Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutually Exclusive Subsets of BH3-Only Proteins Are Activated by the p53 and c-Jun N-Terminal Kinase/c-Jun Signaling Pathways during Cortical Neuron Apoptosis Induced by Arsenite

ABSTRACT The c-Jun N-terminal protein kinase (JNK)/c-Jun and p53 pathways form distinct death-signaling modules in neurons that culminate in Bax-dependent apoptosis. To investigate whether this signaling autonomy is due to recruitment of particular BH3-only proteins, we searched for a toxic signal that would activate both pathways in the same set of neurons. We show that arsenite activates both the JNK/c-Jun and p53 pathways in cortical neurons, which together account for >95% of apoptosis, as determined by using the mixed-lineage kinase (JNK/c-Jun) pathway inhibitor CEP11004 and p53-null mice. Despite the coexistence of both pathways in at least 30% of the population, Bim mRNA and protein expression was increased only by the JNK/c-Jun signaling pathway, whereas Noxa and Puma mRNA and Puma protein expression was entirely JNK/c-Jun independent. About 50% of Puma/Noxa expression was p53 dependent, with the remaining signal being independent of both pathways and possibly facilitated by arsenite-induced reduction in P-Akt. However, functionally, Puma was predominant in mediating Bax-dependent apoptosis, as evidenced by the fact that more than 90% of apoptosis was prevented in Puma-null neurons, although Bim was still upregulated, while Bim- and Noxa-null neurons died similarly to wild-type neurons. Thus, the p53 and JNK/c-Jun pathways can activate mutually exclusive subclasses of BH3-only proteins in the same set of neurons. However, other factors besides expression may determine which BH3-only proteins mediate apoptosis.
Establishment of a Novel Quantitative Hepatitis D Virus (HDV) RNA Assay Using the Cobas TaqMan Platform To Study HDV RNA Kinetics

ABSTRACT Determination of hepatitis D virus (HDV) viremia represents the “gold standard” for the diagnosis of HDV infection. Hepatitis B virus (HBV)-HDV coinfection frequently leads to end-stage liver disease and hepatocellular carcinoma. No commercial assay for HDV RNA quantification that includes automated nucleic acid extraction is available, and in-house PCR tests are not well standardized. However, knowledge of HDV RNA levels may give important information for patient management and could be a useful tool for monitoring the response to antiviral therapies. One platform that is widely used for HBV DNA or HCV RNA quantification is the Cobas Ampliprep/TaqMan system. Using the utility channel of this platform, we established a novel protocol for TaqMan-based HDV RNA quantification after automatic extraction of RNA by the Ampliprep system. The assay was specific and showed linearity over a wide range from 3 × 102 to 107 copies/ml. Reproducibility was demonstrated by determination of the interrun and intrarun variabilities, which were similar to those achieved with the commercially available Cobas TaqMan assays for HCV RNA and HBV DNA. HDV RNA levels were stable in whole blood (n = 4), plasma (n = 3), and serum (n = 3) samples at room temperature for up to 6 days. Importantly, HDV RNA viremia showed only minor fluctuations, with the log10 coefficient of variation being between 1.3 and 11.2% for hepatitis delta patients studied every 2 weeks for up to 3 months (n = 6), while a rapid viral decline was observed early during treatment with pegylated alfa-2a interferon (n = 6). In conclusion, this novel automated HDV RNA assay is a useful tool for monitoring HDV-infected patients both before and during antiviral therapy.
Secreted Form of Amyloid β/A4 Protein Precursor (APP) Binds to Two Distinct APP Binding Sites on Rat B103 Neuron‐Like Cells Through Two Different Domains, but Only One Site Is Involved in Neuritotropic Activity

