cssi/SciSciGPT-SciSciNet huggingface dataset:
Induction of Heterosubtypic Immunity to Influenza Virus by Intranasal Immunization

Recovery from live influenza virus infection is known to induce heterosubtypic immunity. In contrast, immunity induced by inactivated vaccines is predominantly subtype specific. In this study, we investigated the heterosubtypic protective immunity induced by inactivated influenza virus. Intranasal immunization of mice with inactivated influenza virus A/PR8 (H1N1) provided complete protection against the homologous virus and a drift virus within the same subtype, A/WSN (H1N1), but not against the heterosubtypic virus A/Philippines (H3N2). However, coadministration of inactivated virus with cholera toxin as an adjuvant conferred complete heterosubtypic protection, without observed illness, even under conditions of CD4 + or CD8 + T-cell depletion. Analysis of immune correlates prior to challenge and postchallenge indicated that humoral immune responses with cross-neutralizing activity in lungs and in sera play a major role in conferring protective immunity against heterosubtypic challenge. This study has significant implications for developing broadly cross-reactive vaccines against newly emerging pathogenic influenza viruses.
Low-dose D-methionine and N-acetyl-L-cysteine for protection from permanent noise-induced hearing loss in chinchillas.

Objective. Despite efforts at public health awareness and stringent industrial standards for hearing protection, noise-induced hearing loss (NIHL) remains a formidable public health concern. Althou...
The use of the female bitterling as a test for male hormone

Abstract It is shown that the lengthening of the ovipositor of the female bitterling by external stimuli cannot be considered to be a test for estrogenic hormones per se. There are substances excreted in most normal urines which initiate this phenomenon. We have shown that these causative agents are the male hormones and have established in a preliminary way the daily amounts excreted by normal male adults.
An analysis of frequency offset estimation algorithms for OFDM systems

This paper studies the statistical properties of the conventional frequency offset estimation algorithm. Analytical expressions describing the mathematic expectation and the variance are derived for both the integer and the fractional frequency offset estimation algorithms. The theoretical equations presented in this paper provide improved agreement with simulation results in comparison to those previously reported in the literature.
Ankle and hip postural strategies defined by joint torques

Previous studies have identified two discrete strategies for the control of posture in the sagittal plane based on EMG activations, body kinematics, and ground reaction forces. The ankle strategy was characterized by body sway resembling a single-segment-inverted pendulum and was elicited on flat support surfaces. In contrast, the hip strategy was characterized by body sway resembling a double-segment inverted pendulum divided at the hip and was elicited on short or compliant support surfaces. However, biomechanical optimization models have suggested that hip strategy should be observed in response to fast translations on a flat surface also, provided the feet are constrained to remain in contact with the floor and the knee is constrained to remain straight. The purpose of this study was to examine the experimental evidence for hip strategy in postural responses to backward translations of a flat support surface and to determine whether analyses of joint torques would provide evidence for two separate postural strategies. Normal subjects standing on a flat support surface were translated backward with a range of velocities from fast (55 cm/s) to slow (5 cm/s). EMG activations and joint kinematics showed pattern changes consistent with previous experimental descriptions of mixed hip and ankle strategy with increasing platform velocity. Joint torque analyses revealed the addition of a hip flexor torque to the ankle plantarflexor torque during fast translations. This finding indicates the addition of hip strategy to ankle strategy to produce a continuum of postural responses. Hip torque without accompanying ankle torque (pure hip strategy) was not observed. Although postural control strategies have previously been defined by how the body moves, we conclude that joint torques, which indicate how body movements are produced, are useful in defining postural control strategies. These results also illustrate how the biomechanics of the body can transform discrete control patterns into a continuum of postural corrections.
RESPIRATION AND PROTEIN SYNTHESIS IN ESCHERICHIA COLI MEMBRANE-ENVELOPE FRAGMENTS : V. On the Reduction of Nonheme Iron and the Cytochromes by Nicotinamide Adenine Dinucleotide and Succinate

The sensitivity of nicotinamide adenine dinucleotide (NADH) oxidase and succinoxidase to metal chelators, the generation of an electron paramagnetic resonance (EPR) signal upon addition of these substrates, and the rate of formation of the EPR signal relative to the rate of the cytochrome reduction suggest the participation of nonheme iron proteins in the respiratory process of Escherichia coli. The most inhibitory metal chelator, thenoyltrifluoro acetone, inhibited the reduction of nonheme iron and cytochromes but did not prevent the reoxidation of the reduced forms. The EPR signal, dehydrogenase, and oxidase activities evoked by NADH are considerably greater than the corresponding activities evoked by succinate. Because both substrates can reduce almost all of the cytochromes, a model in which fewer succinate dehydrogenase-nonheme iron protein complexes are linked to a common cytochrome chain than NADH dehydrogenase-nonheme iron protein complexes is considered likely.
Mutations in the intersubunit bridge regions of 16S rRNA affect decoding and subunit–subunit interactions on the 70S ribosome

