Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual effect of lithium on NFAT5 activity in kidney cells

Lithium salts are used widely for treatment of bipolar and other mental disorders. Lithium therapy is accompanied frequently by renal side effects, such as nephrogenic diabetes insipidus or chronic kidney disease (CKD), but the molecular mechanisms underlying these effects are still poorly understood. In the present study we examined the effect of lithium on the activity of the osmosensitive transcriptional activator nuclear factor of activated T cells 5 (NFAT5, also known as TonEBP), which plays a key role in renal cellular osmoprotection and urinary concentrating ability. Interestingly, we found different effects of lithium on NFAT5 activity, depending on medium osmolality and incubation time. When cells were exposed to lithium for a relative short period (24 h), NFAT5 activity was significantly increased, especially under isosmotic conditions, resulting in an enhanced expression of the NFAT5 target gene heat shock protein 70 (HSP70). Further analysis revealed that the increase of NFAT5 activity depended primarily on an enhanced activity of the c-terminal transactivation domain (TAD), while NFAT5 protein abundance was largely unaffected. Enhanced activity of the TAD is probably mediated by lithium-induced inhibitory phosphorylation of glycogen synthase kinase 3β (GSK-3β), which is in accordance with previous studies. When cells were exposed to lithium for a longer period (96 h), cellular NFAT5 activity and subsequently expression of HSP70 significantly decreased under hyperosmotic conditions, due to diminished NFAT5 protein abundance, also resulting from GSK-3β inhibition. Taken together, our results provide evidence that lithium has opposing effects on NFAT5 activity, depending on environmental osmolality and exposure duration. The potential impacts of these observations on the diverse effects of lithium on kidney function are discussed.
Simultaneous changes of cell volume and cytosolic calcium concentration in macula densa cells caused by alterations of luminal NaCl concentration

Cell volume and cytosolic Ca2+ concentration ([Ca2+]i) were measured in rabbit macula densa (MD) cells loaded with calcein and Fura Red using confocal microscopy. [Ca2+]i was also analysed with Indo‐1 and fura‐2. We used isolated microperfused thick ascending limbs with attached glomerulus. The results showed that when the luminal NaCl concentration (‘NaCl’) was decreased from 35 to 10 mm, the cell volume decreased by 10.4%, and [Ca2+]i increased by 9.5%. This increase was inhibited in Ca2+‐free solution. When luminal [NaCl] was changed from 35 to 135 mm, the cell volume increased by 15.1%, and [Ca2+]i did not change. The cell volume alterations were not different in Ca2+‐free solutions. Using Indo‐1, basal [Ca2+]i in MD cells was 107.8 nm. When luminal [NaCl] was changed from 135 to 10 mm, [Ca2]i increased by 23.5 nm. Using fura‐2, the basal [Ca2+]i in MD cells was 115.3 nm, and when luminal [NaCl] was changed from 135 or 35 to 10 mm, [Ca2+]i change was 30.1 or 10.6 nm, respectively. An increase in [NaCl] caused no change in [Ca2+]i. In Ca2+‐free solution, no change in [Ca2+]i occurred. A stepwise decrease in luminal [NaCl] resulted in a sigmoid increase in [Ca2+]i in MD cells. The steepest part of the curve was between 70 and 10 mm. In conclusion, we found that MD cells have cell volume regulation, and that [Ca2+]i elevation caused by decreased luminal [NaCl] is independent of the cell volume.
COMPARISON OF ANN AND ANFIS TECHNIQUES IN MODELING DISSOLVED OXYGEN

Dissolved oxygen (DO) is a parameter frequently used to evaluate the water quality on different watersheds and reservoirs. The concentration of DO is so important for the healthy functioning of aquatic ecosystems, and a significant indicator of the state of aquatic ecosystems. In this study, the radial basis neural network (RBNN) and adaptive neuro-fuzzy inference system (ANFIS) method were developed to estimate DO concentration by using various combinations of daily input variables which are pH, discharge, temperature, and electrical conductivity measured by U.S. Geological Survey (USGS). The data of Fountain Creek Stream-Gauging Station (USGS Station No: 07105530) which covers 9 years daily data between1990-1998 were used in the study. The results of the RBNN and ANFIS models were compared with each other. The RBNN model was found to be better than the ANFIS model in estimation of DO concentration.
Assessment of Physical-Chemical Drinking Water Quality in the Logone Valley (Chad-Cameroon)

