Miracle-dz/UniFAR-FTUs huggingface dataset:
Linking β-Catenin to Androgen-signaling Pathway*

The androgen-signaling pathway is important for the growth and progression of prostate cancer cells. The growth-promoting effects of androgen on prostate cells are mediated mostly through the androgen receptor (AR). There is increasing evidence that transcription activation by AR is mediated through interaction with other cofactors. β-Catenin plays a critical role in embryonic development and tumorigenesis through its effects on E-cadherin-mediated cell adhesion and Wnt-dependent signal transduction. Here, we demonstrate that a specific protein-protein interaction occurs between β-catenin and AR. Unlike the steroid hormone receptor coactivator 1 (SRC1), β-catenin showed a strong interaction with AR but not with other steroid hormone receptors such as estrogen receptor α, progesterone receptor β, and glucocorticoid receptor. The ligand binding domain of AR and the NH2terminus combined with the first six armadillo repeats of β-catenin were shown to be necessary for the interaction. Through this specific interaction, β-catenin augments the ligand-dependent activity of AR in prostate cancer cells. Moreover, expression of E-cadherin in E-cadherin-negative prostate cancer cells results in redistribution of the cytoplasmic β-catenin to the cell membrane and reduction of AR-mediated transcription. These data suggest that loss of E-cadherin can elevate the cellular levels of β-catenin in prostate cancer cells, which may directly contribute to invasiveness and a more malignant tumor phenotype by augmenting AR activity during prostate cancer progression.
Extremely red objects in the UKIDSS Ultra Deep Survey Early Data Release

We construct a sample of extremely red objects (EROs) within the UKIDSS Ultra Deep Survey by combining the Early Data Release with optical data from the Subaru/XMM–Newton Deep Field. We find a total of 3715 objects over 2013 arcmin2 with R−K > 5.3 and K≤ 20.3, which is a higher surface density than found by previous studies. This is partly due to our ability to use a small aperture in which to measure colours, but is also the result of a genuine overdensity of objects compared to other fields. We separate our sample into passively evolving and dusty star-forming galaxies using their RJK colours and investigate their radio properties using a deep radio map. The dusty population has a higher fraction of individually detected radio sources and a higher mean radio flux density among the undetected objects, but the passive population has a higher fraction of bright radio sources, suggesting that active galactic nuclei are more prevalent among the passive ERO population.
AN AUDIT OF RISK FACTORS AMONG PATIENTS REPORTING AT A TERTIARY CARE HOSPITAL IN HYDERABAD

Background: Dengue fever & its complications have become a nightmare for common people in Asian countries including Pakistan. Besides environmental factors responsible for its transmission, there are many host factors too involved in its rapid spread. Objective: To assess risk factors for dengue fever among patients reporting at Liaquat University Hospital (LUH) Hyderabad. Study Design, Setting & Study duration: Descriptive cross sectional study was conducted at LUH, Hyderabad for six months i.e. from 15th May 2013 to 15th November 2013. Methods: 481 patients were registered through convenient sampling after informed verbal consent. Patients’ demographic features, clinical presentations & laboratory reports were collected on a preformed proforma. Results: The reporting rate for dengue fever was 18.5% & the mean age of presentation was 28.5 ± 3.5 years. Males were in majority (72.55%) 3 & the average days of admission were 4.5 days; low platelets count (< 50,000/mm ) was recorded in 72% of cases; however 11.64% patients presented with hemorrhagic tendency. Age was strongly associated with thrombocytopenia (p=0.04) & with occurrence of hemorrhage (p=0.03) in both genders; this association was more evident among males (p=0.01). However among uncomplicated cases no association was evident between gender & length of stay in (p=0.35). Conclusions: The alarmingly higher reporting rate of dengue fever necessitates contextual preventive interventions. As younger age & male gender are the major risk factors for this disease; therefore age-specific & gender-specific preventive strategies against this disease are recommended.
The role of PSA density to predict a pathological tumour upgrade between needle biopsy and radical prostatectomy for low risk clinical prostate cancer in the modified Gleason system era.

