Miracle-dz/UniFAR-FTUs huggingface dataset:
HPRT-Deficiency Dysregulates cAMP-PKA Signaling and Phosphodiesterase 10A Expression: Mechanistic Insight and Potential Target for Lesch-Nyhan Disease?

Lesch-Nyhan Disease (LND) is the result of mutations in the X-linked gene encoding the purine metabolic enzyme, hypoxanthine guanine phosphoribosyl transferase (HPRT). LND gives rise to severe neurological anomalies including mental retardation, dystonia, chorea, pyramidal signs and a compulsive and aggressive behavior to self injure. The neurological phenotype in LND has been shown to reflect aberrant dopaminergic signaling in the basal ganglia, however there are little data correlating the defect in purine metabolism to the neural-related abnormalities. In the present studies, we find that HPRT-deficient neuronal cell lines have reduced CREB (cAMP response element-binding protein) expression and intracellular cyclic AMP (cAMP), which correlates with attenuated CREB-dependent transcriptional activity and a reduced phosphorylation of protein kinase A (PKA) substrates such as synapsin (p-syn I). Of interest, we found increased expression of phosphodiesterase 10A (PDE10A) in HPRT-deficient cell lines and that the PDE10 inhibitor papaverine and PDE10A siRNA restored cAMP/PKA signaling. Furthermore, reconstitution of HPRT expression in mutant cells partly increased cAMP signaling synapsin phosphorylation. In conclusion, our data show that HPRT-deficiency alters cAMP/PKA signaling pathway, which is in part due to the increased of PDE10A expression and activity. These findings suggest a mechanistic insight into the possible causes of LND and highlight PDE10A as a possible therapeutic target for this intractable neurological disease.
Development of nc-Si based intrinsic layer for HIT solar cells by ion-beam sputtering

In this paper the method of ion-beam sputtering was applied to produce nanocrystalline silicon (nc-Si) for emitter and intrinsic layers. Nanocrystalline silicon is more stable over time by reducing the degradation under the Staebler-Wronski effect than amorphous silicon. Reduction of surface recombination on the interface between "c-Si/nc-Si" was achieved by forming of nanocrystalline silicon via the ion-beam sputtering.
Prognosis of Defect Propagation Based on Recurrent Neural Networks

Incremental training is commonly applied to training recurrent neural networks (RNNs) for applications involving prognosis. As the number of prognostic time-step increases, the accuracy of prognosis generally decreases, as often seen in long-term prognosis. Revision of the training techniques is therefore necessary to improve the accuracy in long-term prognosis. This paper presents a competitive learning-based approach to long-term prognosis of machine health status. Specifically, vibration signals from a defect-seeded rolling bearing are preprocessed using continuous wavelet transform (CWT). Statistical parameters computed from both the raw data and the preprocessed data are then utilized as candidate inputs to an RNN. Based on the principle of competitive learning, input data were clustered for effective representation of similar stages of defect propagation of the bearing being monitored. Analysis has shown that the developed technique is more accurate in predicting bearing defect progression than the incremental training technique.
Dietary Zinc Is a Key Environmental Modifier in the Progression of IgA Nephropathy

