Miracle-dz/UniFAR-FTUs huggingface dataset:
Key Triggers of Osteoclast-Related Diseases and Available Strategies for Targeted Therapies: A Review

Osteoclasts, the only cells with bone resorption functions in vivo, maintain the balance of bone metabolism by cooperating with osteoblasts, which are responsible for bone formation. Excessive activity of osteoclasts causes many diseases such as osteoporosis, periprosthetic osteolysis, bone tumors, and Paget’s disease. In contrast, osteopetrosis results from osteoclast deficiency. Available strategies for combating over-activated osteoclasts and the subsequently induced diseases can be categorized into three approaches: facilitating osteoclast apoptosis, inhibiting osteoclastogenesis, and impairing bone resorption. Bisphosphonates are representative molecules that function by triggering osteoclast apoptosis. New drugs, such as tumor necrosis factor and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (e.g., denosumab) have been developed for targeting the receptor activator of nuclear factor kappa-B /RANKL/osteoprotegerin system or CSF-1/CSF-1R axis, which play critical roles in osteoclast formation. Furthermore, vacuolar (H+)-ATPase inhibitors, cathepsin K inhibitors, and glucagon-like peptide 2 impair different stages of the bone resorption process. Recently, significant achievements have been made in this field. The aim of this review is to provide an updated summary of the current progress in research involving osteoclast-related diseases and of the development of targeted inhibitors of osteoclast formation.
A pivotal role of cell‐bound but not soluble CD4 molecules in full development of lupus‐like manifestations in MRL‐Faslprcg/Faslprcg mice

The role of CD4 molecules in the autoimmune and lymphoproliferative syndrome caused by murine Fas mutations was studied using the novel systemic lupus erythematosus (SLE) model, MRL‐Faslprcg/Faslprcg (MRL‐lprcg) mice, in combination with the novel mutant CD4 gene producing soluble CD4 (sCD4) instead of membrane‐bound CD4 (mCD4). For this purpose, various autoimmune manifestations were compared among MRL‐lprcg mice homozygous (CD4slprcg), heterozygous (CD4s/mlprcg), and wild‐type (CD4mlprcg) for the CD4 mutation. The mortality, glomerulonephritis, proteinuria, and lymphadenopathy were significantly ameliorated in CD4slprcg compared with CD4mlprcg and CD4s/mlprcg mice, both being comparable in these clinical characteristics. In parallel with the clinical improvement, the serum levels of immunoglobulin, anti‐DNA antibodies, anti‐nuclear antibodies and immune complexes, and the extent of glomerular immune deposition, were significantly lower in the former. The results indicate that mCD4 is important and can not be replaced by sCD4 in full development of SLE‐like manifestations, and suggest that CD4+ T cells may aggravate the autoimmune disease by stimulating autoreactive B cells to produce autoantibodies through their helper activity in Fas mutant models. The sCD4 levels in the serum and spleen elevated with the increased accumulation of B220+CD4−CD8− (double‐negative (DN)) T cells in CD4slprcg mice. This, together with the significantly milder lymphadenopathy associated with lower DN T cell contents in CD4slprcg than CD4mlprcg mice, implies that some of abnormal DN T cells may be derived from cells of the CD4 lineage.
Signal processing system of intelligent sensor with nonlinear characteristic

The scheme of signal processing system of intelligent sensor which does not require the inclusion of devices such as a microprocessor, microcontroller or programmable logic controller is described. When using the scheme of linearization in this sensor, the relative conversion error that is caused by elements such as resistors, capacitors and op-amp can be as low as one hundredth of a percent.
Epidemiologic Relationships Between A1C and All-Cause Mortality During a Median 3.4-Year Follow-up of Glycemic Treatment in the ACCORD Trial

OBJECTIVE Randomized treatment comparing an intensive glycemic treatment strategy with a standard strategy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was ended early because of an unexpected excess of mortality in the intensive arm. As part of ongoing post hoc analyses of potential mechanisms for this finding, we explored whether on-treatment A1C itself had an independent relationship with mortality. RESEARCH DESIGN AND METHODS Participants with type 2 diabetes (n = 10,251 with mean age 62 years, median duration of diabetes 10 years, and median A1C 8.1%) were randomly assigned to treatment strategies targeting either A1C <6.0% (intensive) or A1C 7.0–7.9% (standard). Data obtained during 3.4 (median) years of follow-up before cessation of intensive treatment were analyzed using several multivariable models. RESULTS Various characteristics of the participants and the study sites at baseline had significant associations with the risk of mortality. Before and after adjustment for these covariates, a higher average on-treatment A1C was a stronger predictor of mortality than the A1C for the last interval of follow-up or the decrease of A1C in the first year. Higher average A1C was associated with greater risk of death. The risk of death with the intensive strategy increased approximately linearly from 6–9% A1C and appeared to be greater with the intensive than with the standard strategy only when average A1C was >7%. CONCLUSIONS These analyses implicate factors associated with persisting higher A1C levels, rather than low A1C per se, as likely contributors to the increased mortality risk associated with the intensive glycemic treatment strategy in ACCORD.
Design considerations of a brushless open-slot radial-flux PM hub motor

