cssi/SciSciGPT-SciSciNet huggingface dataset:
Bayesian Mechanism Design

Systems wherein strategic agents compete for limited resources are ubiquitous. For example, the economy, computer networks, social networks, congestion networks, nature, and so on. Assuming the agents' preferences are drawn from a distribution, a reasonable assumption for small mechanisms in a large system, Bayesian mechanism design governs the design and analysis of these systems. This monograph surveys the classical economic theory of Bayesian mechanism design and recent advances from the perspective of algorithms and approximation. Classical economics gives simple characterizations of Bayes-Nash equilibrium and optimal mechanisms when the agents' preferences are linear and single-dimensional. The mechanisms it predicts are often complex and overly dependent on details of the model. Approximation complements this theory and suggests that simple and less-detail-dependent mechanisms can be nearly optimal. Furthermore, techniques from approximation and algorithms can describe good mechanisms beyond the single-dimensional, linear model of agent preferences. This text is an ideal reference for researchers and students working in the area as it presents over a decade of recent work on algorithmic aspects of mechanism design in the context of the classical economic theory of Bayesian mechanism design.
Long-term results of compression treatment for lymphedema.

Abstract Although numerous operations have been devised for lymphedema, most surgeons manage this vexing condition by nonsurgical means. Previous studies by us showed that high-pressure (90 to 100 torr) sequential external pneumatic compression (SEP) reduced both limb girth and volume in a lymphedematous extremity. To assess the long-term effects of a program entailing (1) SEP, (2) elastic compression stockings to maintain the post-SEP girth, and (3) daily skin care, we reviewed the long-term courses of 49 patients managed by one surgeon. Limb girths measured at nine levels on the limb were obtained serially in follow-up (mean 25 months) by an independent observer to provide an objective response to therapy. The relative reduction in lymphedematous tissue was determined by the difference between the pretreatment, postacute treatment, and long-term treatment girths at nine points in the limb. In long-term follow-up, 26 of the patients maintained a full response (reduction at >3 levels), whereas 10 maintained a partial response (reduction at ≤ 3 levels). At late follow-up, calf and ankle girths were reduced by an absolute value of 5.37 ± 1.01 and 4.63 ± 0.88 cm in the full-response group and 5.43 ± 1.58 and 3.98 ± 1.18 cm in the partial-response group over pretreatment measurements. The degree of subcutaneous fibrosis in relationship to the duration of the edema appeared to influence results greatly. The treatment of lymphedema with SEP and compression stockings is associated with long-term maintenance of reduced limb girth in 90% of patients. (J Vasc Surg 1992;16:555–64.)
Exploration of the role of the non-coding RNA SbrE in L. monocytogenes stress response

SbrE is a ncRNA in Listeria monocytogenes, reported to be up-regulated by the alternative sigma factor σB. Initial quantitative RT-PCR (qRT-PCR) experiments on parent strains and isogenic ΔsigB strains demonstrated σB-dependent expression of SbrE across the four L. monocytogenes lineages and in L. innocua. Microarray and proteomics (MDLC/MS/MS with iTRAQ labeling) experiments with the L. monocytogenes parent strain and an isogenic ΔsbrE strain identified a single gene (lmo0636) and two proteins (Lmo0637 and Lmo2094) that showed lower expression levels in the ΔsbrE strain. qRT-PCR demonstrated an increase in SbrE transcript levels in stationary phase L. monocytogenes and in bacteria exposed to oxidative stress (mean log2 transcript levels 7.68 ± 0.57 and 1.70 ± 0.71 greater than in mid-log phase cells, respectively). However, no significant differences in growth or survival between the parent strain and ΔsbrE strain were confirmed under a variety of environmental stress conditions tested. Our data suggest that σB-dependent transcription of SbrE represents a conserved mechanism that contributes, across Listeria species, to fine-tuning of gene expression under specific environmental conditions that remain to be defined.
Pharmacologic mood destabilization: case vignettes.

Bipolar disorder is an illness characterized by inherent mood instability that produces a predisposition to depressive, hypomanic, or manic episodes. This predisposition to affective episodes, rather than the episodes themselves (which can have many causes), is arguably the hallmark of bipolar disorder. Most episodes of bipolar disorder, including the first episode, are depressive. This exposes an inherent flaw in our nosological system, which requires a manic or hypomanic episode for diagnosis of bipolar disorder. Treatment of a depressive episode in undiagnosed bipolar disorder can entail the use of medications that were developed to treat a different disorder (major depressive illness) and that may have mood-destabilizing or activating properties.
Automatic segmentation of piecewise constant signal by hidden Markov models

