Miracle-dz/UniFAR-FTUs huggingface dataset:
Tnni3k alleles influence ventricular mononuclear diploid cardiomyocyte frequency

Recent evidence implicates mononuclear diploid cardiomyocytes as a proliferative and regenerative subpopulation of the postnatal heart. The number of these cardiomyocytes is a complex trait showing substantial natural variation among inbred mouse strains based on the combined influences of multiple polymorphic genes. One gene confirmed to influence this parameter is the cardiomyocyte-specific kinase Tnni3k. Here, we have studied Tnni3k alleles across a number of species. Using a newly-generated kinase-dead allele in mice, we show that Tnni3k function is dependent on its kinase activity. In an in vitro kinase assay, we show that several common human TNNI3K kinase domain variants substantially compromise kinase activity, suggesting that TNNI3K may influence human heart regenerative capacity and potentially also other aspects of human heart disease. We show that two kinase domain frameshift mutations in mice cause loss-of-function consequences by nonsense-mediated decay. We further show that the Tnni3k gene in two species of mole-rat has independently devolved into a pseudogene, presumably associated with the transition of these species to a low metabolism and hypoxic subterranean life. This may be explained by the observation that Tnni3k function in mice converges with oxidative stress to regulate mononuclear diploid cardiomyocyte frequency. Unlike other studied rodents, naked mole-rats have a surprisingly high (30%) mononuclear cardiomyocyte level but most of their mononuclear cardiomyocytes are polyploid; their mononuclear diploid cardiomyocyte level (7%) is within the known range (2–10%) of inbred mouse strains. Naked mole-rats provide further insight on a recent proposal that cardiomyocyte polyploidy is associated with evolutionary acquisition of endothermy.
Preeclampsia: Risk Factors, Diagnosis, Management, and the Cardiovascular Impact on the Offspring

Hypertensive disorders of pregnancy affect up to 10% of pregnancies worldwide, which includes the 3%–5% of all pregnancies complicated by preeclampsia. Preeclampsia is defined as new onset hypertension after 20 weeks’ gestation with evidence of maternal organ or uteroplacental dysfunction or proteinuria. Despite its prevalence, the risk factors that have been identified lack accuracy in predicting its onset and preventative therapies only moderately reduce a woman’s risk of preeclampsia. Preeclampsia is a major cause of maternal morbidity and is associated with adverse foetal outcomes including intra-uterine growth restriction, preterm birth, placental abruption, foetal distress, and foetal death in utero. At present, national guidelines for foetal surveillance in preeclamptic pregnancies are inconsistent, due to a lack of evidence detailing the most appropriate assessment modalities as well as the timing and frequency at which assessments should be conducted. Current management of the foetus in preeclampsia involves timely delivery and prevention of adverse effects of prematurity with antenatal corticosteroids and/or magnesium sulphate depending on gestation. Alongside the risks to the foetus during pregnancy, there is also growing evidence that preeclampsia has long-term adverse effects on the offspring. In particular, preeclampsia has been associated with cardiovascular sequelae in the offspring including hypertension and altered vascular function.
Operating System for the K computer

For the K computer to achieve the world’s highest performance, Fujitsu has worked on the following three performance improvements in the development of the operating system (OS). First, to bring out the maximum hardware performance of our original CPU and interconnect, we provided a mechanism of controlling hardware extensions directly from applications. As the second improvement, we have introduced the synchronization scheduling function that minimizes the synchronization wait time of parallel programs resulting from system interruptions by coordinating job runtime and system runtime between multiple nodes. Third, multiple page size support that allows use of more than one page size has been achieved for improved memory access performance and memory utilization efficiency. This paper also describes the performance improvement functions, usability and robustness of the OS developed.
The unusual conformation of cross‐strand disulfide bonds is critical to the stability of β‐hairpin peptides

