Miracle-dz/UniFAR-FTUs huggingface dataset:
Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)

mTOR (mammalian target of rapamycin) stimulates cell growth by phosphorylating and promoting activation of AGC (protein kinase A/protein kinase G/protein kinase C) family kinases such as Akt (protein kinase B), S6K (p70 ribosomal S6 kinase) and SGK (serum and glucocorticoid protein kinase). mTORC1 (mTOR complex-1) phosphorylates the hydrophobic motif of S6K, whereas mTORC2 phosphorylates the hydrophobic motif of Akt and SGK. In the present paper we describe the small molecule Ku-0063794, which inhibits both mTORC1 and mTORC2 with an IC50 of ∼10 nM, but does not suppress the activity of 76 other protein kinases or seven lipid kinases, including Class 1 PI3Ks (phosphoinositide 3-kinases) at 1000-fold higher concentrations. Ku-0063794 is cell permeant, suppresses activation and hydrophobic motif phosphorylation of Akt, S6K and SGK, but not RSK (ribosomal S6 kinase), an AGC kinase not regulated by mTOR. Ku-0063794 also inhibited phosphorylation of the T-loop Thr308 residue of Akt phosphorylated by PDK1 (3-phosphoinositide-dependent protein kinase-1). We interpret this as implying phosphorylation of Ser473 promotes phosphorylation of Thr308 and/or induces a conformational change that protects Thr308 from dephosphorylation. In contrast, Ku-0063794 does not affect Thr308 phosphorylation in fibroblasts lacking essential mTORC2 subunits, suggesting that signalling processes have adapted to enable Thr308 phosphorylation to occur in the absence of Ser473 phosphorylation. We found that Ku-0063794 induced a much greater dephosphorylation of the mTORC1 substrate 4E-BP1 (eukaryotic initiation factor 4E-binding protein 1) than rapamycin, even in mTORC2-deficient cells, suggesting a form of mTOR distinct from mTORC1, or mTORC2 phosphorylates 4E-BP1. Ku-0063794 also suppressed cell growth and induced a G1-cell-cycle arrest. Our results indicate that Ku-0063794 will be useful in delineating the physiological roles of mTOR and may have utility in treatment of cancers in which this pathway is inappropriately activated.
HELP LDL Apheresis Reduces Plasma Pentraxin 3 in Familial Hypercholesterolemia

Background Pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, is secreted by vascular cells in response to injury, possibly aiming at tuning arterial activation associated with vascular damage. Severe hypercholesterolemia as in familial hypercholesterolemia (FH) promotes vascular inflammation and atherosclerosis; low-density lipoprotein (LDL) apheresis is currently the treatment of choice to reduce plasma lipids in FH. HELP LDL apheresis affects pro- and antiinflammatory biomarkers, however its effects on PTX3 levels are unknown. We assessed the impact of FH and of LDL removal by HELP apheresis on PTX3. Methods Plasma lipids, PTX3, and CRP were measured in 19 patients with FH undergoing chronic HELP LDL apheresis before and after treatment and in 20 control subjects. In the patients assessment of inflammation and oxidative stress markers included also plasma TNFα, fibrinogen and TBARS. Results At baseline, FH patients had higher (p = 0.0002) plasma PTX3 than matched control subjects. In FH PTX3 correlated positively (p≤0.05) with age, gender and CRP and negatively (p = 0.01) with HELP LDL apheresis vintage. The latter association was confirmed after correction for age, gender and CRP. HELP LDL apheresis acutely reduced (p≤0.04) plasma PTX3, CRP, fibrinogen, TBARS and lipids, but not TNFα. No association was observed between mean decrease in PTX3 and in LDL cholesterol. PTX3 paralleled lipids, oxidative stress and inflammation markers in time-course study. Conclusion FH is associated with increased plasma PTX3, which is acutely reduced by HELP LDL apheresis independently of LDL cholesterol, as reflected by the lack of association between change in PTX3 and in LDL levels. These results, together with the finding of a negative relationship between PTX3 and duration of treatment suggest that HELP LDL apheresis may influence both acutely and chronically cardiovascular outcomes in FH by modulating PTX3.
The Distributional Inclusion Hypotheses and Lexical Entailment

