cssi/SciSciGPT-SciSciNet huggingface dataset:
Biomarkers for the Clinical Use of PD-1/PD-L1 Inhibitors in Non–Small-Cell Lung Cancer: A Review

Importance The development of programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) checkpoint inhibitors has changed the landscape of non–small-cell lung cancer (NSCLC) therapy, with 2 approvals from the US Food and Drug Administration of PD-1 inhibitors for second-line therapy. However, the rational use of these agents has been limited by the lack of a definitive predictive biomarker. Observations Tumor PD-L1 expression is associated with an increased likelihood of NSCLC response to these agents, although responses can still occur at a low rate in PD-L1–negative tumors. The use of PD-L1 as a predictive biomarker for use of PD-1/PD-L1 inhibitors is limited by the multitude of PD-L1 antibodies, assays, scoring systems, and thresholds for positivity currently used. Alternative biomarkers such as tumor neoantigens identified through whole-exome sequencing and clinical parameters (eg, smoking or oncogene driver status) may also have predictive value. Biomarkers that can direct the rational use of PD-1/PD-L1 checkpoint inhibitors are crucial given the risk of life-threatening immune-related complications associated with these therapies and the reality that most patients still do not benefit from their use. Conclusions and Relevance The refinement of existing biomarkers and identification of novel predictive biomarkers will be key to ensuring the effective and safe use of these agents. Since most patients still do not benefit from these agents, it is critical to continue to work to define the select patient population who will derive durable benefit from PD-1/PD-L1 inhibition and identify markers that could have predictive value for combination therapies that could expand the population who benefit.
Viewpoints: Letter from the Editor: In This Issue

Dear Readers:In this issue, there is a focus on Dance Advocacy. Susan McGreevy-Nichols has written her “NDEO Works” column about the importance of advocating for dance, not only at the national lev...
Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

Maternal vascular adaptation to pregnancy is critically important to expand the capacity for blood flow through the uteroplacental unit to meet the needs of the developing fetus. Failure of the maternal vasculature to properly adapt can result in hypertensive disorders of pregnancy such as preeclampsia (PE). Herein, we review the endocrinology of maternal adaptation to pregnancy and contrast this with that of PE. Our focus is specifically on those hormones that directly influence endothelial cell function and dysfunction, as endothelial cell dysfunction is a hallmark of PE. A variety of growth factors and cytokines are present in normal vascular adaptation to pregnancy. However, they have also been shown to be circulating at abnormal levels in PE pregnancies. Many of these factors promote endothelial dysfunction when present at abnormal levels by acutely inhibiting key Ca2+ signaling events and chronically promoting the breakdown of endothelial cell-cell contacts. Increasingly, our understanding of how the contributions of the placenta, immune cells, and the endothelium itself promote the endocrine milieu of PE is becoming clearer. We then describe in detail how the complex endocrine environment of PE affects endothelial cell function, why this has contributed to the difficulty in fully understanding and treating this disorder, and how a focus on signaling convergence points of many hormones may be a more successful treatment strategy.
Striving to Be King of Mobile Mountains: Communication and Organizing Through Digital Fitness Technology

This study considers fitness-tracking applications as settings for communicative performances. Qualitative interviews and observations with 41 users of a cycling-focused fitness application revealed communicative themes of qualifying, social sharing, and withholding. Users also assessed other members through social-group comparing and upward comparing. This study develops theory by revealing how individuals use the technology to communicate about their physical acts, and how the context of use facilitates organizing processes. We argue that use of this fitness application extends our understanding of how communication can constitute a community of practice (CoP; Brown & Duguid, 1991; Lave & Wenger, 1991). Primarily, the hybrid online/offline nature of Strava complicates the traditional understanding of communication and CoPs.
Lateral thigh perforator flap for breast reconstruction: Computed tomographic angiography analysis and clinical series.

Summary Purpose Although abdominal-based flaps remain the first choice for autologous breast reconstruction, alternative donor sites are necessary when the abdomen is unavailable. Abdominal donor site suitability is determined, at times, according to deep inferior epigastric perforator (DIEP)-protocol computed tomographic angiography (CTA) results. CTA provides information about the pelvis/upper thigh that can be used to evaluate the suitability of other donor sites. This study aimed to examine the utility of DIEP-protocol CTA in the assessment of a lateral thigh perforator (LTP) flap. Furthermore, a small clinical LTP flap breast reconstruction series was presented. Methods The LTP flap anatomy was studied in 100 DIEP-protocol CT angiographies (200 thighs). Collected data included lateral circumflex femoral artery (LCFA) origin; number, type, and course of LTPs; pedicle characteristics; and reference point measurements. Relative relationships between reference point anatomy and perforator anatomy were analyzed. Results Perforators originated from the LCFA ascending branch (4.6 mm average diameter), averaging 2.6 perforators/thigh. The mean estimated pedicle length was 7.7 cm (±0.7 cm). Septocutaneous perforators were present in 97% (1.8 perforators/thigh). Musculocutaneous perforators were present in 64% (0.9 perforators/thigh). The mean distance between anterior superior iliac spine and perforator was 9.9 cm (±1.5 cm). Perforators were located 0.13 cm (±1.1 cm) below the pubic symphysis. Our LTP flap clinical series featured dissection in the supine position and primary donor site closure and highlighted the difficulty in flap design (six patients, nine LTP flaps). Conclusions LTPs are consistent, reliably present, and radiographically appear to be suitable for microsurgical transfer. DIEP-protocol CTA is an acceptable method for imaging the pertinent LTP anatomy.
Design and Evolution of Enzymes for Non-natural Chemistry

