cssi/SciSciGPT-SciSciNet huggingface dataset:
Diverse Histopathologic and Molecular Responses of Acute Myeloid Leukemia to the FLT3 Inhibitor Quizartinib (AC220)

Abstract 885 Although high clinical response rates to the FLT3 inhibitor quizartinib (AC220) among subjects with relapsed/refractory AML suggest a potential clinical breakthrough, there remains concern that few subjects achieved CR or PR by strict IWG response criteria. Prior reports describe terminal neutrophil differentiation of AML blasts during clinical response to AC220 (Sexuaer, et al. ASH 2011, #943), suggesting that traditional chemotherapy metrics may not prove relevant to measure FLT3 inhibitors9 clinical activity. Here we characterize responses to AC220 from a recent Phase II clinical trial, based on histomorphologic, molecular, and cytogenetic analysis and independent of that study9s modified IWG metrics. We describe at least two distinct types of morphologic responses to AC220 among the 21 subjects treated at our site on this single-arm trial. All subjects had AML that relapsed or was refractory to prior chemotherapy. Subjects received single agent AC220 daily at 90–200 mg and were evaluated by bone marrow aspiration and biopsy on treatment days 15 and 29 and then monthly until blasts were cleared from blood and marrow. 15 of 21 enrolled subjects were FLT3-ITD+; 6 were FLT3 wild type (WT). 14/16 subjects with circulating or extramedullary blasts at study entry showed complete morphologic elimination of these populations. 18/20 subjects with marrow blasts >20% at study entry reduced marrow blasts to Disclosures: Carroll: GlaxoSmithKlein: Research Funding. Perl: Astellas Pharmaceuticals: Consultancy.
CRT-800.18 Implications of Expanding Use of Transcatheter Aortic Valve Replacement to Intermediate Risk Patients in the Veterans Affairs Healthcare System

Recent clinical trial data suggest that Transcatheter Aortic Valve Replacement (TAVR) may be superior to surgical aortic valve replacement (SAVR) in intermediate risk patients. The Objective of this investigation was to assess the implications of expanding TAVR to intermediate risk patients using a
Altruistic Values of Self and In-Groups and Implications for Suffering Alleviation

This chapter attempts to demonstrate that altruistic social identities contribute to the development of an altruistic personal identity that results in relieving others’ suffering. Previous research has primarily focused on self-values or personal identities in predicting altruistic orientations or behaviors; little empirical research has linked personal values to social identities, and almost no work expands this to explore the implications for altruistic obligations that potentially help alleviate the suffering of others. We address this issue using a new cross-national survey, the Moral Schemas, Cultural Conflict, and Socio-Political Action Survey (2015) that includes data from four countries: United States, France, Turkey and South Korea. We operationalize altruistic social identities as identifying with groups that prioritize benevolence and universalism and altruistic personal identities as emphasizing benevolence and universalism for self. Our results mostly support our argument that identifying with groups that value benevolence and caring for others (holding altruistic social identities) contributes to the development of an altruistic personal identity with some exceptions in Turkey and South Korea. These findings have significant implications for future research on the altruistic self and alleviating suffering in different cultural contexts.
Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy

Changes in adaptive immune cells after chemotherapy in adult acute myeloid leukemia (AML) may have implications for the success of immunotherapy. This study was designed to determine the functional capacity of the immune system in adult patients with AML who have completed chemotherapy and are potential candidates for immunotherapy. We used the response to seasonal influenza vaccination as a surrogate for the robustness of the immune system in 10 AML patients in a complete remission post-chemotherapy and performed genetic, phenotypic, and functional characterization of adaptive immune cell subsets. Only 2 patients generated protective titers in response to vaccination, and a majority of patients had abnormal frequencies of transitional and memory B-cells. B-cell receptor sequencing showed a B-cell repertoire with little evidence of somatic hypermutation in most patients. Conversely, frequencies of T-cell populations were similar to those seen in healthy controls, and cytotoxic T-cells demonstrated antigen-specific activity after vaccination. Effector T-cells had increased PD-1 expression in AML patients least removed from chemotherapy. Our results suggest that while some aspects of cellular immunity recover quickly, humoral immunity is incompletely reconstituted in the year following intensive cytotoxic chemotherapy for AML. The observed B-cell abnormalities may explain the poor response to vaccination often seen in AML patients after chemotherapy. Furthermore, the uncoupled recovery of B-cell and T-cell immunity and increased PD-1 expression shortly after chemotherapy might have implications for the success of several modalities of immunotherapy.
A class of generalized Sen poverty indices

Utilizing results from partial poverty orderings, we characterize a class of generalized Sen poverty indices. A generalized Sen poverty index is defined as the weighted area between the line of zero-poverty and the censored generalized Lorenz curve. Unlike the original Sen index, the generalized Sen index can satisfy the key axioms for poverty measurement.
Overview of Migraine: Recognition, Diagnosis, and Pathophysiology

Migraine affects 12% of the population with recurrent attacks, and the features of these vary widely. This condition is likely due to a variety of genetic predilections, which lower the threshold for activating the trigeminovascular system in the brain. Migraine is also an inflammatory disorder. Failure to treat an attack rapidly reduces the chance of rendering the sufferer pain free. There is evidence that migraine can be progressive, is adversely influenced by the burden of migraine, and that aggressive management may be disease modifying.
Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer

Metastatic colorectal cancers (mCRCs) are clinically heterogeneous, but the genomic basis of this variability remains poorly understood. We performed prospective targeted sequencing of 1,134 CRCs. We identified splice alterations in intronic regions of APC and large in-frame deletions in CTNNB1, increasing oncogenic WNT pathway alterations to 96% of CRCs. Right-sided primary site in microsatellite stable mCRC was associated with shorter survival, older age at diagnosis, increased mutations, and enrichment of oncogenic alterations in KRAS, BRAF, PIK3CA, AKT1, RNF43, and SMAD4 compared with left-sided primaries. Left-sided tumors frequently had no identifiable genetic alteration in mitogenic signaling, but exhibited higher mitogenic ligand expression. Our results suggest different pathways to tumorigenesis in right- and left-sided microsatellite stable CRC that may underlie clinical differences.
Educación para la democracia en las escuelas: un desafío pendiente

La crisis valorativa que sufre la sociedad actual y sus efectos se han proyectado en todos los ambitos y muy especialmente en la cultura escolar, la que informada por una racionalidad instrumental, esta mas preocupada de cautelar la consecucion de fines y objetivos institucionales que de formar en valores y desarrollar personas integralmente. Se podria decir que la escuela no ha tomado conciencia respecto de la responsabilidad publica que le cabe en la construccion de una comunidad en la que los estudiantes se eduquen a partir del desarrollo y practica del intercambio y negociacion de creencias y valores, la construccion de relaciones basadas en la cooperacion, el apoyo mutuo, la libre expresion de las ideas y la tolerancia, actitudes y valores que los prepararan efectivamente para la convivencia social democratica.
Recommendation of fiducial marker implantation for better target tracking using MV imager in prostate radiotherapy

Purpose The aim of this study was to develop a model that optimizes the fiducial marker locations in the prostate to increase detectability of the markers in the projected EPID images during VMAT treatments. Methods and materials The fiducial marker tracking capability for each arc was evaluated through a proposed formula. The output of the formula, a detectability score, was calculated with the in-house developed software written in MATLAB (The Mathworks, Inc., Natick, MA, USA). Three unique weighting factors were added to penalize the detectability score. The detectability scores of four different patterns containing 40 combinations of simulated fiducial marker locations were evaluated with 101 previously treated prostate treatment plans (containing 202 individual arcs). The results were analyzed for each pattern group and each marker separation distance on the transverse plane. Results The maximum detectability of the markers occurred when they were placed between 10 and 15 mm from the center of the prostate in the transverse plane and 6-13 mm in the superior-inferior direction. The detectability decreased when the markers were placed beyond 20 mm in both directions. Conclusions The fiducial marker-based detectability score can be used to predict the real-time tracking capability. Suggestions for optimal insertion locations were given to improve prostate motion management using MV imaging.
Integrating Hypotheses of Multiple Recognizers for Improving Mandarin LVCSR Performance

In this paper, we investigate how to improve Mandarin LVCSR performance by integrating multiple hypotheses from recognizers running in parallel. Different recognizers are trained by employing: (1) different phone sets, (2) different front-ends, and (3) different training sets. Nbest hypotheses are merged into a character transition network (CTN) and ROVER is used to select the final recognition decision. Both read and spontaneous speech are tested in the ROVER framework. In comparing with the best individual recognizer in the parallel group, the fully integrated ROVER system achieves a relative Chinese character error reduction of 10.1%.
Sclera and Limbus

While playing only limited and indirect role in vision, the sclera is responsible for much of the globe’s strength and integrity. The proximity of the scleral “shell” to vital tissues such as the choroid, ciliary body, and the retina gives it significant clinical implications. Compared with most ocular tissues, the sclera has few pathologies. The limbus is one of the loci minoris resistantiae of the globe , which is further excerbated by the fact that it is often the site of elective surgical incisions.
The Instruments of Monetary Policy

The goal of monetary policy is to estabhsh and maintain monetary and credit conditions consistent with a healthy economy. Federal Reserve authorities believe that a healthy economy is characterized by high employment, a good and sustainable rate of economic growth, price level stability, and a reasonably stable value for the dollar in terms of foreign currencies. The Fed tries to manipulate the money supply and credit conditions to achieve some or all of these goals. The tools it uses to influence monetary and credit conditions are called the instruments of monetary policy. There are two classes of monetary policy instruments: general and selective. The general instruments of control are reserve requirements, the discount mechanism, and open market operations. The discount mechanism and open market operations influence the total amount of reserve bank credit available to the banking system; the Fed uses them to change bank reserves and the monetary base. Changes in reserve requirements affect the structure and potential volume of bank deposits, money, and commercial bank credit, but leave the monetary base and total reserves the same. Selective tools, which consist of control over margins in the stock market. Regulation Q, and controls over consumer and other kinds of credit (occasionally imposed) are designed to affect the allocation of credit.
Telomerase Regulation, Cell Cycle, and Telomere Stability in Primitive Hematopoietic Cells

