Miracle-dz/UniFAR-FTUs huggingface dataset:
TRPM1 Forms Complexes with Nyctalopin In Vivo and Accumulates in Postsynaptic Compartment of ON-Bipolar Neurons in mGluR6-Dependent Manner

Synaptic transmission between light-sensory photoreceptor cells and downstream ON-bipolar neurons plays an important role for vertebrate vision. This process is mediated by the G-protein-coupled receptor pathway involving glutamate receptor mGluR6 and effector channel TRPM1. The signal transmission occurs on a rapid timescale; however, the molecular organization that ensures timely signaling in this cascade is unknown. Genetic studies in human patients and animal models reveal that ON-bipolar cell signaling depends on the synaptic protein nyctalopin. We have conducted a proteomic search for proteins associated with nyctalopin in the mouse retina and identified TRPM1 as the binding partner. We further demonstrate that nyctalopin additionally interacts with mGluR6 receptor. Disruption of mGluR6 prevented targeting of TRPM1 to the postsynaptic compartment of ON-bipolar neurons. These results reveal a unique macromolecular organization of the mGluR6 cascade, where principal signaling components are scaffolded by nyctalopin, creating an organization essential for the correct localization of the signaling ensemble and ultimately intact transmission of the signal at the first visual synapse.
Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease.

RATIONALE Patients with chronic obstructive pulmonary disease (COPD) are afflicted by comorbidities. Few studies have prospectively evaluated COPD comorbidities and mortality risk. OBJECTIVES To prospectively evaluate COPD comorbidities and mortality risk. METHODS We followed 1,664 patients with COPD in five centers for a median of 51 months. Systematically, 79 comorbidities were recorded. We calculated mortality risk using Cox proportional hazard, and developed a graphic representation of the prevalence and strength of association to mortality in the form of a "comorbidome". A COPD comorbidity index (COPD specific comorbidity test [COTE]) was constructed based on the comorbidities that increase mortality risk using a multivariate analysis. We tested the COTE index as predictor of mortality and explored whether the COTE index added predictive information when used with the validated BODE index. MEASUREMENTS AND MAIN RESULTS Fifteen of 79 comorbidities differed in prevalence between survivors and nonsurvivors. Of those, 12 predicted mortality and were integrated into the COTE index. Increases in the COTE index were associated with an increased risk of death from COPD-related (hazard ratio [HR], 1.13; 95% confidence interval, 1.08-1.18; P < 0.001) and non-COPD-related causes (HR, 1.18; 95% confidence interval, 1.15-1.21; P < 0.001). Further, increases in the BODE and COTE were independently associated with increased risk of death. A COTE score of greater than or equal to 4 points increased by 2.2-fold the risk of death (HR, 2.26-2.68; P < 0.001) in all BODE quartile. CONCLUSIONS Comorbidities are frequent in COPD and 12 of them negatively influence survival. A simple disease-specific comorbidities index (COTE) helps assess mortality risk in patients with COPD.
Clinical practice decision tree for the choice of the first disease modifying antirheumatic drug for very early rheumatoid arthritis: a 2004 proposal of the French Society of Rheumatology

Objective: To elaborate a clinical practice decision tree for the choice of the first disease modifying antirheumatic drug (DMARD) for untreated rheumatoid arthritis of less than six months’ duration. Methods: Four steps were employed: (1) review of published reports on DMARD efficacy against rheumatoid arthritis; (2) inventory of the information available to guide DMARD choice; (3) selection of the most pertinent information by 12 experts using a Delphi method; and (4) choice of DMARDs in 12 clinical situations defined by items selected in step 3 (28 joint disease activity score (DAS 28): ⩽3.2; >3.2 and ⩽5.1; >5.1; rheumatoid factor status (positive/negative); structural damage (with/without)—that is, 3×2×2). Thus, multiplied by all the possible treatment pairs, 180 scenarios were obtained and presented to 36 experts, who ranked treatment choices according to the Thurstone pairwise method. Results: Among the 77 items identified, 41 were selected as pertinent to guide the DMARD choice. They were reorganised into five domains: rheumatoid arthritis activity, factors predictive of structural damage; patient characteristics; DMARD characteristics; physician characteristics. In the majority of situations, the two top ranking DMARD choices were methotrexate and leflunomide. Etanercept was an alternative for these agents when high disease activity was associated with poor structural prognosis and rheumatoid factor positivity. Conclusions: Starting with simple scenarios and using the pairwise method, a clinical decision tree could be devised for the choice of the first DMARD to treat very early rheumatoid arthritis.
Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease

Purpose of reviewHigh levels of fibroblast growth factor 23 (FGF23) cause the rare disorders of hypophosphatemic rickets and are a risk factor for cardiovascular disease and death in patients with chronic kidney disease (CKD). Despite major advances in understanding FGF23 biology, fundamental aspects of FGF23 regulation in health and in CKD remain mostly unknown. Recent findingsAutosomal dominant hypophosphatemic rickets (ADHR) is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage, but affected individuals experience a waxing and waning course of phosphate wasting. This led to the discovery that iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. Unlike osteocytes in ADHR, normal osteocytes couple increased FGF23 production with commensurately increased FGF23 cleavage to ensure that normal phosphate homeostasis is maintained in the event of iron deficiency. Simultaneous measurement of FGF23 by intact and C-terminal assays supported these breakthroughs by providing minimally invasive insight into FGF23 production and cleavage in bone. These findings also suggest a novel mechanism of FGF23 elevation in patients with CKD, who are often iron deficient and demonstrate increased FGF23 production and decreased FGF23 cleavage, consistent with an acquired state that mimics the molecular pathophysiology of ADHR. SummaryIron deficiency stimulates FGF23 production, but normal osteocytes couple increased FGF23 production with increased cleavage to maintain normal circulating levels of biologically active hormone. These findings uncover a second level of FGF23 regulation within osteocytes, failure of which culminates in elevated levels of biologically active FGF23 in ADHR and perhaps CKD.
Germination of Bacterial Endospores with Calcium and Dipicoliniic Acid

Aerobic and anaerobic bacterial endospores can be germinated if calcium chloride and dipicolinic acid are added to well-washed suspensions. Maximum germination is obtained when the calcium and acid are present in a molar ratio of one or more. This suggests that the 1:1 chelate of calcium and dipicolinic acid is the agent that induces germination.
Cyclin-dependent kinase-5 (CDK5) and amyotrophic lateral sclerosis

Cyclin-dependent kinase-5 (CDK5) is a serine-threonine protein kinase that has been implicated in a number of physiological processes in nerve and muscle cells, including neurogenesis, neuritic outgrowth, axonal transport of membrane-bound organelles and myogenesis. CDK5 has also been shown to phosphorylate the important cytoskeletal proteins, neurofilament and tau, both in vitro and in cells. The latter has prompted study into the potential role of CDK5 in the hyperphosphorylation of these proteins as part of the neuropathology seen in amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. More recently, increasing evidence has suggested a role for CDK5 in cellular apoptosis. Apoptosis has been implicated as the final common pathway of cell death in a number of neurodegenerative diseases including ALS. This article sets out to review the physiological and pathological roles ascribed to CDK5 and the possible relevance thereof to the pathogenesis of ALS. (ALS 2000; 1: 319-327)
Variation in net photosynthesis, stomatal characteristics, leaf area and whole-plant phytomass production among ten provenances of neem (Azadirachta indica).

Variation in net photosynthesis, CO(2) exchange parameters, stomatal characteristics, leaf area and seedling dry weight were investigated among 10 provenances of neem (Azadirachta indica A. Juss.). Significant provenance variation was established for net photosynthesis (8.14 to 15.13 &mgr;mol m(-2) s(-1)), stomatal conductance (0.37 to 0.59 mol m(-2) s(-1)), stomatal density (145 to 204 mm(-2)), and total guard cell length (2681 to 3873 &mgr;m). Net photosynthesis was positively correlated with whole-plant dry weight and leaf area. Stomatal density was positively correlated with net photosynthesis, whole-plant dry weight, and leaf area. Total guard cell length was positively correlated with all of these traits. Information on six traits was used in a cluster analysis to construct a dendrogram to assess phenetic relationships among the provenances. With a few exceptions, the dendrogram revealed three major clusters grouped according to rainfall distribution. The study indicated that whole-plant phytomass production of neem seedlings was associated with photosynthesis and stomatal characteristics during the early stages of growth.
Optimizing Television Program Schedules Using Choice Modeling

The authors examine the rescheduling of television programs to maximize the total ratings for one network across a week. The key idea is to design a choice experiment in which television programs are rescheduled and presented to respondents. Respondents read these program schedules (much like the regular TV Guide listings) and give their preferences, including not watching any of the listed programs. Because there are potentially billions of possible schedules, the authors give a procedure for designing a fractional factorial experiment that can accommodate both programs of varying length and constraints on eligible program times. The authors also develop a latent class multinomial logit model for modeling program preferences and present a validation of our experimental procedure and the model. They also present an empirical test of the procedure in which they use the model to predict ratings for all the possible program schedules, not just those constituting the choice sets. In this example, the optimum schedule increases the predicted total weekly ratings during prime time by 18% for a network. The projected increase in total weekly ratings is achieved without the network needing to purchase any new programs; all it needs to do is reschedule eight programs in its existing prime-time lineup.
Nog2p, a putative GTPase associated with pre‐60S subunits and required for late 60S maturation steps

