Miracle-dz/UniFAR-FTUs huggingface dataset:
HMG-CoA Reductase Inhibitors Relieve Endoplasmic Reticulum Stress by Autophagy Inhibition in Rats With Permanent Brain Ischemia

Exploring and expanding the indications of common clinical drugs, such as statins, is important to improve the prognosis of patients with permanent cerebral infarction. It has been suggested that reversing the defects in cellular autophagy and ER stress with statin therapy may be a potential treatment option for reducing ischemic damage. Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (PMCAO) by electrocoagulation surgery. Atorvastatin (ATV, 10 mg/kg/day) or vehicle was administered intraperitoneally. Rats were divided into the vehicle-treated (SHAM), ATV pretreatment for MCAO (AMCAO), and 3-methyladenine (3MA) combined with ATV pretreatment (3MAMCAO) groups. Magnetic resonance imaging, as well as immunohistochemical and Western blot assessments, were performed 24 h after MCAO. Each ATV-treated group demonstrated significant reductions in infarct volume compared with that in the vehicle-treated group at 24 h after MCAO, which was associated with autophagy reduction and ER stress attenuation in neurons and neovascularization. Next, Western blotting was used to detect the levels of the autophagy-related proteins LC3B and P62 and of ER stress pathway proteins. However, 3MA significantly partially inhibited the ER stress pathway via limiting the autophagic flux in the AMCAO group. In conclusion, our results imply that the neuroprotective function of ATV depends on autophagic activity to diminish ER stress-related cell apoptosis in rats with PMCAO and suggest that compounds that inhibit autophagic activity might reduce the neuroprotective effect of ATV after brain ischemia.
AtomLayer: A Universal ReRAM-Based CNN Accelerator with Atomic Layer Computation

Although ReRAM-based convolutional neural network (CNN) accelerators have been widely studied, state-of-the-art solutions suffer from either incapability of training (e.g., ISSAC [1]) or inefficiency of inference (e.g., PipeLayer [2]) due to the pipeline design. In this work, we propose AtomLayer–a universal ReRAM-based accelerator to support both efficient CNN training and inference. AtomLayer uses the atomic layer computation which processes only one network layer each time to eliminate the pipeline related issues such as long latency, pipeline bubbles and large on-chip buffer overhead. For further optimization, we use a unique filter mapping and a data reuse system to minimize the cost of layer switching and DRAM access. Our experimental results show that AtomLayer can achieve higher power efficiency than ISSAC in inference (1.1×) and PipeLayer in training (1.6×), respectively, meanwhile reducing the footprint by 15 ×.
RD5-mediated lack of PE_PGRS and PPE-MPTR export in BCG vaccine strains results in strong reduction of antigenic repertoire but little impact on protection

Tuberculosis is the deadliest infectious disease worldwide. Although the BCG vaccine is widely used, it does not efficiently protect against pulmonary tuberculosis and an improved tuberculosis vaccine is therefore urgently needed. Mycobacterium tuberculosis uses different ESX/Type VII secretion (T7S) systems to transport proteins important for virulence and host immune responses. We recently reported that secretion of T7S substrates belonging to the mycobacteria-specific Pro-Glu (PE) and Pro-Pro-Glu (PPE) proteins of the PGRS (polymorphic GC-rich sequences) and MPTR (major polymorphic tandem repeat) subfamilies required both a functional ESX-5 system and a functional PPE38/71 protein for secretion. Inactivation of ppe38/71 and the resulting loss of PE_PGRS/PPE-MPTR secretion were linked to increased virulence of M. tuberculosis strains. Here, we show that a predicted total of 89 PE_PGRS/PPE-MPTR surface proteins are not exported by certain animal-adapted strains of the M. tuberculosis complex including M. bovis. This Δppe38/71-associated secretion defect therefore also occurs in the M. bovis-derived tuberculosis vaccine BCG and could be restored by introduction of the M. tuberculosis ppe38-locus. Epitope mapping of the PPE-MPTR protein PPE10, further allowed us to monitor T-cell responses in splenocytes from BCG/M. tuberculosis immunized mice, confirming the dependence of PPE10-specific immune-induction on ESX-5/PPE38-mediated secretion. Restoration of PE_PGRS/PPE-MPTR secretion in recombinant BCG neither altered global antigenic presentation or activation of innate immune cells, nor protective efficacy in two different mouse vaccination-infection models. This unexpected finding stimulates a reassessment of the immunomodulatory properties of PE_PGRS/PPE-MPTR proteins, some of which are contained in vaccine formulations currently in clinical evaluation.
Saxagliptin Upregulates Nesfatin-1 Secretion and Ameliorates Insulin Resistance and Metabolic Profiles in Type 2 Diabetes Mellitus

