Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Susceptibility to Chronic Kidney Disease – Some More Pieces for the Heritability Puzzle

Chronic kidney disease (CKD) is a major global health problem with an increasing prevalence partly driven by aging population structure. Both genomic and environmental factors contribute to this complex heterogeneous disease. CKD heritability is estimated to be high (30–75%). Genome-wide association studies (GWAS) and GWAS meta-analyses have identified several genetic loci associated with CKD, including variants in UMOD, SHROOM3, solute carriers, and E3 ubiquitin ligases. However, these genetic markers do not account for all the susceptibility to CKD, and the causal pathways remain incompletely understood; other factors must be contributing to the missing heritability. Less investigated biological factors such as telomere length; mitochondrial proteins, encoded by nuclear genes or specific mitochondrial DNA (mtDNA) encoded genes; structural variants, such as copy number variants (CNVs), insertions, deletions, inversions and translocations are poorly covered and may explain some of the missing heritability. The sex chromosomes, often excluded from GWAS studies, may also help explain gender imbalances in CKD. In this review, we outline recent findings on molecular biomarkers for CKD (telomeres, CNVs, mtDNA variants, sex chromosomes) that typically have received less attention than gene polymorphisms. Shorter telomere length has been associated with renal dysfunction and CKD progression, however, most publications report small numbers of subjects with conflicting findings. CNVs have been linked to congenital anomalies of the kidney and urinary tract, posterior urethral valves, nephronophthisis and immunoglobulin A nephropathy. Information on mtDNA biomarkers for CKD comes primarily from case reports, therefore the data are scarce and diverse. The most consistent finding is the A3243G mutation in the MT-TL1 gene, mainly associated with focal segmental glomerulosclerosis. Only one GWAS has found associations between X-chromosome and renal function (rs12845465 and rs5987107). No loci in the Y-chromosome have reached genome-wide significance. In conclusion, despite the efforts to find the genetic basis of CKD, it remains challenging to explain all of the heritability with currently available methods and datasets. Although additional biomarkers have been investigated in less common suspects such as telomeres, CNVs, mtDNA and sex chromosomes, hidden heritability in CKD remains elusive, and more comprehensive approaches, particularly through the integration of multiple –“omics” data, are needed.
REGULATION OF cGMP SYNTHESIS IN CULTURED PODOCYTES BY VASOACTIVE HORMONES

The podocytes are highly differentiated cells playing a key role in glomerular filtration. Vasoactive factors including angiotensin II (Ang II) and cyclic guanosine 5' monophosphate (cGMP) are synthesized by these cells upon stimulation as well as in the basal state. In this study we have tested whether angiotensin II affects the total synthesis of cGMP in primary culture of rat podocytes. The cells were stimulated with atrial natriuretic peptide (ANP) and/or a nitric oxide (NO) donor, S-nitroso-Nacetyl penicillamine (SNAP), in the absence or presence of Ang II. The cGMP synthesis was determined by radioimmunoassay (RIA). ANP or SNAP alone increased the cGMP synthesis in podocytes although the effects were not additive unless Ang II was present in the medium. Ang II suppressed the ANP-dependent cGMP synthesis whereas SNAP-dependent cGMP production remained unaffected. These effects were prevented by a non-specific antagonist of Ang II receptors (AT), saralasin. Adversely, PD123319, a specific inhibitor of AT2 receptors, augmented inhibition of ANP-dependent and enhanced the NO-dependent cGMP production. Probenecid, an inhibitor of cGMP extrusion from the cells, suppressed the cGMP generation by both ANP and SNAP. We conclude that cGMP synthesis in cultured podocytes is modulated by angiotensin II and that two adversely acting receptors, AT1 and AT2 are involved in this effect. Additionally, production of cGMP might be intrinsically inhibited by cGMP accumulating inside the cells.
Stochastic scattering model for the application of SBR to rough surfaces

A large variety of simulation tools for calculating scattered fields have been published in literature. Basically, there are two main approaches, the so-called numerically exact or full-wave solutions, e.g. using Method of Moments (MoM), and the high-frequency or asymptotic solutions, e.g. using rays for modelling propagation paths. However, most of these simulation tools are limited to perfectly conducting surfaces or homogeneous dielectric bodies with ideally smooth surfaces. The present paper studies the enhancement of a ray tracing code based on the well-known Shooting-and-Bouncing-Rays (SBR) technique for calculating scattered fields of arbitrary objects, whose surfaces are characterised by roughness parameters.
Research on succession influencing factors in the family business

