cssi/SciSciGPT-SciSciNet huggingface dataset:
Deciphering the Code of the Cancer Genome: Mechanisms of Chromosome Rearrangement

Chromosome rearrangement plays a causal role in tumorigenesis by contributing to the inactivation of tumor suppressor genes, the dysregulated expression or amplification of oncogenes and the generation of novel gene fusions. Chromosome breaks are important intermediates in this process. How, when and where these breaks arise and the specific mechanisms engaged in their repair strongly influence the resulting patterns of chromosome rearrangement. Here, we review recent progress in understanding how certain distinctive features of the cancer genome, including clustered mutagenesis, tandem segmental duplications, complex breakpoints, chromothripsis, chromoplexy and chromoanasynthesis may arise.
The link between depression and physical symptoms.

Physical symptoms are common in depression, and, in fact, vague aches and pain are often the presenting symptoms of depression. These symptoms include chronic joint pain, limb pain, back pain, gastrointestinal problems, tiredness, sleep disturbances, psychomotor activity changes, and appetite changes. A high percentage of patients with depression who seek treatment in a primary care setting report only physical symptoms, which can make depression very difficult to diagnose. Physical pain and depression have a deeper biological connection than simple cause and effect; the neurotransmitters that influence both pain and mood are serotonin and norepinephrine. Dysregulation of these transmitters is linked to both depression and pain. Antidepressants that inhibit the reuptake of both serotonin and norepinephrine may be used as first-line treatments in depressed patients who present with physical symptoms. Many physicians consider patients to be in remission when their acute emotional symptoms have abated, but residual symptoms—including physical symptoms—are very common and increase the likelihood of relapse. All symptoms must be measured in order to achieve full remission. There are a number of short yet accurate measurement tools (rating scales) available that effectively measure the remission of physical symptoms as well as emotional symptoms.
Numerical Simulation of DC and RF Glow Discharges

As part of an ongoing research effort on plasma actuators for flow control, a numerical study of DC glow discharges and γ-mode RF glow discharges has been carried out. For simplicity, the study focused on two-dimensional problems. Several experimentally observed features of these discharges were reproduced in the numerical computations, including the expansion of the electrode spot with increasing discharge current. The current results provide a basic validation of the computer code, but detailed experimental data are needed for true code validation.
Comparative Retail Grocery Ceiling Prices in Los Angeles

T HE IMPOSITION of price ceilings under the general maximum price regulation gives an unusual opportunity to compare competitive retail prices for standardized commodities in March, I942. One of the best fields in which to make such a comparison is that of retail groceries in stores of a comparable size in a given area. Small, neighborhood stores cannot appropriately be included since they usually sell on credit and have something of a local monopoly based upon convenience of location. While the "highest price in March" probably did not occur on the same day in all stores, the relative ceiling prices are nevertheless significant indicators of price policy.
Effect of Digitized Mammography Film on Disease Diagnoses

Objective To evaluate the effect of mammography digitized film on disease diagnosis.Materials and Methods To digitizeX-ray films of 72 female patients through medical scanner.Three radiologists interpreted X-ray films and digital images respectively with time interval of four weeks.The interpreting results were analyzed by the DBM MRMC software and ROC curves were painted by Excel 2003.Results The average Az values of two interpretation are 0.922 and 0.859 respectively.There is no significant difference between two results.Conclusion The digitized films of mammography can be consolidated into PACS.
The Influence of Urinary Diversion on Experimental Gastrocystoplasty

Gastrocystoplasty is used to augment the bladder of patients with decreased renal function to prevent development or worsening of metabolic acidosis. We recently observed a perforated peptic ulcer in the gastric portion of a defunctionalized gastrocystoplasty. We postulated that the lack of buffering action of urine precipitated peptic ulcer disease in the gastrocystoplasty. To explore this possibility further, we conducted an experiment. In 12 adult female mongrel dogs (weight 15 to 26 kg.) the bladder was divided into right and left segments. One kidney was removed and both hemibladders were capped with a vascularized segment of gastric body. Thus, 1 side (wet) remained exposed to urine, while the other side (dry) was drained to the abdominal wall with a cystostomy tube. The animals were divided into 2 groups: 9 in group 1 received no drugs to modify gastric secretion and 3 in group 2 received a hydrogen (H2) blocker. Three animals in group 1 had perforation of the vesical part of the dry gastrocystoplasty 2 to 3 weeks postoperatively and were sacrificed. The others were sacrificed 3 to 6 weeks postoperatively. Serum gastrin levels remained normal in all animals. Gross and histological examinations of the augmented bladders in group 1 revealed ulcerations of the bladder segment of the wet and dry gastrocystoplasties but the lesions were more numerous and prominent on the dry side in all animals, particularly those in which the perforations occurred. A peptic ulcer was noted in the gastric portion of the dry gastrocystoplasty in 1 animal. The bladder epithelium of the dry gastrocystoplasty showed glandular metaplasia in several animals in this group. In group 2 the wet gastrocystoplasty showed normal histology except in 1 dog that had mild inflammation and focal superficial ulceration in the vesical portion. On the other hand, the dry gastrocystoplasty showed severe inflammation and ulcerations in 2 animals, and mild inflammation of the vesical portion in 1. There were no perforations in this group. This experiment demonstrates that gastrocystoplasty produces cystitis but that these changes are more prominent in the absence of urine, as indicated by the severity of the lesions, perforations and metaplasia. Peptic ulcer disease occurred in the gastric portion of the dry gastrocystoplasty in 1 animal. The use of H2 blockers decreases the incidence of ulceration in wet gastrocystoplasty but it seems to have less influence on the ulceration of dry gastrocystoplasty. Clinicians must be alerted to the risk of perforation of dry gastrocystoplasty.
Cardiac performance following hypertonic saline.