Background and Aims: Saxagliptin as one of dipeptidyl peptidase-4 (DPP-4) inhibitors can effectively improve glycaemic control in type 2 diabetes mellitus, and nesfatin-1 is regarded as a very important factor in regulating feeding behavior and energy homeostasis. In this trial, we observed the effect of saxagliptin on regulating nesfatin-1 secretion and ameliorating insulin resistance and metabolic profiles in type 2 diabetes mellitus. Methods: One hundred two type 2 diabetes participants (M/F = 48/54) were investigated. Fifty-one (M/F = 24/ 27) of them as the treatment group were treated with oral glucose-lowering agents including saxagliptin, the other 51 (M/F = 24/27) as the control group were treated with oral glucose-lowering agents excluding any DPP4 inhibitors. The parameters of serum nesfatin-1, C-peptide, homeostasis model assessment-b (HOMA-b) function, HOMA insulin resistance (HOMA-IR), glycosylated hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), body mass index (BMI), and blood pressure (BP) at baseline, month 3, 6, and 12 were observed and compared respectively. Results: Saxagliptin significantly upregulated nesfatin-1 secretion (P < 0.001 at 3-, 6-, and 12-months vs. baseline), increased serum C-peptide (P < 0.05, 0.001, and 0.001 at 3-, 6-, and 12-months vs. baseline), improved HOMA-IR and function of HOMA-b (P < 0.001 at 3-, 6-, and 12-months vs. baseline) and metabolic profiles (P < 0.001 with HbA1c at 3-, 6and 12-months; P < 0.001 with LDL-C at 6and 12-months; P < 0.001 and 0.01 with HDL-C at 6and 12-months vs. baseline), declined BMI (P < 0.05 at 6and 12-months vs. baseline) and BP (P < 0.001 with systolic BP (SBP), and mean BP at 6and 12-months, P < 0.01 with diastolic BP at 6and 12-months vs. baseline). Conclusions: Saxagliptin could upregulate nesfatin-1 secretion and ameliorate insulin resistance and metabolic profiles in type 2 diabetes mellitus. Saxagliptin had the potential to play fundamental by upregulating nesfatin-1 secretion besides lowering glucose by inhibiting the degradation of glucagon-like peptide-1.
A comparison of prism adaptation with terminal versus concurrent exposure on sensorimotor changes and spatial neglect

ABSTRACT Prism adaptation (PA) is a technique that induces a temporary change of the alignment between different reference frames. This technique has been shown to reduce many signs of unilateral spatial neglect (USN). Two procedures of prism adaptation have been used. In concurrent exposure participants can see their arm and hand during the movement trajectory, and during terminal exposure, participants can see only the most distal few centimetres. Because the two exposures elicit different proportions of visual and proprioceptive realignment, they could present different rehabilitation efficacies. We compared these procedures in 12 USN patients and 12 healthy participants who performed one session of PA with concurrent exposure and one session with terminal exposure. We compared the effects of the two exposure types on sensorimotor outcomes (visual subjective straight ahead, proprioceptive subjective straight ahead, open loop pointing, and error correction during exposure) and neglect outcomes. We found no significant differences in the effects of the two exposure types on sensorimotor performance of patients and controls, nor on patients’ neuropsychological outcomes. Compared with controls, USN patients showed a significant rightward bias in visual subjective straight ahead pre-adaptation, a slower rate of error correction during prism exposure, and some evidence that visual and proprioceptive shift could be influenced by their neglect. Based on these results, we recommend that prism adaptation be conducted with concurrent exposure for easiness of execution.
Children's Vulnerability to Interparental Conflict: The Protective Role of Sibling Relationship Quality.