Abstract: Recent studies have identified the Alzheimer's disease amyloid β/A4 protein precursor (APP) as a trophic and/or tropic protein on several types of cells, including fibroblasts, primary culture neurons, PC12 cells, and B103 neuron‐like cells. Many trophic proteins bind heparin, and it is believed that the heparin‐binding domain is crucial for the trophic activity of these proteins. APP also binds heparin. The current studies were undertaken to examine the hypothesis that the neuritotropic activity of APP requires heparin binding. It was found that APP produced in E. coli bound B103 cells through detergent‐extractable molecules. Approximately 50% of the binding sites were heparinase‐sensitive, and heparin and heparan sulfate competed for APP binding to these sites. The heparinase‐insensitive sites were recognized by a stretch of 17 amino acids of APP (residues 319–335) that contains the neuritotropic activity of APP. A mutant APP with a deletion at this site was capable of binding to the heparinase‐sensitive sites, although this molecule was not neuritotropic to B103 neuron‐like cells. Therefore, the neuritotropic site and the heparin‐binding site are distinct in APP, and the neuritotropic effect of APP is produced through its binding to detergent‐extractable and heparinase‐insensitive sites.
Female Athlete Triad Screening in National Collegiate Athletic Association Division I Athletes: Is the Preparticipation Evaluation Form Effective?

Objective To evaluate the screening practices and preparticipation evaluation (PPE) forms used to identify college athletes at risk for the female athlete triad (triad). Design Phone and/or e-mail survey. Setting National Collegiate Athletic Association (NCAA) Division I universities. Participants All 347 NCAA Division I universities were invited to participate in a survey, with 257 participating in the survey (74%) and 287 forms collected (83%). Main Outcome Measures Information about the nature of the PPE was requested from team physicians and certified athletic trainers during a phone or e-mail survey. In addition, a copy of their PPE form was requested to evaluate for inclusion of the 12 items recommended by the Female Athlete Triad Coalition for primary screening for the triad. Results All 257 universities (100%) required a PPE for incoming athletes; however, only 83 universities (32%) required an annual PPE for returning athletes. Screening was performed on campus at 218 universities (85%). Eleven universities (4%) were using the recently updated fourth edition PPE. Only 25 universities (9%) had 9 or more of the 12 recommended items included in their forms, whereas 127 universities (44%) included 4 or less items. Relevant items that were omitted from more than 40% of forms included losing weight to meet the image requirements of a sport; using vomiting, diuretics, and/or laxatives to lose weight; and the number of menses experienced in the past 12 months. Conclusions The current PPE forms used by NCAA Division I universities may not effectively screen for the triad.
Components of the COPD Assessment Test (CAT) associated with a diagnosis of COPD in a random population sample

Abstract The aim of this study was to determine if components of the COPD Assessment Test (CAT), a validated health status impairment instrument, had additional utility in identifying patients at risk for COPD in whom spirometry testing is appropriate. This study was part of the Canadian Obstructive Lung Disease prevalence study. Consenting participants ≥ 40 years of age were identified by random digit dialing. Smoking history, 8-item CAT scores, and post-bronchodilator spirometry were recorded for each. Stepwise logistic regression analysis was used to identify variables related to the presence of airway obstruction and a final logistic model was developed which best predicted COPD in this sample. Of the 801 individuals approached, 532 were included: 51 (9.6%) had COPD, the majority (92%) of whom fit GOLD I or II severity criteria. Items that correlated significantly with a COPD diagnosis included the CAT total score (p = 0.01) and its breathlessness (p < 0.0001) and phlegm (p = 0.001) components. The final logistic model included: age (<55 or ≥55 years), smoking status (current, former, never) and the CAT breathlessness score (ordinal scale 0–5). The area under the receiver-operating characteristic curve for this model was 0.77, sensitivity was 77.6%, specificity was 64.9% and the positive likelihood ratio was 2.21. In summary, the triad of smoking history, age at least 55 years and the presence of exertional breathlessness were key elements of a simple model which had reliable measurement properties when tested in a random population. This may help identify patients at risk for COPD for whom spirometry testing is recommended.
Global oligopolistic competition and foreign direct investment: Revisiting and extending the literature

Purpose The purpose of this paper is to re-visit and re-invigorate the oligopolistic industry perspective on multinational corporations (MNC) strategy. Design/methodology/approach Based on insights from the industrial organization tradition and strategic management, the paper brings the original insights of the oligopolistic industry perspective into a modern context by outlining a conceptual framework that may guide future international business (IB) research on MNC strategy in oligopolistic industries. Findings This paper demonstrates how contemporary IB literature pays little attention to a key insight of the early IB literature, namely, that foreign direct investment (FDI) often is driven by strategic interaction among MNCs in oligopolistic industries. Instead, the contemporary IB literature focuses on the FDI as a way to reduce transaction costs and/or as a way to leverage and build capabilities across borders. The paper argues that progressing global concentration in many industries warrants a rediscovery of the oligopolistic perspective on FDI. Originality/value The paper provides a comprehensive and unique literature review of the literature on MNC strategy in oligopolistic industries. Based on this review, the paper develops a novel conceptual framework that may inspire future IB research on MNC strategy in oligopolistic industries.
Evolution of Physician-Industry Relationships in Producing Knowledge of Drug Therapy - Comparison of the United States and Finland

