Miracle-dz/UniFAR-FTUs huggingface dataset:
L1 Is Sequentially Processed by Two Differently Activated Metalloproteases and Presenilin/γ-Secretase and Regulates Neural Cell Adhesion, Cell Migration, and Neurite Outgrowth

ABSTRACT The immunoglobulin superfamily recognition molecule L1 plays important functional roles in the developing and adult nervous system. Metalloprotease-mediated cleavage of this adhesion molecule has been shown to stimulate cellular migration and neurite outgrowth. We demonstrate here that L1 cleavage is mediated by two distinct members of the disintegrin and metalloprotease family, ADAM10 and ADAM17. This cleavage is differently regulated and leads to the generation of a membrane bound C-terminal fragment, which is further processed through γ-secretase activity. Pharmacological approaches with two hydroxamate-based inhibitors with different preferences in blocking ADAM10 and ADAM17, as well as loss of function and gain of function studies in murine embryonic fibroblasts, showed that constitutive shedding of L1 is mediated by ADAM10 while phorbol ester stimulation or cholesterol depletion led to ADAM17-mediated L1 cleavage. In contrast, N-methyl-d-aspartate treatment of primary neurons stimulated ADAM10-mediated L1 shedding. Both proteases were able to affect L1-mediated adhesion and haptotactic migration of neuronal cells. In particular, both proteases were involved in L1-dependent neurite outgrowth of cerebellar neurons. Thus, our data identify ADAM10 and ADAM17 as differentially regulated L1 membrane sheddases, both critically affecting the physiological functions of this adhesion protein.
Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future

The proper development and coordination of the hypothalamic-pituitary-gonadal (HPG) axis are essential for normal reproductive competence. The key factor that regulates the function of the HPG axis is gonadotrophin-releasing hormone (GnRH). Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation. Misregulation in this system can result in delayed or absent puberty and infertility. Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are genetic disorders that are rooted in a GnRH deficiency but often accompanied by a variety of non-reproductive phenotypes such as the loss of the sense of smell and defects of the skeleton, eye, ear, kidney, and heart. Recent progress in DNA sequencing technology has produced a wealth of information regarding the genetic makeup of CHH and KS patients and revealed the resilient yet complex nature of the human reproductive neuroendocrine system. Further research on the molecular basis of the disease and the diverse signal pathways involved will aid in improving the diagnosis, treatment, and management of CHH and KS patients as well as in developing more precise genetic screening and counseling regime.
Organizational Citizenship Pressure, Compulsory Citizenship Behavior, and Work-Family Conflict

We sought to explore the mediating effect of compulsory citizenship behavior in the relationship between organizational citizenship pressure and work–family conflict, and the moderating role of job autonomy in influencing the mediation. Through a 3-wave web-based survey of 312 employees in China, we found that organizational citizenship pressure was positively related to compulsory citizenship behavior, the positive impact of citizenship pressure on work–family conflict was mediated by compulsory citizenship behavior, and job autonomy mitigated the above mediation effect. Our findings provide insight into the mechanisms that underpin the effect of organizational citizenship pressure on work–family conflict.
Improving Compliance in Remote Healthcare Systems Through Smartphone Battery Optimization

Remote health monitoring (RHM) has emerged as a solution to help reduce the cost burden of unhealthy lifestyles and aging populations. Enhancing compliance to prescribed medical regimens is an essential challenge to many systems, even those using smartphone technology. In this paper, we provide a technique to improve smartphone battery consumption and examine the effects of smartphone battery lifetime on compliance, in an attempt to enhance users' adherence to remote monitoring systems. We deploy WANDA-CVD, an RHM system for patients at risk of cardiovascular disease (CVD), using a wearable smartphone for detection of physical activity. We tested the battery optimization technique in an in-lab pilot study and validated its effects on compliance in the Women's Heart Health Study. The battery optimization technique enhanced the battery lifetime by 192% on average, resulting in a 53% increase in compliance in the study. A system like WANDA-CVD can help increase smartphone battery lifetime for RHM systems monitoring physical activity.
International Journal of Surgery Case Reports Laparoscopic Resection of Perforated Duodenal Diverticulum – a Case Report and Literature Review