Initial sizing of a brushless radial-flux permanent magnet (PM) machine is typically based on assumptions regarding the electric- and magnetic- loading together with the motor's active volume. Additional design assumptions include the winding current density and magnetic flux density within the core pack. These initial design decisions are crucial as they largely define the resultant electromagnetic and thermal behaviour of the motor. The general rules regarding the choice of the initial design parameters are well known. However, the effects of the initial sizing on the final motor performance are not widely reported. This paper presents an analysis of design considerations for a brushless open-slot radial-flux PM hub-motor. A number of alternative motor designs are compared to demonstrate the effect of the initial design decisions on final motor performance. Both the electromagnetic and thermal aspects of the motor design are considered. The design variants are characterised by the same electric- and magnetic- loading together with active volume while the winding rated current density and no-load/open-circuit magnetic flux density within the core pack are varied. The employed sizing methodology combines the classical approach with a non-linear magneto-static finite element solver and an optimisation routine. A prototype hub-motor has been manufactured to validate the theoretical findings from the design process. The experimental data shows good agreement with the theoretical findings.
Optimized fast Walsh-Hadamard transform on OpenCL-GPU and OpenCL-CPU

The Walsh-Hadamard transform plays a major role in many image and video coding algorithms. In one hand, its intensive use in these algorithms makes its acceleration a challenge, in order to speed-up the algorithm execution. On the other hand, the available fast implementations are not efficient across different platforms. In this work, a parallel-based implementation of the WHT is proposed for CPU and GPU platforms using the OpenCL standard. OpenCL achieves portability at code level, but its performance suffers when the same code is used for CPUs and GPUs. To achieve top performance, we propose two WHT versions: OpenCL-GPU for GPUs and OpenCL-CPU for CPUs. Broadly, OpenCL-GPU executed on a GPU runs faster than OpenCL-CPU executed on a multicore CPU, with speedups that range from 120.87 to 1016.35. However, OpenCL-GPU performance drops substantially when ran on a multicore CPU machine, where OpenCL-CPU achieves higher performance, as it exploits the OpenCL support for SIMD instructions.
Arsenic–glutathione complexes—their stability in solution and during separation by different HPLC modes

Complexes of arsenic compounds and glutathione are believed to play an essential part in the metabolism and transport of inorganic arsenic and its methylated species. Up to now, the evidence of their presence is mostly indirect. We studied the stability and chromatographic behaviour of glutathione complexes with trivalent arsenic: i.e. AsIII(GS)3, MAIII(GS)2 and DMAIII(GS) under different conditions. Standard ion chromatography using PRP X-100 and carbonate or formic acid buffer disintegrated the complexes, while all three complexes are stable and separable by reversed phase chromatography (0.1% formic acid/acetonitrile gradient). AsIII(GS)3 and MAIII(GS)2 were more stable than DMAIII(GS), which even under optimal conditions tended to degrade on the column at 25 °C. Chromatography at 6 °C can retain the integrity of the samples. These results shed more light on the interpretation of a vast number of previously published arsenic speciation studies, which have used chromatographic separation techniques with the assumption that the integrity of the arsenic species is guaranteed.
ATP-dependent interaction of the cytosolic domains of the inwardly rectifying K+ channel Kir6.2 revealed by fluorescence resonance energy transfer

ATP-sensitive K+ (KATP) channels play important roles in the regulation of membrane excitability in many cell types. ATP inhibits channel activity by binding to a specific site formed by the N and C termini of the pore-forming subunit, Kir6.2, but the structural changes associated with this interaction remain unclear. Here, we use fluorescence resonance energy transfer (FRET) to study the ATP-dependent interaction between the N and C termini of Kir6.2 using a construct bearing fused cyan and yellow fluorescent proteins (ECFP-Kir6.2-EYFP). When expressed in human embryonic kidney cells, ECFP-Kir6.2-EYFP/SUR1 channels displayed FRET that was augmented by agonist stimulation and diminished by metabolic poisoning. Addition of ATP to permeabilized cells or isolated plasma membrane sheets increased FRET. FRET changes were abolished by Kir6.2 mutations that altered ATP-dependent channel closure and channel gating. In the wild-type channel, the ATP concentrations, which increased FRET (EC50 = 1.36 mM), were significantly higher than those causing channel inhibition (IC50 = 0.29 mM). Demonstrating the existence of intermolecular interactions, a dimeric construct comprising two molecules of Kir6.2 linked head-to-tail (ECFP-Kir6.2-Kir6.2-EYFP) displayed less FRET than the monomer in the absence of nucleotide but still exhibited ATP-dependent FRET increases (EC50 = 1.52 mM) and channel inhibition. We conclude that binding of ATP to Kir6.2, (i) alters the interaction between the N- and C-terminal domains, (ii) probably involves both intrasubunit and intersubunit interactions, (iii) reflects ligand binding not channel gating, and (iv) occurs in intact cells when subplasmalemmal [ATP] changes in the millimolar range.
Inertial particle focusing in parallel microfluidic channels for high-throughput filtration

