cssi/SciSciGPT-SciSciNet huggingface dataset:
Evaluation of the risk of perchlorate exposure in a population of late-gestation pregnant women in the United States: Application of probabilistic biologically-based dose response modeling.

Abstract The risk of ubiquitous perchlorate exposure and the dose-response on thyroid hormone levels in pregnant women in the United States (U.S.) have yet to be characterized. In the current work, we integrated a previously developed perchlorate submodel into a recently developed population-based pregnancy model to predict reductions in maternal serum free thyroxine (fT4) levels for late-gestation pregnant women in the U.S. Our findings indicated no significant difference in geometric mean estimates of fT4 when perchlorate exposure from food only was compared to no perchlorate exposure. The reduction in maternal fT4 levels reached statistical significance when an added contribution from drinking water (i.e., 15 μg/L, 20 μg/L, or 24.5 μg/L) was assumed in addition to the 90th percentile of food intake for pregnant women (0.198 μg/kg/day). We determined that a daily intake of 0.45 to 0.50 μg/kg/day of perchlorate was necessary to produce results that were significantly different than those obtained from no perchlorate exposure. Adjusting for this food intake dose, the relative source contribution of perchlorate from drinking water (or other non-dietary sources) was estimated to range from 0.25–0.3 μg/kg/day. Assuming a drinking water intake rate of 0.033 L/kg/day, the drinking water concentration allowance for perchlorate equates to 7.6–9.2 μg/L. In summary, we have demonstrated the utility of a probabilistic biologically-based dose-response model for perchlorate risk assessment in a sensitive life-stage at a population level; however, there is a need for continued monitoring in regions of the U.S. where perchlorate exposure may be higher.
GraphScape: A Model for Automated Reasoning about Visualization Similarity and Sequencing

We present GraphScape, a directed graph model of the vi- sualization design space that supports automated reasoning about visualization similarity and sequencing. Graph nodes represent grammar-based chart specifications and edges rep- resent edits that transform one chart to another. We weight edges with an estimated cost of the difficulty of interpreting a target visualization given a source visualization. We con- tribute (1) a method for deriving transition costs via a partial ordering of edit operations and the solution of a resulting lin- ear program, and (2) a global weighting term that rewards consistency across transition subsequences. In a controlled experiment, subjects rated visualization sequences covering a taxonomy of common transition types. In all but one case, GraphScape's highest-ranked suggestion aligns with subjects' top-rated sequences. Finally, we demonstrate applications of GraphScape to automatically sequence visualization presen- tations, elaborate transition paths between visualizations, and recommend design alternatives (e.g., to improve scalability while minimizing design changes).
Abstract WP350: Pumping Against Gravity - Cardiac Function Affects Fluctuations in Cerebral Blood Flow Caused by Head Position Change in Acute Ischemic Stroke

Introduction: Acute ischemic stroke (AIS) patients often have the head-of-bed (HOB) elevated to 300 while in the Emergency Department (ED). Flat HOB positioning has been shown to impact cerebral fl...
Safety-assured offline-online path planning with reduced storage requirements in simulated surgical training

Optimal path planning and re-planning are essential requirements for efficient robotic and laparoscopy surgical education as they guide instruments through the operating field. Ensuring collision free paths and training under uncertainty, with limited dependence on an expert surgeon's assistance, are key aspects to be considered. In this paper, a hybrid path planning method is introduced to assist in surgical training that combines offline and online approaches for trajectory generation. The proposed offline-online path planner integrates features of offline approaches that guarantee safe navigation with real-time re-planning capability of online planners. It reduces memory storage requirements of the trajectories for online path planning, by more effectively saving them as segments, catering to the portability of the surgical systems. The efficacy of the proposed approach is demonstrated in a simulated training environment for hand-eye coordination tasks on the Computer Assisted Surgical Trainer (CAST) platform.
Wnt/β-Catenin Pathway Activation Mediates Adaptive Resistance to BRAF Inhibition in Colorectal Cancer

One of the most encouraging developments in oncology has been the success of BRAF inhibitors in BRAF-mutant melanoma. However, in contrast to its striking efficacy in BRAF-mutant melanomas, BRAF inhibitor monotherapy is ineffective in BRAF-mutant colorectal cancer. Although many studies on BRAF inhibitor resistance in colorectal cancer have focused on mechanisms underlying the reactivation of the EGFR/RAS/RAF/MEK/ERK pathway, the current study focuses on identifying novel adaptive signaling mechanisms, a fresh angle on colorectal cancer resistance to BRAF inhibition. We found that treatment with BRAF inhibitors (both current and next-generation BRAF inhibitors) upregulated the Wnt/β-catenin pathway in BRAFV600E-mutant colorectal cancer cell lines through activating the cytoplasmic tyrosine kinase focal adhesion kinase (FAK). The results showed that FAK activation upon BRAF inhibitor treatment did not require EGFR or ERK1/2 activation, implying that BRAF inhibitor treatment-induced hyperactivation of Wnt signaling is "pathway reactivation"-independent. BRAF inhibition-induced Wnt pathway activation was further validated in preclinical models of BRAFV600E-mutant colorectal cancer, including cell line xenograft model and a patient-derived xenograft model. Combined inhibition of BRAF/Wnt pathways or BRAF/FAK pathways exerted strong synergistic antitumor effects in cell culture model and mouse xenograft model. Overall, the current study has identified activation of the Wnt/β-catenin pathway as a novel fundamental cause of colon cancer resistance to BRAF inhibition. Our results suggest that although complete vertical pathway blockade is pivotal for effective and durable control of BRAF-mutant colorectal cancer, cotargeting parallel adaptive signaling-the Wnt/β-catenin pathway-is also essential. Mol Cancer Ther; 17(4); 806-13. ©2017 AACR.
Germacrone Dominates the Leaf Oil of Siparuna Grandiflora from Monteverde, Costa Rica:

