Miracle-dz/UniFAR-FTUs huggingface dataset:
Improving Accuracy of Tay Sachs Carrier Screening of the Non-Jewish Population: Analysis of 34 Carriers and Six Late-Onset Patients With HEXA Enzyme and DNA Sequence Analysis

The purpose of this study was to determine whether combining different testing modalities namely β-hexosaminidase A (HEXA) enzyme analysis, HEXA DNA common mutation assay, and HEXA gene sequencing could improve the sensitivity for carrier detection in non-Ashkenazi (AJ) individuals. We performed a HEXA gene sequencing assay, a HEXA DNA common mutation assay, and a HEXA enzyme assay on 34 self-reported Tay-Sachs disease (TSD) carriers, six late-onset patients with TSD, and one pseudodeficiency allele carrier. Sensitivity of TSD carrier detection was 91% for gene sequencing compared with 91% for the enzyme assay and 52% for the DNA mutation assay. Gene sequencing combined with enzyme testing had the highest sensitivity (100%) for carrier detection. Gene sequencing detected four novel mutations, three of which are predicted to be disease causing [118.delT, 965A→T (D322V), and 775A→G (T259A)]. Gene sequencing is useful in identifying rare mutations in patients with TSD and their families, in evaluating spouses of known carriers for TSD who have indeterminate enzyme analysis and negative for common mutation analysis, and in resolving ambiguous enzyme testing results.
Visualizing and identifying intrusion context from system calls trace

Anomaly-based intrusion detection (AID) techniques are useful for detecting novel intrusions without known signatures. However, AID techniques suffer from higher false alarm rate compared to signature-based intrusion detection techniques. In this paper, the concept of intrusion context identification is introduced to address the problem. The identification of the intrusion context can help to significantly enhance the detection rate and lower the false alarm rate of AID techniques. To evaluate the effectiveness of the concept, a simple but representative scheme for intrusion context identification is proposed, in which the anomalies in the intrusive datasets are visualized first, and then the intrusion contexts are identified from the visualized anomalies. The experimental results show that using the scheme, the intrusion contexts can be visualized and extracted from the audit trails correctly. In addition, as an application of the visualized anomalies, an implicit design drawback in t-stide is found after careful analysis. Finally, based on the identified intrusion context and the efficiency comparison, several findings are made which can offer useful insights and benefit future research on AID techniques.
Ameliorative potential of resveratrol on proinflammatory cytokines, hyperglycemia mediated oxidative stress, and pancreatic β‐cell dysfunction in streptozotocin‐nicotinamide‐induced diabetic rats

Chronic exposure of pancreatic β‐cells to supraphysiologic glucose causes adverse β‐cell dysfunction. Thus, the present study was aimed to investigate the hypothesis that oral administration of resveratrol attenuates hyperglycemia, proinflammatory cytokines and antioxidant competence and protects β‐cell ultrastructure in streptozotocin‐nicotinamide‐induced diabetic rats. Oral administration of resveratrol (5 mg/kg body weight) to diabetic rats for 30 days showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), TNF‐α, IL‐1β, IL‐6, NF‐κB p65 unit and nitric oxide (NO) with concomitant elevation in plasma insulin. Further, resveratrol treated diabetic rats elicited a notable attenuation in the levels of lipid peroxides, hydroperoxides and protein carbonyls in both plasma and pancreatic tissues. The diminished activities of pancreatic superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione‐S‐transferase (GST) as well as the decreased levels of plasma ceruloplasmin, vitamin C, vitamin E and reduced glutathione (GSH) in diabetic rats were reverted to near normalcy by resveratrol administration. Based on histological and ultrastructural observations, it is first‐time reported that the oral administration of resveratrol may effectively rescue β‐cells from oxidative damage without affecting their function and structural integrity. The results of the present investigation demonstrated that resveratrol exhibits significant antidiabetic potential by attenuating hyperglycemia, enhancing insulin secretion and antioxidant competence in pancreatic β‐cells of diabetic rats. J. Cell. Physiol. 224: 423–432, 2010. © 2010 Wiley‐Liss, Inc.
SEX DIFFERENCES IN THE ADMINISTRATION-TIME-DEPENDENT EFFECTS OF LOW-DOSE ASPIRIN ON AMBULATORY BLOOD PRESSURE IN HYPERTENSIVE SUBJECTS