OBJECTIVES We evaluate the role of prostate-specific antigen (PSA) density to predict Gleason score upgrade between prostate biopsy material and radical prostatectomy specimen examination in patients with low-risk prostate cancer. METHODS Between January 2007 and November 2011, 133 low-risk patients underwent a radical prostatectomy. Using the modified Gleason criteria, tumour grade of the surgical specimens was examined and compared to the biopsy results. RESULTS A tumour upgrade was noticed in 57 (42.9%) patients. Organ-confined disease was found in 110 (82.7%) patients, while extracapsular disease and seminal vesicles invasion was found in 19 (14.3%) and 4 (3.0%) patients, respectively. Positive surgical margins were reported in 23 (17.3%) patients. A statistical significant correlation between the preoperative PSA density value and postoperative upgrade was found (p = 0.001) and this observation had a predictive value (p = 0.002); this is in contrast to the other studied parameters which failed to reach significance, including PSA, percentage of cancer in biopsy and number of biopsy cores. Tumour upgrade was also highly associated with extracapsular cancer extension (p = 0.017) and the presence of positive surgical margins (p = 0.017). CONCLUSIONS PSA density represents a strong predictor for Gleason score upgrade after radical prostatectomy in patients with clinical low-risk disease. Since tumour upgrade increases the potential for postoperative pathological adverse findings and prognosis, PSA density should be considered when treating and consulting patients with low-risk prostate cancer.
Body Mass Index, Physical Activity, and Serum Markers of Inflammation, Immunity, and Insulin Resistance

Background: Epidemiologic studies examining circulating levels of inflammatory markers in relation to obesity and physical inactivity may aid in our understanding of the role of inflammation in obesity-related cancers. However, previous studies on this topic have focused on a limited set of markers. Methods: We evaluated associations between body mass index (BMI) and vigorous physical activity level, based on self-report, and serum levels of 78 inflammation-related markers. Markers were measured using a bead-based multiplex method among 1,703 men and women, ages 55–74 years, and with no prior history of cancer at blood draw, and selected for case–control studies nested within the Prostate, Lung, Ovarian, and Colorectal Cancer Screening Trial. Analyses were adjusted for age, sex, smoking, case–control study, physical activity, and BMI. Results: Twelve markers were positively associated with BMI after FDR correction. ORs and 95% confidence interval (CI) for highest versus lowest levels of CCL2/MCP-1, CXCL5/ENA-78, sTNFRII, CXCL10/IP-10, CXCL6/GCP2, CCL13/MCP-4, amylin, CRP, C-peptide, CCL19/MIP-3b, insulin, and leptin were: 1.50 (1.14–1.98), 1.52 (1.12–2.05), 1.61 (1.17–2.20), 1.69 (1.25–2.28), 1.74 (1.24–2.44), 1.75 (1.22–2.50), 1.91 (1.31–2.78), 2.41 (1.36–4.25), 2.78 (1.83–4.24), 3.30 (2.28–4.78), 4.05 (2.51–6.55), and 50.03 (19.87–125.99) per 5 kg/m2, respectively. Only CXCL12/SDF-1a was associated with physical activity (≥3 vs. <1 h/wk; OR, 3.28; 95% CI, 1.55–6.94) after FDR correction. Conclusions: BMI was associated with a wide range of circulating markers involved in the inflammatory response. Impact: This cross-sectional analysis identified serum markers could be considered in future studies aimed at understanding the underlying mechanisms linking inflammation with obesity and obesity-related cancers. Cancer Epidemiol Biomarkers Prev; 23(12); 2840–9. ©2014 AACR.
Empirical Analysis of the Reusability of Object-Oriented Program Code in Open-Source Software