The cross‐strand disulfides (CSDs) found in β‐hairpin antimicrobial peptides (β‐AMPs) show a unique disulfide geometry that is characterized by unusual torsion angles and a short Cα‐Cα distance. While the sequence and disulfide bond connectivity of disulfide‐rich peptides is well studied, much less is known about the disulfide geometry found in CSDs and their role in the stability of β‐AMPs. To address this, we solved the nuclear magnetic resonance (NMR) structure of the β‐AMP gomesin (Gm) at 278, 298, and 310 K, examined the disulfide bond geometry of over 800 disulfide‐rich peptides, and carried out extensive molecular dynamics (MD) simulation of the peptides Gm and protegrin. The NMR data suggests Cα‐Cα distances characteristic for CSDs are independent of temperature. Analysis of disulfide‐rich peptides from the Protein Data Bank revealed that right‐handed and left‐handed rotamers are equally likely in CSDs. The previously reported preference for right‐handed rotamers was likely biased by restricting the analysis to peptides and proteins solved using X‐ray crystallography. Furthermore, data from MD simulations showed that the short Cα‐Cα distance is critical for the stability of these peptides. The unique disulfide geometry of CSDs poses a challenge to biomolecular force fields and to retain the stability of β‐hairpin fold over long simulation times, restraints on the torsion angles might be required.
Depletion of Bone Marrow-Derived Fibrocytes Attenuates TAA-Induced Liver Fibrosis in Mice

Bone marrow-derived fibrocytes (FC) represent a unique cell type, sharing features of both mesenchymal and hematopoietic cells. FC were shown to specifically infiltrate the injured liver and participate in fibrogenesis. Moreover, FC exert a variety of paracrine functions, thus possibly influencing the disease progression. However, the overall contribution of FC to liver fibrosis remains unclear. We aimed to study the effect of a specific FC depletion, utilizing a herpes simplex virus thymidine kinase (HSV-TK)/Valganciclovir suicide gene strategy. Fibrosis was induced by oral thioacetamide (TAA) administration in C57BL/6J mice. Hepatic hydroxyproline content was assessed for the primary readout. The HSV-TK model enabled the specific depletion of fibrocytes. Hepatic hydroxyproline content was significantly reduced as a result of the fibrocyte ablation (−7.8%; 95% CI: 0.7–14.8%; p = 0.033), denoting a reduced deposition of fibrillar collagens. Lower serum alanine transaminase levels (−20.9%; 95% CI: 0.4–36.9%; p = 0.049) indicate a mitigation of liver-specific cellular damage. A detailed mode of action, however, remains yet to be identified. The present study demonstrates a relevant functional contribution of fibrocytes to chronic toxic liver fibrosis, contradicting recent reports. Our results emphasize the need to thoroughly study the biology of fibrocytes in order to understand their importance for hepatic fibrogenesis.
IL-10–producing B cells are enriched in murine pericardial adipose tissues and ameliorate the outcome of acute myocardial infarction

Significance Myocardial infarction (MI) remains a leading cause of mortality and morbidity worldwide. Although it is recognized that a balanced and timely terminated proinflammatory response following acute MI is essential in promoting tissue repair/regeneration, the underlying regulatory mechanisms are poorly defined. In this report, we show that IL-10–producing B cells in mice: 1) Are enriched in pericardial adipose tissues (PATs) and influenced by cytokines preferentially expressed in these tissues; 2) expand in PATs following MI and accumulate in the infarcted heart during the resolution of MI-induced inflammation; and 3) facilitate resolution of inflammation and reduce myocardial injury to preserve cardiac function after MI. These findings identify IL-10–producing B cells, in particular those in PATs, as therapeutic targets for MI. Acute myocardial infarction (MI) provokes an inflammatory response in the heart that removes damaged tissues to facilitate tissue repair/regeneration. However, overactive and prolonged inflammation compromises healing, which may be counteracted by antiinflammatory mechanisms. A key regulatory factor in an inflammatory response is the antiinflammatory cytokine IL-10, which can be produced by a number of immune cells, including subsets of B lymphocytes. Here, we investigated IL-10–producing B cells in pericardial adipose tissues (PATs) and their role in the healing process following acute MI in mice. We found that IL-10–producing B cells were enriched in PATs compared to other adipose depots throughout the body, with the majority of them bearing a surface phenotype consistent with CD5+ B-1a cells (CD5+ B cells). These cells were detected early in life, maintained a steady presence during adulthood, and resided in fat-associated lymphoid clusters. The cytokine IL-33 and the chemokine CXCL13 were preferentially expressed in PATs and contributed to the enrichment of IL-10–producing CD5+ B cells. Following acute MI, the pool of CD5+ B cells was expanded in PATs. These cells accumulated in the infarcted heart during the resolution of MI-induced inflammation. B cell-specific deletion of IL-10 worsened cardiac function, exacerbated myocardial injury, and delayed resolution of inflammation following acute MI. These results revealed enrichment of IL-10–producing B cells in PATs and a significant contribution of these cells to the antiinflammatory processes that terminate MI-induced inflammation. Together, these findings have identified IL-10–producing B cells as therapeutic targets to improve the outcome of MI.
An effective patient training for deep inspiration breath hold technique of left-sided breast on computed tomography simulation procedure at King Chulalongkorn Memorial Hospital

