Miracle-dz/UniFAR-FTUs huggingface dataset:
T-Type Ca2+ Channel Inhibition Sensitizes Ovarian Cancer to Carboplatin

Ovarian cancer is the deadliest gynecologic cancer, due in large part to the diagnosis of advanced stage disease, the development of platinum resistance, and inadequate treatment alternatives. Recent studies by our group and others have shown that T-type calcium (Ca2+) channels play a reinforcing role in cancer cell proliferation, cell-cycle progression, and apoptosis evasion. Therefore, we investigated whether T-type Ca2+ channels affect ovarian tumor growth and response to platinum agents. Inhibition of T-type Ca2+ channels with mibefradil or by silencing expression resulted in growth suppression in ovarian cancer cells with a simultaneous increase in apoptosis, which was accompanied by decreased expression of the antiapoptotic gene survivin (BIRC5). Analysis of intracellular signaling revealed mibefradil reduced AKT phosphorylation, increased the levels and nuclear retention of FOXO transcription factors that repress BIRC5 expression, and decreased the expression of FOXM1, which promotes BIRC5 expression. Combining carboplatin with mibefradil synergistically increased apoptosis in vitro. Importantly, mibefradil rendered platinum-resistant ovarian tumors sensitive to carboplatin in a mouse model of peritoneal metastasis. Together, the data provide rationale for future use of T-type channel antagonists together with platinum agents for the treatment of ovarian cancer. Mol Cancer Ther; 15(3); 460–70. ©2016 AACR.
Clustering with feature selection using alternating minimization, Application to computational biology

This paper deals with unsupervised clustering with feature selection. The problem is to estimate both labels and a sparse projection matrix of weights. To address this combina-torial non-convex problem maintaining a strict control on the sparsity of the matrix of weights, we propose an alternating minimization of the Frobenius norm criterion. We provide a new efficient algorithm named K-sparse which alternates k-means with projection-gradient minimization. The projection-gradient step is a method of splitting type, with exact projection on the l 1 ball to promote sparsity. The convergence of the gradient-projection step is addressed, and a preliminary analysis of the alternating minimization is made. The Frobenius norm criterion converges as the number of iterates in Algorithm K-sparse goes to infinity. Experiments on Single Cell RNA sequencing datasets show that our method significantly improves the results of PCA k-means, spectral clustering, SIMLR, and Sparcl methods. The complexity of K-sparse is linear in the number of samples (cells), so that the method scales up to large datasets. Finally, we extend K-sparse to supervised classification.
Hepatic Cytochrome P450 Enzyme Alterations in Humans with Progressive Stages of Nonalcoholic Fatty Liver Disease The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.

Members of the cytochrome P450 (P450) enzyme families CYP1, CYP2, and CYP3 are responsible for the metabolism of approximately 75% of all clinically relevant drugs. With the increased prevalence of nonalcoholic fatty liver disease (NAFLD), it is likely that patients with this disease represent an emerging population at significant risk for alterations in these important drug-metabolizing enzymes. The purpose of this study was to determine whether three progressive stages of human NALFD alter hepatic P450 expression and activity. Microsomes isolated from human liver samples diagnosed as normal, n = 20; steatosis, n = 11; nonalcoholic steatohepatitis (NASH) (fatty liver), n = 10; and NASH (no longer fatty), n = 11 were analyzed for P450 mRNA, protein, and enzyme activity. Microsomal CYP1A2, CYP2D6, and CYP2E1 mRNA levels were decreased with NAFLD progression, whereas CYP2A6, CYP2B6, and CYP2C9 mRNA expression increased. Microsomal protein expression of CYP1A2, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 tended to decrease with NAFLD progression. Likewise, functional activity assays revealed decreasing trends in CYP1A2 (p = 0.001) and CYP2C19 (p = 0.05) enzymatic activity with increasing NAFLD severity. In contrast, activity of CYP2A6 (p = 0.001) and CYP2C9 (diclofenac, p = 0.0001; tolbutamide, p = 0.004) was significantly increased with NAFLD progression. Increased expression of proinflammatory cytokines tumor necrosis factor α and interleukin 1β was observed and may be responsible for observed decreases in respective P450 activity. Furthermore, elevated CYP2C9 activity during NAFLD progression correlated with elevated hypoxia-induced factor 1α expression in the later stages of NAFLD. These results suggest that significant and novel changes occur in hepatic P450 activity during progressive stages of NAFLD.
Pole-Shape Optimization of a Switched-Reluctance Motor for Torque Ripple Reduction