: Measuring the reusability of Object-Oriented (OO) program code is important to ensure a successful and timely adaptation and integration of the reused code in new software projects. It has become even more relevant with the availability of huge amounts of open-source projects. Reuse saves cost, increases the speed of development and improves software reliability. Measuring this reusability is not s straight forward process due to the variety of metrics and qualities linked to software reuse and the lack of comprehensive empirical studies to support the proposed metrics or models. In this paper, a conceptual model is proposed to measure the reusability of OO program code. A comprehensive set of metrics is used to compute the most significant factors of reusability and an empirical investigation is conducted to measure the reusability of the classes of randomly selected open-source Java projects. Additionally, the impact of using inner and anonymous classes on the reusability of their enclosing classes is assessed. The results obtained are thoroughly analyzed to discover the real reusability potential of OO program code and the impact of nesting on it together with suggestions on how to improve this potential.
Multiple HPV genotype infection impact on invasive cervical cancer presentation and survival

Background Invasive cervical cancer (ICC) is the third most common malignant neoplasm affecting Brazilian women. Little is known about the impact of specific HPV genotypes in the prognosis of ICC. We hypothesized that HPV genotype would impact ICC clinical presentation and survival. Methods Women diagnosed with ICC at the Instituto do Câncer do Estado de São Paulo (ICESP) between May 2008 and June 2012 were included in the study and were followed until December 2015. HPV genotype was detected from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples using Onclarity™ system (BD Viper™ LT automated system). Results 292 patients aged 50±14 years were analyzed. HPVDNA was detected in 84% of patients. The HPV genotypes studied were: HPV16 (64%), HPV18 (10%), HPV33-58 (7%), HPV45 (5%), HPV31 (4%) and other high-risk HPV genotypes (11%). HPV genotypes showed different distributions regarding histological type and clinical stage. Patients were followed for 35±21 months. The overall survival at 5 years after diagnosis of cervical cancer was 54%. Age, clinical staging, histological type and multiple HPV genotypes infection detected in the same tumor specimen were associated with poorer overall survival on multivariate Cox proportional hazard analysis (p<0.05). No specific HPV genotype affected survival. Conclusion Multiple HPV genotype infection was associated with poorer ICC survival in our study, compared with single genotype infection. HPV genotyping from FFPE tumor tissue using an automated assay such as the Onclarity BD™ assay provides a simpler alternative for routine clinical use. Impact This is the largest study employing an automated HPV genotyping assay using FFPE of ICC. Multiple HPV genotype infection adversely influenced survival.
On Minimizing the Makespan When Some Jobs Cannot Be Assigned on the Same Machine

We study the classical scheduling problem of assigning jobs to machines in order to minimize the makespan. It is well-studied and admits an EPTAS on identical machines and a (2-1/m)-approximation algorithm on unrelated machines. In this paper we study a variation in which the input jobs are partitioned into bags and no two jobs from the same bag are allowed to be assigned on the same machine. Such a constraint can easily arise, e.g., due to system stability and redundancy considerations. Unfortunately, as we demonstrate in this paper, the techniques of the above results break down in the presence of these additional constraints. Our first result is a PTAS for the case of identical machines. It enhances the methods from the known (E)PTASs by a finer classification of the input jobs and careful argumentations why a good schedule exists after enumerating over the large jobs. For unrelated machines, we prove that there can be no (log n)^{1/4-epsilon}-approximation algorithm for the problem for any epsilon > 0, assuming that NP nsubseteq ZPTIME(2^{(log n)^{O(1)}}). This holds even in the restricted assignment setting. However, we identify a special case of the latter in which we can do better: if the same set of machines we give an 8-approximation algorithm. It is based on rounding the LP-relaxation of the problem in phases and adjusting the residual fractional solution after each phase to order to respect the bag constraints.
Nutritional Supplements and Doping

