Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacodynamic Evaluation of the Target Efficacy of SB939, an Oral HDAC Inhibitor with Selectivity for Tumor Tissue

SB939 is an oral histone deacetylase (HDAC) inhibitor currently in phase II clinical trials potently inhibiting class I, II, and IV HDACs with favorable pharmacokinetic properties, resulting in tumor tissue accumulation. To show target efficacy, a Western blot assay measuring histone H3 acetylation (acH3) relative to a loading control was developed, validated on cancer cell lines, peripheral blood mononuclear cells (PBMC), and in animal tumor models. Exposure of cells to 60 nmol/L (22 ng/mL) SB939 for 24 hours was sufficient to detect an acH3 signal in 25 μg of protein lysate. AcH3 levels of liver, spleen, PBMCs, bone marrow and tumor were measured in BALB/c mice, HCT-116 xenografted BALB/c nude mice, or in SCID mice orthotopically engrafted with AML (HL-60) after oral treatment with SB939. AcH3 could only be detected after treatment. In all tissues, the highest signal detected was at the 3-hour time point on day 1. On day 15, the signal decreased in normal tissues but increased in cancerous tissues and became detectable in the bone marrow of leukemic mice. In all tissues, acH3 correlated with SB939 dose levels (r2 = 0.76–0.94). When applied to PBMCs from 30 patients with advanced solid malignancies in a phase I clinical trial, a dose-dependent (10–80 mg) increase in relative acH3 was observed 3-hour postdose on day 1, correlating with Cmax and AUC of SB939 concentrations in plasma (r = 0.97, P = 0.014). Our data show that the favorable pharmacokinetic and pharmacodynamic properties of SB939 are translated from preclinical models to patients. Mol Cancer Ther; 10(7); 1207–17. ©2011 AACR.
Intrauterine devices and risk of uterine perforation: current perspectives

Uterine perforation is an uncommon complication of intrauterine device insertion, with an incidence of one in 1,000 insertions. Perforation may be complete, with the device totally in the abdominal cavity, or partial, with the device to varying degrees within the uterine wall. Some studies show a positive association between lactation and perforation, but a causal relationship has not been established. Very rarely, a device may perforate into bowel or the urinary tract. Perforated intrauterine devices can generally be removed successfully at laparoscopy.
High Glucose Induced Alteration of SIRTs in Endothelial Cells Causes Rapid Aging in a p300 and FOXO Regulated Pathway

In diabetes, some of the cellular changes are similar to aging. We hypothesized that hyperglycemia accelerates aging-like changes in the endothelial cells (ECs) and tissues leading to structural and functional damage. We investigated glucose-induced aging in 3 types of ECs using senescence associated β-gal (SA β-gal) staining and cell morphology. Alterations of sirtuins (SIRTs) and their downstream mediator FOXO and oxidative stress were investigated. Relationship of such alteration with histone acetylase (HAT) p300 was examined. Similar examinations were performed in tissues of diabetic animals. ECs in high glucose (HG) showed evidence of early senescence as demonstrated by increased SA β-gal positivity and reduced replicative capacities. These alterations were pronounced in microvascular ECs. They developed an irregular and hypertrophic phenotype. Such changes were associated with decreased SIRT (1–7) mRNA expressions. We also found that p300 and SIRT1 regulate each other in such process, as silencing one led to increase of the others’ expression. Furthermore, HG caused reduction in FOXO1’s DNA binding ability and antioxidant target gene expressions. Chemically induced increased SIRT1 activity and p300 knockdown corrected these abnormalities slowing aging-like changes. Diabetic animals showed increased cellular senescence in renal glomerulus and retinal blood vessels along with reduced SIRT1 mRNA expressions in these tissues. Data from this study demonstrated that hyperglycemia accelerates aging-like process in the vascular ECs and such process is mediated via downregulation of SIRT1, causing reduction of mitochondrial antioxidant enzyme in a p300 and FOXO1 mediated pathway.
A protein induced during nerve growth (GAP-43) is a major component of growth-cone membranes