The purpose of this study was to better understand the succession of family business in China. The paper made the systemic analysis of the internal and external environment to explain the succession influencing factors in family business. Based on a review and analysis of the literature, the paper presents a model on the factors that influence the family business succession in China.
The Ectopic Expression of Meiosis Regulatory Genes in Cutaneous T-Cell Lymphomas (CTCL)

Cancer testis (CT) antigens, under normal circumstances are uniquely expressed in testicular germ cells. Recent research has shown that meiosis-specific CT (meiCT) antigens are ectopically expressed in cutaneous T-cell lymphoma (CTCL) and may contribute to increased genomic instability. The aberrant activation of meiosis genes in a mitotic cell is now recognized as a distinctive process, “meiomitosis. ” We have previously demonstrated the ectopic expression of several meiCT antigens in nine patient-derived CTCL cell lines and in expanded peripheral T lymphocytes isolated from Sézary Syndrome patients. In this study we analyzed the transcriptional expression of meiCT genes in Sézary Syndrome patients and healthy controls using publicly-available RNA sequencing (RNA-Seq) data. We corroborated our in silico analysis by examining the expression of 5 meiCT proteins in formalin-fixed, paraffin-embedded (FFPE) lesional samples from CTCL patients. Our results show significant differential gene expression of STAG3, SGO2, SYCP3, and DMC1 in a cohort of Sézary Syndrome patients when compared to healthy controls. Additionally, our study demonstrates a heterogenous expression of meiCT genes involved in initiation (STRA8), sister chromatin cohesion (STAG3, SGO2), homologous chromosome synapsis (SYCP3) and homologous recombination (DMC1) in atypical lymphocytes in FFPE samples. Our results further confirm the ectopic expression of meiCT genes in CTCL which indicates that CTCL malignant cells likely undergo the process of cancer meiomitosis, as opposed to a typical mitotic division. The ectopic expression of meiCT genes together with investigations into the functional mechanisms of cancer meiomitosis will help provide a foundation to develop novel diagnostic tests to distinguish CTCL from benign inflammatory dermatoses and may enable us to develop additional targeted therapies for patients with this malignancy.
Effective Medical Test Suggestions Using Deep Reinforcement Learning

Effective medical test suggestions benefit both patients and physicians to conserve time and improve diagnosis accuracy. In this work, we show that an agent can learn to suggest effective medical tests. We formulate the problem as a stage-wise Markov decision process and propose a reinforcement learning method to train the agent. We introduce a new representation of multiple action policy along with the training method of the proposed representation. Furthermore, a new exploration scheme is proposed to accelerate the learning of disease distributions. Our experimental results demonstrate that the accuracy of disease diagnosis can be significantly improved with good medical test suggestions.
Reversible Electrochemical Phase Change in Monolayer to Bulk-Like MoTe2 by Ionic Liquid Gating.

Transition metal dichalcogenides (TMDs) exist in various crystal structures with semiconducting, semi-metallic, and metallic properties. The dynamic control of these phases is of immediate interest for next generation electronics such as phase change memories. Of the binary Mo and W-based TMDs, MoTe2 is attractive for electronic applications because it has the lowest energy difference (40 meV) between the semiconducting (2H) and semi-metallic (1T') phases, allowing for MoTe2 phase change by electrostatic doping. Here we report phase change between the 2H and 1T' polymorphs of MoTe2 in thicknesses ranging from the monolayer to bulk-like case (73 nm) using an ionic liquid electrolyte at room temperature and in air. We find consistent evidence of a partially reversible 2H-1T' transition using in-situ Raman spectroscopy where the phase change occurs in the top-most layers of the MoTe2 flake. We find a thickness-dependent transition voltage where higher voltages are necessary to drive the phase change for thicker flakes. We also show evidence of electrochemical activity during the gating process by observation of Te metal formation. This finding suggests the formation of Te vacancies which have been reported to lower the energy difference between the 2H and 1T' phase, potentially aiding the phase change process. Our discovery that the phase change can be achieved on the surface layer of bulk-like materials reveals that this electrochemical mechanism does not require isolation of a single layer and the effect may be more broadly applicable than previously thought.
Cytokinin Transporters: Multisite Players in Cytokinin Homeostasis and Signal Distribution