The leaf oil of Siparuna grandiflora (Monimiaceae) has been obtained by hydrodistillation and analyzed by GC-MS. The major components were germacrone (66.9%), germacrene B (8.2%), δ-cadinene (2.5%)...
Enantiospecific Synthesis of (−)-Slaframine and Related Hydroxylated Indolizidines. Utilization of a Nucleophilic Alaninol Synthon Derived from Serine1

A general methodology for the synthesis of indolizidine alkaloids δ-coniceine (12), 1-hydroxyindolizidine (20), desacetoxy slaframine (24), slaframine (34), and an analogue (37) has been developed. This convergent approach utilizes the available chirality in proline and serine and is conceptually different from other approaches. A highly stereoselective coupling of the prolinals with a nucleophilic alaninol synthon provides the precursors for the key cyclization. A novel thermolytic annulation of an oxazolidinone is the key step in the formation of the six-membered piperidine ring. Further elaboration provides the target natural products 24, 34, and 37 in good overall yields.
Microphthalmia and linear skin defects syndrome: Precise diagnosis guides prognosis

Microphthalmia and linear skin defects syndrome (MLS) is a rare X-linked dominant disorder characterized by microphthalmia and linear atrophic plaques of the face and neck. The diagnosis of MLS can be challenging secondary to both its rarity and to clinical overlap with Goltz syndrome. Whereas the skin lesions of MLS are more likely to improve in appearance with age, the lesions of Goltz are typically persistent.
Investigation of Layer Characteristics and Reliability of Electroless Palladium and Autocatalytic Gold (IMPACT 2019)

The development of nano-scale surface finishes over copper pads such as Electroless Palladium and Autocatalytic Gold (EPAG) has been evolved in the recent years due to ever increasing demands in terms of reliability, component miniaturization and signal transmission.Scope of this paper is a full investigation of the layer characteristics and reliability of Electroless Palladium and Autocatalytic Gold. As soldering and bonding are of special interest in the microelectronics industry, the solder joint reliability (SJR) and bonding results will be evaluated. This article will further show the grain characteristics of the intermediate palladium to draw conclusions about its reliability.The palladium layer structure was investigated via electronbackscatter diffraction (EBSD) investigation by means of field emission scanning electron microscopy after preparation with focused ion beam (FIB). The results allow an interpretation of the crystallinity and density of the layer.Increasing I/O counts have led to ever decreasing cross sectional contact areas or, by default, an increase in solder performance expectations. The evaluation of high solder joint reliability demands can be satisfied by high speed shear testing (HSS). For those tests semi-autocatalytic gold was used for activation beneath immersionpalladium. Both pretreated layer systems were compared in their achieved shear energies and therefore SJR.To examine EPAGs bonding abilities the as-received (ASR) mode as well as the aged condition at 175°C for 16h were applied.
Static Malware Analysis Using Machine Learning Algorithms on APT1 Dataset with String and PE Header Features

Static malware analysis is used to analyze executable files without executing the code to determine whether a file is malicious or not. Data analytic and machine learning techniques have been used increasingly to help process the large number of malware files circulating in the wild and detect new attacks. In this paper, we present the design and implementation of six different machine learning classifiers, and two distinct categories of features statically extracted from the executables: strings and Portable Executable header information. A total of twelve malware detectors were implemented for each of the six classifiers to operate with each of the two feature categories separately. These classifiers and feature extraction algorithms were implemented in Python using the scikit-learn machine learning library. The performances in detection accuracy and required processing time of the twelve malware detectors were compared and analyzed.
In vivo endoscopic Doppler optical coherence tomography imaging of mouse colon

Colorectal cancer remains the second deadliest cancer in the United States, despite the high sensitivity and specificity of colonoscopy and sigmoidoscopy. While these standard imaging procedures can accurately detect medium and large polyps, some studies have shown miss rates up to 25% for polyps less than 5 mm in diameter. An imaging modality capable of detecting small lesions could potentially improve patient outcomes. Optical coherence tomography (OCT) has been shown to be a powerful imaging modality for adenoma detection in a mouse model of colorectal cancer. While previous work has focused on analyzing the structural OCT images based on thickening of the mucosa and changes in light attenuation in depth, imaging the microvasculature of the colon may enable earlier detection of polyps. The structure and function of vessels grown to support tumor growth are markedly different from healthy vessels. Doppler OCT is capable of imaging microvessels in vivo. We developed a method of processing raw fringe data from a commercial swept-source OCT system using a lab-built miniature endoscope to extract microvessels. This method can be used to measure vessel count and density and to measure flow velocities. This may improve early detection and aid in the development of new chemopreventive and chemotherapeutic drugs. We present, to the best of our knowledge, the first endoscopic Doppler OCT images of in vivo mouse colon.
Batallas de custodia trans-especie y la reformulación de lazos de familia