Enzymes are used in biocatalytic processes for the efficient and sustainable production of pharmaceuticals, fragrances, fine chemicals, and other products. Most bioprocesses exploit chemistry found in nature, but we are now entering a realm of biocatalysis that goes well beyond. Enzymes have been engineered to catalyze reactions previously only accessible with synthetic catalysts. Because they can be tuned by directed evolution, many of these new biocatalysts have been shown to perform abiological reactions with high activity and selectivity. We discuss recent examples, showcase catalyst improvements achieved using directed evolution, and comment on some current and future implications of non-natural enzyme evolution for sustainable chemical synthesis.
Automatic labeling of continuous wave Doppler images based on combined image and sentence networks

As medical imaging datasets grow, we are approaching the era of big data for radiologic decision support systems. This requires renewed efforts in dataset curation and labeling. We propose a methodology for weak labeling of medical images for attributes such as anatomy and disease that relies on image to sentence transformation. The methodology consists of three models, a convolutional neural network that is trained on a coarse classification task and acts as an image feature generator, a language model to map sentences to a fixed length space, and a multi-layer perceptron that acts as a function approximator to map images to the sentence space. The transform model is trained on matched image-sentence pairs on a dataset of echocardiography studies. For a given image, labels are extracted from the closest sentences to the output of the image-sentence transform. We show that the resulting solution has an 78.2% accuracy in labeling Doppler images with aortic stenosis. We also show that the retrieved sentences are consistent with the true sentences in terms of meaning with an average BLEU score of 0.34, matching the current highly performing machine translation solutions.
Chapter 25. Visualization of Genes by Electron Microscopy

Publisher Summary This chapter describes the visualization of genes by electron microscopy. The analysis of the structure of transcriptionally active or replicating genomes should provide information on nucleoprotein rearrangements that are a consequence of the activation of the genome. A simple procedure is described in detail for the preparation of cellular or nuclear contents for electron microscopy, which allows the ultrastructural analysis of individual genes from single cells. The technique was developed by Miller and Beatty and has been successfully applied to many systems by several investigators. The chapter describes the technique and discusses problems that may be encountered and the ways in which they may be solved. While a great deal of information has been provided by the application of the technique detailed in this chapter, it is likely that its combination with other experimental approaches provides a powerful approach to the detailed understanding of chromosome structure as related to function.
Aging effects on airflow dynamics and lung function in human bronchioles.

Background and objective The mortality rate for patients requiring mechanical ventilation is about 35% and this rate increases to about 53% for the elderly. In general, with increasing age, the dynamic lung function and respiratory mechanics are compromised, and several experiments are being conducted to estimate these changes and understand the underlying mechanisms to better treat elderly patients. Materials and methods Human tracheobronchial (G1 ~ G9), bronchioles (G10 ~ G22) and alveolar sacs (G23) geometric models were developed based on reported anatomical dimensions for a 50 and an 80-year-old subject. The aged model was developed by altering the geometry and material properties of the model developed for the 50-year-old. Computational simulations using coupled fluid-solid analysis were performed for geometric models of bronchioles and alveolar sacs under mechanical ventilation to estimate the airflow and lung function characteristics. Findings The airway mechanical characteristics decreased with aging, specifically a 38% pressure drop was observed for the 80-year-old as compared to the 50-year-old. The shear stress on airway walls increased with aging and the highest shear stress was observed in the 80-year-old during inhalation. A 50% increase in peak strain was observed for the 80-year-old as compared to the 50-year-old during exhalation. The simulation results indicate that there is a 41% increase in lung compliance and a 35%-50% change in airway mechanical characteristics for the 80-year-old in comparison to the 50-year-old. Overall, the airway mechanical characteristics as well as lung function are compromised due to aging. Conclusion Our study demonstrates and quantifies the effects of aging on the airflow dynamics and lung capacity. These changes in the aging lung are important considerations for mechanical ventilation parameters in elderly patients. Realistic geometry and material properties need to be included in the computational models in future studies.
Engaging and Retaining Women in an Engineering and Entrepreneurship Program [Commentary]

