Miracle-dz/UniFAR-FTUs huggingface dataset:
A Regulatory Feedback Loop Between Ca2+/Calmodulin-dependent Protein Kinase Kinase 2 (CaMKK2) and the Androgen Receptor in Prostate Cancer Progression*

Background: Defining molecular mechanisms that regulate AR activity is critical for understanding prostate cancer progression. Results: CaMKK2 increases during disease progression, is transcriptionally regulated by the AR, promotes proliferation, and is required for optimal AR transcriptional activity. Conclusion: CaMKK2 is in a feedback circuit to maintain AR activity. Significance: The CaMKK2 pathway is a promising target for prostate cancer therapy. The androgen receptor (AR) plays a critical role in prostate cancer (PCa) progression, however, the molecular mechanisms by which the AR regulates cell proliferation in androgen-dependent and castration-resistant PCa are incompletely understood. We report that Ca2+/calmodulin-dependent kinase kinase 2 (CaMKK2) expression increases and becomes nuclear or perinuclear in advanced PCa. In the TRAMP (transgenic adenocarcinoma of mouse prostate) model of PCa, CaMKK2 expression increases with PCa progression with many cells exhibiting nuclear staining. CaMKK2 expression is higher in human castration-resistant tumor xenografts compared with androgen-responsive xenografts and is markedly higher in the AR-expressing, tumorigenic cell line LNCaP compared with cell lines that are AR-nonexpressing and/or nontumorigenic. In LNCaP cells, dihydrotestosterone induced CaMKK2 mRNA and protein expression and translocation of CaMKK2 to the nucleus. Conversely, androgen withdrawal suppressed CaMKK2 expression. Knockdown of CaMKK2 expression by RNAi reduced LNCaP cell proliferation and increased percentages of cells in G1 phase, whereas correspondingly reducing percentages in S phase, of the cell cycle. CaMKK2 knockdown reduced expression of the AR target gene prostate-specific antigen at both mRNA and protein levels, AR transcriptional activity driven by androgen responsive elements from the prostate-specific probasin gene promoter and levels of the AR-regulated cell cycle proteins, cyclin D1 and hyperphosphorylated Rb. Our results suggest that in PCa progression, CaMKK2 and the AR are in a feedback loop in which CaMKK2 is induced by the AR to maintain AR activity, AR-dependent cell cycle control, and continued cell proliferation.
Aggressive Reporting under Imprecise Standards A Laboratory Investigation

We study the market consequences of reporting with imprecise accounting standards, such as those in model-based nancial reports. In a laboratory experiment, our participants take advantage of imprecision in standards to report aggressively. Two e ects of aggressive reporting are illiquid asset markets and low asset prices, compared with those arising in a regime in which aggressive reporting is prevented and conservative reporting is imposed. Illiquidity occurs because aggressive reports do not provide rms with a credible way to disclose good news about a worst-case scenario, creating a market friction. On the other hand, lower prices occur because aggressive reports convey news about a best-case scenario, protecting investors against paying information rents. We relate our results to empirical studies and to other experiments on reporting with imprecise standards.
Mu class glutathione S‐transferase mRNA isoform expression in acute lymphoblastic leukaemia

Summary. Glutathione S‐transferases (GSTs) are implicated in cytotoxic drug resistance in leukaemia. In a previous study, expression of mu class GST (GSTM) was associated with poor prognosis in childhood acute lymphoblastic leukaemia (ALL), however, that study did not differentiate between individual GSTM isoforms. This study, therefore, investigated individual GSTM isoform expression in ALL blasts at the mRNA level. Leukaemic blasts from 21 children with ALL were studied. Interindividual variation in the pattern of GSTM mRNA isoform expression was demonstrated. GSTM2 transcript was expressed in all patients in contradistinction to GSTM5, which was not detected in any sample. GSTM3 and GSTM4 expression varied between individuals, with GSTM3 expressed in 62% and GSTM4 in 24% of patients. Lymphoblast expression of GSTM3 was positively related to good prognosis whereas expression of GSTM4 was not related to clinical outcome in this small cohort. No relationship was demonstrated with established indicators of prognosis, including sex, age, immunophenotype and presenting white cell count. The results suggest that expression of GSTM3 may play a role in determining prognosis in childhood ALL and could provide more information for accurate stratification of treatment. Further studies are required to determine whether there is a causal relationship between GSTM3 expression and clinical outcome.
Emergent Patterns of Feedback Strategies in Performing a Closed Motor Skill

