cssi/SciSciGPT-SciSciNet huggingface dataset:
MetaFam: a unified classification of protein families. I. Overview and statistics.

Motivation: Protein sequence classification is becoming an increasingly important means of organizing the voluminous data produced by large-scale genome sequencing projects. At present, there are several independent classification methods. To aid the general classification effort, we have created a unified protein family resource, MetaFam. MetaFam is a protein family classification built upon 10 publicly-accessible protein family databases (Blocks+, DOMO, Pfam, PIR-ALN, PRINTS, PROSITE, ProDom, PROTOMAP, SBASE, and SYSTERS). MetaFam's family supersets', as we call them, are created automatically using set-theory to compare families among the databases. Families of one database are matched to those in another when the intersection of their members exceeds all other possible family pairings between the two databases. Pairwise family matches are drawn together transitively to create a new list of protein family supersets. Results: MetaFam family supersets have several useful features: (1) each superset contains more members than the families from which it is composed, because each of the component family databases only works with a subset of our full non-redundant set of proteins; (2) conflicting assignments can be pinpointed quickly, since our analysis identifies individual members that are in conflict with the majority consensus; (3) family descriptions that are absent from automated databases can frequently be assigned; (4) statistics have been computed comparing domain boundaries, family size distributions, and overall quality of MetaFam supersets; (5) the supersets have been loaded into a relational database to allow for complex queries and visualization of the connections among families in a superset and the consensus of individual domain members; and (6) the quality of individual supersets has been assessed using numerous quantitative measures such as family consistency, connectedness, and size. We anticipate this new resource will be particularly useful to genomic database curators. Availability: Free access to the MetaFam web server is provided to all users at http://metafam.ahc.umn.edu/. Contact: metafam@ahc.umn.edu Supplementary information: Detailed distribution plots on MetaFam 2.0 supersets and its constituent family databases (e.g. superset/family sizes, domain boundary comparisons) are shown at http: //metafam.ahc.umn.edu/mf2.0/stats.html. Statistics on the current release of MetaFam can be found at http://metafam.ahc.umn.edu/current.release/stats.html.
Mctaggart's argument

The argument of J. M. E. McTaggart in ‘The Unreality of Time’ (Mind 1908) fails logically. There is no A series as such, but there is a shifting past-present-future arrangement within and consistent with the earlier-later B series, past being always earlier, future always later, present always a position earlier or later. An exactly similar logical structure is constructible within the number series, by making each number as one goes up it in turn (it does not matter what ‘it’, or ‘present’, means, ontologically). The subsequent argument that past-present-future time falls into contradiction then fails also, and proves to be equivocal.
Focal Organizing Pneumonia on Surgical Lung Biopsy: Causes, Clinicoradiologic Features, and Outcomes

Background Organizing pneumonia (OP) is a histologic pattern that is morphologically distinctive but nonspecific and can be seen in diverse clinical settings. Focal OP has been described as a discrete form of OP, but relatively little is known regarding this clinicopathologic entity. Methods We sought to clarify the clinicoradiologic presentation, underlying causes, and outcomes associated with focal OP by retrospectively reviewing 26 consecutive cases diagnosed by surgical lung biopsy over an 8-year period from January 1, 1997, to December 31, 2004. Results All patients presented with an unifocal opacity detected on chest radiography (20 patients) or CT scans (6 patients). At the time of presentation, 10 patients (38%) had symptoms, including cough, shortness of breath, or chest pain; 16 patients were asymptomatic. Contrast-enhancement CT scanning or positron emission tomography (PET) scan was performed in 11 patients, and the results were positive in all. Surgical procedures included wedge resection in 21 patients (81%), segmentectomy in 3 patients (11%), and lobectomy in 2 patients (8%). Three case of focal OP (12%) were related to infections, but the remaining cases were cryptogenic. Follow-up over a median interval of 11 months (range, 1 to 71 months) yielded no recurrence of OP. Conclusions The radiologic features of focal OP are often indistinguishable from those of lung cancer, and include positivity on contrast-enhancement CT scan and PET scan. Most cases of focal OP are cryptogenic, and infection is identified in a minority of cases. Surgical resection alone appears to suffice in the management of cryptogenic focal OP.
Role and possible mechanisms of clenbuterol in enhancing reverse remodelling during mechanical unloading in murine heart failure.

