cssi/SciSciGPT-SciSciNet huggingface dataset:
TWEAK-Independent Fn14 Self-Association and NF-κB Activation Is Mediated by the C-Terminal Region of the Fn14 Cytoplasmic Domain

The tumor necrosis factor (TNF) superfamily member TNF-like weak inducer of apoptosis (TWEAK) is a pro-inflammatory and pro-angiogenic cytokine implicated in physiological tissue regeneration and wound repair. TWEAK binds to a 102-amino acid type I transmembrane cell surface receptor named fibroblast growth factor-inducible 14 (Fn14). TWEAK:Fn14 engagement activates several intracellular signaling cascades, including the NF-κB pathway, and sustained Fn14 signaling has been implicated in the pathogenesis of chronic inflammatory diseases and cancer. Although several groups are developing TWEAK- or Fn14-targeted agents for therapeutic use, much more basic science research is required before we fully understand the TWEAK/Fn14 signaling axis. For example, we and others have proposed that TWEAK-independent Fn14 signaling may occur in cells when Fn14 levels are highly elevated, but this idea has never been tested directly. In this report, we first demonstrate TWEAK-independent Fn14 signaling by showing that an Fn14 deletion mutant that is unable to bind TWEAK can activate the NF-κB pathway in transfected cells. We then show that ectopically-expressed, cell surface-localized Fn14 can self-associate into Fn14 dimers, and we show that Fn14 self-association is mediated by an 18-aa region within the Fn14 cytoplasmic domain. Endogenously-expressed Fn14 as well as ectopically-overexpressed Fn14 could also be detected in dimeric form when cell lysates were subjected to SDS-PAGE under non-reducing conditions. Additional experiments revealed that Fn14 dimerization occurs during cell lysis via formation of an intermolecular disulfide bond at cysteine residue 122. These findings provide insight into the Fn14 signaling mechanism and may aid current studies to develop therapeutic agents targeting this small cell surface receptor.
Threads cannot be implemented as a library

In many environments, multi-threaded code is written in a language that was originally designed without thread support (e.g. C), to which a library of threading primitives was subsequently added. There appears to be a general understanding that this is not the right approach. We provide specific arguments that a pure library approach, in which the compiler is designed independently of threading issues, cannot guarantee correctness of the resulting code.We first review why the approach almost works, and then examine some of the surprising behavior it may entail. We further illustrate that there are very simple cases in which a pure library-based approach seems incapable of expressing an efficient parallel algorithm.Our discussion takes place in the context of C with Pthreads, since it is commonly used, reasonably well specified, and does not attempt to ensure type-safety, which would entail even stronger constraints. The issues we raise are not specific to that context.
Treatment prospects for persons with severe mental illness in an urban county jail.

Objective: A retrospective study of inmates with severe mental illness in a large, urban county jail aimed to obtain information about their psychiatric and criminal histories and status, the psychiatric services they used while incarcerated, and the challenges they might present in psychiatric treatment after release. Methods: The authors ascertained demographic characteristics, diagnoses, psychiatric and legal histories, and current psychiatric condition and treatment from jail psychiatric records of a random sample of 104 male inmates with mental illness and from electronic county mental health records and state records of criminal histories. Results: Seventy-eight inmates (75%) were diagnosed as having a severe mental illness. Of these, 59 (76%) required inpatient care or its equivalent for part of their time in jail for the current offense. Of the inmates with severe mental illness, 92% had a history of nonadherence to medications before this arrest, 95% had prior arrests, 72% had prior arrests for violent crimes against persons, and 76% were known to have a history of substance abuse. Conclusions: A large percentage of persons with severe mental illness received their acute psychiatric inpatient treatment in the criminal justice system rather than in the mental health system. The persons with severe mental illness in this study would present a major challenge in treatment in any setting given their psychiatric and criminal histories. The resources of the mental health system need to be greatly expanded, with priority given to treating persons who are criminalized or who are in danger of becoming criminalized. (Psychiatric Services 58:782–786, 2007)
Hunger in Children in the United States: Potential Behavioral and Emotional Correlates