Unsafe drinking water is one of the main concerns in developing countries. In order to deal with this problem, a cooperation project was set up by the ACRA Foundation in the Logone valley (Chad-Cameroon). Water supplies were sampled throughout the villages of this area mostly from boreholes, open wells, rivers and lakes as well as some piped waters. The samples were analysed for their physical-chemical and microbiological quality in order to identify the contamination problems and suggest appropriate solutions. Results of the assessment confirmed that in the studied area there are several parameters of health and aesthetic concern. Elevated lead levels were detected both in aquifers and in surface waters, confirming that further investigations of the occurrence of lead contamination in the Logone valley are warranted. In addition, many groundwater sources are negatively impacted by parameters of aesthetic concern, such as turbidity, iron and manganese. Even though they do not affect human health, elevated levels of these parameters cause consumers to abandon improved water supplies, often in favour of surface water sources that are microbiologically contaminated. The use of alternative sources, improvement of water supply structures and water treatment are possible solutions to improve the quality of drinking water in the Logone valley.
Cited Articles Citing Articles E-mail Alerts Regulation of Gastric Carcinogenesis by Helicobacter Pylori Virulence Factors

Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, and strains that possess the cag secretion system, which translocates the bacterial effector CagA into host cells, augment cancer risk. H. pylori strains that express the vacuolating cytotoxin or the outer membrane protein OipA are similarly associated with severe pathologic outcomes. We previously reported that an in vivo adapted H. pylori strain, 7.13, induces gastric adenocarcinoma in rodent models of gastritis. In the current study, we used carcinogenic strain 7.13 as a prototype to define the role of virulence constituents in H. pylori–mediated carcinogenesis. Mongolian gerbils were infected with wild-type strain 7.13 or cagA À , vacA À , or oipA À mutants for 12 to 52 weeks. All infected gerbils developed gastritis; however, inflammation was significantly attenuated in animals infected with the cagA À but not the vacA À or oipA À strains. Gastric dysplasia and cancer developed in >50% of gerbils infected with either the wild-type or vacA À strain but in none of the animals infected with the cagA À strain. Inactivation of oipA decreased B-catenin nuclear localization in vitro and reduced the incidence of cancer in gerbils. OipA expression was detected significantly more frequently among H. pylori strains isolated from human subjects with gastric cancer precursor lesions versus persons with gastritis alone. These results indicate that loss of CagA prevents the development of cancer in this model. Inactivation of oipA attenuates B-catenin nuclear translocation and also decreases the incidence of carcinoma. In addition to defining factors that mediate H. pylori–induced cancer, these results provide insight into mechanisms that may regulate the development of other malignancies arising within the context of inflammatory states.
Approximating Congestion + Dilation in Networks via "Quality of Routing" Games

A classic optimization problem in network routing is to minimize C + D, where C is the maximum edge congestion and D is the maximum path length (also known as dilation). The problem of computing the optimal C* + D* is NP-complete even when either C* or D* is a small constant. We study routing games in general networks where each player i selfishly selects a path that minimizes Ci + Di the sum of congestion and dilation of the player's path. We first show that there are instances of this game without Nash equilibria. We then turn to the related quality of routing (QoR) games which always have Nash equilibria. QoR games represent networks with a small number of service classes where paths in different classes do not interfere with each other (with frequency or time division multiplexing). QoR games have O(log4 n) price of anarchy when either C* or D* is a constant. Thus, Nash equilibria of QoR games give poly-log approximations to hard optimization problems.
Loneliness and Social Isolation in Children with Autism Spectrum Disorders