We propose an automatic signal segmentation algorithm for piecewise constant signals, which is based on hidden Markov models (HMM). It segments the observed data without the need for training data and initial conditions. One of the problems of automatic segmentation using HMM models is the determination of their number of states. The number of states is estimated according to a maximum a posteriori (MAP) criterion. The proposed algorithm is iterative. Its initial conditions are chosen by a tree-structure technique, which is completely data driven. The segmentation is further improved by the multiscale technique. The performance is evaluated by computer simulations.
“WE ARE A FORCE TO BE RECKONED WITH”: BLACK AND LATINA WOMEN'S LEADERSHIP IN THE CONTEMPORARY U.S. LABOR MOVEMENT

In the face of growing race/gender labor market inequality, women-of-color unionists are calling for greater responsiveness of the labor movement to the needs of workers of color. This article details how women of color within the labor movement are pushing for structural change within the institution to increase the voice of women and people of color in the labor movement and explores the significant impact these women are having on the institution of labor. In noting the emergence of black and Latina female leaders, the study explores what factors propelled and continue to motivate their careers, and asks what effect, if any, their leadership has on the labor movement's agenda with respect to diversity. To address these questions, the study relies on interviews with key actors affecting institutional change: black and Latina female union leaders, survey data, resolutions, speeches, current labor force data on black and Latina workers, and data on union involvement by race and gender.
Developing Cultural Sensitivity Through Study Abroad

Study abroad experiences, as a strategy to develop cultural sensitivity, are increasingly popular in nursing education. At a college where resources for developing study abroad were limited, establishing a partnership with an organization experienced in sending medical teams abroad was a means by which a successful study abroad was integrated into a community health nursing course. This collaborative relationship provided the course faculty the opportunity to focus on development of the cultural learning, while the partnering organization coordinated trip logistics. Through the study abroad, the student goals were identified to be developing cultural sensitivity through immersion in two different cultural groups within the country. Additionally, the student’s goals were to be able to meet the community health course clinical objectives. Students’ written reflections included descriptions of how the trip was “life changing” and altered their view of the health care system, their understanding of the relati...
IMPDOS (IMPROVED DOSIMETRY AND RISK ASSESSMENT FOR PLUTONIUM-INDUCED DISEASES): INTERNAL DOSIMETRY SOFTWARE TOOLS DEVELOPED FOR THE MAYAK WORKER STUDY

A collection of software tools developed for the Mayak worker study is described. IMPDOS is software for modelling, data analysis, and activity and dose calculations using the bioassay and postmortem data from Mayak workers provided by Southern Urals Biophysics Institute. The capabilities include: parameter fitting of data for individual cases, Bayesian dose calculations using the fit results for collections of cases with extensive data as a biokinetic prior, and database storage of results for retrieval, analysis and interpretation.
Ligand Binding to Inhibitory Killer Cell Ig-Like Receptors Induce Colocalization with Src Homology Domain 2-Containing Protein Tyrosine Phosphatase 1 and Interruption of Ongoing Activation Signals

Interaction of NK cells with target cells leads to formation of an immunological synapse (IS) at the contact site. NK cells form two distinctly different IS, the inhibitory NK cell IS (NKIS) and the cytolytic NKIS. Cognate ligand binding is sufficient to induce clustering of inhibitory killer cell Ig-like receptors (KIR) and phosphorylation of both the receptor and the phosphatase Src homology domain 2-containing protein tyrosine phosphatase 1 (SHP-1). Recruitment and activation of SHP-1 by a signaling competent inhibitory receptor are essential early events for NK cell inhibition. We have in the present study used three-dimensional immunofluorescence microscopy to analyze distribution of inhibitory KIR, SHP-1, LFA-1, and lipid rafts within the NKIS during cytolytic and noncytolytic interactions. NK clones retrovirally transduced with the inhibitory KIR2DL3 gene fused to GFP demonstrate colocalization of KIR2DL3 with SHP-1 in the center of early inhibitory NKIS. Ligand binding translocates the receptor to the center of the IS where activation signals are accumulating and provides a docking site for SHP-1. SHP-1 and rafts cluster in the center of early inhibitory NKIS and late cytolytic NKIS, and whereas rafts continue to increase in size in cytolytic conjugates, they are rapidly dissolved in inhibitory conjugates. Furthermore, rafts are essential only for cytolytic, not for inhibitory, outcome. These results indicate that the outcome of NK cell-target cell interactions is dictated by early quantitative differences in cumulative activating and inhibitory signals.
Algebraic stabilization of explicit numerical integration for extremely stiff reaction networks

In contrast to the prevailing view in the literature, it is shown that even extremely stiff sets of ordinary differential equations may be solved efficiently by explicit methods if limiting algebraic solutions are used to stabilize the numerical integration. The stabilizing algebra differs essentially for systems well-removed from equilibrium and those near equilibrium. Explicit asymptotic and quasi-steady-state methods that are appropriate when the system is only weakly equilibrated are examined first. These methods are then extended to the case of close approach to equilibrium through a new implementation of partial equilibrium approximations. Using stringent tests with astrophysical thermonuclear networks, evidence is provided that these methods can deal with the stiffest networks, even in the approach to equilibrium, with accuracy and integration timestepping comparable to that of implicit methods. Because explicit methods can execute a timestep faster and scale more favorably with network size than implicit algorithms, our results suggest that algebraically-stabilized explicit methods might enable integration of larger reaction networks coupled to fluid dynamics than has been feasible previously for a variety of disciplines.
Dopamine System Dysregulation and the Pathophysiology of Schizophrenia: Insights From the Methylazoxymethanol Acetate Model

