Miracle-dz/UniFAR-FTUs huggingface dataset:
Deciphering Mode of Action of Heparanase Using Structurally Defined Oligosaccharides*

Background: Heparanase is involved in the pathology of many diseases. Results: Heparanase cleaves heparan sulfate (HS) oligosaccharides in either consecutive or gapped cleavage mode. Conclusion: The susceptibility of glycosidic linkage bonds to heparanase degradation is sensitive to the nonreducing end saccharide structure of the cleavage site. Significance: The results will help us to understand the pathophysiological effects of HS that arise from heparanase activity. Heparan sulfate (HS) is a highly sulfated polysaccharide that serves many biological functions, including regulating cell growth and inflammatory responses as well as the blood coagulation process. Heparanase is an enzyme that cleaves HS and is known to display a variety of pathophysiological effects in cancer, diabetes, and Alzheimer disease. The link between heparanase and diseases is a result of its selective cleavage of HS, which releases smaller HS fragments to enhance cell proliferation, migration, and invasion. Despite its importance in pathological diseases, the structural cues in HS that direct heparanase cleavage and the steps of HS depolymerization remain unknown. Here, we sought to probe the substrate specificity of heparanase using a series of structurally defined oligosaccharide substrates. The sites of heparanase cleavage on the oligosaccharide substrates were determined by mass spectrometry and gel permeation chromatography. We discovered that heparanase cleaves the linkage of glucuronic acid linked to glucosamine carrying 6-O-sulfo groups. Furthermore, our findings suggest that heparanase displays different cleavage modes by recognizing the structures of the nonreducing ends of the substrates. Our results deepen the understanding of the action mode of heparanase.
Analysis of inducers of the E.coli lac repressor system in mammalian cells and whole animals.

Although the inducible prokaryotic lac repressor system has been successfully adapted for control of gene expression in mammalian cells, little information is available on the pharmacokinetics of beta-galactoside inducers in mammalian cells for optimizing this system. These studies directly measure the cell uptake and clearance in cultured cells and animal tissue cells of lac inducers. In these cells, the beta-galactosides, isopropyl beta-D-thiogalactoside (IPTG) and methyl beta-D-thiogalactoside (MTG), are rapidly taken up, exceeding extracellular levels in less than 2 hours. Greater than 5% of this inducer is found in the nuclear fraction, slightly exceeding the cytoplasmic concentration. Although similar in uptake, IPTG is cleared from the cultured cells significantly faster than MTG. In the mouse, the half-life of both inducers in the blood ranges from 15-30 minutes. HPLC analysis of tissue extracts from inducer-injected mice indicates that the inducer is metabolically stable and functionally able to bind to lac repressor. These results should permit improvement in the adaptation of the lac repressor system to mammalian cells and aid in the development of an adaptable system for gene control in transgenic animals.
3D Microfluidic Cell Culture Models for Potential Stem Cell Therapies

Over the last decades stem cell biology has fundamentally transformed our understanding of biological functions on a cellular and organism level and stem cell research has become ubiquitous in today's scientific world. Despite the wide spread use of stem cells in biomedical research, their clinical applications remain in certain situations constrained by potential ethical implications including informed consent, experimental intervention, and embryonic destruction as well as oversight of research [1]. Nevertheless, in recent years cell therapies have been recognized as an important alternative to conventional medical care to alleviate human diseases. Cell therapy, defined as the treatment in which cells are injected into a patient, can be divided into mesenchymal stem cell therapy, hematopoietic stem cell transplantation and allogeneic or autologous cell therapy.
Atypical intraductal proliferation and intraductal carcinoma of the prostate on core needle biopsy: a comparative clinicopathological and molecular study with a proposal to expand the morphological spectrum of intraductal carcinoma

Atypical intraductal proliferation (AIP) of the prostate is histologically worse than high‐grade prostate intraepithelial neoplasia, but lacks the diagnostic criteria of intraductal carcinoma of the prostate (IDC‐P). The aim of this study was to compare the clinicopathological and molecular characteristics (ERG overexpression and PTEN loss) of AIP and IDC‐P in core needle biopsies.
Unicompartmental Knee Arthroplasty for Avascular Osteonecrosis