This study identified self-chosen patterns of feedback usage and how they influenced accuracy and consistency in performing a closed motor skill. Learners completed 100 practice trials with 25 opportunities to receive knowledge of results (KR), the timing of which was self-chosen, followed by 25 no-KR retention trials. The study identified two patterns of self-chosen KR, namely, a faded frequency pattern and a reversed faded frequency pattern. Analyses of variance indicated a significant trial block effect for accuracy in acquisition and no significant main effects or interactions associated with self-chosen patterns of KR. Quantification of regularity of KR patterns yielded correlations indicating that less regularity was associated with greater accuracy in performing the task. These results were congruent with previous research on self-chosen feedback.
Caco‐2 cells as a model for intestinal lipoprotein synthesis and secretion

Caco‐2 cells, an intestinal cell line derived from a human colorectal carcinoma that spontaneously differentiates under standard culture conditions, lends itself to the in vitro study of human gut in view of its efficient intestinal transport processes. Among its multiple biological functions are those related to the absorption, transport, and metabolism of lipids and lipoproteins. Despite their intestinal origin, confluent Caco‐2 cell monolayers primarily express L‐FABP for the uptake of apical dietary long chain fatty acids, incorporating them into triglycerides by the glycerol 3‐phosphate pathway, and assembling very‐low‐density lipoprotein, high‐density lipoprotein, and low‐density lipoprotein. The monoacylglycerol pathway is inactive in Caco‐2 cells. Furthermore, the secretion of newly synthesized triglyceride‐rich lipoproteins is very restricted, despite abundant production of apolipoprotein (apo) B. The regulation of apoB synthesis and its mRNA editing at the enterocyte level has been intensively examined in Caco‐2 cells. Luminal fatty acids, calcium ion, as well as vitamins and hormones are known to modulate the apoB‐48/apoB‐100 at the transcriptional and/or translational level. The regulation of 3‐hydroxy‐3‐methylglutaryl‐CoA reductase and acyl‐CoA: (cholesterol acyltransferase), the key enzymes governing intracellular cholesterol handling, have also been extensively examined in Caco‐2 cells. In many respects this cell line provides an excellent in vitro model for the investigation of intestinal lipoprotein metabolism; however, their limited secretion capacity remains a potential drawback to comparisons with the in vivo physiological state. —Levy, E. , Mehran, M. , Seidman, E. Caco‐2 cells as a model for intestinal lipoprotein synthesis and secretion. FASEB J. 9, 626‐635 (1995)
Profiling chemotherapy-associated myelotoxicity among Chinese gastric cancer population receiving cytotoxic conventional regimens: epidemiological features, timing, predictors and clinical impacts

Objectives: We aim to evaluate the epidemiological features, timing, predictors and clinical impacts of chemotherapy-associated myelotoxicity in Chinese gastric cancer population receiving six established cytotoxic conventional regimens (CF/XP, EC(O)F/EC(O)X, DC(O)F/DC(O)X, PC(O)F/PC(O)X, FOLFOX4, or mFOLFOX7/XELOX). Patients and methods: A 4-year multicenter, prospective, observational study was conducted in multiple hospitals/institutes spanning three major regions in China. A total of 1,285 patients with gastric cancer, treated with six selected regimens between 2010 and 2014 were included. Kaplan-meier analysis was applied to estimate the time to develop myelotoxicity events for each regimen. Multivariable logistic regression model was built to identify predictors associated with chemotherapy-induced myelotoxicity, evaluating detailed specific factors of patients, disease and treatment patterns. Results: Triplet regimens were associated with more moderate-to-severe myelotoxicity events than doublet regimens. DC(O)F/DC(O)X group presented with moderate-to-severe anaemia, thrombocytopenia, and leukopenia earlier than other regimen groups, with median time of 3.5, 4.8 and 3.3 cycles, respectively. PC(O)F/PC(O)X group had a shortest time to develop Moderate-to-Severe neutropenia (median time, 3.3 cycles). Multivariate analysis identified several independent predictors for moderate-to-severe myelotoxicity, including: baseline Hb<12.0 g/dL, male gender, KPS<80, previously treated with surgery, tumor located at gastroesophageal junction(GEJ), DC(O)F/DC(O)X regimen, palliative intent, triplet combination therapy and No. of cycles received≥4. Dose reductions≥20% occurred in 16.7% of patients and treatment delays≥7 days presented in 21.1% of patients, resulting in patients receiving an actual average Relative Dose Intensity (RDI) of 0.733. Conclusions: Myelotoxicity events were frequently observed within the gastric cancer population undertaking multicycle polychemotherapy. Predictive models based on risk factors identified for moderate-to-severe myelotoxicity should enable the targeted use of appropriate supportive care in an effort to facilitate the delivery of full chemotherapy doses on schedule.
A generalized inverse planning tool for volumetric-modulated arc therapy

