cssi/SciSciGPT-SciSciNet huggingface dataset:
cDNA of the yeast retrotransposon Ty5 preferentially recombines with substrates in silent chromatin

The yeast retrotransposon Ty5 preferentially integrates into regions of silent chromatin. Ty5 cDNA also recombines with homologous sequences, generating tandem elements or elements that have exchanged markers between cDNA and substrate. In this study, we demonstrate that Ty5 integration depends upon the conserved DD(35)E domain of integrase and cis-acting sequences at the end of the long terminal repeat (LTR) implicated in integrase binding. cDNA recombination requires Rad52p, which is responsible for homologous recombination. Interestingly, Ty5 cDNA recombines at least three times more frequently with substrates in silent chromatin than with a control substrate at an internal chromosomal locus. This preference depends upon the Ty5 targeting domain that is responsible for integration specificity, suggesting that localization of cDNA to silent chromatin results in the enhanced recombination. Recombination with a telomeric substrate occasionally generates highly reiterated Ty5 arrays, and mechanisms for tandem element formation were explored by using a plasmid-based recombination assay. Point mutations were introduced into plasmid targets, and recombination products were characterized to determine recombination initiation sites. Despite our previous observation of the importance of the LTR in forming tandem elements, recombination cannot simply be explained by crossover events between the LTRs of substrate and cDNA. We propose an alternative model based on single-strand annealing, where single-stranded cDNA initiates tandem element formation and the LTR is required for strand displacement to form a looped intermediate. Retrotransposons are increasingly found associated with chromosome ends, and amplification of Ty5 by both integration and recombination exemplifies how retroelements can contribute to telomere dynamics. The cDNA generated by reverse transcription during retrotransposon and retrovirus replication can enter the genome by two pathways: it can integrate by using the element-encoded integrase or it can recombine with preexisting elements by
Exploring the elite world in the Siyar al-Awliyā’: Urban elites, their lineages and social networks:

Composed by Amīr Khwurd around the middle of the fourteenth century, the Siyar al-Awliyā’ presents a coherent history of the Chishti spiritual order (silsilah) in the Indian subcontinent from the e...
THE CHALLENGES OF BRIDGING PASTORAL CARE EXPERIENCES AND POST-MODERN APPROACHES TO KNOWLEDGE

To any but the most unreconstructed of biblical literalists, the challenge of contemporary religious thought is to keep alive in the postmodern world a religious vision created in a distinctly premodern cultural context, honed to a level of sophistication and lived out courageously through many centuries of premodernity (Lakeland, 1997, p. 39)
Fractionation of a tumor-initiating UV dose introduces DNA damage-retaining cells in hairless mouse skin and renders subsequent TPA-promoted tumors non-regressing

Sunburns and especially sub-sunburn chronic UV exposure are associated with increased risk of squamous cell carcinomas (SCCs). Here we focus on a possible difference in tumor initiation from a single severe-sunburn dose (on day 1, 21 hairless mice) and from an equal dose fractionated into very low sub-sunburn doses not causing any (growth-promoting) epidermal hyperplasia (40 days daily exposure, n=20). From day 47 all mice received 12-O-Tetradecanoylphorbol-13-acetate (TPA) applications (2x/wk) for 20 weeks to promote tumor development within the lifetime of the animals. After the sub-sunburn regimen sparse DNA damage-retaining basal cells (quiescent stem cells, QSCs) remained in the non-hyperplastic epidermis. These cells were forced to divide by TPA. After discontinuation of TPA tumors regressed and disappeared in the 'sunburn group' but persisted and grew in the 'sub-sunburn group' (0.06 vs 2.50 SCCs and precursors ≥4 mm/mouse after 280 days, p=0.03). As the tumors carried no mutations in p53, H/K/N-Ras and Notch1/2, these 'usual suspects' were not involved in the UV-driven tumor initiation. Although we could not selectively eliminate QSCs (unknown phenotype) to establish causality, our data suggest that forcing specifically DNA damage-retaining QSCs to divide--with high mutagenic risk--gives rise to persisting (mainly 'in situ') skin carcinomas.
A Measurement of g2p at Low Q2

Jefferson Lab has been at the forefront of a program to study the polarized structure of nucleons using electron scattering. Measurements of the spin dependent structure functions, g1 and g2, have proven to be powerful tools in testing and understanding QCD. The neutron structure function g2n has been measured extensively in Hall A at Jefferson Lab over a wide range of Q2, but data for g2p remains scarce. This docment will discuss the g2p experiment, which ran in Hall A at Jefferson Lab in the spring of 2012, and will provide the first measurement of g2p in the resonance region; covering 0.02 < Q2 < 0.2 GeV2. The 0th moment of g2 provides a test of the Burkhardt-Cottingham sum rule, which states that the integral of g2 over the Bjorken scaling variable x goes to zero. This sum rule, valid for all values of Q2, has been satisfied for the neutron, but a violation is suggested for the proton at high Q2. The 2nd moment allows for a benchmark test of χPT at low Q2. Specifically, the behavior of the longitudinally-transverse spin polarizability (δLT), as χPT calculations of this quantity deviate significantly from the measured neutron data. This document will discuss the current status of the analysis along with preliminary results.
A Fast Parallel Selection Algorithm on GPUs