Cytokinins (CKs) are a group of mobile adenine derivatives that act as chemical signals regulating a variety of biological processes implicated in plant development and stress responses. Their synthesis, homeostasis, and signaling perception evoke complicated intracellular traffic, intercellular movement, and in short- and long-distance translocation. Over nearly two decades, subsets of membrane transporters have been recognized and implicated in the transport of CKs as well as the related adenylates. In this review, we aim to recapitulate the key progresses in exploration of the transporter proteins involved in cytokinin traffic and translocation, discuss their functional implications in the cytokinin-mediated paracrine and long-distance communication, and highlight some knowledge gaps and open issues toward comprehensively understanding the molecular mechanism of membrane transporters in controlling spatiotemporal distribution of cytokinin species.
Tubulin-VDAC Interaction: Molecular Basis for Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy

Tubulin is a well-established target of microtubule-targeting agents (MTAs), a widely used class of chemotherapeutic drugs. Yet, aside from their powerful anti-cancer efficiency, MTAs induce a dose-limiting and debilitating peripheral neurotoxicity. Despite intensive efforts in the development of neuroprotective agents, there are currently no approved therapies to effectively manage chemotherapy-induced peripheral neuropathy (CIPN). Over the last decade, attempts to unravel the pathomechanisms underlying the development of CIPN led to the observation that mitochondrial dysfunctions stand as a common feature associated with axonal degeneration. Concomitantly, mitochondria emerged as crucial players in the anti-cancer efficiency of MTAs. The findings that free dimeric tubulin could be associated with mitochondrial membranes and interact directly with the voltage-dependent anion channels (VDACs) located in the mitochondrial outer membrane strongly suggested the existence of an interplay between both subcellular compartments. The biological relevance of the interaction between tubulin and VDAC came from subsequent in vitro studies, which found dimeric tubulin to be a potent modulator of VDAC and ultimately of mitochondrial membrane permeability to respiratory substrates. Therefore, one of the hypothetic mechanisms of CIPN implies that MTAs, by binding directly to the tubulin associated with VDAC, interferes with mitochondrial function in the peripheral nervous system. We review here the foundations of this hypothesis and discuss them in light of the current knowledge. A focus is set on the molecular mechanisms behind MTA interference with dimeric tubulin and VDAC interaction, the potential relevance of tubulin isotypes and availability as a free dimer in the specific context of MTA-induced CIPN. We further highlight the emerging interest for VDAC and its interacting partners as a promising therapeutic target in neurodegeneration.
Bayesian Grasp: Robotic visual stable grasp based on prior tactile knowledge

Robotic grasp detection is a fundamental capability for intelligent manipulation in unstructured environments. Previous work mainly employed visual and tactile fusion to achieve stable grasp, while, the whole process depending heavily on regrasping, which wastes much time to regulate and evaluate. We propose a novel way to improve robotic grasping: by using learned tactile knowledge, a robot can achieve a stable grasp from an image. First, we construct a prior tactile knowledge learning framework with novel grasp quality metric which is determined by measuring its resistance to external perturbations. Second, we propose a multi-phases Bayesian Grasp architecture to generate stable grasp configurations through a single RGB image based on prior tactile knowledge. Results show that this framework can classify the outcome of grasps with an average accuracy of 86% on known objects and 79% on novel objects. The prior tactile knowledge improves the successful rate of 55% over traditional vision-based strategies.
Samp1 is functionally associated with the LINC complex and A-type lamina networks