Data from numerous studies have strongly implicated the dopamine (DA) system in the pathophysiology of schizophrenia. The data are particularly robust for the positive or the psychotic symptoms of schizophrenia, which can be mimicked by DA agonists and attenuated by D2 antagonist antipsychotic drugs. Nonetheless, there is little evidence for a major dysfunction within the DA system itself; instead, current research has focused on a disruption in the regulation of the DA system. One region in particular that has shown correlations with DA dysfunction is the limbic portion of the hippocampus, which comprises the ventralmost segment in rats analogous to the anterior aspect in humans. Thus, studies in patients with schizophrenia have shown hyperactivity in the hippocampus that correlates with psychosis as well as a loss of parvalbumin gamma-aminobutyric acid–ergic (GABAergic) inhibitory neurons (1). To examine the pathophysiology of schizophrenia, we employed a developmental disruption model that uses the mitotoxin methylazoxymethanol acetate (MAM). This drug is administered to pregnant rats at gestational day 17 to mimic the second trimester in humans, during which insults have a higher impact on inducing schizophrenia births. The offspring are then examined peripubertally for developmental changes and as adults to test for dysfunctions that correspond to schizophrenia in humans. The adult offspring of MAM-treated rats display many characteristics consistent with schizophrenia (2,3), including neuroanatomic changes (thinning of limbic cortices with an increase in cell packing density, loss of parvalbumin interneurons), behavioral deficits (prepulse inhibition of startle, reversal learning, extradimensional shift, latent inhibition, social interaction), and pharmacologic responses (hyperresponsivity to phencyclidine, increased locomotion to amphetamine). Furthermore, as in humans, there is hyperactivity in the ventral hippocampus (vHipp) and a disruption of rhythmic activity including delta and gamma rhythms (3). There was also a substantial increase in DA neuron population activity. In anesthetized and awake rats, DA neurons exhibit several activity states that are regulated by different systems and differentially affect system function (Figure 1). In the basal state, DA neurons discharge in a slow, irregular tonic firing pattern. However, if the organism is exposed to a behaviorally salient stimulus, DA neurons transition to a rapid burst-firing mode. Thus, burst firing is considered to be the behaviorally relevant phasic response to stimuli. Burst firing is driven by a glutamatergic input arising primarily from the brainstem pedunculopontine tegmentum (PPTg) acting on N-methyl-D-aspartate
Refuse Disposal and Military Behavior at Fort Meigs, a War of 1812 Military Site in Northern Ohio: An Intrasite Analysis

Schiffer (1972, 1976) and South (1977) have discussed the interpretative implications of various types of cultural refuse which are created during the occupation and abandonment of a site. Excavati...
Economic Considerations and Reagan's New Federalism Swap Proposals

Upon coming to office, President Ronald Reagan proposed a number of programs collectively referred to as the New Federalism. These programs were designed to alleviate some of the problems which the president saw as plaguing the intergovernmental system and to accomplish Reagan's goal of decentralizing authority. One of the most highly publicized and debatedindeed, probably the most controversial-aspect of the President's New Federalism package was the "Big Swap" plan. Both versions of this plan, however, were bad deals for the states and their communities, and it would appear that several interrelated economic concerns played a role in the opposition of many state and local officials to these proposals. To demonstrate just how bad these proposals were, the article documents the effect that inflation and recession had had on the fiscal health ofstate and local governments, and the projected impact that these plans would have had on state and local revenue and tax systems.
Carbohydrate balance in competitive runners during successive days of intense training

This study was designed to investigate the effect of intense training on muscle glycogen stores under conditions of controlled carbohydrate (CHO) intake. On two separate occasions, 10 highly trained distance runners increased their training load for 5 days (20 km/day, approximately 80% maximal O2 consumption) while eating a diet whose carbohydrate composition either equaled (EQ-CHO) or contained approximately 50% of the runner's estimated daily expenditure (LO-CHO). Total muscle glycogen levels were lower after the LO-CHO regimen. Photometric analysis of the glycogen content in individual fibers revealed that 27% type I and 17% type II fibers had optical densities less than 0.2 U after the LO-CHO regimen, whereas 7% type I and 0% type II were similarly depleted after the EQ-CHO diet. A linear relationship was observed between the histochemical and direct chemical analysis of muscle glycogen content. Treadmill O2 uptake measured at 185 and 238 m/min was higher during the LO-CHO than the EQ-CHO regimen. Ratings of perceived exertion were higher during the 238-m/min run for the LO-CHO regimen. After 3 days of rest, running economy and perception of effort returned to pretraining levels and muscle glycogen stores were approximately 85% of the pretraining values. Thus when CHO intake was only approximately 50% of the energy requirements there was a marked depletion of muscle glycogen stores, particularly in type I fibers, and a concomitant decrease in running economy and increased perception of fatigue.(ABSTRACT TRUNCATED AT 250 WORDS)
Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia.