Today, parallel selection algorithms that run on Graphical Processing Units (GPUs) hold great promise in providing even more computational power than that of conventional CPUs. To quantify these gains, we examined a new parallel selection algorithm to see exactly what its vast number of simple, data parallel, multithreaded cores meant for performance times, using the current generation of NVIDIA GPUs. Specifically, our team tested how we could utilize a GPU to select elements from a massive array that met specific criteria and store their indices in a target array for additional processing. In this paper, we report optimization techniques and road blocks encountered. Overall, the experimental results demonstrate that our implementation performs an average of 3.67 times faster than Thrust, an open-source parallel algorithms library.
Clinical Pharmacodynamics of High-Dose Methotrexate in Acute Lymphocytic Leukemia

Abstract High-dose methotrexate (500 to 33,600 mg per square meter of body-surface area) with leucovorin rescue is a common component of therapy for acute lymphocytic leukemia. To increase understanding of the relation between the serum concentration and the effect of methotrexate, we conducted a randomized, prospective study of 108 children with "standard-risk" acute lymphocytic leukemia who were treated with 15 doses of methotrexate (1000 mg per square meter) that were infused over 24 hours. The median length of follow-up was 3.5 years from diagnosis for patients still in remission. Variability between patients in methotrexate clearance produced steady-state serum concentrations that ranged from 9.3 to 25.4 μM. Patients with median methotrexate concentrations of less than 16 μM (n = 59) had a lower probability of remaining in remission (P<0.05) than patients with concentrations of 16 μM or more (n = 49). Multivariate analyses indicated that patients with methotrexate concentrations of less than 16 μM we...
Neurotrophins regulate cholinergic synaptic transmission in cultured rat sympathetic neurons through a p75-dependent mechanism.

The sympathetic nervous system regulates many essential physiological systems, and its dysfunction is implicated in cardiovascular diseases. Mechanisms that control the strength of sympathetic outp...
Not only diabetic polyneuropathy but also interstitial cells of Cajal dysfunction is a potential mechanism for diabetic cystopathy

Canda et al. [1] focused on the changes of interstitial cells of Cajal (ICCs) and neuronal tissue related to diabetes. The results of the current study showed that the number of ICCs in the lamina propria and detrusor muscle is decreased in diabetic patients. This may be an underlying pathomechanism of lower urinary tract symptoms in patients with diabetes. Long lasting diabetes results in different urological complications in over 50% of cases. The most common complications include diabetic bladder dysfunction (DBD), diabetic cystopathy, urinary tract infections and sexual dysfunction. Diabetic cystopathy (DC) was first described by Moller in 1976. DC features consist of an increased urinary bladder capacity, post voiding residual volumes and decreased urinary bladder sensation and motor activity as a result of diabetic polyneuropathy. DBD is referred to a wide range of lower urinary tract symptoms that encompass storage complaints (overactive bladder/detrusor overactivity) and voiding complaints (poor urinary bladder emptying or overflow urine incontinence), as well as other less clinically defined phenotypes such as decreased sensation and increased capacity [2–5].
Analysis of the Elders' Long-Term Care Arrangement and Its Influencing Factors in Rural China—Based on a Comparative Analysis between Shanghai and Hubei

By analyzing the survey data from both Shanghai and Hubei,the results show that institutional care has not yet been widely accepted among rural elders in China.The willingness of long-term care(LTC)arrangement differs significantly across the regions;formal LTC arrangement is more acceptable in more economically developed areas than those less developed.Many factors affect their preference of choices.The elders with lower education level,paid job,lower household income,married and living with the spouse are more willing to accept family care;while those with pension and medical insurance coverage are more willing to accept hiring someone outside of their family to take care of them or being admitted to a nursing home.
Teaching game programming with PlayN

This experience report describes the deployment of PlayN in undergraduate game programming courses. PlayN is an open-source library for developing digital games in Java and deploying them to Android, iOS, HTML5, and desktop computers. The experience report is based on four semesters and three different course configurations: in each, PlayN was deployed in a project-oriented pedagogy along with distributed version control, continuous integration, and agile project management techniques. This approach brings several benefits, including exposing students to industrial best practices, showing the benefits of code quality, helping students learn to read source code written by others, and reinforcing concepts of object-orientation, particularly the multiple possible reifications of design patterns. The same configuration that brings these benefits also brings challenges: faculty must invest time in learning the library, its dependencies, and the tooling around them; resources or experience are required to configure and maintain the technology infrastructure, as well as to assist students in overcoming fear and ignorance regarding computing systems -- even their own; and significant time must be invested in creating resources to scaffold the student learning experience.
Feasibility of Tagging Walleye Pollock Captured with Hook and Line Using External Tags