IgA nephropathy (IgAN) shows diverse epidemiological characteristics, resulting from both genetic and acquired (e.g., environmental) causes. Environmental factors, such as diet or exposure to exogenous antigens, may prescribe the progression or prognosis of IgAN. It remains unclear as to how diet and infection influence susceptibility to IgAN. A relationship, such as Toll-like receptors (TLRs), especially TLR9 and TLR4, was demonstrated between IgAN and pathogen-recognition molecules. Recently, zinc (Zn) was discovered to be involved in various immune-related diseases, affecting B, T, and dendritic cells (DCs). This study investigates the relationship between dietary Zn and IgAN development in IgAN-prone mice. Seven-week-old IgAN-prone mice were divided into low, normal, and high Zn diet groups. To assess exogenous pathogen-mediated immune responses, lipopolysaccharide (LPS) was nasally administered. The activity of IgAN was biochemically and pathologically evaluated during the disease course. We also examined in vitro IgA production in spleen cells or in combinations of cocultured B, T, and DCs under various Zn conditions with or without LPS. Dietary conditioning with Zn affected serum immunoglobulins and urinary albumin levels, and mesangial deposition of IgA and IgG. Zn deficiency is associated with IgAN progression through the activation of the TLR4/TIR-domain-containing adapter-inducing interferon-β (TRIF), but not the TLR9, in DCs. Zn supplementation prevented disease aggravation. Our findings indicate that immune conditioning with dietary Zn alters nephritogenic IgA production after mucosal infection.
Overexpressed Cavβ3 Inhibits N-type (Cav2.2) Calcium Channel Currents through a Hyperpolarizing Shift of “Ultra-slow” and “Closed-state” Inactivation

It has been shown that β auxiliary subunits increase current amplitude in voltage-dependent calcium channels. In this study, however, we found a novel inhibitory effect of β3 subunit on macroscopic Ba2+ currents through recombinant N- and R-type calcium channels expressed in Xenopus oocytes. Overexpressed β3 (12.5 ng/cell cRNA) significantly suppressed N- and R-type, but not L-type, calcium channel currents at “physiological” holding potentials (HPs) of −60 and −80 mV. At a HP of −80 mV, coinjection of various concentrations (0–12.5 ng) of the β3 with Cav2. 2α1 and α2δ enhanced the maximum conductance of expressed channels at lower β3 concentrations but at higher concentrations (>2.5 ng/cell) caused a marked inhibition. The β3-induced current suppression was reversed at a HP of −120 mV, suggesting that the inhibition was voltage dependent. A high concentration of Ba2+ (40 mM) as a charge carrier also largely diminished the effect of β3 at −80 mV. Therefore, experimental conditions (HP, divalent cation concentration, and β3 subunit concentration) approaching normal physiological conditions were critical to elucidate the full extent of this novel β3 effect. Steady-state inactivation curves revealed that N-type channels exhibited “closed-state” inactivation without β3, and that β3 caused an ∼40-mV negative shift of the inactivation, producing a second component with an inactivation midpoint of approximately −85 mV. The inactivation of N-type channels in the presence of a high concentration (12.5 ng/cell) of β3 developed slowly and the time-dependent inactivation curve was best fit by the sum of two exponential functions with time constants of 14 s and 8.8 min at −80 mV. Similar “ultra-slow” inactivation was observed for N-type channels without β3. Thus, β3 can have a profound negative regulatory effect on N-type (and also R-type) calcium channels by causing a hyperpolarizing shift of the inactivation without affecting “ultra-slow” and “closed-state” inactivation properties.
A Microrebootable System - Design, Implementation, and Evaluation

A significant fraction of software failures in large scale Internet systems are cured by rebooting, even when the exact failure causes are unknown. However, rebooting can be expensive, causing nontrivial service disruption or downtime even when clusters and failover are employed. In this work we use separation of process recovery from data recovery to enable frequent use of the microreboot, a fine grain recovery mechanism that restarts only suspectedfaulty application components without disturbing the rest . We evaluate this recovery approach on an eBay-like Internet auction application running on our microrebootenabled application server. We find that microreboots recover from most of the same failures as full reboots, but do so an order of magnitude faster, resulting in an order of magnitude savings in lost work. Unlike full reboots, microreboot-based recovery is sufficiently inexpensive to be employed at the first sign of failure, even when mistakes in failure detection are likely. The cost of our microrebootenabling modifications is a reduction of less than 1% in failure-free steady-state throughput.
Energy Optimization using Cross-Layer Protocols in Wireless Sensor Networks