Low levels of telomerase activity have recently been detected in human primitive hematopoietic cells, however, blood cells exhibit telomere shortening on cell proliferation. This challenging observation led us to study telomerase regulation and telomere length in human hematopoietic progenitor cells from fetal liver (FL), cord blood (CB), peripheral blood (PB), and bone marrow (BM). We found telomerase activity in CD34+/CD38+ cells exceeding levels in CD34+/CD38-, CD34- , and mononuclear cells (P < .05). Baseline telomerase activity was highest in BM (n = 5) CD34+ cells, followed by PB (n = 20), CB (n = 11), and FL (n = 1). Within 48 hours to 72 hours of in vitro culture of CD34+ cells in the presence of cytokines (KL, interleukin-3 [IL-3], IL-6, erythropoietin, granulocyte colony-stimulating factor), telomerase activity was upregulated, peaked after 1 week of culture, and decreased to baseline levels or below detection after 3 to 4 weeks. Stimulation of CD34+ cells with single cytokines resulted in no or minor telomerase upregulation, whereas cytokine combinations resulted in a significant telomerase increase (P < .001). There was a correlation between telomerase activity, cell cycle status by BrdU incorporation, and induction of phosphorylated retinoblastoma protein, CDC2, CDK2, cyclin D1, and cyclin A, but not cyclin E and B1 after 72 hours with multiple (but not single) cytokines. In nonexpanding CD34+ cells, telomerase was low or undetectable. Secondary CD34+ cells showed a reduced ability to upregulate telomerase activity. Antiproliferative cytokines such as transforming growth factor-beta1 and high concentrations of all-trans-retinoic acid in cytokine-supported CD34+ cultures downmodulated telomerase activity. Average telomere lengths were 10.4 kbp, 7.4 kbp, and 7.6 kbp in CB, PB, and BM CD34+ cells, respectively. In ex vivo expansion cultures, an average telomeric DNA loss of 1 to 2 kbp over 4 weeks was observed. However, the rate of base pair loss per population doubling was significantly lower during the first 2 weeks, when telomerase was upregulated, than during weeks 3 and 4 of culture. In summary, telomerase is upregulated in response to cytokine-induced proliferation and cell cycle activation in primitive hematopoietic cells. Telomerase is downregulated between weeks 3 and 4 of ex vivo expansion culture linked with decreased proliferation and greater expansion of more mature cell subsets. Our data suggest that telomerase activity in hematopoietic cells reduces, but does not prevent, telomere shortening on proliferation.
Addition of a scripted pre-operative patient education module to an existing ERAS pathway further reduces length of stay

Abstract Background While enhanced recovery pathways (ERAS) appear to be beneficial for post-operative outcomes, there have been no studies evaluating the specific role of patient education within an ERAS pathway. Methods We identified all colectomies performed at our institution since initiation of an ERAS protocol, excluding for mortality and length of stay >30 days. Patients who received preoperative education by a nurse practitioner via a scripted telephone call were compared to patients who did not receive education using the NSQIP database. We then evaluated differences in surgical complications and length of stay among these cohorts. Results Patients who received scripted education phone calls had a significantly shorter mean length of stay when compared to patients that receiving usual care (3.0 ± 2.2 vs 3.7 ± 3.2 days; p = 0.005). Subgroup analysis demonstrates strongest benefit in patients undergoing left colectomy and laparoscopic surgery. Conclusions Scripted patient education modules may shorten length of stays and postoperative complications, even when added to an already existing ERAS bundle, which may translate into significant hospital cost savings.
High levels of branched chain fatty acids in nātto and other Asian fermented foods.

Abstract The mean intake (500 mg/day) of branched chain fatty acids (BCFA) in western countries is from dairy products and beef. We hypothesized that Asian countries with low dairy consumption have an alternative source of BCFA and report the characterization of nātto and selected fermented foods for BCFA content. Nātto BCFA averaged 0.6 (range 0.21–1.43) mg BCFA per g natto (wet weight) and was highly variable. Nātto major BCFA are C14-17 iso- and anteiso-BCFA similar to fluid milk. BCFA concentrations were 1.00 ± 0.64%, 1.63 ± 0.72% and 0.65 ± 0.07%, of total fatty acids in nātto, shrimp paste and fish sauce, respectively. In contrast, saturates, monounsaturates, and major polyunsaturates were more constant (coefficient of variation = 21%, 26% and 4% compared to 64% for nātto BCFA). Detection of fatty acid ethyl esters were confirmed in miso and found in homemade kimchi. Habitual nātto and/or fermented seafood consumption could support BCFA intakes similar to dairy consumption.
Theoretical understanding of the optimum conditions for a mainstream granular nitritation-anammox reactor coupled with anaerobic pretreatment.