Growth cones are specialized structures that form the distal tips of growing axons. During both normal development of the nervous system and regeneration of injured nerves, growth cones are essential for elongation and guidance of growing axons. Developmental and regenerative axon growth is frequently accompanied by elevated synthesis of a protein designated GAP-43. GAP-43 has now been found to be a major component of growth-cone membranes in developing rat brains. Relative to total protein, GAP-43 is approximately 12 times as abundant in growth-cone membranes as in synaptic membranes from adult brains. Immunohistochemical localization of GAP-43 in frozen sections of developing brain indicates that the protein is specifically associated with neuropil areas containing growth cones and immature synaptic terminals. The results support the proposal that GAP-43 plays a role in axon growth.
Mortality Benefit of a Fourth-Generation Synchronous Telehealth Program for the Management of Chronic Cardiovascular Disease: A Longitudinal Study

Background We have shown that a fourth-generation telehealth program that analyzes and responds synchronously to data transferred from patients is associated with fewer hospitalizations and lower medical costs. Whether a fourth-generation telehealth program can reduce all-cause mortality has not yet been reported for patients with chronic cardiovascular disease. Objective We conducted a clinical epidemiology study retrospectively to determine whether a fourth-generation telehealth program can reduce all-cause mortality for patients with chronic cardiovascular disease. Methods We enrolled 576 patients who had joined a telehealth program and compared them with 1178 control patients. A Cox proportional hazards model was fitted to analyze the impact of risk predictors on all-cause mortality. The model adjusted for age, sex, and chronic comorbidities. Results There were 53 (9.3%) deaths in the telehealth group and 136 (11.54%) deaths in the control group. We found that the telehealth program violated the proportional hazards assumption by the Schoenfeld residual test. Thus, we fitted a Cox regression model with time-varying covariates. The results showed an estimated hazard ratio (HR) of 0.866 (95% CI 0.837-0.896, P<.001; number needed to treat at 1 year=55.6, 95% CI 43.2-75.7 based on HR of telehealth program) for the telehealth program on all-cause mortality after adjusting for age, sex, and comorbidities. The time-varying interaction term in this analysis showed that the beneficial effect of telehealth would increase over time. Conclusions The results suggest that our fourth-generation telehealth program is associated with less all-cause mortality compared with usual care after adjusting for chronic comorbidities.
Screen-Printed Curvature Sensors for Soft Robots

Castable elastomers have been used to fabricate soft robotic devices and it has been shown that the technique scales well from prototyping to mass manufacturing. However, similarly scalable techniques for integrating strain or curvature sensors into such devices are still lacking. In this paper, we show that screen-printed silver conductors serve well as curvature sensors for soft robotic devices. The sensors are produced onto elastomer substrates in a single printing step and integrated into soft pneumatic actuators. We characterized the resistance-curvature relationship of the sensors, which allows the curvature of the actuators to be estimated from the sensor measurements. Hysteresis was observed, which does limit the absolute accuracy of the sensors. However, temperature characterizations showed that the sensor measurements are not significantly affected by temperature fluctuations during normal operation. Dynamic experiments showed that the bandwidth of the sensors is larger than the bandwidth of the actuators. We experimentally validated that these sensors can be used to detect whether the motion of an actuator has been blocked, clearing the way toward simple-to-fabricate soft robots that react to their surroundings. Finally, we demonstrate a three-fingered soft robotic gripper with integrated sensors. We conclude that screen-printing is a promising way to integrate curvature sensors into soft robots.
Carotenoid content of thermally processed tomato-based food products

