Miracle-dz/UniFAR-FTUs huggingface dataset:
The Aryl Hydrocarbon Receptor Displaces p300 from E2F-dependent Promoters and Represses S Phase-specific Gene Expression*

The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a wide range of toxic, teratogenic, and carcinogenic effects. TCDD is a ligand for the aromatic hydrocarbon receptor (AHR), a ligand-activated transcription factor believed to be the primary mediator of these effects. Activation of the AHR by TCDD also elicits a variety of effects on cell cycle progression, ranging from proliferation to arrest. In this report, we have characterized further the role of the activated AHR in cell cycle regulation. In human mammary carcinoma MCF-7 and mouse hepatoma Hepa-1 cells, TCDD treatment decreased the number of cells in S phase and caused the accumulation of cells in G1. In Hepa-1 cells, this effect correlated with the transcriptional repression of several E2F-regulated genes required for S phase progression. AHR-mediated gene repression was dependent on its interaction with retinoblastoma protein but was independent of its transactivation function because AHR mutants lacking DNA binding or transactivation domains repressed E2F-dependent expression as effectively as wild type AHR. Overexpression of p300 suppressed retinoblastoma protein-dependent gene repression, and this effect was reversed by TCDD. Chromatin immunoprecipitation assays showed that TCDD treatment caused the recruitment of AHR to E2F-dependent promoters and the concurrent displacement of p300. These results delineate a novel mechanism whereby the AHR, a known transcriptional activator, also mediates gene repression by pathways involving combinatorial interactions at E2F-responsive promoters, leading to the repression of E2F-dependent, S phase-specific genes. The AHR seems to act as an environmental checkpoint that senses exposure to environmental toxicants and responds by signaling cell cycle inhibition.
Interpregnancy Interval and Adverse Pregnancy Outcomes: An Analysis of Successive Pregnancies and: Interpregnancy Interval and Pregnancy Outcomes: Causal or Not?

We read with interest a recent issue of Obstetrics & Gynecology that contains original research1 along with an editorial2 on interpregnancy interval and preterm birth. Dr. Klebanoff casts doubt on the causal nature of the association between short interpregnancy interval and preterm birth, citing the consistency of a lack of association identified by Hanley et al and by Ball et al.3 Both efforts employed within-mother comparisons in which each woman serves as her own control (conditional logistic regression). Our recent findings are not consistent with a lack of association despite employing similar methodology.4 That is, short interpregnancy interval of less than 6 months remained an increased risk for preterm birth even after applying conditional logistic regression. We have responded to his call for additional research. We examined effects of short interpregnancy interval on subsequent preterm birth risks separately for women who delivered their first birth preterm or at term. Using unconditional logistic regression (across-mother comparison), a short interpregnancy interval of less than 6 months was associated with increased odds of preterm birth among women whose first birth was preterm (odds ratio [OR] [95% CI] 1.44 [1.30–1.59]) or term (OR [95% CI] 1.34 [1.28–1.40]). Results remained elevated after applying conditional logistic regression (preterm: OR [95% CI] 1.37 [1.17–1.61]; term: OR [95% CI] 1.16 [1.09–1.24]). These results are consistent with those of a recent Dutch study showing that short interpregnancy interval is associated with increased odds of preterm birth regardless of model type (unconditional or conditional). 5 Next, we investigated whether risk would be altered conditional on delivery route of the first birth. Using unconditional logistic regression revealed that short interpregnancy interval of less than 6 months was associated with increased odds of preterm birth for women whose first delivery was vaginal (OR [95% CI] 1.38 [1.32–1.45]) or cesarean (OR [95% CI] 1.24 [1.13–1.36]). The results were similar when employing conditional logistic regression. That is, elevated odds of preterm birth short interpregnancy interval were observed among vaginal first deliveries (OR [95% CI] 1.21 [1.13–1.30]) and marginally so for cesarean deliveries (OR [95% CI] 1.12 [0.98–1.29]). We share these latest findings in an effort to continue the dialog around the nature of what short interpregnancy interval may or may not be contributing to preterm birth risk.
Tail Risk in Momentum Strategy Returns