Aims Combined left ventricular assist device (LVAD) and pharmacological therapy has been proposed to favour myocardial recovery in patients with end-stage heart failure (HF). Clenbuterol (Clen), a b2adrenoceptor (b2-AR) agonist, has been used as a part of this strategy. In this study, we investigated the direct effects of clenbuterol on unloaded myocardium in HF. Methods and results Left coronary artery ligation or sham operation was performed in male Lewis rats. After 4–6 weeks, heterotopic abdominal transplantation of the failing hearts into normal recipients was performed to induce LV unloading (UN). Recipient rats were treated with saline (Sal) or clenbuterol (2 mg/kg/day) via osmotic minipumps (HF þ UN þ Sal or HF þ UN þ Clen) for 7 days. Non-transplanted HF animals were treated with Sal (Sham þ Sal, HF þ Sal) or clenbuterol (HF þ Clen). LV myocytes were isolated and studied using optical, fluorescence, and electrophysiological techniques. Clenbuterol treatment improved in vivo LV function measured with echocardiography (LVEF (%): HF 35.9+ 2 [16], HF þ Clen 52.1+ 1.4 [16]; P , 0.001; mean+ SEM [n]). In combination with unloading, clenbuterol increased sarcomere shortening (amplitude (mm): HF þ UN þ Clen 0.1+ 0.01 [50], HF þ UN þ Sal 0.07+ 0.01 [38]; P , 0.001) by normalizing the depressed myofilament sensitivity to Ca 2þ (slope of the linear relationship between Ca 2þ transient and sarcomere shortening hysteresis loop during relaxation (mm/ ratio unit): HF þ UN þ Clen 2.13+ 0.2 [52], HF þ UN þ Sal 1.42+ 0.13 [38]; P , 0.05). Conclusion Clenbuterol treatment of failing rat hearts, alone or in combination with mechanical unloading, improves LV function at the whole-heart and cellular levels by affecting cell morphology, excitation–contraction coupling, and myofilament sensitivity to calcium. This study supports the use of this drug in the strategy to enhance recovery in HF patients treated with LVADs and also begins to elucidate some of the possible cellular mechanisms responsible for the improvement in LV function.
Kinesonde Observations of ionosphere modification by intense electromagnetic fields from Platteville, Colorado

Observations by the Kinesonde (a multifrequency, spaced antenna, digitized complex-amplitude radio sounding system) of ionospheric responses to excitation by the high-power transmitter at Platteville, Colo., are described. Increases of echo scintillation rate and intensity at frequencies reflected near and far from the excitation level are shown. Significant onset delays of these responses suggest disturbance propagation velocities of a few kilometers per second. Calculated echolocations show a time-dependent development toward the excitation region, again with a delayed response. Comments are offered regarding the relative utility of ionogram and Kinesonde observations for study of these phenomena.
VEBoC: variation and error-aware design for billions of devices on a chip

Billions of devices on a chip is around the corner and the trend of deep submicron (DSM) technology scaling will continue for at least another decade. Meanwhile, designers also face severe on-chip parameter variations, soft/hard errors, and high leakage power. How to use these billions of devices to deliver power-efficient, high-performance, and yet error-resilient computation is a challenging task. In this paper, we attempt to demonstrate some of our perspectives to address these critical issues. We elaborate on variation-aware synthesis, holistic error modeling, reliable multicore, and synthesis for application-specific multicore. We also present some of our insights for future reliable computing.
Local Generation of Fast Ripples in Epileptic Brain

Aperiodic high-frequency oscillations (>100 Hz) reflect a short-term synchronization of neuronal electrical activity. It has been shown in the epileptic brain that spontaneous oscillations in the frequency range of 250–600 Hz reflect action potential population bursts of synchronously discharging neuronal clusters. These oscillations occur in the early stages of epileptogenesis in areas adjacent to the brain lesion and may trigger the formation of seizure-generating neuronal networks. We studied the extent of the area generating oscillations in the frequency range of 250–600 Hz [fast ripples (FRs)] in intrahippocampal kainic acid-treated rats with spontaneous seizures, by analyzing voltage versus depth profiles of FRs in hippocampal and parahippocampal areas in freely moving animals and by spatial mapping in hippocampal slice preparations in vitro. The strength of inhibition was compared in areas with and without FRs using a paired-pulse paradigm. The extent of the areas generating FRs did not exceed 1 mm3. The areas generating FRs became broader after the application of the GABAA receptor antagonist bicuculline. Paired-pulse fast inhibition at 15–30 msec intervals was similar in areas generating FRs and areas not generating FRs. Our data illustrate that hypothesized clusters of highly interconnected neurons are capable of overcoming interneuron feedback inhibition, resulting in generation of epileptiform bursts, eventually leading to seizure activity.
Computing Many-One Comparisons among Independent Sample Proportions with the SAS System

Levy extended Dunnett's procedure for multiple comparisons to include contrasts defined on proportions, variances, and product-moment correlations. In the present article, an SAS program that uses Levy's method for conducting many-one pairwise comparisons among proportions associated with k independent samples is described. An example from Introduction to Design and Analysis by Keppel, Saufley, and Togunaga was used to illustrate the final analysis of a computer run conducted with this program.
Restriction of Late Cerebral Cortical Progenitors to an Upper-Layer Fate

Early in development, neural progenitors in cerebral cortex normally produce neurons of several layers during successive cell divisions. The laminar fate of their daughters depends on environmental cues encountered just before mitosis. At the close of neurogenesis, however, cortical progenitors normally produce neurons destined only for the upper layers. To assess the developmental potential of these cells, upper-layer progenitors were transplanted into the cerebral cortex of younger hosts, in which deep-layer neurons were being generated. These studies reveal that late cortical progenitors are not competent to generate deep-layer neurons and are instead restricted to producing the upper layers.
Future Funding For Mental Health And Substance Abuse: Increasing Burdens For The Public Sector

