Miracle-dz/UniFAR-FTUs huggingface dataset:
The Syk Kinase SmTK4 of Schistosoma mansoni Is Involved in the Regulation of Spermatogenesis and Oogenesis

The signal transduction protein SmTK4 from Schistosoma mansoni belongs to the family of Syk kinases. In vertebrates, Syk kinases are known to play specialized roles in signaling pathways in cells of the hematopoietic system. Although Syk kinases were identified in some invertebrates, their role in this group of animals has not yet been elucidated. Since SmTK4 is the first Syk kinase from a parasitic helminth, shown to be predominantly expressed in the testes and ovary of adult worms, we investigated its function. To unravel signaling cascades in which SmTK4 is involved, yeast two-/three-hybrid library screenings were performed with either the tandem SH2-domain, or with the linker region including the tyrosine kinase domain of SmTK4. Besides the Src kinase SmTK3 we identified a new Src kinase (SmTK6) acting upstream of SmTK4 and a MAPK-activating protein, as well as mapmodulin acting downstream. Their identities and colocalization studies pointed to a role of SmTK4 in a signaling cascade regulating the proliferation and/or differentiation of cells in the gonads of schistosomes. To confirm this decisive role we performed biochemical and molecular approaches to knock down SmTK4 combined with a novel protocol for confocal laser scanning microscopy for morphological analyses. Using the Syk kinase-specific inhibitor Piceatannol or by RNAi treatment of adult schistosomes in vitro, corresponding phenotypes were detected in the testes and ovary. In the Xenopus oocyte system it was finally confirmed that Piceatannol suppressed the activity of the catalytic kinase domain of SmTK4. Our findings demonstrate a pivotal role of SmTK4 in gametogenesis, a new function for Syk kinases in eukaryotes.
Cav1.4 IT mouse as model for vision impairment in human congenital stationary night blindness type 2

Mutations in the CACNA1F gene encoding the Cav1.4 Ca2+ channel are associated with X-linked congenital stationary night blindness type 2 (CSNB2). Despite the increasing knowledge about the functional behavior of mutated channels in heterologous systems, the pathophysiological mechanisms that result in vision impairment remain to be elucidated. This work provides a thorough functional characterization of the novel IT mouse line that harbors the gain-of-function mutation I745T reported in a New Zealand CSNB2 family.1 Electroretinographic recordings in IT mice permitted a direct comparison with human data. Our data supported the hypothesis that a hyperpolarizing shift in the voltage-dependence of channel activation—as seen in the IT gain-of-function mutant2—may reduce the dynamic range of photoreceptor activity. Morphologically, the retinal outer nuclear layer in adult IT mutants was reduced in size and cone outer segments appeared shorter. The organization of the outer plexiform layer was disrupted, and synaptic structures of photoreceptors had a variable, partly immature, appearance. The associated visual deficiency was substantiated in behavioral paradigms. The IT mouse line serves as a specific model for the functional phenotype of human CSNB2 patients with gain-of-function mutations and may help to further understand the dysfunction in CSNB.
Finding influential neighbors to maximize information diffusion in twitter

The problem of spreading information is a topic of considerable recent interest, but the traditional influence maximization problem is inadequate for a typical viral marketer who cannot access the entire network topology. To fix this flawed assumption that the marketer can control any arbitrary k nodes in a network, we have developed a decentralized version of the influential maximization problem by influencing k neighbors rather than arbitrary users in the entire network. We present several reasonable neighbor selection schemes and evaluate their performance with a real dataset collected from Twitter. Unlike previous studies using network topology alone or synthetic parameters, we use real propagation rate for each node calculated from the Twitter messages during the 2010 UK election campaign. Our experimental results show that information can be efficiently propagated in online social networks using neighbors with a high propagation rate rather than those with a high number of neighbors.
Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration

Recessive Stargardt's macular degeneration is an inherited blinding disease of children caused by mutations in the ABCR gene. The primary pathologic defect in Stargardt's disease is accumulation of toxic lipofuscin pigments such as N-retinylidene-N-retinylethanolamine (A2E) in cells of the retinal pigment epithelium. This accumulation appears to be responsible for the photoreceptor death and severe visual loss in Stargardt's patients. Here, we tested a therapeutic strategy to inhibit lipofuscin accumulation in a mouse model of recessive Stargardt's disease. Isotretinoin (Accutane) has been shown to slow the synthesis of 11-cis-retinaldehyde and regeneration of rhodopsin by inhibiting 11-cis-retinol dehydrogenase in the visual cycle. Light activation of rhodopsin results in its release of all-trans-retinaldehyde, which constitutes the first reactant in A2E biosynthesis. Accordingly, we tested the effects of isotretinoin on lipofuscin accumulation in abcr−/− knockout mice. Isotretinoin blocked the formation of A2E biochemically and the accumulation of lipofuscin pigments by electron microscopy. We observed no significant visual loss in treated abcr−/− mice by electroretinography. Isotretinoin also blocked the slower, age-dependent accumulation of lipofuscin in wild-type mice. These results corroborate the proposed mechanism of A2E biogenesis. Further, they suggest that treatment with isotretinoin may inhibit lipofuscin accumulation and thus delay the onset of visual loss in Stargardt's patients. Finally, the results suggest that isotretinoin may be an effective treatment for other forms of retinal or macular degeneration associated with lipofuscin accumulation.
Primary Data Deduplication - Large Scale Study and System Design

We present a large scale study of primary data deduplication and use the findings to drive the design of a new primary data deduplication system implemented in the Windows Server 2012 operating system. File data was analyzed from 15 globally distributed file servers hosting data for over 2000 users in a large multinational corporation. The findings are used to arrive at a chunking and compression approach which maximizes deduplication savings while minimizing the generated metadata and producing a uniform chunk size distribution. Scaling of deduplication processing with data size is achieved using a RAM frugal chunk hash index and data partitioning - so that memory, CPU, and disk seek resources remain available to fulfill the primary workload of serving IO. We present the architecture of a new primary data deduplication system and evaluate the deduplication performance and chunking aspects of the system.
The Contribution of Parsing to Prosodic Phrasing in an Experimental Text-to-Speech System

While various aspects of syntactic structure have been shown to bear on the determination of phraselevel prosody, the text-to-speech field has lacked a robust working system to test the possible relations between syntax and prosody. We describe an implemented system which uses the deterministic parser Fidditch to create the input for a set of prosody rules. The prosody rules generate a prosody tree that specifies the location and relative strength of prosodic phrase boundaries. These specifications are converted to annotations for the Bell Labs text-to-speech system that dictate modulations in pitch and duration for the input sentence.We discuss the results of an experiment to determine the performance of our system. We are encouraged by an initial 5 percent error rate and we see the design of the parser and the modularity of the system allowing changes that will upgrade this rate.
Analysis of Self-Excitation in Turbine-Generators Induced by Static Blocking Filter

In the Tuoketuo project in North China, a phenomena of system destabilization was impressively recognized during the field test of the subsynchronous resonance (SSR) mitigation device, static blocking filter (SBF). This paper, with the test of the SBF device in the Tuoketuo project as the background, presents a comprehensive analysis to the nature of the system instability. The instability behavior is firstly validated by PSCAD/EMTDC simulation. Through insights into the mechanism of the phenomena, the instability is then determined as self-excitation in generators induced by SBF. To further investigate its characteristics, eigenvalues approach is adopted to analyse the effect of the SBF in-service and the sensitivity of self-excitation to generator parameters. Finally, possible countermeasures are proposed to mitigate this kind of self-excitation.
Unraveling transcriptome dynamics in human spermatogenesis