Momentum strategies exhibit rare but dramatic losses (crashes), which we show are a result of the leverage dynamics of stocks in the momentum portfolio. When the economy is in a hidden turbulent state associated with a depressed and volatile stock market, the short-side of the momentum portfolio becomes highly levered, and behaves like a call option on the market index portfolio, making momentum crashes more likely. We develop a hidden Markov model of the unobserved turbulent state that affects the returns on the momentum strategy and the market index portfolios. We find that the use of a combination of Normal and Student-t distributions for the hidden residuals in the model to construct the likelihood of the realized momentum and market index returns dramatically improves the models ability to predict crashes. The same variable that forecasts momentum crashes also forecasts the correlation between momentum strategy and value strategy, two of the benchmark investment styles often used in performance appraisal of quant portfolio managers. The correlation is conditionally negative only when the probability of the economy being in a turbulent state is high. The conditional correlation is zero otherwise, which is two thirds of the time. Half of the negative value-momentum relation is due to leverage dynamics of stocks in the momentum strategy portfolio. The other half is due to a hidden risk factor, likely related to funding liquidity identified in Asness et al. (2013), which emerges only when the economy is more likely to be in the turbulent state.
Patterns and perceptions of care for treatment of back and neck pain: results of a national survey.

STUDY DESIGN We conducted a nationally representative random household telephone survey to assess therapies used to treat back or neck pain. OBJECTIVES The main outcome was complementary therapies used in the last year to treat back or neck pain. SUMMARY OF BACKGROUND DATA Back pain and neck pain are common medical conditions that cause substantial morbidity. Despite the presumed importance of complementary therapies for these conditions, studies of care for back and neck pain have not gathered information about the use of complementary therapies. METHODS Our nationally representative survey sampled 2055 adults. The survey gathered detailed information about medical conditions, conventional and complementary therapies used to treat those conditions, and the perceived helpfulness of those therapies. RESULTS We found that of those reporting back or neck pain in the last 12 months, 37% had seen a conventional provider and 54% had used complementary therapies to treat their condition. Chiropractic, massage, and relaxation techniques were the most commonly used complementary treatments for back or neck pain (20%, 14%, and 12%, respectively, of those with back or neck pain). Chiropractic, massage, and relaxation techniques were rated as "very helpful" for back or neck pain among users (61%, 65%, and 43%, respectively), whereas conventional providers were rated as "very helpful" by 27% of users. We estimate that nearly one-third of all complementary provider visits in 1997 (203 million of 629 million) were made specifically for the treatment of back or neck pain. CONCLUSIONS Chiropractic, massage, relaxation techniques, and other complementary methods all play an important role in the care of patients with back or neck pain. Treatment for back and neck pain was responsible for a large proportion of all complementary provider visits made in 1997. The frequent use and perceived helpfulness of commonly used complementary methods for these conditions warrant further investigation.
Social Network and Corporate Financial Performance : Conceptual Framework of Board Composition and Corporate Social Responsibility

Although a number of theories propose the relationship among corporate governance, corporate social responsibility (CSR) and corporate financial performance (CFP), existing literature does not provide a consensus of the direction of that relationship, or proposes how to enlarge it social network to absorb external resources. The purpose of this paper is to conceptualize the relationship between the composition of the board and corporate social responsibility (CSR) in the creation and development of a social network in order to improve firms’ financial performance.
Implications of Higher Order Risk Factors for Hedge Fund Performance

This paper investigates the performance of hedge funds adjusted for higher order risk factors. Traditional risk-adjusted performance measures are subject to size distorted in the presence of skewness and kurtosis. A residual augmented least squares approach to model higher order risk moments in returns allows us to estimate a robust risk-adjusted performance measure for hedge funds. In a comparison of two styles of hedge funds, emerging market hedge funds are found to generate superior performance with higher positive significant alpha values than long/short equity funds.
Re-definition, nomenclature and crystal-chemistry of the hellandite group

