods, Poisson distributions provided a powerful method to evaluate the impacts of multiple physical covariates, including temperature and atmospheric circulation patterns (ACPs), on the resulting trends. The analysis demonstrates that non‐stationarity is statistically valid for the majority of observations, independently of their location in the country and the season of the year. However, subsampling can severely hinder the statistical validity of the trends, which can be easily confused with random noise and therefore complicate the decision‐making processes regarding long‐term planning. Scaling effects have a strong impact on the estimates of non‐stationary parameters, as homogenizing the data in space and time reduces the statistical validity of the trends. Trends in EPE statistics (mean, 90 and 99% percentiles) and best‐fitted Generalized Pareto parameters in the tails of the distributions appear to be stronger when approaching the Polar region (Lapland) than away from it, consistent with the Arctic amplification of climate change. ACPs are key covariates in physically explaining these trends. In particular, the Arctic Oscillation (AO) and North Atlantic Oscillation (NAO) can explain statistically significant increases in extreme precipitation in Lapland, Bothnian and South regions of Finland, particularly during summer and fall seasons. Non‐stationarity is statistically valid in the majority of observations but masked by subsampling and spatio‐temporal heterogeneity. Trends on extremes and non‐stationary generalized Pareto parameters stronger when approaching the Polar region (Lapland). Artic Oscillation (AO) and North Atlantic Oscillation (NAO) can explain statistically significant trends. [ABSTRACT FROM AUTHOR]

Abstract: A novel micro‐scale photovoltaic concept, Wafer Integrated Micro‐scale Photovoltaics (WPV), is proposed, analyzed, and experimentally demonstrated. The WPV concept seamlessly integrates multijunction micro‐cells with a multi‐functional silicon platform that simultaneously provides optical concentration, hybrid PV/CPV architecture, and mechanical alignment features. Fabrication and optical performance characterization of the Si platform are described in this paper. Over 100% improvement in the concentration‐acceptance‐angle product (CAP) is demonstrated using the wafer‐embedded micro‐concentrating elements, leading to significantly reduced module material and fabrication costs, sufficient angular tolerance for low‐cost trackers, and an ultra‐compact optical architecture compatible with commercial flat panel infrastructures. The development of a prototypical module with a 400× concentration ratio is described. Outdoor optical characterization of the module shows acceptance angles of ±1.7° and ±2.5° for 90% of on‐axis power and full‐width‐half‐maximum, respectively. The projected performance of the PV/CPV hybrid architecture illustrates its potential for cost‐effective collection of both direct and diffuse sunlight, thereby extending the geographic and market domains for cost‐effective PV system deployment. Leveraging low‐cost micro‐fabrication and high‐level integration techniques, the WPV approach presents a promising route to combine the high performance of multijunction solar cells and the low costs of flat‐plate Si PV systems. [ABSTRACT FROM AUTHOR]

Abstract: The recently introduced geological entropy concept evaluates spatial order/disorder in the structure of the hydraulic conductivity (K) field to explain and predict certain characteristics of transport behavior. This concept is expanded in this work by introducing a novel tool for spatial analysis called entrogram from which a metric called entropic scale (HS) can be calculated to measure the overall persistency of patterns of spatial association in a distributed field and to allow robust comparisons between different spatial structures. The entrogram and the entropic scale concepts are applied here to investigate the link between solute transport behavior and the spatial structure of K fields modeled as the distribution of three hydrofacies in alluvial aquifers. Accurate empirical relationships are found between HS and key transport quantities confirming the clear correlation between transport and the structure of the K field described in terms of its entropic scale. The entrogram analysis is also applied to continuous 2‐D and 3‐D fields having identical lognormal K distributions, but with different connectivity. Comparisons between the entrograms and the calculated HS values for these fields, as well as for their corresponding flow velocity distributions, shed light on the key differences among these structures in 2‐D and in 3‐D, which in turn explain their dissimilar impact on solute transport. The entrogram‐based interpretation of the transport simulations seems to confirm that the geological entropy is a promising approach for predicting solute transport behavior simply from a description of the K field heterogeneity. [ABSTRACT FROM AUTHOR]