Spermatogenesis is a dynamic developmental process that includes stem cell proliferation and differentiation, meiotic cell divisions and extreme chromatin condensation. Although studied in mice, the molecular control of human spermatogenesis is largely unknown. Here, we developed a protocol that enables next-generation sequencing of RNA obtained from pools of 500 individually laser-capture microdissected cells of specific germ cell subtypes from fixed human testis samples. Transcriptomic analyses of these successive germ cell subtypes reveals dynamic transcription of over 4000 genes during human spermatogenesis. At the same time, many of the genes encoding for well-established meiotic and post-meiotic proteins are already present in the pre-meiotic phase. Furthermore, we found significant cell type-specific expression of post-transcriptional regulators, including expression of 110 RNA-binding proteins and 137 long non-coding RNAs, most of them previously not linked to spermatogenesis. Together, these data suggest that the transcriptome of precursor cells already contains the genes necessary for cellular differentiation and that timely translation controlled by post-transcriptional regulators is crucial for normal development. These established transcriptomes provide a reference catalog for further detailed studies on human spermatogenesis and spermatogenic failure. Highlighted Article: Using laser capture microscopy, a comprehensive transcriptomic dataset of well-defined and distinct germ cell subtypes based on morphology and localization in the human testis is generated.
Spin crossover in ferropericlase and velocity heterogeneities in the lower mantle

Significance Seismic tomography reveals Earth’s internal structure in great detail. Lateral variations of seismic wave velocities expose enigmatic mantle structures that, to be deciphered, require independent knowledge of acoustic velocities in minerals. Using density functional theory-based computational methods we show that a spin state change in iron in ferropericlase, the second major phase of the Earth’s lower mantle, produces seismic velocity anomalies that can be misinterpreted as compositional heterogeneity. This spin change reduces thermally induced longitudinal velocity variations between ∼1,500- and 2,000-km depths. This phenomenon is observed in P velocity tomography models and has been thought to be related to a chemical transition in the mantle. The spin change in iron in ferropericlase may offer an alternative interpretation of this phenomenon. Deciphering the origin of seismic velocity heterogeneities in the mantle is crucial to understanding internal structures and processes at work in the Earth. The spin crossover in iron in ferropericlase (Fp), the second most abundant phase in the lower mantle, introduces unfamiliar effects on seismic velocities. First-principles calculations indicate that anticorrelation between shear velocity (VS) and bulk sound velocity (Vφ) in the mantle, usually interpreted as compositional heterogeneity, can also be produced in homogeneous aggregates containing Fp. The spin crossover also suppresses thermally induced heterogeneity in longitudinal velocity (VP) at certain depths but not in VS. This effect is observed in tomography models at conditions where the spin crossover in Fp is expected in the lower mantle. In addition, the one-of-a-kind signature of this spin crossover in the RS/P (∂⁡ln⁡VS/∂⁡ln⁡VP) heterogeneity ratio might be a useful fingerprint to detect the presence of Fp in the lower mantle.
Robustness of n interdependent networks with partial support-dependence relationship

We study both analytically and numerically the robustness of n interdependent networks with partial support-dependence relationship, which reflects real-world networks more realistically. For a starlike network of n Erdős-Rényi (ER) networks, we find that the system undergoes from second-order to first-order phase transition as coupling strength q increases. Moreover, we notice that the region of the first-order transition becomes larger, while the region of the second-order transition becomes smaller as the number of networks n increases. However, for a starlike network of n scale-free (SF) networks, the system undergoes from second-order through hybrid-order to first-order phase transition as q increases. Furthermore, we also observe that the region of the first-order transition remains constant and appears only for q = 1, however, the region of hybrid-order transition gradually becomes larger and the region of the second-order transition becomes smaller as n increases. For a looplike network of n ER networks, we find the giant component p∞ to be independent of the number of networks. Additionally, when the average degree of networks increases, the region of the first-order transition becomes smaller and the region of the second-order transition becomes larger. For the case of n ER networks with partial support-dependence relationship, as average supported degree , n coupled networks become independent and only second-order transition is observed, which is similar to q = 0.
Estimation of Actual Evapotranspiration by Complementary Theory-Based Advection-Aridity Model in the Tarim River Basin, China