This study tested whether the strength of the mediational pathway involving interparental conflict, adolescent emotional insecurity, and their psychological problems depended on the quality of their sibling relationships. Using a multimethod approach, 236 adolescents (Mage = 12.6 years) and their parents participated in three annual measurement occasions. Tests of moderated mediation revealed that indirect paths among interparental conflict, insecurity, and psychological problems were significant for teens with low, but not high, quality bonds with siblings. High-quality (i.e., strong) sibling relationships conferred protection by neutralizing interparental conflict as a precursor of increases in adolescent insecurity. Results did not vary as a function of the valence of sibling relationship properties, adolescent sex, or gender and age compositions of the dyad.
Using GPS Technology to Understand Spatial and Temporal Activity of Kangaroos in a Peri-Urban Environment

Simple Summary Kangaroo–human conflict is increasing in the peri-urban communities of the New South Wales (NSW) north coast in Australia. A way to assist in managing this conflict is to improve our understanding on the ecology of kangaroos in the peri-urban environment. We utilized modern Global Positioning System (GPS) technology to track adult male kangaroo movements in a peri-urban housing estate at Coffs Harbour, Australia, using both collars and temporary glue-on devices. We also assessed the effectiveness of the glue-on devices, which do not require animal recapture for device retrieval. Kangaroos remained predominately within the residential area and moved over short distances with small movement speeds. Movement activity peaked from 6:00 a.m. to 8:00 a.m., coinciding with daily residential activities such as driving to work, putting children on the school bus, hanging out the washing, and putting bins on the street. In addition, the temporary glue-on devices were effective in gaining information on spatial and temporal activity on a day-by-day basis, despite having short deployment lengths. Abstract The increasing kangaroo occurrence in expanding peri-urban areas can be problematic when kangaroos become aggressive towards people and present a collision risk to motor vehicles. An improved understanding on kangaroo spatial and temporal activity patterns in the peri-urban environment is essential to manage kangaroo–human conflict. In this study, we used GPS telemetry to determine activity patterns of male Eastern Grey Kangaroos (Macropus giganteus) in a peri-urban community on the north-coast of New South Wales, Australia. Two types of GPS devices were employed; collars and cheaper alternative glue-on units. Kangaroos moved on average 2.39 km a day, with an average movement rate of 1.89 m/min, which was greatest at dawn. The GPS glue-on devices had short deployment lengths of one to 12 days. Despite limitations in attachment time, the glue-on devices were viable in obtaining daily spatial and temporal activity data. Our results aid towards alleviating conflict with kangaroos by providing new insights into kangaroo movements and activity within a peri-urban environment and introduces a potential cheap GPS alternative for obtaining this data relative to more expensive collars.
Long non-coding RNA ZFAS1 promotes nasopharyngeal carcinoma through activation of Wnt/β-catenin pathway.

OBJECTIVE To investigate the expression characteristics of long non-coding RNA (lncRNA) ZFAS1 in nasopharyngeal carcinoma (NPC) and to further investigate the role and mechanism of ZFAS1 in the occurrence and development of NPC. PATIENTS AND METHODS 76 surgical excision samples from newly diagnosed NPC patients and 76 cases of paracancerous tissues were selected. The expression of ZFAS1 was detected by qRT-PCR (quantitative real-time polymerase chain reaction), and the relationship between the expression of ZFAS1 and the clinical prognosis of patients with NPC was analyzed. After the knockdown, the expression of ZFAS1 in nasopharyngeal carcinoma cell line CNE-1 by small interfering RNA, the effect of ZFAS1 on the biological function of NPC cells was analyzed by cell counting kit-8 (CCK8), colony formation assay, flow cytometry and apoptosis assay. The effect of ZFAS1 on the Wnt/β-catenin pathway was analyzed by Western blot. RESULTS After analyzing the clinical data of enrolled patients, we found that ZFAS1 was overexpressed in NPC patients, which was closely correlated with tumor size and lymph node metastasis of NPC. Moreover, ZFAS1 was negatively correlated to the survival of NPC patients. After interfering with the expression of ZFAS1, the proliferation of NPC cells was significantly decreased, the cell cycle was inhibited and the apoptosis rate was increased. Western Blot showed that ZFAS1 promoted the occurrence of NPC by activating the Wnt/β-catenin pathway. CONCLUSIONS ZFAS1 was overexpressed in NPC and was significantly related to tumor size, lymph node metastasis and poor prognosis of NPC. ZFAS1 could promote NPC by activating Wnt/β-catenin pathway.
ZMYND10 functions in a chaperone relay during axonemal dynein assembly

