Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of calcium in lipopolysaccharide-stimulated tumor necrosis factor and interleukin-1 signal transduction in naive and endotoxin-tolerant murine macrophages.

OBJECTIVE Dysregulated macrophage cytokine production may predispose to organ failure during sepsis. Macrophages pretreated in vitro with low-dose endotoxin (LPSp) become "tolerant" to subsequent lipopolysaccharide (LPS) activation (LPSa), characterized by inhibition of tumor necrosis factor (TNF) and augmentation of interleukin-1 (IL-1). To understand cytokine dysregulation we examined the Ca2+ dependence of TNF and IL-1 signal transduction to LPSa and whether it was altered by LPSp. METHODS Murine peritoneal exudate macrophages received +/- 100 ng/mL of LPSp for 24 hours. Cultures were pretreated for 2 hours with specific signal transduction inhibitors (verapamil, a Ca2+ channel inhibitor; TMB-8, an inhibitor of intracellular Ca2+ release; U73122, an inhibitor of phospholipase C; or W7, a calmodulin inhibitor) before 24 hours LPSa-stimulation. TNF and IL-1 mRNA were estimated 6 hours after LPSa by using reverse transcriptase polymerase chain reaction. Supernatant TNF and IL-1 were measured by bioassay. RESULTS Treatment with verapamil, TMB-8, U73122, or W7 markedly inhibited TNF release by LPSa, but had little effect on IL-1 release. Reprogramming by LPSp did not alter the Ca2+ signal transduction pathways for either cytokine. U73122 and verapamil did prevent the augmentation of IL-1 release seen after LPSp. TNF message was present after LPSa despite reprogrammed inhibition of TNF protein by LPSp. Signal transduction inhibitors that blocked Ca2+ altered TNF and IL-1 message in reprogrammed macrophages in a pattern similar to their effects on naive cells. CONCLUSIONS Intracellular Ca2+ is required for TNF protein release by naive macrophages and TNF mRNA transcription of both naive and LPSp reprogrammed cells, however LPSa-stimulated IL-1 release in peritoneal macrophages does not require Ca2+ dependent signaling pathways.
Role of Liver Transplantation in Cancer Therapy

Fifty-four patients underwent total hepatectomy and liver replacement in the presence of a primary liver malignancy. In 13 recipients in whom the hepatic tumors were incidental to some other endstage liver disease, recurrence was not seen and 12 of the 13 patients are alive after 4 months to 15 1/2 years. In contrast, tumors recurred in 3 of every 4 patients who received liver replacement primarily because of hepatic malignancies that could not be resected by conventional techniques of subtotal hepatectomy and who lived for at least 2 months after transplantation. The most encouraging results were in patients with the fibrolamellar hepatocellular carcinomas that grow slowly and metastasize late, but even with this lesion, the recurrence rate was 57%. In future trials, additional effective anticancer therapy will be needed to improve the results of liver transplantation for primary liver malignancy, but what an improved strategy should be has not yet been defined.
Structural basis of inhibitor affinity to variants of human carbonic anhydrase II.

The activities and structures of certain L198 variants of human carbonic anhydrase II (CAII) have been reported recently [Krebs, J. F. , Rana, F. , Dluhy, R. A. , & Fierke, C. A. (1993) Biochemistry 32, 4496-4505; Nair, S. K. , & Christianson, D. W. (1993) Biochemistry 32, 4506-4514]. In order to understand the structural basis of enzyme-inhibitor affinity, we now report the dissociation rate and equilibrium constants for acetazolamide and dansylamide binding to 13 variants of CAII containing substituted amino acids at position 198. These data indicate that inhibitor affinity is modulated by the hydrophobicity and charge of the 198 side chain. Furthermore, we have determined crystal structures of L198R, L198E, and L198F CAIIs complexed with the transition state analog acetazolamide. The substituted benzyl side chain of L198F CAII does not occlude the substrate association pocket, and it is therefore not surprising that this substitution has minimal effects on catalytic properties and inhibitor binding. Nevertheless, the F198 side chain undergoes a significant conformation change in order to accommodate the binding of acetazolamide; the same behavior is observed for the engineered side chain of L198R CAII. In contrast, the engineered side chain of L198E CAII does not alter its conformation upon inhibitor binding. We conclude that the mobility and hydrophobicity or residue 198 side chains affect enzyme-inhibitor (and enzyme-substrate) affinity, and these structure-function relationships are important for understanding the behavior of carbonic anhydrase isozyme III, which bears a wild-type F198 side chain. (ABSTRACT TRUNCATED AT 250 WORDS)
Managing One Master Data - Challenges and Preconditions