Purpose To observe the effectiveness of the practical instruction sheet and the educational video for left-sided breast treatment in a patient receiving deep inspiration breath hold (DIBH) technique. Two parameters, simulation time and patient satisfaction, were assessed through the questionnaire. Methods Two different approaches, which were the instruction sheet and educational video, were combinedly used to assist patients during DIBH procedures. The guideline was assigned at least 1 week before the simulation date. On the simulation day, patients would fill the questionnaire regarding their satisfaction with the DIBH instruction. The questionnaire was categorized into five levels: extremely satisfied to dissatisfied, sequentially. The patients were divided into four groups: not DIBH technique, DIBH without instruction materials, the DIBH with instruction sheet or educational video, and DIBH with both of instruction sheet and educational video. Results Total number of 112 cases of left-sided breast cancer were analyzed. The simulation time during DIBH procedure significantly reduced when patients followed the instruction. There was no significant difference in simulation time on the DIBH procedures between patient compliance via instruction sheet or educational video or even following both of them. The excellent level was found at 4.6 ± 0.1 and 4.5 ± 0.1, for patients coaching via instruction sheet as well as on the educational video, respectively. Conclusion Patient coaching before simulation could potentially reduce the lengthy time in the simulation process for DIBH technique. Practicing the DIBH technique before treatment is strongly advised.
Transcription Factor bHLH2 Represses CYSTEINE PROTEASE77 to Negatively Regulate Nodule Senescence1[OPEN]

A transcription factor-cysteine protease regulatory module is associated with programmed cell death and reactive oxygen species accumulation in nodule senescence. Legume-rhizobia symbiosis is a time-limited process due to the onset of senescence, which results in the degradation of host plant cells and symbiosomes. A number of transcription factors, proteases, and functional genes have been associated with nodule senescence; however, whether other proteases or transcription factors are involved in nodule senescence remains poorly understood. In this study, we identified an early nodule senescence mutant in Medicago truncatula, denoted basic helix-loop-helix transcription factor2 (bhlh2), that exhibits decreased nitrogenase activity, acceleration of plant programmed cell death (PCD), and accumulation of reactive oxygen species (ROS). The results suggest that MtbHLH2 plays a negative role in nodule senescence. Nodules of wild-type and bhlh2-TALEN mutant plants at 28 d postinoculation were used for transcriptome sequencing. The transcriptome data analysis identified a papain-like Cys protease gene, denoted MtCP77, that could serve as a potential target of MtbHLH2. Electrophoretic mobility shift assays and chromatin immunoprecipitation analysis demonstrated that MtbHLH2 directly binds to the promoter of MtCP77 to inhibit its expression. MtCP77 positively regulates nodule senescence by accelerating plant PCD and ROS accumulation. In addition, the expression of MtbHLH2 in the nodules gradually decreased from the meristematic zone to the nitrogen fixation zone, whereas the expression of MtCP77 showed enhancement. These results indicate that MtbHLH2 and MtCP77 have opposite functions in the regulation of nodule senescence. These results reveal significant roles for MtbHLH2 and MtCP77 in plant PCD, ROS accumulation, and nodule senescence, and improve our understanding of the regulation of the nodule senescence process.
The Influence of Information Technology on the Information and Service Quality for the Teaching and Learning

