cssi/SciSciGPT-SciSciNet huggingface dataset:
Experimental observations of seed growth and accompanying pedestal contamination in a self-seeded, soft x-ray free-electron laser

Measurements of the soft x-ray, self-seeding spectrum at the Linac Coherent Light Source (LCLS) free-electron laser generally display a pedestal-like distribution around the central seeded wavelength. This pedestal limits the spectral purity and can negatively affect some user applications not employing a post-undulator monochromator. In this paper, we investigate the detailed experimental characteristics of both the amplified seed and its accompanying pedestal using data from a number of separate LCLS shifts over the 2015-2018 time period. We find that the amplified seed shows excellent wavelength stability and an exponential growth rate whose dependence upon energy detuning is consistent with theory. The pedestal's spectral distribution and integrated strength vary strongly shot by shot, independent of electron beam energy jitter. Its shot-averaged strength relative to that of the seed grows at least linearly with $z$ and can approach values of 15% or more. The pedestal is comprised of two separate components: (1) normal self-amplified spontaneous emission (SASE) whose total strength is nominally insensitive to energy detuning and laser heater (LH) strength; (2) sideband-like emission whose strength positively correlates with that of the amplified seed and negatively with energy detuning and LH strength. We believe this latter, non-SASE component arises from comparatively long wavelength (i.e., $\ensuremath{\lambda}\ensuremath{\sim}0.3--3\text{ }\text{ }\ensuremath{\mu}\mathrm{m}$) amplitude and phase modulations of the main seeded radiation line. Its shot to shot variability and LH sensitivity suggests an origin connected to growth of the longitudinal microbunching instability on the electron beam.
Understanding Ion Mobility in P2VP/NMP⁺I– Polymer Electrolytes: A Combined Simulation and Experimental Study

There is considerable interest in understanding ion transport in charged polymeric materials for applications in energy storage. In this work, all-atom molecular dynamics simulations and experiment...
Reactive cavitation erosion as a technique for production of functionalized copper hydroxychloride nanomaterials

The production of functionalized clinoatacamite (Cu2(OH)3Cl) nanoparticles from Reactive Cavitation Erosion (RCE) of copper in 1 M aqueous guanidine hydrochloride (GHCl) solution was investigated for applications as potential quantum magnet materials. As-synthesized nanomaterial was characterized by Diffuse-Reflectance Infrared Fourier-Transform Spectroscopy (DRIFTS), XRD, and TEM. These analyses were compared to nanoparticles produced from RCE of Cu in KCl and RCE of Cu in GHCl in oxygen-depleted (Ar) and oxygen-rich (compressed air, CA) solutions to identify possible reaction pathways.
Enhancing the Injectability of High Concentration Drug Formulations Using Core Annular Flows

Highly concentrated biological drug formulations would offer tremendous benefits to global health, yet they cannot be manually injected using commercial syringes and needles due to their high viscosities. Current approaches to address this problem face several challenges such as crosscontamination, high cost, needle clogging, and protein inactivation. This work reports a simple method to enhance formulation injectability using a core annular flow, where the transport of highly viscous fluids through a needle is enabled by coaxial lubrication by a less viscous fluid. A phase diagram to ensure optimally lubricated flow while minimizing the volume fraction of lubricant injected is established. The technique presented here allows for up to a 7x reduction in injection force for the highest viscosity ratio tested. The role of buoyancy-driven eccentricity in governing nominal pressure reduction is also examined. Finally, the findings are implemented into the development of a double barreled syringe that significantly expands the range of injectable concentrations of several biologic formulations.
Epigenomic differences in the human and chimpanzee genomes are associated with structural variation.

Structural variation (SV), including insertions and deletions (indels), is a primary mechanism of genome evolution. However, the mechanism by which SV contributes to epigenome evolution is poorly understood. In this study, we characterized the association between lineage-specific indels and epigenome differences between human and chimpanzee to investigate how SVs might have shaped the epigenetic landscape. By intersecting medium-to-large human-chimpanzee indels (20bp-50kb) with putative promoters and enhancers in cranial neural crest cells (CNCC) and repressed regions in induced pluripotent cells (iPSC), we found that ~12% indels overlap putative regulatory and repressed regions (RRRs), and 15% of these indels are associated with lineage-biased RRRs. Indel-associated putative enhancer and repressive regions are ~1.3 and ~3 times as likely to be lineage-biased, respectively, as those not associated with indels. We found a 2-fold enrichment of medium-sized indels (20bp to 50bp) in CpG island (CGI)-containing promoters than expected by chance. Lastly, from human-specific transposable element insertions, we identified putative regulatory elements, including NR2F1-bound putative CNCC enhancers derived from SVAs and putative iPSC promoters derived from LTR5s. Our results demonstrate that different types of indels are associated with specific epigenomic diversity between human and chimpanzee.
Bendamustine and Bortezomib-Containing Regimens Produce Higher Response Rates and More Durable Responses Versus Cyclophosphamide-Based Therapy in Frontline Waldenstrom Macroglobulinemia