This paper suggests refinements for the Distributional Similarity Hypothesis. Our proposed hypotheses relate the distributional behavior of pairs of words to lexical entailment -- a tighter notion of semantic similarity that is required by many NLP applications. To automatically explore the validity of the defined hypotheses we developed an inclusion testing algorithm for characteristic features of two words, which incorporates corpus and web-based feature sampling to overcome data sparseness. The degree of hypotheses validity was then empirically tested and manually analyzed with respect to the word sense level. In addition, the above testing algorithm was exploited to improve lexical entailment acquisition.
An unexpected cause of muscle pain in diabetes

Diabetic muscle infarction is a rare condition which may present to a rheumatologist. It was first reported in 1965. Two illustrative cases are described here and the mechanisms of pathogenesis discussed. Analysis of the published data, results of the muscle biopsies, and a technetium-99m sestamibi scan suggest that the condition, which occurs against a background of diabetic microangiopathy, can be triggered by an ischaemic event and causes extensive muscle necrosis through hypoxia-reperfusion injury and compartment syndrome.
Musculoskeletal Asymmetry in Football Athletes: A Product of Limb Function over Time.

PURPOSE Asymmetrical loading patterns are commonplace in football sports. Our aim was to examine the influence of training age and limb function on lower-body musculoskeletal morphology. METHODS Fifty-five elite football athletes were stratified into less experienced (≤3 yr; n = 27) and more experienced (>3 yr; n = 28) groups by training age. All athletes underwent whole-body dual-energy x-ray absorptiometry scans and lower-body peripheral quantitative computed tomography tibial scans on the kicking and support limbs. RESULTS Significant interactions between training age and limb function were evident across all skeletal parameters (F16, 91 = 0.182, P = 0.031, Wilks Λ = 0.969). Asymmetries between limbs were significantly larger in the more experienced players than the less experienced players for tibial mass (P ≤ 0.044, d ≥ 0.50), total cross-sectional area (P ≤ 0.039, d ≥ 0.53), and stress-strain indices (P ≤ 0.050, d ≥ 0.42). No significant asymmetry was evident for total volumetric density. More experienced players also exhibited greater lower-body tibial mass (P ≤ 0.001, d ≥ 1.22), volumetric density (P ≤ 0.009, d ≥ 0.79), cross-sectional area (P ≤ 0.387, d ≥ 0.21), stress-strain indices (P ≤ 0.012, d ≥ 0.69), fracture loads (P ≤ 0.018, d ≥ 0.57), and muscle mass and cross-sectional area (P ≤ 0.016, d ≥ 0.68) than less experienced players. CONCLUSIONS Asymmetries were evident in athletes as a product of limb function over time. Chronic exposure to routine high-impact gravitational loads afforded to the support limb preferentially improved bone mass and structure (cross-sectional area and cortex thickness) as potent contributors to bone strength relative to the high-magnitude muscular loads predominantly afforded to the kicking limb.
A Prospective Study Evaluating IOP Changes after Switching from a Therapy with Prostaglandin Eye Drops Containing Preservatives to Nonpreserved Tafluprost in Glaucoma Patients

Purpose. To compare the ocular hypotensive effect of tafluprost with prostaglandin analogues (PGAs) in glaucoma patients. Methods. 89 primary open-angle glaucoma patients treated with bimatoprost, latanoprost, or travoprost for at least 3 months complaining for ocular discomfort were switched to tafluprost. IOP was assessed at baseline and 3 months after switching the therapy by daily curve. Primary outcome was to compare the mean daily IOP of tafluprost with PGAs. Results. The mean daily IOP was 16 ± 2.1 and 16.6 ± 2.0 mm Hg at baseline and after switching to tafluprost, respectively (P > 0.05). When analysis was carried out between tafluprost and each previous PGAs, the comparison between latanoprost and tafluprost and travoprost and tafluprost did not show any statistically significant difference in mean daily IOP and at each time point. The comparison between bimatoprost and tafluprost showed a statistically significant difference in mean daily IOP (P < 0.05) and at each time point (P < 0.05). Conclusions. After 3 months of switching tafluprost showed an overall IOP lowering effect similar to others PGAs. When each PGA was compared with tafluprost, bimatoprost showed to provide a statistically significant additional IOP lowering effect.
Laminin-induced Clustering of Dystroglycan on Embryonic Muscle Cells: Comparison with Agrin-induced Clustering