Tomato-based food products such as tomato paste, tomato sauce, and tomato-based soups are rich in carotenoid compounds and are frequently consumed in the United States. Foods such as these, which are high in carotenoid content, are of interest because of the demonstrated association between consumption of fruits and vegetables and reduced risk of lung and other epithelial cancers in humans. Limited analytical data on the carotenoid content of tomato-based products are available in food tables and data bases; however, they are usually reported only in terms of vitamin A activity. In this study name-brand and store-brand tomato-based food products purchased in three major U.S. cities were extracted and carotenoids were individually identified and quantified by reversed-phase HPLC according to methodology developed in our laboratory. The carotenoids that were detected and quantified included lycopene, lycopene-5,6-diol, lutein, alpha-, beta-, gamma-, and theta-carotenes, neurosporene, phytoene, and phytofluene. As expected, lycopene was the most abundant carotenoid, ranging in concentration from 0.3 mg/100 g in vegetable beef soup to 55 mg/100 g in tomato paste. The concentration of beta-carotene ranged from 0.23 mg/100 g in tomato soup to 1.51 mg/100 g in vegetable beef soup. Lutein was found at very low concentrations (less than 0.2 mg/100 g) in all products analyzed except tomato paste, which contained 0.34 g/100 g.
ScrambleSuit: a polymorphic network protocol to circumvent censorship

Deep packet inspection technology became a cornerstone of Internet censorship by facilitating cheap and effective filtering of what censors consider undesired information. Moreover, filtering is not limited to simple pattern matching but makes use of sophisticated techniques such as active probing and protocol classification to block access to popular circumvention tools such as Tor. In this paper, we propose ScrambleSuit; a thin protocol layer above TCP whose purpose is to obfuscate the transported application data. By using morphing techniques and a secret exchanged out-of-band, we show that ScrambleSuit can defend against active probing and other fingerprinting techniques such as protocol classification and regular expressions. We finally demonstrate that our prototype exhibits little overhead and enables effective and lightweight obfuscation for application layer protocols.
Predicting Continuous Probability Distribution of Image Emotions in Valence-Arousal Space

Previous works on image emotion analysis mainly focused on assigning a dominated emotion category or the average dimension values to an image for affective image classification and regression. However, this is often insufficient in many applications, as the emotions that are evoked in viewers by an image are highly subjective and different. In this paper, we propose to predict the continuous probability distribution of dimensional image emotions represented in valence-arousal space. By the statistical analysis on the constructed Image-Emotion-Social-Net dataset, we represent the emotion distribution as a Gaussian mixture model (GMM), which is estimated by the EM algorithm. Then we extract commonly used features of different levels for each image. Finally, we formulize the emotion distribution prediction as a multi-task shared sparse regression (MTSSR) problem, which is optimized by iteratively reweighted least squares. Besides, we introduce three baseline algorithms. Experiments conducted on the Image-Emotion-Social-Net dataset demonstrate the superiority of the proposed method, as compared to some state-of-the-art approaches.
Pollen Foraging Behaviour of Honey Bee (Apis mellifera L.) in Southern West Bengal, India

ABSTRACT Pollen loads of Apis mellifera were analysed to assess their daily pollen collection, polleniferous flora and their pollen biomass contribution in southern West Bengal, India. After that, the pollen host selection and pollen foraging activity of the bee species were also determined. The average daily harvest of pollen loads per honey bee colony was 8.5 g to 127.2 g. The pollen flow through the colonies was the highest during spring, followed by winter and summer, whereas during the monsoon it was the lowest. The weight of a single pollen load ranged from 3.22 mg to 11.73 mg and greatly varied within each season, but seasonal average values do not statistically differ. Families that contributed major amount of biomass were Arecaceae, Myrtaceae, Brassicaceae, Fabaceae, Pedaliaceae and Apiaceae. Taxa providing large amounts of biomass were Brassica nigra, Eucalyptus globulus, Borassus flabellifer, Sesamum indicum, Acacia auriculiformis, Coriandrum sativum, Cocos nucifera, Phoenix sylvestris and Mikania scandens (Asteraceae). As the bee species foraged on 26.32% (80 plant taxa) of the local angiosperm flora, the broad polylecty category was inferred. The pollen host selection by the bee species significantly depends on the flower availability index (FAi) and pollen availability index (PAi) rather than on an individual flower's pollen quality (in term of pollen morphological characteristics and crude protein content) and pollen quantity (number of pollen grains/flower and amount of pollen biomass/flower). The pollen foraging activity of the bee species varied according to time as well as season. The activity was higher between 9.00 and 10.00 am. Seasonally, the highest activity was observed in spring and the lowest during the monsoon. Furthermore, the ratio of pollen foragers to total incoming foragers also varied according to the time of day as well as the season, and was largely dependent of resource availability.
MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4