BACKGROUND: Duodenum diverticulum is the most common site for diverticular disease of small intestine. Most of duodenal diverticulum are asymptomatic, but complicated or perforated duodenal diverticulum is rare. Nonoperative management is attractive in selected patients, because of higher surgical complications. We suggest the use of a minimally invasive operative method as an alternative approach for the management of complicated duodenal diverticulum, especially when conservative treatment has failed. CASE PRESENTATION: A 67-year-old female was admitted to Emergency Department with sudden onset of severe right upper abdominal pain and fever (38.2 • C) lasted 8 h. Abdominal computed tomographic imaging was performed and a perforated duodenal diverticulum with right-sided anterior pararenal space free air and fluid retention was identified. After assessment and resuscitation, proper treatment modality was selected taking in consideration type, location and complication of duodenal diverticulum. A emergency laparoscopic duodenal diverticulectomy with intraabdominal drainage was performed. Postoperative period was uneventful and patient was discharged on the 10th postoperative day. English literatures discussing laparoscopic management for complicated duodenal diverticulum were carefully reviewed. CONCLUSIONS: Laparoscopic approach showed less complication, shorted hospital stay and better outcome in comparison to conservative, or open surgery. Laparoscopic approach is safe and feasible in selected cases of complicated duodenal diverticulum (laterally located and protruding duodenal divertic-ulum). With advances in laparoscopic instruments and techniques, complicated duodenal diverticulums can be managed safely by laparoscopically.
Can keratin 8 and 17 immunohistochemistry be of diagnostic value in cervical cytology?

Based on results from evaluation of tissue sections from premalignant lesions of the uterine cervix, the authors examined the hypothesis that immunostaining of Papanicolaou‐stained cytologic smears with monoclonal antibodies to keratins 8 and 17 allows detection of cervical intraepithelial neoplasia (CIN) with progressive potential. They also investigated whether detection of these two keratin subtypes could be of help in the analysis of normal and/or poor quality cytology smears.
Ballistic phase of self-interacting random walks

We explain a unified approach to a study of ballistic phase for a large family of self-interacting random walks with a drift and self-interacting polymers with an external stretching force. The approach is based on a recent version of the Ornstein-Zernike theory developed in earlier works. It leads to local limit results for various observables (e.g. displacement of the end-point or number of hits of a fixed finite pattern) on paths of n-step walks (polymers) on all possible deviation scales from CLT to LD. The class of models, which display ballistic phase in the "universality class" discussed in the paper, includes self-avoiding walks, Domb-Joyce model, random walks in an annealed random potential, reinforced polymers and weakly reinforced random walks.
Limits of Arbitrage: Theory and Evidence from the Mortgage-Backed Securities Market

We present the continuous time version of our two period model. The economic conclusions are the same, though the two period model is much simpler to manipulate. Indeed, in general, the continuous time model requires the use of Malliavin calculus. This continuous time version is likely to be useful for practical implementations of the model.
When and What Parents Tell Children About Race: An Examination of Race-Related Socialization Among African American Families

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Automated Identification of Basic Control Charts Patterns Using Neural Networks

The identification of control chart patterns is very important in statistical process control. Control chart patterns are categorized as natural and unnatural. The presence of unnatural patterns means that a process is out of statistical control and there are assignable causes for process variation that should be investigated. This paper proposes an artificial neural network algorithm to identify the three basic control chart patterns; natural, shift, and trend. This identification is in addition to the traditional statistical detection of runs in data, since runs are one of the out of control situations. It is assumed that a process starts as a natural pattern and then may undergo only one out of control pattern at a time. The performance of the proposed algorithm was evaluated by measuring the probability of success in identifying the three basic patterns accurately, and comparing these results with previous research work. The comparison showed that the proposed algorithm realized better identification than others.
Exploring the effects of organizational justice, personal ethics and sanction on internet use policy compliance

Internet security risks, the leading security threats confronting today's organizations, often result from employees' non‐compliance with the internet use policy (IUP). Extant studies on compliance with security policies have largely ignored the impact of intrinsic motivation on employees' compliance intention. This paper proposes a theoretical model that integrates an intrinsic self‐regulatory approach with an extrinsic sanction‐based command‐and‐control approach to examine employees' IUP compliance intention. The self‐regulatory approach centers on the effect of organizational justice and personal ethical objections against internet abuses. The results of this study suggest that the self‐regulatory approach is more effective than the sanction‐based command‐and‐control approach. Based on the self‐regulatory approach, organizational justice not only influences IUP compliance intention directly but also indirectly through fostering ethical objections against internet abuses. This research provides empirical evidence of two additional effective levers for enhancing security policy compliance: organizational justice and personal ethics.
Logico-perceptual and language prerequisites for beginning reading.