The recent development in linear accelerator control systems, named volumetric-modulated arc therapy (VMAT), has generated significant interest in arc-based intensity-modulated radiation therapy (IMRT). The VMAT delivery technique features simultaneous changes in dose rate, gantry angle and gantry rotation speed as well as multi-leaf collimator (MLC) leaf positions while radiation is on. In this paper, we describe a generalized VMAT planning tool that is designed to take full advantage of the capabilities of the new linac control systems. The algorithm incorporates all of the MLC delivery constraints such as restrictions on MLC leaf interdigitation and the MLC leaf velocity constraints. A key feature of the algorithm is that it is able to plan for both single- and multiple-arc deliveries. Compared to conventional step-and-shoot IMRT plans, our VMAT plans created using this tool can achieve similar or better plan quality with less MU and better delivery efficiency. The accuracy of the obtained VMAT plans is also demonstrated through plan verifications performed on an Elekta Synergy linear accelerator equipped with a conventional MLC of 1 cm leaf width using a PreciseBeam® VMAT linac control system.
A Comparison of Requirements Specification Methods from a Software Architecture Perspective

Abstract : One of the key challenges to producing high-quality software architecture is identifying and understanding the software's architecturally significant requirements. These requirements are the ones that have the most far-reaching effect on the architecture. In this report, five methods for the elicitation and expression of requirements are evaluated with respect to their ability to capture architecturally significant requirements. The methods evaluated are requirements specification using natural language, use case analysis, the Quality Attribute Workshop (developed by the Carnegie Mellon (trademark) Software Engineering Institute), global analysis, and an approach developed by Fergus O'Brien. These methods were chosen because they are in widespread use or emphasize the capture of architecturally significant requirements. Three problems must be solved to systematically transform business and mission goals into architecturally significant requirements: (1) the requirements must be expressed in a form that provides the information necessary for design; (2) the elicitation of the requirements must capture architecturally significant requirements; and (3) the business and mission goals must provide systematic input for elicitation process. The primary finding from the evaluation of these methods is that there are promising solutions to the first two problems. However, there is no method for systematically considering the business and mission goals in the requirements elicitation.
ECNU: Using Multiple Sources of CQA-based Information for Answers Selection and YES/NO Response Inference

This paper reports our submissions to community question answering task in SemEval2015, which consists of two subtasks: (1) predict the quality of answers to given question as good, bad, or potentially relevant and (2) identify yes, no or unsure response to a given YES/NO question based on the good answers identified by subtask 1. For both subtasks, we adopted supervised classification method and examined the effects of heterogeneous features generated from community question answering data, such as bag-of-words, string matching, semantic similarity, answerer information, answer-specific features, questionspecific features, etc. Our submitted primary systems ranked the forth and the second for the two subtasks of English data respectively.
Recent declines in reported syphilis rates in eastern Europe and central Asia: are the epidemics over?

