Miracle-dz/UniFAR-FTUs huggingface dataset:
Prospective associations between vitamin D status, vitamin D-related gene polymorphisms, and risk of tobacco-related cancers.

BACKGROUND Experimental evidence has suggested that vitamin D may be protective against tobacco-related cancers through the inhibition of the formation of tumors induced by tobacco carcinogens. To our knowledge, only one previous epidemiologic study investigated the association between vitamin D status and tobacco-related cancer risk, and no study has focused on vitamin D-related gene polymorphisms. OBJECTIVE Our objective was to prospectively study the association between plasma 25-hydroxyvitamin D [25(OH)D] concentrations, vitamin D-related gene polymorphisms, and risk of tobacco-related cancers. DESIGN A total of 209 tobacco-related cancers were diagnosed within the SU.VI. MAX (Supplémentation en vitamines et minéraux antioxydants) cohort (1994-2007) and were matched with 418 controls as part of a nested case-control study. Tobacco-related cancers (i.e., cancers for which tobacco is one of the risk factors) included several sites in the respiratory, digestive, reproductive, and urinary systems. Total plasma 25(OH)D was assessed with the use of an electrochemoluminescent assay. Polymorphisms were determined with the use of a TaqMan assay. Conditional logistic regression models were computed. RESULTS A 25(OH)D concentration ≥30 ng/mL was associated with reduced risk of tobacco-related cancers (OR for ≥30 compared with <30 ng/mL: 0.59; 95% CI 0.35, 0.99; P = 0.046). This association was observed in former and current smokers (OR for ≥30 compared with <30 ng/mL: 0.43; 95% CI: 0.23, 0.84; P = 0.01) but not in never smokers (P = 0.8). The vitamin D receptor (VDR) FokI AA genotype and retinoid X receptor (RXR) rs7861779 TT genotype were associated with increased risk of tobacco-related cancers [OR for homozygous mutant type (MT) compared with wild type (WT): 1.87; 95% CI: 1.08, 3.23; P-trend = 0.02; OR for heterozygous type (HT) plus MT compared with WT: 1.60; 95% CI: 1.07, 2.38; P = 0.02]. CONCLUSIONS In this prospective study, high vitamin D status [25(OH)D concentration ≥30 ng/mL] was associated with decreased risk of tobacco-related cancers, especially in smokers. These results, which are supported by mechanistic plausibility, suggest that vitamin D may contribute to the prevention of tobacco-induced cancers in smokers and deserve additional investigation. The SU.VI. MAX trial was registered at clinicaltrials.gov as NCT00272428.
Oscillations in the CMB from axion monodromy inflation

We study the CMB observables in axion monodromy inflation. These well-motivated scenarios for inflation in string theory have monomial potentials over super-Planckian field ranges, with superimposed sinusoidal modulations from instanton effects. Such periodic modulations of the potential can drive resonant enhancements of the correlation functions of cosmological perturbations, with characteristic modulations of the amplitude as a function of wavenumber. We give an analytical result for the scalar power spectrum in this class of models, and we determine the limits that present data places on the amplitude and frequency of modulations. Then, incorporating an improved understanding of the realization of axion monodromy inflation in string theory, we perform a careful study of microphysical constraints in this scenario. We find that detectable modulations of the scalar power spectrum are commonplace in well-controlled examples, while resonant contributions to the bispectrum are undetectable in some classes of examples and detectable in others. We conclude that resonant contributions to the spectrum and bispectrum are a characteristic signature of axion monodromy inflation that, in favorable cases, could be detected in near-future experiments.
A Transient Receptor Potential Vanilloid 4-Dependent Mechanism of Hyperalgesia Is Engaged by Concerted Action of Inflammatory Mediators