This paper presents a historical perspective on the evolution of relationships between the pharmaceutical industry and physicians in two countries, the United States and Finland. Despite divergence early the twentieth century, and the absence of any large pharmaceutical firms based in Finland, by the 1950s a similar partnership between medical experts and drug companies had developed. In the US, commercial influence in medical research can be divided into five periods: pre-reform (late 19th century – 1905), first reform wave (1905-1930), growing collaboration (1930-1945), merger of interests (1945-1950s, and second reform wave (1960s and 1970s). The history in Finland until the War was different: a preindustrial pattern persisted into the ‘teens, followed by an interwar period in which the fostering of a domestic pharmaceutical industry was a national project and collaboration officially encouraged. After the Second World War the drug industry was no longer local, but the close physician-drug industry relationship largely continued as before. There are indications today that both countries have entered another reform period, this time international in origin. It is hoped that understanding of the origins and nature of relationships between biomedical experts and drug industry will help physicians offer better patient care.
BIOMIMO Design & Test: Motion capture and AR techniques to design and test an orthosis prototype

ldquoBIOMIMO Design & Testrdquo is a software application to aid the process of designing and testing IADs (Intelligent Assist Devices), also known as orthoses. This software combines Augmented Reality (AR), Virtual Reality (VR) and video-based optical motion capture techniques in order to evaluate a prototype without actually constructing it, and to avoid the risk of testing it on a real person. In this paper, as an initial step, it is applied to a 2 DoF (degrees of freedom) arm orthosis.
Regulation of Sucrose Metabolism in Higher Plants: Localization and regulation of Activity of Key Enzymes

Sucrose (Suc) plays a central role in plant growth and development. It is a major end product of photosynthesis and functions as a primary transport sugar and in some cases as a direct or indirect regulator of gene expression. Research during the last 2 decades has identified the pathways involved and which enzymes contribute to the control of flux. Availability of metabolites for Suc synthesis and ‘demand’ for products of sucrose degradation are important factors, but this review specifically focuses on the biosynthetic enzyme sucrose-phosphate synthase (SPS), and the degradative enzymes, sucrose synthase (SuSy), and the invertases. Recent progress has included the cloning of genes encoding these enzymes and the elucidation of posttranslational regulatory mechanisms. Protein phosphorylation is emerging as an important mechanism controlling SPS activity in response to various environmental and endogenous signals. In terms of Suc degradation, invertase-catalyzed hydrolysis generally has been associated with cell expansion, whereas SuSy-catalyzed metabolism has been linked with biosynthetic processes (e.g., cell wall or storage products). Recent results indicate that SuSy may be localized in multiple cellular compartments: (1) as a soluble enzyme in the cytosol (as traditionally assumed); (2) associated with the plasma membrane; and (3) associated with the actin cytoskel-eton. Phosphorylation of SuSy has been shown to occur and may be one of the factors controlling localization of the enzyme. The purpose of this review is to summarize some of the recent developments relating to regulation of activity and localization of key enzymes involved in sucrose metabolism in plants.
Child psychiatric symptoms and psychosocial impairment: relationship and prognostic significance

Background Relatively little is known about the relationships between psychiatric symptoms, diagnosis and psychosocial impairment. Aims To examine these contemporaneous relationships and prognostic significance in a large general population sample. Method Symptoms of major depression, conduct and oppositional defiant disorders were assessed by interview in two waves of the Virginia Twin Study of Adolescent behavioural Development (2800 children aged 8–16 years). Results Manychildren below the DSM–III–R diagnostic threshold, especially for depression, had symptom-related impairment, whereas many children reaching the symptom threshold for conduct and oppositional defiant disorders were little impaired. Impairment score was linearly related to symptom count, with no evidence of any additional impairment at the diagnostic threshold. For depression, only symptoms predicted later symptoms and diagnosis. For conduct and oppositional defiant disorders, impairment was additionally predictive of later symptoms and diagnosis. Conclusions Impairment, in addition to symptoms, is important for both nosology and prognosis.
HIV-hepatitis B virus coinfection: epidemiology, pathogenesis, and treatment