AbstractWe evaluated methods of minimizing mechanical injury to Walleye Pollock Gadus chalcogrammus when tagging them with external identification tags. Walleye Pollock (20–62 cm FL) were captured with hook and line near Auke Bay, Southeast Alaska, and were tagged with either T-bar anchor tags or lock-on tags, which were anticipated to be used for tagging studies in the Gulf of Alaska and Bering Sea. The tested handling procedures included transferring the tagged fish between live tanks either by using a dip net (dipnetted group) or with wet, bare hands (non-dipnetted group). Sixty percent of the dipnetted fish (63 of 105) died, whereas 12% of the non-dipnetted fish (17 of 138) died. Overall, 50% of the deaths occurred within 7 d after capture, and 89% of the deaths occurred within 10 d after capture. Of the dipnetted fish that died, 68% (n = 43) died from dermal infection due to scale loss, whereas 30% of the non-dipnetted fish mortalities were from dermal infection. Additionally, injuries that were reco...
Alzheimer Disease in Down Syndrome

A clinical prospective study of dementia of the Alzheimer type in 96 individuals with Down syndrome over age 35 years is reported from the Eunice Kennedy Shriver Center, Waltham, MA and the Massachusetts General Hospital and Harvard Medical School, Boston, MA.
Open source laboratory sample rotator mixer and shaker

An open-source 3-D printable laboratory sample rotator mixer is developed here in two variants that allow users to opt for the level of functionality, cost saving and associated complexity needed in their laboratories. First, a laboratory sample rotator is designed and demonstrated that can be used for tumbling as well as gentle mixing of samples in a variety of tube sizes by mixing them horizontally, vertically, or any position in between. Changing the mixing angle is fast and convenient and requires no tools. This device is battery powered and can be easily transported to operate in various locations in a lab including desktops, benches, clean hoods, chemical hoods, cold rooms, glove boxes, incubators or biological hoods. Second, an on-board Arduino-based microcontroller is incorporated that adds the functionality of a laboratory sample shaker. These devices can be customized both mechanically and functionally as the user can simply select the operation mode on the switch or alter the code to perform custom experiments. The open source laboratory sample rotator mixer can be built by non-specialists for under US$30 and adding shaking functionality can be done for under $20 more. Thus, these open source devices are technically superior to the proprietary commercial equipment available on the market while saving over 90% of the costs.
Modeling of cellular actuators

Abstract In this part, mathematical methods for modeling the complex interactions between various nested strain amplifiers and experimental techniques for the characterization of cellular actuator arrays are introduced. The two-port network model mathematically represents the characteristics of a single cellular actuator as to how the displacement and force produced by an enclosed piezoelectric actuator are transmitted through the rhomboidal structure. The two-port model provides a more accurate depiction of how the cellular actuator will behave as the assumptions in the idealized model presented in the prior part are relaxed. This mathematical representation can be applied to multi-layer mechanisms by introducing a concept of collapsing, or reducing the innermost layers to an equivalent Norton circuit one-by-one. The collapsing process allows us to quickly and easily identify important bulk properties of the nested actuator as a whole, namely, its blocked force, free displacement, and stiffness. When a large number of cellular actuators are available, the number of combinations in which one could connect actuators is also very large, and the possible topologies are complex. A method, named the “fingerprint method,” automatically generates every possible stochastic actuator array topology for a given number of cells, and calculates actuator array properties such as travel, required actuator strength/displacement, force range, force variance, and robustness for any array topology.
Does the timing of suicide risk assessments influence ratings of risk severity

Clinicians are often tasked with identifying and managing patients who are at risk for suicide. Therefore, greater understanding of factors that impact the efficacy of suicide risk assessments (SRA) are of critical importance. One potential factor that may affect assessments of risk severity is the timing of the evaluation during clinical interview. Given that some patients are reluctant to disclose suicide-related symptoms, it is possible that asking about suicide at the beginning of an interview elicits more false negatives. It is also possible that if risk assessments are conducted in a manner that is encouraging to the patient, timing does not significantly impact patient report. This study examined whether SRA timing within an initial intake interview affects risk severity ratings. Adult psychiatric outpatients (N=169) were randomly assigned to receive a SRA during the beginning or middle of a one-hour intake. We failed to find a significant difference in suicide risk ratings between those who were evaluated at the beginning as compared to the middle of intake (14% versus 15% rated at elevated risk). Findings were not moderated by age, gender, or attempt history. Our results provide preliminary evidence that the timing of SRA may not impact risk severity ratings.
Household chaos as a context for intergenerational transmission of executive functioning.

Abstract Executive functioning (EF) may be transmitted across generations such that strengths or deficiencies in parent EF are similarly manifested in the child. The present study examined the contributions of parent EF and impulsivity on adolescent EF, and investigated whether household chaos is an environmental moderator that alters these transmission processes. American adolescents (N = 167, 47% female, 13–14 years old at Time 1) completed behavioral measures of EF and reported household chaos at Time 1 and one year later at Time 2. Parents completed behavioral measures of EF and self-reported impulsivity at Time 1. Results indicated that lower parent EF at Time 1 predicted lower adolescent EF at Time 2 (controlling for adolescent EF and IQ at Time 1), but only in the context of high household chaos. Findings suggest that household chaos may be a risk factor that compounds influences of poor parent EF and compromises adolescent EF development.
Hydrogel-based microchannels to measure confinement- and stiffness-sensitive Yes-associated-protein activity in epithelial clusters