Objective . Results from a recent series of surveys from 9 states and the District of Columbia by the Community Childhood Hunger Identification Project (CCHIP) provide an estimate that 4 million American children experience prolonged periodic food insufficiency and hunger each year, 8% of the children under the age of 12 in this country. The same studies show that an additional 10 million children are at risk for hunger. The current study examined the relationship between hunger as defined by the CCHIP measure (food insufficiency attributable to constrained resources) and variables reflecting the psychosocial functioning of low-income, school-aged children. Methods . The study group included 328 parents and children from a CCHIP study of families with at least 1 child under the age of 12 years living in the city of Pittsburgh and the surrounding Allegheny County. A two-stage area probability sampling design with standard cluster techniques was used. All parents whose child was between the ages of 6 and 12 years at the time of interview were asked to complete a Pediatric Symptom Checklist, a brief parent-report questionnaire that assesses children9s emotional and behavioral symptoms. Hunger status was defined by parent responses to the standard 8 food-insufficiency questions from the CCHIP survey that are used to classify households and children as “hungry,” “at-risk for hunger,” or “not hungry.” Results . In an area probability sample of low-income families, those defined as hungry on the CCHIP measure were significantly more likely to have clinical levels of psychosocial dysfunction on the Pediatric Symptom Checklist than children defined as at-risk for hunger or not hungry. Analysis of individual items and factor scores on the Pediatric Symptom Checklist showed that virtually all behavioral, emotional, and academic problems were more prevalent in hungry children, but that aggression and anxiety had the strongest degree of association with experiences of hunger. Conclusion . Children from families that report multiple experiences of food insufficiency and hunger are more likely to show behavioral, emotional, and academic problems on a standardized measure of psychosocial dysfunction than children from the same low-income communities whose families do not report experiences of hunger. Although causality cannot be determined from a cross-sectional design, the strength of these findings suggests the importance of greater awareness on the part of health care providers and public health officials of the role of food insufficiency and hunger in the lives of poor children.
Extending knowledge of Escherichia coli metabolism by modeling and experiment

One of the challenges for 'post-genomic' biology is the integration of data from many different sources. Two recent studies independently take steps towards this goal for Escherichia coli, using mathematical modeling and a combination of gene expression and protein levels to predict new gene functions and metabolic behaviors.
Plasma and Tissue Binding Considerations in Drug Disposition

(1983). Plasma and Tissue Binding Considerations in Drug Disposition. Drug Metabolism Reviews: Vol. 14, No. 3, pp. 427-465.
Predictive control and sizing of energy storage to mitigate wind power intermittency

This paper studies how the control algorithm impacts the required capacity of battery energy storage system (BESS) to mitigate wind intermittency. We study a futuristic scenario in which wind generation is traded in the energy market on an hourly basis, and the wind power producer has to procure reserves to handle wind fluctuations. The wind power producer can avoid paying for conventional reserves by charging/discharging BESS to compensate for wind surplus and deficit. We develop control algorithms using the model predictive control (MPC) methodology, which incorporates wind forecasts for the next few hours when determining wind scheduling. The MPC algorithm is developed by solving a non-linear optimization problem to minimize operation costs to the wind power producer. In addition to operation costs, the MPC algorithm considers two practical aspects: the efficiency loss of BESS and the smoothness in wind power scheduling. BESS sizing is studied by parametric analyses. Simulations show that BESS is more effective in reducing operation costs and reducing wind curtailment than conventional reserves. In addition, MPC is a horizon-based control algorithm and can preview future information in its control action. Simulations also show that MPC consistently outperforms an instantaneous heuristic algorithm that does not use future information. Therefore, we confirm that MPC can reduce the BESS capacity required to cover wind uncertainties. Copyright © 2015 John Wiley & Sons, Ltd.
Associative Transitive Loops

In this paper, we investigate the structure of loops in which the associativity relation between pairs of non-trivial elements (i.e., 〈x,y〉 is a group) is transitive. We also look at other properties that come out of the study of this class of loops.
Anthropogenic and physiologically induced stress responses in captive coyotes

Abstract Repeated stressful events can negatively impact overall health by continuous stimulation of the hypothalamic–pituitary–adrenal axis, which leads to depletion of glucose stores and suppression of immune and reproductive function. The influence of stressors on survivability is particularly salient for coyote (Canis latrans) populations, because understanding how coyotes cope with stressors may provide relevant context on coyote adaptation to urbanized ecosystems. Our objectives were to physiologically validate fecal glucocorticoid metabolite (FGM) analysis in coyotes by performing an adrenocorticotropic hormone (ACTH) challenge in 12 captive individuals (6 treatment and 6 control) housed at the United States Department of Agriculture National Wildlife Research Center Predator Research Facility in Millville, Utah; to quantify potential changes in FGM output due to diurnal variation and sex; and to determine the effects of 2 anthropogenic events (placement of a novel cooling fan and state holiday cel...
Archeology as Long‐Term Ethnography

Behavioral variation from year to year is archeologically invisible, yet it may have important effects on the archeological record. Moreover, much of current theory demands that we give attention to such variation. Rather than adopting normative reconstructions from ethnographies, archeologists must view the archeological record as a long-term ethnography, confounded by such variations in behavior. Using an ecological perspective, patterns of behavioral variation can be linked to environmental characteristics, with implications for the archeological record of settlement and subsistence. The Paleolithic and Mesolithic of southwest Germany are used to illustrate this approach.
ENZYMATIC SYNTHESIS OF STRUCTURED LIPIDS: TRANSESTERIFICATION OF TRIOLEIN AND CAPRYLIC ACID