This article contributes to the burgeoning anthropological literature on animal-human relations and trans-species fam­ilies. Increasingly, household pets in the United States are thought of as family members. In fact, these animals are often treated as actual or surrogate kin, be it spouse, child, or sibling. One consequence of this trend is the emergence of legal battles between separating partners for custody of the dog or cat. Despite formal legal codes, which define household animals as personal prop­erty, separating couples nowadays introduce subjective criteria into arguments for or against animal custody. These include, for example, the time each partner spends with the animal, who seems most devoted to the animal, or who occupies a home that would be most advantageous for the animal’s well-being. The cases examined in this article show that, while most judges acknowl­edge the presence of emotion-driven factors in any custody battle, they continue to abide by the definition of companion animals as property. Nonetheless, lawyers nowadays argue that the new trans-species definition of family, together with the enhanced social and affective role of animals, are appropriate for judicial consideration in pet custody lawsuits.
Extent of In Utero Transfer of Tenofovir From Mother to Fetus: A Paired Analysis of Hair Specimens Collected at Birth From a Cohort in the United States

Understanding in utero transfer of antiretrovirals is critical for interpreting safety. Hair levels measure cumulative exposure. We measured tenofovir (TFV) concentrations in hair at delivery among women living with human immunodeficiency virus receiving TFV disoproxil fumarate-based treatment and their infants, using liquid chromatography-tandem mass spectrometry. Among 103 mother-infant pairs, the mean log10 ratio of infant-to-maternal TFV levels was 1.08 (95% confidence interval, .97-1.20). TFV transfer was 60% lower from mothers who had preterm compared with term deliveries and 42% lower from mothers who had cesarean compared with vaginal deliveries. Like prior studies assessing transfer via short-term measures (plasma, cord blood, amniotic fluid), we found high cumulative transfer using hair.
Synthesis of systematic reviews of percutaneous device closure of patent foramen ovale (PFO) for prevention of recurrent cryptogenic stroke: Redundant publications and methodological deficiencies

Critical assessments of systemic reviews and meta-analyses have found them to often be redundant, lacking in novel perspectives, of poor methodological quality, and written by authors with potential conflicts of interest. We sought to investigate these issues as they relate to systemic reviews and meta-analyses of percutaneous patent foramen ovale closure for the prevention of recurrent cryptogenic stroke.
A novel human laboratory model for screening medications for alcohol use disorder.

Alcohol use disorder (AUD) is a highly prevalent, chronic relapsing disorder with a high disease burden in the USA. Pharmacotherapy is a promising treatment method for AUD; however, the few FDA-approved medications are only modestly effective. Medications development for AUD is a high priority research area, but the cumbersome drug development process hinders many potential compounds from reaching approval. One area with major opportunities for improvement is the process of screening novel compounds for initial efficacy, also known as early phase 2 trials. Early phase 2 trials incorporate human laboratory paradigms to assess relevant clinical constructs, such as craving and subjective responses to alcohol. However, these controlled paradigms often lack the ecological validity of clinical trials. Therefore, early phase 2 trials can be more efficient and clinically meaningful if they combine the internal validity of experimental laboratory testing with the external validity of clinical trials. To that end, the current study aims to develop and validate a novel early efficacy paradigm, informed by smoking cessation literature, to screen novel medications for AUD. As an established AUD medication, naltrexone will serve as an active control to test both the practice quit attempt model and the efficacy of a promising AUD pharmacotherapy, varenicline. Individuals with current AUD reporting intrinsic motivation to change their drinking will complete a week-long “practice quit attempt” while on study medication. Participants are randomized and blinded to either naltrexone, varenicline, or placebo. During the practice quit attempt, participants will complete daily visits over the phone and fill out online questionnaires regarding their drinking, alcohol craving, and mood. Additionally, participants will undergo two alcohol cue-reactivity sessions. The successful completion of this study will advance medications development by proposing and validating a novel early efficacy model for screening AUD pharmacotherapies, which in turn can serve as an efficient strategy for making go/no-go decisions as to whether to proceed with clinical trials. ClinicalTrials.gov NCT04249882 . Registered on 31 January 2020.
Machine learning‐based multimodal prediction of language outcomes in chronic aphasia