Nuclear translocation of Yes-associated-protein (YAP) in single cells serves as a key sensor of matrix stiffness. On two-dimensional (2D) polyacrylamide (PA) hydrogels, we found that nuclear YAP localization in epithelial clusters increases with gel stiffness and reduces with cell density. To measure YAP activity in 3D-like confinement of tunable stiffness, we fabricated PA-based microchannels. Here, narrower channels enhanced nuclear YAP localization even in softer extracellular matrix and denser epithelial clusters, both of which reduced YAP activation in 2D. Thus, the presented hydrogel microchannel-based platform may reveal new mechanosensitive cellular signatures in 3D-like settings, which cannot be captured on standard 2D hydrogels.
Reasons Without Values

Author(s): Greenberg, Mark | Abstract: In “How Facts Make Law” (Greenberg 2004), I argue that non-normative contingent facts are not sufficient to determine the content of the law. In the present paper, I take up a challenge raised by Enrique Villanueva (2005). He suggests that, to put it very briefly, descriptive facts can be reasons. Therefore, even if the content of the law depends on reasons, it does not follow that law practices cannot themselves determine the content of the law.Villanueva proposes a value-neutral criterion – textualism. In other words, he suggests that the descriptive facts about the meaning of legal texts are themselves reasons that determine the contribution of law practices to the content of the law. This suggestion depends on too shallow a conception of the requirement of reasons. For the law to be rationally determined, it is not enough that there be some value-neutral criterion that specifies that law practices have certain consequences for the content of the law. There have to be reasons that explain why that criterion, as opposed to all others, is the legally correct one – the one that, in the relevant legal system, determines the contribution of law practices to the content of the law. Normative facts are the best candidates for such reasons. And, in fact, Villanueva’s textualist criterion derives its appeal from normative facts.Reasons play a central role in the ontology of law. The determinants of the content of the law, which include law-determining practices such as statutes and judicial decisions, influence the content of the law in a systematic way. But their influence on the content of the law cannot be brute: there have to be reasons that explain why the determinants have the particular significance that they have. These reasons are part of what makes the determinants have that significance. Hence, the reasons are part of what makes the content of the law what it is. Descriptive facts cannot themselves provide the necessary reasons: given any descriptive fact that is a candidate reason, its significance itself depends on reasons – and, unlike normative facts, descriptive facts cannot determine their own significance. Descriptive facts therefore cannot alone determine the content of the law.
Understanding “Roots and Routes” from a Post-Kantian Tradition of Critique

This essay aims to understand Ananta Kumar Giri’s notions of roots and routes from a post-Kantian tradition of critique as regulative ideas and to show their possibilities to address problems of politics, culture, and society, stemming from nationalist and ethnic self-assertion, within a globalized and transmodern world, specifically, to avoid the common pitfalls of violence and absolutism in the processes of political, social, and cultural mobilization predicated upon ideas of ethnicity and nation. It tries to show—pace common sense—how roots and routes are interrelated, specifically, how there are routes in all our roots and how being with routes does not necessarily produce rootless histories and modernities and, on this basis, to show furthermore how we can understand self, ethnicity, and nation at the cross-roads of roots and routes.
Secondary Stroke Prevention in Atrial Fibrillation: New Insights Into an Old Problem.

See related article, p 1464 The detection and treatment of nonvalvular atrial fibrillation (NVAF) constitute areas of active research yielding novel technologies that result in lively debates among general medicine, cardiology, and neurology specialists. Non–vitamin K antagonist oral anticoagulants (NOAC), approved by Food and Drug Administration (FDA) within the first half of this decade, have been increasingly adopted as first-line agents for stroke prevention in NVAF.1 These medications have shown noninferiority for stroke prevention against warfarin arms with suboptimal international normalized ratio control in patient populations with low mean embolic risk scores for ≈2 years of follow-up. Except ROCKET-AF (Rivaroxaban; The Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) that enrolled a large patient population (55%) presenting after an ischemic stroke or transient ischemic attack, the phase III studies of NOACs mostly included primary prevention cohorts (≈80%).2 The mean time in therapeutic range of patients enrolled in warfarin arms of the 3 most commonly used NOACs was in the 55% to 62% range (rivaroxaban, dabigatran, and apixaban). Comparing NOACs to warfarin in that setting suggested equivalent benefit for embolic prevention and a lower risk of intracerebral hemorrhage (ICH) favoring NOACs in patients who were at low ICH risk during study enrollment. Real-world experience with NOACs has been positive to date when used in patient populations similar to their phase III studies, that is, patients with good kidney function, no prior history of ICH, and no perceived high risk for major hemorrhage. A specific reversal agent for dabigatran was FDA approved for use in emergency procedures or in uncontrolled bleeding, and another drug is awaiting approval for the more commonly used Factor Xa inhibitors. These are good news as reversal of anticoagulation can make …
Hardware mechanisms for distributed dynamic software analysis