The transient receptor potential vanilloid 4 (TRPV4) is a primary afferent transducer that plays a crucial role in neuropathic hyperalgesia for osmotic and mechanical stimuli, as well as in inflammatory mediator-induced hyperalgesia for osmotic stimuli. In view of the clinical importance of mechanical hyperalgesia in inflammatory states, the present study investigated the role of TRPV4 in mechanical hyperalgesia induced by inflammatory mediators and the second-messenger pathways involved. Intradermal injection of either the inflammogen carrageenan or a soup of inflammatory mediators enhanced the nocifensive paw-withdrawal reflex elicited by hypotonic or mechanical stimuli in rat. Spinal administration of TRPV4 antisense oligodeoxynucleotide blocked the enhancement without altering baseline nociceptive threshold. Similarly, in TRPV4−/− knock-out mice, inflammatory soup failed to induce any significant mechanical or osmotic hyperalgesia. In vitro investigation showed that inflammatory mediators engage the TRPV4-mediated mechanism of sensitization by direct action on dissociated primary afferent neurons. Additional behavioral observations suggested that multiple mediators are necessary to achieve sufficient activation of the cAMP pathway to engage the TRPV4-dependent mechanism of hyperalgesia. In addition, direct activation of protein kinase A or protein kinase C ϵ, two pathways that mediate inflammation-induced mechanical hyperalgesia, also induced hyperalgesia for both hypotonic and mechanical stimuli that was decreased by TRPV4 antisense and absent in TRPV4−/− mice. We conclude that TRPV4 plays a crucial role in the mechanical hyperalgesia that is generated by the concerted action of inflammatory mediators present in inflamed tissues.
Baseline In Vitro Activities of the Antimalarials Pyronaridine and Methylene Blue against Plasmodium falciparum Isolates from Kenya

ABSTRACT We have analyzed the in vitro activities of pyronaridine and methylene blue against 59 Plasmodium falciparum isolates from Kenya in association with polymorphisms in Pfcrt (codon 76), Pfmdr1 (codon 86), and Pfnhe (full sequence). The median inhibitory concentrations that kill 50% of parasites were 13.5 and 3.3 nM for pyronaridine and methylene blue, respectively. Their activities were not associated with polymorphisms in these genes. The drugs' high in vitro activities indicate that they would be efficacious against Kenyan isolates in vivo.
Functional Interactions With Adjacent Neurons Temporal Cortex : Visual Response Properties and Presumed Inhibitory Neurons in the Macaque Inferior

[PDF] [Full Text] [Abstract] , December 1, 2004; 16 (12): 2597-2637. Neural Comput. E. Curti, G. Mongillo, G. La Camera and D. J. Amit Coded Random Memories Mean Field and Capacity in Realistic Networks of Spiking Neurons Storing Sparsely [PDF] [Full Text] [Abstract] , November 2, 2005; 25 (44): 10299-10307. J. Neurosci. T. Hirabayashi and Y. Miyashita Depending on the Feature Configuration within a Whole Object Dynamically Modulated Spike Correlation in Monkey Inferior Temporal Cortex
Microbiota organization is a distinct feature of proximal colorectal cancers

Significance We demonstrate, to our knowledge for the first time, that bacterial biofilms are associated with colorectal cancers, one of the leading malignancies in the United States and abroad. Colon biofilms, dense communities of bacteria encased in a likely complex matrix that contact the colon epithelial cells, are nearly universal on right colon tumors. Most remarkably, biofilm presence correlates with bacterial tissue invasion and changes in tissue biology with enhanced cellular proliferation, a basic feature of oncogenic transformation occurring even in colons without evidence of cancer. Microbiome profiling revealed that biofilm communities on paired normal mucosa cluster with tumor microbiomes but lack distinct taxa differences. This work introduces a previously unidentified concept whereby microbial community structural organization exhibits the potential to contribute to disease progression. Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota. Here we show that the mucosal microbiota organization is a critical factor associated with a subset of CRC. We identified invasive polymicrobial bacterial biofilms (bacterial aggregates), structures previously associated with nonmalignant intestinal pathology, nearly universally (89%) on right-sided tumors (13 of 15 CRCs, 4 of 4 adenomas) but on only 12% of left-sided tumors (2 of 15 CRCs, 0 of 2 adenomas). Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa. High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status. However, principal coordinates analysis revealed that biofilm communities on paired normal mucosa, distant from the tumor itself, cluster with tumor microbiomes as opposed to biofilm-negative normal mucosa bacterial communities also from the tumor host. Colon mucosal biofilm detection may predict increased risk for development of sporadic CRC.
Detection of Toxoplasma gondii parasitemia by gene amplification, cell culture, and mouse inoculation