Wireless Sensor Network (WSN) is an emerging technology. It is predicted that in future, WSN will change the human life totally. Energy optimization in Wireless Sensor Network (WSN) is one of the challenging issues. Wireless Sensor Network composed of a set of tiny sensor nodes. The nodes are continuously sense and transmit the data. WSN nodes operate on batteries; due to this WSN has a limited lifetime. So increasing the lifetime of Wireless Sensor Network and Minimizing energy cost in wireless sensor network are twin important problems. Proper selection of routing protocol helps achieve maximum efficiency in energy consumption which intern increases network lifetime. In this paper, three protocols namely Ad-hoc on-Demand Distance Vector (AODV), Destination Sequence Distance Vector (DSDV) and Ad-hoc onDemand Multipath Distance vector (AOMDV) are compared and analyzed. They are compared with IEEE802.11 and IEEE802.15. 4 MAC protocol. MinMax, and MinTotal are used as metrics for this comparison. Matlab and NS-2 are used for simulation.
Cysteine-Rich Secretory Protein-3 (CRISP3) Is Strongly Up-Regulated in Prostate Carcinomas with the TMPRSS2-ERG Fusion Gene

A large percentage of prostate cancers harbor TMPRSS2-ERG gene fusions, leading to aberrant overexpression of the transcription factor ERG. The target genes deregulated by this rearrangement, however, remain mostly unknown. To address this subject we performed genome-wide mRNA expression analysis on 6 non-malignant prostate samples and 24 prostate carcinomas with (n = 16) and without (n = 8) TMPRSS2-ERG fusion as determined by FISH. The top-most differentially expressed genes and their associations with ERG over-expression were technically validated by quantitative real-time PCR and biologically validated in an independent series of 200 prostate carcinomas. Several genes encoding metabolic enzymes or extracellular/transmembrane proteins involved in cell adhesion, matrix remodeling and signal transduction pathways were found to be co-expressed with ERG. Within those significantly over-expressed in fusion-positive carcinomas, CRISP3 showed more than a 50-fold increase when compared to fusion-negative carcinomas, whose expression levels were in turn similar to that of non-malignant samples. In the independent validation series, ERG and CRISP3 mRNA levels were strongly correlated (r(s) = 0.65, p<0.001) and both were associated with pT3 disease staging. Furthermore, immunohistochemistry results showed CRISP3 protein overexpression in 63% of the carcinomas and chromatin immunoprecipitation with an anti-ERG antibody showed that CRISP3 is a direct target of the transcription factor ERG. We conclude that ERG rearrangement is associated with significant expression alterations in genes involved in critical cellular pathways that define a subset of locally advanced PCa. In particular, we show that CRISP3 is a direct target of ERG that is strongly overexpressed in PCa with the TMPRSS2-ERG fusion gene.
Smart Parking System Based On Reservation

: With the increase of economic behavior and the upgrade of living standard, the ratio of people in India who own automobiles and motorcycles have recently increased giving a boost to Metropolitan Traffic. Therefore, parking issues will be a big challenge to facilitate traffic network and ensure urban life quality. Searching for parking space in most metropolitan areas, especially during the rush hours, is difficult for drivers. The difficulty arises from not knowing where the available spaces may be at that time; even if known, many vehicles may pursue very limited parking spaces to cause serious traffic congestion. In this paper, we design and implement a prototype of Smart Parking System based on Reservation (SPSR) that allows drivers to effectively find and reserve the vacant parking spaces. By periodically learning the parking status from the host parking database management in parking lots, the reservation service is affected by the change of physical parking status. The drivers are allowed to access this cyber-physical system with their personal communication devices. Furthermore, we study state-of-the-art parking policies in smart parking systems and compare their performance. The experiment results show that the proposed reservation-based parking policy has the potential to simplify the operations of parking systems, as well as alleviate traffic congestion caused by parking searching.
Procurement Maturity, Alignment and Performance: a Dutch Hospital Case Comparison