Abstract The present study was undertaken to examine cardiovascular function before and after either intravenous or intra-arterial infusion of hypertonic saline (7.5% NaCl) in halothane-anesthetized dogs. A high-fidelity micromanometer and ultrasonic dimension transducers were implanted to measure pressure and wall motion of the left ventricle (LV). Cardiac output (CO) was measured using an electromagnetic flowmeter and thermodilution. The slope (Ees) of the linear regression of the LV pressure-diameter relationship was used as an index of cardiac contractility. Intravenous infusion of hypertonic saline (3 ml/kg) increased mean arterial pressure (MAP, 104 +/- 6 to 116 +/- 6 mmHg), heart rate (HR, 124 +/- 21 to 140 +/- 13 bpm), CO (3.2 +/- 0.9 to 4.2 +/- 0.5 l/m) and Ees (11.6 +/- 2.1 to 14.8 +/- 1.9 mmHg/mm). Systemic vascular resistance (SVR) fell by 18%. The above responses were similar whether infusion was intravenous or intra-arterial into innervated or denervated hind limbs. While nerve blockade at T-4 (xylocaine) attenuated the changes in CO and SVR and completely prevented the tachycardia, the inotropic response remained intact. These studies suggest that the cardiac effects of hypertonic saline infusion are not mediated by pulmonary or peripheral osmoreceptors and the increased contractility may result from a direct myocardial effect of increased osmolality.
SERUM ALBUMIN: AMINO ACID SEQUENCE

Publisher Summary This chapter focuses on amino acid sequence. It reviews the primary structures of bovine and human serum albumin. Elucidation of the amino acid sequence of serum albumin has led to much greater insights into the structure, function, and evolution of this protein than was anticipated. The application of the three-dimensional models of albumin are supported by a variety of evidence, namely, helix content, properties of fragments, reactive groups, binding properties, protein dimensions, and similarity to the G-H region of globin structure. The models are specific enough that details can be tested and refined by further experiments, such as affinity labeling, crosslinking, and further preparation and analysis of properties of fragments.
Core Competencies and the Next Accreditation System

This chapter presents the principles of the accreditation of residency training programs in the United States as provided by the Accreditation Council for Graduate Medical Education, the concept of general or core competencies (patient care, medical knowledge, practice-based learning and improvement, professionalism, interpersonal and communication skills, and systems-based practice), the concept of Milestones as a new, expanded, specialty-specific framework for teaching and evaluating residents, and the Next Accreditation System. The chapter offers general guidance for trainees entering graduate medical education and training in the United States with regard to understanding the next accreditation system and its basic tenets. It also provides recommendations for the implementation of these concepts in the education of international medical graduates entering residency training in the United States.
Ethnic Pluralism: The U.S. Model

The striking feature about American society is not its much- vaunted ethnic pluralism but its capacity to absorb newcomers. This has been much less true of nonwhite groups until fairly recently, but is happening increasingly of late.
An exact approach to ridge regression for big data

Ridge regression is an important approach in linear regression when explanatory variables are highly correlated. Although expressions of estimators of ridge regression parameters have been successfully obtained via matrix operation after observed data are standardized, they cannot be used to big data since it is impossible to load the entire data set to the memory of a single computer and it is hard to standardize the original observed data. To overcome these difficulties, the present article proposes new methods and algorithms. The basic idea is to compute a matrix of sufficient statistics by rows. Once the matrix is derived, it is not necessary to use the original data again. Since the entire data set is only scanned once, the proposed methods and algorithms can be extremely efficient in the computation of estimates of ridge regression parameters. It is expected that the basic knowledge gained in this article will have a great impact on statistical approaches to big data.
Ventilator Management: A Practical Approach to Respiratory Failure in Combat Casualties

The survival of combat casualties from the point of injury to definitive medical care has significantly improved over the last decade. Survival is >95% for casualties who survive their initial injury and are evacuated to definitive care. This improvement can be credited to several factors, including advances in body armor, an improved skill set of prehospital personnel, the presence of forward surgical teams, the availability of surgical and critical care assets in austere environments, and deployment of an increased number of soldiers skilled in basic and advance trauma life support. Early and effective management of battlefield casualties can be successful when the basic principles of prehospital, trauma, and critical care are maintained throughout the entire medical evacuation process. A critical care-trained physician may not be available to treat casualties; thus, all deploying physicians should be familiar with principles of respiratory failure and ventilator management.
OP0068 Practices participating in the ACR'S rheumatology informatics system for effectiveness (RISE) national registry show improvements in quality of care