ContextThe problems of doping in sport and the increasing use of nutritional supplements by athletes are issues that intersect to the degree that a large number of supplements may contain substances that are banned in sport. Many supplements contain substances that are associated with significant health hazards. Athletes consuming such supplement products may jeopardize their sporting status, and their health. ObjectivesTo clarify and summarize the current status of dietary supplements in general, and to describe specific problems that can be associated with supplement use so that sport physicians might be better prepared to address these issues with their athlete-patients. Data SourceAn analysis of recent and relevant literature accessed through MEDLINE, and interactions with clinicians, laboratory scientists, colleagues, and athletes. ConclusionsThe dietary supplement industry is completely unregulated in the United States; as a consequence, an abundance of supplement products of dubious value, content, and quality are now available around the world. It is known that many supplement products contain substances that are prohibited in sport—typically stimulants or anabolic steroid precursors. Many supplements contain substances (e.g., ephedrine) that have been associated with significant morbidity and mortality. Sport practitioners have particular responsibilities in addressing this issue. Athletes need to be aware of the problems that can follow supplement use, and sport authorities need to ensure that nutritional education and guidance for athletes is of the highest standard. The need for the appropriate regulation of dietary supplements is emphasized.
Susceptibility of Rats of Different Ages to Inoculation with Swine Haemagglutinating Encephalomyelitis Virus (a Coronavirus) by Various Routes

Abstract Haemagglutinating encephalomyelitis virus, strain 67N, was used to inoculate 1-, 2-, 4- and 8-week-old rats by the intracerebral (i.c.), intranasal (i.n.), intraperitoneal (i.p.), subcutaneous (s.c.), intravenous (i.v.) and oral routes with graded doses. The routes of infection, in descending order of efficacy, were: i.ci.ns.ci.pi.v. and oral. Rats aged 1 and 2 weeks were generally similar in terms of mortality and mean time to death, regardless of inoculation route, except for the oral route, which had little effect. In comparison with the 1- and 2-week-old rats, the 4-week-old rats were less susceptible to the virus by all routes. Eight-week-old rats inoculated by the i.ci.n. or s.c. routes died, but all those inoculated by other routes survived. To follow the spread of virus in the central nervous system, 4-week-old rats inoculated by the i.c. route were examined. The virus was first detected in the brain on day 1 and in the spinal cord on day 2. The viral titres in both tissues reached a plateau of 107plaque-forming units (PFU)/0·2 g by day 4, at which time clinical signs had developed. By immunohistochemical analysis, virus-specific antigen was found first in the pyramidal cells of the hippocampus and cerebral cortex, and later in the large-sized neurons of the pons and spinal cord. Still later (day 4) immunolabelling was found in Purkinje cells of the cerebellum, but not in the ependymal cells, choroid plexus or other glial cells.
Visual Control of Discrete Aiming Movements

An experiment is reported which investigated the visual control of discrete rapid arm movements. Subjects were required to move as rapidly as possible to several target width-movement distance combinations under both visual and non-visual conditions. The movement time (MT) data were supportive of Fitts' Law in that MT was linearly related and highly correlated to the Index of Difficulty (ID). MT was also similar for different target width-distance combinations sharing the same ID value. The error rate analysis, which compared visual to non-visual Performance, indicated that vision was only used, and to varying degrees, when MT exceeded 200 ms (3.58 ID level). There was some evidence that vision was differentially used within target width-distance combinations sharing the same ID. Estimates of endpoint variability generally reflected the results of the error rate analysis. These results do not support the discrete correction model of Fitts' Law proposed by Keele (1968).
Protein Kinase PKR Amplification of Interferon β Induction Occurs through Initiation Factor eIF-2α-mediated Translational Control*