Autism spectrum disorders (ASD) are a group of developmental disorders (autism, Asperger syndrome, and pervasive developmental disorder not otherwise specified) characterized by impairments in communication and social interaction and restricted repetitive and stereotyped patterns of behavior, interests, and activities. Difficulties with social interaction are considered the core feature of ASD and impact multiple aspects of daily life, including the ability to establish and maintain relationships with others. Some individuals with ASD may seek relationships but do not have the skills needed to successfully engage with others; on the other hand, some individuals with ASD may prefer to be alone and do not appear motivated to establish relationships with others. Both scenarios could result in aloneness. In his description of 11 children with autism, Kanner (1943) noted that “There is from the start an extreme autistic aloneness that, whenever possible disregards, ignores, shuts out anything that comes to the child from the outside” (p. 242). Contact with people was seen as an interference that was dealt with quickly so that the child could “return to the still much desired aloneness. ” “Profound aloneness dominates all behavior” (p. 247). Kanner’s early observations suggested that aloneness was a desired state for children with autism. The children appeared to have a good relationship with objects, but not with people. Indeed, the parents of Donald (Case 1) described him as “happiest when left alone” (p. 218). The distinction between aloneness and loneliness is critical for understanding children with an ASD. As with the case of Donald, aloneness and/or social isolation can be a situation that is pleasurable, similar to when an individual seeks solitude or a desirable state away from the presence/interference of others (Galanaki, 23
Transduction by adeno-associated virus vectors in the rabbit airway: efficiency, persistence, and readministration

The ability of recombinant adeno-associated virus (AAV) vectors to integrate into the host genome and to transduce nondividing cells makes them attractive as vehicles for gene delivery. In this study, we assessed the ability of several AAV vectors to transduce airway cells in rabbits by measuring marker gene expression. AAV vectors that transferred either a beta-galactosidase (beta-gal) or a human placental alkaline phosphatase (AP) gene were delivered to one lobe of the rabbit lung by use of a balloon catheter placed under fluoroscopic guidance. We observed vector-encoded beta-gal or AP staining almost exclusively in the epithelial and smooth muscle cells in the bronchus at the region of balloon placement. The overall efficiency of transduction in the balloon-treated bronchial epithelium was low but reached 20% in some areas. The majority of the staining was in ciliated cells but was also observed in basal cells and airway smooth muscle cells. We observed an 80-fold decrease in marker-positive epithelial cells during the 60-day period after vector infusion, whereas the number of marker-positive smooth muscle cells stayed constant. Although treatment with the topoisomerase inhibitor etoposide dramatically enhanced AAV transduction in primary airway epithelial cells in culture, treatment of rabbits did not improve transduction rates in the airway. Vector readministration failed to produce additional transduction events, which correlated with the appearance of neutralizing antibodies. These results indicate that both readministration and immune modulation will be required in the use of AAV vectors for gene therapy to the airway epithelium.
Inflammation in the Central Nervous System and Th17 Responses Are Inhibited by IFN-γ–Induced IL-18 Binding Protein

Inflammatory responses are essential for immune protection but may also cause pathology and must be regulated. Both Th1 and Th17 cells are implicated in the pathogenesis of autoimmune inflammatory diseases, such as multiple sclerosis. We show in this study that IL-18–binding protein (IL-18bp), the endogenous inhibitor of the Th1-promoting cytokine IL-18, is upregulated by IFN-γ in resident microglial cells in the CNS during multiple sclerosis-like disease in mice. Test of function by overexpression of IL-18bp in the CNS using a viral vector led to marked reduction in Th17 responses and robust inhibition of incidence, severity, and histopathology of disease, independently of IFN-γ. The disease-limiting action of IL-18bp included suppression of APC-derived Th17-polarizing cytokines. IL-18bp thus acts as a sensor for IFN-γ and can regulate both Th1 and Th17 responses in the CNS.
Thylakoid FtsH Protease Contributes to Photosystem II and Cytochrome b6f Remodeling in Chlamydomonas reinhardtii under Stress Conditions[W]