The effect of laminin on the distribution of dystroglycan (DG) and other surface proteins was examined by fluorescent staining in cultures of muscle cells derived from Xenopus embryos. Western blotting confirmed that previously characterized antibodies are reactive in Xenopus. In control cultures, αDG, βDG, and laminin binding sites were distributed as microclusters (<1 μm2 in area) over the entire dorsal surface of the muscle cells. Treatment with laminin induced the formation of macroclusters (1–20 μm2), accompanied by a corresponding decline in the density of the microclusters. With 6 nM laminin, clustering was apparent within 150 min and near maximal within 1 d. Laminin was effective at 30 pM, the lowest concentration tested. The laminin fragment E3, which competes with laminin for binding to αDG, inhibited laminin-induced clustering but did not itself cluster DG, thereby indicating that other portions of the laminin molecule in addition to its αDG binding domain are required for its clustering activity. Laminin-induced clusters also contained dystrophin, but unlike agrin-induced clusters, they did not contain acetylcholine receptors, utrophin, or phosphotyrosine, and their formation was not inhibited by a tyrosine kinase inhibitor. The results reinforce the notion that unclustered DG is mobile on the surface of embryonic muscle cells and suggest that this mobile DG can be trapped by at least two different sets of molecular interactions. Laminin self binding may be the basis for the laminin-induced clustering.
Treatable chondral injuries in the knee: frequency of associated focal subchondral edema.

OBJECTIVE In the knee, chondral flaps and fractures are radiographically occult articular cartilage injuries that can mimic meniscal tears clinically; once correctly diagnosed, these injuries can be treated surgically. We investigated an associated MR imaging finding--focal subchondral bone edema--in a series of surgically proven lesions. MATERIALS AND METHODS Two musculoskeletal radiologists retrospectively reviewed the MR studies of 18 knees with arthroscopically proven treatable cartilage infractions, noting articular surface defects and associated subchondral bone edema; subchondral edema was defined as focal regions of high signal intensity in the bone immediately underlying an articular surface defect on a T2-weighted or short inversion time inversion recovery (STIR) image. RESULTS The first observer saw focal subchondral edema deep relative to a cartilage surface defect in 15 (83%) of the 18 cases; in two additional cases a surface defect was seen without underlying edema. The second observer identified 13 knees (72%) with surface defects and associated subchondral edema and three with chondral surface defects and no associated edema. Subchondral edema was seen more frequently on fat-suppressed images and on STIR images than non-fat-suppressed images. CONCLUSION Focal subchondral edema is commonly visible on MR images of treatable, traumatic cartilage defects in the knee; this MR finding may prove to be an important clue to assist in the detection of these traumatic chondral lesions.
Analysis and Restoration of Daguerreotypes Using Cluster Computing

The Conservation Laboratory of the George Eastman House International Museum of Photography and Film (GEH) and the Department of Computer Science at the University of Rochester (URCS) are collaborating on the problems of preservation and access to daguerreotypes. We use high speed image processing to find, classify, and eliminate defects and artifacts of deterioration. Ultimately we want to produce a usable database and presentation methods for defects and final reconstructions. This TR describes early low-level techniques. We plan to pursue these problems in the future by incorporating more recent techniques: increasingly high-level ideas like semantic feature detectors, robust object recognition, visual-context detection, and trainable, automatic systems.
Downstream Effector Mono(ADP-Ribosyl)Transferase 2 and a Requirement for Ecto-Nicotinamide Adenine Dinucleotide: Rapid Induction of Naive T Cell Apoptosis by

Lymphocytes express a number of NAD-metabolizing ectoenzymes, including mono(ADP-ribosyl)transferases (ART) and ADP ribosylcyclases. These enzymes may regulate lymphocyte functions following the release of NAD in injured or inﬂammatory tissues We report here that extracellular NAD induces apoptosis in BALB/c splenic T cells with an IC 50 of 3–5 m M. Annexin V staining of cells was observed already 10 min after treatment with NAD in the absence of any additional signal. Removal of GPI-anchored cell surface proteins by phosphatidylinositol-speciﬁc phospholipase C treatment rendered cells resistant to NAD-mediated apoptosis. RT-PCR analyses revealed that resting BALB/c T cells expressed the genes for GPI-anchored ART2.1 and ART2.2 but not ART1. ART2-speciﬁc antisera blocked radiolabeling of cell surface proteins with both [ 32 P]NAD and NAD-mediated apoptosis. Further analyses revealed that natural knockout mice for Art2.a (C57BL/6) or Art2.b (NZW) were resistant to NAD-mediated apoptosis. Labeling with [ 32 P]NAD revealed strong cell surface ART activity on T cells of C57BL/6 and little if any activity on cells of NZW mice. T cells of (C57BL/6 3 NZW)F 1 animals showed strong cell surface ART activity and were very sensitive to NAD-induced apoptosis. As in BALB/c T cells, ART2-speciﬁc antisera blocked cell surface ART activity and apoptosis in (C57BL/ 6 3 NZW)F 1 T cells. The fact that T cells of F 1 animals are sensitive to rapid NAD-induced apoptosis suggests that this effect requires
Adoption of Bundled Services with Network Externalities and Correlated Affinities