Background: Since the early 1990s, major syphilis epidemics have occurred in the Newly Independent States (NIS) of the former Soviet Union. The new and rapidly changing societal and economic conditions in these countries challenge their traditional approaches to the control of sexually transmitted infections (STI). Nevertheless, following a steady increase until 1997, reported syphilis incidence has declined during the past 3 years in most parts of the region. We examine these trends against a background of ongoing changes in service delivery, care seeking behaviour, and case finding practices. Methods: National syphilis surveillance data reported to the WHO Regional Office for Europe were compiled and analysed, and supplemented with information presented at recent expert meetings and with results from ongoing research. Results: Since 1997, reported syphilis incidence either stabilised or declined in many locations in the NIS, but further increased in others, especially in rural areas. Congenital syphilis continued to increase in all countries, except Latvia. The proportion of self presenting cases versus cases detected through screening declined, and so did notifications of early compared with late forms of syphilis. Patients increasingly seek care in the private formal and informal healthcare sectors which hardly participate in case reporting. Conclusions: Recent declines in syphilis notifications in the NIS are at least partially a reflection of a reduced intensity of active case finding and of changes in reporting completeness because of a shift in service utilisation from the public to the private/informal sectors. Syphilis rates are still high, indicating that both public and private sectors have to respond more efficiently to the needs of many people at risk of STI. The collection of serial STI prevalence data is recommended to be able to validate trends in notifications.
Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage

von Willebrand disease (VWD) is the most common inherited human bleeding disorder and is caused by quantitative or qualitative defects in von Willebrand factor (VWF). VWF is a secreted glycoprotein that circulates as large multimers. While reduced VWF is associated with bleeding, elevations in overall level or multimer size are implicated in thrombosis. The zebrafish is a powerful genetic model in which the hemostatic system is well conserved with mammals. The ability of this organism to generate thousands of offspring and its optical transparency make it unique and complementary to mammalian models of hemostasis. Previously, partial clones of zebrafish vwf have been identified, and some functional conservation has been demonstrated. In this paper we clone the complete zebrafish vwf cDNA and show that there is conservation of domain structure. Recombinant zebrafish Vwf forms large multimers and pseudo-Weibel-Palade bodies (WPBs) in cell culture. Larval expression is in the pharyngeal arches, yolk sac, and intestinal epithelium. These results provide a foundation for continued study of zebrafish Vwf that may further our understanding of the mechanisms of VWD.
Block diagonalization approach for amplify-and-forward relay systems in MIMO multi-user channels

In this paper, we consider a relay system in multiple-input multiple-output (MIMO) multi-user channels where a single MIMO relay is engaged in communication between multiple source-destination terminal pairs. We propose two amplify-and-forward (AF) relaying schemes which maximize the sum-rate for the interference channel with multiple source-destinations. First, we introduce an iterative scheme which provides a local optimal solution. The proposed scheme iteratively searches an optimum relay matrix by deriving the gradient of the sum-rate and applying the gradient descent algorithm. Next, in order to reduce the computational complexity of the iterative scheme, we propose a block diagonalization (BD) method which utilizes the minimum mean-square error (MMSE) criterion with singular value decomposition (SVD) based rate maximization. Simulation results show that the proposed iterative scheme achieves a near-optimal sum-rate for the given channel model, and the MMSE based BD with the rate maximization approaches the local optimal sum-rate at high signal-to-noise ratio (SNR) regime.
Lack of Evidence for Molecular Mimicry in HIV-Infected Subjects

Previous studies in HIV patients have reported autoantibodies to several human proteins, including erythropoietin (EPO), interferon-α (IFN-α), interleukin-2 (IL-2), and HLA-DR, as potential mediators of anemia or immunosuppression. The etiology of these autoantibodies has been attributed to molecular mimicry between HIV epitopes and self-proteins. Here, the Luciferase Immunoprecipitation System (LIPS) was used to investigate the presence of such autoantibodies in HIV-infected adults. High levels of antibodies to HIV proteins such as capsid (p24), matrix (p17), envelope (gp41), and reverse transcriptase (RT) were detected using LIPS in both untreated and anti-retroviral-treated HIV-infected individuals but not in uninfected controls. LIPS readily detected anti-EPO autoantibodies in serum samples from subjects with presumptive pure red cell aplasia but not in any of the samples from HIV-infected or uninfected individuals. Similarly, subjects with HIV lacked autoantibodies to IFN-α, IL-2, HLA-DR and the immunoglobulin lambda light chain; all purported targets of molecular mimicry. While molecular mimicry between pathogen proteins and self-proteins is a commonly proposed mechanism for autoantibody production, the findings presented here indicate such a process is not common in HIV disease.
Relation of Helicobacter pylori infection to 13-year mortality and incident ischemic heart disease in the caerphilly prospective heart disease study.