FtsH is a ubiquitous protease that mediates the degradation of membrane proteins. The chloroplast FtsH is known for its involvement in repairing photosystem II damaged by light. This work reports the characterization of an ftsh mutant in Chlamydomonas and demonstrates the wider role of FtsH in thylakoid membrane protein maintenance under light as well as nutrient stresses. FtsH is the major thylakoid membrane protease found in organisms performing oxygenic photosynthesis. Here, we show that FtsH from Chlamydomonas reinhardtii forms heterooligomers comprising two subunits, FtsH1 and FtsH2. We characterized this protease using FtsH mutants that we identified through a genetic suppressor approach that restored phototrophic growth of mutants originally defective for cytochrome b6f accumulation. We thus extended the spectrum of FtsH substrates in the thylakoid membranes beyond photosystem II, showing the susceptibility of cytochrome b6f complexes (and proteins involved in the ci heme binding pathway to cytochrome b6) to FtsH. We then show how FtsH is involved in the response of C. reinhardtii to macronutrient stress. Upon phosphorus starvation, photosynthesis inactivation results from an FtsH-sensitive photoinhibition process. In contrast, we identified an FtsH-dependent loss of photosystem II and cytochrome b6f complexes in darkness upon sulfur deprivation. The D1 fragmentation pattern observed in the latter condition was similar to that observed in photoinhibitory conditions, which points to a similar degradation pathway in these two widely different environmental conditions. Our experiments thus provide extensive evidence that FtsH plays a major role in the quality control of thylakoid membrane proteins and in the response of C. reinhardtii to light and macronutrient stress.
The Optimal Design of Social Security Benefits

The United States Social Security system is fairly unique in that it explicitly allows for a progressive formulation of retirement benefits by assigning a larger replacement rate to workers with small pre-retirement wages. In contrast, the public pension systems in other countries often replace a constant fraction of pre-retirement wages, although the length of the “averaging period" is typically shorter relative to the U.S. This paper examines the ex-ante optimal U.S. Social Security benefit structure using the model developed in Nishiyama and Smetters (2007). On one hand, progressivity in the benefit structure provides risk sharing against shocks that are difficult to insure privately. On the other hand, progressivity introduces various marginal tax rates that distort labor supply. Rather surprisingly, we find that the ex-ante best U.S. Social Security replacement rate structure is fairly “flat. ” Intuitively, the relatively long averaging period used in the U.S. system formulation already provides some insurance against negative idiosyncratic shocks, but in a manner that is more efficient than explicit redistribution.
Functional proteomics of adenosine triphosphatase system in the rat striatum during aging

The maximum rates of adenosine triphosphatase (ATPase) systems related to energy consumption were systematically evaluated in synaptic plasma membranes isolated from the striata of male Wistar rats aged 2, 6, 12, 18, and 24 months, because of their key role in presynaptic nerve ending homeostasis. The following enzyme activities were evaluated: sodium-potassium-magnesium adenosine triphosphatase (Na+, K+, Mg2+-ATPase); ouabain-insensitive magnesium adenosine triphosphatase (Mg2+-ATPase); sodium-potassium adenosine triphosphatase (Na+, K+-ATPase); direct magnesium adenosine triphosphatase (Mg2+-ATPase); calcium-magnesium adenosine triphosphatase (Ca2+, Mg2+-ATPase); and acetylcholinesterase. The results showed that Na+, K+-ATPase decreased at 18 and 24 months, Ca2+, Mg2+-ATPase and acetylcholinesterase decreased from 6 months, while Mg2+-ATPase was unmodified. Therefore, ATPases vary independently during aging, suggesting that the ATPase enzyme systems are of neuropathological and pharmacological importance. This could be considered as an experimental model to study regeneration processes, because of the age-dependent modifications of specific synaptic plasma membranes. ATPases cause selective changes in some cerebral functions, especially bioenergetic systems. This could be of physiopathological significance, particularly in many central nervous system diseases, where, during regenerative processes, energy availability is essential.
Yet Another Performance Testing Framework