Mainstream nitritation-anammox processes with anaerobic pretreatment may provide a paradigm-shifting strategy for achieving more energy-efficient and cost-saving wastewater treatment, and most efforts in this area were through bench studies. To better understand the performance of bench systems and make possible predication of key parameters beyond experiments, a mathematical model was developed in this study. The model inputs include hydraulic retention time (HRT), influent chemical oxygen demand (COD), sulfate, ammonium, and nitrate, as well as the bulk dissolved oxygen, while the outputs include the COD degradation, nitrogen removal pathways, and biomass partitioning in the reactor and along the granule radius. The simulated results suggest that the COD/N ratio of anaerobic effluent is highly related to the HRT of the anaerobic pretreatment, and it can significantly impact the fractions of AOB, NOB, anammox bacteria and denitrifiers, as well as their contribution to nitrogen conversion in the subsequent nitritation-anammox reactor. The optimal conditions for achieving a reliable and robust anaerobic pretreatment system is predicted to have an HRTHAR of 11 h that can provide an effluent COD/N ratio of 2 for the subsequent nitritation-anammox reactor to achieve ~93% total nitrogen removal (~76% by anammox) at HRTAMX of 8 h. The proposed model can be valuable to the optimization of the anaerobic pretreatment - mainstream anammox system.
Quantitative assessment of changes in cell growth, size and morphology during telomere-initiated cellular senescence in Saccharomyces cerevisiae

Abstract Telomerase-deficient cells of the budding yeast S. cerevisiae experience progressive telomere shortening and undergo senescence in a manner similar to that seen in cultured human fibroblasts. The cells exhibit a DNA damage checkpoint-like stress response, undergo changes in size and morphology, and eventually stop dividing. In this study, a new assay is described that allowed quantitation of senescence in telomerase-deficient est2 cells with applied statistics. Use of the new technique revealed that senescence was strongly accelerated in est2 mutants that had homologous recombination genes RAD51, RAD52 or RAD54 co-inactivated, but was only modestly affected when RAD55, RAD57 or RAD59 were knocked out. Additionally, a new approach for calculating population doublings indicated that loss of growth capacity occurred after approximately 64 generations in est2 cells but only 42 generations in est2 rad52 cells. Phase contrast microscopy experiments demonstrated that senescing est2 cells became enlarged in a time-dependent manner, ultimately exhibiting a 60% increase in cell size. Progressive alterations in physical properties were also observed, including striking changes in light scattering characteristics and cellular sedimentation rates. The results described herein will facilitate future studies of genetic and environmental factors that affect telomere shortening-associated cell senescence rates using the yeast model system.
A Decade of Agriculture Graduates’ Employability and Career Pathways

There is increasing pressure on universities to produce employable graduates. Currently, the University of New England (UNE) has a suite of undergraduate agriculture courses. The project used an evidence based approach which evaluated graduate’s employability based on their choice of course and the relevance of Australian Threshold Learning Outcomes (TLOs) for Agriculture, which underpin UNE’s agriculture courses. The past decade of UNE agriculture graduates (2005-2016) were invited to participate in an online survey. Of the respondents, 95-100% agreed each TLO was relevant to their current employment. The initial industries that graduates were employed in after graduation were agronomy, agribusiness and animal sciences. Of all graduates who are currently employed in industry, three quarters had changed employers, with two thirds moving to another agricultural industry since commencing work. Over half of the respondents had engaged in additional study from short courses to PhDs, with about 20% studying to become vocational, primary or secondary teachers. For many graduates on-campus residential college life was important for developing positive connections in learning, social activities and employment networks which persisted post-graduation. Survey results were used to inform the development of an online career pathway resource for prospective and current students, and information from the TLO survey has been fed back into unit and course reviews.
Fibronectin receptor integrin α5β1 regulates assembly of PP2A complexes through PDE4D: modulation of vascular inflammation and atherosclerosis

Abstract Fibronectin in the vascular wall promotes inflammatory activation of the endothelium during vascular remodeling and atherosclerosis. These effects are mediated in part by fibronectin binding to integrin α5, which recruits and activates phosphodiesterase 4D5 (PDE4D5) by inducing its dephosphorylation on an inhibitory site Ser651. Active PDE then hydrolyzes anti-inflammatory cAMP to facilitate inflammatory signaling. To test this model in vivo, we mutated the integrin binding site in PDE4D5 in mice. This mutation reduced endothelial inflammatory activation in athero-prone regions of arteries, and, in a hyperlipidemia model, reduced atherosclerotic plaque size while increasing markers of plaque stability. We then investigated the mechanism of PDE4D5 activation. Proteomics identified the PP2A regulatory subunit B55α as the factor recruiting PP2A to PDE4D5. The B55α-PP2A complex localized to adhesions and directly dephosphorylated PDE4D5. This interaction also unexpectedly stabilized the PP2A-B55α complex. The integrin-regulated, pro-atherosclerotic transcription factor Yap is also dephosphorylated and activated through this pathway. PDE4D5 therefore mediates matrix-specific regulation of EC phenotype via an unconventional adapter role, assembling and anchoring a multifunctional PP2A complex with other targets. These results are likely to have widespread consequences for control of cell function by integrins.
A novel boar pheromone mixture induces sow estrus behaviors and reproductive success