Workplace and classroom culture, persistent stereotypes, and gender-specific pressures have all been suggested as reasons for the gender discrepancy in engineering. This article shares some of the behind-the-scenes observations and strategies that have proven successful to recruit, engage, retain, and propel women on their engineering career trajectories. Though the HESE program is small when compared to the engineering student body, our study of the motivations is significant because these observations have been consistently apparent over the past decade of the program's operation, and during that time period participation of women stayed above 50% of the total. The observations detailed here have implications for engineering and entrepreneurship education systems as well as large corporations, governmental agencies, and other societal actors that want to attract and retain women in their organizations.
Introduction to Comparative Reproduction

During the course of mammalian evolution, there have been marked anatomic, endocrine and physiologic changes, the main tendency of which were to insure the protection of young and the survival of the species. These changes involved economy in the production of gametes, reduction in the size of the egg, internal fertilization, the development of the corpus luteum as a temporary endocrine organ and the development of the placenta as a nutritive, excretory, endocrine and protective organ.
Organizing pneumonia related to electronic cigarette use: A case report and review of literature.

Background and objective Electronic cigarettes (e cigarettes) are battery operated devices that produce aerosol by heating a solution typically made up of nicotine, propylene glycol, glycerin and flavouring agents. The use of e cigarettes has risen dramatically in recent years especially among adolescents and young adults. These devices have been marketed as safer alternatives to tobacco smoking by their manufactures despite lack of adequate safety data. Methods We present a case of 40-year-old female patient who developed significant pulmonary toxicity secondary to e cigarette use and searched existing literature relevant to the case. Results To our knowledge this is the second reported case of organizing pneumonia and tenth reported case of pulmonary toxicity related to e cigarette use. Our patient presented with symptoms of worsening dyspnoea and intermittent chest pain for past 1 month. She reported increased use of e cigarettes during this time period to help her quit smoking. Patient developed acute hypoxemic respiratory failure requiring intubation and mechanical ventilation. She was diagnosed with organizing pneumonia on open lung biopsy and was successfully treated with steroids along with abstinence from e cigarette use. Conclusions As the current data on health effects of e cigarettes is limited, case reports can serve important piece of information in this regard. The use of e cigarettes has increased exponentially in recent years and continue to rise; therefore, physicians should be aware of adverse effects and toxicity related to its use.
Effect of homopolymer concentration on LER and LWR in block copolymer/homopolymer blends

Block copolymers (BCPs) can phase separate to form periodic structures with small spacings on the order of the polymer molecular size, thus making BCPs an attractive potential method for extending the resolution limits of optical lithography through various pitch subdivision techniques. In order to direct the self-assembly of BCP thin films, methods such as chemoepitaxy are employed which use the contrast between a chemically preferential pinning stripe and a more neutral background region to guide the phase separated features. Homopolymer is a known blending agent for BCPs that allows for the periodic spacing of their features (pitch, Lo) to be adjusted based on the concentration of homopolymer. This allows for less stringent tolerances on the molecular weight of the BCP in order to achieve a particular Lo. Addition of homopolymer is a relatively simple and potentially attractive method, but such blending may also a effect the resulting line edge and/or line width roughness in the DSA patterns. In this work, detailed molecular dynamics simulations of block copolymer directed self-assembly have been used to show how such behaviors and process performance factors are a effected by the symmetric addition of homopolymers (A and B) to a thin film lamellae forming BCP (A-b-B).
GenotypeTensors: Efficient Neural Network Genotype Callers

We studied the problem of calling genotypes using neural networks. A machine learning approach to calling genotypes requires a training set, an approach to convert genomic sites into tensors and robust model development and evaluation protocols. We discuss each of these components of our approach and compare four types of neural network training protocols, two fully supervised and two semi-supervised approaches. Semi-supervised approaches use unlabeled data to supplement limited quantities of labeled data. Random hyper-parameter searches identified highly performing models that reach indel F1 of 99.4% on a chromosomes 20, 21, 22 and X of NA12878/HG001. We further validate these models by evaluating performance on HG002, an independent sample used in the PrecisionFDA challenge. We apply GenotypeTensors to evaluate the impact of (1) training with small datasets, (2) training models only with sites inside confidence regions, or (3) training with improved true label annotations. A PyTorch open-source implementation of GenotypeTensors is available at https://github.com/CampagneLaboratory/GenotypeTensors. DNANexus cloud applications are provided to help process new datasets both to train model or call genotypes with trained models.
Performance Prediction for Large Scale Parallel Systems.