Abstract Detailed X-ray single-crystal structure refinements and complete (SIMS + EMPA) microprobe chemical analyses of a series of non-metamict samples of hellandite recently found in Latium (Italy), together with a critical re-evaluation of the existing data on hellandite, allow a better understanding of the crystal-chemistry of the hellandite group. Relative to the crystal structure determined by Mellini and Merlino (1977) for a Y-rich sample from Predazzo (Italy), a new tetrahedrally coordinated site has been detected; this may be fully, or in part, occupied by Li and Be. These cations occur at the center of the tetrahedral cavity where the H atom, which is bonded to the O5 O atom, protrudes; thus the H content in hellandite is constrained to values ≤ 2 - (Li + Be + F). A new general formula for hellandite-group minerals is proposed: X4Y2ZT2[B4Si4O22]W2, where X = Na, Ca, Y, LREE3+ at the eightfold-coordinated M3 and M4 sites; Y = Ca, Y, HREE3+, Th4+, U4+ at the eightfold-coordinated M2 site; Z = Al, Mn3+, Fe3+, Ti4+ at the octahedral M1 site; T = ⃞ (vacancy), Li, Be at the new tetrahedrally coordinated site; and W = OH, F, O2- at the O5 site. Eight root end-member compositions were identified; four of these correspond to known compositions: hellandite-(REE), tadzhikite-(REE), and two new minerals, mottanaite-(Ce) and ciprianiite, which are described in a companion paper (Della Ventura et al. 2002). The root-name tadzhikite must be used for samples with Ti4+ > 0.5 apfu, with no reference to the OH content. Hellandite is an REE mineral. Rare-earth elements occur at two distinct sites (M2 and M4), with a strong preference for M2 (particularly HREE). Thus, one or two Levinson modifiers can be added to the root name to correctly describe the species. A sequence of incorporation based on crystalchemical arguments is provided and allows evaluation of the site populations for nomenclature purposes. This redefinition of the hellandite group and the new nomenclature rules have been approved by the IMA Commission on New Minerals and Mineral names (code 00-F).
Twin solutions to semipositone boundary value problems for fractional differential equations with coupled integral boundary conditions

This paper investigates the existence of at least two positive solutions for the following high-order fractional semipositone boundary value problem (SBVP, for short) with coupled integral boundary value conditions:  D0+u(t) + λf(t,u(t), v(t)) = 0, t ∈ (0, 1), D0+v(t) + λg(t,u(t), v(t)) = 0, t ∈ (0, 1), u(j)(0) = v(j)(0) = 0, j = 0, 1, 2, · · · ,n− 2, Dα−1 0+ u(1) = λ1 ∫η1 0 v(t)dt, Dα−1 0+ v(1) = λ2 ∫η2 0 u(t)dt, where n− 1 < α 6 n, n > 3, 0 < η1,η2 6 1, λ, λ1, λ2 are parameters and satisfy λ1λ2(η1η2) < Γ2(α+ 1), D0+ is the standard Riemann-Liouville derivative, and f,g are continuous and semipositone. By using the nonlinear alternative of Leray-Schauder type, Krasnoselskii’s fixed point theorems, and the theory of fixed point index on cone, we establish some existence results of multiple positive solutions to the considered fractional SBVP. As applications, two examples are presented to illustrate our main results. c ©2017 All rights reserved.
Déficit de base y depuración del lactato en el paciente pediátrico con sepsis

El shock septico genera un estado de falla de aporte de oxigeno y nutrientes a la celula, consiguientemente liberacion de productos como el lactato y otros acidos organicos; produciendo un deficit de bases. Objetivo : el presente estudio pretende estimar la correlacion del lactato serico y el deficit de bases como guias en el manejo del shock septico durante las primeras 24 horas Metodos :se realizo un estudio observacional prospectivo; realizando la medicion seriada de lactato y del deficit de base; en pacientes shock septico tratados de acuerdo a recomendaciones de la Campana Sobreviviendo a la Sepsis (CSS) 2013. Resultados : el lactato serico y el deficit de base se depuran en 40% y 5% respectivamente durante las primeras 24 horas; no existe correlacion (p=0.289) al ingreso, observandose posteriormente una correlacion significativa (p=0,000). Los niveles de depuracion en los pacientes fallecidos fueron menores en relacion a los sobrevivientes. Conclusiones : el deficit de base no debe ser considerado como un sustituto fiable para el lactato serico en el paciente con shock septico; aunque probablemente sea de utilidad despues de las 24 horas. Palabras claves : sepsis, shock septico, lactato, deficit de base.
Deletion, rearrangement, and gene conversion; genetic consequences of chromosomal double‐strand breaks in human cells