LOGICO-PERCEPTUAL AND LANGUAGE PREREQUISITES FOR BEGINNING READING (May 1981) Cynthia Miller-Jones , B.A. University of Oregon, M.Ed. University of Massachusetts/Amherst, Ed.D. University of Massachusetts/Amherst Directed by: Professor Ronald K. Hambleton The purpose of the present study was to identify specific aspects of language and logi co-perceptual development that could be causally related to success in beginning reading. Based on the observation that essentially all reading research tended to deal with isolated aspects of the process, it was felt that the integrated nature of children's (and all human) thinking processes was a critical consideration for analysis of possible causal relationships for success in beginning reading. Techniques for approaching questions of causality and research designs that answer those questions were discussed. Based on the theories of Jean Piaget and Noam Chomsky, and a review of the literature, four hypotheses were tested: 1) the more advanced a child's logi co-perceptual skills, the easier he/she will learn to read; 2) the better a child's language comprehension the easier he/she will learn to read; 3) the better he/she visually organizes print (orthography perception), the easier he/she will learn to read; 4) high levels in both language and logi co-perceptual development facilitate learning to read. A combination of a cross-sectional and
Modified UTAUT2 model for m-learning among students in India

Ubiquitous technologies have a great potential to enrich students' academic experience. Students are more interested in using interactive learning techniques apart from the traditional learning techniques. Several research studies for m-learning has been done in the USA, UK concentrating on students undergoing a graduation degree, especially subjects like engineering, arts, maths, science, etc. Hence the need has arisen to conduct a separate research on m-learning in the Indian context. This study proposes a modified UTAUT2 (unified theory of acceptance and use of technology) model with nine core independent determinants predicting the tenth dependent variables construct. Data analysis has been done using both the descriptive (frequency counts, percentages, and means) and inferential statistics (correlation analysis, multiple linear regression analysis and principal component analysis). This study aims to develop a new model that encompasses the factors affecting the utilisation of ubiquitous technology among students in institutes of higher education, particularly in India.
Disability-policy models in European welfare regimes: comparing the distribution of social protection, labour-market integration and civil rights

Abstract This paper examines different models of disability policy in European welfare regimes on the basis of secondary data. OECD data measuring social protection and labour-market integration is complemented with an index which measures the outcomes of disability civil rights. Eurobarometer data is used to construct the index. The country modelling by cluster analysis indicates that an encompassing model of disability policy is mainly prevalent in Nordic countries. An activating and rehabilitating disability-policy model is predominant mainly in Central European countries, and there is evidence for a distinct Eastern European model characterized by relatively few guaranteed civil rights for disabled people. Furthermore, the Southern European model, which indicates a preference for social protection rather than activation and rehabilitation, includes countries which normally have diverse welfare traditions.
Mechanism of Action of a Novel Human ether-a-go-go-Related Gene Channel Activator

1,3-Bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) is a newly discovered activator of human ether-a-go-go-related gene (hERG) K+ channels. Here, we characterize the effects of this compound on cloned hERG channels heterologously expressed in Xenopus laevis oocytes. When assessed with 2-s depolarizations, NS1643 enhanced the magnitude of wild-type hERG current in a concentration- and voltage-dependent manner with an EC50 of 10.4 μM at –10 mV. The fully activated current-voltage relationship revealed that the drug increased outward but not inward currents, consistent with altered inactivation gating. NS1643 shifted the voltage dependence of inactivation by +21 mV at 10 μM and +35 mV at 30 μM, but it did not alter the voltage dependence of activation of hERG channels. The effects of the drug on three inactivation-deficient hERG mutant channels (S620T, S631A, and G628C/S631C) were determined. In the absence of channel inactivation, NS1643 did not enhance hERG current magnitude. The agonist activity of NS1643 was facilitated by mutations (F656 to Val, Met, or Thr) that are known to greatly attenuate channel inhibition by hERG blockers. We conclude that NS1643 is a partial agonist of hERG channels and that the mechanism of activation is reduced channel inactivation.
Engineering a Stable and Selective Peptide Blocker of the Kv1.3 Channel in T Lymphocytes

Kv1.3 potassium channels maintain the membrane potential of effector memory (TEM) T cells that are important mediators of multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. The polypeptide ShK-170 (ShK-L5), containing an N-terminal phosphotyrosine extension of the Stichodactyla helianthus ShK toxin, is a potent and selective blocker of these channels. However, a stability study of ShK-170 showed minor pH-related hydrolysis and oxidation byproducts that were exacerbated by increasing temperatures. We therefore engineered a series of analogs to minimize the formation of these byproducts. The analog with the greatest stability, ShK-192, contains a nonhydrolyzable phosphotyrosine surrogate, a methionine isostere, and a C-terminal amide. ShK-192 shows the same overall fold as ShK, and there is no evidence of any interaction between the N-terminal adduct and the rest of the peptide. The docking configuration of ShK-192 in Kv1.3 shows the N-terminal para-phosphonophenylalanine group lying at the junction of two channel monomers to form a salt bridge with Lys411 of the channel. ShK-192 blocks Kv1.3 with an IC50 of 140 pM and exhibits greater than 100-fold selectivity over closely related channels. After a single subcutaneous injection of 100 μg/kg, ∼100 to 200 pM concentrations of active peptide is detectable in the blood of Lewis rats 24, 48, and 72 h after the injection. ShK-192 effectively inhibits the proliferation of TEM cells and suppresses delayed type hypersensitivity when administered at 10 or 100 μg/kg by subcutaneous injection once daily. ShK-192 has potential as a therapeutic for autoimmune diseases mediated by TEM cells.
SPECIFIC BINDING OF NERVE GROWTH FACTOR (NGF) BY MURINE C 1300 NEUROBLASTOMA CELLS

