Miracle-dz/UniFAR-FTUs huggingface dataset:
Rare Variants in Transcript and Potential Regulatory Regions Explain a Small Percentage of the Missing Heritability of Complex Traits in Cattle

The proportion of genetic variation in complex traits explained by rare variants is a key question for genomic prediction, and for identifying the basis of “missing heritability”–the proportion of additive genetic variation not captured by common variants on SNP arrays. Sequence variants in transcript and regulatory regions from 429 sequenced animals were used to impute high density SNP genotypes of 3311 Holstein sires to sequence. There were 675,062 common variants (MAF>0.05), 102,549 uncommon variants (0.01<MAF<0.05), and 83,856 rare variants (MAF<0.01). We describe a novel method for estimating the proportion of the rare variants that are sequencing errors using parent-progeny duos. We then used mixed model methodology to estimate the proportion of variance captured by these different classes of variants for fat, milk and protein yields, as well as for fertility. Common sequence variants captured 83%, 77%, 76% and 84% of the total genetic variance for fat, milk, and protein yields and fertility, respectively. This was between 2 and 5% more variance than that captured from 600k SNPs on a high density chip, although the difference was not significant. Rare variants captured 3%, 0%, 1% and 14% of the genetic variance for fat, milk and protein yields, and fertility respectively, whereas pedigree explained the remaining amount of genetic variance (none for fertility). The proportion of variation explained by rare variants is likely to be under-estimated due to reduced accuracies of imputation for this class of variants. Using common sequence variants slightly improved accuracy of genomic predictions for fat and milk yield, compared to high density SNP array genotypes. However, including rare variants from transcript regions did not increase the accuracy of genomic predictions. These results suggest that rare variants recover a small percentage of the missing heritability for complex traits, however very large reference sets will be required to exploit this to improve the accuracy of genomic predictions. Our results do suggest the contribution of rare variants to genetic variation may be greater for fitness traits.
The Hsp70/90 cochaperone, Sti1, suppresses proteotoxicity by regulating spatial quality control of amyloid-like proteins

Escape of aberrant proteins from protein quality control leads to accumulation of toxic protein species. Sti1 interacts with Hsp70 to mediate spatial PQC of amyloid-like proteins by regulating their distribution in different intracellular protein-handling depots. Sti1 suppresses proteotoxicity by targeting amyloid-like proteins to perinuclear foci.
Long-term depression and other synaptic plasticity in the cerebellum

Cerebellar long-term depression (LTD) is a type of synaptic plasticity and has been considered as a critical cellular mechanism for motor learning. LTD occurs at excitatory synapses between parallel fibers and a Purkinje cell in the cerebellar cortex, and is expressed as reduced responsiveness to transmitter glutamate. Molecular induction mechanism of LTD has been intensively studied using culture and slice preparations, which has revealed critical roles of Ca2+, protein kinase C and endocytosis of AMPA-type glutamate receptors. Involvement of a large number of additional molecules has also been demonstrated, and their interactions relevant to LTD mechanisms have been studied. In vivo experiments including those on mutant mice, have reported good correlation of LTD and motor learning. However, motor learning could occur with impaired LTD. A possibility that cerebellar synaptic plasticity other than LTD compensates for the defective LTD has been proposed.
The legacy problem in government agencies: an exploratory study

Government organizations continue to be heavily reliant on legacy systems to support their business-critical functions. When practitioners embark on legacy systems replacement projects, they tend to use the legacy software's features as business requirements for its replacement application. This unnecessarily reproduces the business processes that have often emerged from the very technical limitations of the legacy system that is being phased out -- a phenomenon referred to as the "legacy problem. " Public agencies are missing opportunities for innovation when they carry out legacy replacement projects in this conservative manner. Overcoming the legacy problem is "wickedly" difficult because of the complex interrelationships of information technology, organizational culture, and government agencies' normative environments. This paper reports on the use of an online survey and qualitative interviews with practitioners in government agencies to explore the legacy problem. The data revealed that public agencies tend to regard legacy system replacement projects as a distinctly technical issue, and that they do not engage in systematic practices to ensure that unnecessary carryover of the business model embedded in legacy technology does not take place. As a result, legacy feature carryover occurs frequently, because practitioners want to minimize business process changes during new system implementation. The study findings single out the procurement of Commercial Off The Shelf (COTS) software as the most common approach to the replacement of legacy systems. When COTS packages are implemented, vendors (technology providers) shape the requirements discussion and the business analysis surrounding feature selection and customization. These study findings can be instrumental when devising solutions to assist agencies in dealing with the legacy problem.
Trusted data fusion by using cellular automata in wireless sensor networks