In both the design of parallel computer systems and the development of applications, it is very important to have good performance prediction tools. This paper describes a new approach -PetaSIM, which is designed for the rapid prototyping stage of machine or application design. Computers, networks and applications are described as objects in a Java IDL (Interface Definition Language) with special attention to the proper representation of caches and hierarchical memories. PetaSIM represents a prototype for a performance specification language or PSL. We present encouraging initial results for a set of data-intensive applications from the University of Maryland. We discuss the extension of PetaSIM to support applications of the type found in distributed collaborative engineering.
Harmonic Detection for Hybrid Filter

Harmonic distortion can be caused by both active and passive nonlinear devices in a power system. These harmonic currents can cause voltage distortion and excessive power losses in the system. To maintain high quality power supply, the system harmonic levels must be measured and kept under control. Passive, active and hybrid filters can be used in a power system to eliminate harmonic currents at the load sides. In order to compensate harmonic in real time, each harmonic component is detected. Due to this complicated process, it is difficult to improve the processing speed and simplify harmonic detection process. A method of describing the total harmonic distortion in current detection is suggested in order to simplify harmonic detection. The results show that the approach of harmonic detection is applicable to detect each harmonic effectively.
Titanium Implant Surfaces

Commercial implants fabricated from commercially pure titanium (CP) and from titanium alloys 6 aluminum 4 vanadium (Ti6–4) have received a great deal of scrutiny from investigators of corrosion and mechanical properties. In its usual state, cp titanium is a somewhat soft and weak material by metallurgical standards. The Ti 6–4 alloy was developed for the aerospace industry, and while, if properly processed, can have excellent mechanical properties, the composition is not necessarily optimum for biomedical applications. Because titanium and its alloys depend upon a tenacious surface oxide to maintain “biocompatibility”, the surface state of the material is critical to its performance.
Animal Models of Behavioral Effects of Early Lead Exposure

The adverse effects of lead on human health have long been recognized and extensively studied. Nevertheless, relatively few studies have specifically addressed the teratology of lead and even fewer have examined its behavioral teratology. This paper will review the literature on animal models of the behavioral teratology of lead. Only studies of laboratory animals will be included because of the greater experimental control allowable with subhuman subjects. These studies with animal models are an important complement to studies of human subjects, which are by necessity more observational in design. Several reviews of the human clinical and experimental literature are available (e.g., Bornschein, Pearson, & Reiter, 1980; Needleman & Landrigran, 1981; Repko & Corum, 1979; Smith, 1985).
Laser applications in urology

Summary of laser-tissue interactions in urology. Holmium:YAG laser lithotripsy for calculi. Laser treatment of benign prostatic enlargement. Laser incision of urethral and ureteral strictures. Other laser applications in urology for treatment of penile carcinoma, partial nephrectomy, etc.
The Central Vein: FLAIR Signal Abnormalities Associated with Developmental Venous Anomalies in Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: Demyelination is a recently recognized cause of FLAIR hyperintensities associated with developmental venous anomalies. Our purpose was to quantify the prevalence of white matter signal abnormalities associated with developmental venous anomalies in patients with multiple sclerosis compared with controls. MATERIALS AND METHODS: A retrospective, blinded, multireader study compared the prevalence of FLAIR hyperintense signal abnormalities adjacent to developmental venous anomalies in patients with MS compared with controls (patients with developmental venous anomalies without MS). Study findings were positive if a central vein was demonstrated using FLAIR and contrast-enhanced fat-saturated T1 sequences. Imaging parameters also included developmental venous anomaly location, developmental venous anomaly drainage, white matter lesion size, and depth of white matter lesions. Clinical parameters included age, sex, and the presence of confounding variables (hypertension, diabetes, migraines, and/or vasculopathy). RESULTS: FLAIR signal abnormality was present around 47.3% (35/74) of developmental venous anomalies in patients with MS, and 13.5% (10/74) of developmental venous anomalies in the control group (P CONCLUSIONS: The association of developmental venous anomalies and FLAIR hyperintensities was more common in patients with MS, which suggests that the underlying demyelinating pathologic process of MS may be the cause of this propensity in patients with MS. Impaired venous drainage in the territory of developmental venous anomalies may predispose to development of these lesions, and an associated central vein is helpful in understanding an atypical location of MS plaques.
Assessment of the nutrition environment in rural counties in the Deep South.

The nutrition environment, including food store type, may influence dietary choices, which in turn can affect risk of obesity and related chronic diseases such as CHD, diabetes and cancer. The objective of the present study was to elucidate the extent to which healthy foods are available and affordable in various rural food outlets. A subset of the nutrition environment was assessed using the Nutrition Environment Measures Survey in Stores (NEMS-S). The NEMS-S instrument assessed the availability and price of healthy foods (e.g. low-fat/non-fat milk, lean meats and reduced-fat dinner entrees) compared with less healthy counterparts (e.g. whole milk, non-lean meats and regular dinner entrees). The NEMS-S also assessed the quality of fresh fruits and vegetables. Availability, prices and quality of healthy foods were compared between grocery stores (n 24) and convenience stores (n 67) in nine rural counties in Alabama. Mean availability subscale score (possible range 0 to 30; higher score indicates a greater number of healthier foods were available) for grocery stores was 22·6 (sd 8·1), compared with 6·6 (sd 5·2) in convenience stores (P < 0·0001); and mean price subscale score (possible range −9 to 18; higher score indicates that healthier options were less expensive than the less healthy options) for grocery stores was 2·4 (sd 2·7), compared with 0·7 (sd 1·2) in convenience stores (P = 0·0080). Mean total NEMS-S score (possible range −9 to 54) in grocery stores was 29·8 (sd 10·9) compared with 7·3 (sd 7·1) in convenience stores (P < 0·0001). Both grocery and convenience stores could be strategic points of intervention to improve the nutrition environment in the counties that were surveyed.
Dispersion in Tissue-Mimicking Gels Measured with Shear Wave Elastography and Torsional Vibration Rheometry