Abstract: Mitochondria are the energy‐generating hubs of the cell. In spite of considerable advances, our understanding of the factors that regulate the molecular circuits that govern mitochondrial function remains incomplete. Using a genome‐wide functional screen, we identify the poorly characterized protein Zinc finger CCCH‐type containing 10 (Zc3h10) as regulator of mitochondrial physiology. We show that Zc3h10 is upregulated during physiological mitochondriogenesis as it occurs during the differentiation of myoblasts into myotubes. Zc3h10 overexpression boosts mitochondrial function and promotes myoblast differentiation, while the depletion of Zc3h10 results in impaired myoblast differentiation, mitochondrial dysfunction, reduced expression of electron transport chain (ETC) subunits, and blunted TCA cycle flux. Notably, we have identified a loss‐of‐function mutation of Zc3h10 in humans (Tyr105 to Cys105) that is associated with increased body mass index, fat mass, fasting glucose, and triglycerides. Isolated peripheral blood mononuclear cells from individuals homozygotic for Cys105 display reduced oxygen consumption rate, diminished expression of some ETC subunits, and decreased levels of some TCA cycle metabolites, which all together derive in mitochondrial dysfunction. Taken together, our study identifies Zc3h10 as a novel mitochondrial regulator. [ABSTRACT FROM AUTHOR]

Neuroactive steroid levels are altered in several experimental models of peripheral neuropathy, and on this basis, they have been proposed as protective agents. For the first time, the levels of these molecules were assessed here in sterol regulatory element binding protein -1c knock-out male mice (i.e., an experimental model of peripheral neuropathy) and compared with observations in wild type animals. The levels of neuroactive steroids have been evaluated by liquid chromatography-tandem mass spectrometry in plasma and sciatic nerve at 2 and 10 months of age and these analyses were implemented analyzing the gene expression of crucial steroidogenic enzymes in sciatic nerve. Data obtained at 2 months of age showed high levels of pregnenolone in sciatic nerve, associated with low levels of its first metabolite, progesterone, and further metabolites (i.e., 5α-pregnane-3,20-dione and 5α-pregnan-3β-ol-20-one). High levels of testosterone and 17β-estradiol were also observed. At 10 months of age, the neuroactive steroid profile showed some differences. Indeed, low levels of pregnenolone and high levels of 5α-pregnan-3α-ol-20-one and 5α-pregnan-3β-ol-20-one were observed. The analysis of the gene expression of steroidogenic enzymes considered here generally followed these changes. Interestingly, the levels of pregnenolone and progesterone were unmodified in plasma suggesting a specific effect of sterol regulatory element binding protein-1c on neurosteroidogenesis. Because this peripheral neuropathy is due to altered fatty acid biosynthesis, data reported here support the belief that the cross-talk between this biosynthetic pathway and neuroactive steroids may represent a possible therapeutic strategy for peripheral neuropathy. [ABSTRACT FROM AUTHOR]

We propose a novel approach to link solute transport behavior to the physical heterogeneity of the aquifer, which we fully characterize with two measurable parameters: the variance of the log K values ( [ABSTRACT FROM AUTHOR]

Cervical length ( CL) screening has been successfully utilised to identify asymptomatic women, with a singleton pregnancy, at risk of preterm birth ( PTB), thereby providing an opportunity to offer interventions that may reduce that risk. Cervical length screening with ultrasound is most effectively performed with a transvaginal approach. Universal cervical length screening, encompassing all singleton pregnancies rather than restricting screening to those considered at increased risk of PTB, is currently not widely used, despite a growing body of evidence in support of its utility for PTB prevention. There are a number of barriers that may prevent or restrict the implementation of a universal CL screening program. These include cost, availability of vaginal progesterone and other treatment options, reluctance of women to undergo transvaginal ultrasound and the perceptions and beliefs of medical practitioners. Given that mid-pregnancy CL measurement is a recognised predictor of spontaneous PTB, that most cases of PTB occur with no prior maternal history and that there are interventions available that may reduce the risk of PTB, we believe there is a clear role for routine CL screening to be adopted as a component of the fetal morphology ultrasound examination. As a strategy to reduce PTB rates, discussion and counselling about PTB prevention and CL screening should be adopted as a core element of prenatal care. [ABSTRACT FROM AUTHOR]