The complexity of modern software makes it difficult to ship correct programs. Errors can cost money and lives, so developers often use automated software analysis tools to hunt for bugs. By automatically analyzing a program's runtime operation, dynamic analysis tools can find subtle errors that would normally escape the notice of even careful human testers. These dynamic analyses are more likely to find errors if they observe the program under numerous and varied runtime situations, so, ideally, users would analyze programs as they run them. Regrettably, these tests cause orders-of-magnitude slowdowns, which few users would tolerate. This dissertation presents methods of accelerating dynamic software analyses in order to distribute these trials to users. It begins by observing that the overhead that any individual observes can be lowered by allowing each user to analyze a small, random sample of the program's operations. It then describes a sampling mechanism for dynamic dataflow analyses that only requires access to the virtual memory system. Other dynamic software analyses cannot use this technique, so the remainder of this dissertation focuses on novel hardware-based acceleration mechanisms. The first, Testudo, allows faster and more accurate dataflow analysis sampling by storing meta-data in an on-chip cache and stochastically removing these values whenever it overflows. Next, a method for performing demand-driven data race detection using existing hardware performance counters is detailed. These counters make inter-cache sharing events visible to software, allowing the data race detector to be enabled only when needed. Finally, fine-grained memory monitoring is a crucial for every analysis studied in this work. This dissertation closes by examining a hardware mechanism for allowing unlimited fine-grained watchpoints, which can be used to reduce the overheads of many analyses. In total, this dissertation demonstrates that hardware designers can play a role in mitigating software bugs, as many of the acceleration mechanisms explored in this work require hardware support in one form or another. Taken together, these works represent a step forward for accelerating dynamic software analyses and distributing them to end-users.
Type 1 IFN and PD-L1 Coordinate Lymphatic Endothelial Cell Expansion and Contraction during an Inflammatory Immune Response

Lymph node (LN) expansion during an immune response is a complex process that involves the relaxation of the fibroblastic network, germinal center formation, and lymphatic vessel growth. These processes require the stromal cell network of the LN to act deliberately to accommodate the influx of immune cells to the LN. The molecular drivers of these processes are not well understood. Therefore, we asked whether the immediate cytokines type 1 IFN produced during viral infection influence the lymphatic network of the LN in mice. We found that following an IFN-inducing stimulus such as viral infection or polyI:C, programmed cell death ligand 1 (PD-L1) expression is dynamically upregulated on lymphatic endothelial cells (LECs). We found that reception of type 1 IFN by LECs is important for the upregulation of PD-L1 of mouse and human LECs and the inhibition of LEC expansion in the LN. Expression of PD-L1 by LECs is also important for the regulation of LN expansion and contraction after an IFN-inducing stimulus. We demonstrate a direct role for both type 1 IFN and PD-L1 in inhibiting LEC division and in promoting LEC survival. Together, these data reveal a novel mechanism for the coordination of type 1 IFN and PD-L1 in manipulating LEC expansion and survival during an inflammatory immune response.
Energy balance of pregnant vicuñas (Vicugna vicugna) in the Chilean High Andes

Energy unbalance may be the cause of low fertility rates found in vicunas. The objective of this study was to estimate the temporal variation of the nutritional status in pregnant vicunas from a herd kept under captivity in the Chilean High Andes. The hypothesis under study is that animals are able to maintain the energy balance during the dry season. Six pregnant vicunas were examined in August, October and January (year 2015-2016). Reproductive status was estimated by ultrasonography and plasma progesterone concentration. Live weight (LW) and body condition score (BCS: 1-5 scale) were measured for each animal. A blood sample was taken to estimate the plasma concentrations of total protein (Biuret method), cholesterol (CHODPAP method), triglycerides (GPO-PAP method), β-hydroxybutyrate (enzymatic method) and non-esterified fatty acids (NEFA; enzymatic colorimetric method). Vicuna groups had similar LW, BCS, plus similar plasma concentrations of metabolites, total protein and progesterone. Females did not increase their LW during gestation and their BCS in January (2.9) was below the recommendations for late pregnancy in camelids (BCS 3.5). NEFA and β-hydroxybutyrate values were higher than those expected under nutritional energy balance signalling a lipolytic and ketogenic metabolic response, respectively. The absence of weight gain and the values of NEFA and β-hydroxybutyrate show that pregnant vicunas suffer a negative energy balance during the dry season in the Chilean High Andes. This can cause abortion and contribute to low fertility rates of the herds. It is suggested to provide pregnant vicunas with food supplements up to birthing, in years of severe drought. Key words : vicuna, nutritional status, negative energy balance.
The Effects of Mandatory Arbitration of Employment Discrimination Claims: Perceptions of Justice and Suggestions for Change

The ability of employers to require employees to submit claims of discrimination to final and binding arbitration in lieu of exercising their statutory rights represents a significant change in public policy. The methods traditionally used by enforcing agencies to investigate discrimination claims provide assistance and intervention that redress power asymmetries between employees and employers. Depriving employees of these enforcement mechanisms and requiring them to use arbitration may have adverse effects on perceptions of justice, both in procedural and distributive terms. We propose that mutuality, equality, and remediality are issues that must be addressed in situations of mandatory arbitration. We also suggest that mandatory arbitration may have other effects including expanding the scope of issues well beyond discrimination claims.
Absolute lymphocyte count in patients with glioblastoma treated with temozolomide chemoradiation.

e13564Background: Standard glioblastoma (GBM) management includes radiotherapy, chemotherapy, and steroids; all of which can result in immunosuppression and a low absolute lymphocyte count (ALC). P...
Membrane and nuclear initiated estrogenic regulation of homeostasis.