The transmembrane inner nuclear membrane (INM) protein Samp1 is required for anchoring centrosomes near the nuclei. Using high-resolution fluorescence microscopy we show that Samp1 is distributed in a distinct and characteristic pattern in the nuclear envelope (NE), where it partially colocalizes with the LINC complex protein Sun1. By studying the localization of Samp1 deletion mutants and fusion proteins, we conclude that the cysteine-rich N-terminal half of Samp1 is nucleoplasmically exposed and is responsible for targeting to the INM. It contains four conserved CxxC motifs with the potential to form zinc fingers. The distribution of cysteine-to-alanine substitution mutants, designed to prevent zinc finger formation, showed that NE localization of Samp1 depends on intact CxxC motifs. Overexpression of Samp1 zinc finger mutants produced an abnormal dominant phenotype characterized by disrupted organization of a selective subset NE proteins, including emerin, Sun1, endogenous Samp1 and, in some cases, lamin A/C, but not lamin B, Sun2 or nucleoporins. Silencing of Samp1 expression showed that emerin depends on Samp1 for its correct localization in the NE. Our results demonstrate that Samp1 is functionally associated with the LINC complex protein Sun1 and proteins of the A-type lamina network.
Heterogeneous causal effects with imperfect compliance: a novel Bayesian machine learning approach

This paper introduces an innovative Bayesian machine learning algorithm to draw inference on heterogeneous causal effects in the presence of imperfect compliance (e.g., under an irregular assignment mechanism). We show, through Monte Carlo simulations, that the proposed Bayesian Causal Forest with Instrumental Variable (BCF-IV) algorithm outperforms other machine learning techniques tailored for causal inference (namely, Generalized Random Forest and Causal Trees with Instrumental Variable) in estimating the causal effects. Moreover, we show that it converges to an optimal asymptotic performance in discovering the drivers of heterogeneity in a simulated scenario. BCF-IV sheds a light on the heterogeneity of causal effects in instrumental variable scenarios and, in turn, provides the policy-makers with a relevant tool for targeted policies. Its empirical application evaluates the effects of additional funding on students' performances. The results indicate that BCF-IV could be used to enhance the effectiveness of school funding on students' performance by 3.2 to 3.5 times.
Antimicrobial Susceptibility of Group B Streptococci Isolated from a Variety of Clinical Sources

The minimal inhibitory concentration of 10 antibiotics for 244 isolates of group B streptococci was determined. Susceptibility to penicillin G, ampicillin, cephalothin, chloramphenicol, and carbenicillin was uniform. Tetracycline and bacitracin resistance among these isolates was frequent (87.5 and 97.9%, respectively). Three strains (1.2%) failed to be inhibited by 100 μg of lincomycin or clindamycin per ml. Susceptibility of these 244 strains to the agents tested was unrelated to source of the isolate, year of isolation, or strain serotype. No apparent change in the suceptibility of group B streptococci to penicillin G has occurred during the past 2 decades.
Improving Clinical Manufacturing of IL-15 Activated Cytokine-Induced Killer (CIK) Cells

Cytokine-induced killer (CIK) cells are an immunotherapeutic approach to combat relapse following allogeneic hematopoietic stem cell transplantation (HSCT) in acute leukemia or myelodysplastic syndrome (MDS) patients. Prompt and sequential administration of escalating cell doses improves the efficacy of CIK cell therapy without exacerbating graft vs. host disease (GVHD). This study addresses manufacturing-related issues and aimed to develop a time-, personal- and cost-saving good manufacturing process (GMP)-compliant protocol for the generation of ready-for-use therapeutic CIK cell doses starting from one unstimulated donor-derived peripheral blood (PB) or leukocytapheresis (LP) products. Culture medium with or without the addition of either AB serum, fresh frozen plasma (FFP) or platelet lysate (PL) was used for culture. Fresh and cryopreserved CIK cells were compared regarding expansion rate, viability, phenotype, and ability to inhibit leukemia growth. Cell numbers increased by a median factor of 10-fold in the presence of FFP, PL, or AB serum, whereas cultivation in FFP/PL-free or AB serum-free medium failed to promote adequate CIK cell proliferation (p < 0.01) needed to provide clinical doses of 1 × 106 T cells/kG, 5 × 106 T cells/kG, 1 × 107 T cells/kG, and 1 × 108 T cells/kG recipient body weight. CIK cells consisting of T cells, T- natural killer (T-NK) cells and a minor fraction of NK cells were not significantly modified by different medium supplements. Moreover, neither cytotoxic potential against leukemic THP-1 cells nor cell activation shown by CD25 expression were significantly influenced. Moreover, overnight and long-term cryopreservation had no significant effect on the composition of CIK cells, their phenotype or cytotoxic potential. A viability of almost 93% (range: 89–96) and 89.3% (range: 84–94) was obtained after freeze-thawing procedure and long-term storage, respectively, whereas viability was 96% (range: 90-97) in fresh CIK cells. Altogether, GMP-complaint CIK cell generation from an unstimulated donor-derived PB or LP products was feasible. Introducing FFP, which is easily accessible, into CIK cell cultures was time- and cost-saving without loss of viability and potency in a 10-12 day batch culture. The feasibility of cryopreservation enabled storage and delivery of sequential highly effective ready-for-use CIK cell doses and therefore reduced the number of manufacturing cycles.
Jet Power of Jetted Active Galactic Nuclei: Implications for Evolution and Unification