Background: Waldenstrom macroglobulinemia (WM) is an incurable IgM-secreting lymphoplasmacytic lymphoma. Primary therapy for symptomatic WM patients often consists of combination therapy with an alkylating agent or proteasome inhibitor with rituximab. However, randomized studies comparing these treatment regimens are lacking in WM patients. Methods: We retrospectively searched our database for WM patients who received primary therapy with bendamustine-rituximab (Benda-R), bortezomib-dexamethasone-rituximab (BDR), or cyclophosphamide-dexamethasone-rituximab (CDR) between 2005 and 2016. Pertinent clinical data were collected. Response was assessed based on current criteria. Univariate and multivariate regression models were fitted to evaluate the association between clinical variables and response. Time to events was estimated using the Kaplan-Meier method. The Cox regression method was used to fit univariate and multivariate models for progression-free (PFS) and overall survival (OS). P Results: 182 patients with WM were identified who received frontline therapy with Benda-R (n=57), BDR (n=88), and CDR (n=37). No differences in sex, hemoglobin level, platelet count, B2M, bone marrow involvement, IPSSWM, and MYD88 and CXCR4 mutational status were observed between treatment groups (p>0.05 for all comparisons). Patients treated with BDR were more likely 4,000 mg/dl, and receive treatment for symptomatic hyperviscosity versus patients treated with Benda-R and CDR. Patients with extramedullary disease and peripheral neuropathy were more likely to be treated with Benda-R and CDR, respectively (p 4,000 mg/dl had lower odds of major response to therapy (OR 0.3, 95% CI 0.1-0.8; p=0.02), whereas patients who received maintenance rituximab had higher odds of both a major response (OR 13.9, 95% CI 4.4-44.1; p 3 mg/l (HR 2.33, 95% CI 1.37-3.96; p=0.002) and serum IgM level >4,000 mg/dl (HR 1.85, 95% CI 1.08-3.20; p=0.02). A decreased risk of progression was associated with both Benda-R (HR 0.2, 95% CI 0.1-0.5; p Conclusions: Primary therapy with Benda-R, BDR, and CDR produces high response rates and durable PFS in patients with WM. The risk of progression is lower in patients treated with Benda-R and BDR when compared to CDR. Maintenance rituximab is associated with both major and deep responses to therapy as well as superior PFS and OS. Disclosures Castillo: Pharmacyclics: Consultancy, Research Funding; Millennium: Research Funding; Abbvie: Research Funding; Janssen: Consultancy, Research Funding. Treon: Pharmacyclics: Consultancy, Research Funding.
Consensus decision-making: performance of heuristics and mental models

Abstract Consensus decision-making, found in settings ranging from formal institutions to ad hoc groups, represents a critical component of human social interaction. In such cases, decision-makers often must agree to a course of action with awareness of others' behavior (e.g., votes) but not group members' underlying motivations and strategies. How, then, should individual agents/decision-makers balance the payoffs of available options against the time it takes to reach consensus (ranging from quick consensus to stalemate)? In the current research, a novel, repeated consensus task was played by simulated agents. These agents differed in how they a) evaluated the available options and b) anticipated the choices of fellow group members. While intuition may suggest that intractably selfish agents will outcompete those willing to compromise, the data demonstrate that socially minded agents – i.e., one type that employed a simple heuristic and two types that employed sophisticated social cognition – were the only ones to exhibit evolutionarily stable strategies. However, sophisticated cognition did not guarantee good performance, suggesting that caution is warranted in trying to “outsmart” competing agents. While these agents were restricted to simple behaviors, the approach and models described here provide a potentially useful framework for studying consensus in humans.
Extended duration venous thromboembolism prophylaxis with betrixaban for patients re-admitted with venous thromboembolism

Patients hospitalized for an acute medical illness remain at risk of developing venous thromboembolism (VTE) post-discharge. Betrixaban, an oral direct Factor Xa inhibitor, is approved for extended VTE thromboprophylaxis in acutely ill medical patients. The primary objective of this study was to evaluate patients re-admitted with VTE within 30 days of discharge to determine if they would have been eligible for extended duration VTE prophylaxis during the index admission. We used three different sets of eligibility criteria: the APEX study criteria, the Bevyxxa® (betrixaban) package insert, and Mass General Brigham HealthCare System’s Center for Drug Policy Guidelines. A secondary aim was to describe the reasons for ineligibility. Within 30 days of the index hospital admission, 226 patients were re-admitted with new VTE between January 2017 and December 2018. Of these, 134 (59%) were excluded based on pre-defined exclusion criteria. Of the remaining 92, 22 patients (23.9%) were eligible based on the APEX study criteria, 26 patients (28.2%) based on Mass General Brigham HealthCare System’s Center for Drug Policy Guidelines, and 92 patients (100%) based on the Bevyxxa® package insert. There were 22 patients (23.9%) who were eligible for VTE prophylaxis with betrixaban based on all three criteria. Appropriate betrixaban use may have prevented some of the VTE events and re-admissions that occurred within 30 days of initial hospital discharge.
Five considerations for engaging with Big Data from a rhetorical-humanistic perspective