Diagnosis of Toxoplasma gondii infection is difficult, especially in immunosuppressed people. The AIDS epidemic has increased the number of people at risk and increased the need for better diagnostic methods. We have compared three methods for detection of T. gondii parasitemia. Rabbits were infected subcutaneously with 10(4) T. gondii tachyzoites. Blood samples were obtained, and buffy coat or leukocyte fractions were prepared. We sought the T. gondii B1 gene by gene amplification by the polymerase chain reaction, and we sought viable T. gondii cells by inoculating fibroblast cell cultures and by mouse inoculation. Thirty-two blood samples were obtained from seven infected rabbits, and 18 were obtained from four control, uninfected rabbits. Parasitemia was detected in 20 of 32 samples (62%) from infected samples by mouse inoculation, 12 of 32 samples (37%) by gene amplification and detection, and 8 of 32 samples (25%) by cell culture. Mouse inoculation requires use of live animals and has a long turnaround time. Currently, cell culture is the least sensitive but most practical and widely available method for the detection of T. gondii parasitemia. Gene amplification and detection was more sensitive than cell culture and may become available in clinical laboratories as techniques are developed further and automated.
Phase I clinical evaluation of a new iron oxide MR contrast agent

The safety and magnetic resonance (MR) imaging potential of BMS 180549, a new superparamagnetic iron oxide contrast agent, were evaluated in a phase I, open‐label, placebo‐controlled study involving 41 healthy subjects. No clinically significant postdose changes in physical examination findings, vital signs, or electrocardiogram results were reported for any of the subjects evaluated. No clinically significant changes in clinical laboratory values were noted by the investigators. Fourteen adverse events considered not serious and considered possibly or definitely related to the drug were reported, three of which required minor treatment. Relaxation time measurements in plasma samples showed a strong, dose‐dependent, and persistent decrease in T1 and T2 values. Significant changes in MR signal intensity of the blood pool and wellperfused organs (liver and spleen) were noted on both T1‐ and T2‐weighted images. Changes in signal intensity of cervical lymph nodes were also observed at the higher doses and late postdose imaging times.
Research on Social Networking Sites and Social Support from 2004 to 2015: A Narrative Review and Directions for Future Research

The article presents a narrative review of scholarship on social support through social networking sites (SNSs) published from 2004 to 2015. By searching keywords related to social support and SNSs in major databases for social sciences, we identified and content analyzed directly relevant articles (N = 88). The article summarizes the prevalence of theory usage; the function of theory usage (e.g., testing a theory, developing a theory); major theories referenced; and methodologies, including research designs, measurement, and the roles of social support and SNS examined in this literature. It also reports four themes identified across the studies, indicating the trends in the current research. Based on the review, the article presents a discussion about study sites, conceptualization of social support, theoretical coherence, the role of social networks, and the dynamic relationships between SNS use and social support, which points out potential avenues for shaping a future research agenda.
On the positive aspects of customers: Customer‐initiated support and affective crossover in employee–customer dyads

This study examines psychological resources for service employees and their customers, which enhance the service experiences of both parties during service conversations. We investigate whether customer behaviour (customer-initiated support) positively impacts on employees' affect. We also examine the crossover of employees' affect on customers' affect. State positive affect (PA) was assessed in 82 employees of car dealerships and 421 customers on 2 occasions (before and after the conversation). Multi-level analyses showed the hypothesized positive impact of customer behaviour on employees' PA and in turn of employees' PA on customers' PA. Results are integrated in an overall process model whereby customers' PA leads to customer-initiated support, which increases employees' PA and in turn enhances customers' PA. Results suggest direct and indirect crossover effects. This study extends research on customer behaviour offering a positive slant on customer behaviour and suggests to actively involve customers in the service process in order to promote their positive behaviour towards employees.
Paradigms of Personality Assessment