Molecular chaperones promote the folding and macromolecular assembly of a diverse set of substrate ‘client’ proteins. How the ubiquitous chaperone machinery directs its activities towards a specific set of substrates and whether this selectivity could be targeted for therapeutic intervention is of intense research. Through the use of mouse genetics, imaging and quantitative proteomics we uncover that ZMYND10 is a novel co-chaperone for the FKBP8-HSP90 chaperone complex during the biosynthesis of axonemal dynein heavy chains required for cilia motility. In the absence of ZMYND10, defects in dynein heavy chains trigger broader dynein motor degradation. We show that FKBP8 inhibition phenocopies dynein motor instability in airway cells, and human disease-causing variants of ZMYND10 disrupt its ability to act as FKBP8-HSP90 co-chaperone. Our study indicates that the motile ciliopathy Primary Ciliary Dyskinesia (PCD) should be considered a cell-type specific protein-misfolding disease and opens the potential for rational drug design that could restore specificity to the ubiquitous chaperone apparatus towards dynein subunits.
Comparison of Wearable Trackers’ Ability to Estimate Sleep

Tracking physical activity and sleep patterns using wearable trackers has become a current trend. However, little information exists about the comparability of wearable trackers measuring sleep. This study examined the comparability of wearable trackers for estimating sleep measurement with a sleep diary (SD) for three full nights. A convenience sample of 78 adults were recruited in this research with a mean age of 27.6 ± 11.0 years. Comparisons between wearable trackers and sleep outcomes were analyzed using the mean absolute percentage errors, Pearson correlations, Bland–Altman Plots, and equivalent testing. Trackers that showed the greatest equivalence with the SD for total sleep time were the Jawbone UP3 and Fitbit Charge Heart Rate (effect size = 0.09 and 0.23, respectively). The greatest equivalence with the SD for time in bed was seen with the SenseWear Armband, Garmin Vivosmart, and Jawbone UP3 (effect size = 0.09, 0.16, and 0.07, respectively). Some of the wearable trackers resulted in closer approximations to self-reported sleep outcomes than a previously sleep research-grade device, these trackers offer a lower-cost alternative to tracking sleep in healthy populations.
Mapping dengue risk in Singapore using Random Forest

Background Singapore experiences endemic dengue, with 2013 being the largest outbreak year known to date, culminating in 22,170 cases. Given the limited resources available, and that vector control is the key approach for prevention in Singapore, it is important that public health professionals know where resources should be invested in. This study aims to stratify the spatial risk of dengue transmission in Singapore for effective deployment of resources. Methodology/principal findings Random Forest was used to predict the risk rank of dengue transmission in 1km2 grids, with dengue, population, entomological and environmental data. The predicted risk ranks are categorized and mapped to four color-coded risk groups for easy operation application. The risk maps were evaluated with dengue case and cluster data. Risk maps produced by Random Forest have high accuracy. More than 80% of the observed risk ranks fell within the 80% prediction interval. The observed and predicted risk ranks were highly correlated (ρ ≥0.86, P <0.01). Furthermore, the predicted risk levels were in excellent agreement with case density, a weighted Kappa coefficient of more than 0.80 (P <0.01). Close to 90% of the dengue clusters occur in high risk areas, and the odds of cluster forming in high risk areas were higher than in low risk areas. Conclusions This study demonstrates the potential of Random Forest and its strong predictive capability in stratifying the spatial risk of dengue transmission in Singapore. Dengue risk map produced using Random Forest has high accuracy, and is a good surveillance tool to guide vector control operations.
Moving beyond the distinction between concrete and abstract concepts

