Miracle-dz/UniFAR-FTUs huggingface dataset:
The Mitochondrial Genome of Elodia flavipalpis Aldrich (Diptera: Tachinidae) and the Evolutionary Timescale of Tachinid Flies

Tachinid flies are natural enemies of many lepidopteran and coleopteran pests of forests, crops, and fruit trees. In order to address the lack of genetic data in this economically important group, we sequenced the complete mitochondrial genome of the Palaearctic tachinid fly Elodia flavipalpis Aldrich, 1933. Usually found in Northern China and Japan, this species is one of the primary natural enemies of the leaf-roller moths (Tortricidae), which are major pests of various fruit trees. The 14,932-bp mitochondrial genome was typical of Diptera, with 13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes. However, its control region is only 105 bp in length, which is the shortest found so far in flies. In order to estimate dipteran evolutionary relationships, we conducted a phylogenetic analysis of 58 mitochondrial genomes from 23 families. Maximum-likelihood and Bayesian methods supported the monophyly of both Tachinidae and superfamily Oestroidea. Within the subsection Calyptratae, Muscidae was inferred as the sister group to Oestroidea. Within Oestroidea, Calliphoridae and Sarcophagidae formed a sister clade to Oestridae and Tachinidae. Using a Bayesian relaxed clock calibrated with fossil data, we estimated that Tachinidae originated in the middle Eocene.
Hollow-core negative curvature fiber: a novel platform for lab-on-a-fiber

Hollow-core photonic crystal fiber (HC-PCF) has been proved to be a versatile platform for lab-on-a-fiber applications. By filling the fiber with various gases, liquids or solid materials, the light-matter interaction could be greatly enhanced. Many novel optical phenomena that are unattainable in free-space could be easily identified inside the fiber. Such a platform offers a promising route for creating compact, integrable and biocompatible all-fiber multifunctional optical devices. Here, we review our recent progress in developing a novel HC-PCF coined "hollow-core negative curvature fiber" (NCF) that could provide light guidance at spectral ranges covering from UV, visible, NIR to MIR. These NCFs show attributes of low transmission loss, octave-spanning transmission bandwidth, high damage threshold and single modeness. As a proof-of-concept demonstration for lab-on-a-fiber applications, we filled one of the fibers with ethanol (refractive index 1.36) to form a liquid-core anti-resonant fiber. At a low volume of 1 μL, Raman signal from ethanol was observed at a pump power of 2 mW. Such a high performance NCF opens a window for applications in fiber-enhanced spectroscopy, biochemical sensing and nano-plasmonics.
Constitutive Endocytosis and Turnover of the Neuronal Glycine Transporter GlyT2 Is Dependent on Ubiquitination of a C-Terminal Lysine Cluster

Inhibitory glycinergic neurotransmission is terminated by sodium and chloride-dependent plasma membrane glycine transporters (GlyTs). The mainly glial glycine transporter GlyT1 is primarily responsible for the completion of inhibitory neurotransmission and the neuronal glycine transporter GlyT2 mediates the reuptake of the neurotransmitter that is used to refill synaptic vesicles in the terminal, a fundamental role in the physiology and pathology of glycinergic neurotransmission. Indeed, inhibitory glycinergic neurotransmission is modulated by the exocytosis and endocytosis of GlyT2. We previously reported that constitutive and Protein Kinase C (PKC)-regulated endocytosis of GlyT2 is mediated by clathrin and that PKC accelerates GlyT2 endocytosis by increasing its ubiquitination. However, the role of ubiquitination in the constitutive endocytosis and turnover of this protein remains unexplored. Here, we show that ubiquitination of a C-terminus four lysine cluster of GlyT2 is required for constitutive endocytosis, sorting into the slow recycling pathway and turnover of the transporter. Ubiquitination negatively modulates the turnover of GlyT2, such that increased ubiquitination driven by PKC activation accelerates transporter degradation rate shortening its half-life while decreased ubiquitination increases transporter stability. Finally, ubiquitination of GlyT2 in neurons is highly responsive to the free pool of ubiquitin, suggesting that the deubiquitinating enzyme (DUB) ubiquitin C-terminal hydrolase-L1 (UCHL1), as the major regulator of neuronal ubiquitin homeostasis, indirectly modulates the turnover of GlyT2. Our results contribute to the elucidation of the mechanisms underlying the dynamic trafficking of this important neuronal protein which has pathological relevance since mutations in the GlyT2 gene (SLC6A5) are the second most common cause of human hyperekplexia.
Small Nucleolar RNA-Derived MicroRNA hsa-miR-1291 Modulates Cellular Drug Disposition through Direct Targeting of ABC Transporter ABCC1