Introduction:Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia.Methods:A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria.Results:Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group (P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during ...
28 Pilot study of a novel partnership for installing smoke alarms development of an injury prevention smart phone application

Objective Families with young children are at increased risk for home fires. Fire departments have used a number of approaches to increase the uptake of smoke alarms in high-risk homes with mixed success. This presentation will describe a pilot study that partnered a nurse home visiting program for high-risk, low-income families with a local fire department in Phoenix, AZ to instal smoke alarms. Methods During a regularly scheduled home visit, nurses with the Nurse-Family Partnership (NFP) at the Maricopa County Department of Public Health informed their clients about an opportunity to have smoke alarms installed in their home. Nurses sent a referral to the Phoenix Fire Department (PFD) for a free smoke alarm installation for free. PFD volunteers accompanied nurses during a following appointment to instal smoke alarms and to provide safety education. Mixed Methods were used for the evaluation, including a 3-month follow-up survey of knowledge, observation of smoke alarms, and in-depth interviews with key informants from NFP and PFD. Results 58 clients enrolled in the pilot study. To date, 41 smoke alarm installation visits and 33 follow-up surveys have been completed. Before the program, 56% (n = 23/41) of homes had no working smoke alarm. PFD installed 54 smoke alarms into 41 homes; every home had at least one smoke alarm by the end of the home visit. At follow-up, all homes maintained at least one smoke alarm. Clients increased knowledge scores by 30%. Interviewees from both NFP and PFD spoke highly of the program, found it to be consistent with their organisations’ missions, and would like it to continue. Final analyses of the full sample of follow-ups and of the qualitative interviews will be presented. Conclusion Pairing home visiting nurses with local fire departments can be a successful approach to increasing the number of high-risk homes with smoke alarms.
Risk, Liability, and Economic Issues with Long-Term CO2 Storage—A Review

Given a scarcity of commercial-scale carbon capture and storage (CCS) projects, there is a great deal of uncertainty in the risks, liability, and their cost implications for geologic storage of carbon dioxide (CO2). The probabilities of leakage and the risk of induced seismicity could be remote, but the volume of geologic CO2 storage (GCS) projected to be necessary to have a significant impact on increasing CO2 concentrations in the atmosphere is far greater than the volumes of CO2 injected thus far. National-level estimates of the technically accessible CO2 storage resource (TASR) onshore in the United States are on the order of thousands of gigatons of CO2 storage capacity, but such estimates generally assume away any pressure management issues. Pressure buildup in the storage reservoir is expected to be a primary source of risk associated with CO2 storage, and only a fraction of the theoretical TASR could be available unless the storage operator extracts the saltwater brines or other formation fluids that are already present in the geologic pore space targeted for CO2 storage. Institutions, legislation, and processes to manage the risk, liability, and economic issues with CO2 storage in the United States are beginning to emerge, but will need to progress further in order to allow a commercial-scale CO2 storage industry to develop in the country. The combination of economic tradeoffs, property rights definitions, liability issues, and risk considerations suggests that CO2 storage offshore of the United States may be more feasible than onshore, especially during the current (early) stages of industry development.
Abstract 3801: Role of microRNAs in resveratrol induced breast cancer cell death

Purpose: Breast cancer is the second most common type of cancer in women and several drugs are currently being used against this disease. In spite of the availability of promising chemotherapeutic drugs, it is often observed that tumor cells develop resistance to these drugs rendering them ineffective after prolonged use. Identifying alternative and effective treatment options is thus crucial to improve the life expectancy of breast cancer patients. Resveratrol, a dietary agent is being considered as a potential drug candidate due to its pro-apoptotic properties against cancer cells. Additionally, recently microRNAs (miRNAs), which are small non-coding single stranded RNA molecules, are gaining ground as novel cancer therapeutics due to their capability to alter cell functions including apoptosis. The current study aims to elucidate resveratrol-induced apoptosis in breast cancer cells and to investigate if the effects are mediated via tumor-suppressor miRNAs that negatively regulates anti-apoptotic proteins responsible for development and progression of breast cancer. Objective: The overall objective of this study is to elucidate whether resveratrol-induced apoptosis in breast cancer cells (MCF-7 and MDA-MB-231) is mediated via tumor-suppressor miRNAs. Experimental setup: Cell viability was tested using the cell titer glo assay followed by evaluation of apoptosis induction by Hoechst staining. Western blotting was employed to confirm caspase activation. miRNA expression changes in cells treated with resveratrol was confirmed using a miScript miRNA profiling kit. The role of selected miRNAs was further investigated by transfection experiments using miRNA mimic and inhibitor and Western blotting. Results: Resveratrol induced a dose dependent effect on cell viability and induced apoptosis in treated breast cancer cells. MiRNA data analysis revealed several miRNAs to be regulated in breast cancer cells. MiRNAs hsa-miR-542-3p and hsa-miR-122-5p were the most down-regulated and up-regulated in MCF-7 and MDA-MB-231 cells respectively. Transfection experiments confirmed that the observed effects of resveratrol might be mediated by tumor suppressive miRNAs identified. Conclusion: Resveratrol induces apoptosis in breast cancer cells and this effect is mediated through regulation of key tumor suppressive miRNAs. The conclusions drawn from the study highlights the importance of resveratrol in conjunction with miRNAs as a good therapeutic alternative to induce tumor suppression. Citation Format: Rajkumar Venkatadri, Clayton Wright, Vivek Kaushik, Yogesh Kulkarni, Juan Sebastian Yakisich, Anand Krishnan V. Iyer, Neelam Azad. Role of microRNAs in resveratrol induced breast cancer cell death. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3801. doi:10.1158/1538-7445.AM2015-3801
Rethinking Gaia: Stengers, Latour, Margulis:

At its inception innocent of philosophical or metaphysical designs, the Gaia hypothesis of James Lovelock and Lynn Margulis was soon liberated from the precincts of scientific cultivation to enter ...
Precipitation timing and soil heterogeneity regulate the growth and seed production of the invasive grass red brome

Invasions of exotic grasses are increasing the spatial extent and temporal frequency of wildfire. Mitigation efforts to prevent wildfire depend on understanding the biophysical agents that drive spatial and temporal distributions of exotic grasses. We examined the growth and reproduction of the exotic grass red brome (Bromus rubens L.) in response to precipitation timing in the fall period, fertile-island topography, and fire history in the Mojave Desert. Tiller density, shoot height, shoot biomass, and seed production were measured. Early precipitation timing (mid-October versus late November) triggered early germination and led to greater red brome density (1.5-fold), shoot height (1.9-fold), shoot biomass (6.8-fold) and seed production (3.9-fold). Soil cores collected from beneath shrubs (fertile-islands) versus shrub inter-spaces also produced red brome with enhanced shoot height (1.5-fold), and seed production (1.9-fold). The legacy effect of wildfires on soils (10 years after the fires) had no significant effect on the growth or reproduction of red brome. Soils beneath shrubs had significantly less gravel and higher mineral nitrogen (N) concentrations than soils from shrub inter-spaces. Soil gravel % was negatively correlated with red brome density, height, biomass and seed production while mineral N tended to have weak positively correlations with red brome density and seed production. These results suggest that the growth and reproduction of red brome is influenced by fall precipitation timing and soil characteristics. Management planning for fire intervention should consider fall precipitation patterns, soil characteristics and shrub topography as important determinants of red brome growth and fire potential.
An architecture for active and passive knowledge management systems

Knowledge management systems (KMSs) offer an environment for organizations to manage their information assets (e.g., documents, databases, etc.). Existing KMSs passively employ knowledge by querying a database, showing a document, displaying a Web page, etc. KMSs can be extended to incorporate active components, such as expert systems and business rule systems. Currently, business rules reside in application code and database triggers. A KMS with an embedded expert system using business rules from the organization, combined with the connectivity of a server in a client/server architecture, provides an excellent environment for automating business activities at both local and enterprise levels. The segregation of business rules into the knowledge tier (KT) should lower the cost of development and maintenance, increase accuracy and ensure corporation-wide consistency. In addition, knowledge verification tools are now being developed that will allow the computerization of less structured tasks, enabling another round of increased efficiency through computerization.
Phase II Study of Low-Dose Pomalidomide in Patients with Myelofibrosis and Significant Anemia (hemoglobin <10g/dL)