The small and large subunits of the ribosome are held together by a series of bridges, involving RNA-RNA, RNA-protein and protein-protein interactions. Some 12 bridges have been described for the Escherichia coli 70S ribosome. In this work, we have targeted for mutagenesis, some of the 16S rRNA residues involved in the formation of intersubunit bridges B3, B5, B6, B7b and B8. In addition to effects on subunit association, the mutant ribosomes also affect the fidelity of translation; bridges B5, B6 and B8 increase decoding errors during elongation, while disruption of bridges B3 and B7b alters the stringency of start codon selection. Moreover, mutations in the bridge B5, B6 and B8 regions of 16S rRNA also correct the growth and decoding defects associated with alterations in ribosomal protein S12. These results link bridges B5, B6 and B8 with the decoding process and are consistent with the recently described location of translation factor EF-Tu on the ribosome and the proposed involvement of h14 in activating Guanosine-5'-triphosphate (GTP) hydrolysis by aminoacyl-tRNA • EF-Tu • GTP. These observations are consistent with a model in which bridges B5, B6 and B8 contribute to the fidelity of translation by modulating GTP hydrolysis by aminoacyl-tRNA • EF-Tu • GTP ternary complexes during the elongation phase of protein synthesis.
Identification of G protein-coupled receptor signaling pathway proteins in marine diatoms using comparative genomics

Background: The G protein-coupled receptor (GPCR) signaling pathway plays an essential role in signal transmission and response to external stimuli in mammalian cells. Protein components of this pathway have been characterized in plants and simpler eukaryotes such as yeast, but their presence and role in unicellular photosynthetic eukaryotes have not been determined. We use a comparative genomics approach using whole genome sequences and gene expression libraries of four diatoms (Pseudo-nitzschia multiseries, Thalassiosira pseudonana, Phaeodactylum tricornutum and Fragilariopsis cylindrus) to search for evidence of GPCR signaling pathway proteins that share sequence conservation to known GPCR pathway proteins. Results: The majority of the core components of GPCR signaling were well conserved in all four diatoms, with protein sequence similarity to GPCRs, human G protein α- and β-subunits and downstream effectors. There was evidence for the Gγ-subunit and thus a full heterotrimeric G protein only in T. pseudonana. Phylogenetic analysis of putative diatom GPCRs indicated similarity but deep divergence to the class C GPCRs, with branches basal to the GABAB receptor subfamily. The extracellular and intracellular regions of these putative diatom GPCR sequences exhibited large variation in sequence length, and seven of these sequences contained the necessary ligand binding domain for class C GPCR activation. Transcriptional data indicated that a number of the putative GPCR sequences are expressed in diatoms under various stress conditions in culture, and that many of the GPCR-activated signaling proteins, including the G protein, are also expressed. Conclusions: The presence of sequences in all four diatoms that code for the proteins required for a functional mammalian GPCR pathway highlights the highly conserved nature of this pathway and suggests a complex signaling machinery related to environmental perception and response in these unicellular organisms. The lack of evidence for some GPCR pathway proteins in one or more of the diatoms, such as the Gγ-subunit, may be due to differences in genome completeness and genome coverage for the four diatoms. The high divergence of putative diatom GPCR sequences to known class C GPCRs suggests these sequences may represent another, potentially ancestral, subfamily of class C GPCRs.
Adjuvant HER2/neu peptide cancer vaccines in breast cancer

Active cancer immunotherapy remains an exciting and rapidly advancing field in oncology. Peptide cancer vaccines are an attractive therapeutic option as they are safe and easily produced and administered. Peptide cancer vaccines may be most effective in patients with a lower disease burden, when cancer tolerance is minimized. Our experience with three peptide cancer vaccines, E75, GP2 and AE37, in clinically disease-free breast cancer patients provides encouraging results that this method may be effective. Furthermore, the combined results of the initial trials suggest that the vaccine administered may need to be tailored to the specific subtype of cancer and tumor antigen expression level to achieve maximum effectiveness. The results also suggest that combining peptide vaccines with other immunotherapy may lead to a synergistic effect.
Drug Treatment in Children with Juvenile Rheumatoid Arthritis: Past, Present, and Future

Rheumatology made its debut as a legitimate subspecialty of pediatrics sometime in the 1940s in Europe, and in the 1970s in North America. Therapy of juvenile rheumatoid arthritis has evolved from salicylates and gold injections to newer, less toxic nonsteroidal anti-inflammatory drugs and methotrexate. Corticosteroids remain as important drugs when life-threatening complications or blinding iridocyclitis develop. Immune response modifiers and gene therapies offer considerable potential for eventually halting or curing the disease but have yet to make a substantial impact on therapy. Methods for the correct conduct and interpretation of data from clinical trials are discussed.
Maze alternation in the planarian, Dugesia tigrina