Previous studies have revealed sex differences in blood pressure (BP) regulation, pathophysiology of hypertension, and treatment responses to medication. On the other hand, low-dose aspirin has been shown to reduce BP when administered at bedtime, as opposed to upon awakening, in hypertensive subjects and pregnant women at risk for preeclampsia. The purpose of this research was to investigate the potential sex differences in the administration-time-dependent influence of aspirin on BP. We studied 130 men and 186 women with untreated mild hypertension, 44.1 ± 13.2 yrs of age, randomized to receive aspirin (100 mg/day) either on awakening or at bedtime daily for three months. BP was measured for 48 h before and after treatment. With ASA on awakening, ambulatory BP was unchanged in men and slightly but significantly elevated in women (1.7/1.4 mmHg in the 48 h SBP/DBP means, respectively; p < 0.023). BP was significantly reduced after aspirin at bedtime and to a larger extent in women (−8.0/−5.6 mmHg in SBP/DBP) than men (5.5/3.4 mmHg, respectively; p < 0.009 between men and women). Factors influencing a stronger response of BP to aspirin at bedtime included female sex, elevated fasting glucose, and high glomerular filtration rate. This study corroborates the significant administration-time-dependent effect of low-dose aspirin on ambulatory BP in subjects with untreated mild hypertension, while documenting significant sex differences in the BP response to aspirin. Accordingly, results indicate that bedtime is the optimal time for aspirin ingestion in both men and women. This timed administration of low-dose aspirin could provide a cost-effective valuable approach for BP control and potential added cardiovascular protection, especially in hypertensive women. (Author correspondence: rhermida@uvigo.es)
Bisbibenzyls, novel proteasome inhibitors, suppress androgen receptor transcriptional activity and expression accompanied by activation of autophagy in prostate cancer LNCaP cells

Abstract Context: Bisbibenzyl compounds have gained our interests for their potential antitumor activity in malignant cell-types. Objective: The objective of this study is to investigate the effect of bisbibenzyl compounds riccardin C (RC), marchantin M (MM), and riccardin D (RD) on androgen receptor (AR) in prostate cancer (PCa) cells. Materials and methods: After exposure to 10 μM of the compounds for 24 h, cell cycle and cell survival analyses were performed using FACS and MTT assay to confirm the effect of these bisbibenzyls on PCa LNCaP cells. Changes in the AR expression and function, as the result of exposure to the compounds, were investigated using real-time PCR, ELISA, transient transfection, western blotting (WB), immunoprecipitation, and immunofluorescence staining (IF). Chemical-induced autophagy was examined by WB, IF, and RNAi. Results: RC, MM, and RD reduced the viability of LNCaP cells accompanied with arrested cell cycle in the G0/G1 phase and induction of apoptosis. Further investigation revealed that these compounds significantly inhibited AR expression at mRNA and protein levels, leading to the suppression of AR transcriptional activity. Moreover, inhibition of proteasome activity by bisbibenzyls, which in turn caused the induction of autophagy, as noted by induction of LC3B expression, conversion, and accumulation of punctate dots in treated cells. Co-localization of AR/LC3B and AR/Ub suggested that autophagy contributed to the degradation of polyubiquitinated-AR when proteasome activity was suppressed by the bisbibenzyls. Discussion and conclusion: Suppression of proteasome activity and induction of autophagy were involved in bisbibenzyl-mediated modulation of AR activities and apoptosis, suggesting their potential in treating PCa.
Classical Mechanics