Eukaryotic ribosome maturation depends on a set of well ordered processing steps. Here we describe the functional characterization of yeast Nog2p (Ynr053cp), a highly conserved nuclear protein. Nog2p contains a putative GTP‐binding site, which is essential in vivo. Kinetic and steady‐state measurements of the levels of pre‐rRNAs in Nog2p‐depleted cells showed a defect in 5.8S and 25S maturation and a concomitant increase in the levels of both 27SBS and 7SS precursors. We found Nog2p physically associated with large pre‐60S complexes highly enriched in the 27SB and 7S rRNA precursors. These complexes contained, besides a subset of ribosomal proteins, at least two additional factors, Nog1p, another putative GTP‐binding protein, and Rlp24p (Ylr009wp), which belongs to the Rpl24e family of archaeal and eukaryotic ribosomal proteins. In the absence of Nog2p, the pre‐60S ribosomal complexes left the nucleolus, but were retained in the nucleoplasm. These results suggest that transient, possibly GTP‐dependent association of Nog2p with the pre‐ribosomes might trigger late rRNA maturation steps in ribosomal large subunit biogenesis.
An intellectual capital perspective of competitive advantage in nonprofit organisations

Very little systematic research has focused on applying the concept of intellectual capital (IC) within the nonprofit context; particularly in the highly competitive nonprofit environment. Based on a review of the existing literature, this paper firstly contributes to filling this gap by building an argument that IC can be utilised as a competitive tool in nonprofit organisations (NPOs). Secondly, an IC conceptual framework is proposed that explicitly links the attainment of competitive advantage with positive outcomes for NPOs. Finally, the paper discusses how the IC conceptual framework can be effectively utilised to foster competitive advantage in the nonprofit sector.
Combining Science and Traditional Ecological Knowledge: Monitoring Populations for Co-Management

Using a combination of traditional ecological knowledge and science to monitor populations can greatly assist co-management for sustainable customary wildlife harvests by indigenous peoples. Case studies from Canada and New Zealand emphasize that, although traditional monitoring methods may often be imprecise and qualitative, they are nevertheless valuable because they are based on observations over long time periods, incorporate large sample sizes, are inexpensive, invite the participation of harvesters as researchers, and sometimes incorporate subtle multivariate cross checks for environmental change. A few simple rules suggested by traditional knowledge may produce good management outcomes consistent with fuzzy logic thinking. Science can sometimes offer better tests of potential causes of population change by research on larger spatial scales, precise quantification, and evaluation of population change where no harvest occurs. However, science is expensive and may not always be trusted or welcomed by customary users of wildlife. Short scientific studies in which traditional monitoring methods are calibrated against population abundance could make it possible to mesh traditional ecological knowledge with scientific inferences of prey population dynamics. This paper analyzes the traditional monitoring techniques of catch per unit effort and body condition. Combining scientific and traditional monitoring methods can not only build partnership and community consensus, but also, and more importantly, allow indigenous wildlife users to critically evaluate scientific predictions on their own terms and test sustainability using their own forms of adaptive management.
A comparative investigation of organizational commitment in government, public, and private organizations in Qatar

The purpose of this study was to investigate the antecedents and consequences of commitment in the developing nation of Qatar. Specifically, the influence of personal variables, job characteristics, organizational characteristics, and facets of job satisfaction of employees were investigated in relation to affective, continuance, and normative commitment. A survey questionnaire was used to collect data from a random sample of 780 employees from government, public, and private sector companies and completed questionnaires were received from 544 employees representing a response rate of 69.7%. Research data were tested using Pearson's correlation, Analysis of variance, and T-Tests. Statistically significant relationships were found between affective I normative commitment and almost all of the personal characteristics. However, only two demographic variables were statistically related to continuance commitment. Results indicated that employees with a high level of education, who were male, married with dependents, with long tenure and contract employment, reported higher levels of commitment than others. Interestingly, non Qatari employees showed higher levels of commitment than Qatari employees. Relationships between job and organizational characteristics and components of organizational commitment were found to be significant, although the relationships were only weak to moderate. Generally, the results indicated that the lack of equity, inefficient personal growth, lack of job security, lack of autonomy, lack of task identity, and insufficient feedback on performance were stated as possible reasons for low commitment in this study. Relationships were also found between job satisfaction variables and affective and normative commitment. However, relationships between continuance commitment and job satisfaction variables were weak. Regarding consequences of OC, the research found that increasing organizational commitment among employees led to lower turnover intentions and more acceptance of organizational changes.
Estimation of polyvinyl alcohol cryogel mechanical properties with four ultrasound elastography methods and comparison with gold standard testings