This essay offers five conceptual entry points for engaging with Big Data from a rhetorical perspective. These five concepts—data in/as relationships, observability/action, patterns, diachronicity, and audience—serve as points of deep conceptual commonality between definitions of Big Data and principles in rhetorical studies, and are offered here as considerations for critiquing uses of Big Data from a rhetorical-humanistic perspective, as well as for guiding rhetorical work that uses Big Data.
Neuropredictome: a data-driven predictome for cognitive, psychiatric, medical, and lifestyle factors on the brain

ABSTRACT Most neuroimaging studies individually provide evidence on a narrow aspect of the human brain function, on distinct data sets that often suffer from small sample sizes. More generally, the high technical and cost demands of neuroimaging studies (combined with the statistical unreliability of neuroimaging pilot studies) may lead to observational bias, discouraging discovery of less obvious associations that nonetheless have important neurological implications. To address these problems, we built a machine-learning based classification framework, NeuroPredictome, optimized for the reliability and robustness of its associations. NeuroPredictome is grounded in a large-scale dataset, UK-Biobank (N=19,831), which includes resting and task functional MRI as well as structural T1-weighted and diffusion tensor imaging. Participants were assessed with respect to a comprehensive set of 5,034 phenotypes, including the physical and lifestyle factors most relevant to general medicine. Results generated by data-driven classifiers were then cross-validated, using deep-learning textual analyses, against 14,371 peer-reviewed research articles, providing an unbiased hypothesis-generator of linkages between diverse phenotypes and the brain. Our results show that neuroimaging reveals as many neurological links to physical and lifestyle factors as to cognitive factors, supporting a more integrative approach to medicine that considers disease interactions between multiple organs and systems.
Miniature K-Band Radar for Agricultural Remote Sensing

Remote sensing for agricultural applications employs multi-spectral data collection. While optical-wavelength normalized difference vegetation index (NDVI) is the most common, smart agriculture can benefit from the addition of longer wavelengths to the sensing techniques. A radar operating in the 12.5 cm band (23 to 25 GHz spectrum) is described. The design leverages low-cost commercial ICs and coherent calibration cancellation techniques to sense at standoff distances as short as 10 cm, while providing a small size, weight, and power (SWaP) solution suitable for a variety of platforms. Field trials are overviewed on crops ranging from soybean to grain sorghum validating the ability to measure crop height and structure with high spatial resolution.
POCUS for Nephrologists - Basic Principles and a General Approach

Point-of-care ultrasonography (POCUS) has evolved as a valuable adjunct to physical examination in the recent past and various medical specialties have embraced it. However, POCUS training and scope of practice remain relatively undefined in nephrology. The utility of diagnostic POCUS beyond kidney and vascular access is under-recognized. Assessment of fluid status is a frequent dilemma faced by nephrologists in day-to-day practice where multiorgan POCUS can enhance the sensitivity of conventional physical examination. POCUS also reduces fragmentation of care, facilitates timely diagnosis, and expedites management. Although the need for further imaging studies is obviated in selected patients, POCUS is not meant to serve as an alternative to consultative imaging. In addition, the utility of POCUS depends on the skills and experience of the operator, which in turn depend on the quality of training. In this review, we discuss the rationale behind nephrologists performing POCUS, discuss patient examples to illustrate the basic principles of focused ultrasonography, and share our experience-based opinion about developing a POCUS training program at the institutional level.
Vitamin D Status and Risk of Cystic Fibrosis-Related Diabetes: A Retrospective Single Center Cohort Study

Objective: Cystic fibrosis-related diabetes (CFRD) affects up to half of the people with cystic fibrosis (CF) by adulthood. CFRD is primarily caused by pancreatic dysfunction that leads to insufficient insulin release and/or insulin resistance. Exocrine pancreatic insufficiency in people with CF is associated with fat-soluble vitamin malabsorption, including vitamins A, D, E, and K. This study examined the relationship between vitamin D status, assessed by serum 25-hydroxyvitamin D (25(OH)D), and the development of CF-related diabetes (CFRD) in adults with CF. Methods: This was a retrospective cohort study of adults seen at a single CF center. The data were extracted from the electronic medical records and the Emory Clinical Data Warehouse, a data repository of health information from patients seen at Emory Healthcare. We collected age, race, the first recorded serum 25-hydroxyvitamin D (25(OH)D) concentration, body mass index (BMI), and onset of diabetes diagnosis. Log-rank (Mantel–Cox) tests were used to compare the relative risk of CFRD onset in the subjects with stratified vitamin D status and weight status. A sub-group analysis using chi-square tests assessed the independence between vitamin D deficiency and CFRD risk factors, including gender and CF mutation types (homozygous or heterozygous for F508del, or others). Unpaired t-tests were also used to compare the BMI values and serum 25(OH)D between the CF adults based on the CFRD development. Results: This study included 253 subjects with a mean age of 27.1 years (±9.0), a mean follow-up time period of 1917.1 (±1394.5) days, and a mean serum 25(OH)D concentration of 31.8 ng/mL (±14.0). The majority (52.6%) of the subjects developed CFRD during the study period. Vitamin D deficiency (defined as 25(OH)D < 20 ng/mL) was present in 25.3% of the subjects. Close to two thirds (64.1%) of the subjects with vitamin D deficiency developed CFRD during the study. Vitamin D deficiency increased the risk of developing CFRD (chi-square, p = 0.03) during the course of the study. The time to the onset of CFRD stratified by vitamin D status was also significant (25(OH)D < 20 ng/mL vs. 25(OH)D ≥ 20 ng/mL) (95% CI: 1.2, 2.7, p < 0.0078). Conclusion: Our findings support the hypothesis that adults with CF and vitamin D deficiency are at a higher risk of developing CFRD and are at risk for earlier CFRD onset. The maintenance of a serum 25(OH)D concentration above 20 ng/mL may decrease the risk of progression to CFRD.
High-Resolution Thermal-Wave Imaging Using the Photoinductive Effect

