Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Pathways: Fatty Acid Synthase

Therapies that target tumor metabolism represent a new horizon in anticancer therapies. In particular, cancer cells are dependent on the generation of lipids, which are essential for cell membrane synthesis, modification of proteins, and localization of many oncogenic signal transduction enzymes. Because fatty acids are the building blocks of these important lipids, fatty acid synthase (FASN) emerges as a unique oncologic target. FASN inhibitors are being studied preclinically and beginning to transition to first-in-human trials. Early generation FASN inhibitors have been studied preclinically but were limited by their pharmacologic properties and side-effect profiles. A new generation of molecules, including GSK2194069, JNJ-54302833, IPI-9119, and TVB-2640, are in development, but only TVB-2640 has moved into the clinic. FASN inhibition, either alone or in combination, holds promise as a novel therapeutic approach for patients with cancer. Clin Cancer Res; 21(24); 5434–8. ©2015 AACR.
TP-PPV: Piecewise Nonlinear, Time-Shifted Oscillator Macromodel Extraction For Fast, Accurate PLL Simulation

We present a novel method for generating small, accurate PLL macromodels that capture transient response and jitter performance with unprecedented accuracy, while offering large speedups. The method extracts and uses a highly accurate oscillator phase macromodel termed the TP-PPV macromodel. The core idea behind the novel extraction procedure is to combine concepts from strongly nonlinear trajectory piecewise macromodeling techniques together with PPV-based time shifted nonlinear phase macromodels. As a result, TP-PPV generated macromodels offer excellent global as well as local fidelity. These properties are necessary for handing large excursions in PLL control voltages during capture/lock in, e.g., hopping frequency synthesizers. We validate TP-PPV on a 5-stage interpolative ring VCO based PLL and compare results against full simulation, as well as against prior macromodels. We show that, unlike prior macromodels that only work well when the control voltage of the VCO has small excursions, the TP-PPV macromodel provides near-perfect matches against full SPICE level simulation over a wide range of design scenarios, while achieving speedups of about three orders of magnitude
Simultaneous Comparison of Many Triphasic Defibrillation Waveforms

Biphasic defibrillation waveforms are now accepted as being more effective at terminating ventricular fibrillation (VF) than monophasic waveforms. If two phases are better than one, this naturally leads to the hypothesis that additional phases improve efficacy. This study tests the hypothesis by adding one additional phase. We examined the efficacy of 18 different triphasic waveforms simultaneously. We tested the rate of recovery, i.e., successful defibrillation, of 21 guinea pigs (820-1,050 g) using triphasic, monophasic and biphasic defibrillation waveforms. The biphasic and monophasic were control waveforms. VF was electrically induced twenty times per animal and a single defibrillation attempt was made using a test waveform VF episode. Every waveform was adjusted to the energy required to defibrillate that animal 50% of the time, using a biphasic waveform as a control. The success rate of each triphasic waveform was pair-wise compared to the biphasic and monophasic control using the adjusted McNemar statistical test. Of the 18 triphasic waveforms tested, two were significantly poorer than the monophasic control (p<0.05). One was superior to the biphasic waveform (p<0.1), but not statistically so. We concluded that, while adding a phase to a monophasic waveform does improve efficacy, adding an additional phase to a biphasic waveform does not necessarily improve efficacy.
Experimental evaluation of power differential relay for transmission line protection

An experimental evaluation of a power differential relay is conducted and the results are described. The experimental setup consists of a generator connected to the network via a transmission line protected by the power deferential relay. The relay input signals, fundamental active and reactive powers, are locally computed from the complex product of the current and voltage phasors at each end on sample-by-sample basis. The relay setting is refined and it is examined for different internal and external fault conditions as well as during power swings. Response of the active and reactive power detectors is evaluated in the time domain. Test cases provide evidence of the efficacy of the proposed technique.
Crossing the Hands Increases Illusory Self-Touch