Dispersion, or the frequency dependence of mechanical parameters, is a primary confounding factor in elastography comparisons. We present a study of dispersion in tissue-mimicking gels over a wide frequency band using a combination of ultrasound shear wave elastography (SWE), and a novel torsional vibration rheometry which allows independent mechanical measurement of SWE samples. Frequency-dependent complex shear modulus was measured in homogeneous gelatin hydrogels of two different bloom strengths while controlling for confounding factors such as temperature, water content and material aging. Furthermore, both techniques measured the same physical samples, thereby eliminating possible variation caused by batch-to-batch gel variation, sample geometry differences and boundary artifacts. The wide-band measurement, from 1 to 1800 Hz, captured a 30%-50% increase in the storage modulus and a nearly linear increase with frequency of the loss modulus. The magnitude of the variation suggests that accounting for dispersion is essential for meaningful comparisons between SWE implementations.
Utility of Fine Needle Aspiration for Diagnosis of Plasmacytoma

Plasmacytomas are rare extramedullary plasma cell neoplasms that present in bone and/or soft tissue. Diagnosis can require a variety of laboratory approaches such as serum protein electrophoresis, bone marrow biopsy, Bence Jones protein assays, and imaging. However, few case reports describe using fine needle aspiration for diagnosis. We present a case of a plasmacytoma diagnosis in a 55-year-old patient, who initially presented to the emergency room with symptoms of chest pain. Imaging revealed right apical and medial lung mass extending just posterior to the trachea with invasion and destruction of the anterolateral T3 vertebral body. Multiple smaller hypodensities were also present in thoracic vertebral bodies, ribs, and sternum. Biopsies were performed on the mediastinal mass. Fine needle aspiration revealed groups of mature and immature plasma cells at various stages of maturation. Flow cytometry demonstrated a kappa light chain-restricted plasma cell population. Paraffin immunoperoxidase studies showed that the neoplastic cells bore monotypic kappa light chains. The patient’s presentation emphasizes the utility of fine needle aspiration, in conjunction with other ancillary studies, for diagnosing plasmacytomas. J Med Cases. 2019;10(2):37-40 doi: https://doi.org/10.14740/jmc3223
Health System and Beneficiary Costs Associated With Intensive End-of-Life Medical Services.

Importance Despite recommendations to reduce intensive medical treatment at the end of life, many patients with cancer continue to receive such services. Objective To quantify expected beneficiary and health system costs incurred in association with receipt of intensive medical services in the last month of life. Design, Setting, and Participants This retrospective cohort study used data collected nationally from Medicare and the Veterans Health Administration for care provided in fiscal years 2010 to 2014. Participants were 48 937 adults aged 66 years or older who died of solid tumor and were continuously enrolled in fee-for-service Medicare and the Veterans Health Administration in the 12 months prior to death. The data were analyzed from February to August 2019. Exposures American Society of Clinical Oncology metrics regarding medically intensive services provided in the last month of life, including hospital stay, intensive care unit stay, chemotherapy, 2 or more emergency department visits, or hospice for 3 or fewer days. Main Outcomes and Measures Costs in the last month of life associated with receipt of intensive medical services were evaluated for both beneficiaries and the health system. Costs were estimated from generalized linear models, adjusting for patient demographics and comorbidities and conditioning on geographic region. Results Of 48 937 veterans who received care through the Veterans Health Administration and Medicare, most were white (90.8%) and male (98.9%). More than half (58.9%) received at least 1 medically intensive service in the last month of life. Patients who received no medically intensive service generated a mean (SD) health system cost of $7660 ($1793), whereas patients who received 1 or more medically intensive services generated a mean (SD) health system cost of $23 612 ($5528); thus, the additional financial consequence to the health care system for medically intensive services was $15 952 (95% CI, $15 676-$16 206;P Conclusions and Relevance Given the low income of many elderly patients in the United States, the financial consequences of medically intensive services may be substantial. Costs of medically intensive services at the end of life, including patient financial consequences, should be considered by both physicians and families.
The Use of the Barriers to Baccalaureate Nursing Education Instrument Among ADN Students: Purpose, Reliability, and Validity.