Background: RNA-dependent protein kinase PKR regulates interferon induction. Results: Knockdown of PKR or mutation of initiation factor eIF-2α results in increased IκB-α protein levels and decreased IFN-β induction in RNA-transfected and virus-infected cells. Conclusion: PKR amplifies IFN-β induction through an eIF-2α translational control response. Significance: PKR functions together with additional RNA sensors to modulate signaling leading to interferon gene induction. The protein kinase PKR is activated by RNA with double-stranded (ds) structure and subsequently impairs translation through phosphorylation of protein synthesis initiation factor eIF-2α. PKR also mediates activation of signal transduction pathways leading to interferon beta (IFN-β) gene induction following virus-infection or RNA transfection. We previously demonstrated in measles virus-infected cells that PKR is required for the maximal induction of IFN-β gene expression by the interferon promoter stimulator gene 1 (IPS-1) adaptor-dependent cytosolic RNA sensor pathway. While both IPS-1 and PKR are important mediators of IFN-β induction, with PKR contributing to an enhanced NF-κB activation, the mechanism by which PKR enhances NF-κB activity and amplifies IFN-β induction is unresolved. Herein we tested the possibility that PKR could activate signal transduction pathways indirectly through translational control responses. Following transfection with synthetic or natural dsRNAs or infection with measles virus, we observed increased mRNA but decreased protein levels for the inhibitor of NF-κB signaling, IκB-α, that correlated with PKR activation and eIF-2α phosphorylation. Importantly, knockdown of PKR increased IκB-α protein levels and impaired IFN-β induction. Additionally, inhibition of translation by cycloheximide treatment rescued IFN-β induction following PKR knockdown but not IPS-1 knockdown. Mutation of eIF-2α to prevent phosphorylation also impaired IFN-β induction in PKR-sufficient virus-infected cells. These results suggest that an eIF-2α-dependent translation inhibition mechanism is sufficient to explain the PKR-mediated amplification of IPS-1-dependent IFN-β induction by foreign RNA.
Health status, mood, and cognition in experimentally induced subclinical hypothyroidism.

OBJECTIVE The objective of the study was to determine whether subclinical hypothyroidism causes decrements in health status, mood, and/or cognitive function. DESIGN This was a double-blinded, randomized, crossover study of usual dose l-thyroxine (L-T4) (euthyroid arm) vs. lower dose L-T4 (subclinical hypothyroid arm) in hypothyroid subjects. PATIENTS Nineteen subjects on L-T4 therapy for primary hypothyroidism participated in the study. MEASUREMENTS Subjects underwent measurements of health status, mood, and cognition using validated instruments: Short Form 36, Profile of Mood States, and tests of declarative memory (paragraph recall, complex figure), working memory (N-back, subject ordered pointing, digit span backward), and motor learning (pursuit rotor). The same measures were repeated after 12 wk on each of the study arms. RESULTS Mean TSH levels increased to 17 mU/liter on the subclinical hypothyroid arm (P < 0.0001). Mean free T4 and free T3 levels remained within the normal range. The Profile of Mood States fatigue subscale and Short Form 36 general health subscale were slightly worse during the subclinical hypothyroid arm. Measures of working memory (N-back, subject ordered pointing) were worse during the subclinical hypothyroid arm. These differences did not depend on mood or health status but were related to changes in free T4 or free T3 levels. There were no decrements in declarative memory or motor learning. CONCLUSIONS We found mild decrements in health status and mood in L-T4-treated hypothyroid subjects when subclinical hypothyroidism was induced in a blinded, randomized fashion. More importantly, there were independent decrements in working memory, which suggests that subclinical hypothyroidism specifically impacts brain areas responsible for working memory.
A novel stuck-at based method for transistor stuck-open fault diagnosis

While most of the fault diagnosis tools are based on gate level fault models, for instance the stuck-at model, many faults are actually at the transistor level. The stuck-open fault is one example. In this paper we introduce a method which extends the use of available gate level stuck-at fault diagnosis tools to stuck-open fault diagnosis. The method transforms the transistor level circuit description to a gate level description where stuck-open faults are represented by stuck-at faults, so that the stuck-open faults can be diagnosed directly by any of the stuck-at fault diagnosis tools. The transformation is only performed on selected gates and thus has little extra computational cost. This method also applies to the diagnosis of multiple stuck-open faults within a gate. Successful diagnosis results are presented using wafer test data and an internal diagnosis tool from Philips
Spontaneous regression of metastases from malignant melanoma: a case report

A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases; this report is the first to document complete spontaneous regression of cerebral metastases from malignant melanoma by means of computed tomography scans. Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour in the absence of all treatment or in the presence of therapy, which is considered inadequate to exert a significant influence on neoplastic disease. The incidence of spontaneous regression of metastases from malignant melanoma is approximately one per 400 patients, and possible mechanisms include immunologic, endocrine, inflammatory and tumour nutritional factors. Our patient engaged in alternative therapies and was taking a number of different dietary supplements, none of which can be medically recommended, but the combination of which possibly strengthened the immune system and thereby the host defense against the melanoma metastases.