Switched-reluctance motors produce acoustic noise and vibration caused by torque ripple. Applications of these motors where silent operation is desirable, such as in home appliances, has, thus, been limited. This paper describes a proposal for a new stator pole face having a nonuniform air-gap and a pole shoe attached to the lateral face of the rotor pole. These additions minimize the undesired torque ripple. The effects of each design parameter were investigated using a time-stepping finite-element method. The parameters were optimized by utilizing response surface method (RSM) combined with (1 + 1) evolution strategy. It has been shown, through numerical tests, that the optimized shape gives higher average torque and drastically reduced torque ripple
New Results for the Heterogeneous Multi-Processor Scheduling Problem using a Fast, Effective Local Search and Random Disruption

The efficient scheduling of independent computational tasks in a heterogeneous computing environment is an important problem that occurs in domains such as Grid and Cloud computing. Finding optimal schedules is an NP-hard problem in general, so we have to rely on approximate algorithms to come up schedules that are as near to optimal as possible. In our previous work on this problem, we applied a fast, effective local search to generate reasonably good schedules in a short amount of time and used ant colony optimisation (ACO) to incrementally improve those schedules over a longer time period. In this work, we replace the ACO component with a random disruption algorithm and find that this produces results which are competitive with the current state of the art over a 90 second execution time. We also ran our algorithm for a longer time period on 12 well-known benchmark instances and as a result provide new upper bounds for these instances.
The impact of pay satisfaction and school achievement on high school principals’ turnover intentions

In recent years, a principal supply shortage crisis has emerged in the USA. This problem has been exacerbated by an increase in principal departures, which has been found to be negatively related to school outcomes. While research exists on several determinants of principal turnover, any examination of the relationship between principals’ affective reaction to pay relative to their intent to leave their position at a particular school is missing from the literature. This research seeks to fill this void by examining the association between California (USA) high school principals’ pay satisfaction and turnover intentions (n=156). The importance of potential referent sources (i.e., teachers within the school districts, other high school principals within the school district, and other high school principals in different school districts) for pay satisfaction and the relationship between achievement and turnover intentions were also examined. This study uses a two-stage structural equation modelling approach and finds evidence to suggest that high school principals’ pay satisfaction is influenced by the salaries of comparative peers and is negatively associated with principals’ intention to turnover. Achievement was not found to be related to turnover intentions. Policy implications and future research recommendations are discussed.
Factors influencing the case-fatality rate of Legionnaires' disease.

SETTING The extent of the public health problem posed by Legionnaires' disease (LD) is not always well- appreciated. OBJECTIVE To determine the characteristics and factors associated with the case fatality rate (CFR) of LD in Catalonia, Spain. DESIGN Confirmed cases of LD reported during 1993-2004 were studied. Age, sex, hospitalisation, the type of diagnostic confirmation test and the personal risk factors for LD of cases were collected. Comparative bivariate and multivariate analyses according to origin (community-acquired or nosocomial) and nature (sporadic or outbreaks) were performed. RESULTS Of 1938 cases reported, 164 died (case-fatality rate [CFR] 8.5%). The CFR fell from 35% in 1993 to 5.6% in 2004, and was higher in sporadic than in outbreak-associated cases (10% vs. 4.7%) and in nosocomial than community-acquired cases (31.7% vs. 6.8%). In community-acquired cases, the CFR was associated with age >70 years (OR 3.42, 95%CI 2.02-5.79), cancer (OR 4.58, 95%CI 2.36-8.90) and diagnostic confirmation methods other than Legionella urinary antigen test. The CFR of nosocomial cases was not associated with any of these factors. CONCLUSIONS The CFR of LD fell during the study period due to the incorporation of new diagnostic techniques and improved detection of outbreaks.
Knee Disarticulation: Survival, Wound Healing and Ambulation. A Historic Cohort Study

The aim of this study was to analyze survival, wound healing and ambulation after knee disarticulation (KD). A historic cohort study using medical records and nursing home records was performed. Data included demographics, reason for amputation, concomitant diseases, survival, wound healing, re-amputation and ambulation. Data of 80 patients (71 unilateral and nine bilateral amputees) were available for evaluation. Median follow-up was 9.9 years (IQR: 4.1; 14.3 years). Mean age of amputation was 76.9 (± 9.6) years. Reason for amputation was gangrene in 72 patients. Most common concomitant (96%) disease was peripheral arterial disease (PAD). Survival after 1, 6 and 12 months was 87%, 65% and 52%, respectively. Delayed wound healing occurred in 42% (n = 16) of the patients with two or three concomitant diseases and in 15% (n = 6) of the patients with no or one concomitant disease. Trans-femoral re-amputation was performed in nine (12%) patients. Of the 61 discharged KD amputees, 36 (59%) were provided with a prosthesis. Eventually 21 (34%) patients became household walkers.
The Effects of Product Scandals on Parent Brands: Linguistic Signatures of a Protective Mechanism