Recent studies have combined multiple neuroimaging modalities to gain further understanding of the neurobiological substrates of aphasia. Following this line of work, the current study uses machine learning approaches to predict aphasia severity and specific language measures based on a multimodal neuroimaging dataset. A total of 116 individuals with chronic left-hemisphere stroke were included in the study. Neuroimaging data included task-based functional magnetic resonance imaging (fMRI), diffusion-based fractional anisotropy (FA)-values, cerebral blood flow (CBF), and lesion-load data. The Western Aphasia Battery was used to measure aphasia severity and specific language functions. As a primary analysis, we constructed support vector regression (SVR) models predicting language measures based on (i) each neuroimaging modality separately, (ii) lesion volume alone, and (iii) a combination of all modalities. Prediction accuracy across models was subsequently statistically compared. Prediction accuracy across modalities and language measures varied substantially (predicted vs. empirical correlation range: r = .00-.67). The multimodal prediction model yielded the most accurate prediction in all cases (r = .53-.67). Statistical superiority in favor of the multimodal model was achieved in 28/30 model comparisons (p-value range: <.001-.046). Our results indicate that different neuroimaging modalities carry complementary information that can be integrated to more accurately depict how brain damage and remaining functionality of intact brain tissue translate into language function in aphasia.
Impatience implication of weakly Paretian orders: Existence and genericity

Abstract We study order theoretic and topological implications for impatience of weakly Paretian, representable orders on infinite utility streams. As a departure from the traditional literature, we do not make any continuity assumptions in proving the existence of impatient points. Impatience is robust in the sense that there are uncountably many impatient points. A general statement about genericity of impatience cannot be made for representable, weakly Paretian orders. This is shown by means of an example. If we assume a stronger sensitivity condition, then genericity obtains.
Influence of amount and frequency of protein supplementation to steers consuming low-quality, cool-season forage: intake, nutrient digestibility, and ruminal fermentation.

This experiment evaluated the influence of protein supplementation frequency (SF) and amount offered on intake, nutrient digestibility, and ruminal fermentation by rumen-fistulated beef steers consuming low-quality [2.9% crude protein (CP); dry matter (DM) basis], cool-season forage. Seven Angus × Hereford steers (300 ± 27 kg) fitted with ruminal cannulas were randomly assigned to 1 of 7 treatments in an incomplete 7 × 4 Latin square. Treatments, in a 2 × 3 factorial design plus a non-supplemented control (CON), consisted of 2 levels of supplemental soybean meal, 100% (F) or 50% (H) of the estimated rumen-degradable protein requirement, provided daily (D), once every 5 d (5D), or once every 10 d (10D). Experimental periods were 30 d and dry matter intake (DMI) was measured from days 19 to 28. On days 21 (all supplements provided) and 30 (only daily supplements provided; day immediately prior to supplementation for 5D and 10D treatments) ruminal fluid was collected for ruminal pH, ammonia-N (NH3), volatile fatty acids (VFA), and determination of ruminal fermentation variables. Forage and total DM, organic matter (OM), and nitrogen (N) intake increased with supplementation (P ≤ 0.04). However, a linear effect of SF × amount of supplement interaction was observed for forage and total DM, OM, and N intake (P ≤ 0.04), with each variable decreasing as SF decreased, but the decrease being greater with F vs. H. Apparent total tract DM, OM, and neutral detergent fiber digestibility was not affected by supplementation or amount of supplement provided (P ≥ 0.10). In contrast, N digestibility increased with supplementation and for F vs. H (P 5 d, can be a management tool to maintain acceptable levels of DMI, nutrient digestibility, and ruminal fermentation while reducing supplementation cost.
Tufts Medical Center Experience With Long-Term Follow-Up of Vestibular Schwannoma Treated With Gamma Knife Stereotactic Radiosurgery: Novel Finding of Delayed Pseudoprogression.

Abstract Purpose Our purpose was to evaluate the long-term outcomes of patients with vestibular schwannoma (VS) treated with Gamma Knife stereotactic radiosurgery (GKSRS) with modern techniques, with attention to posttreatment tumor growth dynamics, dosimetric predictors, and late toxicities. Methods and Materials One hundred twelve patients with VS were treated with GKSRS with a median dose of 12.5 Gy to the 50% isodose line treated between 2004 and 2015, with patients followed up to 15 years. Target and organ-at-risk doses were recorded, and tumor diameter/volume, audiologic decline, and trigeminal/facial nerve preservation were tracked from treatment onward. Results GKSRS yielded local control of 5, 10, and 15 years at 96.9%, 90.0%, and 87.1% respectively. Pseudoprogression was found in 45%, with a novel pattern detected with peak swelling at 31 months. Pseudoprogression was associated with smaller tumor diameter at treatment and fewer treatment isocenters, but not with the development of any toxicity, nor was it predicted by any dosimetric factor. Median time to hearing loss was 3.4 years with actuarial hearing preservation at 2, 5, and 10 years of 66.5%, 43.1%, and 37.6%, with rate of hearing loss correlating with maximum cochlea and modiolus doses. Trigeminal and facial nerve preservation rates were 92.7% and 97.6%, respectively. Increasing maximum tumor dose was associated with facial paresthesia. Conclusions Modern GKSRS is a safe and effective treatment for VS on long-term follow-up, with high levels of facial and trigeminal nerve preservation. A novel pattern of pseudoprogression has been identified suggesting longer imaging follow-up may be needed before initiating salvage in those without symptomatic progression. Several tumor and dosimetric predictors have been suggested for the development of different toxicities, requiring further evaluation.
Supporting Families with Children Who Display Severe Challenging Behavior