Abstract Reproduction and energy balance are inextricably linked in order to optimize the evolutionary fitness of an organism. With insufficient or excessive energy stores a female is liable to suffer complications during pregnancy and produce unhealthy or obesity-prone offspring. The quintessential function of the hypothalamus is to act as a bridge between the endocrine and nervous systems, coordinating fertility and autonomic functions. Across the female reproductive cycle various motivations wax and wane, following levels of ovarian hormones. Estrogens, more specifically 17β-estradiol (E2), coordinate a triumvirate of hypothalamic neurons within the arcuate nucleus (ARH) that govern the physiological underpinnings of these behavioral dynamics. Arising from a common progenitor pool of cells, this triumvirate is composed of the kisspeptin (Kiss1ARH), proopiomelanocortin (POMC), and neuropeptide Y/agouti-related peptide (AgRP) neurons. Although the excitability of these neuronal subpopulations is subject to genomic and rapid estrogenic regulation, kisspeptin neurons are the most sensitive, reflecting their integral function in female fertility. Based on the premise that E2 coordinates autonomic functions around reproduction, we will review the recent findings on the synaptic interactions between Kiss1, AgRP and POMC neurons and how the rapid membrane-initiated and intracellular signaling cascades activated by E2 in these neurons are critical for control of homeostatic functions supporting reproduction.
Cognitive function in patients with chronic lymphocytic leukemia: a cross-sectional study examining effects of disease and treatment.

Cancer-related cognitive impairment (CRCI) has not been objectively assessed in chronic lymphocytic leukemia (CLL). It is currently unclear how much of CRCI is attributable to disease, treatment, o...
Daily harmonics of ionospheric total electron content from satellite altimetry

Abstract Daily harmonics of the ionosphere’s total electron content (TEC) can be mapped using Global Navigation Satellite Systems (GNSS), as recently accomplished by Lean and colleagues. Here those harmonics are determined (over oceans only) by tidal analysis of ionospheric path delay from dual-frequency radar altimetry. Data from TOPEX, Jason-1, and Jason-2 altimeters are used, with focus on periods of medium to high solar activity. Diurnal-band signals are aliased by the altimeter sampling, but TOPEX-Jason orbits were designed to achieve acceptable tidal aliasing. Altimeter maps reveal where corresponding GNSS-based maps are in error, generally near the geomagnetic equator where high-wavenumber features are overly smoothed. When ocean tides are deduced from single-frequency altimetry, a task that relies on accurate GNSS-based ionospheric path corrections, any TEC errors leak directly into the tide solutions. TEC errors near and west of the Weddell Sea are likely problematic for the CryoSat-2 mission.
High temperature nanomechanical and nanotribological behavior of sub-5 nm nitrogen-doped carbon overcoat films

Abstract Elevated temperature tribological properties of ultra-thin nitrogen-doped carbon overcoat (NCOC) protective film for magnetic disks were investigated. NCOC with three different thicknesses (2.5, 3.5, and 4.5 nm) were examined in terms of both chemical and mechanical properties at temperatures up to 300 °C. The chemical changes were traced by XPS, revealing that the configuration of both carbon and nitrogen elements change partially from sp3- to sp2-hybridizations with exposure of NCOC samples to annealing. The friction coefficient, wear rate, and deformation of the NCOC films were measured using nanoscratch/wear experiments. Three sets of mechanical experiments verified the operating temperature and thickness dependence of the tribological behavior of the NCOC films. The NCOC samples show that the average wear depth is acceptably small after exposure to annealing, thus offering durable films for high temperature applications. Noteworthy, the permanent reduction in mechanical properties associated with annealing reduces in the presence of N dopants.
The History of Botulinum Neurotoxins: From 1820 to 2020

Nearly 200 years ago (1820), a young German physician Justinus Kerner predicted that the agent responsible for “sausage poisoning “could have therapeutic implications. The agent Clostridium botulinum was discovered at the end of the nineteenth century by the Belgian bacteriologist Emile Van Ermengem. Close to end of World War II, the toxin was isolated and purified by Lamanna and Duff and was prepared and produced for clinical use by Schantz. Allen Scott, following a series of studies in monkeys, published the first utility of botulinum neurotoxin (BoNT) in humans for correcting strabismus in 1980. The past 40 years witnessed the development of vast clinical indications of botulinum neurotoxin (BoNT) therapy. This chapter, in addition to the older historical data, also briefly discusses the contribution of some of contemporary basic scientists and clinical neurotoxicologists who are responsible for the therapeutic success of BoNT therapy in medical and surgical fields.
Moving on Sand

The challenges of moving people or equipment across sand can be a significant impediment to the researcher, and indeed have been important in shaping the history of commerce and warfare in desert regions. We describe in this section some of these issues—which are now no longer confined to the Earth, since humanity can now claim getting vehicles stuck on Mars among its achievements.
Gun Regulation Exceptionalism and Adolescent Violence: A Comparison to Tobacco.