Spending on mental health (MH) and substance abuse (SA) treatment is expected to double between 2003 and 2014, to $239 billion, and is anticipated to continue falling as a share of all health spending. By 2014, our projections of SA spending show increasing responsibility for state and local governments (45 percent); deteriorating shares financed by private insurance (7 percent); and 42 percent of SA spending going to specialty SA centers. For MH, Medicaid is forecasted to fund an increasingly larger share of treatment costs (27 percent), and prescription medications are expected to capture 30 percent of MH spending by 2014.
Lower bounds for arithmetic problems

The problems we are dealing with are: Primality testing is the problem of determining whether a given n-bit integer is prime or not; Modular exponentiation is the problem of computing a b mod m for all n-bit integers a,b,m with m>0; Jacobi symbol is the problem of computing the Jacobi symbol Jac(a,b) for all n-bit integers a,b with b odd, b>1, and gcd(a,b)=1.
Analysis of the scattering by an unbounded rough surface

This paper is concerned with the mathematical analysis of the solution for the wave propagation from the scattering by an unbounded penetrable rough surface. Throughout, the wavenumber is assumed to have a nonzero imaginary part that accounts for the energy absorption. The scattering problem is modeled as a boundary value problem governed by the Helmholtz equation with transparent boundary conditions proposed on plane surfaces confining the scattering surface. The existence and uniqueness of the weak solution for the model problem are established by using a variational approach. Furthermore, the scattering problem is investigated for the case when the scattering profile is a sufficiently small and smooth deformation of a plane surface. Under this assumption, the problem is equivalently formulated into a set of two-point boundary value problems in the frequency domain, and the analytical solution, in the form of an infinite series, is deduced by using a boundary perturbation technique combined with the transformed field expansion approach. Copyright © 2012 John Wiley & Sons, Ltd.
Is levofloxacin necessary to prevent postoperative infections of auricular second-intention wounds?

BACKGROUND Surgeons may prescribe oral quinolones after auricular procedures to prevent postoperative infections, especially those caused by Pseudomonas aeruginosa. OBJECTIVE This study compares the efficacy of levofloxacin and local wound care to local wound care alone in preventing postoperative infection of auricular second-intention wounds. MATERIALS AND METHODS This study was a prospective, randomized trial of 84 consecutive patients (82 in the final analysis) who underwent Mohs micrographic surgery for an auricular neoplasm and had a wound left to heal by second intention. After surgery, patients were randomly assigned to receive either local wound care or local wound care with concurrent 500 mg of levofloxacin by mouth daily. RESULTS Overall, 85.4% of patients had no complications. Complications included 12.2% of patients with inflammatory chondritis and 2.4% of patients with infection. No infections with P. aeruginosa were observed. No statistical significance was observed between the two treatment groups. CONCLUSION Levofloxacin is not necessary to prevent postoperative infections of auricular second-intention wounds after Mohs surgery.
Morphology of PET Cords at Different Stages of Simulated Tire Building

The effect of simulated tire-building steps on morphological characteristics of polyethylene terephthalate (PET) cords and their final dimensional stability is reported. Twisted single-ply cords we...
Improvements In US Diet Helped Reduce Disease Burden And Lower Premature Deaths, 1999–2012; Overall Diet Remains Poor

Evaluation of time trends in dietary quality and their relation to disease burden provides essential feedback for policy making. We used an index titled the Alternate Healthy Eating Index 2010 to evaluate trends in dietary quality among 33,885 US adults. From 1999 to 2012 the index increased from 39.9 to 48.2 (perfect score = 110). Gaps in performance on the index across socioeconomic groups persisted or widened. Using data relating index scores to health outcomes in two large cohorts, we estimated that the improvements in dietary quality from 1999 to 2012 prevented 1.1 million premature deaths. Also, this improvement in diet quality resulted in 8.6 percent fewer cardiovascular disease cases, 1.3 percent fewer cancer cases, and 12.6 percent fewer type 2 diabetes cases. Although the steady improvement in dietary quality likely accounted for substantial reductions in disease burden from 1999 to 2012, overall dietary quality in the United States remains poor. Policy initiatives are needed to ensure further improvements.
The Effect of Voluntary Internal Control Audits on the Cost of Capital

In this paper, we investigate whether companies that voluntarily have their internal controls audited by an external auditor enjoy a lower cost of capital. Using a sample of companies that voluntarily have their internal controls audited by an external auditor and a control group of companies that report on the strength of internal controls but do not have management’s internal control assertions audited, we first model the determinants of voluntary internal control audits. We find that companies issuing equity or debt and those with stronger monitoring mechanisms (i.e., Big 4 auditors and higher institutional ownership) are more likely to voluntarily purchase internal control audits. Next, we test whether companies that voluntarily purchase internal control audits enjoy a lower cost of capital relative to companies that do not purchase internal control audits and find that the cost of equity and the cost of debt capital are significantly lower for those companies choosing to have their internal controls audited. Our findings are important because they demonstrate an important benefit that small companies can derive from purchasing internal control audits.
Optimizing a Nav1.5 Markov-Model with a Genetic Algorithm