600 planarians (Dugesia tigrina) made 0, 1, 2,3, 4, or 5 forced 90° right-hand turns immediately before reaching a T choice point. There were 100 Ss in each of 6 groups, and each S was given one trial only. The proportion of Ss that turned left at the choice point increased with the number of forced 90° right turns preceding the choice point. The proportions ranged from.43 to.76.
Authority and Information

Authority often relies on information whose collection and transmission by subordinates its very exercise discourages. In this paper, we study how the allocation of authority affects the production, transmission, and strategic use of subjective intelligence relying on exhaustive data on credit decisions. Exploiting the exogenous variation in branch-headquarters distance we find that the center is more likely to delegate authority the further away line units are. Consistent with economic theory, more autonomous branches produce more soft information; conversely, the more information they produce, the more real authority they enjoy. Our findings also identify incentives to strategically use soft information in response to local competition as a further channel through which the delegation of authority affects investment success. Finally, we provide strong evidence that in equilibrium the delegation of authority helps to overcome distance related obstacles to corporate-decision making through subjective intelligence.
Carboxytransphosphorylase VIII. LIGAND-MEDIATED INTERACTION OF SUBUNITS AS A POSSIBLE CONTROL MECHANISM IN PROPIONIBACTERIA

Abstract Phosphoenolpyruvate carboxytransphosphorylase from Propionibacterium shermanii catalyzes the conversion of P-enolpyruvate, orthophosphate, and CO2 to oxalacetate and pyrophosphate. The enzyme occurs in three enzymatically active forms, tetramer, dimer, and monomer, but only the tetrameric and monomeric forms have been isolated from the bacteria. The dimeric form was initially observed by Haberland et al. (Haberland, M. E., Willard, J. M., and Wood, H. G. (1972) Biochemistry 11, 712–722) in reacting enzyme sedimentation centrifugation, and it was shown that dissociation of the tetrameric enzyme and association of monomeric enzyme to dimeric forms occurred during catalysis of the forward reaction. We have now shown that the association-dissociation is not caused by the substrates but by the product, oxalacetate. When the forward reaction is conducted in the presence of hydrogen peroxide, which oxidizes oxalacetate to malonate, no dimer formation is observed. In addition to oxalacetate, malate and fumarate induce the subunit interactions. Our results show that the dimeric species is less active than the tetrameric species. Preincubation of the tetrameric enzyme at dilute concentrations in malate buffer results in a loss of 50% of the activity within 5 min. This loss in activity is strongly dependent on the concentration of protein, there being less loss of activity with higher concentrations of protein in the malate buffer. The tetramer-dimer interaction is in equilibrium since only a single peak is observed on centrifugation in malate buffer, and as the protein concentration of the tetrameric form is decreased the s20, obs value decreases until it approaches that of the dimer. At the same time, there is a loss in enzymatic activity which correlates with the increase in the dimeric form. The monomeric species has a specific activity about one-fourth that of the tetrameric species, and the activity is not affected by the presence of malate although there is total conversion of monomeric into dimeric species. The continued presence of an effector is required for maintenance of the dimeric species from either tetramer or monomer. Sedimentation equilibrium studies in malate buffer gave a molecular weight of 224,000 for the dimeric species formed from monomeric enzyme. When tetrameric enzyme was employed a nonlinear log Y versus r2 plot was observed reflecting the equilibrium between tetramers and dimers induced by the presence of an effector. The malate-treated tetrameric enzyme is more susceptible to proteolytic attack by trypsin and chymotrypsin than the untreated enzyme. It is proposed that the ligand-induced subunit interactions play a role in the control of the propionic acid fermentation.
Death beyond disavowal: The impossible politics of difference

Bringing out our dead“I felt called by the dead, and I felt that I had to acknowledge those who had died, as a way of reckoning with, to quote Audre Lorde, ‘the deaths we are expected to live’” (15...
Nonuniform contraction in the isolated cat papillary muscle

Microspheres infused into the coronary microcirculation were used as markers to define segments within isolated cat papillary muscles. Video recording and analysis provided measurements of the variations of segment lengths as the muscles contracted at lengths of 76-100% Lmax. In all muscles, segments in the center region were found to shorten during muscle isometric contraction while those in the end regions lengthened. Central shortening was typically 10-15%. In the passive state, segment lengths varied directly with muscle length over a broad range characterized by low force. Segments in the center region, however, displayed an abrupt transition to high stiffness at a certain length while end regions continued to stretch. Force-length relationships obtained for the presumably healthy center segment are significantly different from those obtained for the whole muscle. These results suggest that there may be major difficulties with the interpretation of mechanical measurements on papillary muscles unless contractile inhomogeneity is eliminated or taken into account.
Drug Trafficking, Political Violence, and U.S. Policy in Colombia under the Clinton Administration