Background and purpose Challenges abound as to the goal of "80% BSN by 2020." This study reports the use and the psychometric properties of the Barriers to Baccalaureate Nursing Education instrument among associate degree nursing students. Methods Analyses included content validity, component analysis with oblique rotation, and hypothesis testing. Results Four factors with total variance explained of 61.24% emerged: Dispositional, Situational, and two Institutional barriers. Reliability coefficients ranged .62-.88. Group differences in subscale scores based on educational level, number of dependents, hours worked, and age were found along with correlations. Conclusions The instrument demonstrated adequate validity and reliability. A structural framework toward understanding the barriers to baccalaureate education among students and nurses is provided. Future studies should include psychometric testing for further refinement, validity, and reliability.
One for All: A Pooled Approach to Classify Functional Impacts of Multiple Mutations.

Understanding common biological consequences of heterogenous mutations in complex polygenic conditions is challenging. In this issue of Cell Stem Cell, Cederquist et al. (2020) implement an in vitro pooled assay where 30 high-confidence ASD mutations engineered in subclones of a human pluripotent stem cell line can be investigated in parallel to reveal their effects on prefrontal cortex neurogenesis.
Structural aspects and activation mechanism of human secretory group IIA phospholipase

Phospholipases are important probes for understanding structure–function relationships of membrane proteins. Many neurotoxins have phospholipase activity, and they have been recognized to be potential therapeutic agents for biological warfare. Understanding the modes of action of these enzymes is important for the development of effective therapeutic strategies. Human secretory phospholipases A2 (sPLA2) interact with cellular membranes and catalyze the hydrolysis of phosphate ester bonds of phospholipids. The activity of these enzymes increases tremendously upon binding to a hydrophobic interface. Using molecular dynamics (MD) simulations in implicit solvent and membrane environments, we investigated alterations in structure and conformation of human sPLA2 upon its interaction with a membrane that may be associated with the activation of the enzyme. In 50 ns MD simulations, starting from six different initial orientations of the protein relative to the membrane surface, the enzyme consistently adopted a membrane-bound configuration in close agreement with the known experimental data. The simulations also reproduced the experimentally determined distribution of hydrophobic and polar side chains on the interfacial binding surface. Differences in the dynamic behavior of the enzyme between the solvent and membrane-bound states were observed. In nonpolar media, the enzyme underwent major conformational rearrangements, which exposed the active site to the membrane. The increased mobility of the surface loop and the β-wing regions is required for the conformational change, which is essentially induced by the movement of N-terminal helix. Several active site residues underwent structural changes that reorganize the binding site for substrate catalysis. Overall, the results provided a valuable insight into the interfacial behavior of sPLA2 enzyme and suggested that membrane binding is essential but insufficient for sPLA2 activation.
Density functional theory investigation on the degradation mechanisms of 3-nitro-1,2,4-triazol-5-one (NTO) in water

The degradation mechanisms of 3-nitro-1,2,4-triazol-5-one (NTO) in the bulk water were explored at the density functional theory (DFT) level using the M06-2X functional and the 6-311G(d,p) basis set; the effect of bulk water solution was considered using the conductor-like polarizable continuum model (CPCM) approach. The initial dissociation step of NTO may be triggered by UV light, radicals, and heat. Our computed results suggest that radical-induced reactions should be suitable for the initial degradation of NTO in water. The follow-up further degradation illustrated that the product fragments may include urazole, NO, NO2, HONO, CO2, di-imide, and N2. It was revealed that hydroxide ions can accelerate the degradation of NTO in water.
Assessment of government support policies for the individualâ€™s income in Iraq for the period of (2003-2006)

Government support policies are part of economic policies which aim at achieving overall stability and access to the standard of living of social groups with limited income Through (social protection network â€“ supporting the Ration card-Providing loans to the unemployed without interest) Or for general sectors such as health, education, agriculture and housing. These policies are applied in most countries of the world, but their application varies from one state to another depending on the philosophy of its economic system and that governmental support represents a stream of spending that the state decides to pay without being matched by a stream of goods and services. From this point of view, government support policies are one of the most important macro policies that achieve economic growth and achieve social balance as it allows directing part of the public expenditure to address the phenomenon of poverty in terms of enabling the low-income classes to have the opportunity to live through redistributing income across different support groups In accordance with government support policies and in line with the requirements of the national strategy to counter poverty in Iraq .
Direct visualization and profiling of protein misfolding and aggregation in live cells.

Abstract Over the past few years, research tools have been developed to monitor the multistep protein aggregation process in live cells, a process that has been associated with a growing number of human diseases. Herein, we describe recent advances in methods that can either survey the distribution of aggregation at the level of the cellular proteome using mass spectroscopy or discern the multistep aggregation process of specific proteins of interest via fluorescence signals. Future development and application of such technologies are expected to provide insights on mechanisms, diagnosis, and treatment of diseases rooted in protein aggregation.
Human Age Estimation from Gene Expression Data using Artificial Neural Networks.