Background The ACR launched the RISE registry in 2014 to facilitate quality improvement on a national scale. The registry passively extracts electronic health record (EHR) data from rheumatology practices, aggregates and analyzes these data centrally, and feeds performance on quality measures back to clinicians using a web-based dashboard. Objectives We used data from RISE to 1) examine variation in performance on quality measures across practices, and 2) evaluate trends in measure performance over time. Methods RISE9s informatics platform continuously collects data from the EHRs of participating practices, allowing centralized aggregation and analysis of quality measures. We analyzed data collected between July 1, 2014-July 1, 2016 on all patients seen by 294 clinicians across 63 practices. Measures in the areas of rheumatoid arthritis, drug safety, preventive care and gout were examined. Performance on quality measures, defined as the percentage of eligible patients receiving recommended care, was examined at the practice level. To examine trends in performance over time, we took the subset of practices that continuously participated in RISE since its inception (n=44), and developed 1) control charts and 2) logistic regression models, in which the outcome was practice-level performance each month and the predictor was time. Results Data from 289,812 patients was examined. Mean (SD) age was 59 (16) years, 75% were female, 21% were racial/ethnic minorities, and 37% had public insurance. Most rheumatologists were in a group practice (73%); 25% were in solo practice and 2% part of a larger health system. Performance on measures varied significantly across practices (Table). The largest gaps were observed for gout and preventive care. For 4 of 5 measures for which the Medicare program has set national benchmarks, average performance of RISE practices exceeded targets. Of 11 measures, performance improved over time on 5 measures (p Conclusions We found significant variation in performance on quality measures across RISE practices, with the largest gaps seen in gout care and preventive care. Some practices have achieved a very high level of performance. Over time, RISE practices demonstrated improvement in over half of the measures examined. As rheumatologists aim to improve quality of care, RISE will, by design, allow participants to measure, benchmark, and continuously monitor performance improvement. Disclosure of Interest None declared
Expanded Role for EKLF/KLF1 Within the Hematopoietic Lineage

Erythroid Kruppel-like factor (EKLF) is a transcriptional activator that was originally identified in 1993 and has since provided a significant window into the carefully orchestrated process of erythroid gene expression, particularly as it plays a critical role in β-like hemoglobin switching. However, later observations have suggested other roles for this protein. This presentation discusses the lines of evidence that together open up a new hematopoietic horizon for EKLF function.
Abstract 16308: Vitamin K Epoxide Reductase Complex 1 (vkorc1) a New Insight into the Molecular Design, Operation and Mechanism of Warfarin Inhibition

Gamma-carboxylation of vitamin K dependent proteins are dependent on the formation of reduced vitamin K by VKOR.VKORC1 is believed to be a subunit of a VKOR enzyme complex in the ER membrane and harbors a warfarin sensitive CXXC redox center. Previous kinetic studies proposed that warfarin binds strongly to CXXC center in VKOR when present in its oxidized form. In this work, we presented new model of warfarin inhibition of VKOR. Extracted rat liver microsomes were pre reduced with 5 mM Tris(hydroxypropyl)Phosphine (THP) and VKOR inhibition was measured by warfarin. In some of the experiments, oxidized extracted microsomes were used to determine the VKOR inhibition by warfarin. In both the oxidized and reduced microsomes warfarin was able to completely abolish the VKOR activity regardless of reduced or oxidized state of VKOR CXXC redox center. Our finding of warfarin inhibition does not agree with the previous model of VKOR inhibition by warfarin which suggests that warfarin only inhibits VKOR activity when the CXXC redox center of VKOR is reduced. To further extend our previous finding that Protein disulfide isomerase (PDI) plays an important role in the reduction of VKOR CXXC redox center, we added purified recombinant PDI to rat liver extracted microsomes, which had been washed extensively to completely remove indigenous PDI from the microsomes. To these membranes, we reconstituted the VKOR complex by adding the purified recombinant PDI and VKOR activity was triggered by reduced RNAse. In control experiments, purified PDI was not added to the washed microsomes. Washed and extracted microsomes, when reconstituted with purified PDI, triggered VKOR supported gamma carboxylase activity. Furthermore, we have purified recombinant rat VKOR from sf9 insect cells and assess the role of PDI in VKOR activity in presence of reduced RNase and lipid rich buffer. In our vitro system, reduced RNase triggered VKOR activity in presence of PDI suggests an important role of PDI in modulating VKOR activity. In addition, we co-immunolocalized PDIVKOR complex in ER of HEK293 cells supports our previous finding that PDI interacts with VKOR in the ER. Our new findings presented here modify our current understanding of operation of the posttranslational gamma carboxylation system in the ER.
PLENUM-2A, A Program for Transient Analysis of Liquid-Metal Fast Breeder Reactor Outlet Plenums

A new computer program, PLENUM-2A, has been developed to predict the conditions in the outlet plenum of a liquid-metal fast breeder reactor after a transient scram. This program divides the tansient into three main consecutive discrete states. Two additional stages, one occurring before the transiet begins and the other occurring as the transient ends, are also considered. The three main stages are described in detail, and calculations and experimental results are compared. The agreement between the calculations and experimental data is very good.
Plasma 25-Hydroxyvitamin D and the Longitudinal Risk of Sepsis in the REGARDS Cohort.