In this paper, we introduce a new protocol, named TDFCA (Trusted Data Fusion by using Cellular Automata) in Wireless sensor Networks. TDFCA uses Cellular Automata rules to find the most suitable cluster head, perform data fusion, and find the most trusted neighbors for sending the fusion result to base station. The network is intended for the long-term monitoring of packets produced by jammer nodes. The data flow of the network is mainly toward a cluster head node, which is responsible for collecting data generated by sensor nodes. When the network is first deployed, an initialization algorithm is performed and preliminary clusters and cluster heads are determined. Since the network nodes are battery powered, one of the important measures of effectiveness is power efficiency. Therefore, TDFCA tries not only to increase the trust value of the fusion result, but also to maximize the network's lifetime. Finally, simulation results are presented.
Measurements Clustering for Robustness Improvement of Indoor WLAN Propagation Models

For indoor Wireless Local Area Networks (WLANs) planning, an accurate propagation modelling is required. Semi-empirical models represent an effici ent approach to the indoor channel coverage prediction. Their parameters are estimated from measurement results. In the case called ill-conditioned, the Least Square ( LS) regression leads to a bad estimation of the model parameters and thus to numerical instability. In this paper, we present an approach based on the K-means clustering method which allows us to increase the estimation stability. Clustering is used to select uning points for having a robust estimation. Index Terms – K-means, Radio Channel Modelling, Indoor Propagation, WLAN.
Leptin suppresses anti-Mullerian hormone gene expression through the JAK2/STAT3 pathway in luteinized granulosa cells of women undergoing IVF.

STUDY QUESTION Do the adipocytokines, leptin and adiponectin affect the granulosa cell expression of anti-Mullerian hormone (AMH) and its receptor (AMHR-II)? SUMMARY ANSWER Leptin suppresses AMH mRNA levels in human luteinized granulosa cells through the JAK2/STAT3 pathway, while adiponectin has no such effect. WHAT IS KNOWN ALREADY AMH is one of the most reliable markers of ovarian reserve. Serum AMH levels decline with obesity. Obesity is associated with elevated leptin and reduced adiponectin levels. STUDY DESIGN, SIZE AND DURATION This prospective study included 60 infertile women undergoing fresh IVF and ICSI cycles utilizing autologous oocytes at Montefiore's Institute for Reproductive Medicine and Health between July 2010 and April 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS Follicular fluid was collected from small (SFs; <14 mm) and large follicles (LFs; ≥14 mm) from 38 participants. Total RNA was extracted separately from mural and cumulus granulosa cells and mRNA levels were measured by RT-PCR. In an additional group of participants (N = 22), primary cumulus and mural granulosa cells (pooled SFs and LFs) were cultured in media alone or with addition of either leptin (N = 7), adiponectin (N = 8) or JAK2/STAT3 inhibitor + leptin (N = 7), and AMH and AMHR-II mRNA levels measured. Levels of AMH, leptin and adiponectin protein were measured in follicular fluid. MAIN RESULTS AND THE ROLE OF CHANCE AMH and AMHR-II mRNA and follicular fluid AMH protein levels were inversely correlated with age. AMH mRNA expression was six times higher in cumulus compared with mural granulosa cells in SFs (P< 0.05) and eight times higher in cumulus compared with mural granulosa cells in LFs (P < 0.001). In follicular fluid, leptin protein level positively correlated (r = 0.7, P = 0.03), while adiponectin protein level inversely correlated (r = -0.46, P = 0.02) with BMI. Leptin treatment suppressed AMH and AMHR-II mRNA in both cumulus and mural granulosa cells (all P < 0.05). In the presence of JAK2/STAT3 inhibitor, leptin treatment did not alter AMH but continued to suppress AMHR-II mRNA in cumulus cells (P = 0.02). Adiponectin treatment did not alter AMH or AMHR-II mRNA levels. LIMITATIONS, REASONS FOR CAUTION This study included a luteinized granulosa cell model as these cells were collected from women who were hyperstimulated with gonadotrophins. The results obtained may not fully extrapolate to non-luteinized granulosa cells. WIDER IMPLICATIONS OF THE FINDINGS Leptin may program abnormal AMH signaling, thereby resulting in ovarian dysfunction. This study opens a new perspective for understanding the low ovarian reserve seen in obese women and provides new insights into potential mechanisms that explain the lower AMH seen in obese women. Whether our findings explain the worse response to ovulation induction observed in obese women needs to be further elucidated.
Quantification of the effects of ocean acidification on sediment microbial communities in the environment: the importance of ecosystem approaches