Over the past several decades, we have developed quality behavioral assessments and interventions for challenging behaviors among individuals with a variety of severe developmental and cognitive di...
Narrative review of management controversies for paraesophageal hernia

Objective To review management controversies in paraesophageal hernia and options for surgical repair. Background Paraesophageal hernia is an increasingly common problem. There are controversies over whether and when paraesophageal hernias should be surgically repaired. In addition, if these hernias are to be repaired, the method of repair, need for mesh reinforcement, need for fundoplication, and need for gastropexy are not uniformly accepted. Methods Recent literature was reviewed on need for repair, approach (open, laparoscopic or robotic surgery), method of repair (primary suture, use of relaxing incisions, use of mesh reinforcement), materials and configuration of mesh reinforcement, need and type of fundoplication, and need for gastropexy, with emphasis on surgical outcomes. Conclusions The extant literature suggests that paraesophageal hernia should be approached in a patient-centered, precision medicine manner. In general, hernia reduction, sac excision and primary suture approximation of the hiatal crura are mandatory. Use of mesh should be based on individual risk factors; if mesh is used, biological meshes appear to have a more favorable safety profile, with the "reverse C" or keyhole configuration allowing for increase in crural tensile strength at it most vulnerable areas. Use and choice of fundoplication or magnetic sphincter augmentation should be based on individual considerations. Finally, gastropexy is generally ineffective and should be used only in extreme circumstances.
Conceptual design and selection of a bladder type pressure compensation system for subsea actuators to prevent failure due to seawater head

Subsea valves and actuators are typically installed at very deep-water depths between 1 and 3 km. The seawater column at such depths applies a high amount of pressure on subsea valves and actuators. Therefore, one way to make sure that subsea equipment and components can withstand the tremendous external pressure of the seawater is to make the component wall thick enough, as is the practice for subsea valves. Subsea actuators, unlike valves, are not designed thick enough since actuators shells are not pressurized by internal fluid. The alternative solution to prevent the implosion and failure of actuators due to seawater pressure head, and to avoid increasing material cost by increasing wall thickness, is to use a pressure balance compensation system. The main research question is twofold: how to select between the available compensation systems in the industrial world and how to implement conceptual design for the selected compensation system. The research does not include a detailed design of the compensation system. The spring type pressure compensation system is reviewed in this paper and is not recommended due to the possibility of spring damage due to high cycling load. Installing the pressure compensation on the surface and connecting the compensation oil fluid to the subsea equipment through piping or tubing is more costly, less efficient and heavier compared to a bladder type compensation system. Bladder type compensation, also known as closed compensation, is widely used for subsea actuators as an environmentally friendly solution. This paper proposes a conceptual design for this type of compensation system that includes a wall thickness calculation according to American Society of Mechanical Engineers Sec. VIII Div. 02 requirements, as well as pressure relief valves installed on the compensation system according to American Petroleum Institute (API) 526 requirements.
Brain region-specific disruption of mitochondrial bioenergetics in cynomolgus macaques fed a Western versus a Mediterranean diet.

We show that compared with cynomolgus macaques fed a Mediterranean diet, a Western diet resulted in diminished bioenergetic pattern between brain regions related to blood glucose and insulin levels...
Eichler Integrals in Several Variables

In this chapter we study the cohomology of A g . In sections 3, 4, 5 we study the Betti cohomology of A g (ℂ) and its Hodge structure, and show the degeneration of various spectral sequences. Our method, developed in [F 1], is based on the Bernstein-Gelfand-Gelfand (abbreviated as BGG) resolution (cf. [BGG]), Mumford’s extension of equivariant vector bundles to toroidal compactifications (cf. [Mum 6]) and Deligne’s Hodge theory (cf. [D 2], [D 3]). Making use of geometric information available in our present case, we obtain results not contained in [F 1]. In some sense the major work is contained in section 2, where we compute the formal cohomology of toroidal compactifications of fibre products of the universal abelian scheme. In section 6 we describe (but do not present) the p-adic analogue, namely the p-adic etale cohomology groups, which turn out to be crystalline (hence Hodge-Tate) Galois representations and closely related to the crystalline cohomology groups. (Since the crystalline cohomology is closely tied to the de Rham cohomology as is well-known, this analogy is a very good one.) The first section furnishes geometric information needed for studying cohomology, namely explicit compactification of the fibre products of the universal abelian scheme.
Moderate Alcohol Induces Stress Proteins HSF1 and hsp70 and Inhibits Proinflammatory Cytokines Resulting in Endotoxin Tolerance