The study of signatures of aging in terms of genomic biomarkers can be uniquely helpful in understanding the mechanisms of aging and developing models to accurately predict the age. Prior studies have employed gene expression and DNA methylation data aiming at accurate prediction of age. In this line, we propose a new framework for human age estimation using information from human dermal fibroblast gene expression data. First, we propose a new spatial representation as well as a data augmentation approach for gene expression data. Next in order to predict the age, we design an architecture of neural network and apply it to this new representation of the original and augmented data, as an ensemble classification approach. Our experimental results suggest the superiority of the proposed framework over state-of-the-art age estimation methods using DNA methylation and gene expression data.
The Privatization of Nature Conservation in Russia

An American geographer describes and evaluates the first attempt to establish a large, privately operated nature reserve and sustainable agricultural economy in post-Soviet Russia. A 5,200 ha preserve along the Amur River, known as Murav'yovka Park, was acquired as a 50-year lease from nearby collective farms. The preserve's role as an important breeding area for migratory cranes is examined in the context of international conservation efforts and funding; other functions (e.g., agricultural production, environmental education) also are discussed, based on field observations in 1998. Developments at Murav'yovka are symptomatic of broader problems involved with privatizing nature conservation in contemporary Russia. Journal of Economic Literature, Classification Numbers: Q20, Q24, Q26. 1 figure, 2 tables, 28 references.
Regeneration in Annelids

Annelids, like many other invertebrate animals, replace lost body parts in a process called regeneration. However, the ability to regenerate lost segments is present in some groups and not others, for example leeches do not regenerate lost segments. Anterior and posterior regeneration involves the formation of a bud containing stem cells that differentiate into the new head or tail segments. Annelid regeneration also involves remodelling of surviving body fragments. The ability of annelids to regenerate tail segments appears to be nearly universal among species capable of regeneration. The ability to regenerate head segments, although common, is not universal and can depend on the number of segments lost. The absence and presence of regeneration across annelid groups, including closely related species, suggests that regeneration ability may be an ancient trait that has been lost in some species during annelid evolution. Why regeneration varies among annelid species remains an intriguing question for life scientists. Key Concepts: Annelids vary in their capability for regenerating body segments, including among closely related species. The ability of annelids to regenerate posterior segments appears to be nearly universal. The ability of annelids to regenerate anterior segments, although common, is not universal and is often limited depending on the number of segments lost. Annelid regeneration may involve both epimorphic and morphallactic mechanisms. Multiple losses and gains of regeneration ability have likely occurred during annelid evolution. Why regenerative ability among annelids varies extensively remains unclear. Keywords: annelid; polychaete; oligochaete; leech; regeneration; epimorphosis; morphallaxis; segment; nervous system; evolution
Two Essays on District of Columbia v. Heller

The first of these companion essays, Heller and the New Originalism, forthcoming in the Ohio State Law Journal, argues that the new originalism, as exemplified in Heller, does not avoid the general kinds of difficulties associated with the old originalism, at least to the extent that the new originalism is defended as providing, in Justice Scalia's terms, a solid, rock-hard Constitution. It describes several difficulties with the new originalism as displayed in Heller, including the assumption that meanings are stable over long periods of time, the possibility that meanings of constitutional terms are contested at the time the terms are inserted into the Constitution, and the difficulty that meanings are necessarily indexed to the conditions under which words are used. The second essay, Heller and the Perils of Compromise, forthcoming in the Lewis & Clark Law Review, describes the ways in which the absolutist rhetoric about the appropriate method of constitutional interpretation that predominates in Justice Scalia's majority opinion in Heller is in tension with the asserted presumptive constitutionality of numerous gun regulations, and argues that interest-balancing of the sort Justice Scalia criticizes is inevitable in constitutional interpretation, even within Justice Scalia's assertedly non-balancing approach. It speculates that the compromises embedded in Heller make it likely that the decision will unravel, leading either to quite robust restrictions on gun regulation or, more likely, a quite weak Second Amendment. I suggest that the Heller decision may be for the Second Amendment what early decisions were for the so-called Federalism and Takings Revolutions: decisions that promised real change in prevailing constitutional doctrine, but that failed to deliver on the promise.
Cerebral white matter: neuroanatomy, clinical neurology, and neurobehavioral correlates.