Background: Markov models of cardiac voltage-gated Na+ (NaV) channels have been widely used for cell and tissue simulations of cardiac electrophysiology. These NaV1.5 models are of varying complexity. Simple models with few states cannot account for all of the kinetics observed with multiple protocols. Increasingly complex models become computationally infeasible for multi-scale simulations and their results are difficult to interpret.Methods: Following previously published work for the neuronal Na+ channel, we have implemented a genetic algorithm to optimize model topology and rate parameters for the cardiac sodium channel. The advantage of this approach is a flexible topology, with unnecessary states and edges removed in favor of model plausibility and computational speed. We improved this model by parallelizing the computation and including subpopulations with random mutation rates. Patch-clamp data for model parameterization was collected by recording transiently transfected HEK293T cells expressing Nav1.5 channels 24 hours post-transfection. The temperature of the recordings was controlled at various temperatures ranging from room temperature to physiological temperatures. Models were successfully fit to patch-clamp protocols, consisting of activation curves, inactivation, recovery from inactivation, and activation current traces.Results: The final optimization employed 32 subpopulations each with 50 members and was run for 2000 generations. After 2 x 106 models were evaluated, the algorithm yielded a model composed of 8 states and 10 interconnecting edges. The model was able to reproduce 20ms, 100ms, and 1000ms inactivation holds, activation, and recovery from inactivation protocols with high fidelity. Fast kinetic data was reproduced by fitting traces for −30mV, −10mV, and 10 mV directly. This novel model fits a wide range of experimentally collected data and contains significantly fewer parameters than current, widely used models.
Analysis of HIV antibody detection results in Anqing city from 2005 to 2008

Objective To analyze the results of HIV antibody detection in Anqing city from 2005 to 2008 and provide basic information for controlling HIV/AIDS spreading.Methods According to the National Guideline for HIV/AIDS Detection,sample were firstly detected with HIV antibody primary screening test,the positive in primary screening test were then detected with re-screening tests,and samples positive in re-screening test were finally confirmed with Western blot(WB).Results Out of 20605 samples examined from 2005 to 2008,105 were positive in primary screening test.43 were confirmed positive by WB.Further analysis showed that all the examined belonged to 11 populations,9 populations found positive,with clinical suspicious constituted the highest ratio,followed by the prisoners,voluntary counseling/testing(VCT),positive spouses and children and homosexuals.Most were migrant farmer worker at age of 20~40 years old.Conclusions Primary screening test in laboratories for HIV infection in various populations enhances identification of HIV infected persons.However,confirmation of HIV infection relies on WB.We should strengthen HIV antibody detection in various populations,and especially intensify management and HIV antibody detection of migrant farmer workers so as to detect more HIV-infected persons and promote control of HIV spreading.
Differentiation between Schizoid and Avoidant Personalities: An Empirical Test*:

A number of authors have questioned the rationale for subdividing the DSM-II schizoid diagnosis into three separate personality disorders in DSM-III, the schizoid, avoidant, and schizotypal. The pr...
Bacterial, particulate, and environmental factors driving E. coli attachment

viii CHAPTER 1: GENERAL INTRODUCTION 1 CHAPTER 2. LITERATURE REVIEW 3 Pathogens and water quality 3 Waterborne disease and water impairment 3 Fecal indicator organisms and water quality standards 4 TMDLs and modeling of bacterial transport 6 Bacterial attachment 7 Definition of bacterial attachment 7 Bacterial attachment in the environment 9 Partitioning methods for bacterial attachment 10 Properties impacting bacterial attachment 12 References 17 CHAPTER 3. DIVERSITY IN PROPERTIES OF E. COLI DERIVED FROM STREAM WATER AND SEDIMENT 23 Abstract 23 23 Introduction 24 Materials and Methods 26 E. coli sampling and analysis 26 Computer-assisted rep-PCR DNA fingerprint analysis 27 Cell Properties 28 Data analyses 30 Results and Discussion 31 E. coli strain selection and dendrogram 31 E. coli property comparison between two environmental habitats 31
The military: Afghanistan, Guantánamo, Iraq

The CIA has always operated to a significant degree outside the law. The military, by contrast, is at its core an institution committed to discipline and order, strictly governed by the laws of war. So the fact that illegal abusive tactics were officially authorized at the Pentagon's highest levels is in some sense more shocking than the CIA's crimes. We should expect more of the military. (David Cole, “What to Do About the Torturers?,” New York Review of Books , January 15, 2009) As long as the United States – or any state, for that matter – has the power to detain at pleasure and in secret, abuse of detainees is inevitable. (Michael Ignatieff, in Kenneth Roth et al ., eds., Torture , New York: The New Press, 2005, p. 23) As the previous chapters have showed, when the United States used military force in Afghanistan in the Fall of 2001 and then opened the Guantanamo prison facility in January 2002, it deconstructed the international legal framework for the protection of prisoners in war, even as it declared a Global War on Terror (GWOT). The result was extensive abuse of prisoners, much of it intended by high policy makers. Iraq was supposed to be different, since the George W. Bush Administration declared the 1949 Geneva Conventions fully applicable to a situation of armed invasion and occupation, including those provisions pertaining to prisoners. But Iraq was not fundamentally different in 2003–2005.
Snow data assimilation-constrained land initialization improves seasonal temperature prediction