Binge or moderate alcohol exposure impairs host defense and increases susceptibility to infection because of compromised innate immune responses. However, there is a lack of consensus on the molecular mechanism by which alcohol mediates this immunosuppression. In this study, we show that cellular stress proteins HSF1 and hsp70 play a mechanistic role in alcohol-mediated inhibition of the TLR4/MyD88 pathway. Alcohol exposure induced transcription factor HSF1 mRNA expression and DNA binding activity in primary human monocytes and murine macrophages. Furthermore, HSF1 target gene hsp70 mRNA and protein are upregulated by alcohol in monocytes. In vitro pre-exposure to moderate alcohol reduced subsequent LPS-induced NF-κB promoter activity and downstream TNF-α, IL-6 and IL-1β production in monocytes and macrophages, exhibiting endotoxin tolerance. Mechanistic analysis demonstrates that alcohol-induced HSF1 binds to the TNF-α promoter in macrophages at early time points, exerting transrepression and decreased TNF-α expression. Furthermore, association of hsp70 with NF-κB subunit p50 in alcohol-treated macrophages correlates with reduced NF-κB activation at later time points. Hsp70 overexpression in macrophages was sufficient to block LPS-induced NF-κB promoter activity, suggesting alcohol-mediated immunosuppression by hsp70. The direct crosstalk of hsp70 and HSF1 was further confirmed by the loss of alcohol-mediated endotoxin tolerance in hsp70- and HSF1-silenced macrophages. Our data suggest that alcohol-mediated activation of HSF1 and induction of hsp70 inhibit TLR4-MyD88 signaling and are required for alcohol-induced endotoxin tolerance. Using stress proteins as direct drug targets would be clinically relevant in alcohol abuse treatment and may serve to provide a better understanding of alcohol-mediated immunosuppression.
Tamiflu, the Takings Clause, and Compulsory Licenses: An Exploration of the Government's Options for Accessing Medical Patents

As the United States and the world prepare to battle potential pandemics such as the avian flu,1 new conflicts have arisen between governments and private owners of patents for medical vaccines and treatments. Such conflicts center in part around the growing concerns of domestic and international governments over the availability of Tamiflu, a privately held, patented medication used to treat the avian flu virus.2 Governments fear that Roche, the holder of the exclusive worldwide rights of the Tamiflu patent,3 lacks the capacity to produce enough Tamiflu treatment to combat a large outbreak of the virus. Property law provides the U.S. government with two options for gaining access to medical patents such as Tamiflu. First, the government may use compulsory licensing, which has traditionally been utilized to gain
Barriers to accessing care in patients with chronic hepatitis C: the impact of depression

Aliment Pharmacol Ther 2010; 32: 1163–1173 Summary Background Patients with hepatitis C viral (HCV) may perceive barriers to accessing speciality care for HCV, and these barriers may be related to depressive symptoms. Aim To evaluate the relationship between barriers to care, demographics, and depressive symptoms. Methods A cross-sectional analysis of 126 patients referred for HCV at two speciality HCV clinics. Barriers to care, depressive symptoms and sociodemographics were measured using standardized instruments. A retrospective chart review was conducted to collect clinical outcome data. Results Depressive symptoms were reported in 26%. Common barriers included lack of personal financial resources; lack of HCV knowledge in the community; lack of professionals competent in HCV care; stigmatization of HCV; and long distances to clinics offering care. After we controlled for sociodemographics, depression accounted for an additional 7–18% of variability in all barriers (all p values <0.01). Lower depression, marital and employment status were associated with subsequent receipt of HCV treatment in 38% (45/120) of patients; perceived barriers were not. Conclusions Depression is independently associated with perceived barriers to care. Higher depressive scores, but not perceived barriers, were associated with nontreatment. Healthcare providers who diagnose HCV need to be cognizant of numerous perceived barriers to accessing HCV care, and the impact that depression may have on these perceptions and receipt of treatment.
Parametric surface representation using convolution integrals

A novel surface representation scheme based on convolution integrals has been proposed for improving the efficiency of computer representation of surfaces. The representation is a parametric representation which uses (possibly complex) exponential functions instead of low-degree polynomials. Preliminary investigations indicate that the representation (under suitable restrictions) is robust and is applicable to a wide class of commonly occurring surfaces. >
Escherichia coli sepsis and prolonged hypophosphatemia following exertional heat stroke.

Because of the increasing emphasis on physical activity, sports medicine represents a growing proportion of medical care. Climatic heat stress, including heat stroke, is of sufficient concern that its preventability has been addressed by the American Academy of Pediatrics.1 Although heat stroke is defined by the triad of hyperpyrexia, anhydrosis, and altered mental status, the clinical course of these patients may include multiple complications.2-8 In this article we describe a previously unrecognized etiologic relationship between two of these complications, which may permit early identification and prevention of life-threatening consequences to heat stroke. Two cases of Gram-negative sepsis have been described in previously healthy young adults suffering from fatal exertional heat stroke.7,8
The generation of peptide: MHCII-specific TH17 cells in response to intranasal bacterial infection requires IL-6 and TGF-β1, produced from a distinct mucosal dendritic cell subset. (LYM3P.740)

Intranasal infections preferentially generate TH17 cells while intravenous infections induce TH1 cells. We explored the basis for these anatomic preferences by tracking endogenous polyclonal CD4+ T cells specific for a p:MHCII ligand derived from the mucosal pathogen Streptococcus pyogenes (Sp). Sp p:MHCII-specific CD4+ T cells were first activated in the cervical lymph nodes (CLN) following intranasal inoculation and then migrated to the spleen and nasal-associated lymphoid organs. The effector cell population generated in the CLN consisted of TH17 cells and TFH cells. Sp-induced TH17 formation was associated with IL-6 and TGF-β1 production by Batf3- CD103- CD301b+ dendritic cells that were located in the CLN but not the spleen. Thus, the tendency of intranasal infection to induce TH17 cells is related to cytokine production by specialized dendritic cells that drain this site.
Osmotically Induced Excretion of Putrescine by Mutants of Escherichia coli Defective in Potassium Transport