Globalization has influenced the competition paradigm of higher education institutions in the world. The situation keeps changing, depending on the economy and information technology as the backbone of business processes in organizations. Higher education institutions should have added values to win the competition. Furthermore, the awareness of the society about the importance of formal education, particularly higher education, will make colleges/universities strategic institutions generating high quality human resources. The success of col-leges/universities is determined by service quality, which can be identified through the satisfaction of their customers, students and lecturers. To increase customer satisfaction and be able to compete in the globalization era, as well as generate greater profits, colleges/universities need to identify factors which influence information system services to increase customer satisfaction. Employing descriptive analysis, the study reveals that the purpose and service quality of information technology positively affect the teaching and learning process at colleges/universties.
Stratified and prognostic value of admission lactate and severity scores in patients with community-acquired pneumonia in emergency department

Abstract Background: Community-acquired pneumonia (CAP) is a potentially life-threatening condition. The aim of this study is to investigate the stratified and prognostic value of admission lactate and severity scores (confusion, urea >7 mmol/L, respiratory rate ≥30/min, blood pressure <90 mm Hg systolic and/or ≤60 mm Hg diastolic, and age ≥65 years [CURB65], pneumonia severity index [PSI], sequential organ failure assessment [SOFA], qSOFA) in patients with CAP in emergency department. Methods: Adult patients diagnosed with CAP admitted between January 2017 and January 2019 were enrolled and divided into severe CAP (SCAP) group and nonSCAP (NSCAP) group according to international guidelines, death group, and survival group according to 28-day prognosis. Predicting performance of parameters above was compared using receiver operating characteristic curves and logistic regression model. Cox proportional hazard regression model was used to identify variables independently associated with 28-day mortality. Results: A total of 350 patients with CAP were enrolled. About 196 patients were classified as SCAP and 74 patients died after a 28-day follow-up. The levels of CURB65, PSI, SOFA, qSOFA, and admission lactate were higher in the SCAP group and death group. SOFA showed advantage in predicting SCAP, while qSOFA is superior in predicting 28-day mortality. The combination of SOFA and admission lactate outperformed other combinations in predicting SCAP, and the combination of qSOFA and lactate showed highest superiority over other combinations in predicting 28-day mortality. Conclusion: The SOFA is a valuable predictor for SCAP and qSOFA is superior in predicting 28-day mortality. Combination of qSOFA and admission lactate can improve the predicting performance of single qSOFA.
Scoring Alternatives for Mental Speed Tests: Measurement Issues and Validity for Working Memory Capacity and the Attentional Blink Effect

Research suggests that the relation of mental speed with working memory capacity (WMC) depends on complexity and scoring methods of speed tasks and the type of task used to assess capacity limits in working memory. In the present study, we included conventional binding/updating measures of WMC as well as rapid serial visual presentation paradigms. The latter allowed for a computation of the attentional blink (AB) effect that was argued to measure capacity limitations at the encoding stage of working memory. Mental speed was assessed with a set of tasks and scored by diverse methods, including response time (RT) based scores, as well as ex-Gaussian and diffusion model parameterization. Relations of latent factors were investigated using structure equation modeling techniques. RT-based scores of mental speed yielded substantial correlations with WMC but only weak relations with the AB effect, while WMC and the AB magnitude were independent. The strength of the speed-WMC relation was shown to depend on task type. Additionally, the increase in predictive validity across RT quantiles changed across task types, suggesting that the worst performance rule (WPR) depends on task characteristics. In contrast to the latter, relations of speed with the AB effect did not change across RT quantiles. Relations of the model parameters were consistently found for the ex-Gaussian tau parameter and the diffusion model drift rate. However, depending on task type, other parameters showed plausible relations as well. The finding that characteristics of mental speed tasks determined the overall strength of relations with WMC, the occurrence of a WPR effect, and the specific pattern of relations of model parameters, implies that mental speed tasks are not exchangeable measurement tools. In spite of reflecting a general factor of mental speed, different speed tasks possess different requirements, supporting the notion of mental speed as a hierarchical construct.
TF-Net