In this study, we introduce inertial microfluidics in straight, parallel channels for high-throughput particle filtration. We show that particles flowing through low aspect ratio rectangular microchannels can be focused into four particle streams, distributed at the centers of each wall face, or into two particle streams, at the centers of the longest channel walls, depending on the particles' size. For high-throughput filtration, we fabricated scalable, single inlet and two outlet, parallel channel microdevices, using a high-density 3D microfluidic PDMS channel manufacturing technology, in a design that allows for easy integration with other downstream on-chip functions we recently described. We demonstrate filtration of 24 µm particles from a suspension mixture in a microdevice with four parallel channels. The filtration efficiency at a non-optimized flow rate of 0.8 ml/min was 82%.
Vascular Endothelial Growth Factor-C Stimulates the Migration and Proliferation of Kaposi’s Sarcoma Cells*

Recent evidence suggesting vascular endothelial growth factor-C (VEGF-C), which is a regulator of lymphatic and vascular endothelial development, raised the question whether this molecule could be involved in Kaposi’s sarcoma (KS), a strongly angiogenic and inflammatory tumor often associated with infection by human immunodeficiency virus-1. This disease is characterized by the presence of a core constituted of three main populations of “spindle” cells, having the features of lymphatic/vascular endothelial cells, macrophagic/dendritic cells, and of a mixed macrophage-endothelial phenotype. In this study we evaluated the biological response of KS cells to VEGF-C, using an immortal cell line derived from a KS lesion (KS IMM), which retains most features of the parental tumor and can induce KS-like sarcomas when injected subcutaneously in nude mice. We show that VEGFR-3, the specific receptor for VEGF-C, is expressed by KS IMM cells grown in vitro and in vivo. In vitro, VEGF-C induces the tyrosine phosphorylation of VEGFR-2, a receptor also for VEGF-A, as well as that of VEGFR-3. The activation of these two receptors in KS IMM cells is followed by a dose-responsive mitogenic and motogenic response. The stimulation of KS IMM cells with a mutant VEGF-C unable to bind and activate VEFGR-2 resulted in no proliferative response and in a weak motogenic stimulation, suggesting that VEGFR-2 is essential in transducing a proliferative signal and cooperates with VEGFR-3 in inducing cell migration. Our data add new insights on the pathogenesis of KS, suggesting that the involvement of endothelial growth factors may not only determine KS-associated angiogenesis, but also play a critical role in controlling KS cell growth and/or migration and invasion.
Iterative Soft/Hard Thresholding With Homotopy Continuation for Sparse Recovery

In this note, we analyze an iterative soft/hard thresholding algorithm with homotopy continuation for recovering a sparse signal <inline-formula><tex-math notation="LaTeX">$x^{\dagger}$</tex-math></inline-formula> from noisy data of a noise level <inline-formula><tex-math notation="LaTeX">$\epsilon$</tex-math></inline-formula>. Under suitable regularity and sparsity conditions, we design a path, along which the algorithm can find a solution <inline-formula> <tex-math notation="LaTeX">$x^*$</tex-math></inline-formula>, which admits a sharp reconstruction error <inline-formula> <tex-math notation="LaTeX">$\Vert x^* - x^{\dagger} \Vert _{\ell ^\infty } = O(\epsilon)$</tex-math></inline-formula> with an iteration complexity <inline-formula><tex-math notation="LaTeX">$O(\frac{\ln \epsilon }{\ln \gamma } np)$ </tex-math></inline-formula>, where <inline-formula><tex-math notation="LaTeX">$n$</tex-math></inline-formula> and <inline-formula><tex-math notation="LaTeX">$p$</tex-math></inline-formula> are problem dimensionality and <inline-formula><tex-math notation="LaTeX">$\gamma \in (0,1)$</tex-math></inline-formula> controls the length of the path. Numerical examples are given to illustrate its performance.
A heterochromatin protein 1 homologue in Caenorhabditis elegans acts in germline and vulval development