Abstract 1757 Introduction: Pomalidomide (POM) is a new investigational immunomodulatory drug (iMID) that has shown promise in the treatment of patients with myelofibrosis (MF) by improving their hemoglobin and eliminating a need for blood transfusions. This significant clinical activity was seen in up to 36% of patients (according to International Working Group for Myelofibrosis Research and Therapy response criteria) when POM was used at the low (0.5mg) continuous daily oral dose, with or without concomitant use of prednisone. Based on these results, Phase III blinded, placebo-controlled study is underway globally, for possible approval of POM, as a single agent, for MF patients with significant anemia and transfusion dependency. However, the response criteria utilized in the Phase III study is more robust and clinically meaningful transfusion dependency/independency criteria, so called “Gale criteria” (Gale et al. Leuk Res. 2011 Jan;35(1):8-11.). Patients are also assessed for an increase in hemoglobin of 2g/dL from baseline, for a duration of at least 8 weeks. Our single-center Phase II open-label study examined the efficacy of a single agent, low dose (0.5mg/day) POM in improving hemoglobin and reducing/eliminating transfusion requirements (based on Gale criteria) specifically in patients with MF and significant anemia (hemoglobin Patients & Results: 28 patients, 14 male and 14 female, were enrolled in the study: 10 (35%) had post essential thrombocythemia MF, 17 (60%) had primary MF and 1 (3%) post polycythemia vera MF. Median age was 65 years (range 38–84) and 12 (42%) were previously treated (none with thalidomide or lenalidomide). Twelve (42%) had splenomegaly; 2 had prior splenectomy. Eighteen had diploid karyotype and 17 had JAK2V617F mutation. All patients had to have hemoglobin After median follow up of more than a year, 11 (40%) patients were still on therapy. Median number of cycles given to patients was 11. Twelve patients were taken off the study for no response, 2 transformed to acute leukemia, 3 died from unrelated causes. The therapy was well tolerated; there were no instances of Grade 3/4 neutropenia or thrombocytopenia or non-hematologic toxicity. By Gale criteria 2 of 8 transfusion dependent patients achieved transfusion independence; both were JAK2 mutation negative and did not have splenomegaly. No patient experienced sustained increase in hemoglobin of 2g/dL from baseline. Updated results will be presented at the meeting. Conclusion: POM administered to patients with MF with significant anemia at an oral dose of 0.5 milligrams daily has a good safety profile and modest clinical activity. Disclosures: Verstovsek: Celgene: Research Funding.
Optofluidic droplet lasers on polycarbonate chip

We demonstrated optofluidic droplet lasers using micro-nozzle structures. Easy fabrication, reproducible generation and manipulation of microdroplets provide a promising platform to achieve integrated laser system on chip.
Design of a Bluetooth-enabled low energy electrocardiogram monitoring system

This paper describes a system design of a Bluetooth-enabled low energy (BlE) electrocardiogram (ECG) monitoring system, which was developed during undergraduate computer engineering capstone courses spanning over two semesters. The BLE ECG monitoring system integrates Bluetooth wireless communication feature into an Android application with an electronic circuit detecting ECG signals. The portable system collects vital signals from an ECG detection circuit and wirelessly transfers the data to an Android application running on a smartphone. This paper presents the system design concepts, development of the prototype, system testing, and other technical aspects of the system design throughout the capstone project.
HIV/AIDS Global Epidemic

The HIV/AIDS epidemic is now in its third decade since the discovery of the virus responsible for the disease in 1981. While the first cases of AIDS were first recognized in young men who have sex with men in the United States and Europe in the 1980s, it soon became clear that the virus could be spread through contaminated blood products and heterosexual sex. At the time of its discovery, acquired immunodeficiency syndrome (AIDS) was a new disease with high mortality, and the discovery of a new human virus as its cause in 1983 created new challenges for prevention, treatment, and vaccine efforts, many of which remain unmet today. Human immunodeficiency virus type 1 (HIV-1), as the causative agent of AIDS, has been the subject of intense research over the past three decades, in an effort to understand the biological properties of this new virus, its relatedness to other known retroviruses, characterize its epidemiology, and discover drugs and vaccines to control the epidemic.
Advanced Electron Microscopy for Complex Nanotechnology

From this point forward, the focus of this thesis will be on electron microscopy. In this chapter, I examine complex nanostructures with applications in nanotechnology that are highly dependent on morphological, structural, compositional, and optical effects. The electron microscope is the ideal tool for this kind of analysis, and I show here a wide range of different STEM techniques that can be used to characterize complex nanotechnology with nanoscale precision.
TGF-β Signaling Pathway and MicroRNAs in Cardiovascular Disease

Transforming growth factor-β (TGF-β) signaling has long been known to influence development and function of different organs, including the cardiovascular system. In addition to the canonical pathways of Smad-dependent transcriptional regulation of protein-coding genes, recent studies have shown TGF-β influence on microRNA (miRNA) expression to play a critical role in TGF-β-dependent biological effects. A number of miRNAs, such as miR-143, miR-145, miR-21, miR-155, and miR-26a, are identified as critical downstream mediators of the TGF-β-family signaling. Deregulation of miRNA expression can result in various developmental defects and diseases. In this review, we summarize the latest view of the effects of miRNAs associated with TGF-β-family signaling on the cardiovascular system.
Software for Random Number Generation

Random number generators are widely available in a variety of software packages. As Park and Miller (1988) state, however, “good ones are hard to find”.
Interpreting the ASTM “Content Standard for Digital Geospatial Metadata”

ASTM and the Federal Geographic Data Committee have developed a content standard for spatial metadata to facilitate documentation, discovery, and retrieval of digital spatial data using vendor-independent terminology. Spatial metadata elements are identifiable quality and content characteristics of a data set that can be tied to a geographic location or area. Several Office of Management and Budget Circulars and initiatives have been issued that specify improved cataloguing of and accessibility to federal data holdings. An Executive Order further requires the use of the metadata content standard to document digital spatial data sets. Collection and reporting of spatial metadata for field investigations performed for the federal government is an anticipated requirement. This paper provides an overview of the draft spatial metadata content standard and a description of how the standard could be applied to investigations collecting spatially-referenced field data.
Numbers and Cultures