This chapter examines the impact of U.S. and Colombian government drug control policies on the evolution of drug cultivation, drug trafficking, and political violence in Colombia during the 1990s. Its central thesis is that the Washington/Bogota-backed war on drugs in Colombia over the decade did not merely fail to curb the growth of the Colombian drug trade and attendant corruption, but actually proved counterproductive. Among the most important unintended consequences were the explosion of drug cultivation and production activities; the dispersion and proliferation of organized crime; and the expansion and intensification of political violence and guerrilla warfare in the country. As a result, Colombia at the outset of 2000 faced more serious threats to its national security and political stability than it had in 1990. It concludes that the massive escalation of the flawed anti-drug strategies of the past decade proposed by the Clinton administration in January 2000 is more likely to worsen Colombia’s ongoing problems of spiraling violence and insecurity than to resolve them.
High Capacity Transport - 100G and Beyond

Modern high capacity optical transport systems use coherent transmission and digital signal processing to overcome many physical impairments. Coherent optical transmission methods are explained and measured performances are shown for commercial coherent systems at 100 Gb/s. Future directions for high capacity transport beyond 100Gb/s are discussed.
The Age of Regicide

This study of royalty and monarchical government in France and England over the course of a crucial century will be important reading for all historians of politics, political thought, religion, or...
Hybrid all-optical networks: Routing and wavelength assignment

Hybrid all-optical networks that integrate OCS and OBS technologies have been recently proposed to facilitate next-generation applications like cloud and grid computing. In this paper, we propose an ILP formulation and a heuristic based on genetic algorithm for routing and wavelength assignment problem in hybrid all-optical networks. The proposed model aims to minimize wavelength contentions by minimizing the overlapping paths in the hybrid networks. Experimental simulations show that the heuristic effectively minimizes the wavelength contention in the hybrid networks.
Chronic GVHD Is Associated with a BAFF Driven BCR-Activated B Cell Repertoire.

We recently showed that high levels of B cell Activating Factor (BAFF) after allogeneic hematopoietic stem cell transplantation (HSCT) correlate with chronic GVHD development. BAFF promotes survival and differentiation of human BCR-activated (CD27+) B cells into Ig-secreting cells (ISC). To examine whether BAFF drives ISC in cGVHD, CD27+ peripheral B subsets and plasma BAFF levels were examined in 57 patients ≥ 12 months after HSCT. Significantly higher BAFF levels were found in active and inactive cGVHD groups compared to control patients with no cGVHD. Patients with cGVHD had a relative reduction in naive B cells compared to controls, resulting in a preponderance of CD27+ B cells (Table 1). Both pre-germinal center [pre-GC (IgD+)] and post-GC (IgDLo) subsets had significantly increased CD27+ in active cGVHD (Table 2). When BAFF levels were compared with cell number, only active disease patients had a positive correlation between BAFF and plasmablasts (r=+0.51, p-value=0.013), suggesting CD27+ post-GC B cells are highly BAFF-dependent in cGVHD. Active and inactive cGVHD patients had a positive correlation between BAFF and number of CD27+ pre-GC cells (r=+0.5, r=+0.49, respectively, p-value=0.02 each). In vitro analysis of these infrequent B subpopulations was accomplished using a large-volume lymphocyte donation from an untreated active cGVHD patient. Plasmablast and pre-GC purified populations had distinctly higher apoptotic rates attenuated in vitro by BAFF. CD27+ pre-GC B cells were induced by BAFF to differentiate into post-GC plasmablasts, indicating that survival and differentiation effects likely explain the correlations between BAFF and pre and post-GC CD27+ B subsets in patients. Increased BAFF levels in patients with inactive disease also correlated with lower total B (r=−0.59, p=0.003) and memory subset numbers (r=−0.57, p=0.005) suggesting that simultaneous B cell turnover and reconstitution may occur as disease becomes inactive. Thus, peripheral CD27+ B cells differentiate into potentially alloreactive ISC in presence of excess BAFF without need for further antigen stimulation. These results implicate BAFF and BCR-activated B cells in cGVHD and provide a rationale for therapeutic use of BAFF antagonists in this disease.
Residual Enoxaparin Activity, Anti-Xa Levels, and Concerns About the American Society of Regional Anesthesia and Pain Medicine Anticoagulation Guidelines

Currently, the American Society of Regional Anesthesia and Pain Medicine (ASRA) anticoagulation guidelines recommend that before the performance of a neuraxial procedure a minimum of 24 hours should elapse following a treatment dose of enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily). The guidelines have since their inception also consistently recommended against the routine use of anti-Xa level monitoring for patients receiving enoxaparin. However, we noted in our clinical practice that anti-Xa levels were frequently still elevated despite patients meeting the time-based recommendation for treatment dose enoxaparin. To further investigate the possibility that residual anticoagulant activity may persist longer than 24 hours after a treatment dose of enoxaparin, we assessed anti-Xa level activity in patients presenting for elective surgery. Despite nearly universal compliance with ASRA's anticoagulation guidelines (1 sample was drawn at 23.25 hours), anti-Xa activity was found to be elevated in 11 of 19 patients. While 10 patients had an anti-Xa level within the peak prophylactic range (0.2-0.5 IU/mL), 1 patient's level was found to still be in the peak therapeutic range (0.5-1.0 IU/mL). These findings suggest that significant anticoagulant activity may persist longer than previously appreciated after the last treatment dose of enoxaparin and that the current time-based ASRA recommendation may not be conservative enough. Further research is needed to delineate the level of anti-Xa activity below which it is likely safe to proceed with a neuraxial procedure, but it may be time to reconsider the utility of anti-Xa level monitoring when it is available.
Computing Polynomials with Positive Coefficients using Stochastic Logic by Double-NAND Expansion