Murine C 1300 neuroblastoma cells bind with high avidity on their membrane surface the nerve growth factor (NGF), a protein capable of inducing differentiation of sympathetic nerve cells. The total binding capacity of NGF by the cells was quantitatively measured by a radioimmunoassay technique, using 125I-labeled NGF. An average number of about 106 molecules of NGF could be bound, at saturation, by each cell with an average relative association constant of about 107 liters/mol. Using synchronized cells, it was found, however, that either the number of molecules of ligand bound or the avidity of the binding interaction between NGF and cells varied depending upon their growth cycle, the maximal-binding occurring during the G1 and early S phase. Binding of [125I]NGF was suppressed by trypsin treatment of the cells, however new receptor sites were rapidly replaced onto the membrane surface within 1–2 h. Cells exposed to 3 M KCl released into the supernate a protein product exhibiting similar high avidity for NGF. Acrylamide gel electrophoresis suggested a restricted molecular heterogeneity of this product, with a major component in the 52,000 mol wt region. Antibodies made specific to this protein were capable, in the absence of the complement, of inhibiting the binding of [125I]NGF by the cells and in the presence of the complement they killed them.
The intrinsically disordered C-terminal domain of the measles virus nucleoprotein interacts with the C-terminal domain of the phosphoprotein via two distinct sites and remains predominantly unfolded

Measles virus is a negative‐sense, single‐stranded RNA virus within theMononegavirales order,which includes several human pathogens, including rabies, Ebola, Nipah, and Hendra viruses. Themeasles virus nucleoprotein consists of a structured N‐terminal domain, and of an intrinsically disordered C‐terminal domain, NTAIL (aa 401–525), which undergoes induced folding in the presence of the C‐terminal domain (XD, aa 459–507) of the viral phosphoprotein. With in NTAIL, an α‐helical molecular recognition element (α‐MoRE, aa 488–499) involved in binding to P and in induced folding was identified and then observed in the crystal structure of XD. Using small‐angle X‐ray scattering, we have derived a low‐resolution structural model of the complex between XD and NTAIL, which shows that most of NTAIL remains disordered in the complex despite P‐induced folding within the α‐MoRE. The model consists of an extended shape accommodating the multiple conformations adopted by the disordered N‐terminal region of NTAIL, and of a bulky globular region, corresponding to XD and to the C terminus of NTAIL (aa 486–525). Using surface plasmon resonance, circular dichroism, fluorescence spectroscopy, and heteronuclear magnetic resonance, we show that NTAIL has an additional site (aa 517–525) involved in binding to XD but not in the unstructured‐to‐structured transition. This work provides evidence that intrinsically disordered domains can establish complex interactions with their partners, and can contact them through multiple sites that do not all necessarily gain regular secondary structure.
Neural Mechanisms for Integrating Prior Knowledge and Likelihood in Value-Based Probabilistic Inference

In Bayesian decision theory, knowledge about the probabilities of possible outcomes is captured by a prior distribution and a likelihood function. The prior reflects past knowledge and the likelihood summarizes current sensory information. The two combined (integrated) form a posterior distribution that allows estimation of the probability of different possible outcomes. In this study, we investigated the neural mechanisms underlying Bayesian integration using a novel lottery decision task in which both prior knowledge and likelihood information about reward probability were systematically manipulated on a trial-by-trial basis. Consistent with Bayesian integration, as sample size increased, subjects tended to weigh likelihood information more compared with prior information. Using fMRI in humans, we found that the medial prefrontal cortex (mPFC) correlated with the mean of the posterior distribution, a statistic that reflects the integration of prior knowledge and likelihood of reward probability. Subsequent analysis revealed that both prior and likelihood information were represented in mPFC and that the neural representations of prior and likelihood in mPFC reflected changes in the behaviorally estimated weights assigned to these different sources of information in response to changes in the environment. Together, these results establish the role of mPFC in prior-likelihood integration and highlight its involvement in representing and integrating these distinct sources of information.