The goal of this article is to develop a principled understanding of when it is beneficial to bundle technologies or services whose value is heavily dependent on the size of their user base, that is, exhibits positive exernalities. Of interest is how the joint distribution, and in particular the correlation, of the values users assign to components of a bundle affect its odds of success. The results offer insight and guidelines for deciding when bundling new Internet technologies or services can help improve their overall adoption. In particular, successful outcomes appear to require a minimum level of value correlation. Categories and Subject Descriptors (2012): Networks -- Network Algorithms -- Network economics; Networks -- Network properties -- Network dynamics; Information systems -- Information systems applications -- Collaborative and social computing systems and tools; Security and privacy -- Human and societal aspects of security and privacy; Human-centered computing -- Collaborative and social computing theory, concepts and paradigms
Evaluation of Alere i Influenza A&B for Rapid Detection of Influenza Viruses A and B

ABSTRACT Rapid and accurate diagnosis of influenza is important for infection control, as well as for patient management. Alere i Influenza A&B is an isothermal nucleic acid amplification-based integrated system for detection and differentiation of influenza virus A and influenza virus B. The performance of the Alere i Influenza A&B was screened using frozen nasopharyngeal-swab specimens collected in viral transport medium (VTM) that were originally tested fresh with the FilmArray Respiratory Panel (RP) assay during the 2012–2013 influenza outbreak. In total, 360 VTM specimens were selected for Alere i Influenza A&B testing: 40 influenza virus A H1N1-2009 (influenza virus A-1), 40 influenza virus A H3N2 (influenza virus A-3), 37 influenza virus A “equivocal” or “no subtype detected” (influenza virus A-u), 41 influenza virus B, and 202 influenza virus-negative specimens, as initially determined by the FilmArray RP assay. The Alere assay showed sensitivities of 87.2%, 92.5%, 25.0%, and 97.4% for influenza virus A-1, influenza virus A-3, influenza virus A-u, and influenza virus B, respectively, after discordant resolution by Prodesse ProFLU+ PCR. The specificities were 100% for both influenza virus A and influenza virus B. In general, the Alere i Influenza A&B provided good sensitivity, although the assay did show poorer sensitivity with samples determined to have low influenza virus A titers by Prodesse ProFlu+ PCR (a mean real-time PCR threshold cycle [C T ] value of 31.9 ± 2.0), which included the majority of the samples called influenza virus A “equivocal” or “no subtype detected” by a single BioFire FilmArray RP test. The integrated, rapid, and simple characteristics of the Alere i Influenza A&B assay make it a potential candidate for point-of-care testing, with a test turnaround time of less than 15 min.
MicroRNA Profile Predicts Recurrence after Resection in Patients with Hepatocellular Carcinoma within the Milan Criteria

Objective Hepatocellular carcinoma (HCC) is difficult to manage due to the high frequency of post-surgical recurrence. Early detection of the HCC recurrence after liver resection is important in making further therapeutic options, such as salvage liver transplantation. In this study, we utilized microRNA expression profiling to assess the risk of HCC recurrence after liver resection. Methods We examined microRNA expression profiling in paired tumor and non-tumor liver tissues from 73 HCC patients who satisfied the Milan Criteria. We constructed prediction models of recurrence-free survival using the Cox proportional hazard model and principal component analysis. The prediction efficiency was assessed by the leave-one-out cross-validation method, and the time-averaged area under the ROC curve (ta-AUROC). Results The univariate Cox analysis identified 13 and 56 recurrence-related microRNAs in the tumor and non-tumor tissues, such as miR-96. The number of recurrence-related microRNAs was significantly larger in the non-tumor-derived microRNAs (N-miRs) than in the tumor-derived microRNAs (T-miRs, P<0.0001). The best ta-AUROC using the whole dataset, T-miRs, N-miRs, and clinicopathological dataset were 0.8281, 0.7530, 0.7152, and 0.6835, respectively. The recurrence-free survival curve of the low-risk group stratified by the best model was significantly better than that of the high-risk group (Log-rank: P = 0.00029). The T-miRs tend to predict early recurrence better than late recurrence, whereas N-miRs tend to predict late recurrence better (P<0.0001). This finding supports the concept of early recurrence by the dissemination of primary tumor cells and multicentric late recurrence by the ‘field effect’. Conclusion microRNA profiling can predict HCC recurrence in Milan criteria cases.
A New Iris Segmentation Method Based on Improved Snake Model and Angular Integral Projection