Structured lipids were successfully synthesized by lipase-catalyzed trans-esterification (acidolysis) of caprylic acid and triolein in nonaqueous medium. Twelve commercially available lipases (10%, w/w substrates) were screened for their ability to form structured lipid by incubating 100 mg triolein and 65.3 mg caprylic acid in 3 ml hexane at 55C for 24 h. The products were analyzed by reverse-phase high performance liquid chromatography (HPLC) with evaporative light scattering detection. Monocapryloolein was the major component of the products (57.4 mol %) and IM60 lipase from Rhizomucor miehei was the best biocatalyst. Dicapryloolein and triolein contents were 35.4% and 5.3%, respectively. Temperature, mole ratio, time course, incubation media, added water, enzyme load, and substrate concentration were also investigated in this study. The results suggest that it is possible to synthesize structured lipids with lipase as biocatalyst.
Achievement Level, Social Class, and the Self-Concepts of Mildly Handicapped Children

To illustrate the effects of socioeconomic status (SES) and within classroom academic standing on the self—concepts of mildly handicapped children, self—concept scores were collected on 169 elementary school children who divided their school day between special classes and the educational mainstream. The sample was divided into four groups based on SES (high or low) and level of academic achievement in comparison to other handicapped classmates (high or low). High achievers reported higher self—concept scores than low achievers and low SES students had higher self—concept scores than high SES children. The results are interpreted in terms of the influence of social comparison groups on children's perceptions of their own competence. The results suggest that mildly handicapped children from high SES levels who remain inadequate academically in comparison to their special—class peers have self—concepts significantly lower than those of all other students.
On grasping and coordinated manipulation by a multifingered robot hand

Two problems in the study of multifingered robot hands are considered, namely grasp planning and the determination of coordinated control laws with point contact models. using the dual notions of grasp stability and manipulability, and a procedure previously developed for task modeling, the structure grasp quality measures are defined. These measures are then integrated to devise a grasp planning algorithm. Based on the assumption of point contact models, a computed-torque-like control algorithm is developed for the coordinated manipulation of a multifingered robot hand. This control algorithm, which takes into account both the dynamics of the object and the dynamics of the hand, is computationally effective and can be generalized to allow rolling motion of the object with respect to the fingertip. >
A Study of Physician Recommendations for Reversible Contraceptive Methods Using Standardized Patients

CONTEXT: Health care providers may influence patients choice of contraceptive method yet little is known about the recommendations they make to their patients. METHODS: In 2007-2008 a total of 468 physicians at four family medicine and obstetrics and gynecology meetings were randomly assigned to view one of 18 videos of a patient seeking contraceptive advice; the patients were standardized for most relevant behaviors and characteristics but differed by race and ethnicity socioeconomic status and gynecologic history. Participants provided their demographic and practice characteristics and completed a survey about their contraceptive recommendations for the patient. Multivariate logistic regression analyses were conducted to identify associations between physician characteristics and recommendations for specific contraceptive methods. RESULTS: The most frequently recommended methods were the pill (89%) and ring (80%) followed by the levonor-gestrel IUD (64%) patch (56%) injectable (49%) and copper IUD (45%). Oral contraceptives were more likely to be recommended by private practice physicians than by academic physicians (odds ratio 2.9). Recommendations for the ring were less common among family physicians and those 56 or older than among obstetrician-gynecologists and those 35 or younger (0.6 and 0.3 respectively) and more common among physicians in private practice than among those in academia (2.4). The patch and injectable were more commonly recommended by family physicians than by obstetrician-gynecologists (2.6 and 2.5 respectively). Both IUD types were recommended less often by physicians 36 or older than by younger ones (0.2-0.5). DISCUSSION: The advice women receive about contraception may vary according to the characteristics of their provider. Research on the reasons for these differences is needed. Copyright (c) 2011 by the Guttmacher Institute.
STABILIZER: statistically sound performance evaluation

Researchers and software developers require effective performance evaluation. Researchers must evaluate optimizations or measure overhead. Software developers use automatic performance regression tests to discover when changes improve or degrade performance. The standard methodology is to compare execution times before and after applying changes.Unfortunately, modern architectural features make this approach unsound. Statistically sound evaluation requires multiple samples to test whether one can or cannot (with high confidence) reject the null hypothesis that results are the same before and after. However, caches and branch predictors make performance dependent on machine-specific parameters and the exact layout of code, stack frames, and heap objects. A single binary constitutes just one sample from the space of program layouts, regardless of the number of runs. Since compiler optimizations and code changes also alter layout, it is currently impossible to distinguish the impact of an optimization from that of its layout effects.This paper presents Stabilizer, a system that enables the use of the powerful statistical techniques required for sound performance evaluation on modern architectures. Stabilizer forces executions to sample the space of memory configurations by repeatedly re-randomizing layouts of code, stack, and heap objects at runtime. Stabilizer thus makes it possible to control for layout effects. Re-randomization also ensures that layout effects follow a Gaussian distribution, enabling the use of statistical tests like ANOVA. We demonstrate Stabilizer's efficiency (
Coal Hollow: Photographs and Oral Histories

Reviewed Medium: book Authors: Ken Light and Melanie Light Year: 2005 Pages: 151 Publisher: University of California Press ISBN: 0-520-24654-3 (hard cover). Prices: $34.95 USD(hard cover).
Physiological and growth responses of switchgrass (Panicum virgatum L.) in native stands under passive air temperature manipulation