Extended Abstract Brand architectures involving a parent brand can improve the perception of their associated brands and allow for a simple and cost saving introduction of new products (Smith, 1992). New or established product brands may benefit from associations with parent brands (Aaker & Keller, 1989; Sattler, Völckner, & Zatloukal, 2002). The opportunity of such positive transfer effects, however, comes at a price: The transfer is neither restricted to positive affect, Abstract Previous research on preferences for sequences of outcomes shows that people prefer some sequences over others. For example, people prefer sequences where positive and negative outcomes are spread out over time (Loewenstein and Prelec, 1993). Although previous research presents us with valuable insights into the sequence evaluation process, the conditions under which these sequence preferences hold have not received much attention. Previous research has shown that mood and ego depletion have a profound influence on the level and quantity of information that is processed and as a result on the decision making process (Schwarz, 2001; Baumeister, Bratslavsky, Muraven, and Tice, 1998). Therefore, we believe that when looking at sequence preferences, these two mechanisms can not be overlooked.This research presents the results of an experiment designed to test a theoretical framework in which the combined effect of mood and ego depletion influences preferences for sequences of service experiences. We argue that ego depletion and mood play an important role in service encounters and that the initial mood state of the customer will influence which components of the service are considered important for the evaluation of the service. In addition, certain events within a service encounter require active self-control by the customer, Extended Abstract Chinese manufacturers favor the use of digit 8 and avoid using the digit 4 in their pricing as buyers in China connote digit 8 with “enrichment” and digit 4 with “death” (Simmons and Schindler 2003). This numeric superstition also results in a price premium for properties on the 8th floor in Cantonese societies (Chau, Ma and Ho 2001). Many American hotels skip from the 12th floor to the 14th floor to avoid having guests stay on the unlucky 13th floor (Mowen and Carlson 2003). Why do so many people, usually well-educated members of a modern, scientific society, engage in these behaviors? What motivates such behavior? The objective of this research is to present a comprehensive model of the mechanisms driving superstitious behavior among individuals and highlight its relevance both in terms of theory and practice. There are five basic problems with existing models of
A practical method for constructing LR (k) processors

A practical method for constructing LR(k) processors is developed. These processors are capable of recognizing and parsing an input during a single no-backup scan in a number of steps equal to the length of the input plus the number of steps in its derivation. The technique presented here is based on the original method described by Knuth, but decreases both the effort required to construct the processor and the size of the processor produced. This procedure involves partitioning the given grammar into a number of smaller parts. If an LR(k) processor can be constructed for each part (using Knuth's algorithm) and if certain conditions relating these individual processors are satisfied, then an LR(k) processor for the entire grammar can be constructed for them. Using this procedure, an LR(1) parser for ALGOL has been obtained.
Electrical conductivity of orthopyroxene: Implications for the water content of the asthenosphere

Electrical conductivity of minerals is sensitive to water content and hence can be used to infer the water content in the mantle. However, previous studies to infer the water content in the upper mantle were based on pure olivine model of the upper mantle. Influence of other minerals particularly that of orthopyroxene needs to be included to obtain a better estimate of water content in view of the high water solubility in this mineral. Here we report new results of electrical conductivity measurements on orthopyroxene, and apply these results to estimate the water content of the upper mantle of Earth. We found that the electrical conductivity of orthopyroxene is enhanced by the addition of water in a similar way as other minerals such as olivine and pyrope garnet. Using these new results, we calculate the electrical conductivity of pyrolite mantle as a function of water content and temperature incorporating the temperature and water fugacity-dependent hydrogen partitioning. Reported values of asthenosphere conductivity of 4 × 10−2−10−1 S/m corresponds to the water content of 0.01–0.04 wt%, a result in good agreement with the petrological model of the upper mantle.
Function of mutant and wild-type plexinB1 in prostate cancer cells

Semaphorins act as chemotactic cues for cell movement via their transmembrane receptors, plexins. Somatic missense mutations in the plexinB1 gene coupled with overexpression of the protein frequently occur in prostate tumors, indicating a role for plexinB1 in the pathogenesis of prostate cancer. However, the effect of semaphorin/plexin signaling is highly context dependent and whether plexinB1 acts as an inducer or inhibitor of prostate tumor progression in this context is not known.
Stomach-specific Biomarkers (GastroPanel) Can Predict the Development of Gastric Cancer in a Caucasian Population: A Longitudinal Nested Case-Control Study in Siberia.