We present the first systematic study to quantify the impact of land initialization on seasonal temperature prediction in the Northern Hemisphere, emphasizing the role of land snow data assimilation (DA). Three suites of ensemble seasonal integrations are conducted for coupled land–atmosphere runs. The land component is initialized using datasets from (1) no DA, (2) assimilating MODIS snow cover fraction (SCF), and (3) assimilating both MODIS SCF and GRACE terrestrial water storage. Results show that snow DA improves temperature predictions especially in the Tibetan Plateau (by 5–20%) and high latitudes. Improvements at low latitudes are seen immediately and last up to 60 days, whereas improvements at high latitudes only appear later in transitional seasons. At high latitudes, assimilating GRACE data results in marked and prolonged improvements (by ~25%) due to large initial snow mass changes. This study has great implications for future land DA and seasonal climate prediction studies.
Social Justice Art: A Framework for Activist Art Pedagogy

(2015). Social Justice Art: A Framework for Activist Art Pedagogy. Studies in Art Education: Vol. 56, No. 4, pp. 386-388.
Assessing the accuracy of the OMRON HEM-907XL oscillometric blood pressure measurement device in patients with nondialytic chronic kidney disease.

The OMRON HEM−907XL is a commercial oscillometric blood pressure (BP) monitor that was used in the Systolic Blood Pressure Intervention Trial (SPRINT), in which 28% of participants had chronic kidney disease (CKD). This study examined the accuracy of the monitor in nondialytic patients with CKD. Eighty-seven patients met inclusion criteria. The authors used a modified Association for the Advancement of Medical Instrumentation (AAMI) protocol, with one observer recording measurements from the monitor and two blinded physicians obtaining simultaneous aneroid values by auscultation. Using AAMI method 1, there was a 2.5±9.5 mm Hg difference in OMRON and aneroid systolic BP, and a −1.6±6.5 mm Hg difference in diastolic BP. Using AAMI method 2, there was a 5.1±7.4 mm Hg difference in systolic BP and a −0.2±5.4 mm Hg difference in diastolic BP. In patients with CKD, the OMRON HEM-907XL appears to be accurate for measuring diastolic BP, but did not perform as well for systolic BP.
Pulmonary metastasectomy with therapeutic intent for soft-tissue sarcoma.

Abstract Objective Soft-tissue sarcoma is a heterogeneous disease that frequently includes the development of pulmonary metastases. The purpose of this study is to determine factors associated with improved survival among patients with soft-tissue sarcoma to help guide selection for pulmonary metastasectomy. Methods We reviewed a prospectively maintained database and identified 803 patients who underwent pulmonary metastasectomy for metastatic soft-tissue sarcoma between September 1991 and June 2014; of these, 539 patients undergoing 760 therapeutic-intent pulmonary metastasectomies were included. Clinicopathologic variables and characteristics of treatment were examined. The outcomes of interest were overall survival and disease-free survival. Survival was estimated with the Kaplan-Meier method and compared between variables with the log-rank test. Factors associated with hazard of death and recurrence were identified via the use of univariable and multivariable Cox proportional hazards models. Results Median overall survival was 33.2 months (95% confidence interval, 29.9-37.1), and median disease-free survival was 6.8 months (95% confidence interval, 6.0-8.0). In multivariable analyses, leiomyosarcoma histologic subtype ( P = .007), primary tumor size ≤10 cm ( P = .006), increasing time from primary tumor resection to development of metastases ( P P = .001), and minimally invasive resection ( P = .023) were associated with lower hazard of death. Disease-free interval ≥1 year ( P = .002), and 1 pulmonary metastasis ( P Conclusions In a large single-institution study, primary tumor histologic subtype and size, numbers of pulmonary metastases, disease-free interval, and selection for minimally invasive resection are associated with increased survival in patients undergoing pulmonary metastasectomy for soft-tissue sarcoma.
HIV virions sense plasma membrane heterogeneity for cell entry

It has been proposed that cholesterol in host cell membranes plays a pivotal role for cell entry of HIV. However, it remains largely unknown why virions prefer cholesterol-rich heterogeneous membranes to uniformly fluid membranes for membrane fusion. Using giant plasma membrane vesicles containing cholesterol-rich ordered and cholesterol-poor fluid lipid domains, we demonstrate that the HIV receptor CD4 is substantially sequestered into ordered domains, whereas the co-receptor CCR5 localizes preferentially at ordered/disordered domain boundaries. We also show that HIV does not fuse from within ordered regions of the plasma membrane but rather at their boundaries. Ordered/disordered lipid domain coexistence is not required for HIV attachment but is a prerequisite for successful fusion. We propose that HIV virions sense and exploit membrane discontinuities to gain entry into cells. This study provides surprising answers to the long-standing question about the roles of cholesterol and ordered lipid domains in cell entry of HIV and perhaps other enveloped viruses.
Cerebral Structure and Cognitive Performance in African Americans and European Americans With Type 2 Diabetes.