Procurement is an important supporting business function, with which competitive advantage can potentially be achieved. In this paper, the relation between maturity and alignment in procurement on the one hand, and procurement performance on the other, is investigated in the case study setting of three Dutch hospitals. The hospitals are benchmarked and it is shown that an increase in maturity of their organization, processes and IT is needed to achieve more alignment and hence better procurement performance. Our general finding is that there is a positive relation between maturity and alignment and performance in procurement. Possible implications for theory and practice are given, as well as directions for future research in this area.
Enhanced external counterpulsation reduces indices of central blood pressure and myocardial oxygen demand in patients with left ventricular dysfunction

Enhanced external counterpulsation (EECP) therapy decreases angina episodes and improves quality of life in patients with left ventricular (LV) dysfunction. However, the underlying mechanisms relative to the benefits of EECP therapy in patients with LV dysfunction have not been fully elucidated. The purpose of this study was to investigate the effects of EECP on indices of central haemodynamics, aortic pressure wave reflection characteristics, and estimates of LV load and myocardial oxygen demand in patients with LV dysfunction. Patients with chronic stable angina and LV ejection fraction < 40% but > 30%, were randomized to either an EECP group (LV ejection fraction = 35.1 ± 4.6%; n = 10) or sham‐EECP group (LV ejection fraction = 34.3 ± 4.2%; n = 7). Pulse wave analysis of the central aortic pressure waveform and LV function were evaluated by applanation tonometry before and after 35 1‐h sessions of EECP or sham‐EECP. Enhanced external counterpulsation therapy was effective in reducing indices of LV wasted energy and myocardial oxygen demand by 25% and 19%, respectively. In addition, indices of coronary perfusion pressure and subendocardial perfusion were increased by 9% and 30%, respectively, after EECP. Our data indicate that EECP may be useful as adjuvant therapy for improving functional classification in heart failure patients through reductions in central blood pressure, aortic pulse pressure, wasted LV energy, and myocardial oxygen demand, which also suggests improvements in ventricular–vascular interactions.
Basic Fibroblast Growth Factor‐Induced Increase in zif/268 and c‐fos mRNA Levels Is Ca2+ Dependent in Primary Cultures of Hippocampal Neurons

Abstract: Basic fibroblast growth factor (bFGF) is present in the developing rat brain and has been shown to provide critical trophic support for hippocampal neurons in culture. The influence of bFGF on the expression of mRNAs encoding the transcription factors zif/268 and c‐fos was studied in primary cultures of hippocampal neurons (derived from rat embryos) using reverse transcription‐coupled PCR. In these cultures grown for 3 days in the absence of serum, bFGF causes a dramatic and transient increase in the levels of zif/268 and c‐fos, within 15 and 30 min, respectively. A similar induction of these two early genes occurs following activation of protein kinase C (PKC). The bFGF‐induced activation persists after PKC desensitization but is inhibited by chelation of intracellular Ca2+. These results suggest that in primary cultures of hippocampal neurons, bFGF induces the expression of immediate early genes through a pathway that requires Ca2+ mobilization.
Medically unexplained symptoms in frequent attenders of secondary health care: retrospective cohort study

Abstract Objective: To estimate the prevalence of medically unexplained symptoms in patients who most frequently attend outpatient services. Design: Retrospective cohort study over three years with review of case notes. Setting: Secondary care services in the South Thames (West) NHS region. Participants: Outpatient attenders with new appointments in 1993. Main outcome measures: Number of outpatient appointments, and number of consultation episodes for medically unexplained conditions. Results: Medical records of 361 of 400 sampled frequent attenders were examined, and 971 consultation episodes were recorded. Ninety seven (27%) had one or more consultation episodes in which the condition was medically unexplained; 208 (21%) of the 971 consultation episodes were medically unexplained. Abdominal pain, chest pain, headache, and back pain were commonly found to be medically unexplained. Conclusions: Medically unexplained symptoms present in most hospital specialties and account for a considerable proportion of consultations by frequent attenders in secondary care. What is already known on this topic Frequent attenders in all medical settings account for a disproportionate amount of healthcare resources In primary care, frequent attenders commonly present with symptoms that remain medically unexplained What this study adds Medically unexplained symptoms are also common among frequent attenders in secondary care and present in most specialties Symptoms that are particularly likely to remain unexplained in this group include gastrointestinal complaints, back pain, and headache
On the boundary values of harmonic functions