Abstract Androstenone is a molecule found in boar saliva and fat, which has been thought to be the male pig sexual pheromone. We previously identified and confirmed three boar-unique molecules in saliva, namely, quinoline (Q), androstenol (AL) and androstenone (AN). This study quantified the sexual behavioral responses of the molecules among post-weaning sows (days 4 and 5). Among 947 weaned sows, the percentage of sexual behaviors was increased by Boar Saliva Analog (BSA; a mixture of Q, AL and AN) relative to a vehicle control (isopropyl alcohol; ISO) or each molecule alone. A sexual behavior score was calculated for each molecule that combined standing still, pricked ears and vocalizations. BSA caused an increase in the standing reflex (standing still), pricked ears and vocalizations compared to ISO. BSA increased sexual behavior score by 63.9% over ISO while androstenone increased the sexual behavior score by only 13.5% over ISO. BSA was more effective than androstenone alone in the induction of sexual behaviors. It cuased more weaned sows to express behavioral estrus and to stand for insemination at a higher rate than boar exposure alone. Thus, the overt expression of sexual behaviors in weaned sows caused by BSA strongly suggests that the boar sexual pheromone is likely to be a mixture of three unique volatile molecules.
Neuronal network remodeling and Wnt pathway dysregulation in the intra-hippocampal kainate mouse model of temporal lobe epilepsy

Mouse models of mesial temporal lobe epilepsy recapitulate aspects of human epilepsy, which is characterized by neuronal network remodeling in the hippocampal dentate gyrus. Observational studies suggest that this remodeling is associated with altered Wnt pathway signaling, although this has not been experimentally examined. We used the well-characterized mouse intrahippocampal kainate model of temporal lobe epilepsy to examine associations between hippocampal neurogenesis and altered Wnt signaling after seizure induction. Tissue was analyzed using immunohistochemistry and confocal microscopy, and gene expression analysis was performed by RT-qPCR on RNA extracted from anatomically micro-dissected dentate gyri. Seizures increased neurogenesis and dendritic arborization of newborn hippocampal dentate granule cells in peri-ictal regions, and decreased neurogenesis in the ictal zone, 2-weeks after kainate injection. Interestingly, administration of the novel canonical Wnt pathway inhibitor XAV939 daily for 2-weeks after kainate injection further increased dendritic arborization in peri-ictal regions after seizure, without an effect on baseline neurogenesis in control animals. Transcriptome analysis of dentate gyri demonstrated significant canonical Wnt gene dysregulation in kainate-injected mice across all regions for Wnt3, 5a and 9a. Intriguingly, certain Wnt genes demonstrated differential patterns of dysregulation between the ictal and peri-ictal zones, most notably Wnt5B, 7B and DKK-1. Together, these results demonstrate regional variation in Wnt pathway dysregulation early after seizure induction, and surprisingly, suggest that some Wnt-mediated effects might actually temper aberrant neurogenesis after seizures. The Wnt pathway may therefore provide suitable targets for novel therapies that prevent network remodeling and the development of epileptic foci in high-risk patients.
Long-read sequencing to interrogate strain-level variation among adherent-invasive Escherichia coli isolated from human intestinal tissue

Adherent-invasive Escherichia coli (AIEC) are a pathovar linked to inflammatory bowel diseases (IBD), especially Crohn’s disease, and colorectal cancer. AIEC have no known molecular or genomic markers, but instead are defined by in vitro functional attributes. Futhermore, it is unknown if strains classified as AIEC truly colonize intestinal tissues better than non-AIEC strains. To evaluate strain-level variation among tissue-associated E. coli, we must develop a sequencing approach capable of long reads and with the ability to exclude mammalian DNA. We also must evaluate genomic variation among strains that have demonstrated ability to colonize intestinal tissues. Here we have assembled complete genomes using ultra-long-read nanopore sequencing for a model AIEC strain, NC101, and seven strains isolated from the intestinal mucosa of Crohn’s disease and non-Crohn’s tissues. We show these strains can colonize the intestinal tissue in a Crohn’s disease mouse model and induce varying levels of inflammatory cytokines from cultured macrophages. We demonstrate these strains can be quantified and distinguished in the presence of 99.5% mammalian DNA and from within a fecal population. Analysis of global genomic structure and specific sequence variation within the ribosomal RNA operon provides a framework for efficiently tracking strain-level variation of closely-related E. coli and likely other commensal/pathogenic bacteria impacting intestinal inflammation in mice and IBD patients.
Examining the “Gang Penalty” in the Juvenile Justice System: A Focal Concerns Perspective:

There are hundreds of thousands of juvenile gang members in the United States who are at heightened risk of criminal offending, violent victimization, and incarceration. Importantly, however, incar...
Abraham Lincoln and the Duty of Zealous Representation: The Matson Slave Case

“Abraham Lincoln, lawyer for the slave-owner, Robert Matson,” does fit the description of a Great Emancipator. The fact remains that he did work zealously for Matson. This article argues that the Matson case does not contradict Lincoln’s well-known reputation for hatred of slavery. Rather, in that case he acted in the tradition of John Adams who risked his reputation to represent the British soldiers who perpetrated the Boston Massacre.The article first describes Lincoln’s participation in the Matson case, including an analysis of the habeas corpus hearing that preceded it. It continues with a description of Lincoln’s skills as a trial lawyer. It then discusses the antebellum ethical rule enunciated by Lord Brougham and other leading scholars who said that zealous advocacy was required for even the most odious clients. The article concludes that Lincoln was following this rule and that the rule is still valid today. It maintains that Lincoln was acting on the highest level of professionalism in the sole case where he represented a slave owner.
Surgical Mask Particle Filtration Efficiency (PFE)