This paper proposes a novel method, referred to as \textit{double-NAND expansion}, to implement polynomials with all positive coefficients using unipolar stochastic logic. %The inputs and outputs of these circuits lie between 0 and 1, and are encoded using unary bit streams. Prior work has addressed implementation of polynomials with alternately positive and negative coefficients and non-increasing magnitudes, using stochastic logic based on Horner's rule. However, Horner's expansion is not applicable to implementation of polynomials with all positive coefficients. The proposed double-NAND expansion leads to implementations of polynomials using no more than 2n NAND gates where n represents the degree of the polynomial. %While the Horner's rule leads to cascaded AND-NAND gates, the proposed expansion leads to cascaded double-NAND gates.The proposed implementations are compared with those based on multiplexers, Bernstein polynomial method, finite state machine method and factorization. The paper also considers implementations of several functions expressed as polynomials using truncated Mclaurin series based on the proposed approach. The experimental results show that the proposed method outperforms the prior methods in terms of accuracy, hardware complexity, and critical path.
Primary small-cell carcinoma of the breast.

Early diagnosis of rare breast cancers is expected to occur more frequently as screening compliance improves and diagnostic modalities become more sensitive. Well-defined treatment algorithms exist...
MRI-guided Dose-escalated Salvage Radiotherapy for Bulky Bladder Neck Recurrence of Prostate Cancer.

Nearly 30% of patients treated with radical prostatectomy for prostate cancer ultimately develop biochemical recurrences, and nearly a quarter of men with nonpalpable biochemical recurrences have gross local recurrences identified with magnetic resonance imaging (MRI). The only curative intervention for patients with recurrent disease after radical prostatectomy is salvage radiotherapy - this is particularly true for patients with gross local recurrences. Furthermore, even in patients with an incurable metastatic disease, a local recurrence can be the source of significant morbidity and should be addressed. Delivering a sufficient dose of radiation in the postoperative setting to control gross disease while minimizing toxicity poses a significant technical challenge. Because of the inherent uncertainty in the verification of gross disease positioning with standard onboard imaging technologies, large margins must be used. Larger margins, in turn, will lead to larger volumes of tissue receiving high doses of radiation, potentially increasing long-term toxicity. Herein, we present the case of a patient with a bulky gross recurrence (>40 cm3) at the bladder neck and synchronous metastatic disease who was referred for salvage radiotherapy after a multidisciplinary consensus recommendation to pursue local therapy for mitigating urinary morbidity from the bulky tumor. The case illustrates the utilization of MRI-guided radiotherapy to allow significant margin reduction, thereby facilitating the delivery of an escalated dose of radiotherapy to a bulky recurrence.
Patients at high risk of tuberculosis recurrence

Recurrent tuberculosis (TB) continues to be a significant problem and is an important indicator of the effectiveness of TB control. Recurrence can occur by relapse or exogenous reinfection. Recurrence of TB is still a major problem in high-burden countries, where there is lack of resources and no special attention is being given to this issue. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 47%. This variability is related to differences in regional epidemiology of recurrence and differences in the definitions used by the TB control programs. In addition to treatment failure from noncompliance, there are several key host factors that are associated with high rates of recurrence. The widely recognized host factors independent of treatment program that predispose to TB recurrence include gender differences, malnutrition; comorbidities such as diabetes, renal failure, and systemic diseases, especially immunosuppressive states such as human immunodeficiency virus; substance abuse; and environmental exposures such as silicosis. With improved understanding of the human genome, proteome, and metabolome, additional host-specific factors that predispose to recurrence are being identified. Information on temporal and geographical trends of TB cases as well as studies with whole-genome sequencing might provide further information to enable us to fully understand TB recurrence and discriminate between reactivation and new infection. The recently launched World Health Organization End TB Strategy emphasizes the importance of integrated, patient-centered TB care. Continued improvement in diagnosis, treatment approaches, and an understanding of host-specific factors are needed to fully understand the clinical epidemiological and social determinants of TB recurrence.
Evaluating the Cultural Fit of Hunting and Angling Among Minority Sportspersons in North Carolina

Culture defines leisure-specific behaviors, relationships, institutions, identities, and understandings of reality, but culture's role in U.S. hunting and fishing is poorly understood among diverse...
Memory as a property of nature