Deep Neural Networks (DNNs) have become an essential component of various applications. While today’s DNNs are mainly restricted to cloud services, network connectivity, energy, and data privacy problems make it important to support efficient DNN computation on low-cost, low-power processors like microcontrollers. However, due to the constrained computation resources, it is challenging to execute large DNN models on microcontrollers. Using sub-byte low-precision input activations and weights is a typical method to reduce DNN computation. But on byte-addressable microcontrollers, the sub-byte computation is not well supported. The sub-byte inputs and weights need to be unpacked from bitstreams before computation, which incurs significant computation and energy overhead. In this paper, we propose the TF-Net pipeline to efficiently deploy sub-byte DNNs on microcontrollers. While TF-Net allows for a range of weight and input precision, we find Ternary weights and Four-bit inputs provide the optimal balance between model accuracy, computation performance, and energy efficiency. TF-Net first includes a training framework for sub-byte low-precision DNN models. Two algorithms are then introduced to accelerate the trained models. The first, direct buffer convolution, amortizes unpacking overhead by caching unpacked inputs. The second, packed sub-byte multiply-accumulate, utilizes a single multiplication instruction to perform multiple sub-byte multiply-accumulate computations. To further accelerate DNN computation, we propose two instructions, Multiply-Shift-Accumulate and Unpack, to extend the existing microcontroller instruction set. On the tested networks, TF-Net can help improve the computation performance and energy efficiency by 1.83× and 2.28× on average, respectively.
Cyclin D1 is Associated with Radiosensitivity of Triple-Negative Breast Cancer Cells to Proton Beam Irradiation

Proton therapy offers a distinct physical advantage over conventional X-ray therapy, but its biological advantages remain understudied. In this study, we aimed to identify genetic factors that contribute to proton sensitivity in breast cancer (BC). Therefore, we screened relative biological effectiveness (RBE) of 230 MeV protons, compared to 6 MV X-rays, in ten human BC cell lines, including five triple-negative breast cancer (TNBC) cell lines. Clonogenic survival assays revealed a wide range of proton RBE across the BC cell lines, with one out of ten BC cell lines having an RBE significantly different from the traditional generic RBE of 1.1. An abundance of cyclin D1 was associated with proton RBE. Downregulation of RB1 by siRNA or a CDK4/6 inhibitor increased proton sensitivity but not proton RBE. Instead, the depletion of cyclin D1 increased proton RBE in two TNBC cell lines, including MDA-MB-231 and Hs578T cells. Conversely, overexpression of cyclin D1 decreased the proton RBE in cyclin D1-deficient BT-549 cells. The depletion of cyclin D1 impaired proton-induced RAD51 foci formation in MDA-MB-231 cells. Taken together, this study provides important clues about the cyclin D1-CDK4-RB1 pathway as a potential target for proton beam therapy in TNBC.
Auditory Cortex Contributes to Discrimination of Pure Tones

Abstract The auditory cortex is topographically organized for sound frequency and contains highly selective frequency-tuned neurons, yet the role of auditory cortex in the perception of sound frequency remains unclear. Lesion studies have shown that auditory cortex is not essential for frequency discrimination of pure tones. However, transient pharmacological inactivation has been reported to impair frequency discrimination. This suggests the possibility that successful tone discrimination after recovery from lesion surgery could arise from long-term reorganization or plasticity of compensatory pathways. Here, we compared the effects of lesions and optogenetic suppression of auditory cortex on frequency discrimination in mice. We found that transient bilateral optogenetic suppression partially but significantly impaired discrimination performance. In contrast, bilateral electrolytic lesions of auditory cortex had no effect on performance of the identical task, even when tested only 4 h after lesion. This suggests that when auditory cortex is destroyed, an alternative pathway is almost immediately adequate for mediating frequency discrimination. Yet this alternative pathway is insufficient for task performance when auditory cortex is intact but has its activity suppressed. These results indicate a fundamental difference between the effects of brain lesions and optogenetic suppression, and suggest the existence of a rapid compensatory process possibly induced by injury.