Background African Americans typically perform worse than European Americans on cognitive testing. Contributions of cardiovascular disease (CVD) risk factors and educational quality to cognitive performance and brain volumes were compared in European Americans and African Americans with type 2 diabetes. Methods Association between magnetic resonance imaging-determined cerebral volumes of white matter (WMV), gray matter (GMV), white matter lesions (WMLV), hippocampal GMV, and modified mini-mental state exam (3MSE), digit symbol coding (DSC), Rey Auditory Verbal Learning Test (RAVLT), Stroop, and verbal fluency performance were assessed in Diabetes Heart Study Memory in Diabetes (MIND) participants. Marginal models incorporating generalized estimating equations were employed with serial adjustment for risk factors. Results The sample included 520 African Americans and 684 European Americans; 56 per cent female with mean ± SD age 62.8 ± 10.3 years and diabetes duration 14.3 ± 7.8 years. Adjusting for age, sex, diabetes duration, BMI, HbA1c, total intracranial volume, scanner, statins, CVD, smoking, and hypertension, WMV (p = .001) was lower and WMLV higher in African Americans than European Americans (p = .001), with similar GMV (p = .30). Adjusting for age, sex, education, HbA1c, diabetes duration, hypertension, BMI, statins, CVD, smoking, and depression, poorer performance on 3MSE, RAVLT, and DSC were seen in African Americans (p = 6 × 10-23-7 × 10-62). Racial differences in cognitive performance were attenuated after additional adjustment for WMLV and nearly fully resolved after adjustment for wide-range achievement test (WRAT) performance (p = .0009-.65). Conclusions African Americans with type 2 diabetes had higher WMLV and poorer cognitive performance than European Americans. Differences in cognitive performance were attenuated after considering WMLV and apparent poorer educational quality based on WRAT.
Prediction of off-target activities for the end-to-end design of CRISPR guide RNAs

The CRISPR-Cas9 system provides unprecedented genome editing capabilities. However, off-target effects lead to sub-optimal usage and additionally are a bottleneck in the development of therapeutic uses. Herein, we introduce the first machine learning-based approach to off-target prediction, yielding a state-of-the-art model for CRISPR-Cas9 that outperforms all other guide design services. Our approach, Elevation, consists of two interdependent machine learning models-one for scoring individual guide-target pairs, and another which aggregates these guide-target scores into a single, overall summary guide score. Through systematic investigation, we demonstrate that Elevation performs substantially better than competing approaches on both tasks. Additionally, we are the first to systematically evaluate approaches on the guide summary score problem; we show that the most widely-used method performs no better than random at times, whereas Elevation consistently outperformed it, sometimes by an order of magnitude. We also introduce an evaluation method that balances errors between active and inactive guides, thereby encapsulating a range of practical use cases; Elevation is consistently superior to other methods across the entire range. Finally, because of the large scale and computational demands of off-target prediction, we have developed a cloud-based service for quick retrieval. This service provides end-to-end guide design by also incorporating our previously reported on-target model, Azimuth. (https://crispr.ml:please treat this web site as confidential until publication).
Antibiosis and Tolerance Discovered in USDA-ARS Sorghums Resistant to the Sugarcane Aphid (Hemiptera: Aphididae)1

Abstract The sugarcane aphid Melanaphis sacchari (Zehntner) was discovered infesting grain sorghum close to Beaumont, TX, near the Texas and Louisiana state line a few kilometers inland from the Gulf Coast in the late summer of 2013, and has been a perennial pest of grain, forage, and sweet sorghums. Our research was aimed at identifying sorghum germplasm that expresses host-plant resistance to the sugarcane aphid. We originally screened 36 lines including two known resistant sorghums (Tx2783 and DKS-37-07) and two known susceptible sources (WSH 117 and MORCH 858). From this screen, two pollinator lines (R.11143 and R.11259) developed by the USDA-ARS in Lubbock, TX, exhibited tolerance as indicated by damage ratings and growth characteristics, such as plant height, number of leaves, and chlorophyll content. Line R.11143 had a slight net gain in chlorophyll content in the infested plants compared to the noninfested plants, indicating a highly tolerant sorghum. The R.11143 and R.11259 lines also expressed s...
On Model-Based Software Development

Due to its many advantages, the growing use in software practice of Model-Based Development (MBD) is a promising trend. However, major problems in MBD of software remain, for example, the failure to integrate formal system requirements models with current code synthesis methods. This chapter introduces FMBD, a formal MBD process for building software systems which addresses this problem. The goal of FMBD is to produce high assurance software systems which are correct by construction. The chapter describes three types of models built during the FMBD process, provides examples from an avionics system to illustrate the models, and proposes three major challenges in MBD as topics for future research.
Left Posterior Oblique Plane