Photoinductive imaging is a newly devised technique for photothermal imaging based on eddy-current detection of thermal waves [1]. Thermal waves produce a localized modulation in the specimen’s electrical conductivity, which can be detected by its effect on the impedance of a nearby eddy-current coil. This photoinductive effect can be used to image surface or near-surface cracks, voids, or inclusions. The method is limited in practice to conducting specimens, but it can be used to inspect thin, nonconducting coatings on metallic substrates, as we demonstrate here. One promising feature of photoinductive imaging is its potential for high resolution, especially when compared with the resolution possible with eddy-current probes alone. The objective of the present study was to exploit the high resolution capability inherent in this technique by adapting a photoinductive sensor developed for a fiber optic probe [2] to an existing photoacoustic microscope. In this paper we explore using this technique for typical applications in nondestructive evaluation.
Expert System Verification and Validation Part I: Defining the Concepts

The goal of this paper is to distinguish between verification and validation as they relate to the total expert system evaluation process. Our thesis is that V&V are two distinct processes, which together completely encompass the needed elements of expert system evaluation. Our approach is to state and defend definitions of these terms, and then to demonstrate their application in practice. The definitions derive the meanings of the terms “verification” and “validation” from the literature and common usage. From the definitions, we demonstrate the application of V&V to a forest products facility expert system.
Specific Heat of 2nd Layer He4 Films

Today I will present some recent heat capacity results on the 2nd monolayer of He4 adsorbed on graphite. One might ask why study the 2nd layer, of what importance is it? Well, I believe that a comparison of phenomena occurring on the 2nd and 1st layers will confirm some of the interpretations of monolayer behavior and will lend evidence in those regimes where the interpretations are still in doubt. But further, the 2nd layer appears in some ways a superior system for investigation of 2-Dimensional film phenomena thus making it an interesting system in its own right.
Laser Ablation Inductively Coupled Plasma Mass Spectrometry in Forensic Science

The application of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to the elemental analysis of forensic matrices offers many advantages for solid sampling, including direct characterization of solids, the elimination of the need for chemical procedures for dissolution, minimal sample consumption, and a reduced risk of contamination from the sample preparation procedures associated with sample digestion. This article aims at summarizing the recent literature describing the use of LA-ICP-MS in the field of forensic examinations with selected applications, highlighting the forensic analyses of a variety of matrices and analytes of interest and including the advantages, limitations, and future trends in this field. A critical evaluation of the parameters of forensic interest is discussed in detail, including the analytical performance of the technique, discrimination potential (when comparing samples), the impact of sample homogeneity/heterogeneity at the microscale, reproducibility, quality control, sampling strategies, sampling size requirements, availability of matrix-matched standards, data analysis, and the interpretation of results. Practical considerations such as the selection of laser wavelength and carrier gas, the use of internal standardization, and quantification strategies are discussed as also the unique requirements of quality control and method validation and acceptance in court. Keywords: elemental analysis; forensic; evidence; laser ablation; glass; paint; soils; mass spectrometry
The INQUERY Retrieval System

As larger and more heterogeneous text databases become available, information retrieval research will depend on the development of powerful, efficient and flexible retrieval engines. In this paper, we describe a retrieval system (INQUERY) that is based on a probabilistic retrieval model and provides support for sophisticated indexing and complex query formulation. INQUERY has been used successfully with databases containing nearly 400,000 documents.
Managing the risk of invasive breast cancer in women at risk for breast cancer and osteoporosis: the role of raloxifene

Raloxifene hydrochloride is a selective estrogen receptor modulator (SERM) that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting. Raloxifene significantly improves serum lipids and serum markers of cardiovascular disease risk, but it has no significant effect on the risk of primary coronary events. A meta-analysis of randomized, double-blind, placebo-controlled trials of raloxifene for osteoporosis showed the odds of fracture risk were 0.60 (95% confidence interval [CI] = 0.49–0.74) for raloxifene 60 mg/day compared with placebo. During 8 years of follow-up in an osteoporosis trial, the raloxifene group had a 76% reduction in the incidence of invasive ER-positive breast cancer compared with the placebo group. In the STAR trial, the incidence of invasive breast cancer was 4.30 per 1000 women-years with raloxifene and 4.41 per 1000 with tamoxifen; RR = 1.02; 95% CI, 0.82–1.28. The effect of raloxifene on invasive breast cancer was, therefore, equivalent to that of tamoxifen with more favorable rates of adverse effects including uterine malignancy and clotting events. Millions of postmenopausal women could derive net benefit from raloxifene through reduced rates of fracture and invasive breast cancer.
Are we making the grade? Practices and reported efficacy measures of primate conservation education programs.