Prerequisite to memory is a past distinct from present. Because wave evolution is both continuous and time-reversible, the undisturbed quantum system lacks a distinct past and therefore the possibility of memory. With the quantum transition, a reversibly evolving superposition of values yields to an irreversible emergence of definite values in a distinct and transient moment of time. The succession of such moments generates an irretrievable past and thus the possibility of memory. Bohm’s notion of implicate and explicate order provides a conceptual basis for memory as a general feature of nature akin to gravity and electromagnetism. I propose that natural memory is an outcome of the continuity of implicate time in the context of discontinuous explicate time. Among the ramifications of natural memory are that laws of nature can propagate through time much like habits and that personal memory does not require neural information storage.
Interleukin-6–Induced Inhibition of Multiple Myeloma Cell Apoptosis: Support for the Hypothesis That Protection Is Mediated Via Inhibition of the JNK/SAPK Pathway

The mechanism by which interleukin-6 (IL-6) protects multiple myeloma (MM) plasma cells from apoptosis induced by anti-fas antibodies and dexamethasone was studied. Anti-apoptotic concentrations of IL-6 had no effect on cell-cycle distribution or activation of RAF-1 or ERK in dexamethasone- or anti-fas-treated 8226 and UCLA #1 MM cell lines. However, IL-6-dependent protection of viability correlated with an inhibition of dexamethasone- and anti-fas-induced activation of jun kinase (JNK) and AP-1 transactivation. To test the hypothesis that cytokine-induced protection was mediated through inhibition of JNK/c-jun, we also inhibited c-jun function in 8226 cells via introduction of a mutant dominant negative c-jun construct. Mutant c-jun-containing MM cells were also resistant to anti-fas-induced apoptosis but were significantly more sensitive to dexamethasone-induced apoptosis. These results support the notion that IL-6 protects MM cells against anti-fas through its inhibitory effects on JNK/c-jun but indicate protection against dexamethasone occurs through separate, yet unknown pathways.
The Vital Role of the Collateral Source Rule in United States Healthcare Financing

The collateral source rule plays a vital role in both the healthcare financing and legal systems in the United States. While for many years the rule has been under fire from various tort reform advocates, and has taken some severe hits over that time, it remains as important today as it was when first developed over one-hundred and fifty years ago. Long understood as a rule of evidentiary consequence, modern legal scholars seem to have lost track of both the origins and of the real value of the rule and, as such, application has been constricted unnecessarily. While the costs of both the American tort and healthcare structures are undeniably high, abrogating the collateral source rule is neither the best nor the most plausible way to lower those costs.Made necessary by the unique multi-payer cost sharing nature of healthcare financing in the United States, the collateral source rule serves a number of vital roles in supporting the way in which medical providers spread the costs of caring for the uninsured and underinsured. As such, the rule remains vital to balancing medical costs and to ensuring a viable healthcare provider market. Furthermore, in individual cases, the equities of most situations depend on application of the collateral source rule to properly balance competing interests.Warnings about the evils of double recovery from the defendant’s bar are overdramatic and grossly misrepresent the actual facts as viewed from the broader vantage point of sound public policy. In Part I of this paper I review the origin and application of the collateral source rule in California including a brief discussion of the impact of the Howell case. In Part II I discuss the nature of the fragmented healthcare financing system in the United States today. In Part III I argue for a continued application of the collateral source rule, including to the negotiated rate differential, in personal injury cases in California.
Teaching captcha in a PHP programming course

CAPTCHA is a popular protection mechanism used by many web sites to defend against attacks from software robots which attempt to gather information or automatically fill in forms and submit them assuming someone's identity. In this paper, the authors describe how students can be taught the basic concepts of CAPTCHA programming through hands-on coding activities. The authors also discuss sample PHP code examples that can be used to illustrate the coding techniques. Instructors can use these code examples to demonstrate the various types of CAPTCHA applications.
Community Colleges: Enhancing Opportunity or Reinforcing Disadvantage?

Currently, more than 6.5 million students are enrolled in community colleges around the country, representing approximately half of the undergraduate population in the United States. According to the American Association of Community Colleges (AACC), these institutions serve as the \gateway to postsecondary education for many minority, low-income, and fi rst generation postsecondary education students." Given the large numbers of disadvantaged and non-traditional students, most community colleges o ffer a broad range of support services, everything from mentoring to childcare to tutoring. This study provides an empirical test of the effectiveness of support services on the achievement of disadvantaged and minority students. It uses coarsened exact matching (CEM) along with linear regression to compare the achievement of students from Hous- ton Community College (HCC), one of the largest and most diverse community colleges in the country, based on their service usage. This study is designed to enhance our understanding of the impact that academic support services have on the achievement of disadvantaged students, and whether the community college system more generally truly off ers a `gateway to education' for minorities and low-income students.
Oil Spill Drift and Fate Model

This paper describes an operational forecasting model of oil spill drift and fate. The model is aimed at predicting the behaviour of oil spills in the St. Lawrence River, and at providing decision support for planning responses and clean-up operations. A software system links the spill model to environmental data, wind forecasts and hydrodynamic models. The present paper focuses on the formulation and algorithms of the oil spill drift and fate model. Processes of mechanical spreading dispersion, weathering, as well as adhesion to shorelines are included. A discrete parcel approach is also employed to track the spill.
Anti-LGBT victimization, fear of violence at school, and suicide risk among adolescents.