Part I: The Five Paradigms and Their Convergences. The Psychodynamic Paradigm. The Interpersonal Paradigm. The Personological Paradigm. The Multivariate Paradigm. The Empirical Paradigm. Convergences Among Paradigms: The Individual and Society. Part II: A Collaborative Case Study. McAdams, Personological Assessment. Behrends, Blatt, Psychodynamic Assessment. Pincus, Gurtman, Interpersonal Assessment. Costa, Piedmont, Multivariate Assessment. Ben-Porath, Empirical Assessment. Trobst, Wiggins, Constructive Alternativism in Personality Assessment. Appendix A. Thematic Apperception Test (TAT) Protocol. Appendix B-1. Rorschach Protocol. Appendix B-2. Rorschach Scoring. Appendix B-3. Rorschach Scoring Summary. Appendix C. Object Relations Inventory (ORI) Protocol.
Allosteric Communication between the Pyridoxal 5′-Phosphate (PLP) and Heme Sites in the H2S Generator Human Cystathionine β-Synthase*

Background: Long range allosteric communication between the heme and PLP cofactors occurs in human cystathionine β-synthase. Results: Seven mutations in the PLP pocket were studied, including one described in homocystinuric patients. Conclusion: The mutations perturb the heme electronic environment 20 Å away and increase propensity for forming an inactive species. Significance: Bidirectional communication between heme and PLP occurs via an α-helix; its disruption is associated with disease. Human cystathionine β-synthase (CBS) is a unique pyridoxal 5′-phosphate (PLP)-dependent enzyme that has a regulatory heme cofactor. Previous studies have demonstrated the importance of Arg-266, a residue at the heme pocket end of α-helix 8, for communication between the heme and PLP sites. In this study, we have examined the role of the conserved Thr-257 and Thr-260 residues, located at the other end of α-helix 8 on the heme electronic environment and on activity. The mutations at the two positions destabilize PLP binding, leading to lower PLP content and ∼2- to ∼500-fold lower activity compared with the wild-type enzyme. Activity is unresponsive to PLP supplementation, consistent with the pyridoxine-nonresponsive phenotype of the T257M mutation in a homocystinuric patient. The H2S-producing activities, also impacted by the mutations, show a different pattern of inhibition compared with the canonical transsulfuration reaction. Interestingly, the mutants exhibit contrasting sensitivities to the allosteric effector, S-adenosylmethionine (AdoMet); whereas T257M and T257I are inhibited, the other mutants are hyperactivated by AdoMet. All mutants showed an increased propensity of the ferrous heme to form an inactive species with a 424 nm Soret peak and exhibited significantly reduced enzyme activity in the ferrous and ferrous-CO states. Our results provide the first evidence for bidirectional transmission of information between the cofactor binding sites, suggest the additional involvement of this region in allosteric communication with the regulatory AdoMet-binding domain, and reveal the potential for independent modulation of the canonical transsulfuration versus H2S-generating reactions catalyzed by CBS.
An analytical model for IEEE 802 . 15 . 4 non-beacon enabled CSMA / CA in multihop wireless sensor networks

In this paper we propose a new analytical model for the IEEE 802.15. 4 non-beacon enabled CSMA/CA. Previous models often assume that the probability of channel busy assessment is independent of the back-off stage. We show that this condition does not hold for the IEEE 802.15. 4 and propose a modeling approximation. In our analysis, we consider multihop topologies and unsaturated traffic. We discuss the challenges imposed by these conditions and propose efficient and effective modeling strategies. The main objective of the model is to derive robust estimates for the probability of channel access failures in multihop topologies. The accuracy of the model is confirmed by comparing the predicted values against the results obtained through extensive network simulations in a wide range of scenarios considering different network topologies, number of nodes, and traffic loads.
Knockdown of T‐bet expression in Mart‐127–35‐specific T‐cell‐receptor‐engineered human CD4+ CD25− and CD8+ T cells attenuates effector function