We construct samples of jetted active galactic nuclei (AGNs) with low-frequency radio data from the recently released TGSS AD1 catalog at 150 MHz. With these samples, we compare the properties of jet power for blazars, radio-loud narrow-line Seyfert 1 galaxies (RL-NLS1s), young radio sources (YRSs), and radio galaxies. The jet–disk connection, and the unification of jetted AGNs are explored. On the Eddington ratio–Eddington-scaled jet power plane, jetted AGNs can generally be divided into two populations. Low power radio galaxies, low excitation FR IIs (LEG/FR IIs), and most YRSs show larger jet power than accretion power, while on the contrary FSRQs, RL-NLS1s, and high excitation FR IIs (HEG/FR IIs) show larger accretion power than jet power. LEG/FR IIs share similar jet power properties with HEG/FR IIs, while their accretion properties are different from the latter. These facts suggest an evolutional sequence from HEG/FR IIs, LEG/FR IIs to FR Is, where the accretion and jet activities get dimmed gradually. LEG/FR IIs are the transitional objects that accretion processes have switched off, while jets are still active. After correcting the contribution from the radio core of blazars, the unification between blazars and radio galaxies is confirmed with the jet power distributions. The unification that involved RL-NLS1s is more complicated than the simple scenarios of black hole growth or orientation effect. In addition, our results manifest that low synchrotron peaked BL Lac objects (LBLs) contain two distinct groups regarding the distribution of jet power, with one group being similar to FSRQs and the other similar to intermediate synchrotron peaked BL Lac objects. The LBLs with higher jet powers might be the aligned counterparts of LEG/FR IIs.
Online Markov Decoding: Lower Bounds and Near-Optimal Approximation Algorithms

We resolve the fundamental problem of online decoding with general $n^{th}$ order ergodic Markov chain models. Specifically, we provide deterministic and randomized algorithms whose performance is close to that of the optimal offline algorithm even when latency is small. Our algorithms admit efficient implementation via dynamic programs, and readily extend to (adversarial) non-stationary or time-varying settings. We also establish lower bounds for online methods under latency constraints in both deterministic and randomized settings, and show that no online algorithm can perform significantly better than our algorithms. Empirically, just with latency one, our algorithm outperforms the online step algorithm by over 30\% in terms of decoding agreement with the optimal algorithm on genome sequence data.
Ultrasensitive Optical Detection of Water Pressure in Microfluidics Using Smart Reduced Graphene Oxide Glass

Despite recent progresses in the field of microfluidics, the effect of liquid pressure on the detection accuracy has been rarely studied. Here, we perform a quantitative analysis of such effect, by utilizing the sensitive optical responses of graphene to the refractive index (RI) change of its surrounding environment. We utilize a reflection coupling configuration by combining the total internal reflection (TIR) and ultrasonic waves. The high-performance graphene is processed on common glasses by using the solution-processable oxidation-reduction method. We find that the RI change of water caused by a pressure as small as 500 Pa generated by the liquid level change in the microfluidics can be measured directly. The detection accuracy and response time limits are approximately 280 Pa and 100 ns, respectively. The Maxwell's boundary conditions, Fresnel's law, and Pascal's law are used in theoretical analyses. This work highlights the importance of liquid pressure in microfluidics and provides guidance in designing and accurate detection of microfluidic devices.