Chromosomal double‐strand breaks (DSBs) in mammalian cells are usually repaired through either of two pathways: end‐joining (EJ) or homologous recombination (HR). To clarify the relative contribution of each pathway and the ensuing genetic changes, we developed a system to trace the fate of DSBs that occur in an endogenous single‐copy human gene. Lymphoblastoid cell lines TSCE5 and TSCER2 are heterozygous (+/−) or compound heterozygous (−/−), respectively, for the thymidine kinase gene (TK), and we introduced an I‐SceI endonuclease site into the gene. EJ for a DSB at the I‐SceI site results in TK‐deficient mutants in TSCE5 cells, while HR between the alleles produces TK‐proficient revertants in TSCER2 cells. We found that almost all DSBs were repaired by EJ and that HR rarely contributes to the repair in this system. EJ contributed to the repair of DSBs 270 times more frequently than HR. Molecular analysis of the TK gene showed that EJ mainly causes small deletions limited to the TK gene. Seventy percent of the small deletion mutants analyzed showed 100‐ to 4,000‐bp deletions with a 0‐ to 6‐bp homology at the joint. Another 30%, however, were accompanied by complicated DNA rearrangements, presumably the result of sister‐chromatid fusion. HR, on the other hand, always resulted in non‐crossing‐over gene conversion without any loss of genetic information. Thus, although HR is important to the maintenance of genomic stability in DNA containing DSBs, almost all chromosomal DSBs in human cells are repaired by EJ. Environ. Mol. Mutagen. 42:288–298, 2003. © 2003 Wiley‐Liss, Inc.
Dialysis Membrane Manipulation for Endotoxin Removal

In the dialysis clinic, water is an essential vehicle to deliver life-saving treatment to patients suffering from varying degrees of kidney failure, both acute and chronic. Clean water is vital, as the key ingredient used to prepare hemodialysis fluid (dialysate solution), and online generation of substitution fluid for hemodiafiltration. Generally all fluids used to treat patients suffering from kidney failure may come into contact with the blood of the patient, whether directly or indirectly (across a membrane), and theoretically could transport contaminants resulting in a negative impact on patient health. Of the microbiological contaminants found in water, endotoxin is given considerable attention, given its difficulty for removal and inactivation from water and water distribution systems (Smeets et al., 2003; Perez-Garcia & Rodriguez-Benitez, 2000) and its inherent pyrogenicity (G. Lonnemann, 2000). Endotoxins are found in all gram-negative bacteria, although slight differences in chemical structure are found between varying bacterial strains. The term endotoxin is typically used to describe a complex of protein and lipopolysaccharide (LPS) molecules found in the outer cell wall of gram-negative bacteria, that either slough off during growth, or are released upon cell lysis. Endotoxin and lipopolysaccharide are typically used interchangeably in literature, although in clinical discussion the term endotoxin is most often used, as it is the metric used to monitor water and dialysis fluid quality. Lipopolysaccharide is a vital component of the outer membrane of gram-negative bacteria, providing numerous physiological functions and comprising nearly 75% of the bacterium outer surface area (Raetz, 1991). Lipopolysaccharides consist of three components: a long heteropolysaccharide chain (O-specific chain) which represents a surface antigen; a core oligosaccharide; and a lipid component termed lipid A used as an anchor in the outer cell membrane (Rietschel et al., 1994; Gorbet & Sefton, 2005). Molecular weights of most lipopolysaccharides are 10 – 20 kDa; however, due to their amphiphilic nature, LPS molecules can form aggregates (100 – 1000 kDa) which are too large to pass through dialysis membranes. It has been shown that components of lipopolysaccharide (lipid A) are able to pass through dialysis membranes, can elicit a pyrogenic response (Naveh-Many et al., 1999), and contribute to long-term morbidity and inflammation (H. Schiffl, 2000; Raj et al., 2009). Lipid A is the most conserved component of lipopolysaccharide throughout all gramnegative bacteria, and as such is responsible for the majority of the pyrogenic activity. Lipid A consists of a phosphorylated N-acetylglucosamine (NAG) dimmer connected to saturated
FOXA 1 regulates androgen receptor variant activity in models and castrate-resistant prostate cancer