The particle filtration efficiency (PFE) of surgical (procedure) masks is a key differentiator of its classification and therefore, its use by healthcare workers. Surgical masks are regulated by the Food and Drug Administration (FDA). The FDA Guidance document has adopted a number of ASTM standards for establishing the criteria for the classification of masks. ASTM F2299 is recommended for the measurement of PFE with minor modifications. Both ASTM F2299 and the FDA Guidance Document fail however to establish standard test procedures and therefore, it is possible to attain diverging results. This creates a major problem in one’s ability to be able to relate the measured performance across different masks on the market. In this paper, we outline the deficiencies of these test methods and discuss the challenges that need to be addressed by FDA and other regulatory agencies.
Blockage Robustness in Access Point Association for mmWave Wireless LANs with Mobility

Millimeter-wave wireless LANs are targeted for use with bandwidth-intensive applications such as virtual/augmented reality and real-time high-definition video. To maintain high throughput while addressing mmWave signal blockages, multiple access points (APs) within one room to improve line-of-sight conditions is considered a promising approach. In a scenario with fixed and mobile (human) obstacles, we mathematically analyze LoS blockages produced by mobility, and use the analysis to develop a multi-AP association scheme. Our scheme statically assigns primary and backup APs in order to maximize blockage robustness and perform load balancing among APs. Simulation results show that: 1) our static approach can provide blockage tolerance close to that of an expensive dynamic probing approach while achieving higher throughput, 2) the use of client mobility patterns, if known, can improve our static approach even further, and 3) our approach achieves significantly better fairness and load balancing than existing approaches.
Mechanisms of differential desensitization of metabotropic glutamate receptors

G protein-coupled receptors (GPCRs) interact with intracellular transducers to control both signal initiation and desensitization, but the distinct mechanisms that control the regulation of different GPCR subtypes are unclear. Here we use fluorescence imaging and electrophysiology to examine the metabotropic glutamate receptor (mGluR) family. We find distinct properties across subtypes in both rapid desensitization and internalization, with striking differences between the group II mGluRs. mGluR3, but not mGluR2, undergoes glutamate-dependent rapid desensitization, internalization, trafficking, and recycling. We map differences between mGluRs to variable Ser/Thr-rich sequences in the C-terminal domain (CTD) that control interaction with both GPCR kinases and β-arrestins. Finally, we identify a cancer-associated mutation, G848E, within the mGluR3 CTD that enhances β-arrestin coupling and internalization, enabling an analysis of mGluR3 β-arrestin-coupling properties and revealing biased variants. Together, this work provides a framework for understanding the distinct regulation and functional roles of mGluR subtypes.
Early pediatric Cochlear implantation: An update.

The criteria and candidacy for pediatric cochlear implantation (CI) has significantly transformed over the past few decades and continues to evolve with technological advancements, and recognition of benefit in more diverse populations. Prolonged auditory deprivation among patients with profound sensorineural hearing loss has been shown to cause widespread degeneration in the central auditory system. Thus, there is increasing evidence advocating for earlier implantation within a critical neuroplastic window. However, there is a lack of consensus on this optimal age of implantation. Historically, there were concerns regarding surgical feasibility and safety, anesthesia risk, and logistical considerations in very young infants <12 months. Recent literature has investigated surgical safety and anesthesia risk as well speech and language outcomes with early implantation, resulting in the long-awaited reduction in approved age by the FDA (<9 months for certain devices). This article reviews logistical considerations, surgical safety, anesthesia risk, and language developmental outcomes associated with early CI (<12 months).
Selecting Relevant Genes From Microarray Datasets Using a Random Forest Model

Recent studies have demonstrated microarray expression data can be used to identify gene regulatory pathways. However, one of the major challenges is to utilize the large microarray data (genes and micro-RNAs) to have an efficient computational model. Therefore, there is an urgent need to reduce the dimensionality of these large sets using machine learning methods without compromising the accuracy. This requires an appropriate machine learning algorithm to select the significant features from these large datasets. Therefore, in this study, we use a supervised method based on a Random Forest to identify significant features from three microarray datasets from prenatal nicotine, alcohol, and nicotine and alcohol exposure groups in two different cell types (dopamine and non-dopamine neurons). Our approach was computationally efficient to reduce the dimensionality of extremely large microarray datasets. Furthermore, our results indicated that using only the top 20% of features was sufficient to confirm the genetic pathways previously identified when using all of the features in the model.
Operative Treatment of Distal Radius Fractures in Patients With Parkinson Disease.