In the central Great Plains of North America, climate change predictions include increases in mean annual temperature of 1.5–5.5 °C by 2100. Ecosystem responses to increased temperatures are likely to be regulated by dominant plant species, such as the potential biofuel species Panicum virgatum (switchgrass) in the tallgrass prairie. To describe the potential physiological and whole-plant responses of this species to future changes in air temperatures, we used louvered open-sided chambers (louvered OSC; 1 9 1 m, adjustable height) to passively alter canopy temperature in native stands of P. virgatum growing in tallgrass prairie at varying topographic positions (upland/lowland). The altered temperature treatment decreased daily mean temperatures by 1 °C and maximum temperatures by 4 °C in May and June, lowered daytime stomatal conductance and transpiration, decreased tiller density, increased specific leaf area, and delayed flowering. Among topographic contrasts, aboveground biomass, flowering tiller density, and tiller weight were greater in lowland sites compared to upland sites, with no temperature treatment interactions. Differences in biomass production responded more to topography than the altered temperature treatment, as soil water status varied considerably between topographic positions. These results indicate that while water availability as a function of topography was a strong driver of plant biomass, many leaf-level physiological processes were responsive to the small decreases in daily mean and maximum temperature, irrespective of landscape position. The varying responses of leaf-level gas exchange and whole-plant growth of P. virgatum in native stands to altered air temperature or topographic position illustrate that accurately forecasting yields for P. virgatum in mixed communities will require greater integration of physiological responses to simulated climate change (increased temperature) and resource availability over natural environmental gradients (soil moisture).
Isolation of Factors Causing Enhanced Lymphocyte Adherence to High Endothelial Venules in Vitro

Circulating T and B lymphocytes bind to high endothelial cell venules (HEV) as the first step in their emigration from blood into lymph nodes (1–7). We have used an in vitro lymphocyte-HEV binding assay to probe the molecular mechanism of this process (8–12) and have isolated a glycoprotein factor from lymph which appears to be derived from shed lymphocyte surface molecules mediating the binding reaction (13, 14). The factor inhibits HEV binding in vitro, apparently by blocking sites to which lymphocytes normally attach. We now report the isolation from lymph and TDL supernatants of components designated adherence enhancing factors (AEF) which cause increased lymphocyte binding to HEV in vitro. These AEF have biological effects which suggest that they may play a physiological role in lymphocyte recirculation by promoting recognition between lymphocytes and high endothelium.
Brain Tumor Angiogenesis: Drug Delivery and New Inhibitors

Despite enormous advances in clinical medicine, the prognosis of primary malignant brain neoplasms remains dismal. Currently, the most effective therapies result in a median survival of less than one year, with the majority of patients dying within two years (Black, 1991). In order to develop more effective methods for combatting this disease, we took advantage of two biological properties that are critical to glioma growth: first, the observation that malignant gliomas are predominantly a local disease usually recurring within two centimeters of the original focus (Hochberg and Pruitt, 1980); and second, the increasing evidence that brain tumors, like most solid tumors, are angiogenesis-dependent (Brem, et. al., 1988).
Calibration of a system for measurements of diffusion coefficients of fission products in HTGR/VHTR core materials

High temperature gas-cooled reactors utilize new grades of graphite as a structural component and barrier to fission product release. In this work, we present a novel method to measure the diffusion coefficient of fission products in graphite and demonstrate calibration of the system for quantification of Cs release rates from graphite. Spheres of graphite were loaded with Cs metal. The Cs released from the graphite spheres was transported directly to an inductively coupled plasma mass spectrometer for release measurements using a carbon particle helium jet. Cs calibration factors were determined using neutron activation analysis.
Developing blood brain barrier to trypan blue.

SummaryTrypan blue injected into developing rat embryos (10 days to birth) fails to stain the central nervous system. This impermeability in the developing central nervous system exists at the time when blood vessels invade the brain. It cannot be assumed, however, that the mechanisms which prevent protein-bound dyes from penetrating the cerebral blood vessels are the same for all other substances.
Simulating Ensemble-Averaged Surface-Enhanced Raman Scattering

The ability to simulate surface-enhanced Raman scattering (SERS) is a vital tool in elucidating the chemistry of molecules near the vicinity of plasmonic metal nanoparticles. However, typical methods do not include the dynamics of the molecule(s) of interest and are often limited to a single or few molecules. In this work, we combine molecular dynamics simulations with the dressed-tensor formalism to simulate the SERS spectra of Ag nanoparticles coated with a full monolayer of pyridine molecules. This method allows us to simulate the ensemble-averaged SERS spectra of more realistic large scale systems, while accounting for the organization of molecules in the hotspots. Through these simulations, we find that the preferential binding location and orientation of the molecules, the choice of electrodynamics method, and the inclusion of field gradient effects influence both the enhancement distribution and the spectral signatures. We also show that both the translational and rotational motions of a pyridine m...
Men at Risk: Special Education and Incarceration