We investigated whether strengths of the relationships between anti–lesbian, gay, bisexual, and transgender (LGBT) victimization, fear of violence at school, and suicide risk differ by sexual orientation among a predominantly ethnic minority sample of adolescents. Using the 2012 District of Columbia
Trends of Contraceptive Choices Among Young Women in Inner City Houston.

Abstract Study Objective Although long-acting reversible contraceptives (LARC) such as intrauterine devices and subdermal implants remain the most effective methods of contraception for teenagers, most adolescents continue to use less reliable methods. The purpose of this study was to determine: (1) the distribution of contraceptive type according to age of the patients in our clinic system (Baylor Teen Health Clinic); and (2) the differences in this distribution over the past decade. Design This study was a comprehensive chart review of at least 15,500 charts for the years 2005 to 2014. Setting Baylor Teen Health Clinic. Participants, Interventions, and Main Outcome Measures Charts of patients less than 25 years of age who attended one of the 9 Baylor Teen Health Clinics were reviewed. Contraceptive uptake by age and year was the main outcome measured. Results The percentage of women younger than age 25 years who used LARC increased for all age groups from 2005 to 2014, with the greatest increase for women 20-24 years old ( Conclusion More efforts need to be placed on determining the reasons for low LARC uptake despite greatest efficacy in this young, vulnerable population.
Development of Streptococcus pneumoniae Pan-Group Quorum-Sensing Modulators

The rapid increase in multidrug-resistant pathogens is a major health concern that could bring mankind back to the pre-antibiotic era. Streptococcus pneumoniae is a highly recombinogenic opportunistic pathogen that causes a variety of deadly diseases and rapidly develops resistance to current antibiotic treatments. S. pneumoniae pathogenicity is dependent on a cell-density communication mechanism, or quorum sensing (QS), termed the competence regulon. In this work, we set out to design signal-based QS modulators capable of affecting the two specificity groups found in S. pneumoniae. Through systematic analysis and rational design, we were able to construct peptide-based pan-group QS activators and inhibitors with activities in the nanomolar range. These novel analogues are privileged scaffolds for the development of anti-virulence therapeutics against S. pneumoniae infections.
Fourth-order accurate fractional-step IMEX schemes for the incompressible Navier–Stokes equations on moving overlapping grids

Abstract Two efficient fractional-step schemes for the incompressible Navier–Stokes equations in two and three dimensions are described. The schemes are fourth-order accurate in space and time, and are based on solving the velocity-pressure form of the equations. Both schemes employ predictor-corrector time-stepping approaches. The first is an explicit Adams-type scheme, while the second is an IMEX-BDF-type scheme in which the viscous/advective terms in the equations are treated implicitly/explicitly. The equations and boundary conditions are discretized in space using fourth-order accurate finite-difference approximations. The formulation of discrete boundary conditions for each stage of the fractional-step scheme is found to be critical to the accuracy and stability of the approach. A WENO-based scheme, called BWENO, provides upwind dissipation and ensures robustness of the schemes for problems where the solution is under-resolved on the grid (e.g. near boundary or shear layers). Complex, and possibly moving, domains are handled efficiently using composite overlapping grids. A variety of problems in two and three dimensions, some for which exact solutions are either known or manufactured, are used to verify the stability and accuracy of the new schemes.
An Approach to Consolidating Pediatric Hospital Beds During the COVID-19 Surge.

* Abbreviation: IQR — : interquartile range On April 3, 2020, in response to the coronavirus disease 2019 pandemic, the Children’s Hospital Association of the United States issued guidance for coordinating pediatric hospital care and increasing general hospital surge capacity.1 Observing that ∼200 hospitals already care for 50% of all pediatric admissions, it called for immediate consolidation of pediatric care within experienced pediatric facilities and coordinated efforts between children’s and community hospitals to benefit both adult and pediatric patients. The goal was to expand adult capacity in community hospitals caring for older patients while, at the same time, providing care for pediatric patients in settings where customized pediatric resources are available. Because local conditions vary, flexibility and thoughtful coordination across hospital systems were … Address correspondence to Michael L. McManus, MD, MPH, Boston Children’s Hospital, Bader 6th Floor, 300 Longwood Ave, Boston, MA 02115. E-mail: michael.mcmanus{at}childrens.harvard.edu
Learning Spiking Neural Network Models of Drosophila Olfaction