Significance MuSK myasthenia gravis (MG) is a debilitating autoimmune disease: one-third of MuSK MG patients experience a life-threatening respiratory crisis, and long-term immunosuppression is the only current treatment option. Here we show that pathogenic human IgG4 MuSK antibodies bind to the first Ig-like domain in MuSK and prevent Lrp4 from binding MuSK, thereby inhibiting Agrin-stimulated MuSK phosphorylation. This inhibitory mechanism is likely responsible for disrupting the structure of the synapse, compromising synaptic transmission and causing disease. Our findings therefore suggest that therapeutic strategies designed to increase MuSK activity may prove effective in treating MuSK MG. Moreover, our studies provide mechanistic understanding of an IgG4-mediated autoimmune disease and may shed light on the mechanisms of other IgG4-mediated autoimmune diseases. Myasthenia gravis (MG) is a severely debilitating autoimmune disease that is due to a decrease in the efficiency of synaptic transmission at neuromuscular synapses. MG is caused by antibodies against postsynaptic proteins, including (i) acetylcholine receptors, the neurotransmitter receptor, (ii) muscle-specific kinase (MuSK), a receptor tyrosine kinase essential for the formation and maintenance of neuromuscular synapses, and (iii) low-density lipoprotein receptor-related protein 4 (Lrp4), which responds to neural Agrin by binding and stimulating MuSK. Passive transfer studies in mice have shown that IgG4 antibodies from MuSK MG patients cause disease without requiring complement or other immune components, suggesting that these MuSK antibodies cause disease by directly interfering with MuSK function. Here we show that pathogenic IgG4 antibodies to MuSK bind to a structural epitope in the first Ig-like domain of MuSK, prevent binding between MuSK and Lrp4, and inhibit Agrin-stimulated MuSK phosphorylation. In contrast, these IgG4 antibodies have no direct effect on MuSK dimerization or MuSK internalization. These results provide insight into the unique pathogenesis of MuSK MG and provide clues toward development of specific treatment options.
Postprandial Glucose Improves the Risk Prediction of Cardiovascular Death Beyond the Metabolic Syndrome in the Nondiabetic Population

OBJECTIVE With increasing evidence about the cardiovascular risk associated with postprandial nonfasting glucose and lipid dysmetabolism, it remains uncertain whether the postprandial glucose concentration increases the ability of metabolic syndrome to predict cardiovascular events. RESEARCH DESIGN AND METHODS This was an observational study of 15,145 individuals aged 35–75 years without diabetes or cardiovascular diseases. Postprandial glucose was obtained 2 h after a lunch meal. Metabolic syndrome was diagnosed using the criteria of the U.S. National Cholesterol Education Program Adult Treatment Panel III. Cardiovascular and all-cause deaths were primary outcomes. RESULTS During a median follow-up of 6.7 years, 410 individuals died, including 82 deaths from cardiovascular causes. In a Cox model adjusting for metabolic syndrome status as well as age, sex, smoking, systolic blood pressure, LDL, and HDL cholesterol levels, elevated 2-h postprandial glucose increased the risk of cardiovascular and all-cause death (per millimole per liter increase, hazard ratio 1.26 [95% CI 1.11–1.42] and 1.10 [1.04–1.16], respectively), with significant trends across the postprandial glucose quintiles. Including 2-h postprandial glucose into a metabolic syndrome–included multivariate risk prediction model conferred a discernible improvement of the model in discriminating between those who died of cardiovascular causes and who did not (integrated discrimination improvement 0.4, P = 0.005; net reclassification improvement 13.4%, P = 0.03); however, the improvement was only marginal for all-cause death. CONCLUSIONS Given the risk prediction based on metabolic syndrome and established cardiovascular risk factors, 2-h postprandial glucose improves the predictive ability to identity nondiabetic individuals at increased risk of cardiovascular death.
Pegging to the Dollar and the Euro