To understand how ocean acidification (OA) influences sediment microbial communities, naturally CO2-rich sites are increasingly being used as OA analogues. However, the characterization of these naturally CO2-rich sites is often limited to OA-related variables, neglecting additional environmental variables that may confound OA effects. Here, we used an extensive array of sediment and bottom water parameters to evaluate pH effects on sediment microbial communities at hydrothermal CO2 seeps in Papua New Guinea. The geochemical composition of the sediment pore water showed variations in the hydrothermal signature at seep sites with comparable pH, allowing the identification of sites that may better represent future OA scenarios. At these sites, we detected a 60% shift in the microbial community composition compared with reference sites, mostly related to increases in Chloroflexi sequences. pH was among the factors significantly, yet not mainly, explaining changes in microbial community composition. pH variation may therefore often not be the primary cause of microbial changes when sampling is done along complex environmental gradients. Thus, we recommend an ecosystem approach when assessing OA effects on sediment microbial communities under natural conditions. This will enable a more reliable quantification of OA effects via a reduction of potential confounding effects.
Mechatronic design of a high-resolution, portable, compact 3D dynamic shape display device

3D surface display is a form of display that can be simultaneously viewable by multiple users from many viewing positions, without the need for any headgears. It provides actual stereoscopic display such that users can focus on an object with correct depth representations without any eye strains. Existing designs of the surface display are usually done in large scale, whereby the compactness of the system is not taken into consideration. This work focus on design of a portable compact surface display system with high resolution. The design has a set of linear actuators which in turn connected to pins, each represents a pixel of the object to be displayed. The heights of the pins can be changed by controlling the actuator which in turn produces a high resolution tangible 3D object appearing from the surface. A Graphical User Interface (GUI) is designed with MATLAB-Arduino interface provides the simulated and actual display. The use of micro-actuators and pins makes the system of higher resolution than existing display systems available in the market.
Combined reduction of intercellular coupling and membrane excitability differentially affects transverse and longitudinal cardiac conduction.

AIMS Reduced excitability and gap junction expression are commonly found in electrically remodelled diseased hearts, but their contribution to slow conduction and arrhythmias is unclear. In this study, we have investigated the effect of isolated and combined reductions in membrane excitability and intercellular coupling on impulse propagation and arrhythmogeneity in genetically modified mice. METHODS AND RESULTS Cx43 and Scn5a(1798insD/+) heterozygous (HZ) mice were crossbred to create a mixed offspring: wild-type (WT, n = 15), Cx43 HZ (n = 14), Scn5a(1798insD/+) (Scn5a) HZ (n = 17), and Cx43/Scn5a(1798insD/+) (Cx43/Scn5a) HZ (n = 15) mice. After ECG recording, epicardial activation mapping (208 recording sites) was performed on Langendorff-perfused hearts. Arrhythmia inducibility was tested by one to three premature stimuli and burst pacing. Conduction velocity longitudinal (CV(L)) and transverse (CV(T)) to fibre orientation and dispersion of conduction were determined during S1-S1 pacing (150 ms). Connexin43 (Cx43) and sodium channel Nav1.5 protein expression and myocardial tissue collagen content were determined by immunohistology. Compared with WT animals, P, QRS, and QTc intervals were prolonged in Scn5a HZ and Cx43/Scn5a HZ, but not in Cx43 HZ animals. Scn5a HZ mice showed decreased CV(L) in right ventricle (RV) but not in left ventricle compared with WT. In the RV of Cx43/Scn5a HZ, CV(T) was reduced, but CV(L) was not different from WT. Arrhythmia inducibility was low and not increased in either single- or double-mutant mice. CONCLUSION Reduction of both electrical coupling and excitability results in normal conduction velocity parallel to fibre orientation but in pronounced conduction slowing transverse to fibre orientation in RV only, although this does not affect arrhythmogeneity.
A computationally efficient, non-equilibrium, carrier temperature dependent semiconductor gain model for FDTD simulation of optoelectronic devices