Conservation education is often employed alongside primate conservation efforts with the aim of changing knowledge, attitudes, and behaviors toward non-human primates. Recommended best-use practices include longevity, use of program incentives, collaboration among educators, and adaptive program assessment, among others. This study surveys primate conservation education programs (PCEPs) to assess the frequency of suggested best-use practices, and to investigate impacts on program efficacy. Online surveys were collected from PCEPs in 2013–2014 (N = 43). The majority of programs reported lengths of 5–10 years, with participant involvement ranging widely from a day to several years. Non-economic and economic incentives were distributed by approximately half of all programs, with programs that provided economic incentives reporting positive participant attitude changes more frequently than those that did not (P = 0.03). While >70% of PCEPs consulted with community leaders, local teachers, and research scientists, only 45.9% collaborated with other conservation educators and only 27% collaborated with cultural experts such as cultural anthropologists. Programs that collaborated with other conservation educators were more likely to report reductions in threats to primates, specifically to bushmeat hunting and capture of primates for the pet trade (P = 0.07). Formal program evaluations were employed by 72.1% of all programs, with the majority of programs using surveys to assess changes to participant attitudes and knowledge. Formal evaluations of participant behavior, community attitudes and behaviors, and threats to primate populations were less common. While results indicate that PCEPs follow many suggested best-use practices, program impacts may be enhanced by greater discussion of economic incentivization, increased collaboration between conservation educators, and improved commitment to adaptive evaluation of changes to behaviors in addition to attitudes and knowledge. Am. J. Primatol. 77:434–448, 2015. © 2014 Wiley Periodicals, Inc.
The impact of primary and persistent cytomegalovirus infection on the progression of acute colitis in a murine model.

Cytomegalovirus (CMV) infects 60–100% of the population worldwide. CMV has been implicated in many diseases through the induction of inflammation. Inflammatory bowel disease (IBD) affects over 1 million Americans annually. IBD, in particular ulcerative colitis, has been associated with CMV infection. Here we use a murine model to test if both primary and persistent CMV infections exacerbate colitis. C57Bl/6J mice were injected with Mock inoculum or murine CMV (mCMV) 4 d (primary infection) or 6 wks (persistent infection) before inducing colitis. Colitis was induced by administering 3% DSS (dextran sodium sulfate) in the drinking water for 6 days. Distilled water was given to controls. Disease activity index (DAI), derived from scores for stool consistency, body weight loss, occult blood, and rectal bleeding, was recorded daily. DAI increased early with DSS treatment in Mocks when compared with water-treated controls. This was accelerated by both primary and persistent mCMV and appeared to be primarily due to the earlier appearance of gross bleeding vs. their Mock controls. Mocks reached similar DAI values by day 6. Myeloperoxidase was modestly elevated in the mCMV 4 d-DSS over the Mock 4 d-DSS, however there was no such synergism in the 6 wk groups. Histology was comparable in Mock and mCMV groups. Taken together our findings show that mCMV accelerated the development of acute colitis although a milder model of colitis may be needed to better delineate the impact of the virus on disease progression. Further work focusing on disruption of barrier function and bleeding may help determine the underlying mechanisms.
Polyisoprenyl phosphate signaling: topography in human neutrophils.