Background:Owing to the many unique disease characteristics of Parkinson disease (PD)—namely resting tremors, muscular rigidity, and poor bone quality—we hypothesized that this patient population w...
BATS TRANSIT AND FORAGE OVER NEARSHORE ENVIRONMENTS IN THE NORTHERN GULF OF ALASKA

We present evidence of bats transiting and foraging over the ocean along nearshore environments in the northern Gulf of Alaska. Acoustic surveys were conducted on 2 sea-based vessels that anchored overnight off the coasts of 2 national parks (July–August 2019). We documented Little Brown Myotis (Myotis lucifugus) transiting and foraging over the ocean at 14 sites within the nearshore zone at an average off-coast distance of 298 m (s = 154). Little Brown Myotis inhabiting coastal habitats in Alaska are utilizing nearshore environments similar to Vespertilionid bats in the North Atlantic.
Protein Kinase A and 5' AMP-Activated Protein Kinase Signaling Pathways Exert Opposite Effects on Induction of Autophagy in Luteal Cells.

In the absence of pregnancy the ovarian corpus luteum undergoes regression, a process characterized by decreased production of progesterone and structural luteolysis involving apoptosis. Autophagy has been observed in the corpus luteum during luteal regression. Autophagy is a self-degradative process important for balancing sources of cellular energy at critical times in development and in response to nutrient stress, but it can also lead to apoptosis. Mechanistic target of rapamycin (MTOR) and 5' AMP-activated protein kinase (AMPK), key players in autophagy, are known to inhibit or activate autophagy, respectively. Here, we analyzed the signaling pathways regulating the initiation of autophagy in bovine luteal cells. In vivo studies showed increased activating phosphorylation of AMPKα (Thr172) and elevated content of LC3B, a known marker of autophagy, in luteal tissue during PGF2α-induced luteolysis. In vitro, AMPK activators (1) stimulated phosphorylation of regulatory associated protein of MTOR (RPTOR) leading to decreased activity of MTOR, (2) increased phosphorylation of Unc-51-Like Kinase 1 (ULK1) and Beclin 1 (BECN1), at sites specific for AMPK and required for autophagy initiation, (3) increased levels of LC3B, and (4) enhanced colocalization of autophagosomes with lysosomes indicating elevated autophagy. In contrast, LH/PKA signaling in luteal cells (1) reduced activation of AMPKα and phosphorylation of RPTOR, (2) elevated MTOR activity, (3) stimulated phosphorylation of ULK1 at site required for ULK1 inactivation, and (4) inhibited autophagosome formation as reflected by reduced content of LC3B-II. Pretreatment with AICAR, a pharmacological activator of AMPK, inhibited LH-mediated effects on RPTOR, ULK1 and BECN1. Our results indicate that luteotrophic signaling via LH/PKA/MTOR inhibits, while luteolytic signaling via PGF2α/Ca2+/AMPK activates key signaling pathways involved in luteal cell autophagy.
Stochastic Methods for Generative Systems Analysis

A very important part in the process of transmission of information is that of generation of the words. For some time past we tried to consider the process of generation of the words by generative systems, from a stochastic point of view involving Markov chains. Because the sequences of intermediate word (called derivations) by which a word can be generated are finite, it results that finite Markov chains will be connected to the process. In order to our discussion should be as general as possible we consider generative systems free of any restrictions. The model of such systems is offered by the most general class of formal grammars from the so-called Chomsky hierarchy, namely the phrase-structure grammars. The novelty that we have proposed consists in a new organization of the process of generation of the words by considering the set of all the derivations split into equivalence classes, each of them containing derivations of the same length. In this way our results are available up to an equivalence.
A 500 megabyte/second disk array

Applications at the Army High Performance Computing Research Center's (AHPCRC) Graphic and Visualization Laboratory (GVL) at the University of Minnesota require a tremendous amount of I/O bandwidth and this appetite for data is growing. Silicon Graphics workstations are used to perform the post-processing, visualization, and animation of multi-terabyte size datasets produced by scientific simulations performed of AHPCRC supercomputers. The M.A.X. (Maximum Achievable Xfer) was designed to find the maximum achievable I/O performance of the Silicon Graphics CHALLENGE/Onyx-class machines that run these applications. Running a fully configured Onyx machine with 12-150MHz R4400 processors, 512MB of 8-way interleaved memory, 31 fast/wide SCSI-2 channel each with a Ciprico disk array controller we were able to achieve a maximum sustained transfer rate of 509.8 megabytes per second. However, after analyzing the results it became clear that the true maximum transfer rate is somewhat beyond this figure and we will need to do further testing with more disk array controllers in order to find the true maximum.
Data collection and analysis in systems biology

Systems biology studies biological systems by systematically perturbing them (biologically, genetically, or chemically); monitoring the global biological response at the gene, protein, and informational pathway level; integrating these data; and ultimately, formulating mathematical models that describe the structure of the system and its response to individual perturbations. The key technologies that enable systems biology are reviewed with a focus on high-throughput measurement technologies and computational modeling approaches for integrating the resulting large-scale data. Keywords: systems biology; functional genomics; bioinformatics; computer-aided design
Secrecy and Democracy: Who Controls Information in the National Security State?