– This paper aims to provide a framework of the multidimensional concept of one master data. Preconditions required for successful one master data implementation and usage in large high‐tech companies are presented and related current challenges companies have today are identified. , – This paper is qualitative in nature. First, literature was studied to find out the elements of one master data. Second, an interview study was carried out in eight high‐tech companies and in three expert companies. , – One master data management framework is the composition of data, processes and information systems. Accordingly, the key challenges related to the data are that the definitions of master data are unclear and overall data quality is poor. Challenges on processes related to managing master data are inadequately defined data ownership, incoherent data management practices and lack of continuous data quality practices. Integrations between applications are fundamental challenge to tackle when constructing an holistic one master data. , – Studied companies are vanguards in the area of master data management (MDM), providing good views on topical issues in large companies. This study offers a general view of the topic but not describes special company situations as companies need to adapt the presented concepts for their specific case. Significant implication for future research is that MDM can no more be classified and discussed as only an IT problem but it is a managerial challenge which requires structural changes on mindset how issues are handled. , – This paper provides a better understanding over the issues which are impacting on the implementation of one master data. The preconditions of implementing and executing one master data are: an organization wide and defined data model; clear data ownership definitions; pro‐active data quality surveillance; data friendly company culture; the clear definitions of roles and responsibilities; organizational structure that supports data processes; clear data process definitions; support from the managerial level; and information systems that utilize the unified data model. The list of preconditions is wide and it also describes the incoherence of current understanding about MDM. This list helps business managers to understand the extent of the concept and to see that master data management is not only an IT issue. , – The existing practical research on master data management is limited and, for example, the general challenges have not been reported earlier. This paper offers practical research on one master data. The obtained results illustrates the extent of the topic and the fact that business relevant data management is not only an IT (application) issue but requires understanding of the data, its utilization in organization and supporting practices such as data ownership.
Novel multi-layer SIW broadband coupler for Nolen matrix design in Ku band

All the components needed for a 4 times 4 Nolen matrix have been presented for application in multi-layer SIW technology. In particular, a novel 2-layers SIW broad-band coupler has been introduced. The wide coupling dynamic range of this coupler, being stable over a relatively wideband (up to 2 GHz in the Ku-Band), makes it a reliable element for building multiple beam-forming matrix like the one specified. The components can also be of interest for other beam forming networks, like Butler matrices. Moreover, an original low-loss, 2-layers waveguide transition is developed for the realization of such matrices in multi-layers topology in SIW technology. It is expected that these multi-layer components will lead to compact beam forming network topologies. Further investigations are on going, mainly to simulate and realize the foreseen 4x4 Nolen matrix.
An update on the epidemiology of AIDS in Missouri.

It has been 13 years since the initial report from the Centers for Disease Control and Prevention (CDC) describing the condition that came to be known as the acquired immunodeficiency syndrome (AIDS). Because of the public health significance of the AIDS epidemic, an elaborate national surveillance system, involving CDC along with state and local health departments, came to be established. The surveillance system now provides detailed information about the epidemiology of AIDS in this country. At the national level, through September 1993, 339,250 cases of AIDS have been reported to CDC; 204,390 of these individuals have died, for a case-fatality rate of 60.2%. Human immunodeficiency virus (HIV) infection/AIDS is now the leading cause of death in American men aged 25-44, and the fourth leading cause of death for women in this age group. The AIDS epidemic continues to disproportionately affect minorities. For blacks, the cumulative incidence rate is approximately 3.7 times that of whites; for Hispanics it is approximately 2.7 times that of whites. The majority of AIDS cases nationally are attributable to transmission of HIV among men who have sex with other men. However, the annual incidence of AIDS is currently rising faster among women than among men, and AIDS incidence is increasing more rapidly among persons who are reported to have acquired their infection through heterosexual contact than among persons in other exposure categories. Along with the increase in the number of cases in women, there has been a corresponding increase in the number of pre- or perinatally-acquired cases in children. (ABSTRACT TRUNCATED AT 250 WORDS)
ReFlex, a haptic wrist interface for motor learning and rehabilitation

Haptic interfaces have played an important role in the investigation of human factors, the identification of passive joint properties and gaining a better understanding of how the central nervous system learns to compensate for external dynamic perturbations through neuromuscular adaptation. Such devices further promise novel therapeutic approaches in neurorehabilitation, by assisting the patient to train functional tasks in an as-needed manner. With the aim of gaining deeper insights into the role of haptic feedback in motor learning and neurorehabilitation, we have developed a novel robotic wrist interface, the ReFlex, using a hybrid actuation approach, allowing to display a wider range of output impedances as well as a safe and efficient means of blocking the output for isometric training and rendering stable resistive force fields. This wrist module is mounted on a highly adjustable platform based on the consideration of constraints imposed by human factors and biomechanics. The system gives access and space for the placement of surface electrodes for electromyography of the main wrist and finger flexor/extensor muscle groups. We present the design of the ReFlex and analyze its performances in displaying forces and blocking the output. A method to increase the maximum brake torque and apparent output stiffness is described and validated.
Disability Studies and Educational Leadership Preparation: The Moral Imperative