BACKGROUND Low baseline plasma 25-hydroxyvitamin D (25(OH)D) is associated with increased risk of acute respiratory infections, but its association with long-term risk of sepsis remains unclear. METHODS We performed a case-cohort analysis of participants selected from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a US cohort of 30239 adults aged ≥45 years. We measured baseline plasma 25(OH)D in 711 sepsis cases and in 992 participants randomly selected from the REGARDS cohort. We captured sepsis events by screening records with International Classification of Disease methods and then adjudicating clinical charts for significant, suspected infection and severe inflammatory response syndrome criteria on presentation. RESULTS In the study sample, the median age of participants was 65.0 years, 41% self-identified as black, and 45% were male. Mean plasma 25(OH)D concentration was 25.8 ng/mL; for 31% of participants, it was 33.6 ng/mL, lower 25(OH)D groups were associated with higher hazards of sepsis (16.5-22.4 ng/mL; hazard ratio [HR]; 3.21; 95% confidence interval [CI], 1.98 to 5.21 and <16.5 ng/mL; HR, 6.81, 95% CI, 3.95 to 11.73). Results did not materially differ in analyses stratified by race or age. CONCLUSIONS In the REGARDS cohort of community-dwelling US adults, low plasma 25(OH)D measured at a time of relative health was independently associated with increased risk of sepsis.
Chronic Therapy with Sacubitril/Valsartan Reduces Plasma Troponin-I Level in Dogs with Experimentally-Induced Cardiorenal Syndrome

Introduction Ongoing loss of cardiomyocytes occurs in heart failure (HF) and contributes to progressive worsening of the HF state. Sacubitril/Valsartan (S/Val), a combined angiotensin-II receptor blocker (Val) and neprilysin inhibitor (S) in a 1:1 molar ratio, was shown to reduce the risk of cardiovascular death or HF hospitalization in patients with HF and reduced left ventricular (LV) ejection fraction (EF). Chronic therapy with S/VAL was also shown to improve LV systolic function in dogs with experimentally-induced cardiorenal syndrome. Objective This study tested the hypothesis that chronic therapy with S/Val in dogs with cardiorenal syndrome ameliorates ongoing loss of cardiomyocytes as evidenced by lowering plasma levels of troponin-I (TnI). Methods 14 dogs with coronary microembolization-induced HF and renal dysfunction induced by unilateral nephrectomy with imposed stenosis of the contralateral renal vein, were randomized to 3 months therapy with S/Val (100 mg once daily, n=7) or no therapy (control, CON, n=7). LV EF was measured before (PRE) and at 12 weeks after initiating therapy with S/Val (POST). High sensitivity plasma TnI was measured when animals were normal (NL) and again after induction of cardiorenal syndrome and subsequently at 2, 4, and 12 weeks after initiating S/Val therapy. TnI levels were determined using a commercially available Ultra-Sensitive Dog Cardiac Troponin-I Elisa kit and the concentration was expressed in ng/ml. Results In CON dogs, LV EF was unchanged from PRE to POST (35 ± 1 vs. 36 ± 1 %) but increased significantly from PRE to POST in S/Val-treated dogs (34 ± 1 vs. 41 ± 2 %, p Table ) and remained elevated throughout the follow-up period. In contrast, in S/Val-treated dogs, TnI levels decreased gradually during the therapy period ( Table ). Conclusions In dogs with cardiorenal syndrome, S/Val reduces plasma TnI levels compared to untreated CON. This observations suggests that chronic therapy with S/Val attenuates or prevents ongoing loss cardiomyocytes, a characteristic feature of the HF state.
Evaluation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) mutagenicity using in vitro and in vivo Pig-a assays.

Abstract 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a genotoxic carcinogen found in tobacco and tobacco smoke. Several in vitro and in vivo assays have been used for evaluating the genotoxicity of tobacco smoke and tobacco smoke constituents like NNK, yet it is not clear which in vitro assays are most appropriate for extrapolating the in vitro responses of these test agents to animal models and humans. The Pig-a gene mutation assay can be performed in vitro, in laboratory animals, and in humans, a potential benefit in estimating in vivo responses from in vitro data. In the current study we used Pig-a as a reporter of gene mutation both in vitro, in L5178Y/Tk+/− cells, and in vivo, in Sprague-Dawley rats. NNK significantly increased Pig-a mutant frequency in L5178Y/Tk+/− cells, but only at concentrations of 100 μg/ml and greater, and only in the presence of S9 activation. Pig-a mutations in L5178Y/Tk+/− cells were detected in 80% of the NNK-induced mutants, with the predominate mutation being G→A transition; vehicle control mutants contained deletions. In the in vivo study, rats were exposed to NNK daily for 90 days by inhalation, a common route of exposure to NNK for humans. Although elevated mutant frequencies were detected, these responses were not clearly associated with NNK exposure, so that overall, the in vivo Pig-a assays were negative. Thus, while NNK induces mutations in the in vitro Pig-a assay, the in vivo Pig-a assay has limited ability to detect NNK mutagenicity under conditions relevant to NNK exposure in smokers.
Modified endoscopic endonasal approach with a minimally invasive transoral approach—an adjunct to infrapetrous approaches