This chapter applies our reasoning about structure in physics to two formulations of classical mechanics, Lagrangian and Newtonian mechanics, that are generally taken to be completely equivalent. It argues that these two formulations differ in both the type and amount of structure presupposed by their dynamical laws, as revealed by the invariances of the equations representing the laws as well as the theories’ statespace structures. This suggests that these are not fully equivalent theories: they differ in dynamical structure. There are also various metaphysical differences between them. The chapter goes on to argue that the minimize-structure rule tells us to choose one over the other. Along the way, the idea that preferred or natural coordinate systems indicate underlying structure is discussed.
Initial Experience with the High‐Density Mesh Ablation Catheter for Pulmonary Vein Isolation

Background: Pulmonary vein isolation (PVI) is usually performed with multiple point‐by‐point radiofrequency ablation with a second multielectrode circular mapping catheter to validate isolation. We evaluated a 30‐mm high‐density mesh electrode (HDMA) for mapping and PVI in patients with recurrent atrial fibrillation (AF).
Comparative analysis of ocean color measurements of IRS-P4 OCM and SeaWiFS in the Arabian Sea

The Indian Remote Sensing P4 (IRS-P4) satellite has carried an Ocean Color Monitor (OCM) sensor for investigations on ocean color parameters in open and coastal seas. The Sea-viewing Wide Field-of-view Sensor (SeaWiFS) sensor of the National Aeronautics and Space Administration is also an ocean color instrument, which is in concurrent operation with IRS-P4 OCM. Results of an intercomparison analysis are described for ocean color data from OCM and SeaWiFS, using a consistent methodology for atmospheric correction and bio-optical algorithms. Near synchronous data of OCM and SeaWiFS sensors was obtained on March 22, 2000 over parts of the Arabian Sea. The OCM and SeaWiFS image data were processed to estimate normalized water-leaving radiance (nL/sub w/) in 443-, 490-, 510-, and 555-nm spectral bands. A comparison was made for 10/spl times/10 colocated pixels of OCM and SeaWiFS images. Differences were observed in the estimated values of nL/sub w/ [443] and nL/sub w/ [490], respectively, obtained by OCM, when compared to SeaWiFS. However, OCM estimated nL/sub w/ [510] and nL/sub w/ [555] were comparable to that of SeaWiFS. An intercalibration approach for OCM was adopted using SeaWiFS calibration as "standard". An intercomparison of the top-of-the-atmosphere radiance measured by OCM and SeaWiFS sensor was performed for colocated pixels having similar viewing geometry. Individual OCM bands were vicariously recalibrated, and a gain coefficient for each OCM band was derived through this procedure. The OCM data for March 22, 2000 were reprocessed using derived gain coefficients, and new gain coefficients were further tested on an independent dataset of March 18, 2000. Results obtained for the recalibrated OCM data showed a better match up with the ocean color estimation obtained by SeaWiFS.
Approximation and Kernelization for Chordal Vertex Deletion

The Chordal Vertex Deletion (ChVD) problem asks to delete a minimum number of vertices from an input graph to obtain a chordal graph. In this paper we develop a polynomial kernel for ChVD under the parameterization by the solution size, as well as poly(opt) approximation algorithm. The first result answers an open problem of Marx from 2006 [WG 2006, LNCS 4271, 37-48].
Impact of occupational cadmium exposure on spirometry, sputum leukocyte count, and lung cell DNA damage among Indian goldsmiths.