Performance testing is one of the vital activities spanning the whole life cycle of software engineering. While there are a considerable number of performance testing products and open source tools available, they are either too expensive and complicated for small projects, or too specific and simple for diverse performance tests. This paper presents a general-purpose testing framework for both simple and small, and complicated and large-scale performance testing. Our framework proposes an abstraction to facilitate performance testing by separating the application logic from the common performance testing functionalities. This leads to a set of general-purpose data models and components, which form the core of the framework. The framework has been prototyped on both . NET and Java platforms and was used for a number of performance-related projects.
Signal to noise ratio optimization for a CMUT based medical ultrasound imaging system

CMUTs offers key performance benefits compared to their piezoelectric counterparts. However, CMUTs are not widely adopted in commercial ultrasound imaging systems due to low signal to noise ratio (SNR) in the obtained images. Tunable parameters of the CMUT include the membrane material, radius, thickness, gap height, electrode size, and bias voltage. The aim of this work is to optimize these parameters to provide a solution for low SNR problem of CMUTs. In medical imaging, the device will be used in pulse echo mode for which both good receive sensitivity and high output pressure is required. Optimizing these performance metrics will end up in conflicting design parameters, such as a high gap for large pressure output whereas a small gap for better receive sensitivity. In this work, we develop a methodology for the investigation of the round-trip behavior of the transducer and try to co-optimize transmit and receive characteristics of the device to maximize the SNR of the received signal by tuning the bias voltage.
The Causative Classification of Stroke system: An international reliability and optimization study

Background:Valid and reliable ischemic stroke subtype determination is crucial for well-powered multicenter studies. The Causative Classification of Stroke System (CCS, available at http://ccs.mgh.harvard.edu) is a computerized, evidence-based algorithm that provides both causative and phenotypic stroke subtypes in a rule-based manner. We determined whether CCS demonstrates high interrater reliability in order to be useful for international multicenter studies. Methods:Twenty members of the International Stroke Genetics Consortium from 13 centers in 8 countries, who were not involved in the design and development of the CCS, independently assessed the same 50 consecutive patients with acute ischemic stroke through reviews of abstracted case summaries. Agreement among ratings was measured by kappa statistic. Results:The &kgr; value for causative classification was 0.80 (95% confidence interval [CI] 0.78–0.81) for the 5-subtype, 0.79 (95% CI 0.77–0.80) for the 8-subtype, and 0.70 (95% CI 0.69–0.71) for the 16-subtype CCS. Correction of a software-related factor that generated ambiguity improved agreement: &kgr; = 0.81 (95% CI 0.79–0.82) for the 5-subtype, 0.79 (95% CI 0.77–0.80) for the 8-subtype, and 0.79 (95% CI 0.78–0.80) for the 16-subtype CCS. The &kgr; value for phenotypic classification was 0.79 (95% CI 0.77–0.82) for supra-aortic large artery atherosclerosis, 0.95 (95% CI 0.93–0.98) for cardioembolism, 0.88 (95% CI 0.85–0.91) for small artery occlusion, and 0.79 (0.76–0.82) for other uncommon causes. Conclusions:CCS allows classification of stroke subtypes by multiple investigators with high reliability, supporting its potential for improving stroke classification in multicenter studies and ensuring accurate means of communication among different researchers, institutions, and eras. GLOSSARYCCS = Causative Classification of Stroke System; CI = confidence interval; ISGC = International Stroke Genetics Consortium.
Latent subject-centered modeling of collaborative tagging

Collaborative tagging or social bookmarking is a main component of Web 2.0 systems and has been widely recognized as one of the key technologies underpinning next-generation knowledge management platforms. In this article, we propose a subject-centered model of collaborative tagging to account for the ternary cooccurrences involving users, items, and tags in such systems. Extending the well-established probabilistic latent semantic analysis theory for knowledge representation, our model maps the user, item, and tag entities into a common latent subject space that captures the “wisdom of the crowd” resulted from the collaborative tagging process. To put this model into action, we have developed a novel way to estimate the probabilistic subject-centered model approximately in a highly efficient manner taking advantage of a matrix factorization method. Our empirical evaluation shows that our proposed approach delivers substantial performance improvement on the knowledge resource recommendation task over the state-of-the-art standard and tag-aware resource recommendation algorithms.