We report a Finite Difference Time Domain (FDTD) model incorporating carrier heating/cooling for the first time. The proposed model thermalizes non equilibrium carrier distributions through carrier temperature dependent intraband transition terms. This multi-level, multi-electron model is formulated to be computationally efficient despite its physical complexity and hence presents potential for the development of powerful general optoelectronic device simulators for devices of arbitrary geometry. Results of carrier distribution thermalization and comparisons to non linear gain experiments are provided to validate the model.
A new concept of virtual cellular manufacturing

The research in virtual cellular manufacturing (VCM) systems area gains momentum as markets have become more globalised. This is due to turbulent customer demands, characterised by frequent changes in product mix and volume. Therefore, if companies are interested in implementing manufacturing systems that can be quickly restructured with minimal cost and time, the approach of virtual cellular manufacturing gives considerable benefits. VCM systems physically resemble the traditional functional layout. Within this setting, group technology (GT) philosophy is used to gain the advantages accompanying with traditional cellular manufacturing (CM) systems. VCM is being used with broad applicability in manufacturing sector to reduce job set-up and flow times. Decisions for pooling of jobs into families, release of part families to the shop, and temporary machine dedication will lead to improvement in shop performance i.e. in terms of job flow time and system utilisation. The goal of this paper is to develop a new concept of VCM and address its operational issues through a numerical illustration. Based on the numerical results, we also outline a factorial design of simulation experiments for future research.
FPGA based design of low power reconfigurable router for Network on Chip (NoC)

FPGA based design of reconfigurable router for NoC applications is proposed in the present work. Design entry of the proposed router is done using Verilog Hardware Description Language (Verilog HDL). The router designed in the present work has four channels (namely, east, west, north and south) and a crossbar switch. Each channel consists of First in First out (FIFO) buffers and multiplexers. FIFO buffers are used to store the data and the input and output of the data are controlled using multiplexers. Firstly, south channel is designed which includes the design of FIFO and multiplexers. After that, the crossbar switch and other three channels are designed. All these designed channels, FIFO buffers, multiplexers and crossbar switches are integrated to form the complete router architecture. The proposed design is simulated using Modelsim and the RTL view is obtained using Xilinx ISE 13.4. Xilinx SPARTAN-6 FPGAs are used for synthesis of proposed design. Power dissipation of the proposed reconfigurable router is reduced using Power gating technique. Total power is calculated by the use of XPower Analyzer tool. Obtained results show that the proposed design consumes less power compared to the previously designed reconfigurable routers.
Detection of PrPres in Genetically Susceptible Fetuses from Sheep with Natural Scrapie

Scrapie is a transmissible spongiform encephalopathy with a wide PrPres dissemination in many non-neural tissues and with high levels of transmissibility within susceptible populations. Mechanisms of transmission are incompletely understood. It is generally assumed that it is horizontally transmitted by direct contact between animals or indirectly through the environment, where scrapie can remain infectious for years. In contrast, in utero vertical transmission has never been demonstrated and has rarely been studied. Recently, the use of the protein misfolding cyclic amplification technique (PMCA) has allowed prion detection in various tissues and excretions in which PrPres levels have been undetectable by traditional assays. The main goal of this study was to detect PrPres in fetal tissues and the amniotic fluid from natural scrapie infected ewes using the PMCA technique. Six fetuses from three infected pregnant ewes in an advanced clinical stage of the disease were included in the study. From each fetus, amniotic fluid, brain, spleen, ileo-cecal valve and retropharyngeal lymph node samples were collected and analyzed using Western blotting and PMCA. Although all samples were negative using Western blotting, PrPres was detected after in vitro amplification. Our results represent the first time the biochemical detection of prions in fetal tissues, suggesting that the in utero transmission of scrapie in natural infected sheep might be possible.
Decreased Activities of Apolipoprotein M Promoter Are Associated with the Susceptibility to Coronary Artery Diseases