0. A classical result of Fatou states that if u(z) is harmonic and bounded in lzl < 1 then u has a nontangential limit at almost every point ei? The same conclusion holds if u is only bounded from below. These results have a local analogue -namely, if u(z) is harmonic in lzl < 1 and at each point ei0 of a measurable set E there is some cone in which u(z) is bounded from either above or below then u(z) has a nontangential limit at almost every eiO & E. With the aid of conformal mapping one can show the above results hold for regions of the plane more general than lzl < 1. Methods similar to those used for lzl < 1 may be applied to functions which are harmonic in the unit ball of Euclidean (n + 1)-space. However, since we lack a conformal mapping theorem for more general domains DcE +1 the situation there is more technically complicated. Known results for certain kinds of domains D c E, + 1 are due to Brelot and Doob [2], Calderon [3], Carleson [4] and Widman [7], and the purpose of this paper is to obtain nontangential boundary values for functions which are harmonic in still more general types of domains D' En + 1 and bounded from above or below in cones. The domains which we consider are all regular domains for the solution of the Dirichlet problem. For a regular domain D, our result may be stated as follows. Let EC aD and suppose for each Q E E there is a cone with vertex Q which is exterior to D. Then if u is harmonic in D and is bounded from above or below in a cone with vertex Q for each Q E E, u has a finite nontangential limit at each Q E E except for a set of harmonic measure zero. It is natural that the exceptional set be one of harmonic measure zero since if Ec AD is any set of harmonic measure zero it is easy to construct a positive harmonic function with boundary value +oo at each point of E. Our main result is a consequence of the basic result that if u is harmonic and bounded in a starlike Lipschitz domain D, then u has a finite nontangential limit at each Q E AD except for a set of harmonic measure zero. In ? 1 of this paper we define the terms starlike Lipschitz domain, nontangential limit, and harmonic measure. We also include some elementary consequences of these definitions and some essential theorems on the differentiation of integrals.
NBER WORKING PAPER SERIES PEER EFFECTS AND THE IMPACT OF TRACKING: EVIDENCE FROM A RANDOMIZED EVALUATION IN KENYA

This paper provides experimental evidence on the impact of tracking primary school students by initial achievement. In the presence of positive spillover effects from academically proficient peers, tracking may be beneficial for strong students but hurt weaker ones. However, tracking may help everybody if heterogeneous classes make it difficult to teach at a level appropriate to most students. We test these competing claims using a randomized evaluation in Kenya. One hundred and twenty one primary schools which all had a single grade one class received funds to hire an extra teacher to split that class into two sections. In 60 randomly selected schools, students were randomly assigned to sections. In the remaining 61 schools, students were ranked by prior achievement (measured by their first term grades), and the top and bottom halves of the class were assigned to different sections. After 18 months, students in tracking schools scored 0.14 standard deviations higher than students in non-tracking schools, and this effect persisted one year after the program ended. Furthermore, students at all levels of the distribution benefited from tracking. A regression discontinuity analysis shows that in tracking schools scores of students near the median of the pre-test distribution score are independent of whether they were assigned to the top or bottom section. In contrast, in non-tracking schools we find that on average, students benefit from having academically stronger peers. This suggests that tracking was beneficial because it helped teachers focus their teaching to a level appropriate to most students in the class. Esther Duflo Department of Economics MIT, E52-252G 50 Memorial Drive Cambridge, MA 02142 and NBER eduflo@mit.edu Pascaline Dupas Department of Economics UCLA 8283 Bunche Hall Los Angeles, CA 90095 and NBER pdupas@econ.ucla. edu Michael Kremer Harvard University Department of Economics Littauer Center M20 Cambridge, MA 02138 and NBER mkremer@fas.harvard. edu