OBJECTIVES/HYPOTHESIS To evaluate the potential of a minimally invasive transoral-transpalatal approach (MITA) to the retrocarotid petrous apex, as an adjunct to endoscopic endonasal approaches (EEAs). STUDY DESIGN Cadaver study. METHODS Five cadaveric specimens were dissected raising an inverted U-shaped palatal mucoperiosteal flap, and drilling a rectangular palatotomy (between the greater palatine foramens, and just anterior to the palatine aponeurosis). This allowed a transpterygoid EEA with cross-court access (contralateral line of sight), followed by an extradural clivectomy that exposed the petroclival junction bilaterally. Surgical targets were marked on the posterior and medial surface of the petrous internal carotid artery (ICA), at its anterior genu, midhorizontal portion, and posterior genu. For each target and approach, the surgical freedom and angles of approach (in the horizontal and vertical planes) were calculated and statistically compared. RESULTS Compared to EEA, the MITA resulted in greater surgical freedom for all targets, with the highest values at the anterior genu (1,661.37 mm2 vs. 312.76 mm2 , P <.001), and maintaining superiority in this regard all the way to the posterior genu (847.84 mm3 vs. 138.91 mm3 , P < .005). MITA also offered greater angles of approach for all targets. CONCLUSIONS This study suggests that the MITA may be indicated to supplement the exposure provided by a transpterygoid EEA. This technique, associated with low potential morbidity, offers an alternative to internal carotid lateralization while managing extradural lesions that are adjacent to the petrous ICA. LEVEL OF EVIDENCE NA Laryngoscope, 129:339-343, 2019.
A sociolinguistic indicator of group membership

Previous research into the acoustical paralinguistic features of dyadic interview conversations by this author have shown that conversation partners adapt features of their paralinguistic expression to one another, and that this adaptation is continually reconstituted as the conversation proceeds over time. The research reported herein shows that the adaptation phenomenon is also capable of quantitatively and objectively selecting out specific conversations associated with persons who share membership in a consolidated group. It is apparent in this study that members of a consolidated group, in comparison with disparate individuals, engage in a kind of paralinguistic cryptocommunication constitting a code signifying their membership. This form of communication is obviously not consciously known and controlled by conversation partners, for the means of extricating it derives from the employment of several intricate computer routines. In the final portion of this article, prominent competing explanations of the results are discussed. These alternate explanations generally take the form of technical artifacts that offer a more prosaic account of the research results. In order to dispel these looming technical artifactual possibilities, various critical tests are advanced. The results of this research are a substantial and innovative step in the refinement of method and instrumentation to further our understanding of the sociolinguistic binding medium of group membership.
CEMAP: General Usage Guide

Abstract : CEMAP software is a wide-ranging solution to the many practical and logistical problems that analysts face when performing the basic data processing steps necessary for using analytic software. CEMAP transforms real-world source data into a form that is specifically formatted to the exacting requirements of particular social network analysis software. This report provides the concepts important to CEMAP as well as step-by-step instructions on how an analyst uses CEMAP as either a stand-alone or ORA/Automaphosted interactive system, or as an automated command-line batch system. Taking the short time to learn how to use CEMAP, which is easy, will save a great deal of time in one's workflow within the analytic process and will put a wealth of popular real-world datasets within easy reach. This report guides the reader through the major aspects of CEMAP from the perspective of the role the operator plays in the work flow from raw data extract, transformation, and the loading of network data, for subsequent analysis.
Development of data-driven models for the flow cytometric crossmatch.

Abstract HLA laboratories use virtual crossmatching (VXM) to predict recipient and donor compatibility using HLA antibody data and donor HLA type. Increasingly, transplant centers are utilizing VXM as the final compatibility determination prior to transplant. However, the VXM interpretation is based on HLA experience of individual transplant centers. This study developed data-driven algorithms that predicted flow cytometric crossmatch (FCXM) outcomes using HLA antibody mean fluorescent intensity (MFI) data and donor HLA typing without the need for human interpretation. Two algorithms were evaluated; an MFI Optimal-Threshold model and a Least-Squares-Fitting model. The Optimal-Threshold model correctly determined between 81.5% and 85.5% of T or B-cell responses. A class I antibody MFI threshold of 4670 was optimal for predicting T-cell response while an antibody MFI threshold of 6180 was optimal for predicting B-cell responses. HLA class I antibodies had a 1.47-fold greater influence on FCXM outcomes than class II antibodies. HLA-B antibodies influenced T and B-cell responses more than HLA-A or -C (-B > -A > -C). The Least-Squares-Fitting model increased accuracy to 94.1% and 88.8% for T and B-cell responses, respectively. The algorithms described here provide enhanced FCXM prediction and novel insights into the influence of specific HLA antibodies on the crossmatch outcome.
Linkage of Non-receptor Tyrosine Kinase Fyn to mGlu5 Receptors in Striatal Neurons in a Depression Model