Multidrug resistance–associated protein 1 (MRP1/ABCC1) is an important membrane transporter that contributes to cellular disposition of many endobiotic and xenobiotic agents, and it can also confer multidrug resistance. This study aimed to investigate the role of human noncoding microRNA-1291 (hsa-miR-1291) in regulation of ABCC1 and drug disposition. Bioinformatics analyses indicated that hsa-miR-1291, localized within the small nucleolar RNA H/ACA box 34 (SNORA34), might target ABCC1 3′-untranslated region (3′UTR). Using splinted ligation small RNA detection method, we found that SNORA34 was processed into hsa-miR-1291 in human pancreatic carcinoma PANC-1 cells. Luciferase reporter assays showed that ABCC1 3′-UTR-luciferase activity was decreased by 20% in cells transfected with hsa-miR-1291 expression plasmid, and increased by 40% in cells transfected with hsa-miR-1291 antagomir. Furthermore, immunoblot study revealed that ABCC1 protein expression was sharply reduced in hsa-miR-1291–stably transfected PANC-1 cells, which was attenuated by hsa-miR-1291 antagomir. The change of ABCC1 protein expression was associated with an alternation in mRNA expression. In addition, hsa-miR-1291–directed downregulation of ABCC1 led to a greater intracellular drug accumulation and sensitized the cells to doxorubicin. Together, our results indicate that hsa-miR-1291 is derived from SNORA34 and modulates cellular drug disposition and chemosensitivity through regulation of ABCC1 expression. These findings shall improve the understanding of microRNA-controlled epigenetic regulatory mechanisms underlying multidrug resistance and interindividual variability in pharmacokinetics.
Population-Level HIV Declines and Behavioral Risk Avoidance in Uganda

Uganda provides the clearest example that human immunodeficiency virus (HIV) is preventable if populations are mobilized to avoid risk. Despite limited resources, Uganda has shown a 70% decline in HIV prevalence since the early 1990s, linked to a 60% reduction in casual sex. The response in Uganda appears to be distinctively associated with communication about acquired immunodeficiency syndrome (AIDS) through social networks. Despite substantial condom use and promotion of biomedical approaches, other African countries have shown neither similar behavioral responses nor HIV prevalence declines of the same scale. The Ugandan success is equivalent to a vaccine of 80% effectiveness. Its replication will require changes in global HIV/AIDS intervention policies and their evaluation.
A comprehensive study of metal-coated short carbon fibers, graphite particles, and hybrid fillers for induction heating

Induction heating or welding can be performed by considering the combined effect of ferromagnetic heating due to magnetic hysteresis losses and eddy current heating due to conductive material. Nonconducting thermoplastic composite parts can be joined or welded by induction heating using a susceptor sheet filled with nickel-coated carbon fibers (NiCCFs) and nickel-coated graphite particles (NiCGPs) or both with polypropylene (PP) thermoplastic matrix. Above the percolation threshold, NiCCFs can serve as conductive materials and nickel coating will provide the ferromagnetic heating. NiCCF/PP and NiCCF/NiCGP/PP susceptor sheets were developed via melt mixing using a twin-screw extruder and sheets were produced by Calendering process. Induction heating tests were performed on a circular pancake coil and at frequencies below 1 MHz. In induction heating, fiber heating by Joule loss, junction heating (i.e. dielectric heating and contact resistance heating), as well as magnetic hysteresis effect were observed in both the cases. Heating in hybrid filler was higher at lower filler concentrations; however, with higher concentrations, heating reduced. Reduction in induction heating maybe due to a reduction in electrical conductivity was observed. Electrical conductivity was measured in fibers direction by a Keithley electrometer using a four-point measuring method and temperature was measured by an infrared thermal camera. Microstructure characterization was performed by X-ray computed microtomography and light microscopy.
A biomimetic adaptive algorithm and low-power architecture for implantable neural decoders