This article compares the landscape of tobacco regulations to the landscape of gun regulations, with a focus on regulations that target youth. This article argues that guns are significantly less r...
Novel myeloperoxidase-derived HLA-A2-restricted peptides as therapeutic targets against myeloid leukemia.

Abstract Background aims Human myeloperoxidase has been shown to be overexpressed in many types of leukemia, such as chronic myeloid leukemia, acute myeloid leukemia and myelodysplastic syndrome. The authors identified two myeloperoxidase-derived HLA-A2-restricted peptides, MY4 and MY8, as novel leukemia-associated antigens. Methods Ex vivo-elicited MY4- and MY8-specific cytotoxic T lymphocytes were generated, and tested for leukemia cell lysis in vitro and in NOD/SCID AML xenograft model. Results These MY4- and MY8-specific cytotoxic T lymphocytes killed leukemic blasts while sparing healthy donor bone marrow cells. In addition, co-injection of MY4- and MY8-specific cytotoxic T lymphocytes into nonobese diabetic/severe combined immunodeficiency mice with acute myeloid leukemia drastically reduced tumor burden in vivo. The authors also found that MY4- and MY8-specific T cells could be detected in the peripheral blood mononuclear cells of allogeneic stem cell transplant recipients. Conclusions These antigen-specific T cells were significantly increased in blood samples from patients compared with healthy donors, suggesting that both MY4 and MY8 are immunogenic and that MY4- and MY8-specific cytotoxic T lymphocytes may play a role in reducing leukemia in vivo. Thus, the discovery of MY4 and MY8 as novel leukemia-associated antigens paves the way for targeting these antigens in immunotherapy against myeloid leukemia.
CLL-140: Chronic Lymphocytic Leukemia Presenting as a Solitary Breast Mass

An 80-year-old woman with a past medical history of hypertension and no prior history of malignancy underwent a screening mammogram followed by a breast ultrasound that showed a right breast mass. She remained asymptomatic. The physical exam did not reveal any palpable lymphadenopathy nor hepatosplenomegaly. Peripheral blood smear showed absolute lymphocytosis of 69% with a normal total white blood cell count of 8.1 without dysplastic cells, blasts, anemia, or thrombocytopenia. Breast ultrasound showed an irregular hypoechoic mass measuring 0.7 x 0.5 x 0.5 cm. Subsequent US-guided core biopsy showed non-Hodgkin B-cell lymphoma positive for cluster designation (CD)20 and CD5. Bone marrow aspirate and core biopsy revealed clusters of small-to-medium atypical lymphocytes positive for CD20, CD79a (weak), with a co-expression of CD5 (strong) and CD23CD138, findings that are compatible with Small Lymphocytic Lymphoma (SLL)/Chronic Lymphocytic Leukemia (CLL). Positron Emission Tomography scan showed an uptake within the right breast only. She is being managed with observation and close follow-up. Breast lymphoma (BL) represents around 0.5% of malignant breast neoplasms. Diffuse Large B-Cell Lymphoma (DLBCL) and follicular lymphoma are the predominant subtypes. SLL and CLL are subtypes of non-Hodgkin lymphoma originating from a B-cell lineage. While there have been reported cases of CLL and SLL manifesting as BL, the incidence still is very low and limited to case reports. Moreover, they have been reported to be found concomitantly with breast carcinoma. Most BL are asymptomatic when found incidentally on screening imaging, as in our patient. A hypoechoic round mass is the most common reported appearance. There are no current established guidelines for the treatment of BL. In our patient, we followed the recommendations for managing CLL. Not all breast masses are adenocarcinoma. It is critical to keep in mind the differential diagnosis lymphoproliferative disorders, melanoma, lung cancer, and gynecological malignancies.
George Yancy’s Across Black Spaces Before and During the Corona Disaster

George Yancy’s existential analyses of Black life in anti-Black and anti-intellectual US society have been evocative and magisterial. The different parts of his Across Black Spaces both reprise his earlier work and take it further with new notes of concern. I suggest that COVID-19 is metaphysical, that Yancy’s work is uniquely important for studies of race in the United States and as an intervention in our collective intellectuality. However, I suggest that we might move discussions of race ahead by considering the intransigent nature of White racial status. (I begin and end this symposial review with discussion of my own existential situation.). © 2020 Society for Applied Philosophy
The Mathematics of Sex: How Biology and Society Conspire to Limit Talented Women and Girls

Preface: Setting the Stage 1. Why Care About Women in Science? 2. A Multidimensional Problem 3. Opening Arguments: Environment 4. Opening Arguments: Biology 5. Challenges to the Environmental Position 6. Challenges to the Biological Position 7. Background and Trend Data 8. Comparisons Across Societies, Cultures, and Developmental Stages 9. Conclusions and Synthesis 10. What Next? Research and Policy Recommendations Epilogue References
Computers in Engineering Organization Management