Tissue-mimicking phantoms are very useful in the field of tissue characterization and essential in elastography for the purpose of validating motion estimators. This study is dedicated to the characterization of polyvinyl alcohol cryogel (PVA-C) for these types of applications. A strict fabrication procedure was defined to optimize the reproducibility of phantoms having a similar elasticity. Following mechanical stretching tests, the phantoms were used to compare the accuracy of four different elastography methods. The four methods were based on a one-dimensional (1-D) scaling factor estimation, on two different implementations of a 2-D Lagrangian speckle model estimator (quasistatic elastography methods), and on a 1-D shear wave transient elastography technique (dynamic method). Young's modulus was investigated as a function of the number of freeze-thaw cycles of PVA-C, and of the concentration of acoustic scatterers. Other mechanical and acoustic parameters, such as the speed of sound, shear wave velocity, mass density, and Poisson's ratio, also were assessed. The Poisson's ratio was estimated with good precision at 0.499 for all samples, and the Young's moduli varied in a range of 20 kPa for one freeze-thaw cycle to 600 kPa for 10 cycles. Nevertheless, above six freeze-thaw cycles, the results were less reliable because of sample geometry artifacts. However, for the samples that underwent less than seven freeze-thaw cycles, the Young's moduli estimated with the four elastography methods showed good matching with the mechanical tensile tests with a regression coefficient varying from 0.97 to 1.07, and correlations R2 varying from 0.93 to 0.99, depending on the method
Determining the Factors of Bank Performance with a Focus on Risk and Technical Efficiency

Unlike in the non-financial sector, the measurement of bank performance has to incorporate the multi task nature of banking and reflect the requirements of various stakeholders besides shareholders such as the regulators and the depositors who are equally important. To incorporate these features we measure a bank's technical efficiency, and various types of risk exposure and examine the impact of these measures on market to book values. We use panel regression to analyze the relationship of bank criteria with market to book values and our results show technical efficiency is priced in the market as well as the risk measures such as short-term repricing gap , adjusted return on solvency as well as the adjusted income cost ratio. We also find the takeovers to have a positive impact on market to book value.
UVB and UVA radiation-mediated damage to isolated and cellular DNA

Abstract The effects of solar light on cellular DNA are mostly explained by both direct excitation of nucleobases and photosensitized reactions that are mediated by UVB and UVA radiation, respectively. A large body of information is now available on the main photodynamic reactions to DNA, which involve guanine as the preferential target of both one-electron oxidation and singlet oxygen oxidation, as the result of type I and type II mechanisms. Most of the final products of the photosensitized reactions of guanine base in isolated DNA have been characterized, and comprehensive mechanisms for their formation have been proposed. Further insights into the mechanisms of solar radiation-induced modifications within cellular DNA have been gained from accurate measurement of the main photoproducts using recently designed sensitive chromatographic and biochemical methods. Thus, the distribution pattern of the 12 possible bipyrimidine photoproducts has been shown to be similar in the DNA of UVB-irradiated rodent and human cells. Cyclobutyl pyrimidine dimers are also generated at di-thymine and thymine-cytosine sites within nuclear DNA upon exposure to UVA radiation as the likely result of triplet energy transfer. In addition, oxidative reactions that involved mostly singlet oxygen, and to a lesser extent, . OH radicals are also implicated, although less efficiently.
Antimicrobial Activities against 84 Listeria monocytogenes Isolates from Patients with Systemic Listeriosis at a Comprehensive Cancer Center (1955-1997)

ABSTRACT Listeriosis is a serious complication in patients undergoing treatment for cancer. We present antimicrobial susceptibility profiles of 84 clinical Listeria monocytogenes isolates. During 1955 to 1997, in vitro susceptibility for penicillin (97.6%), ampicillin (90.7%), erythromycin (98.8%), tetracycline (96.9%), and gentamicin (98.0%) remained unchanged. All isolates were susceptible to amikacin, ciprofloxacin, imipenem, rifampin, trimethoprim-sulfamethoxazole (TMP-SMX), and vancomycin. High prevalence of clindamycin resistance (96.2%) was unexpected. Ampicillin plus gentamicin is standard therapy for systemic listerosis, and TMP-SMX may be used for patients with beta-lactam intolerance. In vitro susceptibility profiles for carbapenem and fluoronated quinolone are promising, although clinical validation is critically needed before routine use is advocated, especially for listeric patients with severe cellular immune defects.
Low-frequency MEMS energy harvesters for the supplying of vehicle diagnostic systems

The possibility to harvest energy from environmental vibrations is very attractive for the supplying of miniaturized devices and sensor networks in the case of vehicle diagnostic. The design and fabrication of MEMS harvesters based on the capacitive transduction is presented; the setup of experimental desk for the characterization of energy harvesters is also introduced.