To determine the relationship of polyisoprenyl phosphate (PIPP) remodeling and signaling to the activation state of human neutrophils (PMN), we examined the impact of leukotriene B(4) (LTB(4)) on the conversion of a unique bioactive isoprenoid (presqualene diphosphate: PSDP), recently identified as a novel endogenous signaling molecule. LTB(4) initiated rapid decrements in total PSDP that were concurrent with the respiratory burst (e.g., O(-2) formation). PSDP was identified in nuclear (39%)-, granule (36%)-, and plasma membrane (16%)-containing fractions of PMN. LTB(4) receptor (BLT) activation led to a decrease in nuclear PSDP and concomitant increase in granule-associated PSDP. In addition, PMN nuclei displayed PSDP associated with chromatin as established by mass spectrometry. Together, these results indicate that PSDP is present in membranes and receptor activation rapidly initiates subcellular PIPP remodeling (i.e., conversion) and distribution predominantly to granule membranes. Moreover, identification of nuclear PSDP provides the basis for novel roles for PIPP and PSDP in nuclear-associated signaling events.
Abstract 1091: CCR4+ regulatory T cells progressively accumulate in the presence of leukocyte-derived CCL22/CCL17 in an experimental model of glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. One hallmark of GBM is the accumulation of infiltrating regulatory T cells (Tregs), a highly immunosuppressive T cell subset that suppresses T cell-mediated GBM rejection. Previous work has demonstrated that the Treg-recruiting chemokine, CCL22, is expressed by patient-resected GBM. Importantly, the number of Tregs expressing CCR4, the cognate chemokine receptor for CCL22 and CCL17, is increased in the peripheral blood of GBM patients. To investigate the therapeutic potential of targeting the CCR4 chemokine-receptor axis in brain tumors, we performed FACS analysis to determine the level of CCR4-expressing Tregs and other T cell populations. In addition, we analyzed the mRNA expression levels of the Treg-recruiting chemokines CCL22 and CCL17 in different cellular populations by Percoll gradient isolation followed by qRT-PCR. Using the orthotopic GL261 model of GBM, we found a progressive accumulation of CCR4+ Tregs in the brain tumor. Coincidently, the expression of CCL17 and CCL22 was predominantly localized to the tumor-infiltrating leukocytes, rather than the tumor tissue itself. Finally, we tested the potential impact of a CCR4 antagonist on Treg recruitment and CD8+/Foxp3+ T cell ratio. We found that CCR4 antagonist treatment was able to increase the CD8+/Foxp3+ T cell ratio during the early time points post-GL261 injection. These results implicate the chemokine receptor CCR4 as a therapeutic target for further investigation as a potential strategy to target Treg trafficking to GBM. Citation Format: Alan L. Chang, Derek A. Wainwright, Mahua Dey, Yu Han, Maciej S. Lesniak. CCR4+ regulatory T cells progressively accumulate in the presence of leukocyte-derived CCL22/CCL17 in an experimental model of glioblastoma multiforme. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1091. doi:10.1158/1538-7445.AM2014-1091
High-Energy Diets, Fatty Acids and Endothelial Cell Function: Implications for Atherosclerosis

Diets high in fat and/or calories can lead to hypertriglyceridemia and postprandial lipemia and thus are considered a risk factor for the development of atherosclerosis. Plasma chylomicron levels are elevated in humans after consuming a high-fat meal, and hepatic synthesis of VLDL is increased when caloric intake is in excess of body needs. High lipoprotein lipase activity and subsequent hydrolysis of triglyceride-rich lipoproteins may be an important source of elevated concentrations of fatty acid anions in the proximity to the endothelium and hence a major risk factor for atherosclerosis. We have shown that selected fatty acids, as well as lipoprotein lipase-derived remnants of lipoproteins isolated from hypertriglyceridemic subjects, can activate vascular endothelial cells and disrupt endothelial integrity. Our studies suggest that omega-6 fatty acids, and especially linoleic acid, cause endothelial cell dysfunction most markedly as well as can potentiate TNF-mediated endothelial cell injury. We propose that high-energy diets, and especially diets rich in linoleic acid, are atherogenic by contributing to an imbalance in cellular oxidative stress/antioxidant status of the endothelium, which can lead to activation of oxidative stress-responsive transcription factors, inflammatory cytokine production and the expression of adhesion molecules. Our data also suggest that nutrients, which have antioxidant and/or membrane stabilizing properties, can protect endothelial cells. These findings contribute to the understanding of the interactive role of high fat/calorie diets and subsequent hypertriglyceridemia with inflammatory components and nutrients that exhibit antiatherogenic properties in the development of atherosclerosis. Moreover, results from our research further support the concept that high-fat/calorie diets and associated postprandial hypertriglyceridemia are significant risk factors for atherosclerosis.
Pulmonary hypertension and right-sided heart failure in an adult llama with hepatic disease.

Case Description—A 13-year-old llama was examined because of lethargy, inappetence, and syncope. Clinical Findings—Physical examination revealed muffled heart and lung sounds and peripheral edema. Clinicopathologic abnormalities included lymphopenia, hyperglycemia, prerenal azotemia, mild hyponatremia, mild hypoalbuminemia, and high γ-glutamyltransferase and creatine kinase activities. On ultrasonography, the liver appeared hyperechoic and ascites and pleural effusion were seen. Echocardiography revealed severe dilatation of the right atrium, right ventricle, and pulmonary artery; severe tricuspid regurgitation; and high right ventricular systolic pressure consistent with right-sided heart failure secondary to pulmonary hypertension. Treatment and Outcome—Treatment with furosemide was attempted, but because of failing health, the llama was euthanized 4 weeks later. Macronodular cirrhosis of the liver, glomerulonephritis, and intimal fibrosis and medial hypertrophy of muscular pulmonary arteries were seen ...
Enterohepatic circulation of indomethacin and its role in intestinal irritation.