Lesions of the cerebral white matter (WM) result in focal neurobehavioral syndromes, neuropsychiatric phenomena, and dementia. The cerebral WM contains fiber pathways that convey axons linking cerebral cortical areas with each other and with subcortical structures, facilitating the distributed neural circuits that subserve sensorimotor function, intellect, and emotion. Recent neuroanatomical investigations reveal that these neural circuits are topographically linked by five groupings of fiber tracts emanating from every neocortical area: (1) cortico-cortical association fibers; (2) corticostriatal fibers; (3) commissural fibers; and cortico-subcortical pathways to (4) thalamus and (5) pontocerebellar system, brain stem, and/or spinal cord. Lesions of association fibers prevent communication between cortical areas engaged in different domains of behavior. Lesions of subcortical structures or projection/striatal fibers disrupt the contribution of subcortical nodes to behavior. Disconnection syndromes thus result from lesions of the cerebral cortex, subcortical structures, and WM tracts that link the nodes that make up the distributed circuits. The nature and the severity of the clinical manifestations of WM lesions are determined, in large part, by the location of the pathology: discrete neurological and neuropsychiatric symptoms result from focal WM lesions, whereas cognitive impairment across multiple domains—WM dementia—occurs in the setting of diffuse WM disease. We present a detailed review of the conditions affecting WM that produce these neurobehavioral syndromes, and consider the pathophysiology, clinical effects, and broad significance of the effects of aging and vascular compromise on cerebral WM, in an attempt to help further the understanding, diagnosis, and treatment of these disorders.
Functional Imaging of Nervous Systems Using Voltage‐Sensitive Dyes

Voltage-sensitive dyes are small molecules that bind to cell membranes and change their optical properties, absorption or fluorescence, in response to changes in membrane potential, the voltage across the membrane. These optical changes are extremely rapid and tend to be linear reporters of local electrical events. Thus, these ‘potentiometric probes’ behave as molecular voltmeters and can be used, with a high-speed camera or other image dissector, for functional imaging of electrical activity including action potentials, synaptic potentials, and passive (electrotonic) signals. No physical contact with the object is required and spatial and temporal resolution is limited primarily by signal-to-noise considerations. Such millisecond time-resolved functional imaging can be of single cells, of regions of cells or of nervous systems, of cardiac muscle or of any other electrically active tissue. In the nervous system, functional imaging of electrical activity can lead to an understanding of the spatio-temporal relationships between neurons and of their functional connectivity. Key Concepts: In electrically excitable cells, the membrane potential can change extremely rapidly. Some coloured molecules (dyes) change their optical properties in response to changes in the local electric field. Changes in the optical properties of the molecules that stain-cell membranes can be used to follow rapid changes in membrane potential. A high-speed camera, usually with a microscope, can be used together with these dyes to monitor the electrical activity at hundreds or even thousands of sites, virtually simultaneously. Functional imaging of electrical activity can lead to an understanding of the spatio-temporal relationships in nervous systems, and to the functional connectivity among neurons. Keywords: imaging; fluorescence; voltage-sensitive dye; membrane potential; action potential
The Call of Vocation in Julius Caesar and Coriolanus

AbstractIn the classical worlds of Julius Caesar and Coriolanus Shakespeare finds the conditions in which to isolate and analyze the Christian doctrine of vocation, the idea that individuals are destined to fill a place in the body politic or the congregation of believers. Many of Shakespeare's plays pit character against calling. In the Roman tragedies the tension is especially acute. The principals struggle to discern a call in a world dismembered by revolution to the point that a voice can come from a wound. Repeatedly, civic turmoil is described in terms of creation and apocalypse; vocation, hinted at through plot turns and Pauline phrasing, should span and structure the interim. But both plays present a monolithic title character whose all‐consuming integrity threatens to annihilate the society that produced him. Under the pressure of events, Brutus' identity splits, while his co‐conspirators scramble for parts that suddenly seem too few to go around. Coriolanus despises “the many” and their trades t...
Ionizing radiation effects on commercial 256 K EEPROM's

The effects of both steady-state and pulsed ionizing radiation on five types of electronically erasable programmable read-only memories (EEPROM's) was determined. Write- and read-failure levels and the changes in access time and standby current were determined for total dose. Data upset, latchup and burnout tests were made in the dose-rate environment. >
The effect of prior exercise on oral glucose tolerance in late gestational women.

Glucose tolerance deteriorates over the course of a normal human pregnancy as a result of increased peripheral insulin resistance. In contrast, physical exercise has been shown to improve glucose tolerance and blunt the insulin response to a glucose load in insulin-resistant individuals. The purpose of this study was to determine the effect of exercise on glucose tolerance and the insulin response in healthy women during the third trimester of pregnancy (33 weeks of gestation). Five subjects underwent oral glucose tolerance tests (a) 30 min following a 30-min exercise bout on a cycle ergometer at a relative intensity of 50% maximal aerobic capacity, and (b) on a control day without prior exercise. The area under the glucose concentration curve was not different between trials, while the area under the insulin concentration curve was decreased by 23% in the exercise trial compared with the control trial (P < 0.05). These results suggest that the insulin response to a glucose load is improved in late gestational women by a single bout of moderate intensity exercise.