A survey, conducted in Spring 1978, based upon 179 responses, indicated that 72% of engineering organizations utilize electronic data processing in the management of their organizations. The paper describes the extent of data processing use by type and size of organization, considers the various types of applications, describes the choice between in-house and outside service organizations, reports variations in both input techniques and output presentation, and summarizes the computer hardware used in these organizations.
Factors in the Cause of Death in Carcinoma of the Cervix: A Study of Fifty-Seven Cases Coming to Necropsy

This study is based upon 57 consecutive cases of carcinoma of the cervix in which autopsy examinations were performed. Thirty-one of these were studied at the University Hospitals. The remaining 26 were taken from the autopsy records in the Department of Pathology at the University of Minnesota. Microscopic sections were studied except in a few instances in which they could not be obtained. An attempt has been made to determine the immediate lethal factors and the frequency with which they occur. No attempt is made to determine the efficacy of the treatment. Ureteral Stricture Stricture of the ureters with consequent hydronephrosis and hydroureters was the most striking and constant autopsy finding in this series of cases, being present in 42 cases, or 75 per cent. This is in accord with the observations of others. Ernst Holzbach in 48 carcinpmas of the cervix coming to autopsy found 31 bilateral and 10 unilateral strictures, Sampson found that the factors responsible for structures were external pressure of a mass of carcinoma around the ureters as a result of parametrial extension and lymphatic metastasis, and added infection and edema. Carson states that metastasis may occur to the lymphatics of the ureters. Constriction by metastatic processes was not, however, very common in our series. It occurred only three times and was located in the midportion of the ureter. In this series both ureters were constricted in 30 cases (52 per cent); one ureter in 13 cases (21 per cent). Of the unilateral strictures 7 were on the right and 5 on the left.
Collateral Damage: The Impact of ACTA and the Enforcement Agenda on the World's Poorest People

ACTA is billed as a trade agreement, and it is likely to have a far reaching impact on the poorest people in the world. ACTA's purported aim is to increase the efficacy of enforcement of intellectual property. However, like the enforcement agenda that gave rise to it, ACTA's provisions threaten access to medicines, access to learning materials, and access to markets by developing countries, and in so doing threaten development. 1 S.J.D. Candidate, Duke University School of Law.
Gene selection for multiclass prediction of microarray data

Gene expression data from microarrays have been successfully applied to class prediction, where the purpose is to classify and predict the diagnostic category of a sample by its gene expression profile. A typical microarray dataset consists of expression levels for a large number of genes on a relatively small number of samples. As a consequence, one basic and important question associated with class prediction is: how do we identify a small subset of informative genes contributing the most to the classification task? Many methods have been proposed but most focus on two-class problems, such as discrimination between normal and disease samples. This paper addresses selecting informative genes for multiclass prediction problems by jointly considering all the classes simultaneously. Our approach is based on the power of the genes in discriminating among the different classes (e.g., tumor types) and the existing correlation between genes. We formulate the expression levels of a given gene by a one-way analysis of variance model with heterogeneity of variances, and determine the discriminatory power of the gene by a test statistic designed to test the equality of the class means. In other words, the discriminatory power of a gene is associated with a Behrens-Fisher problem. Informative genes are chosen such that each selected gene has a high discriminatory power and the correlation between any pair of selected genes is low. Test statistics considered in this paper include the ANOVA F test statistic, the Brown-Forsythe test statistic, the Cochran test statistic, and the Welch test statistic. Their performances are evaluated over several classification methods applied to two publicly available microarray datasets. The results show that Brown-Forsythe test statistic achieves the best performance.
Expanding the Genetic Code

Proteins, the molecules that carry out most of the functions required for life, are built from 20 genetically encoded amino acids In his essay that won the Amersham Biosciences and Science Prize for young scientists, [Lei Wang][1] describes how he engineered the bacteria Escherichia coli to make unnatural amino acids. The biosynthesis strategy mimics the way that the common 20 amino acids are encoded. These additional building blocks allow the design of proteins with new properties. [1]: http://www.sciencemag.org/cgi/content/full/302/5645/584
Limited proteolysis of the bovine pancreatic secretory trypsin inhibitor at acid pH.

Abstract The bovine pancreatic secretory trypsin inhibitor (Kazal's inhibitor) undergoes a limited and specific proteolysis by catalytic amounts of trypsin in the presence of calcium ions at acidic pH. The pH optimum for both the initial rate of reaction and the extent of reaction is pH 2.7. Incubation of inhibitor with 0.7 mole % trypsin at pH 2.7 for 3 hours at 25° results in the modification of 25% of the inhibitor molecules. We have shown, by isolation and characterization of peptide fragments, that a single arginyl-isoleucyl peptide bond (residues 18 and 19) is hydrolyzed. This modified inhibitor is active, but is inactive when arginine 18 is removed by carboxypeptidase B. The features of the reaction thus far examined are similar to those described by Ozawa and Laskowski (J. Biol. Chem., 241, 3955 (1966)) for the soybean trypsin inhibitor-trypsin system. On this basis the arginine residue at position 18 is identified as the reactive site of the inhibitor.