The newly launched euro has already accumulated some "trackers"--that is, countries that attempt to maintain exchange rate stability with it. In this paper, we ask whether the existence of trackers should be a matter of concern for the European Union. To gain some perspective, we review the historical experience of the US with respect to dollar trackers. We identify and analyse the countries most likely to track the euro. Although the aggregate size of the group of potential euro trackers is small relative to the euro zone, we argue that this does not justify an attitude of benign neglect. Rather, we make recommendations for EU policy towards euro trackers, arguing in favour of some limited and conditional support for stable bilateral exchange rates. Copyright 1999 by Blackwell Publishers Ltd.
Molecular Profiling of Aromatase Inhibitor–Treated Postmenopausal Breast Tumors Identifies Immune-Related Correlates of Resistance

Purpose: Estrogen withdrawal by treatment with aromatase inhibitors is the most effective form of endocrine therapy for postmenopausal estrogen receptor–positive (ER+) breast cancer. However, response to therapy varies markedly and understanding of the precise molecular effects of aromatase inhibitors and causes of resistance is limited. We aimed to identify in clinical breast cancer those genes and pathways most associated with resistance to aromatase inhibitors by examining the global transcriptional effects of AI treatment. Experimental Design: Baseline and 2-week posttreatment biopsies were obtained from 112 postmenopausal women with ER+ breast cancer receiving neoadjuvant anastrozole. Gene expression data were obtained from 81 baseline and 2-week paired samples. Pathway analysis identified (i) the most prevalent changes in expression and (ii) the pretreatment genes/pathways most related to poor antiproliferative response. Results: A total of 1,327 genes were differentially expressed after 2-week treatment (false discovery rate < 0.01). Proliferation-associated genes and classical estrogen-dependent genes were strongly downregulated whereas collagens and chemokines were upregulated. Pretreatment expression of an inflammatory signature correlated with antiproliferative response to anastrozole and this observation was validated in an independent study. Higher expression of immune-related genes such as SLAMF8 and TNF as well as lymphocytic infiltration were associated with poorer response (P < 0.001) and validated in an independent cohort. Conclusions: The molecular response to aromatase inhibitor treatment varies greatly between patients consistent with the variable clinical benefit from aromatase inhibitor treatment. Higher baseline expression of an inflammatory signature is associated with poor antiproliferative response and should be assessed further as a novel biomarker and potential target for aromatase inhibitor-treated patients. Clin Cancer Res; 19(10); 2775–86. ©2013 AACR.
Effect of antenna polarization on the capacity of a multiple element system in an indoor environment

We analyze the behavior of a multiple element antenna system in an indoor environment based on the measurements taken in the Lucent Bell Labs building in Crawford Hill, NJ, with a system of 12 transmitters and 15 receivers. In particular, we investigate the capacity behavior with respect to the polarization of the transmitting/receiving elements and the distance between the transmitting and the receiving arrays. The analysis of the power rolloff versus distance clearly demonstrates the different propagation characteristics of the horizontally versus the vertically polarized electric fields. Under strong line-of-sight (LOS) conditions (hallway environment), the power of the horizontally polarized waves falls off faster with distance than that of the vertically polarized fields. Also, the cross-polarization coupling is about -15 dB. Under nonline-of-sight (NLOS) conditions (labs), both polarizations display similar rolloff behavior with distance and the cross-polarization coupling is about 0 dB. There is a power loss of at least 15 dB under NLOS conditions relative to LOS conditions. The average received signal power affects the system capacity. In the hallway, horizontally polarized systems achieve lower capacities than their vertically polarized counterparts. Also the achievable capacity in the labs is much lower than that in the hallway, because of the lower average received power. The comparison of single polarization systems to hybrid polarization systems shows that combined polarization systems perform better in terms of achievable capacity. Therefore, there lies an advantage in using both electric field polarizations. However, under strong LOS conditions the channel itself inherently limits the capacity behavior of the system.