Manipulation of hand posture, such as crossing the hands, has been frequently used to study how the body and its immediately surrounding space are represented in the brain. Abundant data show that crossed arms posture impairs remapping of tactile stimuli from somatotopic to external space reference frame and deteriorates performance on several tactile processing tasks. Here we investigated how impaired tactile remapping affects the illusory self-touch, induced by the non-visual variant of the rubber hand illusion (RHI) paradigm. In this paradigm blindfolded participants (Experiment 1) had their hands either uncrossed or crossed over the body midline. The strength of illusory self-touch was measured with questionnaire ratings and proprioceptive drift. Our results showed that, during synchronous tactile stimulation, the strength of illusory self-touch increased when hands were crossed compared to the uncrossed posture. Follow-up experiments showed that the increase in illusion strength was not related to unfamiliar hand position (Experiment 2) and that it was equally strengthened regardless of where in the peripersonal space the hands were crossed (Experiment 3). However, while the boosting effect of crossing the hands was evident from subjective ratings, the proprioceptive drift was not modulated by crossed posture. Finally, in contrast to the illusion increase in the non-visual RHI, the crossed hand postures did not alter illusory ownership or proprioceptive drift in the classical, visuo-tactile version of RHI (Experiment 4). We argue that the increase in illusory self-touch is related to misalignment of somatotopic and external reference frames and consequently inadequate tactile-proprioceptive integration, leading to re-weighting of the tactile and proprioceptive signals.The present study not only shows that illusory self-touch can be induced by crossing the hands, but importantly, that this posture is associated with a stronger illusion.
Risk for Renal Cell Carcinoma in Chronic Hepatitis C Infection

Background: Chronic infection with hepatitis C virus (HCV) confers increased risk for chronic renal disease, and numerous reports suggest an association with renal cell carcinoma (RCC), a cancer with rapidly rising global incidence. We sought to determine whether HCV infection confers an increased risk for developing RCC. Methods: With the use of administrative data from a large, integrated, and ethnically diverse healthcare system, we did a cohort study of 67,063 HCV-tested patients between 1997 and 2006 who were followed for the development of RCC until April 2008. Results: A search of the health system cancer registry for patients with the diagnosis of kidney cancer showed that RCC was diagnosed in 0.6% (17 of 3,057) of HCV-positive patients versus 0.3% (177 of 64,006) of HCV-negative patients. The mean age at RCC diagnosis was much younger in HCV-positive individuals (54 versus 63; P < 0.001). The univariate hazard ratio for RCC among HCV patients was 2.20 (95% confidence interval, 1.32-3.67; P = 0.0025). In a multivariate model that included the risk factors age, African-American race, male gender, and chronic kidney disease, the overall hazard ratio for RCC among HCV patients was 1.77 (95% confidence interval, 1.05-2.98; P = 0.0313). Conclusion: Chronic HCV infection confers a risk for the development of RCC. Impact: Clinicians should consider newly identified renal lesions in patients with chronic HCV infection with a heightened suspicion for neoplasm, and newly diagnosed cases of RCC may require more careful surveillance for the presence of HCV infection. Additional studies are required to confirm these findings and to explore potential mechanisms of oncogenesis. Cancer Epidemiol Biomarkers Prev; 19(4); 1066–73. ©2010 AACR.
Citation for Published Item: Use Policy Homers at the Interface between Reward and Pain