BACKGROUND/AIM Atrophic gastritis (AG) is the most important risk condition for gastric cancer (GC). A panel of stomach-specific serum biomarkers: pepsinogen (PG) I, pepsinogen (PG) II, gastrin-17 (G-17), and IgG antibodies to H. pylori (HP-Ab) detects the extent and grade of AG. The aim of the present study was to assess the predictive value of this 4-biomarker panel (GastroPanel, Biohit Oyj, Helsinki, Finland) in a case-control setting nested within a cohort of Caucasian population in Western Siberia. PATIENTS AND METHODS Both the cases and controls for the study derived from a population-based cohort of 45-69-year-old subjects (n=9,360) in the HAPIEE (Health, Alcohol and Psychosocial Factors In Eastern Europe) study, enrolled in Novosibirsk, Siberia during 2003-2005. Cases represent all GCs reported to the Cancer Registry until 2012, being matched (1:2) with healthy controls (COs). Altogether 156 (52 GCs and 104 COs) serum samples collected at study entry were available for GastroPanel analysis. Conditional logistic regression models (uni- and multivariate) were used to analyze this matched case-control setting. RESULTS The biomarker levels below cut-off at baseline predicted the development of GC as follows: PGI (OR=2.9; 95%CI=1.3-6.4), PGII (OR=9.0; 95%CI=1.8-44.3), PGI/PGII (OR=3.3; 95%CI=1.5-7.3); G-17 (OR=1.8; 95%CI=0.7-4.8), and HP-Ab (OR=0.4; 95%CI=0.1-1.3). In the multivariate model adjusted for sex, age, and all GastroPanel markers, PGI/PGII ratio was the most powerful independent predictor of GC (OR=2.9; 95% CI=1.01-8.0). CONCLUSION For the first time in a Caucasian population, we demonstrated that PGI, PGII and PGI/PGII ratio are reliable longitudinal predictors of incidence of GC.
Indoor Environmental Exposures for Children with Asthma Enrolled in the HEAL Study, Post-Katrina New Orleans

Background: Rain and flooding from Hurricane Katrina resulted in widespread growth of mold and bacteria and production of allergens in New Orleans, Louisiana, which may have led to increased exposures and morbidity in children with asthma. Objectives: The goal of the Head-off Environmental Asthma in Louisiana (HEAL) study was to characterize post-Katrina exposures to mold and allergens in children with asthma. Methods: The homes of 182 children with asthma in New Orleans and surrounding parishes were evaluated by visual inspection, temperature and moisture measurements, and air and dust sampling. Air was collected using vacuum-pump spore traps and analyzed for > 30 mold taxa using bright field microscopy. Dust was collected from the children’s beds and bedroom floors and analyzed for mouse (Mus m 1), dust mite (Der p 1), cockroach (Bla g 1), and mold (Alternaria mix) allergens using ELISA. Results: More than half (62%) of the children were living in homes that had been damaged by rain, flooding, or both. Geometric mean indoor and outdoor airborne mold levels were 501 and 3,958 spores/m3, respectively. Alternaria antigen was detected in dust from 98% of homes, with 58% having concentrations > 10 µg/g. Mus m 1, Der p 1, and Bla g 1 were detected in 60%, 35%, and 20% of homes, respectively, at low mean concentrations. Conclusions: Except for Alternaria antigen in dust, concentrations of airborne mold (ratio of indoor to outdoor mold) and dust allergens in the homes of HEAL children were lower than measurements found in other studies, possibly because of extensive post-Katrina mold remediation and renovations, or because children moved into cleaner homes upon returning to New Orleans.
The yeast p24 complex regulates GPI-anchored protein transport and quality control by monitoring anchor remodeling

Two functions of the p24 complex are described: one connects GPI-anchored proteins to COPII proteins at ER exit sites to facilitate their incorporation into ER-derived vesicles, and the other serves in quality control of GPI-anchored proteins to retrieve unremodeled GPI-anchored proteins from the Golgi back to the ER.
Quantifying Maintainability in Feature Oriented Product Lines

Families of products are steadily emerging for distinct settings such as embedded systems, navigational systems, financial applications or even web applications. This shifts the attention from individual product-centric development to software product line development where the focus is on constructing reusable assets from which customer-specific products are obtained. This paper tackles the maintenance of an entire family of products, describing our approach to quantifying maintainability. We report our experience measuring the maintainability index of each product in the family, and then propose a generalization of the results in terms of the entire family or product line. This exposes a number of benefits towards the improvement of product-line maintainability, enhancing ultimately customer-specific products.
Lexical and referential cues to sentence interpretation: an investigation of children's interpretations of ambiguous sentences

This paper reports on an investigation of children's (aged 3;5–9;8) comprehension of sentences containing ambiguity of prepositional phrase (PP) attachment. Results from a picture selection study (N=90) showed that children use verb semantics and preposition type to resolve the ambiguity, with older children also showing sensitivity to the definiteness of the object NP as a cue to interpretation. Study 2 investigated three- and five-year-old children's (N=47) ability to override an instrumental interpretation of ambiguous PPs in order to process attributes of the referential scene. The results showed that while five-year-olds are capable of incorporating aspects of the referential scene into their interpretations, three-year-olds are not as successful. Overall, the results suggest that children are attuned very early to the lexico-semantic co-occurrences that have been shown to aid ambiguity resolution in adults, but that more diffuse cues to interpretation are used only later in development.