Miracle-dz/UniFAR-FTUs huggingface dataset:
Ephrin-B/EphB Signaling Is Required for Normal Innervation of Lingual Gustatory Papillae

The innervation of taste buds is an excellent model system for studying the guidance of axons during targeting because of their discrete nature and the high fidelity of innervation. The pregustatory epithelium of fungiform papillae is known to secrete diffusible axon guidance cues such as BDNF and Sema3A that attract and repel, respectively, geniculate ganglion axons during targeting, but diffusible factors alone are unlikely to explain how taste axon terminals are restricted to their territories within the taste bud. Nondiffusible cell surface proteins such as Ephs and ephrins can act as receptors and/or ligands for one another and are known to control axon terminal positioning in several parts of the nervous system, but they have not been studied in the gustatory system. We report that ephrin-B2 linked β-galactosidase staining and immunostaining was present along the dorsal epithelium of the mouse tongue as early as embryonic day 15.5 (E15.5), but was not detected at E14.5, when axons first enter the epithelium. Ephrin-B1 immunolabeling was barely detected in the epithelium and found at a somewhat higher concentration in the mesenchyme subjacent to the epithelium. EphB1 and EphB2 were detected in lingual sensory afferents in vivo and geniculate neurites in vitro. Ephrin-B1 and ephrin-B2 were similarly effective in repelling or suppressing outgrowth by geniculate neurites in vitro. These in vitro effects were independent of the neurotrophin used to promote outgrowth, but were reduced by elevated levels of laminin. In vivo, mice null for EphB1 and EphB2 exhibited decreased gustatory innervation of fungiform papillae. These data provide evidence that ephrin-B forward signaling is necessary for normal gustatory innervation of the mammalian tongue.
The protein kinase PERK/EIF2AK3 regulates proinsulin processing not via protein synthesis but by controlling endoplasmic reticulum chaperones

Loss-of-function mutations of the protein kinase PERK (EIF2AK3) in humans and mice cause permanent neonatal diabetes and severe proinsulin aggregation in the endoplasmic reticulum (ER), highlighting the essential role of PERK in insulin production in pancreatic β cells. As PERK is generally known as a translational regulator of the unfolded protein response (UPR), the underlying cause of these β cell defects has often been attributed to derepression of proinsulin synthesis, resulting in proinsulin overload in the ER. Using high-resolution imaging and standard protein fractionation and immunological methods we have examined the PERK-dependent phenotype more closely. We found that whereas proinsulin aggregation requires new protein synthesis, global protein and proinsulin synthesis are down-regulated in PERK-inhibited cells, strongly arguing against proinsulin overproduction being the root cause of their aberrant ER phenotype. Furthermore, we show that PERK regulates proinsulin proteostasis by modulating ER chaperones, including BiP and ERp72. Transgenic overexpression of BiP and BiP knockdown (KD) both promoted proinsulin aggregation, whereas ERp72 overexpression and knockdown rescued it. These findings underscore the importance of ER chaperones working in concert to achieve control of insulin production and identify a role for PERK in maintaining a functional balance among these chaperones.
Likelihood procedure for testing changes in skew normal model with applications to stock returns

ABSTRACT The skew normal distribution family is an attractive distribution family due to its mathematical tractability and inclusion of the normal distribution as the special case. It has wide applications in many applied fields such as finance, economics, and medical research. Such a distribution family has been studied extensively since it was introduced by Azzalini in 1985 for the first time. Yet, few work has been done on the study of change point problem related to this distribution family. In this article, we propose the likelihood ratio test (LRT) to detect changes in the parameters of the skew normal distribution associated with some asymptotic results of the test statistic. Simulations have been conducted under different scenarios to investigate the performance of the proposed method. Comparisons to some other existing method indicate the comparable power of the method in detecting changes in parameters of the skew normal distribution model. Applications on two real data: Brazilian and Tanzanian stock returns illustrate the detection procedure.
Role of cardiac electronic implantable device in the stratification and management of embolic risk of silent atrial fibrillation: are all atrial fibrillations created equal?

ABSTRACT Introduction: Ischemic strokes may be associated with atrial fibrillation (AF). AF detection is critical in ischemic stroke survivors, often recommending a switch from antiplatelet therapy to oral anticoagulants for secondary prevention. Areas covered: Cardiac implantable electronic devices (CIED) with their long-term recording capability allows to document AF and to quantify the arrhythmia burden. Recent series in pacemaker and implantable cardioverter-defibrillator (ICD) recipients with no prior stroke showed that short episodes of AF increased stroke risk compared with those without AF recorded. Detection of AF by CIEDs represent a unique opportunity for promp prevention of embolic risk in silent AF. It will be attractive to identify AF before a stroke occurs. Expert commentary: The purpose of this article is to review the role of CIED to detect AF, to quantify the role of AF burden, and to guide primary and secondary stroke prevention.
House Dust Mite Allergen Characterisation: Implications for T-Cell Responses and Immunotherapy