Abstract The accumulative biliary secretion of indomethacin and its conjugate(s), based upon biliary clearance constants and areas portal and peripheral plasma profiles, has been determined for five laboratory species and estimated for man. This parameter, termed Σ bile % , ranges approximately 30-fold from 13 per cent of dosage in the rabbit to 362 per cent in the dog, and provides a quantitative correlate to the wide species variation in sensitivity to indomethacin-related intestinal lesions. Extrapolation of the Σ bile % vs. intestinal toxicity relationship to man predicts a therapeutic ratio of ca. 20:1 with respect to intestinal irritation. The pharmacokinetic modeling derived for the present purpose should be of general utility in the quantitation of enterohepatic recycling of drugs or metabolites whose loci of intended or untoward effects include the liver or gut.
Simulation of hot-carrier induced MOS circuit degradation for VLSI reliability analysis

A new integrated simulation tool is presented for estimating the hot-carrier induced degradation of nMOS transistor characteristics and circuit performance. This reliability simulation tool incorporates: (1) an accurate 1-dimensional MOSFET model for representing the electrical behavior of locally damaged transistors; and (2) physical models for both fundamental device-degradation mechanisms (charge trapping and interface trap generation). Hot-carrier induced oxide damage can be specified by only a few parameters, avoiding extensive parameter extractions for the characterization of device damage. A repetitive simulation scheme ensures accurate prediction of the circuit-level degradation process under dynamic operating conditions. The evolution of hot-carrier related damage in each device is automatically simulated at predetermined time intervals, instead of extrapolating the long-term degradation using only the initial simulation results. Thus, the gradual variation of dynamic stress conditions is accounted for during the long-term damage estimates. >
Antibody response to bacteriophage hyaluronidase in acute glomerulonephritis after group A streptococcal infection

In a test of the hypothesis that lysogeny of group A streptococci by a temperate bacteriophage might confer nephritogenicity, 283 sera from 69 patients were examined for IgG and IgM antibodies to M 49 streptococcal bacteriophage hyaluronidase. The IgG and IgM response to bacteriophage hyaluronidase was greatest in M 49 streptococci-infected individuals with nephritis, but M 49 streptococci-infected subjects without nephritis also had a greater immune response than did subjects infected with serotypes other than M 49. Although antibody to bacterial hyaluronidase was detected in all Streptococcus-infected groups, antibody to M 49 streptococcal bacteriophage hyaluronidase usually was found in only M 49 streptococci-infected patients. Although the greatest IgG and IgM antibody response to bacteriophage hyaluronidase can be demonstrated in individuals with glomerulonephritis, the antibody response does not indicate a direct relation of lysogeny and nephritis because subjects with and without nephritis after M 49 streptococcal infection all had a significant rise in antibody titer.
The search for high-yield, low-risk antihypertensive treatment.

Like many scientific puzzles, several layers of the hypertension onion have been removed, revealing a core of tougher problems to solve. In the last 3 decades, clinical studies have confirmed that aggressive pharmacologic treatment of severe, moderate, and even mild hypertension leads to better survival and less cardiovascular morbidity. These studies employed well-established, traditional therapies, especially thiazide diuretics (at progressively lower dosages) and beta-adrenergic receptor antagonists (beta-blockers). At higher doses and in their original formulations, thiazides and beta-blockers were not always well tolerated, and many competing drug classes are now also commonly used in patients with hypertension, including a-blockers, calcium antagonists, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and direct vasodilators. It remains uncertain whether these alternative treatments have similar long-term benefits on morbidity and mortality. Short-term blood pressure reductions alone have proven suboptimal predictors of preventing target organ damage and long-term survival. Accordingly, much attention has shifted back to betablockers and diuretics. The key issues appear to be whether clinicians should prefer the well-proven use of thiazides and beta-blockers until similar benefits are shown for alternative antihypertensive drug classes, and whether the long-term advantages of these drugs outweigh their short-term potential for cognitive dysfunction, depression, sexual dysfunction, and other toxicity in some patients. Indeed, some recent reports of the use of beta-blockers after myocardial infarction indicate net benefit even among patients who have relative contraindications to their administration (1). The available data about the cognitive effects of betablockers are somewhat conflicting. A review of 55 studies concluded that impaired perceptual, motor, and cognitive functions were the most frequent adverse effects from beta-blocker therapy, but also noted that favorable effects were almost as frequent as unfavorable ones. Three studies that compared different drug classes directly (2‐ 4) and one meta-analysis (5) found small differences in safety and efficacy among drug classes during 1 to 3 years of follow-up.
Bioavailability of hydrochlorothiazide from tablets and suspensions.

The bioavailability of hydrochlorothiazide was determined following single oral 25-, 50-, 100-, and 200-mg tablet and suspension doses in 12 healthy male volunteers. Plasma and urine levels of hydrochlorothiazide were determined by HPLC. Plasma levels of hydrochlorothiazide were satisfactorily described by a triexponential function. Mean peak plasma levels, Cmax (127–135, 270–280, and 437–490 ng/mL from the 25-, 50-, and 100-mg doses, respectively) were dose proportional, as were areas under plasma profiles, AUC0→36. Mean percentage recovery of unchanged hydrochlorothiazide in 48-h urine samples accounted for 50–59, 54–55, 60–63, and 54–57% of the 25-, 50-, 100-, and 200-mg doses, respectively. There were no significant differences among these values. Correlation coefficients between 48-h urinary recovery of hydrochlorothiazide and the plasma values (Cmax and AUC0→36) for the 25-, 50-, and 100-mg doses were 0.73 and 0.84. There were no differences in the net increases in electrolyte excretion among the treatments during the 0-12-h postdose period. The systematic availability of hydrochlorothiazide, unlike that of chlorothiazide, is dose proportional in the therapeutic range.
Maybe ignorance is not always bliss: The disparate treatment of Hispanics within the child welfare system