This article details the experience of two instructors of P12 educational leadership programs in two university settings in different states, NY and NJ, as they seek to disrupt ableist thinking among educational leadership candidates. Analysis of data on placement of students with disabilities in New York and New Jersey from the period of 2014 to the present and state Department of Education field memos were used to contextualize their analysis of critical incidents relevant to their teaching experiences. The authors offer a critique of the Least Restrictive Environment (LRE) Continuum as it has been used to segregate students with disabilities from their non-disabled peers and offer suggestions for how educational leadership preparation should include a Disability Studies (DS) framework as a foundation to disrupt these taken for granted practices. Login for full text: [Word] [PDF] [TXT] Disability Studies and Educational Leadership Preparation: The Moral Imperative by Joshua Bornstein & Holly Manaseri is licensed under a Creative Commons Attribution 4.0 International License. Based on a work at http://rdsjournal.org/index.php/journal/article/view/818. Permissions beyond the scope of this license may be available at https://www.rds. hawaii.edu.
How to Integrate Character Education in Science Learning

Character education plays an important role in our lives. The Government of Indonesia is promoting the strengthening of character education in all aspects, including in education. Each teacher is expected to integrate character education in every subject, including science subjects. However, the findings show that science teachers have difficulty in integrating these two things. The purpose of this paper is to express the pattern of character education integration in science learning. The research method used is the development research by using ADDIE model training design (Analysis, Design, Development, Implementation and Evaluation). Based on the results of the application of the ADDIE model in the field, the results show (1) the science teacher's understanding of the basic concepts of character education (2) the training materials required by science teachers and (3) pattern of character education in science learning. The study concludes that the integration of character education in science learning is practiced in the context of relevant learning, planned in instructional design and assessed through appropriate assessment instruments. The results of this study are expected to be applied in science learning in the classrooms.
Functional evaluation of regenerated and misrouted low threshold mechanoreceptors and polymodal nociceptors in the skin of Rat hindfeet after crush lesions to the sciatic nerve

Tracer studies on motor axons after nerve crush injuries have indicated that misrouting may occur even when the endoneurium is intact. Misrouting of regenerated polymodal nociceptive C-fibres and low threshold mechanoreceptive axons have been studied functionally in 50 rats three months after unilateral crush lesions to the sciatic nerve. Two weeks before evaluation the tibial fascicle (or the peroneal fascicle) above the lesion was cut and tied off. In this way only functional regeneration of misrouted axons was tested. Misrouted low threshold mechanoreceptive axons and polymodal nociceptor C-fibres were found after regeneration in both glabrous and hairy skin. We conclude that functional misdirection of both myelinated and unmyelinated sensory axons innervating either glabrous or hairy skin can occur after a crush lesion to a peripheral nerve in rats.
Insulin pump-long-term effects on glycemic control: an observational study at 10 diabetes clinics in Sweden.

AIM This study examined long-term effects of continuous subcutaneous insulin infusion (CSII) in clinical practice on glycemic control in patients with type 1 diabetes. SUBJECTS AND METHODS We evaluated all type 1 diabetes patients at 10 diabetes outpatient clinics in Sweden who had been treated with CSII for at least 5.5 years and had valid glycated hemoglobin (HbA1c) data before starting pump use and at 5 years ± 6 months. Controls treated with multiple daily insulin injections (MDI) over a time-matched period were also evaluated. RESULTS There were 331 patients treated with CSII at least 5.5 years at the 10 clinics. Of these, 272 (82%) fulfilled the inclusion criteria. Patients treated with CSII were younger than those treated with MDI (mean age, 38.6 vs. 45.6 years; P<0.001), more were women (56% vs. 43%; P<0.001), and diabetes duration was shorter (mean, 15.1 years vs. 20.1 years; P<0.001). After adjusting for variables differing at baseline and influencing the change in HbA1c over the study period, the reduction in HbA1c remained statistically significant at 5 years and was estimated to be 0.20% (95% confidence interval [CI] 0.07-0.32) (2.17 mmol/mol [95% CI 0.81-3.53]) (P=0.002). The corresponding adjusted reduction at years 1 and 2 was 0.42% (95% CI 0.31-0.53) (4.59 mmol/mol [95% CI 3.41-5.77]) (P<0.001) and 0.43% (95% CI 0.31-0.55) (4.71 mmol/mol [95% CI 3.38-6.04]) (P<0.001), respectively. The effect of insulin pump use versus controls on HbA1c decreased significantly with time (P<0.001). CONCLUSIONS Use of CSII in clinical practice in Sweden is associated with an approximately 0.2% (2 mmol/mol) reduction in HbA1c after 5 years.
A systematic literature review of UK university–industry collaboration for knowledge transfer: A future research agenda