The cadaver for the left posterior oblique sections was that of a 33-year-old white male who willed his body to the Alabama Anatomical Board prior to a judicial execution in the electric chair. The trachea was intubated a few minutes following death and the lungs fully expanded. The postmortem radiograph of the chest demonstrated normal structures with some early evidence of chronic obstructive pulmonary disease. By Alabama statute, an autopsy limited to the head was performed. The body was placed in the freezer in a neutral supine position where it remained for 49 months prior to sectioning.
Making commodity PCs fit for signal processing

Commodity PCs are on the verge of being capable of performing a variety of signal processing tasks that previously required special purpose hardware. Advances in the speed and width of their processors and internal buses allow these machines to manipulate data at rates that would allow their users to interact with a diverse range of sampled media, such as the raw RF spectrum and ultrasound. However, today's PCs lack an I/O system capable of delivering the appropriate bandwidth to these signal processing applications. These applications demand high continuous throughput I/O that smooths the inter-sample jitter introduced by interrupts, I/O bus latency, scheduling latency, etc. This paper presents a system that provides this functionality. Our system is composed of two tightly integrated parts: a PCI device that provides high raw I/O bus throughput and operating system enhancements to manage the device and provide low overhead transfers across the boundary between kernel and user space. The performance is excellent, providing up to 512 Mbits/sec of continuous throughput for an application. A description of both parts of the system is given, along with performance measurements, and a brief description of an application.
Neuroscience: Memory Encoding in the Absence of Cell Firing.

Summary New research suggests that rats can learn new spatial information in the absence of cell firing. A small enhancement of GABAergic inhibition with a low dose of muscimol blocked cell firing but left long-term potentiation induction intact, while behaviorally it blocked memory retrieval but left memory encoding intact.
Analysis of the partial molar excess entropy of dilute hydrogen in liquid metals and its change at the solid-liquid transition

Abstract A systematic change in the partial molar enthalpy of mixing ( Δ h ¯ H mix ) and partial molar excess entropy ( Δ s ¯ H ex ) for dilute hydrogen-metal systems at the solid-liquid transition is reported. Expressions for Δ h ¯ H mix and Δ s ¯ H ex are derived from the Fowler model of hydrogen solubility, and the change in Δ s ¯ H ex at melting is bounded. The theoretical bound is in agreement with measured data. A connection is made between the change in Δ s ¯ H ex and short range order in the metal-hydrogen system.
Effect of glenoid perforation during total shoulder arthroplasty on glenoid component cement fixation and suprascapular nerve.

BackgroundArthritic glenoids are susceptible to vault perforation during total shoulder arthroplasty. We investigated the effects of glenoid perforation and subsequent cement extrusion on the supra...
Deep phenotyping of symptom domains in late-life depression associated with distinct cognitive and disability profiles

Introduction Late-life depression (LLD) is often characterized by heterogeneous symptom presentation, impaired cognitive performance, and increased disability. This heterogeneity is not well captured by diagnostic criteria or severity rating scales. Formal assessment of specific depressive symptoms may help unravel this heterogeneity as specific symptoms may be related to alterations in specific neural pathways. The purpose of this study is to determine whether specific symptom presentations are associated with distinct cognitive and disability profiles. Methods We examined 74 depressed participants 60 years and older who completed clinical assessments, self-report of disability using the WHODAS 2.0 questionnaire, and self-report questionnaires assessing specific symptoms, including worry, rumination, insomnia, fatigue, anhedonia, and apathy. Participants also completed a neuropsychological test battery. We examined the relationship between symptom questionnaires using cluster analyses and combined scores of scales in the same cluster using a z-score transformation to create composite variables. We took a similar approach with neuropsychological testing, allowing us to create composite cognitive domain z-scores, and we examined the relation between symptom domain scores with cognitive domain performance, disability, and other clinical measures while controlling for age, sex, and depression severity. We applied Bonferroni correction to account for multiple comparisons. Results In cluster analysis, symptom domains were grouped into three clusters: fatigue/insomnia, anhedonia/apathy, and rumination/worry. When examining cognitive domain performance, the fatigue/insomnia score was associated with slower processing speed (df = 1, 68, WaldX2 = 7.34, P = 0.0067). The anhedonia/apathy score was not associated with any specific cognitive domains. The rumination/worry score was associated with poor episodic memory (df = 1, 68, Wald X2 = 6.90, P = 0.0086). For disability, fatigue/insomnia and anhedonia/apathy scores were positively associated with greater disability, but rumination/worry was not. The fatigue/insomnia score was specifically associated with worse scores in disability domains of getting around (df = 1, 68, WaldX2 = 16.89, P = Conclusions We found that specific symptom domains grouped into three clusters (fatigue/insomnia, anhedonia/apathy, and rumination/worry) are associated with distinct cognitive and disability profiles. Examination of other symptom domains may further elucidate clinically relevant phenotypes. Further work is needed to examine the underlying neural bases of these symptoms and evaluate if treatment of those symptoms can improve the associated specific cognitive and disability profiles.
Respiratory axon regeneration in the chronically injured spinal cord.