The estimated percentage of individuals who are incarcerated with Traumatic Brain Injury (TBI) ranges from 25 to 87 % depending on whether one is considering a county jail, or a state or federal prison (Schofield et al., Brain Injury, 20(5), 499–506, 2006; Slaughter, Fann, & Ehde, Brain Injury, 17(9), 731–741, 2003; Morrell et al., Journal of Offender Rehabilitation, 27(3–4), 1–8, 1998). Many individuals are incarcerated with either an identified or unidentified TBI, while others sustain some type of head injury while incarcerated. In addition, many incarcerated individuals have a history of receiving special education services, with a small percentage falling within the TBI classification category. This chapter will discuss the percentage of incarcerated individuals who received special education services, the types of crimes often associated with incarcerated individuals with developmental and psychological disabilities, and prevalence of TBI among incarcerated individuals. The discussion related to TBI will focus on outlining the difficulties in accurately estimating the percentage of individuals with TBI and the difficulties in identifying TBI among incarcerated individuals. Finally, the need for screening, assessment, and treatment of individuals with TBI within the correctional system is reviewed.
A Compatible Topology Discovery Framework

As the fast development of information network technology,computer network is going to be a more and more important role as the development of industry.There are more and more equipments operating on the network,which makes more and more new network emerge.Hence,it is complicated and difficult to manage and maintain the network.For better manage and maintain the network,the automatic software system is needed to help manage and maintain the network.As an important function in the network management system,automatic discovery of network topology can discover the network equipments precisely and automatically.Different network need take different algorithms.This paper designed and implemented a topology discovery architecture which is portable among different networks based on JAVA and XML.The architecture can greatly reduce the complexity of developing new topology discovery system.
ACA-mandated elimination of cost sharing for preventive screening has had limited early impact.

Objectives The Affordable Care Act eliminated patient cost sharing for evidence-based preventive care, yet the impact of this policy on colonoscopy and mammography rates is unclear. We examined the elimination of cost sharing among small business beneficiaries of Humana, a large national insurer. Study design This was a retrospective interrupted time series analysis of whether the change in cost-sharing policy was associated with a change in screening utilization, using grandfathered plans as a comparison group. Methods We compared beneficiaries in small business nongrandfathered plans that were required to eliminate cost sharing (intervention) with those in grandfathered plans that did not have to change cost sharing (control). There were 63,246 men and women aged 50 to 64 years eligible for colorectal cancer screening, and 30,802 women aged 50 to 64 years eligible for breast cancer screening. The primary outcome variables were rates of colonoscopy and mammography per person-month, with secondary analysis of colonoscopy rates coded as preventive only. Results There was no significant change in the level or slope of colonoscopy and mammography utilization for intervention plans relative to the control plans. There was also no significant relevant change among those colonoscopies coded as preventive. Conclusions The results suggest that the implementation of the policy is not having its intended effects, as cost sharing rates for colonoscopy and mammography did not change substantially, and utilization of colonoscopy and mammography changed little, following this new policy approach.
A Rare Case of Primary Angiosarcoma of Ovary in a Postmenopausal Woman

Primary angiosarcoma of the ovary is a rare and aggressive subset accounting for less than 1% of ovarian malignancies. We present a rare case of primary angiosarcoma of the ovary in a 52-year-old healthy postmenopausal woman who presented with mild abdominal pain, distension and poor appetite of 1 week duration. On abdominal examination, right iliac fossa fullness with shifting dullness was noted. A CT of abdomen and pelvis revealed a right 10.5 cm complex solid cystic mass with ascites and peritoneal nodularity. Her CA125 was 560 U/mL. She subsequently underwent full surgical staging and optimal debulking surgery. Final histology confirmed angiosarcoma of ovary grade 3 FIGO stage IIA ovarian cancer. A repeat CT of abdomen and pelvis done 4 weeks later prior to starting chemotherapy showed large 6.5 × 6 cm pelvic peritoneal deposits with cystic septation and solid components. Her disease progressed despite palliative chemotherapy and she unfortunately passed away several months after surgery. We reiterate that primary angiosarcoma of the ovary is an aggressive tumor with poor prognosis despite optimal surgical treatment. J Med Cases. 2016;7(9):393-395 doi: http://dx.doi.org/10.14740/jmc2606w
Are We Ready to Recommend a College Readiness Index? A Reply to Gaertner and McClarty (2015)

In an article published in Educational Measurement: Issues and Practice, Gaertner and McClarty (2015) discuss a college readiness index based, in part, on nonacademic or noncognitive factors measured in middle school. Such an index is laudable as it incorporates important constructs beyond academic achievement measures that may be important in assessing college readiness. It also holds potential in identifying areas of need at a critical time and can theoretically inform important interventions that may be necessary prior to the later stages of high school. However, one of the noncognitive factors—motivation—appeared to be theoretically incomplete, underrepresented, and contained items irrelevant to the construct of academic motivation. We offer our concerns about the validity of this factor as measured by the index and the associated implications about the consequences of using this to inform educational interventions. Through this commentary, we hope to offer constructive feedback on future research that can build upon Gaertner and McClarty's important work.
Feasiblity and Implication of Bidirectional Sequencing Using a Multiplex Framework 2 Region Primer for Somatic Mutation Analysis of the Immunoglobulin (IgH) Heavy Chain in Chronic Lymphocytic Leukemia (CLL).