Algorithmically and energetically efficient computational architectures that operate in real time are essential for clinically useful neural prosthetic devices. Such devices decode raw neural data to obtain direct control signals for external devices. They can also perform data compression and vastly reduce the bandwidth and consequently power expended in wireless transmission of raw data from implantable brain-machine interfaces. We describe a biomimetic algorithm and micropower analog circuit architecture for decoding neural cell ensemble signals. The decoding algorithm implements a continuous-time artificial neural network, using a bank of adaptive linear filters with kernels that emulate synaptic dynamics. The filters transform neural signal inputs into control-parameter outputs, and can be tuned automatically in an on-line learning process. We provide experimental validation of our system using neural data from thalamic head-direction cells in an awake behaving rat.
Consistency Checking of Natural Language Temporal Requirements using Answer-Set Programming

OF DISSERTATION Consistency Checking of Natural Language Temporal Requirements using Answer-Set Programming Successful software engineering practice requires high quality requirements. Inconsistency is one of the main requirement issues that may prevent software projects from being success. This is particularly onerous when the requirements concern temporal constraints. Manual checking whether temporal requirements are consistent is tedious and error prone when the number of requirements is large. This dissertation addresses the problem of identifying inconsistencies in temporal requirements expressed as natural language text. The goal of this research is to create an efficient, partially automated, approach for checking temporal consistency of natural language requirements and to minimize analysts’ workload. The key contributions of this dissertation are as follows: (1) Development of a partially automated approach for checking temporal consistency of natural language requirements. (2) Creation of a formal language Temporal Action Language (TeAL), which provide a means to represent natural language requirements precisely and unambiguously. (3) Development of a front end to semi-automatically translate natural language requirements into TeAL. (4) Development of a translator from TeAL to the ASP language. Validation results to date show that the front end tool makes the task of translating natural language requirements into TeAL more accurate and efficient, and the translator generates ASP programs that correctly detect the inconsistencies in the requirements.
Association of Food Insecurity with Children's Behavioral, Emotional, and Academic Outcomes: A Systematic Review

Objective: Food Insecurity (FI) occurs in 21% of families with children and adolescents in the United States, but the potential developmental and behavioral implications of this prevalent social determinant of health have not been comprehensively elucidated. This systematic review aims to examine the association between FI and childhood developmental and behavioral outcomes in western industrialized countries. Method: This review provides a critical summary of 23 peer reviewed articles from developed countries on the associations between FI and adverse childhood developmental behavioral outcomes including early cognitive development, academic performance, inattention, externalizing behaviors, and depression in 4 groups–infants and toddlers, preschoolers, school age, and adolescents. Various approaches to measuring food insecurity are delineated. Potential confounding and mediating variables of this association are compared across studies. Alternate explanatory mechanisms of observed effects and need for further research are discussed. Results: This review demonstrates that household FI, even at marginal levels, is associated with children's behavioral, academic, and emotional problems from infancy to adolescence across western industrialized countries - even after controlling for confounders. Conclusions: While the American Academy of Pediatrics already recommends routine screening for food insecurity during health maintenance visits, the evidence summarized here should encourage developmental behavioral health providers to screen for food insecurity in their practices and intervene when possible. Conversely, children whose families are identified as food insecure in primary care settings warrant enhanced developmental behavioral assessment and possible intervention.
Modulation of hERG potassium currents in HEK‐293 cells by protein kinase C. Evidence for direct phosphorylation of pore forming subunits