This systematic review establishes what is currently known and, more importantly, what is not known about knowledge transfer (KT) between UK universities and industries. The review focuses on four central measures related to university–industry (U–I) collaboration for KT that have been previously identified in the literature: motivations; activities; barriers; and outcomes. Different rationales underpin existing studies and we frame these using two perspectives: the sociopolitical perspective and the contextual perspective. To date studies with a sociopolitical perspective have largely focused upon ‘motivations’ to engage in U–I collaboration but largely from academics’ perspectives and tangible activities and outcomes have been the foci of the contextual perspective on KT but these have rarely been sector specific. We discuss these and other major findings in terms of policy implications for future research funding.
Regression B‐spline smoothing in Bayesian disease mapping: with an application to patient safety surveillance

In the context of Bayesian disease mapping, recent literature presents generalized linear mixed models that engender spatial smoothing. The methods assume spatially varying random effects as a route to partially pooling data and ‘borrowing strength’ in small‐area estimation. When spatiotemporal disease rates are available for sequential risk mapping of several time periods, the ‘smoothing’ issue may be explored by considering spatial smoothing, temporal smoothing and spatiotemporal interaction. In this paper, these considerations are motivated and explored through development of a Bayesian semiparametric disease mapping model framework which facilitates temporal smoothing of rates and relative risks via regression B‐splines with mixed‐effect representation of coefficients. Specifically, we develop spatial priors such as multivariate Gaussian Markov random fields and non‐spatial priors such as unstructured multivariate Gaussian distributions and illustrate how time trends in small‐area relative risks may be explored by splines which vary in either a spatially structured or unstructured manner. In particular, we show that with suitable prior specifications for the random effects ensemble, small‐area relative risk trends may be fit by ‘spatially varying’ or randomly varying B‐splines. A recently developed Bayesian hierarchical model selection criterion, the deviance information criterion, is used to assess the trade‐off between goodness‐of‐fit and smoothness and to select the number of knots. The methodological development aims to provide reliable information about the patterns (both over space and time) of disease risks and to quantify uncertainty. The study offers a disease and health outcome surveillance methodology for flexible and efficient exploration and assessment of emerging risk trends and clustering. The methods are motivated and illustrated through a Bayesian analysis of adverse medical events (also known as iatrogenic injuries) among hospitalized elderly patients in British Columbia, Canada. Copyright © 2007 John Wiley & Sons, Ltd.
Achieving stability through editing and chaperoning: regulation of MHC class II peptide binding and expression

Summary: In antigen‐presenting cells (APCs), loading of major histocompatibility complex class II (MHC II) molecules with peptides is regulated by invariant chain (Ii), which blocks MHC II antigen‐binding sites in pre‐endosomal compartments. Several molecules then act upon MHC II molecules in endosomes to facilitate peptide loading: Ii‐degrading proteases, the peptide exchange factor, human leukocyte antigen‐DM (HLA‐DM), and its modulator, HLA‐DO (DO). Here, we review our findings arguing that DM stabilizes a globally altered conformation of the antigen‐binding groove by binding to a lateral surface of the MHC II molecule. Our data imply changes in the interactions between specificity pockets and peptide side chains, complementing data from others that suggest DM affects hydrogen bonds. Selective weakening of peptide/MHC interactions allows DM to alter the peptide repertoire. We also review our studies in cells that highlight the ability of several factors to modulate surface expression of MHC II molecules via post‐Golgi mechanisms; these factors include MHC class II‐associated Ii peptides (CLIP), DM, and microbial products that modulate MHC II traffic from endosomes to the plasma membrane. In this context, we discuss possible mechanisms by which the association of some MHC II alleles with autoimmune diseases may be linked to their low CLIP affinity.
Household Debt, Consumption, and Income Inequality

ABSTRACT Using the Johansen and Engle–Granger cointegration tests, we show that there is one cointegrating relationship between household debt, consumption, and income inequality in the United States for the period from 1929 to 2009. Given this result, we use a Vector Error-Correction model to further understand the dynamics among the three variables. Results indicate that increases in income inequality and consumption directly contribute to increases in household debt. Interestingly, the results reveal some feedback from household debt to income inequality. We also show that debt-driven consumption should be viewed with caution as the results show that increases in household debt correspond with future declines in the rate of consumption.