The Src family kinase (SFK) is a subfamily of non-receptor tyrosine kinases. The SFK member Fyn is enriched at synaptic sites in the limbic reward circuit and plays a pivotal role in the regulation of glutamate receptors. In this study, we investigated changes in phosphorylation and function of the two key SFK members (Fyn and Src) and SFK interactions with a metabotropic glutamate (mGlu) receptor in the limbic striatum of adult rats in response to chronic passive stress, i.e., prolonged social isolation which is a pre-validated animal paradigm modeling depression in adulthood. In rats that showed typical anhedonic/depression-like behavior after chronic social isolation, phosphorylation of SFKs at a conserved and activation-associated autophosphorylation site (Y416) was not altered in the two subdivisions of the striatum, the nucleus accumbens and caudate putamen. The total level of phosphorylation and kinase activity of individual Fyn and Src immunopurified from the striatum also remained stable after social isolation. Noticeably, Fyn and Src were found to interact with a Gαq-coupled mGlu5 receptor in striatal neurons. The interaction of Fyn with mGlu5 receptors was selectively elevated in socially isolated rats. Moreover, social isolation induced an increase in surface expression of striatal mGlu5 receptors, which was reduced by an SFK inhibitor. These results indicate that Fyn interacts with mGlu5 receptors in striatal neurons. Adulthood social isolation in rats enhances the Fyn-mGlu5 interaction, which appears to be critical for the upregulation of surface mGlu5 receptor expression in striatal neurons.
A Unified Knee and Ankle Design for Robotic Lower-Limb Prostheses

The recent development in robotic lower-limb prostheses have helped amputees restore their joint functions and enabled them to perform diverse and energetically challenging daily locomotive activities, which are usually beyond the functionality of the passive prostheses. Although robotic knee prosthesis and ankle prosthesis have their common purpose of restoring joint functions for lower-limb amputees, they have generally been treated as distinct, standalone devices. Realizing such common objective and leveraging the similarities between the knee and ankle design, in this paper, a new unified design approach is proposed, which adopts a Common Core Components Knee-Ankle Prosthesis design. This research specifically targets the robotic knee/ankle joint design unification as a major goal, while fulfilling their biomechanical requirements, especially the torque, speed, and range of motion and form factor requirements associated with the knee/ankle joints. Based on such requirements, a unified knee/ankle joint design was developed, which features an identical transmission mechanism and system layout while still providing the desired level of flexibility (joint-specific customization) through swappable timing-belt pulleys.
Fully synthetic neuroimaging data for replication and exploration.

Abstract Scientific transparency, data exploration, and education are advanced through data sharing. However, risk for disclosure of personal information and institutional data sharing regulations can impede human subject/patient data sharing and thus limit open science initiatives. Sharing fully synthetic data is an alternative when it is not possible to share real or observed data. Here we describe a data sharing approach that borrows principles and methods from multiple imputation to replace observed values with synthetic values, thereby creating a fully synthetic neuroimaging dataset that accurately represents the covariance structure of the observed dataset. Predictor tables composed of demographic, site, behavioral and total intracranial volume (ICV) variables from 264 pediatric cases were used to create synthetic predictor tables, which were then used to synthesize gray matter images derived from T1-weighted data. The synthetic predictor tables demonstrated pooled variance and statistical estimates that closely approximated the observed data, as reflected in measures of efficiency and statistical bias. Similarly, the synthetic gray matter data accurately represented the variance and voxel-level associations with predictor variables (age, sex, verbal IQ, and ICV). The magnitude and spatial distribution of gray matter effects in the observed imaging data were replicated in the pooled results from the synthetic datasets. This approach for generating fully synthetic neuroimaging data has widespread potential for data sharing, including replication, new discovery, and education. Fully synthetic neuroimaging datasets can enable data-sharing because it accurately represents patterns of variance in the original data, while diminishing the risk of privacy disclosures that can accompany neuroimaging data sharing.
Steroid binding activity is retained in a 16-kDa fragment of the steroid binding domain of rat glucocorticoid receptors.