AbstractIn this study, the complementary relationship between actual evapotranspiration (ETa) and potential evapotranspiration (ETp) was verified in the Tarim River basin (TRB) in northwest China. The advection–aridity (AA) model that is based on the complementary relationship (CR) was used to calculate ETa. Spatial and temporal trends in the estimated annual ETa and the factors that influenced ETa were investigated. The multiyear average ETa in the TRB for the period from 1961 to 2014 was 178.5 mm. There was an overall significant increasing trend (at a rate of 10.6 mm decade−1) in ETa from 1961 to 2014; ETa increased at a rate of 22.9 mm decade−1 from 1961 to 1996 and decreased at a rate of 33.9 mm decade−1 from 1996 to 2014. Seasonally, ETa was strongest in summer, followed by spring and autumn. The spatial distributions of the annual and seasonal ETa were mostly consistent, with higher ETa values in the northeast, northwest, and southwest of the TRB, and lower ETa values in the mostly desert lands in .
Post Cold Frontal Clouds at the ARM Eastern North Atlantic Site: An Examination of the Relationship Between Large‐Scale Environment and Low‐Level Cloud Properties

Using cloud and environment observations from the Atmospheric Radiation Measurement (ARM) program Eastern North Atlantic site and an automated cold front detection routine, cloud properties in post cold front (PCF) periods are examined and compared to similar conditions of subsidence (non‐PCF). PCF periods exhibit stronger subsidence and wind speed than non‐PCF periods, with weaker inversions and stronger surface temperature contrasts. Low‐level clouds are predominant and are found to have higher cloud base and top heights, colder cloud top temperature, and greater vertical extent and liquid water path during PCF than non‐PCF periods. The environmental metric that is best correlated with cloud boundaries for both PCF and non‐PCF periods is the difference in potential temperature between the sea surface and 800 hPa, a parameter used to locate cold air outbreak conditions. However, the cloud vertical extent and liquid water path are found to be better correlated with sea‐air temperature contrast, a parameter related to turbulent surface fluxes. The strength of the relationships between the cloud characteristics and these metrics does not differ for PCF and non‐PCF periods. However, the strength of the metrics differs between PCF and non‐PCF periods and can explain cloud property differences. The results suggest both the properties of the boundary layer and the presence of an upper‐level cyclone associated with the cold front determine PCF cloud properties.
Computational assessment of drug-induced effects on the electrocardiogram: from ion channel to body surface potentials

Understanding drug effects on the heart is key to safety pharmacology assessment and anti‐arrhythmic therapy development. Here our goal is to demonstrate the ability of computational models to simulate the effect of drug action on the electrical activity of the heart, at the level of the ion‐channel, cell, heart and ECG body surface potential.
On the interactions between cellulose and xylan, a biomimetic simulation of the hardwood cell wall

The plant cell wall exhibits a hierarchical structure, in which the organization of the constituents on different levels strongly affects the mechanical properties and the performance of the material. In this work, the interactions between cellulose and xylan in a model system consisting of a bacterial cellulose/glucuronoxylan (extracted from aspen, Populus tremula) have been studied and compared to that of a delignified aspen fiber material. The properties of the materials were analyzed using Dynamical Mechanical Analysis (DMA) with moisture scans together with dynamic Infra Red -spectroscopy at dry and humid conditions. The results showed that strong interactions existed between the cellulose and the xylan in the aspen holocellulose. The same kinds of interactions were seen in a water-extracted bacterial cellulose/xylan composite, while unextracted material showed the presence of xylan not interacting with the cellulose. Based on these findings for the model system, it was suggested that there is in hardwood one fraction of xylan that is strongly associated with the cellulose, taking a similar role as glucomannan in softwood.
Alcohol Consumption and Visual Impairment in a Rural Northern Chinese Population