BACKGROUND Cadmium is frequently used in manual jewelry industries. Although its toxicity on lung function is well-known, the mechanism is not well-understood. METHODS Among 26 goldsmiths exposed to cadmium (mean age 35.9 ± 5.0 years) and 17 referent workers without direct exposure (36.6 ± 6.6 years), we measured blood and urinary cadmium concentration and performed spirometry and quantified leukocytes and comet formation in the cells from spontaneously expectorated sputum samples. RESULTS The goldsmiths had higher cadmium concentration in urine (mean 6.14 ± 1.63 vs. 0.47 ± 0.17 μg/dl) and blood (0.90 ± 0.23 vs. 0.02 ± 0.007 μg/dl) than the referents, which were inversely associated with FEV1 /FVC. Cadmium exposure also resulted in higher neutrophils (%) and lower macrophage (%) prevalence in the sputum and also caused substantial DNA damage in the lung cells among the goldsmiths than the referents (69 vs. 14%). CONCLUSION Altered lung function among cadmium-exposed goldsmiths was associated with enhanced inflammatory response and increased cellular DNA damage in the lungs.
New surfactant protein C gene mutations associated with diffuse lung disease

Background: Mutations in the surfactant protein C gene (SFTPC) have been recently associated with the development of diffuse lung disease, particularly sporadic and familial interstitial lung disease (ILD). Objective: We have investigated the prevalence and the spectrum of SFTPC mutations in a large cohort of infants and children with diffuse lung disease and suspected with surfactant dysfunction. Method and results: 121 children were first screened for the common SFTPC mutation, p.Ile73Thr (I73T). Ten unrelated patients were shown to carry this mutation. The I73T mutation was inherited in six cases, and appeared de novo in four. The 111 patients without the I73T mutation were screened for the entire coding sequence of SFTPC. Of these, eight (seven unrelated) subjects were shown to carry a novel mutant allele of SFTPC. All these seven new mutations are located in the BRICHOS domain except the p.Val39Ala (V39A) mutation, which is in the surfactant protein C (SP-C) mature peptide. Conclusions: Our results confirm that SFTPC mutations are a frequent cause of diffuse lung disease, and that I73T is the most frequent SFTPC mutation associated with diffuse lung disease.
Statins can improve proteinuria and glomerular filtration rate loss in chronic kidney disease patients, further reducing cardiovascular risk. Fact or fiction?

Introduction: The prevalence of chronic kidney disease (CKD), a risk factor for cardiovascular disease (CVD), is increasing worldwide. Statin treatment, the cornerstone of prevention or treatment of CVD, might have beneficial effects on urine protein excretion and renal function as determined by the glomerular filtration rate, whereas it might protect from acute kidney injury (AKI), mainly due to contrast-induced AKI. These beneficial effects on CKD may not be drug class effects; specific statins at specific doses may help prevent CKD deterioration and reduce CVD risk. We analysed all statin studies that had renal and CVD endpoints as main outcome measures. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched up to February 2015. Areas covered: We consider the effects of statins on microalbuminuria, proteinuria, glomerular filtration rate, AKI associated with angiography or percutaneous coronary intervention and on CVD event rates in patients with CKD. Expert opinion: Current evidence points towards the need to prescribe high-potency statins in patients with CKD, before a major decline in kidney function occurs. This may reduce CVD risk and delay the progress of CKD. Administration of either atorvastatin or rosuvastatin can prevent contrast-induced AKI before angiography or percutaneous coronary intervention. The combination of simvastatin + ezetimibe may decrease vascular events in patients with advanced CKD.
Alternative staging of regional lymph nodes in gastric cancer

The TNM pN stage based on the number of metastatic lymph nodes is an independent prognostic factor in gastric cancer. Many studies have highlighted the phenomenon of stage migration and problems in comparing groups of patients with different numbers of total lymph nodes harvested within TNM staging. The current version of UICC/AJCC and JGCA TNM classifications postulates a minimal number of 16 lymph nodes as the base for N stage determination. Alternative systems such as lymph node ratio (LNR), positive to negative lymph node ratio (PNLNR), and LOGODDS (or LODDS), were implemented to increase the quality of LN assessment. These methods have reached the background in the literature, but to date no standard approach according to the cut-offs for the stages has been implemented. LOGODDS is the method that most reflects the number of harvested lymph nodes. The rationale for alternative staging methods, their correlations, and limitations are presented.
Thermo-hydrodynamic analysis of large-eccentricity hydrodynamic bearings with texture on journal surface