The data analyzing clinical and radiological outcomes after modern unicompartmental knee arthroplasty (UKA) for spontaneous and secondary avascular osteonecrosis are limited. We determined whether: (1) UKA for osteonecrosis was as reliable for alleviating pain and improving function (measured by Knee Society scores) as it is for osteoarthritis, (2) lower limb alignment could be restored after UKA for osteonecrosis, and (3) UKA for osteonecrosis is as durable as UKA for osteoarthritis (measured by survivorship at 12 years). We retrospectively reviewed 30 patients (31 knees) with osteonecrosis; 21 knees had spontaneous osteonecrosis and 10 had secondary osteonecrosis. Mean patient age was 71 years. Clinical and radiological evaluations were performed by an independent observer at a minimum followup of 3 years (mean, 7 years; range, 3-16 years). Reliable pain relief and function improvement were obtained in 30 knees (96%). Restoration of an appropriate lower-limb mechanical axis was achieved for 27 knees (88%). The Kaplan-Meier survivorship was 96.7% at 12 years. Our data suggest UKA is a reasonable solution for restoring clinical function and radiological lower-limb alignment for spontaneous or secondary osteonecrosis limited to one compartment of the knee, with a durable survivorship.Level of Evidence: Level IV, retrospective study. See the Guidelines for Authors for a complete description of levels of evidence.
Organizational Learning Ambidexterity, Strategic Flexibility, and New Product Development

Although organizational ambidexterity has gained momentum in recent innovation research, previous literature still offers a confusing and partial picture about how to leverage ambidexterity for new product development because of two limitations. First, previous research mainly focuses on static resource endowment and thus offers little insight about how firms should dynamically reconfigure resource portfolios to leverage organizational ambidexterity. Second, conceptual confusion on the notion of the balance dimension of organization ambidexterity still exists. This study seeks to explore how firms should dynamically reconfigure resource portfolios to leverage organizational ambidexterity for new product development and to bring greater conceptual clarity to the notion of balance. By extending the static resource assumption, which is central to the extant debate in organizational ambidexterity literature, this research unpacks ambidexterity into a relative exploratory dimension and an interactive dimension. We further investigated the moderating effect of resource flexibility and coordination flexibility on the impacts of the two dimensions on new product development performance. Based on the dynamic resource management view and organizational learning theory, we proposed six hypotheses and collected data from 213 firms through a survey to examine the hypotheses. Our results indicate that relative exploratory dimension and interactive dimension have different effects on new product development. Specifically, the relative exploratory dimension has an inverse U-shaped effect on new product development while the interactive dimension has a positive effect. Furthermore, we find that resource flexibility and coordination flexibility have positive moderating effects on the relationships between the two dimensions of ambidexterity and new product development performance. Our study contributes to the ambidexterity research in three ways. First, from a dynamic resource management view, this study extends previous ambidexterity research from a static view to a dynamic view by exploring the moderating effects of resource flexibility and coordination flexibility. Second, we extend the understanding on ambidexterity by bringing greater conceptual clarity to the notion of balance. Third, this research provides new evidence on the effects of ambidextrous learning on new product development performance in transition economy such as China, where ambidextrous learning is crucial for firms to adapt to a dynamic environment.
Reversal of DNA alkylation damage by two human dioxygenases

The Escherichia coli AlkB protein protects against the cytotoxicity of methylating agents by repair of the DNA lesions 1-methyladenine and 3-methylcytosine, which are generated in single-stranded stretches of DNA. AlkB is an α-ketoglutarate- and Fe(II)-dependent dioxygenase that oxidizes the relevant methyl groups and releases them as formaldehyde. Here, we identify two human AlkB homologs, ABH2 and ABH3, by sequence and fold similarity, functional assays, and complementation of the E. coli alkB mutant phenotype. The levels of their mRNAs do not appear to correlate with cell proliferation but tissue distributions are different. Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an α-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. AlkB, ABH2, and ABH3 can also repair 1-ethyladenine residues in DNA with the release of acetaldehyde.
Relationship of Spikes, Synaptic Activity, and Local Changes of Cerebral Blood Flow

The coupling of electrical activity in the brain to changes in cerebral blood flow (CBF) is of interest because hemodynamic changes are used to track brain function. Recent studies, especially those investigating the cerebellar cortex, have shown that the spike rate in the principal target cell of a brain region (i.e. the efferent cell) does not affect vascular response amplitude. Subthreshold integrative synaptic processes trigger changes in the local microcirculation and local glucose consumption. The spatial specificity of the vascular response on the brain surface is limited because of the functional anatomy of the pial vessels. Within the cortex there is a characteristic laminar flow distribution, the largest changes of which are observed at the depth of maximal synaptic activity (i.e. layer IV) for an afferent input system. Under most conditions, increases in CBF are explained by activity in postsynaptic neurons, but presynaptic elements can contribute. Neurotransmitters do not mediate increases in CBF that are triggered by the concerted action of several second messenger molecules. It is important to distinguish between effective synaptic inhibition and deactivation that increase and decrease CBF and glucose consumption, respectively. In summary, hemodynamic changes evoked by neuronal activity depend on the afferent input function (i.e. all aspects of presynaptic and postsynaptic processing), but are totally independent of the efferent function (i.e., the spike rate of the same region). Thus, it is not possible to conclude whether the output level of activity of a region is increased based on brain maps that use blood-flow changes as markers.
Neonatal Herpes Should be a Reportable Disease