Klugmann and Szumlinski. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full DRO policy for further details. Pain alters opioid reinforcement, presumably via neuroadaptations within ascending pain pathways interacting with the limbic system. Nerve injury increases expression of glu-tamate receptors and their associated Homer scaffolding proteins throughout the pain processing pathway. Homer proteins, and their associated glutamate receptors, regulate behavioral sensitivity to various addictive drugs. Thus, we investigated a potential role for Homers in the interactions between pain and drug reward in mice. Chronic constriction injury (CCI) of the sciatic nerve elevated Homer1b/c and/or Homer2a/b expression within all mesolimbic structures examined and for the most part, the Homer increases coincided with elevated mGluR5, GluN2A/B, and the activational state of various downstream kinases. Behaviorally, CCI mice showed pain hypersensitivity and a conditioned place-aversion (CPA) at a low heroin dose that supported conditioned place-preference (CPP) in naïve controls. Null mutations of Homer1a, Homer1, and Homer2, as well as transgenic disruption of mGluR5-Homer interactions, either attenuated or completely blocked low-dose heroin CPP, and none of the CCI mutant strains exhibited heroin-induced CPA. However, heroin CPP did not depend upon full Homer1c expression within the nucleus accumbens (NAC), as CPP occurred in controls infused locally with small hairpin RNA-Homer1c, although intra-NAC and/or intrathecal cDNA-Homer1c,-Homer1a, and-Homer2b infusions (to best mimic CCI's effects) were sufficient to blunt heroin CPP in uninjured mice. However, arguing against a simple role for CCI-induced increases in either spinal or NAC Homer expression for heroin CPA, cDNA infusion of our various cDNA constructs either did not affect (intrathe-cal) or attenuated (NAC) heroin CPA. Together, these data implicate increases in glutamate receptor/Homer/kinase activity within limbic structures, perhaps outside the NAC, as …
Biological studies on free endotoxin and a non-toxic material from culture supernatant fluids of Escherichia coli 078K80.

SUMMARY: A description is given of the biological properties of two substances produced extracellularly by a strain of Escherichia coli 078 K 80, grown in aerated liquid culture. One of the materials was of high molecular weight and possessed the properties of endotoxin extracted from whole organisms by chemical methods. In mice this material was toxic, induced non-specific resistance to infection with Salmonella typhi, necrotized Sacroma 180, and elicited the local and general Shwartzman reactions. In rabbits it was strongly pyrogenic, dermonecrotic, and induced formation of precipitating antibodies. Heat, chemicals and enzymes did not affect its toxicity, but acid hydrolysis rendered it non-toxic. We have called this substance ‘free endotoxin’. The other material was of lower molecular weight and apart from inducing nonspecific resistance to infection with S. typhi in mice, it had none of the properties of the endotoxin.
Inhibition of interleukin-1 responsiveness by type II receptor gene transfer: a surface "receptor" with anti-interleukin-1 function

The hypothesis that the type II receptor (RII) acts as a decoy for interleukin-1 (IL-1) was tested by gene transfer in cells expressing only the type I receptor (8387 fibroblasts). RII-transfected cells showed defective responsiveness to IL-1 in terms of NFkappaB activation, cytokine gene expression and production. Blocking monoclonal antibodies against RII restored the capacity of RII- transfected cells to respond to IL-1 beta. Hence defective IL-1 responsiveness of RII-transfected cells requires surface expression of the molecule. RII-transfected cells showed normal responsiveness to TNF, which shares functional properties and elements in the signal transduction pathway with IL-1. Cells transfected with a deletion mutant of RII missing 26 of 29 amino acids of the cytoplasmic portion of the molecule showed impaired responsiveness to IL-2. Cells transfected with full-length or the cytoplasmic deletion mutant of RII released copious amounts of RII in the supernatant. However, transfected cells showed defective responsiveness to brief exposure to IL-1, in the absence of measurable released RII. These results indicate that impairment of the responsiveness to IL-1 following RII gene transfer was dependent upon surface expression of the molecule, specific for IL-1 and unaffected by truncation of the cytoplasmic portion. Thus, the type II "receptor" is a decoy surface molecule, regulated by antiinflammatory signals, whose only known function is to capture and block IL-1.
Progesterone and estrogen receptors and mammary neoplasia in the Iowa Women's Health Study: how many kinds of breast cancer are there?