Marxists have been prominent in the historical development of the sociology of mathematics. They have not, however, been completely successful in sustaining a consistent materialist argument. The reason for this is that they have been influenced by the pervasive notion that the more abstract forms of mathematics approximate (if they do not fully represent) universal and eternal relationships in the “real world’. But Spengler forces us to question the limitations of Marxism because his analysis of mathematics appears to carry the Marxist sociology of mathematics to its extreme conclusion. It is Spengler, not the Marxists, who stands diametrically opposed to Mannheim.
Do Symptoms of Depression Interact with Substance Use to Affect HIV Continuum of Care Outcomes

Few studies examine how depression and substance use interact to affect HIV control. In 14,380 persons with HIV (PWH), we used logistic regression and generalized estimating equations to evaluate how symptoms of depression interact with alcohol, cocaine, opioid, and methamphetamine use to affect subsequent retention in care, maintaining an active prescription for ART, and consistent virologic suppression. Among PWH with no or mild depressive symptoms, heavy alcohol use had no association with virologic suppression (OR 1.00 [0.95–1.06]); among those with moderate or severe symptoms, it was associated with reduced viral suppression (OR 0.80 [0.74–0.87]). We found no interactions with heavy alcohol use on retention in care or maintaining ART prescription or with other substances for any outcome. These results highlight the importance of treating moderate or severe depression in PWH, especially with comorbid heavy alcohol use, and support multifaceted interventions targeting alcohol use and depression.
Relationship between caffeine intake and autosomal dominant polycystic kidney disease progression: a retrospective analysis using the CRISP cohort.

Caffeine has been proposed, based on in vitro cultured cell studies, to accelerate progression of autosomal dominant polycystic kidney disease (ADPKD) by increasing kidney size. Since ADPKD patients are advised to minimize caffeine intake, we investigated the effect of caffeine on disease progression in the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP), a prospective, observational cohort study. Our study included 239 patients (mean age = 32.3 ± 8.9 ys; 188 caffeine consumers) with a median follow-up time of 12.5 years. Caffeine intake reported at baseline was dichotomized (any vs. none). Linear mixed models, unadjusted and adjusted for age, race, sex, BMI, smoking, hypertension, genetics and time, were used to model height-adjusted total kidney volume (htTKV) and iothalamate clearance (mGFR). Cox proportional hazards models and Kaplan-Meier plots examined the effect of caffeine on time to ESRD or death. Caffeine-by-time was statistically significant when modeling ln(htTKV) in unadjusted and adjusted models (p 0.05). Moreover the results were similar when outcomes were modeled as a function of caffeine dose. We conclude that caffeine does not have a significant detrimental effect on disease progression in ADPKD.
Discovery of Small-Molecule Inhibitors Targeting the E3 Ubiquitin Ligase Activity of the Herpes Simplex Virus 1 ICP0 Protein Using an In Vitro High-Throughput Screening Assay

Herpes simplex virus 1 (HSV-1) has infected more than 80% of the population. Reactivation of the virus causes diseases ranging in severity from benign cold sores to fatal encephalitis. Current treatments involve viral DNA replication inhibitors, but the emergence of drug-resistant mutants is observed frequently, highlighting the need for novel antiviral therapies. Infected cell protein 0 (ICP0) of HSV-1 is encoded by an immediate early gene and plays a fundamental role during infection, because it enables viral gene expression and blocks antiviral responses. One mechanism by which ICP0 functions is through an E3 ubiquitin ligase activity that induces the degradation of targeted proteins. A ΔICP0 virus or mutants with deficiencies in E3 ligase activity cannot counteract beta interferon (IFN-β)-induced restriction of viral infection, are highly immunogenic, are avirulent, and fail to spread. Thus, small molecules interfering with essential and conserved ICP0 functions are expected to compromise HSV-1 infection. We have developed a high-throughput screening assay, based on the autoubiquitination properties of ICP0, to identify small-molecule inhibitors of ICP0 E3 ubiquitin ligase activity. Through a pilot screening procedure, we identified nine compounds that displayed dose-dependent inhibitory effects on ICP0 but not on Mdm2, a control E3 ubiquitin ligase. Following validation, one compound displayed ICP0-dependent inhibition of HSV-1 infection. This compound appeared to bind ICP0 in a cellular thermal shift assay, it blocked ICP0 self-elimination, and it blocked wild-type but not ICP0-null virus gene expression. This scaffold displays specificity and could be used to develop optimized ICP0 E3 ligase inhibitors.IMPORTANCE Since acyclovir and its derivatives were launched for herpesviruses control almost four decades ago, the search for novel antivirals has waned. However, as human life expectancy has increased, so has the number of immunocompromised individuals who receive prolonged treatment for HSV recurrences. This has led to an increase in unresponsive patients due to acquired viral drug resistance. Thus, novel treatments need to be explored. Here we explored the HSV-1 ICP0 E3 ligase as a potential antiviral target because (i) ICP0 is expressed before virus replication, (ii) it is essential for infection in vivo, (iii) it is required for efficient reactivation of the virus from latency, (iv) inhibition of its E3 ligase activity would sustain host immune responses, and (v) it is shared by other herpesviruses. We report a compound that inhibits HSV-1 infection in an ICP0-dependent manner by inhibiting ICP0 E3 ligase activity.
Intelligence mindset shapes neural learning signals and memory