Gene transfer to create tumour epitope‐specific cytolytic T cells for adoptive immunotherapy of cancer remains an area of active inquiry. When the Mart‐127–35‐specific DMF5 T‐cell receptor (TCR) is transferred into peripheral human CD4+ T cells, the reprogrammed cells exhibit a T helper type 1 (Th1) phenotype with significant multifactorial effector capabilities. The T‐bet transcription factor plays an important role in determination of the Th1 differentiation pathway. To gain a deeper understanding of how T‐bet controls the outcome of human T‐cell reprogramming by gene transfer, we developed a system for examining the effects of short hairpin RNA‐mediated T‐bet gene knockdown in sorted cell populations uniformly expressing the knockdown construct. In this system, using activated peripheral human CD4+ CD25− and CD8+ T cells, T‐bet knockdown led to attenuation of the interferon‐γ response to both antigen‐specific and non‐specific TCR stimulation. The interleukin‐2 (IL‐2) antigen‐specific response was not attenuated by T‐bet knockdown. Also, in TCR‐reprogrammed CD8+ cells, the cytolytic effector response was attenuated by T‐bet knockdown. T‐bet knockdown did not cause redirection into a Th2 differentiation pathway, and no increased IL‐4, IL‐10, or IL‐17 response was detected in this system. These results indicate that T‐bet expression is required for maintenance of the CD4+ CD25− and CD8+ effector phenotypes in TCR‐reprogrammed human T cells. They also suggest that the activation protocol necessary for transduction with retrovectors and lentivectors may commit the reprogrammed cells to the Th1 phenotype, which cannot be altered by T‐bet knockdown but that there is, nevertheless, a continuous requirement of T‐bet expression for interferon‐γ gene activation.
Do Internet Shopping Aids Make a Difference? An Empirical Investigation

Some Internet shoppers use online shopping aids to help them search for products and services, and to assist them in making in-depth comparisons among alternatives. By presenting comparison information on salient criteria (e.g., price) from multiple vendors of a specific product, online shopping aids can increase the number of alternatives considered, while reducing search time and costs. In this paper, we report the results of an experiment intended to examine online shopping perceptions between two Internet shopping groups: one that used an online shopping aid and another that did not use the aid. Our results show that online shopping aids are convenient and reduce search efforts. Based on the findings, we discuss possible implications for research and practice.
The structure of creative cognition in the human brain

Creativity is a vast construct, seemingly intractable to scientific inquiry—perhaps due to the vague concepts applied to the field of research. One attempt to limit the purview of creative cognition formulates the construct in terms of evolutionary constraints, namely that of blind variation and selective retention (BVSR). Behaviorally, one can limit the “blind variation” component to idea generation tests as manifested by measures of divergent thinking. The “selective retention” component can be represented by measures of convergent thinking, as represented by measures of remote associates. We summarize results from measures of creative cognition, correlated with structural neuroimaging measures including structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS). We also review lesion studies, considered to be the “gold standard” of brain-behavioral studies. What emerges is a picture consistent with theories of disinhibitory brain features subserving creative cognition, as described previously (Martindale, 1981). We provide a perspective, involving aspects of the default mode network (DMN), which might provide a “first approximation” regarding how creative cognition might map on to the human brain.
A measure of robust stability for an identified set of parametrized transfer functions

Defines a measure of robustness for a set of parameterized transfer functions as delivered by classical prediction error identification and that contains the true system at a prescribed probability level. This measure of robustness is the worst case Vinnicombe distance between the model and the plants in the uncertainty region. We show how it can be computed exactly using LMI-based optimization. In addition, we show that this measure is directly connected to the size of the set of controllers that are guaranteed to stabilize all plants in the uncertainty region, i.e., the smaller the worst case Vinnicombe distance for an uncertainty region, the larger the set of model-based controllers that are guaranteed to stabilize all systems in this uncertainty region.