Proteins of the highly conserved heterochromatin protein 1 (HP1) family have been found to function in the dynamic organization of nuclear architecture and in gene regulation throughout the eukaryotic kingdom. In addition to being key players in heterochromatin‐mediated gene silencing, HP1 proteins may also contribute to the transcriptional repression of euchromatic genes via the recruitment to specific promoters. To investigate the role played by these different activities in specific developmental pathways, we identified HP1 homologues in the genome of Caenorhabditis elegans and used RNA‐mediated interference to study their function. We show that one of the homologues, HPL‐2, is required for the formation of a functional germline and for the development of the vulva by acting in an Rb‐related pathway. We suggest that, by acting as repressors of gene expression, HP1 proteins may fulfil specific functions in both somatic and germline differentiation processes throughout development.
Human Pluripotent Stem Cell-Derived Cardiomyocytes: Response to TTX and Lidocain Reveals Strong Cell to Cell Variability

Stem cell derived cardiomyocytes generated either from human embryonic stem cells (hESC-CMs) or human induced pluripotent stem cells (hiPSC-CMs) hold great promise for the investigation of early developmental processes in human cardiomyogenesis and future cell replacement strategies. We have analyzed electrophysiological properties of hESC-CMs (HES2) and hiPSC-CMs, derived from reprogrammed adult foreskin fibroblasts that have previously been found to be highly similar in terms of gene expression. In contrast to the similarity found in the expression profile we found substantial differences in action potentials (APs) and sodium currents at late stage (day 60) of in vitro differentiation with higher sodium currents in hiPSC-CMs. Sensitivity to lidocain was considerably reduced in hESC-CMs as compared to hiPSC-CMs, and the effect could not be explained by differences in beating frequency. In contrast, sensitivity to tetrodotoxin (TTX) was higher in hESC-CMs suggesting different contributions of TTX-sensitive and TTX-resistant sodium channels to AP generation. These data point to physiological differences that are not necessarily detected by genomics. We conclude that novel pharmacological screening-assays using hiPSC-CMs need to be applied with some caution.
Learning object-level impedance control for robust grasping and dexterous manipulation

Object-level impedance control is of great importance for object-centric tasks, such as robust grasping and dexterous manipulation. Despite the recent progress on this topic, how to specify the desired object impedance for a given task remains an open issue. In this paper, we decompose the object's impedance into two complementary components-the impedance for stable grasping and impedance for object manipulation. Then, we present a method to learn the desired object's manipulation impedance (stiffness) using data obtained from human demonstration. The approach is validated in two tasks, for robust grasping of a wine glass and for inserting a bulb, using the 16 degrees of freedom Allegro Hand mounted with the SynTouch tactile sensors.
Evolution of mortality over time in patients receiving mechanical ventilation.

RATIONALE Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear. OBJECTIVES To estimate whether mortality in mechanically ventilated patients has changed over time. METHODS Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models. MEASUREMENTS AND MAIN RESULTS We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80-0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67-0.92). CONCLUSIONS Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved. Clinical trials registered with www.clinicaltrials. gov (NCT01093482).
Application of the dq0 transformation in the three-phase grid-connected PV systems with active and reactive power control

This paper presents a three-phase grid-connected photovoltaic generation system with unity power factor for any situation of solar radiation. The model of the PWM inverter and a control strategy using dq0 transformation are proposed. The system operates as an active filter capable of compensate harmonic components and reactive power, generated by the other loads connected to the system. An input voltage clamping technique is proposed to control the power between the grid and photovoltaic system, where it is intended to achieve the maximum power point operation. Simulation results and analyses are presented to validate the proposed methodology for grid connected photovoltaic generation system.
An Updated Geophysical Model for AMSR-E and SSMIS Brightness Temperature Simulations over Oceans

In this study, we considered the geophysical model for microwave brightness temperature (BT) simulation for the Atmosphere-Ocean System under non-precipitating conditions. The model is presented as a combination of atmospheric absorption and ocean emission models. We validated this model for two satellite instruments—for Advanced Microwave Sounding Radiometer-Earth Observing System (AMSR-E) onboard Aqua satellite and for Special Sensor Microwave Imager/Sounder (SSMIS) onboard F16 satellite of Defense Meteorological Satellite Program (DMSP) series. We compared simulated BT values with satellite BT measurements for different combinations of various water vapor and oxygen absorption models and wind induced ocean emission models. A dataset of clear sky atmospheric and oceanic parameters, collocated in time and space with satellite measurements, was used for the comparison. We found the best model combination, providing the least root mean square error between calculations and measurements. A single combination of models ensured the best results for all considered radiometric channels. We also obtained the adjustments to simulated BT values, as averaged differences between the model simulations and satellite measurements. These adjustments can be used in any research based on modeling data for removing model/calibration inconsistencies. We demonstrated the application of the model by means of the development of the new algorithm for sea surface wind speed retrieval from AMSR-E data.