A new approach to high-concentration photovoltaics (HCPV) based on a parabolic trough primary concentrator is presented. The design diverges from the standard HCPV arrangement of a two-axis tracking point-focus concentrator, and rather employs a simpler parabolic trough primary concentrator to reduce cost. To break the 2D limit of concentration, and bring the system into the realm of HCPV, the system employs an array of rotating secondary concentrators is arranged along the focal line of the parabolic trough. The resulting line-to-point (LTP) focus geometry allows the system to achieve a geometric concentration of 590×, yet still maintains the advantages of having a linear trough primary concentrator, namely manufacturability, economy, and scalability. A full-scale prototype of the system was constructed in Biasca, Switzerland. During on-sun tests a flux concentration of 364 suns was measured at the exit of the secondary concentrator, the highest reported concentration for any parabolic-trough-based system. Moreover, the system reached a peak efficiency of 20.2%, the highest measured solar-to-DC efficiency for a parabolic trough-based solar collector. Long-term performance is estimated by means of a coupled optical-electrical model validated vis-à-vis the experimental results. This work serves as an experimental proof-of-concept for high-concentration trough-based collectors, thereby opening new avenues for reducing the cost of HCPV systems. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

DNA methylation plays key roles in mammalian cells and is modulated by a set of proteins which recognize symmetrically methylated nucleotides. Among them, the protein MECP2 shows multifunctional roles repressing and/or activating genes by binding to both methylated and unmethylated regions of the genome. The interest for this protein markedly increased from the observation that its mutations are the primary cause of Rett syndrome, a neurodevelopmental disorder which causes mental retardation in young females. Thus, the present study is aimed to investigate the effects of some of these known pathogenic missense mutations (i.e. R106Q, R106W, R111G, R133C and R133H) on the MECP2 folding and DNA binding by molecular dynamics simulations. The effects of the simulated mutations are also parameterized by using a here proposed new tool, named Rescore+, implemented in the VEGA ZZ suite of programs, which calculates a set of scoring functions on all frames of a trajectory or on all complexes contained in a database thus allowing an easy rescoring of results coming from MD or docking simulations. The obtained results revealed that the reported loss of the MECP2 function induced by the simulated mutations can be ascribed to both stabilizing and destabilizing effect on DNA binding. The study confirms that MD simulations are particularly useful to rationalize and predict the mutation effects offering insightful information for diagnostics and drug design. [ABSTRACT FROM AUTHOR]

We present an investigation of the scale dependence of hydraulic parameters in fractured media based on the concept of transfer functions (TF). TF methods provide an inexpensive way to perform aquifer parameter estimation, as they relate the fluctuations of an observation time series (hydraulic head fluctuations) to an input function (aquifer recharge) in frequency domain. Fractured media are specially sensitive to this approach as hydraulic parameters are strongly scale-dependent, involving nonstationary statistical distributions. Our study is based on an extensive data set, involving up to 130 measurement points with periodic head measurements that in some cases extend for more than 30 years. For each point, we use a single-porosity and dual-continuum TF formulation to obtain a distribution of transmissivities and storativities in both mobile and immobile domains. Single-porosity TF estimates are compared with data obtained from the interpretation of over 60 hydraulic tests (slug and pumping tests). Results show that the TF is able to estimate the scale dependence of the hydraulic parameters, and it is consistent with the behavior of estimates from traditional hydraulic tests. In addition, the TF approach seems to provide an estimation of the system variance and the extension of the ergodic behavior of the aquifer (estimated in approximately 500 m in the analyzed aquifer). The scale dependence of transmissivity seems to be independent from the adopted formulation (single or dual-continuum), while storativity is more sensitive to the presence of multiple continua. [ABSTRACT FROM AUTHOR]