Abstract Background: A somatic mutation rate of >2% of the immunoglobulin (IgH) heavy chain gene, in comparison to germline DNA, is a positive prognostic indicator in chronic lymphocytic leukemia (CLL). Genomic DNA is amplified using the Biomed-2 multiplex PCR primer set, sequenced in the reverse direction only using a 3′ JH primer, and compared to the germline sequence in VBase, a comprehensive directory of all human germline variable region sequences compiled from over a thousand published sequences. It is unknown whether forward sequencing using the multiplex 5′ Biomed-2 primers in a single reaction is feasible or whether doing so improves the accuracy of the mutational analysis. Methods: DNA was extracted from peripheral blood or bone marrow mononuclear cells from patients with CLL using the QIAGEN QIAspin DNA mini-kit. The FR2 region of the IgH gene was amplified using tube B of the Biomed-2 multiplex PCR primer set, separated in 2% agarose gel, excised, and prepared for sequencing using the QIAGEN QIAquick gel extraction kit. Bidirectional DNA sequencing was performed with the full set of multiplex 5′ FR2 primers combined in one reaction for the forward sequence and in a second reaction with the Biomed-2 3′ JH primer for the reverse sequence. A consensus sequence was obtained and mutation rates were calculated based on the consensus sequence and the reverse sequence separately. Results: The FR2 region was amplified from 30 CLL patients. 20 samples produced bidirectional consensus DNA sequences, 2 sequenced only with multiplex FR2 primers, 6 sequenced only with a JH primer, and 2 produced no sequences. Compared with unidirectional JH sequencing, bidirectional sequencing did not reassign any patient in the germline IgH group to the mutated category. In 15 patients, the uni- and bi-directional sequencing were identical. In 4 patients, a single basepair difference was noted. A random permutation test yields a two-sided p-value as 12.5%, indicating that no significant difference was detected between the uni- and bi-directional sequencing. Multiplex bidirectional sequencing did provide sequence information within the CDR3 region at the 3′ terminus of the amplimer which is partially truncated when using the JH primer alone. Conclusion: Bidirectional sequencing does not provide a somatic IgH mutation rate that differs significantly from that obtained from the reverse sequence alone and does not likely influence the IgH mutational prognostic assignment. Nonetheless, the bidirectional consensus sequence adds bases in the CDR3 region which can be used for research applications such as the generation of patient-specific primers for PCR. It is also noteworthy that multiplex PCR using the Biomed-2 primers is feasible.
Modeling heterogeneous traffic flow: A pragmatic approach

Abstract Modeling dynamics of heterogeneous traffic flow is central to the control and operations of today’s increasingly complex transportation systems. We develop a macroscopic heterogeneous traffic flow model. This model considers interplay of multiple vehicle classes, each of which is assumed to possess homogeneous car-following behavior and vehicle attributes. We propose the concepts of road capacity split and perceived equivalent density for each class to model both lateral and longitudinal cross-class interactions across neighboring cells. Rather than leveraging hydrodynamic analogies, it establishes pragmatic cross-class interaction rules aspired by capacity allocation and approximate inter-cell fluxes. This model generalizes the classical Cell Transmission Model (CTM) to three types of traffic regimes in general, i.e. free flow, semi-congestion, and full congestion regimes. This model replicates prominent empirical characteristics exhibited by mixed vehicular flow, including formation and spatio-temporal propagation of shockwaves, vehicle overtaking, as well as oscillatory waves. Those features are validated against numerical experiments and the NGSIM I-80 data. Realistic class-specific travel times can be computed from this model efficiently, which demonstrates the feasibility of applying this multi-class model to large-scale real-world networks.
Cost-effectiveness analysis of umeclidinium/vilanterol for the management of patients with moderate to very severe COPD using an economic model