Escherichia coli is known to excrete putrescine rapidly after a sudden elevation in the osmolarity of the medium. We report here that mutants defective in the transport of potassium ions display a greatly diminished rate of [(14)C]putrescine excretion.
Establishing a predictive performance indicator for real‐time hybrid simulation

SUMMARY Real-time hybrid simulation (RTHS) is increasingly being recognized as a powerful cyber-physical technique that offers the opportunity for system evaluation of civil structures subject to extreme dynamic loading. Advances in this field are enabling researchers to evaluate new structural components/systems in cost-effective and efficient ways, under more realistic conditions. For RTHS, performance metric clearly needs to be developed to predict and evaluate the accuracy of various partitioning choices while incorporating the dynamics of the transfer system, and computational/communication delays. In addition, because of the dynamics of the transfer system, communication delays, and computation delays, the RTHS equilibrium force at the interface between numerical and physical substructures is subject to phase discrepancy. Thus, the transfer system dynamics must be accommodated by appropriate actuator controllers. In this paper, a new performance indicator, predictive performance indicator (PPI), is proposed to assess the sensitivity of an RTHS configuration to any phase discrepancy resulting from transfer system dynamics and computational/communication delays. The predictive performance indicator provides a structural engineer with two sets of information as follows: (i) in the absence of a reference response, what is the level of fidelity of the RTHS response? and (ii) if needed, what partitioning adjustments can be made to effectively enhance the fidelity of the response? Moreover, along with the RTHS stability switch criterion, this performance metric may be used as an acceptance criteria for conducting single-degree-of-freedom RTHS. Copyright © 2014 John Wiley & Sons, Ltd.
Prediction of salt sensitivity.

The overall prevalence of salt sensitivity was studied in 75 men stratified by diagnosis (hypertensive v normotensive) and race (black v white). All were studied in a crossover design employing a 200 mEq and 10 mEq Na/day. High salt led to a decrease in diastolic pressure for all groups (P less than .002). For systolic pressure, there was no salt effect on blood pressure across the whole group; however amongst the hypertensives, particularly the black hypertensives, high salt led to increases in systolic pressure (P less than .022). Obese patients were more likely to increase their systolic pressure in response to salt loading (P less than .05). The patients whose pressure increased on high salt were those who manifested less of a decrease in plasma levels of norepinephrine and renin in response to salt loading (both P less than .05). Systolic salt sensitivity was predicted with high statistical power (R = 0.689, P less than .00001) by a multiple regression equation employing: race; diagnosis; the change in renin and norepinephrine levels with diet; and the change in BP sensitivity to infused norepinephrine across the two diets. In view of the findings of increased norepinephrine, renin and diastolic pressure on low salt and in view of the particular physiological and epidemiological setting associated with systolic salt sensitivity, one wonders about the advisability of across-the-board recommendations of low salt diets for all hypertensive patients.
Synthesis of the ribosomal P-site substrate CCA-pcb.

CCA-pcb (cytidylyl-(3‘5‘)-cytidylyl-(3‘5‘)-3‘(2‘)-O-(N-(6-d-(+)-biotinoylaminohexanoyl)-l-phenylalanyl)adenosine), a ribosomal P-site substrate, was synthesized by phosphoramidite chemistry in 26 steps with an overall yield of 18%, starting from biotin. The synthesis relies on the judicious selection of orthogonal silyl protecting groups for the 5‘-hydroxyls and acid-labile protecting groups (DMTr, AcE, and MeE) at other reactive sites to ensure the intactness of the labile ester. Both 3‘-esterification and nucleotide coupling were accomplished by in situ activation with imidazolium ions.
The role of the 5' untranslated region (UTR) in glucose-dependent mRNA decay.

When S. cerevisiae are grown with glucose, SDH2 mRNA encoding the iron protein of the succinate dehydrogenase complex is unstable and present at low level. In yeast grown without glucose, SDH2 mRNA is stable and its level rises. Addition of glucose to a glucose-limited culture causes the SDH2 mRNA level to fall rapidly with a half-life of approximately 5-7 min. Previously the 5'UTR of the mRNA of SDH2 was shown to be necessary and sufficient to destabilize it in glucose (Lombardo et al., 1992). We now show that the SDH1 and SUC2 5'UTRs are capable of conferring glucose-sensitive mRNA instability. We also examine how changes in the SDH2 5'UTR affect glucose-triggered degradation. Finally, we show that changes in mRNA stability are correlated with changes in translational efficiency for these transcripts.
National Electronic Library for Health (NeLH)

The British National Electronic Library for Health aims to provide both healthcare professionals and the public with knowledge to support healthcare related decisions. This meta resource is essentially an electronic clearinghouse of various initiatives within the UK and the National Health Service (NHS). The main site is free to all users, but only registered NHS health providers can access some of the linked sites. The main site home …
I Was Pleased a Moment Ago: How Pleasure Varies With Background and Foreground Reference Points