Neonatal herpes is a devastating disease, the most serious complication of genital herpes, one of the most common serious congenital or perinatal infections, and the most frequent complication of sexually transmitted infections among children. Nevertheless, neonatal herpes is not reportable to health authorities in most states. The potential for prevention has been enhanced by recent diagnostic and therapeutic advances, and the disease meets widely accepted criteria for reporting, including incidence rates that exceed those of comparable conditions, epidemiologic instability, disease severity, direct and indirect socioeconomic costs, concern by persons at risk, the potential for prevention by public health interventions, and the prospect that the resulting data would influence public health policy. The absence of national surveillance contributes to beliefs by healthcare providers and the public health community that genital and neonatal herpes are uncommon conditions that affect small segments of society, beliefs that directly interfere with prevention. Neonatal herpes should be a reportable condition.
Exploring the effect of relationship duration on the association between core service benefits, relational benefits and relationship outcomes

Customer relationships provide a means of achieving competitive advantage primarily because of the economic advantage derived from customer retention. As a result, developing and maintaining a loyal customer base over the duration of the service relationship is of critical importance to service firms. Although service relationships develop over a series of service encounters, extant theory is yet to address the dynamic nature of such relationships. Differences in customer perceptions of relationship quality and loyalty between new service relationships and enduring service relationships are yet to be determined. This paper presents a conceptual framework that models the effect of core service benefits and relational benefits on relationship quality and loyalty, and considers the effect of relationship experience or duration on the associations between these constructs.
Antimicrobial Resistance in Indicator Escherichia coli Isolates from Free-Ranging Livestock and Sympatric Wild Ungulates in a Natural Environment (Northeastern Spain)

ABSTRACT Antimicrobial resistance was assessed in indicator Escherichia coli isolates from free-ranging livestock and sympatric wild boar (Sus scrofa) and Iberian ibex (Capra pyrenaica) in a National Game Reserve in northeastern Spain. The frequency of antimicrobial resistance was low (0% to 7.9%). However, resistance to an extended-spectrum cephalosporin and fluoroquinolones was detected.
The tax systems in Mozambique, Tanzania and Zambia: capacity and constraints

Strengthening the tax systems in developing countries is a key priority area for Norwegian development assistance. The purpose of this study is to systematise and analyse existing knowledge of the capacity and constraints of the tax systems in selected African countries, and to advice Norwegian authorities on how this knowledge can be translated into practical, effective and concrete development policies. This report focuses on Mozambique, Tanzania and Zambia. It examines current work to strengthening the tax systems in each of the three countries, identifies gaps and provides recommendations for Norwegian support for effective and accountable taxation. CM I R po Rt R 211: 3 The tax systems in Mozambique, Tanzania and Zambia: Capacity and constraints
Why some corporations pay more tax than necessary

It has been noticed in several countries that many corporations do not claim all of their allowable tax depreciation deductions, despite incurring a higher tax cost. There are several possible explanations. First, the uniform reporting accounting system (typical of many European countries) can under certain circumstances constrain dividends. The dividend constraint can, however, be loosened by forgoing some tax depreciation. We find no support for this hypothesis. Second, we find strong evidence that corporations with bad economic performance tend to underutilize their deductions, suggesting that corporations use costly "window-dressing" on their accounting measures. Third, we find support for the hypothesis that tax compliance costs discourage the utilization of accelerated depreciation, especially by small firms. Fourth, we find weak support for the hypothesis that there is substitution between tax depreciation and private debt due to competition between the benefits of private bank monitoring and the tax savings from using tax debt, as suggested in earlier literature. Our empirical analysis is possible due to unusual access to extremely detailed individual firm tax returns forms in Norway, combined with the 1992 Norwegian tax reform that provided a natural experiment for testing some of the hypotheses. We use the time-series and cross-sectional variation across Norwegian corporations in 1988, 1991, 1992 and 1993.
Neurally Adjusted Ventilatory Assist: A Ventilation Tool or a Ventilation Toy?