Retention of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the requirement for the development of more effective AR targeting therapies. A key mechanism of resistance to anti-androgens is through expression of constitutively active AR variants (AR-Vs) that are refractory to next-generation therapies, including Enzalutamide and Abiraterone. By maintaining an androgenic gene signature, AR-Vs drive tumour survival and progression in castrate conditions. Critically, however, our understanding of the mechanics of AR-V-driven transcription is limited, particularly with respect to dependency on pioneer factor function. Here we show that depletion of FOXA1 in the CWR22Rv1 CRPC cell line abrogates the oncogenic potential of AR-Vs. Gene expression profiling reveals that approximately 41% of the AR-V transcriptome requires FOXA1 and that depletion of FOXA1 attenuates AR-V binding at a sub-set of analysed co-regulated genes. Interestingly, AR-V levels are elevated in cells depleted of FOXA1 as a consequence of attenuated negative feedback on the AR gene, but is insufficient to maintain cell growth as evidenced by marked anti-proliferative effects in FOXA1 knockdown cells. In all, our data suggests that AR-Vs are dependent on FOXA1 for sustaining a pro-proliferative gene signature and agents targeting FOXA1 may represent novel therapeutic options for CRPC patients.
Scalable Concurrent Hash Table in Java

Sequential performance of CPU’s is reaching its limits, which makes concurrent computing a necessity for improving software performance. This requires not only concurrent, but also scalable data structures. Concurrent hash table implementations exist in Java, however these suffer from poor scalability. In this research we developed a new hash table with improved scalability over existing implementations and high sequential performance. The goal was to implement a hash table design by Laarman et al. in Java in order to provide developers with new means for creating scalable concurrent software, while also offering the benefits Java provides such as portability and maintainability. Throughput and speedup of the new hash table was compared with three existing implementations. With a maximum speedup 14.3 on 32 cores, the new implementation greatly improved upon existing implementations. Results from Laarman’s paper regarding a C implementation of the hash table design in LTSmin were also compared. This literature-based comparison found that their benchmark achieved larger speedup than we obtained with our implementation. Even though Java used to be stigmatized as a slow language, we found that it provides sufficient means for creating scalable algorithms, and usage should be considered over lower-level languages, as it allows for great scalability without sacrificing portability and maintainability.
Blast-related mild traumatic brain injury in the acute phase: Acute stress reactions partially mediate the relationship between loss of consciousness and symptoms

Abstract Primary objective: The objective was to compare symptoms in service members diagnosed with a blast-related mTBI (mild traumatic brain injury) with a loss of consciousness (LOC) to those without LOC. Research design: Clinicians saw US military personnel within 72 hours of sustaining a blast-related mTBI and at a follow-up visit 48–72 hours later (n = 210). Methods and procedures: Demographics, post-concussive symptoms, diagnosis of acute stress reaction (ASR) and simple reaction time data from the Automated Neuropsychological Assessment Metric (ANAM) were collected. Main outcomes and results: ASRs were significantly more likely in patients reporting LOC versus patients reporting no LOC. At the first post-injury visit, LOC was associated with difficulty sleeping, hearing loss, memory problems and reporting more symptoms. A follow-up analysis explored if symptomatic differences were influenced by ASR. Adjusting for ASR, the statistical relationships between LOC and symptoms were weaker (i.e. reduced Odds Ratios). At the follow-up visit, difficulty sleeping was associated with LOC before and after adjusting for ASR. Patients with both ASR and LOC had the slowest simple reaction times. Conclusions: Results suggest ASR may partially mediate symptom presentation and cognitive dysfunction in the acute phase following blast-related mTBI. Future research is warranted.