T cells are central regulators and mediators of allergic sensitisation and disease. The house dust mite allergens are a biochemically diverse group of proteins which are present in extracts and the environment in a wide range of concentrations. Here the importance of ascertaining the contribution of the different allergens to Th2 lymphokine production and the development of allergy is discussed as well as the effect of allelic polymorphisms and inter-species sequence diversity on T-cell activation. The imbalances in allergen concentrations in commercial extracts, the sequence variations from allergens in the environment and the poor discrimination of allergy due to different mite species points to areas of improvement and the development of novel immunotherapeutic strategies and reagents.
Calcium dependence of spontaneous neurotransmitter release

Spontaneous release of neurotransmitters is regulated by extracellular [Ca2+] and intracellular [Ca2+]. Curiously, some of the mechanisms of Ca2+ signaling at central synapses are different at excitatory and inhibitory synapses. While the stochastic activity of voltage‐activated Ca2+ channels triggers a majority of spontaneous release at inhibitory synapses, this is not the case at excitatory nerve terminals. Ca2+ release from intracellular stores regulates spontaneous release at excitatory and inhibitory terminals, as do agonists of the Ca2+‐sensing receptor. Molecular machinery triggering spontaneous vesicle fusion may differ from that underlying evoked release and may be one of the sources of heterogeneity in release mechanisms.
A GA-based method for sales order allocation in a MTS/MTO supply chain

Today's manufacturing environment has shifted from mass production to mass customization where products are specially catered to customers' varying preferences. To avoid having high inventory levels in this high mix low volume environment, supply chains are adopting the Make-To-Order (MTO) production strategy. This allows companies to have intermediate inventory for generic parts and the remaining production processes only resume when demand is known. However, with this strategy, the new challenge is to ensure fulfilment of orders before their respective due dates. To address such challenge, this paper proposes a Genetic Algorithm (GA)-based method for the allocation of customized orders to different MTO production sites. The proposed method generates an allocation plan that minimizes the transportation and backorder cost. Efforts have been made to improve solution accuracy by incorporating in the GA's fitness function estimates of each allocated order's completion date based on actual conditions in a job shop manufacturing environment.
Effects of search strategies on fault diagnosis performance

This paper investigates the effects of two diagnostic search strategies (decision table search and hypothesis-and-test search) on fault diagnosis performance, and whether cognitive styles could mediate these effects. A simulated nuclear power plant main control room prototype was employed as a test case for fault diagnosis experiments. Performance was measured by diagnosis accuracy, completion time, frequency of display switching occurrences, mental workload, and self-reported confidence level in the diagnosis task. Results revealed a significant effect of search strategy on the number of display switches, with significantly fewer occurrences for the group using the decision table search strategy as compared to that of the hypothesis-and-test search strategy group. No significant effect of search strategy was observed on the other diagnosis performance measures after controlling for possible effects of cognitive styles. The results suggest a potential advantage of using a decision table search strategy for fault diagnosis given its smaller associated magnitude of display switching.
Stillinger–Weber potential for elastic and fracture properties in graphene and carbon nanotubes

This paper presents a new framework for determining the Stillinger–Weber (SW) potential parameters for modeling fracture in graphene and carbon nanotubes. In addition to fitting the equilibrium material properties, the approach allows fitting the potential to the forcing behavior as well as the mechanical strength of the solid, without requiring ad hoc modification of the nearest-neighbor interactions for avoiding artificial stiffening of the lattice at larger deformation. Consistent with the first-principles results, the potential shows the Young’s modulus of graphene to be isotropic under symmetry-preserving and symmetry-breaking deformation conditions. It also shows the Young’s modulus of carbon nanotubes to be diameter-dependent under symmetry-breaking loading conditions. The potential addresses the key deficiency of existing empirical potentials in reproducing experimentally observed glass-like brittle fracture in graphene and carbon nanotubes. In simulating the entire deformation process leading to fracture, the SW-potential costs several factors less computational time compared to the state-of-the-art interatomic potentials that enables exploration of the fracture processes in large atomistic systems which are inaccessible otherwise.
The role and therapeutic targeting of IL-6 in rheumatoid arthritis

ABSTRACT Introduction: Rheumatoid arthritis (RA) is an autoimmune chronic disease with joint and systemic inflammation and it has been found that interleukin-6 (IL-6) plays a key role in RA. Indeed, various clinical studies have proved that the first-in-class IL-6 inhibitor, tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody, showed outstanding efficacy in RA. Areas covered: We review here the role of IL-6 in the inflammatory conditions and how IL-6 contributes to pathogenesis of RA, what induces IL-6 and how IL-6 expression is regulated. Furthermore, clinical studies of tocilizumab for RA are summarized, Expert commentary: We review and discuss the prospects for future applications of IL-6 targeting therapy and new therapeutic strategies targeting IL-6. Finally, we discuss relevant issues with regard to the clinical management of IL-6 blockade in RA.
Efficient Decoupling Capacitor Placement Based on Driving Point Impedance