The present study investigated the correlation among genetic polymorphisms of the proximal promoter region of apolipoprotein M (apoM) gene, the polymorphisms in relation to apoM expressions and the susceptibility to coronary artery diseases (CAD) in a Han Chinese population. Four common polymorphic sites, i.e., T-1628G, C-1065A, T-855C and T-778C, were confirmed, and a new deletion mutation C-724del was found, in 206 CAD patients and 209 non-CAD patients using direct DNA sequencing analyses. Occurrences of alleles T-1628G, T-855C and C-724del were significantly higher in CAD patients compared to non-CAD patients. Moreover we examined all these polymorphisms in relation to apoM expression by applying luciferase reporter assay. It demonstrated that constructs -855C and 724del showed obvious decreased luciferase activities, i.e., (0.93±0.15 vs. 2.11±0.15; P=0.012) and (1.13±0.25 vs. 2.11±0.15; P=0.009) respectively, which indicates these two polymorphisms could confer decreased apoM expressions. Meanwhile the occurrences of these two SNP were also significantly higher in the CAD patients than in non-CAD patients. It is therefore reasonable to speculate that down-regulated apoM expressions in relation to these polymorphisms may affect HDL and cholesterol metabolism in vivo and further influence the susceptibility to CAD, although the underlying mechanisms need further investigation.
Utility-based asynchronous flow control algorithm for wireless sensor networks

In this paper, we formulate a flow control optimization problem for wireless sensor networks with lifetime constraint and link interference in an asynchronous setting. Our formulation is based on the network utility maximization framework, in which a general utility function is used to characterize the network performance such as throughput. To solve the problem, we propose a fully asynchronous distributed algorithm based on dual decomposition, and theoretically prove its convergence. The proposed algorithm can achieve the maximum utility. Extensive simulations are conducted to demonstrate the efficiency of our algorithm and validate the analytical results.
Evidence that intraluminal pressure affects high potassium- and serotonin-induced contractions differently in the bovine middle cerebral artery: an in vitro study.

The effects of changing intraluminal pressure on contractions induced by 70 mM potassium (K+) and 10(-7), 10(-6), and 10(-5) M serotonin (5-HT) were studied in vitro in bovine middle cerebral arteries. Changes in vessel outside diameter in whole-mounted cylindrical sections of artery were detected with a photoelectric infrared device. High K+-or 5-HT (10(-5)M)-induced contractions peaked at 25 mm Hg and were significantly correlated with increasing intraluminal pressure between 25 and 175 mm Hg. Contractions induced with lower concentrations of 5-HT (10(-6), 10(-7) M), norepinephrine, and histamine peaked at 75 mm Hg but were not significantly correlated with rising pressure. Phentolamine (2 X 10(-6) M) added to the extraluminal bath had negligible influence on pressure's ability to affect K+- and 5-HT-induced contractions differently. Reducing bath temperature to 27 degrees C reduced the K+ response at each pressure, but similar temperature changes had little affect on the 5-HT-induced contractions. The K+ response became less sensitive to increasing pressure at low temperatures. Nifedipine (10(-7) M) almost totally eliminated K+-induced contractions, while significantly reducing the responses to all concentrations of 5-HT. The 5-HT responses appeared more sensitive to increasing intraluminal pressure in the presence of nifedipine. Maximum Ca++-induced contractions in the presence of 10(-5) M 5-HT and high K+ occurred at 25 mm Hg, while Ca++-induced contractions and Ca++-induced contractions in the presence of 10(-7) 5-HT or K+ plus 5-HT were maximum at 75 mm Hg. (ABSTRACT TRUNCATED AT 250 WORDS)