Segmenting iris region is fundamental for iris-based biometric systems. The overall performance of an iris recognition system is highly dependent on accurate iris segmentation. In this paper, a new algorithm for iris segmentation is proposed towards more accurate and efficient segmentation, it detects the precise pupil contour and localizes the limbic boundary. An improved snake model is presented, wherein a new external energy function is designed. This external energy is computed based on the Angular Integral Projection Function (AIPF). First, the AIPF is combined with the improved snake to detect the pupil boundary. For that, pupil boundary points are detected by using the AIPF, and circle fitting is followed to localize the circular pupil boundary giving the initial snake contour. Then, the precise pupil contour is detected by deploying the improved snake. Second, as another contribution of this work, the limbic boundary is localized by combining the AIPF with a technique to extract outlier boundary points based on Mahalanobis distance. Experimental results on CASIA V3.0 iris image database show that the improved snake model is comparable with conventional snake model, and the whole segmentation performance of the proposed algorithm outperforms those of other well- known existing methods in both terms of accuracy and processing time.
Cardiovascular Molecular Imaging 1

Joseph C. Wu, MD, PhD Frank M. Bengel, MD Sanjiv S. Gambhir, MD, PhD The goal of this review is to highlight how molecular imaging will impact the management and improved understanding of the major cardiovascular diseases that have substantial clinical impact and research interest. These topics include atherosclerosis, myocardial ischemia, myocardial viability, heart failure, gene therapy, and stem cell transplantation. Traditional methods of evaluation for these diseases will be presented first, followed by methods that incorporate conventional and molecular imaging approaches.
Measuring quality of life in people referred for specialist care of acne: comparing generic and disease-specific measures.

OBJECTIVE Our purpose was to compare 3 approaches to the measurement of quality of life in patients referred for specialist care of acne. METHODS A questionnaire was sent to 130 patients referred for management of their acne. Follow-up questionnaires were sent 4 and 12 months after treatment began. The questionnaire contained a generic index measure (EuroQol EQ-5D), a generic profile measure (Short Form 36), and a disease-specific measure (Dermatology Life Quality Index). Pretreatment results for the EQ-5D were compared with normative data. The responsiveness of the EQ-5D was compared with that of the other measures. RESULTS Before treatment, the sample reported substantially more pain/discomfort and anxiety/depression on the EQ-5D compared with a population sample. The disease-specific measure was more responsive to change compared with both generic measures. CONCLUSION Our study highlights the importance of combining information from generic measures with information from instruments designed specifically for use in people with skin disease.
LOCATION AND REMOVAL OF DESLORELIN ACETATE IMPLANTS IN FEMALE AFRICAN LIONS (PANTHERA LEO)

Abstract: Contraception is necessary to manage zoo animal populations and to be able to house animals in groups without producing additional unwanted offspring. In felids and canids, an association between exposure to progestins and the occurrence of endometrial and mammary gland pathology has been documented. Therefore, the Association of Zoos and Aquariums (AZA) Wildlife Contraceptive Center recommends the use of deslorelin acetate for long-term contraception in carnivores. Return to cyclicity after deslorelin treatment has been variable; some individuals show ovarian suppression for long periods after the expected end of the deslorelin efficacy. In an attempt to reduce the time to reversal, techniques to locate and remove previous implants are being developed. This report documents the successful implementation of high-frequency ultrasonography in lions (Panthera leo) to locate and direct surgical removal of multiple deslorelin implants placed at least 2 yr previously as well as the return of follicular activity in both females at 7 months post-removal of implants.