Abstract Purpose: To investigate alcohol drinking status and the association between drinking patterns and visual impairment in an adult population in northern China. Methods: Cluster sampling was used to select samples. The protocol consisted of an interview, pilot study, visual acuity (VA) testing and a clinical examination. Visual impairment was defined as presenting VA worse than 20/60 in any eye. Drinking patterns included drinking quantity (standard drinks per week) and frequency (drinking days in the past week) Results: Information on alcohol consumption was obtained from 8445 subjects, 963 (11.4%) of whom reported consuming alcohol. In multivariate analysis, alcohol consumption was significantly associated with older age (p < 0.001), male sex (p < 0.001), and higher education level (p < 0.01). Heavy intake (>14 drinks/week) was associated with higher odds of visual impairment. However, moderate intake (>1–14 drinks/week) was significantly associated with lower odds (adjusted odds ratio, OR, 0.7, 95% confidence interval, CI, 0.5–1.0) of visual impairment (p = 0.03). Higher drinking frequency was significantly associated with higher odds of visual impairment. Multivariate analysis showed that older age, male sex, and higher education level were associated with visual impairment among current drinkers. Age- and sex-adjusted ORs for the association of cataract and alcohol intake showed that higher alcohol consumption was not significantly associated with an increased prevalence of cataract (OR 1.2, 95% CI 0.4–3.6), whereas light and moderate alcohol consumption appeared to reduce incidence of cataract. Conclusion: Drinking patterns were associated with visual impairment. Heavy intake had negative effects on distance vision; meanwhile, moderate intake had a positive effect on distance vision.
Deletion of ARNT (Aryl Hydrocarbon Receptor Nuclear Translocator) in β-Cells Causes Islet Transplant Failure with Impaired β-Cell Function

Background Replacing β-cells by islet-transplantation can cure type 1 diabetes, but up to 70% of β-cells die within 10 days of transplantation. ARNT (Aryl hydrocarbon Receptor Nuclear Translocator) regulates β-cell function, and potentially survival. Lack of ARNT impairs the ability of β-cells to respond to physiological stress and potentiates the onset of diabetes, but the exact role of ARNT in graft outcome is unknown. Aim To investigate the effect of β-cell deletion of ARNT on graft outcomes. Methods Islets were isolated from donor mice which had β-cell specific ARNT-deletion (β-ARNT) or littermate floxed controls. The islets were transplanted into diabetic SCID recipients in ratios of (a) 3 donors: 1 recipient, (b) 1 donor: 1 recipient or (c) ½ of the islets from 1 donor: 1 recipient. After 28 days, the kidney containing the graft was removed (nephrectomy) to exclude regeneration of the endogenous pancreas. Results In the supra-physiological-mass model (3∶1), both groups achieved reasonable glycaemia, with slightly higher levels in β-ARNT-recipients. In adequate-mass model (1∶1), β-ARNT recipients had poor glucose control versus floxed-control recipients and versus the β-ARNT donors. In the low-β-cell-mass model (½:1) β-ARNT transplants completely failed, whereas controls had good outcomes. Unexpectedly, there was no difference in the graft insulin content or β-cell mass between groups indicating that the defect was not due to early altered β-cell survival. Conclusion Outcomes for islet transplants lacking β-cell ARNT were poor, unless markedly supra-physiological masses of islets were transplanted. In the 1∶1 transplant model, there was no difference in β-cell volume. This is surprising because transplants of islets lacking one of the ARNT-partners HIF-1α have increased apoptosis and decreased islet volume. ARNT also partners HIF-2α and AhR (aryl hydrocarbon receptor) to form active transcriptional complexes, and further work to understand the roles of HIF-2α and AhR in transplant outcomes is needed.