The steroid binding domain of the rat glucocorticoid receptor is considered as extending from amino acids 550 to 795. However, such a synthetic protein (i.e. amino acids 547-795; Mr approximately 31,000) has been reported to show very little affinity for the potent synthetic glucocorticoid dexamethasone. We now disclose that digestion of steroid-free rat glucocorticoid receptors with low concentrations of trypsin yields a single species, of Mr = 16,000, that is specifically labeled by dexamethasone 21-mesylate. This 16-kDa fragment retains high affinity binding for [3H]dexamethasone that is only approximately 23-fold lower than that seen with the intact 98-kDa receptor. Analysis of the protease digestion patterns obtained both with trypsin and with lysylendopeptidase C allowed us to deduce the proteolytic cleavage maps of the receptor with these enzymes. From these protease maps, the sequence of the 16-kDa fragment was identified as being threonine 537 to arginine 673. These results show that glucocorticoid receptor fragments smaller than 34 kDa do bind steroids and that the amino acids Thr537-Arg673 constitute a core sequence for ligand binding within the larger steroid binding domain. The much slower kinetics in generating the 16-kDa fragment from affinity-labeled receptors suggests that steroid binding causes a conformation change in the receptor near the cleavage sites.
Shannon Entropy as a metric for conditional gene expression in Neurospora crassa

Neurospora crassa has been an important model organism for molecular biology and genetics for over 60 years. N. crassa has a complex life cycle, with over 28 distinct cell types and is capable of transcriptional responses to many environmental conditions including nutrient availability, temperature, and light. To quantify variation in N. crassa gene expression, we analyzed public expression data from 97 conditions and calculated the Shannon Entropy value for Neurospora9s approximately 11,000 genes. Entropy values can be used to estimate the variability in expression for a single gene over a range of conditions and be used to classify individual genes as constitutive or condition-specific. Shannon entropy has previously been used measure the degree of tissue specificity of multicellular plant or animal genes. We use this metric here to measure variable gene expression in a microbe and provide this information as a resource for the N. crassa research community. Finally, we demonstrate the utility of this approach by using entropy values to identify genes with constitutive expression across a wide range of conditions and to identify genes that are activated exclusively during sexual development.
The Transit Light Curve (TLC) Project. II. Two Transits of the Exoplanet OGLE-TR-111b

As part of our ongoing effort to measure exoplanet sizes and transit times with greater accuracy, we present I band observations of two transits of OGLE-TR-111b. The photometry has an accuracy of 0.15-0.20% and a cadence of 1-2 minutes. We derive a planetary radius of 1.067 +/- 0.054 Jupiter radii and a stellar radius of 0.831 +/- 0.031 solar radii. The uncertainties are dominated by errors in the photometry, rather than by systematic errors arising from uncertainties in the limb darkening function or the stellar mass. Both the stellar radius and the planetary radius are in agreement with theoretical expectations. The transit times are accurate to within 30 seconds, and allow us to refine the estimate of the mean orbital period: 4.0144479 +/- 0.0000041 days.
Myxopapillary Ependymoma and Rare Tumors

This chapter explores the details of five intradural extramedullary tumors of the spinal canal, including myxopapillary ependymoma (MPE), ganglioneuroma (GN), paraganglioma (PGL), malignant peripheral nerve sheath tumors (MPNST), and lipomas. While myxopapillary ependymoma, paraganglioma, and lipoma are commonly found in the intradural extramedullary space, ganglioneuroma and MPNST are extremely rare in this location and are more commonly found in other areas of the body. Intradural extramedullary tumors pose the risk of spinal cord compression and associated symptoms, such as pain, weakness, and motor and sensory dysfunction. These tumors are challenging to diagnose due to their rarity, non-specific symptoms, and radiologic similarity to other more common soft tissue tumors, with the exception of lipomas, which are more clearly identifiable and often occur concomitantly with occult spinal dysraphism. Definitive diagnosis of MPE, GN, PGL, and MPNST require histochemical and immunohistochemical assay and analysis for biomarkers, and even so, some are not correctly diagnosed until after they are resected and further analyzed. MPE, GN, PGL, and MPNST are all treated via surgical resection, while adjuvant chemotherapy and radiation for these tumors is still controversial and under investigation. Treatment for lipoma is also surgical resection. Prognosis is generally favorable for MPE, GN, PGL, and lipoma, but very poor for MPNST. This chapter outlines the clinical presentation, demographics, location, pathologic findings, treatment and prognosis, and differential diagnoses of the five tumors, and creates a comprehensive and systematic analysis of rare intradural extramedullary spinal cord tumors.
The Relation between Environmental, Demographic, and Geographical Factors, and COVID-19 Diffusion: A Case Study

This study analyses data on COVID-19 cases alongside environmental, demographic and geographic data. This study focuses on Italy that has had rapid diffusion of COVID-19 in society during the first wave of COVID-19 pandemic in 2020. Results show that cities with little wind, high humidity and frequently high levels of air pollution — exceeding safe levels of ozone or particulate matter — had higher numbers of COVID-19 related infected individuals and deaths. Overall, then, results here suggest that that geo-environmental factors may have accelerated the spread of COVID-19 in polluted cities of North Italy, leading to a higher number of infected individuals and deaths. Implications of environmental and sustainable science are discussed.
Longitudinal effects of cigarette pictorial warning labels among young adults