From the perspective of the situated conceptualization framework, the primary purpose of concepts is for categorizing and integrating elements of situations to support goal-directed action (including communication and social interaction). To the extent that important situational elements are categorized and integrated properly, effective goal-directed action follows. Over time, frequent patterns of co-occurring concepts within situations become established in memory as situated conceptualizations, conditioning the conceptual system and producing habitual patterns of conceptual processing. As a consequence, individual concepts are most basically represented within patterns of concepts that become entrained with specific kinds of physical situations. In this framework, the concrete versus abstract distinction between concepts is no longer useful, with two other distinctions becoming important instead: (i) external versus internal situational elements, (ii) situational elements versus situational integrations. Whereas concepts for situational elements originate in distributed neural networks that provide continual feeds about components of situations, concepts for situational integrations originate in association areas that establish temporal co-occurrence relations between situational elements, both external and internal. We propose that studying concepts in the context of situated action is necessary for establishing complete accounts of them, and that continuing to study concepts in isolation is likely to provide relatively incomplete and distorted accounts. This article is part of the theme issue ‘Varieties of abstract concepts: development, use and representation in the brain’.
Race-, Age-, and Gender-Based Characteristics and Toxicities of Targeted Therapies on Phase I Trials

Background: The impact of age-, gender-, and race-based differences on safety and efficacy in phase I clinical trials has not been well studied. Methods: We analyzed data from phase I clinical trials evaluating targeted biologic agents in patients with advanced solid malignancies. Race and gender distribution of enrolled patients was compared to the referral population demographics at the city, metro, and state levels. The association between age, gender, and race with type, frequency, and severity of treatment-emergent toxicities and clinical benefit was assessed using univariate and multivariable models. Results: Data from 117 eligible patients – Blacks/Caucasians/Others (27/85/5); male/female (66/51) – were obtained. Blacks were younger than Caucasian patients (median age of 56 vs. 62 years, p = 0.004). Nausea/vomiting was more frequent in female patients (43 vs. 24%, p = 0.03), while hematologic toxicity was more likely in Whites. While median time on treatment was comparable (113 vs. 91; p = 0.840), the median overall survival was significantly shorter for Blacks versus Caucasians (7.4 vs. 11.4 months; p = 0.0227). Black race (HR 2.11; 95% CI 1.24–3.60; p = 0.006) and older age (HR 1.03; 95% CI 1.00–1.06; p = 0.029) were associated with an increased risk of death. Conclusions: Age-, gender-, and race-based disparities were observed with specific toxicity and survival outcomes on phase I clinical trials of anticancer agents.
Sharp Analytical Capacity Upper Bounds for Sticky and Related Channels

We study natural examples of binary channels with synchronization errors. These include the duplication channel, which independently outputs a given bit once or twice, and geometric channels that repeat a given bit according to a geometric rule, with or without the possibility of bit deletion. We apply the general framework of Cheraghchi (STOC 2018) to obtain sharp analytical upper bounds on the capacity of these channels. Previously, upper bounds were known via numerical computations involving the computation of finite approximations of the channels by a computer and then using the obtained numerical results to upper bound the actual capacity. While leading to sharp numerical results, further progress on the full understanding of the channel capacity inherently remains elusive using such methods. Our results can be regarded as a major step towards a complete understanding of the capacity curves. Quantitatively, our upper bounds sharply approach, and in some cases surpass, the bounds that were previously only known by purely numerical methods. Among our results, we notably give a completely analytical proof that, when the number of repetitions per bit is geometric (supported on 0,1,2,…) with mean growing to infinity, the channel capacity remains substantially bounded away from 1.
Multi-variable LSTM neural network for autoregressive exogenous model

In this paper, we propose multi-variable LSTM capable of accurate forecasting and variable importance interpretation for time series with exogenous variables. Current attention mechanism in recurrent neural networks mostly focuses on the temporal aspect of data and falls short of characterizing variable importance. To this end, the multi-variable LSTM equipped with tensorized hidden states is developed to learn hidden states for individual variables, which give rise to our mixture temporal and variable attention. Based on such attention mechanism, we infer and quantify variable importance. Extensive experiments using real datasets with Granger-causality test and the synthetic dataset with ground truth demonstrate the prediction performance and interpretability of multi-variable LSTM in comparison to a variety of baselines. It exhibits the prospect of multi-variable LSTM as an end-to-end framework for both forecasting and knowledge discovery.