To improve the performance of a heavy-loaded and high-speed hydrodynamic bearing, partial texture is designed on the journal surface. A three-dimensional thermo-hydrodynamic analysis model is developed based on the computational fluid dynamics method. Thermal conduction of bearing bush and journal, heat convection on the air-bearing surface, viscosity–temperature effect, and cavitation effect are taken into account. Performance of textured and un-textured high-speed journal bearing under different eccentricity ratios and different external loads is compared. The results indicated that partial texture on journal surface can play a positive role for large eccentricity ratio conditions in this study, and the textured bearing has a higher load carrying capacity, a lower maximum oil pressure, and a lower oil temperature rise than the un-textured bearing based on an optimal design of texture.
Exfoliated Graphene for Photothermal Biomedical Applications

When a material’s size is reduced to the nanoscale, it is well understood that in addition to the dramatically increased surface area to volume ratio, new properties emerge distinct from those present in the bulk material. When graphite is exfoliated down to graphene, several altered and highly attractive properties emerge which may enable new photothermal roles as well as allowing significant improvements to existing strategies. One such nanosize tuning method that is highly suitable for layered materials is surfactant assisted liquid exfoliation of the bulk material to single and few layered sheets. Successfully isolated graphene presents a range of remarkable properties such as an unsurpassed thermal conductivity of ≈ 5000 W m K, a very high mechanical strength with a Young’s modulus of ≈ 1 TPa, a broad optical absorptivity with a transmission of 97.7 % independent of wavelength in the visible spectrum (and a large portion of the infrared), as well as an ultrahigh electron mobility of ≈ 200,000 cm V s. The development of photothermal agents for a range of biomedical applications is an area of huge interest and promise with high impact outcomes possible. In this study, single and few layer graphene has been explored for use as a photothermal agent for a range of biomedical roles such as thermal ablation of cancerous cells and photothermally controllable drug release. With this focus, several biomedical photothermal applications were explored including the thermal ablation of cancerous glioma-neuroblastoma cells through photothermal conversion at the target site by the graphene microplates. By exploiting the significant absorption of graphene in the near-infrared, substantial amounts of energy can be delivered deep within biological tissue allowing a highly-localized region of dramatic heating to be achieved resulting in tissue ablation and cell death.
Novel agents for advanced pancreatic cancer

Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer.
Visual and Auditory Augmented Concurrent Feedback in a Complex Motor Task

In general, concurrent augmented feedback has been shown to effectively enhance learning in complex motor tasks. However, to optimize technical systems that are intended to reinforce motor learning, a systematic evaluation of different augmented feedback designs is required. Until now, mainly visual augmented feedback has been applied to enhance learning of complex motor tasks. Since most complex motor tasks are mastered in response to information visually perceived, providing augmented concurrent feedback in a visual manner may overload the capacities of visual perception and cognitive processing. Thus, the aim of this work was to evaluate the practicability of auditory feedback designs supporting a three-dimensional rowing-type movement in comparison with visual feedback designs. We term a feedback design practical if the provided information can easily be perceived and interpreted, and immediately be used to support the movement. In a first experiment, it became evident that participants could interpret three-dimensional auditory feedback designs based on stereo balance, pitch, timbre, and/or volume. Eleven of 12 participants were able to follow the different target movements using auditory feedback designs as accurately as with a very abstract visual feedback design. Visual designs based on superposition of actual and target oar orientation led to the most accurate performance. Considering the first experimental results, the feedback designs were further developed and again evaluated. It became evident that a permanent visual display of the target trajectories could further enhance movement accuracy. Moreover, results indicated that the practicability of the auditory designs depends on the polarity of the mapping functions. In general, both visual and auditory concurrent feedback designs were practical to immediately support multidimensional movement. In a next step, the effectiveness to enhance motor learning will be systematically evaluated.