The human ether‐a‐go‐go related gene (hERG) potassium channel is expressed in a variety of tissues including the heart, neurons and some cancer cells. hERG channels are modulated by several intracellular signalling pathways and these provide important mechanisms for regulating cellular excitability. In this study, we investigated muscarinic modulation of hERG currents and direct phosphorylation of channel subunits expressed in HEK‐293 cells at physiologically relevant temperatures by protein kinase C (PKC). Activation of Gαq/11‐coupled M3‐muscarinic receptors with methacholine, reduced current amplitudes at all potentials with minor effects on the voltage dependence of activation and inactivation. The response to methacholine was insensitive to intracellular BAPTA, but was attenuated by either acute inhibition of PKC with 300 nm bisindolylmaleimide‐1 (bis‐1) or chronic down‐regulation of PKC isoforms by 24 h pretreatment of cells with phorbol 12‐myristate 13‐acetate (PMA). Stimulation of PKC with 1‐oleoyl 2‐acetylglycerol (OAG), an analogue of diacylglycerol (DAG), mimicked the actions of muscarinic receptor stimulation. Direct phosphorylation of hERG was measured by [32P]orthophosphate labelling of immunoprecipitated protein with an anti‐hERG antibody. Basal phosphorylation was high in unstimulated cells and further increased by OAG. The OAG dependent increase was abolished by bis‐1 and down‐regulation of PKC, but basal levels of phosphorylation were unchanged. Deletion of the amino‐terminus of hERG prevented both the modulation of channel activity and the increase of phosphorylation by OAG. Our results are consistent with calcium and/or DAG sensitive isotypes of PKC modulating hERG currents through a mechanism that involves direct phosphorylation of sites on the amino terminus of hERG.
The ins and outs of gradual type inference

Gradual typing lets programmers evolve their dynamically typed programs by gradually adding explicit type annotations, which confer benefits like improved performance and fewer run-time failures. However, we argue that such evolution often requires a giant leap, and that type inference can offer a crucial missing step. If omitted type annotations are interpreted as unknown types, rather than the dynamic type, then static types can often be inferred, thereby removing unnecessary assumptions of the dynamic type. The remaining assumptions of the dynamic type may then be removed by either reasoning outside the static type system, or restructuring the code. We present a type inference algorithm that can improve the performance of existing gradually typed programs without introducing any new run-time failures. To account for dynamic typing, types that flow in to an unknown type are treated in a fundamentally different manner than types that flow out. Furthermore, in the interests of backward-compatibility, an escape analysis is conducted to decide which types are safe to infer. We have implemented our algorithm for ActionScript, and evaluated it on the SunSpider and V8 benchmark suites. We demonstrate that our algorithm can improve the performance of unannotated programs as well as recover most of the type annotations in annotated programs.
Oral ethanol self-administration in rhesus monkeys: behavioral and neurochemical correlates.

BACKGROUND Previous research has revealed that orally administered ethanol serves as a reinforcer in nonhuman primates. The purposes of the present study were to examine the relationship between ethanol preferences and intakes in two distinct self-administration contexts and to reveal some of the behavioral and neurochemical correlates of oral ethanol self-administration in monkeys. METHODS Three cohorts of 13 to 29 rhesus monkeys (Macaca mulatta) were socially housed and given daily, 1-hr, one-spout access to an ethanol solution (8.4%, w/v) sweetened with aspartame. Twelve of these monkeys were subsequently selected, individually housed, and given daily, 2-hr, two-spout access to a range of ethanol concentrations (0.25-16%, w/v) concurrently with water. RESULTS These monkeys (National Institute on Alcohol Abuse and Alcoholism group) showed a marked preference for ethanol (0.5-4%, w/v) over water, and ethanol preferences were 3-fold greater than those of a second group of 12 monkeys (University of Michigan group) purchased from a commercial vendor. Ethanol consumption was consistent across the self-administration paradigms. Monkeys that consumed large quantities of ethanol under the one-spout, social-housing conditions continued to drink large quantities of ethanol under the two-spout, individual-housing conditions (r = 0.86). An association between ethanol preferences and intakes was also demonstrated. Monkeys with the greatest preferences for ethanol over water under the two-spout choice conditions consumed the largest quantities of ethanol (r = 0.82). Finally, cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations were inversely related to ethanol preference but not to ethanol intake. CONCLUSIONS These results indicate that ethanol consumption is stable across contexts and is positively correlated with the preference for ethanol over water.
On the Formalization of Higher Inductive Types and Synthetic Homotopy Theory