We have considered nanoparticles (NPs) of Fe, Co and Ni, three transition metals sharing similar chemical properties. NP dissolution, conducted by radioactive tracer method and inductively coupled plasma mass spectrometry, indicated that NiNPs and FeNPs released in the medium a much smaller amount of ions than that released by Co NPs. The two considered methodological approaches, however, gave comparable but not identical results. All NPs are readily internalized by the cells, but their quantity inside the cells is less than 5%. Cytotoxicity and gene expression experiments were performed on SKOV-3 and U87 cells. In both cell lines, CoNPs and NiNPs were definitely more toxic than FeNPs. Real-time polymerase chain reaction experiments aimed to evaluate modifications of the expression of genes involved in the cellular stress response (HSP70, MT2A), or susceptible to metal exposure (SDHB1 and MLL), or involved in specific cellular processes (caspase3, IQSEC1 and VMP1), gave different response patterns in the two cell lines. HSP70, for example, was highly upregulated by CoNPs and NiNPs, but only in SKOV-3 cell lines. Overall, this work underlines the difficulties in predicting NP toxicological properties based only on their chemical characteristics. We, consequently, think that, at this stage of our knowledge, biological effects induced by metal-based NPs should be examined on a case-by-case basis following studies on different in vitro models. Moreover, with the only exception of U87 exposed to Ni, our results suggest that metallic NPs have caused, on gene expression, similar effects to those caused by their corresponding ions. Copyright © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A 77-year-old man with ischemic cardiomyopathy and a cardiac resynchronization therapy-defibrillator (CRT-D) device came to our attention due to incessant ventricular tachycardia and multiple implantable cardioverter defibrillator (ICD) shocks. An electrocardiogram showed non-sustained monomorphic ventricular tachycardias (NSVTs) constantly occurring after each biventricular stimulation. During an electrophysiological study, NSVTs reproducibly recurred only after right ventricular (RV) pacing; LV pacing did not induce any NSVTs. The activation map was consistent with a localized reentry at the interventricular septum, and a double exit; at the LV exit site, a single radiofrequency energy application immediately interrupted the occurrence of the NSVTs. Current evidence supports LV pacing to be pro-arrhythmogenic in few CRT patients. This unusual case shows that RV pacing during CRT could produce frequent ventricular arrhythmias and arrhythmic storm. Catheter ablation can be considered an effective therapeutic option, especially when CRT maintenance is highly advisable. [ABSTRACT FROM AUTHOR]

Aims Ciliated hepatic foregut cysts (CHFCs) are retained benign lesions of the liver. However, a case of squamous cell metaplasia and five cases of squamous cell carcinoma arising from a CHFC have been described. The potential of malignant transformation makes the identification of new biomarkers necessary. As the cancer/testis antigen sperm protein 17 (Sp17) has been detected in oral and oesophageal squamous cell carcinomas, the aim of this study was to investigate the expression of Sp17 and AKAP-associated sperm protein (ASP), which has a shared N-terminal sequence with Sp17, in four surgically resected CHFCs. Methods and results CHFC specimens were taken from two patients who attended the Medical College of Wisconsin, Milwaukee, USA and two patients who attended the Fundación Jiménez Díaz, Madrid, Spain. CHFCs were found to be immunopositive for Sp17 and ASP. Both proteins were localized to the cytoplasm of ciliated cells lining the cysts, and their cilia. Confocal microscopy demonstrated that Sp17 and ASP overlapped in the same region of the cell. Conclusion Sp17 and ASP cancer/testis antigens were found in ciliated cells of four CHFCs. Further characterization of Sp17 and ASP in patients with CHFCs may provide significant clues for understanding the molecular mechanisms underlying their predisposition to develop squamous cell carcinomas. [ABSTRACT FROM AUTHOR]

We analyzed the behavior of convergent flow tracer tests performed in a 3-D heterogeneous sandbox in presence of connected gravel channels under laboratory-controlled conditions. We focused on the evaluation of connectivity metrics based on characteristic times calculated from experimental breakthrough curves (BTCs), and the selection of upscaling model parameters related to connectivity. A conservative compound was injected from several piezometers in the box, and depth-integrated BTCs were measured at the central pumping well. Results show that transport was largely affected by the presence of gravel channels, which generate anomalous transport behavior such as BTC tailing and double peaks. Connectivity indicators based on BTC peak times provided better information about the presence of connected gravel channels in the box. One of these indicators, β, was defined as the relative temporal separation of the BTCs peaks from the BTCs centers of mass. The mathematical equivalence between β and the capacity coefficient adopted in mass transfer-based formulations suggests how connectivity metrics could be directly embedded in mass transfer formulations. This finding is in line with previous theoretical studies and was corroborated by reproducing a few representative experimental BTCs using a 1-D semianalytical bimodal solution embedding a mass transfer term. Model results show a good agreement with experimental BTCs when the capacity coefficient was constrained by measured β. Models that do not embed adequate connectivity metrics or do not adequately reproduce connectivity showed poor matching with observed BTCs. [ABSTRACT FROM AUTHOR]