We present research in the modeling of neurons within Drosophila (fruit fly) olfaction. We describe the process from data collection, to model creation, and spike generation. Our approach utilizes computational elements such as spiking neural networks that employ leaky integrate-and-fire neurons with adaptive firing behavior that more closely mimick biological neurons. We describe the methods of several learning implementations in both software and hardware. Finally, we present both quantitative and qualitative results on learning spiking neural network models.
Purinergic Signaling: Impact of GPCR Structures on Rational Drug Design

The purinergic signaling system includes membrane-bound receptors for extracellular purines and pyrimidines, and enzymes/transporters that regulate receptor activation by endogenous agonists. Receptors include: adenosine (A1 , A2A , A2B, and A3 ) and P2Y (P2Y1 , P2Y2 , P2Y4 , P2Y6 , P2Y11 , P2Y12 , P2Y13 , and P2Y14 ) receptors (all GPCRs), as well as P2X receptors (ion channels). Receptor activation, especially accompanying physiological stress or damage, creates a temporal sequence of signaling to counteract this stress and either mobilize (P2Rs) or suppress (ARs) immune responses. Thus, modulation of this large signaling family has broad potential for treating chronic diseases. Experimentally determined structures represent each of the three receptor families. We focus on selective purinergic agonists (A1 , A3 ), antagonists (A3 , P2Y14 ), and allosteric modulators (P2Y1 , A3 ). Examples of applying structure-based design, including the rational modification of known ligands, are presented for antithrombotic P2Y1 R antagonists and anti-inflammatory P2Y14 R antagonists and A3 AR agonists. A3 AR agonists are a potential, nonaddictive treatment for chronic neuropathic pain.
Infection of immune competent macrophages expressing functional Slc11a1 alters global gene expression, regulation of metal ions, and infection outcomes

Abstract Nutritional immunity involves cellular and physiological responses to invading pathogens, such as limiting iron availability, increasing exposure to bactericidal copper, and manipulating zinc to restrict the growth of pathogens. Manipulation of zinc at the host-pathogen interface depends on both the pathogen’s identity and the nature of the host cell. Here we examine infection of bone marrow-derived macrophages from 129S6/SvEvTac mice by Salmonella Typhimurium. Unlike Balb/c and C57BL/6 mice, 129S6/SvEvTac mice possess a functional Slc11a1 (Nramp-1), a phagosomal transporter of divalent cations. We carried out global RNA sequencing upon treatment with live or heat-killed Salmonella at 2 Hrs and 18 Hrs post-infection and observed widespread changes in metal transport, metal-dependent, and metal homeostasis genes, suggesting significant remodeling of iron, copper, and zinc availability by host cells. Changes in host cell gene expression suggest infection increases cytosolic zinc while simultaneously limiting zinc within the phagosome. Using a genetically encoded sensor, we demonstrate that cytosolic labile zinc increases 36-fold 12 hrs post-infection. Further, manipulation of zinc in the media alters bacterial clearance and replication, with zinc depletion inhibiting both processes. Comparing our results to published data on infection of C57BL/6 macrophages revealed notable differences in metal regulation and the global immune response, with 129S6 macrophages transitioning from M1 to M2 polarization over the course of infection and showing signs of recovery. Our results reveal that functional Slc11a1 profoundly affects the transcriptional landscape upon infection. Further, our results indicate that manipulation of zinc at the host-pathogen interface is more nuanced than that of iron or copper. 129S6 macrophage leverage intricate means of manipulating zinc availability and distribution to limit the pathogen’s access to zinc while simultaneously ensuring sufficient zinc to support the immune response. Author summary Metal ions play an important role in influencing how immune cells such as macrophages respond to infection by pathogens. Because metal ions are both essential to survival, as well toxic when present is excessive amounts, the host and the pathogen have evolved diverse strategies to regulate metal acquisition and availability. Here, we show that the metal transporter slc11a1 plays a critical role in defining the host response to Salmonella infection. Infection causes widespread changes in expression of metal regulatory genes to limit the pathogen’s access to iron, increase its exposure to copper, and remodel zinc to ensure increased zinc in the cytosol and limited zinc for the pathogen. Macrophages expressing functional slc11a1 have a different profile of metal regulation and vastly different outcomes compared to immune compromised macrophage, demonstrating significantly different nutritional immune responses in immune competent versus immune compromised macrophages.
Power and Thermal Modeling of In-3D-Memory Computing

In-memory computing is an efficient big-data processing method that allows for performance scalability. Although 3D-memory is an established technology to integrate in-memory computing due to the 3D-stacked logic and memory layers, there are thermal issues and power budgets that restrict the integration of this concept in a 3D-stacked memory. In this paper, we investigate the power and thermal behavior of the in-3D-memory computing device based on thermal circuit modeling. When the logic layers consume 1 W/cm2 in each layer, the maximum power available in the logic layer is 11.4 W/cm2 and 7.3 W/cm2 for the 4 and 16-layer stack. For high-rise stacked memory, passive heat sinks cannot sustain the operating temperature below 85 C. In this work, the validity of the proposed simulation results is compared with a conventional simulator.