Intelligence mindset, which denotes individual beliefs about whether intelligence is fixed versus malleable, shapes academic success, but the neural mechanisms underlying mindset-related differences in learning are unknown. Here, we probe the effects of individual differences in mindset on neural responses to negative feedback after a competence threat manipulation. We hypothesized that when their competence was threatened, participants with fixed mindsets would interpret further negative feedback as punishing. After receiving either no score or a competence-threatening IQ score, participants performed a learning task with feedback that emphasized either the evaluative or informational weight of negative feedback. Participants who experienced the competence threat had the strongest predictive relationships between mindset, performance, and caudate activation. The competence threat may have compounded the subjective punishment of negative feedback for fixed mindsets relative to growth mindsets, causing poorer learning from negative feedback in the evaluative context and inflexible striatal responses to negative feedback across feedback contexts.
Complex History of Codiversification and Host Switching of a Newfound Soricid-Borne Orthohantavirus in North America.

Orthohantaviruses are tightly linked to the ecology and evolutionary history of their mammalian hosts. We hypothesized that in regions with dramatic climate shifts throughout the Quaternary, orthohantavirus diversity and evolution are shaped by dynamic host responses to environmental change through processes such as host isolation, host switching, and reassortment. Jemez Springs virus (JMSV), an orthohantavirus harbored by the dusky shrew (Sorex monticola) and five close relatives distributed widely in western North America, was used to test this hypothesis. Total RNAs, extracted from liver or lung tissue from 164 shrews collected from western North America during 1983–2007, were analyzed for orthohantavirus RNA by reverse transcription polymerase chain reaction (RT-PCR). Phylogenies inferred from the L-, M-, and S-segment sequences of 30 JMSV strains were compared with host mitochondrial cytochrome b. Viral clades largely corresponded to host clades, which were primarily structured by geography and were consistent with hypothesized post-glacial expansion. Despite an overall congruence between host and viral gene phylogenies at deeper scales, phylogenetic signals were recovered that also suggested a complex pattern of host switching and at least one reassortment event in the evolutionary history of JMSV. A fundamental understanding of how orthohantaviruses respond to periods of host population expansion, contraction, and secondary host contact is the key to establishing a framework for both more comprehensive understanding of orthohantavirus evolutionary dynamics and broader insights into host–pathogen systems.
On the Correlation between Total Condensate and Moist Heating in Tropical Cyclones and Applications for Diagnosing Intensity

AbstractWhile the transfer of moist enthalpy from the ocean to the atmosphere is the fundamental energy source for tropical cyclones, the release of latent heat in moist convection is the mechanism...
Neurofilament light is a treatment-responsive biomarker in CLN2 disease.

OBJECTIVE Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare, progressive, fatal neurodegenerative pediatric disorder resulting from deficiencies of the lysosomal enzyme tripeptidyl peptidase 1 that are caused by mutations in TPP1. Identifying biomarkers of CLN2 disease progression will be important in assessing the efficacy of therapeutic interventions for this disorder. Neurofilament light is an intrinsic component of healthy neurons; elevated circulating extracellular neurofilament light is a biomarker of neuropathology in several adult-onset neurological diseases. Our objective was to assess whether circulating neurofilament light is a biomarker that is responsive to enzyme replacement therapy (ERT) in CLN2 disease. METHODS Using an ultrasensitive immunoassay, we assessed plasma neurofilament light changes during disease progression in a canine model of CLN2 disease and in ERT clinical trial CLN2 disease patients. RESULTS In tripeptidyl peptidase 1 (TPP1)-null dogs (N = 11), but not in control dogs [N = 6 (TPP1+/- ) and N = 27 (WT)], neurofilament light levels increased more than tenfold above initial low baseline levels during disease progression. Before treatment in 21 human subjects with CLN2 disease (age range: 1.72-6.85 years), neurofilament light levels were 48-fold higher (P < 0.001) than in 7 pediatric controls (age range: 8-11 years). Pretreatment neurofilament light did not significantly correlate with disease severity or age. In CLN2 disease subjects receiving ERT, neurofilament light levels decreased by 50% each year over more than 3 years of treatment. INTERPRETATION Our data indicate that circulating neurofilament light is a treatment-responsive biomarker in CLN2 disease and could contribute to understanding of the pathophysiology of this devastating pediatric disorder.