To better investigate the GPCR structures, we have recently proposed to explore their flexibility by simulating the bending of their Pro-containing TM helices so generating a set of models (the so-called chimeras) which exhaustively combine the two conformations (bent and straight) of these helices. The primary objective of the study is to investigate whether such an approach can be exploited to enhance the reliability of the GPCR models generated by distant templates. The study was focused on the human mAChR1 receptor for which a presumably reliable model was generated using the congener mAChR3 as the template along with a second less reliable model based on the distant β2-AR template. The second model was then utilized to produce the chimeras by combining the conformations of its Pro-containing helices (i.e., TM4, TM5, TM6 and TM7 with 16 modeled chimeras). The reliability of such chimeras was assessed by virtual screening campaigns as evaluated using a novel skewness metric where they surpassed the predictive power of the more reliable mAChR1 model. Finally, the virtual screening campaigns emphasize the opportunity of synergistically combining the scores of more chimeras using a specially developed tool which generates highly predictive consensus functions by maximizing the corresponding enrichment factors. [ABSTRACT FROM AUTHOR]

In patients with left ventricular assist device (LVAD), a minority of post-operative ventricular tachycardias (VTs) is caused by contact between the inflow cannula and the endocardium. Currently, electrophysiologic characteristics and pathologic features of this condition are lacking. We report on a case of a successfully ablated mechanical VT. After VT recurrence, heart transplantation took place. Pathologic observations were consistent with direct tissue injury and inflammation, eventually contributing to persisting arrhythmias. Radiofrequency catheter ablation can be a safe and effective option to treat arrhythmias caused by inflow cannula interference in the short term, although a high recurrence rate is expected. [ABSTRACT FROM AUTHOR]

The study reports a flexible structure-based approach aimed at identifying binding sites within target proteins starting from a well-defined reference binding site. The method, named SPILLO potential binding sites searcher (SPILLO-PBSS), includes a suitably designed tolerance which allows an efficient recognition of the potential binding sites regardless of both involved residues and protein conformation. Hence, the proposed method overcomes the rigidity which affects the available approaches and which prevents a proper analysis of distorted binding sites. We apply SPILLO-PBSS to several test cases, including the search for the guanosine diphosphate binding site in distorted H-Ras proteins and the identification of acetylcholine binding proteins from among a library of heterogeneous resolved proteins. Tests are also performed to compare SPILLO-PBSS with other related and available methods. The encouraging results confirm the notable potentialities of this approach and lay the foundation for its use to analyze and predict target proteins on a proteome-wide scale. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aquifer hydraulic properties such as hydraulic conductivity ( K) are ubiquitously heterogeneous and typically only a statistical characterization can be sought. Additionally, statistical anisotropy at typical characterization scales is the rule. Thus, regardless of the processes governing solute transport at the local (pore) scale, transport becomes non-Fickian. Mass-transfer models provide an efficient tool that reproduces observed anomalous transport; in some cases though, these models lack predictability as model parameters cannot readily be connected to the physical properties of aquifers. In this study, we focus on a multirate mass-transfer model (MRMT), and in particular the apparent capacity coefficient ( β), which is a strong indicator of the potential of immobile zones to capture moving solute. We aim to find if the choice of an apparent β can be phenomenologically related to measures of statistical anisotropy. We analyzed an ensemble of random simulations of three-dimensional log-transformed multi-Gaussian permeability fields with stationary anisotropic correlation under convergent flow conditions. It was found that apparent β also displays an anisotropic behavior, physically controlled by the aquifer directional connectivity, which in turn is controlled by the anisotropic correlation model. A high hydraulic connectivity results in large β values. These results provide new insights into the practical use of mass-transfer models for predictive purposes. [ABSTRACT FROM AUTHOR]