Background Bronchodilators such as long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) are central to the pharmacological management of COPD. Dual bronchodilation with umeclidinium/vilanterol (UMEC/VI; 62.5/25 μg) is a novel LAMA/LABA combination approved for maintenance treatment for patients with COPD. Objective The objective of this study was to assess the cost-effectiveness of maintenance treatment with UMEC/VI compared with tiotropium (TIO) 18 μg, open dual LAMA + LABA treatment, or no long-acting bronchodilator treatment in patients with moderate to very severe COPD. Methods A Markov model was developed to estimate the costs and outcomes associated with UMEC/VI treatment in patients with moderate to very severe COPD (GSK study number: HO-13-13411). Clinical efficacy, costs, utilities, and mortality obtained from the published literature were used as the model inputs. Costs are presented in US dollars based on 2015 prices. The model outputs are total costs, drug costs, other medical costs, number of COPD exacerbations, and quality-adjusted life-years (QALYs). Costs and outcomes were discounted at a 3% annual rate. Incremental cost-effectiveness ratios were calculated. One-way and probabilistic sensitivity analyses were conducted to assess the effects of changing parameters on the uncertainty of the results. Results UMEC/VI treatment for moderate to very severe COPD was associated with lower lifetime medical costs ($82,344) compared with TIO ($88,822), open dual LAMA + LABA treatment ($114,442), and no long-acting bronchodilator ($86,751). Fewer exacerbations were predicted to occur with UMEC/VI treatment compared with no long-acting bronchodilator treatment. UMEC/VI provided an 0.11 and 0.25 increase in QALYs compared with TIO and no long-acting bronchodilator treatment, and as such, dominated these cost-effectiveness analyses. Sensitivity analyses confirmed that the results were robust. Conclusion The results from this model suggest that UMEC/VI treatment would be dominant compared with TIO and no long-acting bronchodilator treatment, and less costly than open dual LAMA + LABA treatment in patients with moderate to very severe COPD.
THE NATURAL NUMBERS

This chapter discusses various approaches to the most important kind of numbers in all of mathematics, namely, the natural numbers. The inclusion of the number zero as the first one among the natural numbers is in accordance with the usage of most logicians, though many mathematicians do not include the number zero among the natural numbers but take the number one to be the first of these numbers. The natural numbers are the numbers used for counting things, where the things being counted are finitely many in number. The chapter also presents a certain well-known elementary axiomatic theory for the arithmetic of the natural numbers. The particular theory considered is the theory N or first-order Peano arithmetic. Its underlying logic is an elementary predicate logic with identity and operation symbols F°, in which the nonlogical constants are the following four constants: (1) 0, (2) S, (3) +, and (4) . . The first of these constants is an individual constant, the second is a singulary operation symbol, and the third and fourth are binary operation symbols.
Prevalence of chemopreventive agent use among hospitalized women at high risk for breast cancer.

e13050Background: Preventing breast cancer would be highly valued by all women. Recent attention about risk stratification for breast cancer in women stems from opportunities for risk reduction using chemopreventive agents like tamoxifen and raloxifen. Effectiveness of primary prevention for women at highest risk for breast cancer has resulted in strategies for implementing chemoprevention guidelines. The purpose of the current study was to characterize the current utilization of chemoprevention agents among hospitalized women who are at higher risk for breast cancer. Methods: A cross sectional bedside survey of 250 women aged 50-75 years hospitalized to a general medicine service was conducted. Reproductive history, family history for breast cancer, chemopreventive agents use, and medical comorbidities data was collected for all patients. Chi square and t-tests were utilized to analyze population characteristics. Results: Mean age for the study population was 61.5 years (SD 7.5), and mean 5-year Gail ris...
Quantifying root water extraction after drought recovery using sub-mm in situ empirical data

Root-specific responses to stress are not well-known, and have been largely based on indirect measurements of bulk soil water extraction, which limits mechanistic modeling of root function. Here, we used neutron radiography to examine in situ root-soil water dynamics of a previously droughted black cottonwood (Populus trichocarpa) seedling, contrasting water uptake by the two major components of the root system that differed in initial recovery rate as apparent by ‘new’ (whiter, thinner), or ‘old’ (darker, thicker) parts of the fine root system. The smaller diameter ‘new’ roots had greater water uptake per unit surface area than the larger diameter ‘old’ roots, but they had less total surface area leading to less total water extraction; rates ranged from 0.0027–0.0116 g cm−2 h−1. The finest most-active roots were not visible in the radiographs, indicating the need to include destructive sampling. Analysis based on root-free bulk soil hydraulic properties indicated substantial redistribution of water via saturated/unsaturated flow and capillary wicking across the layers - suggesting water uptake dynamics following an infiltration event may be more complex than approximated by common soil hydraulic or root surface area modeling approaches. Our results highlight the need for continued exploration of root-trait specific water uptake rates in situ, and impacts of roots on soil hydraulic properties – both critical components for mechanistic modeling of root function.
A Lipoylated Metabolic Protein Released by Staphylococcus aureus Suppresses Macrophage Activation.