The goal of this dissertation is to present synthetic homotopy theory in the setting of homotopy type theory. We will present various results in this framework, most notably the construction of the Atiyah-Hirzebruch and Serre spectral sequences for cohomology, which have been fully formalized in the Lean proof assistant.
Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice

Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage‐specific reverse cholesterol transport, m‐RCT) is an important antiatherogenic pathway. Because exposure of mice to physical restraint, a model of psychological stress, increases serum levels of corticosterone, and as bile acid homeostasis is disrupted in glucocorticoid‐treated animals, we investigated if chronic intermittent restraint stress would modify m‐RCT by altering the enterohepatic circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5 days exhibited increased transit through the large intestine and enhanced fecal bile acid excretion. Of the transcription factors and transporters that regulate bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X receptor (FXR), the bile salt export pump (BSEP), and the intestinal fibroblast growth factor 15 (FGF15) were reduced, whereas those of the ileal apical sodium‐dependent bile acid transporter (ASBT), responsible for active bile acid absorption, remained unchanged. Neither did the hepatic expression of cholesterol 7α‐hydroxylase (CYP7A1), the key enzyme regulating bile acid synthesis, change in the stressed mice. Evaluation of the functionality of the m‐RCT pathway revealed increased fecal excretion of bile acids that had been synthesized from macrophage‐derived cholesterol. Overall, our study reveals that chronic intermittent stress in mice accelerates m‐RCT specifically by increasing fecal excretion of bile acids. This novel mechanism of m‐RCT induction could have antiatherogenic potential under conditions of chronic stress.
The response of regional integrated backscatter levels and regional strain to inotropic stimulation and acute ischemia

Integrated backscatter (IB) and its cyclic variation (CVIB) are echocardiographic parameters used for myocardial tissue characterization. The purpose of this study was to examine the potential mechanisms underlying the CVIB. The relationship between changes in integrated backscatter and regional myocardial strain was investigated by studying the response of both curves to inotropic stimulation and acute ischemia. Changes in integrated backscatter closely paralleled changes in wall thickening but wall thickening alone could not explain our experimental findings. The results presented in this study further support the hypothesis that changes in tissue reflectivity during the cardiac cycle are induced by regional myocardial 3D strain.
Sodium and Calcium Current-Mediated Pacemaker Neurons and Respiratory Rhythm Generation

The breathing motor pattern in mammals originates in brainstem networks. Whether pacemaker neurons play an obligatory role remains a key unanswered question. We performed whole-cell recordings in the preBötzinger Complex in slice preparations from neonatal rodents and tested for pacemaker activity. We observed persistent Na+ current (INaP)-mediated bursting in ∼5% of inspiratory neurons in postnatal day 0 (P0)-P5 and in P8-P10 slices. INaP-mediated bursting was voltage dependent and blocked by 20 μm riluzole (RIL). We found Ca2+ current (ICa)-dependent bursting in 7.5% of inspiratory neurons in P8-P10 slices, but in P0-P5 slices these cells were exceedingly rare (0.6%). This bursting was voltage independent and blocked by 100 μm Cd2+ or flufenamic acid (FFA) (10-200 μm), which suggests that a Ca2+-activated inward cationic current (ICAN) underlies burst generation. These data substantiate our observation that P0-P5 slices exposed to RIL contain few (if any) pacemaker neurons, yet maintain respiratory rhythm. We also show that 20 nm TTX or coapplication of 20 μm RIL + FFA (100-200 μm) stops the respiratory rhythm, but that adding 2 μm substance P restarts it. We conclude that INaP and ICAN enhance neuronal excitability and promote rhythmogenesis, even if their magnitude is insufficient to support bursting-pacemaker activity in individual neurons. When INaP and ICAN are removed pharmacologically, the rhythm can be maintained by boosting neural excitability, which is inconsistent with a pacemaker-essential mechanism of respiratory rhythmogenesis by the preBötzinger complex.