Young adults are influenced by cigarette package marketing. Pictorial warning labels are a recommended intervention. Evidence demonstrates pictorial warnings impact negative emotion, risk perceptions, and motivation to quit smoking, but there is limited research on their effects over time. This study analyzes data from a randomized trial of young adult smokers (N = 229) exposed to a pictorial or text-only cigarette warning. We assessed changes in fear, anger, risk perceptions, and motivation to quit smoking after 4 weeks using latent change score modeling and over 3 months using latent growth modeling. Latent change results showed exposure was associated with increases in fear, anger, and motivation to quit after 4 weeks. Latent growth showed exposure was associated with increases in motivation to quit smoking over 3 months, but not other outcomes. Findings suggest pictorial warning labels produce an emotional response and increase motivation to quit among young adult smokers.
We are each other’s breath: tracing interdependency through critical poetic inquiry

In this paper, we utilize poetic methods that seek to surface, but not overdetermine, the unanticipated relational excess produced through literacy practices. Karen, a queer white woman, and Jordan...
Student Perception of and Role in Determining Catholic Identity.

Much of the concern of Catholic identity revolves around students’ experiences of Catholicism at Catholic colleges and universities. Given this concern, it is surprising how little attention has been focused on student perceptions of Catholic identity. In the spring of 2013, the author gathered data from more than 1,000 students at over 20 different institutions on their understanding of the religious identity of their Catholic college or university. This research yielded two main results: First, across institutions, students noted the presence of Catholicism in the classroom, as well as opportunities for worship and service. Second, student perceptions of Catholic identity are affected by their residential life and, even more so, the presence of Catholic students on campus. The conclusion of these fi ndings is that, regardless of an institution’s curriculum and policies, students have a signifi cant role in defi ning the institution’s Catholic identity.
What the Market Will Bear? Ethical and Professional Issues in Medical Fees

Every profession is both a business and a calling. Professionals provide valued services, incur overhead in providing those services, and require compensation. Physicians, like other professionals, have traditionally maintained the right to self-regulate. With the universal penetration of third-party payers and managed care in the US over the last 30–40 years, physicians no longer set their own fees. With new paradigms have come new rules, new economic realities, and new moral and ethical challenges.
A Review of “Model Policies and Procedures for Not-For-Profit Organizations”

The nonprofit sector is big business. According to The Nonprofit Almanac 2008, published by the Urban Institute, nonprofit organizations received $1 trillion in revenue in 2006 and contributed $489...
The effect of asset and ownership structure on political risk: Some evidence from Mitterrand's election in France

Abstract Previous research suggests that political risk varies considerably from firm to firm. Yet few empirical tests of the cross-sectional variation in political risk exist. French assets were massively revalued the day after Mitterrand was elected in 1981, providing a unique opportunity to test for the effect of firm-specific factors on political risk. Although foreign ownership tends to increase political risk, other factors can reduce it. A simple model of political behavior is presented in which politicians value, among other things, economic growth. A foreign firm with significant future growth options is likely to experience less political risk than other foreign firms and, under certain circumstances, less risk than even other domestic firms. Tests of these hypotheses are conducted using data from the French and U.S. capital markets. The results are generally consistent with the hypotheses.
An acousto-ultrasonic NDE technique for monitoring material anisotropy

A simpler and better way of monitoring the anisotropy of fiber-reinforced composite materials, based on the acousto-ultrasonic approach, is presented. In this approach, time of flight of the acousto-ultrasonic waves AU, rather than the stress wave factor, is measured. Two fundamental Lamb modes are generated under the first critical frequency: one is the first antisymmetric mode traveling with a slower velocity while the another is the first symmetric mode traveling with a faster speed. The later one is sensitive to the azimuthal angle and nearly nondispersive, and has a phase velocity very close to that of the bulk longitudinal wave of the material. Experimental data measured from two methods, TOF measurement and slope method, are compared with theoretical results; a good agreement is obtained for monitoring the material anisotropy. There is a great potential for this AU approach in material-property evaluation and in quantitative measurements of defects and debonding of fiber-reinforced composites. However, more studies are needed to better understand the effect of the fiber/matrix bonding on the measurements and to extract more information from the AU signals.
Metaepistemology and skepticism

Although the terminology is relatively new, it has been possible for some time now to distinguish two quite different sorts of questions in epistemology — metaepistemological questions and normative epistemological questions. The terminology is borrowed from and the distinction parallels the metaethical/normative distinction in ethics. Just as in doing metaethics one is concerned with analyzing concepts fundamental to ethical thought, so in doing metaepistemology one is concerned with analyzing concepts fundamental to epistemological thought, such concepts as knowledge, evidence, and justification. Similarly, just as in doing normative ethics one is concerned with deciding to what if anything the ethical concepts apply, so in doing “normative” epistemology one is trying to determine what one knows, what one is justified in believing, what constitutes good evidence for believing what. Classical issues concerning skepticism seem to fall most naturally into “normative” epistemology. The arguments of the skeptic most often presuppose metaepistemological positions but there is often far too little explicit discussion of the nature of knowledge or justified belief. Those of us who think that metaethics always takes logical priority over normative ethics will no doubt feel that metaepistemology takes logical priority over normative issues in epistemology and we may understandably feel that the way to get to the bottom of traditional skeptical problems is to first arrive at the correct metaepistemological position.