Characterization of breast tumors on both estrogen receptor (ER) and progesterone receptor (PR) status suggests distinct biological and clinical profiles. We hypothesized that these tumor subtypes might also show specific differences in their relations with epidemiologic risk factors. Risk factors were assessed via a questionnaire mailed in January 1986 to 37,105 cancer-free women, ages 55-69 years: the Iowa Women's Health Study. To the end of 1992 (241,627 person-years of follow-up), 939 incident breast cancers were ascertained by the Iowa population-based Surveillance, Epidemiology, and End Results Cancer Registry. Joint ER and PR status was determined on a total of 610 (65%) tumors. Three patterns of association were seen in relation to epidemiologic risk factors. Endogenous hormone exposure variables--parity, age at first birth, age at menarche, body mass index, and body fat distribution as defined by waist-to-hip ratio--showed their expected pattern of associations only with PR+ breast cancers. In age- adjusted and polychotomous logistic regression analyses, both ER-PR- and ER+PR- breast cancers showed evidence of an inverted pattern of associations with several risk factors compared with that seen for ER+PR+ cancers [including parity (ER-PR-), waist-to-hip ratio (ER-PR-), body mass index (both), body mass index at age 18 years (ER-PR-), history of bilateral oophorectomy (ER+PR-), and oral contraceptive use (ER+PR-)]. Family history was not associated with ER+PR- cancers; only 8 (8%) of 99 patients with this subtype had a family history of breast cancer compared with 16% of all other types combined. (ABSTRACT TRUNCATED AT 250 WORDS)
Common Ancestry of Herpesviruses and Tailed DNA Bacteriophages

ABSTRACT Comparative analysis of capsid protein structures in the eukaryote-infecting herpesviruses (Herpesviridae) and the prokaryote-infecting tailed DNA bacteriophages (Caudovirales) revealed a characteristic fold that is restricted to these two virus lineages and is indicative of common ancestry. This fold not only serves as a major architectural element in capsid stability but also enables the conformational flexibility observed during viral assembly and maturation. On the basis of this and other emerging relationships, it seems increasingly likely that the very diverse collection of extant viruses may have arisen from a relatively small number of primordial progenitors.
HIV associated thrombotic microangiopathy

Thrombotic microangiopathy (TMA) is a known complication of HIV infection. Endothelial cell injury appears to be the primary event causing platelet activation and deposition in the microvasculature. Direct cytopathic roles of HIV as well as other factors such as malignancy, drugs, and infectious agents have been implicated in the pathogenesis of HIV-TMA. Although the the majority of patients present in a more advanced stage of HIV disease, TMA can be the initial presenting symptom of HIV infection. Clinical features are those of idiopathic TMA, and the diagnosis should be suspected in any patient with new onset thrombocytopenia and microangiopathic haemolytic anaemia. Therapy with plasma exchange or infusion appears to be efficacious. A rapid diagnosis and institution of plasmapheresis is crucial for a favourable outcome. The long term prognosis of HIV-TMA is unfavourable and may depend on the stage of HIV infection. The recent data after the use of highly active retroviral treatment, however, are unavailable and current prognosis is therefore uncertain.
Quantification of experimental Salmonella enteritidis carrier state in B13 leghorn chicks.

Quantification of the carrier state of Salmonella enteritidis in chicks (i.e., persistent asymptomatic association of S. enteritidis with the host), should provide an optimized means for further investigations into this problem. We therefore developed an experimental carrier state model by oral inoculation of low doses (10(2)-10(4)) of S. enteritidis in B13 chicks at different ages. Liver, spleen, and ceca colonizations by the challenge strains were measured weekly by enumeration of S. enteritidis colony-forming units (CFU) for 7-12 weeks. High mortality rates, incompatible with the carrier state, were observed in chicks inoculated with 10(2) organisms of either a parental strain of S. enteritidis (5556) or a mutant resistant to streptomycin (Smr) and nalidixic acid (Nalr) (strain 1009) at 1 day old. Both strains colonized organs similarly, allowing us to use subsequently the SmrNalr mutant strain. The selected low doses of S. enteritidis induced no deaths in chicks inoculated at 1 or 3 weeks of age. However, inoculation of 3-week-old chicks did not induce a satisfactory carrier state; organ colonization by S. enteritidis was weak and transient, even after inoculation of 10(8) SE. In contrast, some birds infected at 1 week of age presented the challenge strain in the liver and spleen for 3 weeks after inoculation and in the ceca for 12 weeks postchallenge. Most of these birds were colonized by S. enteritidis in the liver and in the ceca for 3 weeks and 10 weeks, respectively, following inoculation. Generally, CFU levels were highest during the first week(s) after inoculation and then decreased progressively. Levels of S. enteritidis were lower in the liver and spleen than in the ceca. Oral inoculation of 1-week-old birds with 5 x 10(4) S. enteritidis provided the required model, allowing quantification of the carrier state of S. enteritidis in chicks.
Energy Absorption of Structures and Materials