Abstract Previous studies indicate that the proportion of culturally diverse children to White children is increasing in public social service agencies. In addition, culturally diverse children are more likely to receive more intensive and punitive services, are more likely to stay within the system for longer periods of time and are reported more often to Child Protective Services. The purpose of the study was to explore how child welfare practices with Hispanic children are different from those applied with White non-Hispanic children. This study was a retrospective, two year, longitudinal, survival analysis of differential child welfare placement outcomes of White non-Hispanic and Hispanic children/families which had substantiated cases of abuse/neglect (n=1001). Findings demonstrate that although cases reported for abuse/neglect are relatively proportionate between Hispanic and White non-Hispanic children, substantiated cases are more likely to occur with Hispanic children. These children are more likely to be placed out of the home more quickly and for longer periods of time than their White non-Hispanic counterparts. The current study demonstrates the need for increased cultural awareness among Child Welfare professionals, especially in terms of assessment and case decision making, and the need for the development of culturally sensitive training modules for CPS and case management personnel.
Increasing Activity to Reduce Obesity in Adolescent Girls: A Research Review

Objective To provide a systematic review of physical activity intervention research conducted with adolescent girls (12–19 years of age and/or in middle or high school) in the United States and Canada during the past two decades. Data Sources Published articles in English were identified in searches using MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycLIT, EMBASE, Science Citation Index, and the Cochrane Controlled Trials Register, with the keywords adolescent health, obesity, physical activity, and exercise, between the dates of May 1980 and November 2003. Study Selection Research studies with interventions that started within the adolescent time period. Only 7 studies met the inclusion criteria. Data Extraction The publication year, sample description, study design, interventions used, and outcomes were extracted from each study. Data Synthesis The 7 studies were published between 1989 and 2003, included girls and boys in the overall sample (no studies with girl‐only samples), used randomized controlled trial or quasi‐experimental designs, and included multicomponent interventions. Body mass index, fitness levels, exercise, and weight were measured as outcomes. Conclusions Although the results were not consistent across studies, they suggest that school‐based, multicomponent interventions that were also designed to decrease sedentary behavior were effective in increasing physical activity in adolescent girls. Future research should focus on determinants of long‐term adherence and the duration and intensity of interventions necessary to prevent obesity in adolescent girls.
Viscoelectric effects in reverse osmosis

Abstract The equations of motion and conservation, which include the effect of the electric field, together with the Poisson equation, have been solved for a single charged cylindrical pore, over a wide range of conditions, to compute the flow rate of water as well as the fluxes of salt and the rejection coefficient. The calculations have been carried out for both constant surface potential and constant surface charge. At constant surface potential and if the surface potential is sufficiently large, the flow of water is decreased by the electrical field by a large amount. For instance, the decrease can be as large as 90% for a surface potential of 75 mV. At constant surface charge, the decrease is about 20% for a surface charge of 10 4 esu/cm 2 . The rejection coefficient is somewhat lower when the viscoelectric effect is taken into account. A membrane can reject salt, only up to a maximum value for a given set of conditions. This maximum is primarily determined by the electrical properties of the pore walls, and to a very large extent by the diffusivities of the co-ions and counterions. Besides the numerical calculations, some approximate analytical solutions are also presented.
The Effect of Topical Application of Dextran on the Gingiva of the Beagle Dog

Dextrans derived from Leuconostoc mesenteroides were placed on clinically healthy gingiva of Beagle dogs once a day for 21 days. Control gingival tissues received saline. Both healthy controls and dextran-treated tissues were brushed daily. Inflamed control tissues were obtained by allowing plaque to accumulate for 21 days. Tissues receiving daily application of dextran solutions developed chronic gingival inflammation but displayed no clinical signs of gingivitis. Healthy control gingival tissues showed no clinical signs of gingivitis and minor histologic inflammatory changes. Tissues exposed to dental plaque showed the typical clinical and histological inflammatory changes of gingivitis. Thus dextran, a substance similar to the extracellular polysaccharide found in dental plaque, was able to penetrate the sulcular epithelium, enter healthy gingival connective tissue and cause chronic inflammation. This connective tissue inflammation occurred without inducing any of the clinical signs of gingivitis. Therefore, it is concluded that dextran produced one component of the gingivitis response, chronic histologic inflammation, independent of another major component of the disease, clinical inflammation.
When is it meaningful to estimate an extinction probability

Recently Don Ludwig has shown that calculations of extinction probabilities based on currently available data are often meaningless due to the large uncertainty accompanying the estimates. Here we address two questions posed by his findings. Can one ever calculate extinction probabilities accurately? If so, how much data would be necessary? Our analysis indicates that reliable predictions of long-term extinction probabilities are likely to require unattainable amounts of data. Analytic calculations based on diffusion approximations indicate that reliable predictions of extinction probabilities can be made only for short-term time horizons (10% to 20% as long as the period over which the population has been monitored). Simulation results for unstructured and structured populations (three stage classes) agree with these calculations.