The pleasure of an outcome is often evaluated relative to salient reference points. In the background, increasing sequences of positive outcomes are more enjoyable than decreasing sequences. In the foreground, outcomes that could have been worse are often more enjoyable than those that could have been better. How does pleasure vary when both background and foreground reference points are salient? Using a repeated gambling task in which participants make a choice, learn the outcome, watch their cumulative earnings change, and rate the pleasure of the outcome, we explore this question. Pleasure depends on background and foreground reference points, but the immediate events tend to dominate. The relatively narrow focus on the most recent reference points leads to myopic pleasure. We offer a modified version of decision affect theory to account for the results and explore the implications for consumer satisfaction.
Early Identification and Recruitment of Hispanic Teacher Candidates

While America's minority student popu lation is increasing, the teacher pool is becoming increasingly white. For His panics, the country's fastest growing minority, the situation is critical. Zapata reviews the issues regarding Hispanic involvement in teaching and presents Project: / Teach as a viable model for recruiting Hispanic high school students into teaching.
A Definition, Classification, and Report on Rural Civil Organization in China

This article explores a definition and typology of rural civil organization and proceeds with an analysis of several of the most active types. Its discussion departs from a broadly-used definition of “civil organizations” into an explanation of “rural civil organization”. Next, it applies a classification system based on three parameters: civil organization-State relationship; civil organization-members relationship; and models for satisfying members’ needs. Finally, it introduces recent developments from the most important important types of rural civil organization.
Ventricular Tachycardia Ablation Remains Treatment of Last Resort in Structural Heart Disease: Argument for Earlier Intervention

VT Ablation Treatment of Last Resort. Introduction: Despite advances in ablation of ventricular tachycardia (VT), recognized toxicity of amiodarone, and potential harm of implantable cardioverter defibrillator (ICD) shocks, there appears to be reluctance to pursue catheter ablation. Methods and Results: We tested the hypothesis that patients with structural heart disease and VT are referred late for ablation and may have worse outcomes as a result. Consecutive patients with VT and structural heart disease referred to a single center, between January 2008 and April 2009 were studied. Patients with prior VT ablations were excluded. Late referrals were defined as those with 2 or more episodes of VT, separated by at least 1 month. Ninety-eight consecutive patients were analyzed. Ninety-six percent of patients had an ICD implanted prior to ablation, 58% were in VT storm and 67% taking ≥400 mg daily of amiodarone or amiodarone intolerant (10%). Thirty-six patients fit the definition of early referral and 62 late. Overall acute procedural success was achieved in 89%. Amiodarone dose decreased from a mean and median of 559 and 400 mg daily preablation to 98 and 0 postablation (P < 0.01). Mean and median VT episodes decreased from 17 and 6 in the month preceding ablation to 1 and 0 in the 6 months following ablation (P < 0.01). In Kaplan–Meier analysis, the early referral group had superior 1-year VT free survival (P = 0.01). Conclusions: VT ablation is frequently reserved for patients receiving recurrent ICD shocks despite high dose amiodarone. Stronger consideration should be given to earlier referral for VT ablation in patients with structural heart disease. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1123-1128, October 2011)
CO‐ORDINATION OF MONETARY, BANK SUPERVISORY, AND LOAN AGENCIES OF THE FEDERAL GOVERNMENT

In a recent issue of this Journal, Professor Bach has summarized a study of the relationships among federal banking agencies which he made for the Commission on Organization of the Executive Branch of the Government, commonly called the Hoover Commission.' As Mr. Bach points out, the recommendations in his report differ in part from those of the Commission. In this article I would like to present an analysis of relationships which differs in important respects from that portrayed by Professor Bach, and to offer a proposal for co-ordination of monetary, bank supervisory, and loan agencies which differs both from his recommendation and that of the Hoover Commission, but conforms with the general character of the report of the Commission.2
A fast optimization algorithm for multicriteria intensity modulated proton therapy planning.

Purpose: To describe a fast projection algorithm for optimizing intensity modulated proton therapy (IMPT) plans and to describe and demonstrate the use of this algorithm in multicriteria IMPT planning. Methods: The authors develop a projection-based solver for a class of convex optimization problems and apply it to IMPT treatment planning. The speed of the solver permits its use in multicriteria optimization, where several optimizations are performed which span the space of possible treatment plans. The authors describe a plan database generation procedure which is customized to the requirements of the solver. The optimality precision of the solver can be specified by the user. Results: The authors apply the algorithm to three clinical cases: A pancreas case, an esophagus case, and a tumor along the rib cage case. Detailed analysis of the pancreas case shows that the algorithm is orders of magnitude faster than industry-standard general purpose algorithms (MOSEK’s interior point optimizer, primal simplex optimizer, and dual simplex optimizer). Additionally, the projection solver has almost no memory overhead. Conclusions: The speed and guaranteed accuracy of the algorithm make it suitable for use in multicriteria treatment planning, which requires the computation of several diverse treatment plans. Additionally, given the low memory overhead of the algorithm, the method can be extended to include multiple geometric instances and proton range possibilities, for robust optimization.