With rapidly increasing switching speeds and surge current requirements, placement of local decoupling capacitors is becoming critically important in high-speed low-power designs. In this paper, utilizing the driving-point impedance (viewed from the device pin) as a metric, a new method is presented for the placement of decoupling capacitors in parallel-plate power ground pairs of high-speed circuits. In the proposed approach, instead of using the traditional trial-and-error method to identify an appropriate placement distance, the process is formulated in the form of a transcendental function. The resulting function is solved using Newton–Raphson (N-R) iterations to give a direct solution for the distance. Also, an analytical representation based on Hankel functions for the driving point impedance and its derivatives is developed to speed up the N-R iterations. The proposed method is validated by comparing the results with the full-wave electromagnetic simulations.
Power planning of sundargarh town

Power planning is the process of predicting the future load. This paper presents a methodology to evaluate the amount of power supply provided to a region and the power demand of Sundargarh town. The D. Gs sets are surveyed to analyze the reliability of power supply for the projection process by determining the present and past scenario of energy demand and by considering the number of load shedding and whether the energy supplied to the region is sufficient or not through the two medium term and long term methods of load forecasting one is Econometric approach and other is End use approach which includes the statistical information about the customer classes, energy demand and different factors of load forecasting like weather and time factors that are essential basis for projection of future energy demand. From the present and past scenario of load demand a load curve is obtained. Though power supply is not sufficient enough still D. Gs are there to en capsule the power supply to a degree.
A soft multi-module manipulator with variable stiffness for minimally invasive surgery

This work presents a soft manipulator for minimally invasive surgery inspired by the biological capabilities of the octopus arm. The multi-module arm is composed of three identical units, which are able to move thanks to embedded fluidic actuators that allow omnidirectional bending and elongation, typical movements of the octopus. The use of soft materials makes the arm safe, adaptable and compliant with tissues. In addition, a granular jamming-based stiffening mechanism is integrated in each module with the aim of tuning the stiffness of the manipulator and controlling the interactions with biological structures. A miniaturized camera and a pneumatic gripper have been purposely designed and integrated on the tip of the manipulator making it usable in real working conditions. This work reports the design and the fabrication process of the manipulator, the theoretical and experimental evaluation of the stiffness and the analysis of the motion workspace. Finally, pick and place tests with the fully integrated system are shown.
Strong Heterogeneity in Advances in Cryopreservation Techniques in the Mammalian Orders

Between 1970 and 2012, vertebrate abundance has declined by 58% with an average annual decline of 2%, calling for serious action to prevent a mass extinction and an irreversible loss of biodiversity. Cryobanks and cryopreservation have the potential to assist and improve ex situ and in situ conservation strategies by storing valuable genetic material. A great deal of studies concerning cryopreservation have been performed within the class Mammalia, although no systematic overview has previously been presented. The objective of this study is therefore to evaluate the status, pattern and future of cryopreservation within Mammalia. A strong disproportional distribution of studies in examined orders is displayed. For the majority of examined orders less than 10% of species has been examined. However, the cryopreservation of germplasm has in several cases been successful and resulted in successful applications of assisted reproductive techniques (ARTs). Various obstacles are associated with the development of cryopreservation protocols, and among them the most prominent is interspecific differences in cryotolerance. Extrapolation of protocols in closely related species is considered the most applicable procedure, and a future supplement to overcome this problem is the examination and comparison of cryobiological traits. Successful protocols have been developed for the vast majority of domesticated mammals, which gives incentive for the further extrapolation of protocols in threatened species.
The inhibitory effect of miR-375 targeting sp1 in colorectal cancer cell proliferation.