Abstract Promoting the combination of robust regeneration of damaged axons and synaptic reconnection of these growing axon populations with appropriate neuronal targets represents a major therapeutic goal following spinal cord injury (SCI). A key impediment to achieving this important aim includes an intrinsic inability of neurons to extend axons in adult CNS, particularly in the context of the chronically-injured spinal cord. We tested whether an inhibitory peptide directed against phosphatase and tensin homolog (PTEN: a central inhibitor of neuron-intrinsic axon growth potential) could restore inspiratory diaphragm function by reconnecting critical respiratory neural circuitry in a rat model of chronic cervical level 2 (C2) hemisection SCI. We found that systemic delivery of PTEN antagonist peptide 4 (PAP4) starting at 8 weeks after C2 hemisection promoted substantial, long-distance regeneration of injured bulbospinal rostral Ventral Respiratory Group (rVRG) axons into and through the lesion and back toward phrenic motor neurons (PhMNs) located in intact caudal C3-C5 spinal cord. Despite this robust rVRG axon regeneration, PAP4 stimulated only minimal recovery of diaphragm function. Furthermore, re-lesion through the hemisection site completely removed PAP4-induced functional improvement, demonstrating that axon regeneration through the lesion was responsible for this partial functional recovery. Interestingly, there was minimal formation of putative excitatory monosynaptic connections between regrowing rVRG axons and PhMN targets, suggesting that (1) limited rVRG-PhMN synaptic reconnectivity was responsible at least in part for the lack of a significant functional effect, (2) chronically-injured spinal cord presents an obstacle to achieving synaptogenesis between regenerating axons and post-synaptic targets, and (3) addressing this challenge is a potentially-powerful strategy to enhance therapeutic efficacy in the chronic SCI setting. In conclusion, our study demonstrates a non-invasive and transient pharmacological approach in chronic SCI to repair the critically-important neural circuitry controlling diaphragmatic respiratory function, but also sheds light on obstacles to circuit plasticity presented by the chronically-injured spinal cord.
A Diagnostic Circuit for Crosstalk Detection in Microelectrode Arrays

Current leakage between channels in microelectrode arrays is a sign of device failure and can lead to shorting of neural signals. The purpose of this project is to detect crosstalk between 32 channels of electrodes. We designed an embedded crosstalk detection system that can stimulate each electrode individually with a constant-current pulse and record voltage transients of the stimulated and adjacent electrodes to generate a matrix of crosstalk values. Charge injection in a phosphate buffered saline solution was used to check the condition of each electrode. A semi-wet condition was then used to determine the percent crosstalk between the channels. The analysis showed that there was minimal crosstalk between the electrodes, except for a known physical defect on the probe. The measurement technique enabled by the electronics circuit has the potential to be used in functional testing and screening of implantable devices.
Production of Medicines from Engineered Proteins in Plants

Plants have always played a predominant role in both the nutritional and medical components of human health. Innovations in plant biology, in particular plant biotechnology, have helped these disciplines advance significantly. While some of our modern drugs have their origins in plant species, many pharmaceuticals that are commercially available today using conventional production systems such as yeast or mammalian cells can now be generated within the plant material itself, through a novel approach known as molecular pharming. This chapter describes the use of plants as a production platform to generate medicines to address infectious and chronic diseases. Examples of biologics produced in plants, from vaccines, monoclonal antibodies to therapeutic agents are described. The development of nanoparticles for cancer therapy based on plant viruses is also discussed. The chapter concludes with a projection of future applications for plant-based pharmaceuticals.
Maternal Complications and Prescription Opioid Exposure During Pregnancy: Using Marginal Structural Models.

Prescription opioids are frequently used for pain management in pregnancy. Studies examining perinatal complications in mothers who received prescription opioids during pregnancy are still limited. The aim of this study was to assess the association of prescription opioid use and maternal pregnancy and obstetric complications. This retrospective cohort study with the Rhode Island (RI) Medicaid claims data linked to vital statistics throughout 2008–2015 included pregnant women aged 12–55 years with one or multiple live births. Women were excluded if they had cancer, opioid use disorder, or opioid dispensing prior to but not during pregnancy. Main outcomes included adverse pregnancy and obstetric complications. Marginal Structural Cox Models with time-varying exposure and covariates were applied to control for baseline and time-varying covariates. Analyses were conducted for outcomes that occurred 1 week after opioid exposure (primary) or within the same week as exposure (secondary). Sensitivity studies were conducted to assess the effects of different doses and individual opioids. Of 9823 eligible mothers, 545 (5.5%) filled one or more prescription opioid during pregnancy. Compared with those unexposed, no significant risk was observed in primary analyses, while in secondary analyses opioid-exposed mothers were associated with an increased risk of cesarean antepartum depression (HR 3.19; 95% CI 1.22–8.33), and cardiac events (HR 9.44; 95% CI 1.19–74.83). In sensitivity analyses, results are more prominent in high dose exposure and are consistent for individual opioids. Prescription opioid use during pregnancy is associated with an increased risk of maternal complications.