Description: The prediction of damage to structures caused by accidental collision – whether to automobiles, offshore installations or simply the packaging around an electrical appliance – is a crucial factor in their design. This important new study focuses on the way in which structures and materials can be designed to absorb kinetic energy in a controllable and predictable manner. An investigation into energy absorption requires an understanding of materials engineering, structural mechanics, the theory of plasticity and impact dynamics. Whilst a great deal of research has been undertaken on various aspects of these subjects, this knowledge is diffuse and widely scattered. Based on their extensive research and experience in the field, Guoxing Lu and Tongxi Yu have synthesised the most recent developments and latest research to form a detailed and comprehensive treatment of the subject.
EFFECTS OF DELIVERY METHOD ON SEROLOGICAL RESPONSES OF BIGHORN SHEEP TO A MULTIVALENT PASTEURELLA HAEMOLYTICA SUPERNATANT VACCINE

The safety and efficacy of a remotely delivered multivalent Pasteurella haemolytica supernatant vaccine (serotypes A2 and T10) were examined in captive Rocky Mountain bighorn sheep (Ovis canadensis canadensis). Twenty bighorn sheep were grouped according to baseline leukotoxin neutralizing antibody titers (≤2 or .2 log2−1) and vaccination history (previously vaccinated or unvaccinated). Within these groups, animals were randomly assigned to one of two delivery treatments: hand injection (control) or biobullet implantation. All bighorns received a single dose from the same lot of vaccine (n = 10/treatment); four additional animals were injected intramuscularly with 0.9% saline as unvaccinated sentinels. Mild, transient lameness one day after hand injection or biobullet implantation was the only adverse effect. Serum neutralizing antibody titers to P. haemolytica leukotoxin differed between delivery treatments (P = 0.009) and among baseline titer/vaccination history groups (P = 0.013). Neutralizing titers were higher among hand-injected bighorns. Although neutralizing titers were lower among implanted bighorns than hand-injected controls at 1 wk (P = 0.002) and 2 wk (P = 0.021) after vaccination, seroconversion rates in response to implantation (6/10) and hand injection (9/10) did not differ (P = 0.303). Agglutinating antibody titers to T10 were high and did not vary over time or between delivery treatments. Agglutinating antibody titers to A2 in the hand-injected controls were not different (P ≥ 0.07) than those in bighorns vaccinated with biobullet implantation. These data demonstrate that although hand injection elicits higher absolute titers, biobullet implantation may also stimulate effective antibody responses to P. haemolytica supernatant vaccine. Further evaluation of biobullet vaccination against pneumonic pasteurellosis in free-ranging populations of wild bighorn sheep is warranted.
Algorithmic Prediction of Health-Care Costs

The rising cost of health care is one of the world's most important problems. Accordingly, predicting such costs with accuracy is a significant first step in addressing this problem. Since the 1980s, there has been research on the predictive modeling of medical costs based on (health insurance) claims data using heuristic rules and regression methods. These methods, however, have not been appropriately validated using populations that the methods have not seen. We utilize modern data-mining methods, specifically classification trees and clustering algorithms, along with claims data from over 800,000 insured individuals over three years, to provide rigorously validated predictions of health-care costs in the third year, based on medical and cost data from the first two years. We quantify the accuracy of our predictions using unseen (out-of-sample) data from over 200,000 members. The key findings are: (a) our data-mining methods provide accurate predictions of medical costs and represent a powerful tool for prediction of health-care costs, (b) the pattern of past cost data is a strong predictor of future costs, and (c) medical information only contributes to accurate prediction of medical costs of high-cost members.