OBJECTIVE Sp1 is a member of super zinc finger structure family that participates in cancer cells' apoptosis, proliferation, survival, and differentiation. This study detected the expressions of miR-375 and sp1 in colorectal cancer tissue and cells to analyze their impact on cell proliferation. PATIENTS AND METHODS Colorectal cancer patients in our hospital were enrolled. HCT-116 cell was transfected with miR-375 mimics, mimics control, and miR-375 + sp1, respectively. RT-PCR and Western blot were applied to detect expressions of miR-375 and sp1 at mRNA and protein level in colorectal cancer tissue, para-carcinoma tissue, and normal colorectal tissue. RT-PCR and Western blot were used to test levels of miR-375 and sp1 in HCT-116 cells after transfection. MTT assay was performed to determine HCT-116 cell proliferation. RESULTS Our data showed that miR-375 was downregulated, while sp1 was overexpressed in colorectal cancer tissue compared with that in para-carcinoma tissue and normal control (p < 0.05). MiR-375 level was elevated, while sp1 mRNA was declined after miR-375 mimic transfection (p < 0.05). Compared with miR-375 mimic group, the levels of miR-375 and sp1 showed no difference in miR-375 + sp1 group (p > 0.05). Of note, the increase of MiR-375 and reduction of sp1 were in a time-dependent manner (p < 0.05). The cell proliferation rate in miR-375 mimic group was significantly decreased compared with that in mimic control and blank group (p < 0.05). The cell proliferation rate in miR-375 + sp1 group was significantly higher than that miR-375 group, but still lower than the control (p < 0.05). The proliferation rate gradually declined in a time-dependent manner (p < 0.05). CONCLUSIONS MiR-375 was decreased and sp1 level was enhanced in colorectal cancer. MiR-375 suppresses the proliferation of colorectal cancer cells via the inhibition of sp1 expression at posttranscriptional level.
Social Support in Worksite Smoking Cessation: Qualitative Analysis of the EASE Project

Purpose. Mobilize and study social support in EASE, a worksite smoking cessation program. Design. Qualitative study of social support in two pilot and two test worksites. Setting. Collaboration with American Lung Association of eastern Missouri to implement program in 12 companies between 1982 and 1985. Subjects. Ninety-eight participants in cessation clinics at pilot and test sites and 350 randomly sampled respondents from among all 877 employees at test sites. Intervention. Steering committees included representatives of management and line employees and tailored the program from plans and materials for program promotion, self-help manuals, and a standard curriculum for a Group Comprehensive Clinic. Measures. Implementation and participation from project records. Outcomes and perceptions of social support from surveys of employees. Results. Twelve to 24 months after program initiation, smoking cessation among active participants ranged from 21% to 41%. Consistent with emphasis on promoting support for quitting throughout the worksite, 10% to 25% of nonparticipants were abstinent at follow-ups, exceeding national base rates. Surveys indicated greater importance of social support than of program's procedures or materials and greater benefits of social ties to nonsmokers than to others attempting to quit. Differences among companies in both reported social support for nonsmoking and cessation rates paralleled differences in Steering Committees' activities and organizational support for the program. Conclusion. Though limited by lack of experimental controls, this qualitative study of active program participants as well as random samples of all employees indicates social support can be a strength of worksite smoking cessation programs.
Induction of Immunoglobulin Heavy-Chain Transcription through the Transcription Factor Bright Requires TFII-I

ABSTRACT Bright/ARID3a/Dril1, a member of the ARID family of transcription factors, is expressed in a highly regulated fashion in B lymphocytes, where it enhances immunoglobulin transcription three- to sixfold. Recent publications from our lab indicated that functional, but not kinase-inactive, Bruton's tyrosine kinase (Btk) is critical for Bright activity in an in vitro model system, yet Bright itself is not appreciably tyrosine phosphorylated. These data suggested that a third protein, and Btk substrate, must contribute to Bright-enhanced immunoglobulin transcription. The ubiquitously expressed transcription factor TFII-I was identified as a substrate for Btk several years ago. In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels. These data suggest that Bright functions as a three-component protein complex in the immunoglobulin locus and tie together previous data indicating important roles for Btk and TFII-I in B lymphocytes.
ADAMTS5 deficiency protects against non‐alcoholic steatohepatitis in obesity

Increased prevalence of obesity is paralleled by an increase in non‐alcoholic steatohepatitis (NASH). We previously found that the expression of ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin type 1 motifs; member 5) is enhanced in expanding adipose tissue. However, no information is available on a potential role in liver pathology. We studied the effect of ADAMTS5 deficiency on NASH in mice.
A Bayesian Probabilistic Approach for Acoustic Emission‐Based Rail Condition Assessment

The investigation described in this article aims at developing a Bayesian‐based approach for probabilistic assessment of rail health condition using acoustic emission monitoring data. It comprises the following three phases: (i) formulation of a frequency‐domain structural health index (SHI), via a linear transformation method, tailored to damage‐sensitive frequency bandwidth; (ii) establishment of data‐driven reference models, using Bayesian regression about the real and imaginary parts of the SHI derived with monitoring data from the intact rail; and (iii) quantitative evaluation of discrimination between the new observations representative of current rail health condition and the baseline model predictions in terms of Bayes factor. If the deviation of the new observations from the predictions is within an acceptable tolerance, no damage is flagged, and the new data are further used to update and refine the reference models. If the observations deviate substantially from the model predictions in a probabilistic sense, damage is signaled, damage severity is quantified, and damage location determined. The proposed approach is examined by using field monitoring data acquired from an instrumented railway turnout, and the coincidence between the assessment results and the actual health conditions demonstrates its effectiveness in damage detection, localization, and quantification.