Summary The virulence factors of pathogenic microbes often have single functions that permit immune suppression. However, a proportion possess multiple activities and are considered moonlighting proteins. By examining secreted virulence factors of Staphylococcus aureus , we determine that the bacterial lipoic acid synthetase LipA suppresses macrophage activation. LipA is known to modify the E2 subunit of the metabolic enzyme complex pyruvate dehydrogenase (E2-PDH) with a fatty acid derivative, lipoic acid, yielding the metabolic protein lipoyl-E2-PDH. We demonstrate that lipoyl-E2-PDH is also released by S. aureus and moonlights as a macrophage immunosuppressant by reducing Toll-like receptor 1/2 (TLR1/2) activation by bacterial lipopeptides. A LipA-deficient strain induces heightened pro-inflammatory cytokine production, which is diminished in the absence of TLR2. During murine systemic infection, LipA suppresses pro-inflammatory macrophage activation, rendering these cells inefficient at controlling infection. These observations suggest that bacterial metabolism and immune evasion are linked by virtue of this moonlighting protein.
Diffusion and conformational dynamics of single DNA molecules crowded by cytoskeletal proteins

The high concentrations of proteins crowding cells greatly influence intracellular DNA dynamics. These crowders, ranging from small mobile proteins to large cytoskeletal filaments such as semiflexible actin and rigid microtubules, can hinder diffusion and induce conformational changes in DNA. While previous studies have mainly focused on the effect of small mobile crowders on DNA transport, we examine the impact of crowding by actin filaments and microtubules. Further, because actin filaments and microtubules are formed by polymerization of actin monomers and tubulin dimers, respectively, we also investigate the role that the polymerization state of each protein plays in DNA transport and in the time-varying conformational changes of single DNA molecules diffusing in in vitro networks of polymerized and monomeric actin and tubulin. We find that crowding by actin monomers slows DNA diffusion while tubulin crowding actually increases diffusion coefficients. Monomeric actin crowding DNA diffusion, more than when actin is polymerized, while crowding by tubulin dimers increases DNA diffusion more than when tubulin is polymerized (microtubules). Further, we find unexpected relationships between DNA coil size and diffusion when crowded. All crowding conditions lead to some degree of DNA compaction, but less compaction enables faster dynamics.
iPat: intelligent prediction and association tool for genomic research.

Summary The ultimate goal of genomic research is to effectively predict phenotypes from genotypes so that medical management can improve human health and molecular breeding can increase agricultural production. Genomic prediction or selection (GS) plays a complementary role to genome-wide association studies (GWAS), which is the primary method to identify genes underlying phenotypes. Unfortunately, most computing tools cannot perform data analyses for both GWAS and GS. Furthermore, the majority of these tools are executed through a command-line interface (CLI), which requires programming skills. Non-programmers struggle to use them efficiently because of the steep learning curves and zero tolerance for data formats and mistakes when inputting keywords and parameters. To address these problems, this study developed a software package, named the Intelligent Prediction and Association Tool (iPat), with a user-friendly graphical user interface. With iPat, GWAS or GS can be performed using a pointing device to simply drag and/or click on graphical elements to specify input data files, choose input parameters and select analytical models. Models available to users include those implemented in third party CLI packages such as GAPIT, PLINK, FarmCPU, BLINK, rrBLUP and BGLR. Users can choose any data format and conduct analyses with any of these packages. File conversions are automatically conducted for specified input data and selected packages. A GWAS-assisted genomic prediction method was implemented to perform genomic prediction using any GWAS method such as FarmCPU. iPat was written in Java for adaptation to multiple operating systems including Windows, Mac and Linux. Availability and implementation The iPat executable file, user manual, tutorials and example datasets are freely available at http://zzlab.net/iPat. Contact zhiwu.zhang@wsu.edu.
Salomon’s House in London

In Bacon’s New Atlantis the king of that island had ruled ‘that every twelve years there should be sent forth out of this kingdom two ships, appointed to several voyages.’ These were sent forth ‘to give us knowledge of the affairs and state of those countries to which they were designed: and especially of the sciences, arts, manufactures, and inventions of all the world; and withal to bring unto us books, instruments, and patterns of every kind.’ 1 When Huygens sailed out from Holland to England he did so in just this inquiring spirit, to learn what he could in England of ‘sciences, arts, manufactures, and inventions’ and to take back for his own country’s benefit whatever information he could get.
Preparation of Novel Polyamide 6 Blends Made by Reactive Extrusion Compounding

The preparation of polymer blends is normally undertaken by mixing polymers in the melt state, typically in a compounding extruder, whereby the applied shear can be varied and hence the blend microstructure controlled. In immisicible blends, which are thermodynamically unstable, phase morphology can be further modified through the use of compatibilising additives, such as block copolymers, which generally leads to improved physical properties. Compatibilisation can also be achieved by reactive modification of one or more of the polymer phases, including chemical changes to the polymer structure. This paper discusses a novel approach to the preparation of polymer blends, through the in-situ polymerisation of monomer in the presence of a secondary polymer phase during passage through a co-rotating twin-screw extruder. When prepared in this manner, not only can the molecular mass of the polymerising monomer be influenced, but there is the potential for improved compatibility in the blend, possibly arising from chemical interaction between the phases or the formation of interpenetrating network structures. Furthermore, the phase microstructure in the blend can be strongly affected by the mixing conditions employed inside the compounder, in particular the levels of shear generated, through adjustment of screw profile and operating conditions. This approach to reactive compounding will be illustrated with reference to the preparation and characterisation of polyamide 6 (PA6) blends, by polymerisation of ∊-caprolactam in the presence of polypropylene (PP) and ethylene-propylene rubber (EPR).