Mechanical ventilation has, since its introduction into clinical practice, undergone a major evolution from controlled ventilation to various modes of assisted ventilation. Neurally adjusted ventilatory assist (NAVA) is the newest development. The implementation of NAVA requires the introduction of a catheter to measure the electrical activity of the diaphragm (EAdi). NAVA relies, opposite to conventional assisted ventilation modes, on the EAdi to trigger the ventilator breath and to adjust the ventilatory assist to the neural drive. The amplitude of the ventilator assist is determined by the instantaneous EAdi and the NAVA level set by the clinician. The NAVA level amplifies the EAdi signal and determines instantaneous ventilator assist on a breath-to-breath basis. Experimental and clinical data suggest superior patient-ventilator synchrony with NAVA. Patient-ventilator asynchrony is present in 25% of mechanically ventilated patients in the intensive care unit and may contribute to patient discomfort, sleep fragmentation, higher use of sedation, development of delirium, ventilator-induced lung injury, prolonged mechanical ventilation, and ultimately mortality. With NAVA, the reliance on the EAdi signal, together with an intact ventilatory drive and intact breathing reflexes, allows integration of the ventilator in the neuro-ventilatory coupling on a higher level than conventional ventilation modes. The simple monitoring of the EAdi signal alone may provide the clinician with important information to guide ventilator management, especially during the weaning process. Although, until now, little evidence proves the superiority of NAVA on clinically relevant end points, it seems evident that patient populations (eg, COPD and small children) with major patient-ventilator asynchrony may benefit from this new ventilatory tool.
Community Psychiatric Nurse Teams: Intensive Support Versus Generic Care

Background. This study evaluated whether a community psychiatric nurse (CPN) team providing a comprehensive aftercare service, using a case management approach, improves psychopathology and social functioning of the long-term mentally ill, and reduces hospital use compared with a generic CPN team. Method. Patients suffering from severe and persistent mental health problems were randomised to intensive aftercare or generic care after referral to the CPN manager. Each group contained 41 patients who were assessed at baseline and at 6, 12 and 18 months by an independent research psychologist. Outcome measures included the GAS, PSE, SAS, patient and relatives' satisfaction, number of admissions, and length of stay. Results. No difference between the groups was found on any of the outcome measures, despite the much higher number of contacts of the intensive (n = 52) versus generic CPNs (n = 13) and the much greater range of interventions. Conclusions. Intensive aftercare for people with persistent mental health problems was not found to be of greater benefit than generic CPN care. Many factors need to be considered for aftercare to be effective, including community resources, process of care, and staff training.
The Environment in which Cultural Industries Operate and Some Implications

Abstract: In this paper we argue that the performance and actions of companies in the cultural industries can only be understood in the context of the environment in which the industries operate. We examine the microeconomic environment, the regulatory environment, the technological environment, and the global competitive environment of the cultural industries and consider some of the implications for public policy and for the conduct and competitive strategies of companies. The approach adopted is to identify the major issues, provide a state-of-the-art review of the literature, and identify where additional research is needed. The argument is made that economic analysis of the environment is essential to an understanding of the conduct of companies in cultural industries. Such economic analysis permits explanation of, for example, how companies are likely to respond to changes in the external environment, why products of the cultural industries are traded extensively, why the U.S. dominates that trade, and why some particular business strategies are increasingly important. We argue that economic analysis is a prerequisite to sound public policy formulation because companies tend to respond to regulations according to their economic interests. Resume: Dans cet article, nous affirmons que les actions et les resultats d'entreprises dans les industries culturelles ne peuvent etre comprises qu'en faisant reference au milieu ou ces industries fonctionnent. En consequence, nous examinons les milieux de la micro-economie, de la reglementation, de la technologie et de la concurrence globale des industries culturelles, et considerons quelques-uns de leurs effets sur la politique publique et la conduite et les strategies competitives des compagnies. L'approche adoptee consiste a identifier les questions majeures, effectuer un examen tres actuel de la documentation sur le sujet, et identifier quelles recherches additionnelles seraient requises. Nous affirmons que l'analyse economique du milieu est essentielle afin de comprendre pourquoi les entreprises dans les industries culturelles agissent comme elles le font. Une telle analyse economique peut nous permettre par exemple d'expliquer comment les entreprises reagiraient face a un changement dans l'environnement externe, pourquoi les produits des industries culturelles font l'objet d'un commerce si intense, pourquoi les Etats-Unis dominent ce commerce, et pourquoi certaines strategies commerciales deviennent de plus en plus importantes. Nous affirmons que l'analyse economique est une condition prealable a la formulation d'une politique publique saine, parce que les entreprises tendent a privilegier leurs interets economiques quand ils reagissent a de nouvelles reglementations.
Web Vulnerability Study of European Insurance Sites

The rise of online commerce has brought about advantages for consumers wishing to research and purchase auto insurance from online agents, and the global market for this business is rising. However, along with benefits come issues related to security of auto insurance Web applications. Unsecured Web applications are a major problem with overall computer security, and can lead to problems with consumer trust. Government legal mandates and individual company technical solutions are two methods that are being used to attempt to mitigate this issue. This study analyzes 60 auto insurance Web sites in three Western European countries to determine the level of Web application security, and what types of vulnerabilities are common in the sites. It also reviews some technical and procedural methods firms can take to ease some of these problems.