BACKGROUND Associations have been suggested between Helicobacter pylori seropositivity, cardiovascular risk factors, and ischemic heart disease (IHD). The effect of this common infection on mortality is uncertain. METHODS AND RESULTS Plasma specimens collected during 1979 to 1983 from 1796 men in Caerphilly, South Wales, were analyzed for IgG antibodies to H pylori. Cause of death and occurrence of incident IHD events were ascertained over an average of 13.7 years from death certificates, hospital records, and ECG changes at 5-yearly follow-up examinations. Seventy percent of men were seropositive. The prevalence of IHD at entry was similar in men with and without H pylori antibodies (odds ratio [OR], 1.10; 95% CI, 0.87 to 1.40). Seropositivity was significantly (P<0.05) associated with poorer socioeconomic status currently and in childhood, shorter stature, and poorer ventilatory function at entry but not with age, smoking, body mass index, blood pressure, total cholesterol, HDL cholesterol, LDL cholesterol, fibrinogen, plasma viscosity, or heat shock protein antibodies. Thirteen-year incidence of IHD was not significantly associated with H pylori (OR, 1.05; 95% CI, 0.80 to 1.39), but there was a stronger relationship with all-cause mortality (OR, 1.46; 95% CI, 1.12 to 1.92) and fatal IHD (OR, 1.54; 95% CI, 1.03 to 2.30). After adjustment for cardiovascular risk factors and both adult and childhood socioeconomic status, ORs were slightly reduced and lost statistical significance (OR=1.32 [95% CI, 0.99 to 1.78] for all-cause mortality and OR=1.52 [95% CI, 0.99 to 2.34] for fatal IHD). CONCLUSIONS H pylori infection is unlikely to be as strong a risk factor for IHD as some previous studies have suggested, but its relationship to mortality, including fatal IHD, deserves further investigation. The mechanism underlying these associations is unlikely to involve hypertension, circulating lipid profile, fibrinogen, or cross-reacting antibodies to bacterial heat shock proteins.
COMPUTER SIMULATION OF BUBBLE FORMATION

Properties of liquid metals (Li, Pb, Na) containing nanoscale cavities were studied by atomistic Molecular Dynamics (MD). Two atomistic models of cavity simulation were developed that cover a wide area in the phase diagram with negative pressure. In the first model, the thermodynamics of cavity formation, stability and the dynamics of cavity evolution in bulk liquid metals have been studied. Radial densities, pressures, surface tensions, and work functions of nano-scale cavities of various radii were calculated for liquid Li, Na, and Pb at various temperatures and densities, and at small negative pressures near the liquid-gas spinodal, and the work functions for cavity formation in liquid Li were calculated and compared with the available experimental data. The cavitation rate can further be obtained by using the classical nucleation theory (CNT). The second model is based on the stability study and on the kinetics of cavitation of the stretched liquid metals. A MD method was used to simulate cavitation in a metastable Pb and Li melts and determine the stability limits. States at temperatures below critical (T < 0.5Tc) and large negative pressures were considered. The kinetic boundary of liquid phase stability was shown to be different from the spinodal. The kinetics and dynamics of cavitation were studied. The pressure dependences of cavitation frequencies were obtained for several temperatures. The results of MD calculations were compared with estimates based on classical nucleation theory.
Automatic Data Fusion with HumMer

Heterogeneous and dirty data is abundant. It is stored under different, often opaque schemata, it represents identical real-world objects multiple times, causing duplicates, and it has missing values and conflicting values. The Humboldt Merger (HumMer) is a tool that allows ad-hoc, declarative fusion of such data using a simple extension to SQL.Guided by a query against multiple tables, HumMer proceeds in three fully automated steps: First, instance-based schema matching bridges schematic heterogeneity of the tables by aligning corresponding attributes. Next, duplicate detection techniques find multiple representations of identical real-world objects. Finally, data fusion and conflict resolution merges duplicates into a single, consistent, and clean representation.