In national security matters, we give executive officials largely unchecked power to conceal from the public and even from Congress whatever information they choose to consider sensitive. We thus disconnect part of the essential machinery of democracy. Secrecy is nothing new, but in an era of transnational terrorism and expanded conceptions of what “national security” means, secrecy’s potential for eroding checks and balances is growing, even under a President ostensibly committed to greater openness in government. Democratic values and sound national security policy both suffer as a result.This Article argues that information access is central to legitimate governance and that in matters involving classified information, we have needlessly constrained democratic processes, as a result of misdirected fears and misplaced reverence for executive expertise. Many capabilities necessary for sound secrecy decisions can be found only in Congress or the courts. Discomfort with the executive information monopoly is increasingly evident in judicial decisions and legislative initiatives, but these acts of resistance remain halting and uneven. This Article attempts to give coherence to the often-tentative efforts by the other branches to claim a coordinate role. Building on congressional and judicial strengths, it develops an oversight framework more consonant with our constitutional design – an information democracy that combines robust national security safeguards with maximum feasible transparency and accountability.
8 Relative clause attachment in bilinguals and monolinguals

Abstract This chapter presents evidence from a group of experiments comparing the perceptual strategies employed by Spanish-English bilinguals to those used by their monolingual counterparts. The data show that language history affects the way readers assign structure to ambiguous syntactic constituents, but in different ways off-line and on-line. Off-line, bilinguals depart from the monolingual model in their attachment of relative clauses in their non-dominant language, and exhibit language-independent strategy use—with input in either language, bilinguals have behavior patterns similar to those of monolinguals of their dominant language. On-line, however, bilinguals appear to have no reliable attachment preferences, unlike monolinguals, who uniformly prefer attachment to the low site. The bilinguals' departure from the monolingual model is not taken to be indicative of a qualitative difference between monolingual and bilingual sentence processing. Instead, this result is attributed to a lack of sensitivity in the experimental procedure, which taps early processing with monolinguals, but misses the opportunity with bilinguals, whose reading times are overall slower.
Performance of a quad-ridged feed in a wideband Radio Telescope (EuCAP 2011)

A new quad-ridged, flared horn achieving nearly constant beamwidth and excellent return loss over a 6:1 frequency bandwidth is described. The system performance in two Radio Telescopes: 1) A 12-meter symmetric dual shaped reflector system intended for geodetic very long baseline interferometry and 2) A 15-meter offset dual shaped reflector intended for the SKA is presented showing it to be excellent wideband feed choice.
Reconnecting Farms and Ecosystems-- If It Pays

The Farm as Natural Habitat . Reconnecting Food Systems with Ecosystems. Dana L. Jackson and Laura L. Jackson, Eds. Island, Washington, DC, 2002. 312 pp. $50. ISBN 1-55963-846-X. Paper, $25. ISBN 1-55963-847-8. The contributors argue for a sustainable agriculture that would feed us while protecting and restoring biodiversity in rural landscapes.
Autocrine induction of major histocompatibility complex class I antigen expression results from induction of beta interferon in oncogene-transformed BALB/c-3T3 cells

By varying growth conditions, we identified a novel mechanism of autocrine regulation of major histocompatibility complex (MHC) class I gene expression by induction of beta interferon gene expression in transformed BALB/c-3T3 cells. Low-serum conditions enhanced MHC class I antigen expression in v-rasKi- and v-mos-transformed BALB/c-3T3 cells but not in untransformed BALB/c-3T3 cells. Transformed and untransformed cells grown under standard serum conditions (10% bovine calf serum) expressed similar cell surface levels of MHC class I antigens. However, low-serum conditions (0.5% bovine calf serum) induced four- to ninefold increases in cell surface levels of MHC class I antigens in both v-rasKi- and v-mos-transformed cells but not in untransformed cells. These increases in MHC class I gene expression were seen at both the mRNA and cell surface protein levels and involved not only the heavy-chain component of the class I antigens but also beta 2 microglobulin. Beta 1 interferon mRNA and beta interferon-inducible 2',5'-oligoadenylate synthetase mRNA were induced by growth under low-serum conditions in transformed BALB/c-3T3 cells, and antibodies to beta interferon blocked the induction of MHC class I antigen expression by serum deprivation in these cells. These results demonstrate that growth under low-serum conditions leads to induction of beta interferon expression in oncogene-transformed cells which then directly mediates autocrine enhancement of MHC class I gene expression.
The cellular compartmentalization of macrophage-associated nominal antigen: immunologically relevant macrophage-associated antigen may not require an intracellular phase of macrophage handling

It has been hypothesized that internalization and "processing" of the nominal antigen by antigen-presenting cells may be a mandatory event in antigen handling prior to cell surface presentation of the immunologically relevant moiety to T lymphocytes. In previous functional and immunochemical analyses of macrophage (M phi)-associated nominal antigen, we obtained data strongly suggesting that an immunologically relevant pool of antigen was detectable on the surface of M phi pulsed with a soluble protein antigen and then aged for 3-24 h. To provide further information about requisite events of M phi antigen handling, we have attempted to this study to determine the origin of the nominal antigen associated with the surface of the pulsed-aged cell using the terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT) as the antigen. The surface-bound GLT, after a 24-h culture, appeared to be derived from GLT initially surface-associated after the pulse. No evidence was obtained to support the notion that a significant quantity of GLT, initially internalized after the pulse exposure, was recompartmentalized to the cell surface. The turnover of cell-surface GLT resembled the turnover of M phi membrane proteins in general. These results, therefore, imply that the crucial events of M phi antigen handling of GLT may entirely be a cell surface phenomenon.