&NA; HIV infection has a significant impact on the natural history of chronic hepatitis B virus (HBV) infection, with increased levels of HBV DNA, accelerated progression of liver disease and increased liver-associated mortality compared with HBV monoinfection. Widespread uptake and early initiation of HBV-active antiretroviral therapy has substantially improved the natural history of HIV–HBV coinfection but the prevalence of liver disease remains elevated in this population. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease and seroconversion in HIV–HBV coinfection in the era of HBV-active antiretroviral therapy and the effects of HIV directly on liver disease. We also review novel therapeutics for the management of HBV with a particular emphasis on clinical strategies being developed for an HBV cure and an HIV cure and their impact on HIV–HBV coinfected individuals.
[Incidentally discovered adrenal masses in the Department of Internal Medicine, Endocrinology and Hemostatic Disorders, Medical University of Gdansk].

UNLABELLED Clinically silent adrenal masses (incidentaloma) are incidentally discovered lesions when noninvasive imaging methods (ultrasonography--USG, computer tomography--CT, magnetic resonance imaging--MRI) are performed for the reason other than known or suspected adrenal disease. Most of studies report the prevalence of adrenal incidentaloma range between 1 and 10% in radiological series. MATERIAL AND METHODS Between 1993 and 03.2004 we observed 198 patients with incidentalomas of adrenal glands (144 females--72.7% and 54 males--27.3%). RESULTS After endocrinological evaluation, 164 patients were qualified for surgery. In 119 (72.5%) cases open adrenalectomy was performed, and in 45 (27.5%) laparoscopic adrenalectomy was done. Adrenocortical adenoma was diagnosed in 54.9%, adrenal hyperplasia in 8.5%, adrenal carcinoma in 6.7%, pheochromocytoma in 12.9% (in 3.1% of all cases malignant pheochromocytoma was diagnosed), in 4.9% others malignant tumors (primary or metastatic), in 4.9% adrenal cysts and in 7.1% other rare adrenal pathologies were found. CONCLUSION All malignancies were found in tumors with the diameter over 3 cm. In tumors with diameter over 6 cm malignant cases were found in 70.8%.
Contrasting Enzymatic Activities of Topoisomerase IV and DNA Gyrase from Escherichia coli*

DNA gyrase and topoisomerase IV (Topo IV) have distinct roles as unlinking enzymes during DNA replication despite 40% sequence identity between them. DNA gyrase unlinks replicating DNA by introducing negative supercoils while Topo IV decatenates the two daughter molecules. For this study, we measured the rates of unlinking of various topoisomers of DNA by DNA gyrase and Topo IV. Each enzyme has marked preferences for certain strand-passage reactions. DNA gyrase is a relatively poor decatenase, catalyzing strand-passage events that result in supercoiling at rates several orders of magnitude faster than those causing decatenation. Topo IV, in contrast, decatenates linked circles 10-40 times more quickly than it removes the intramolecular crossings from supercoiled DNA. Supercoiled catenanes are unlinked at an even more increased rate by Topo IV. Thus, the supercoils augment decatenation rather than compete with catenane crossings for their removal. Knot crossings and the crossings of multiply interlinked catenanes are also preferentially removed by Topo IV. This ability of Topo IV to selectively unlink catenated molecules mirrors its key role in decatenation of replicating chromosomes in vivo.
Transmission of radiation-induced acentric chromosomal fragments to micronuclei in normal human fibroblasts.

A simplifying assumption made when calculating the probability of a chromosomal aberration resulting in a micronucleus is that virtually all radiation-induced micronuclei result from acentric fragments. In the present study we used antibodies to chromosomal centromeres (kinetochores) to determine the frequency of centric versus acentric micronuclei in normal human fibroblasts exposed to 6 Gy of 60Co gamma rays while they were in density-inhibited growth. Up to 14% of the micronuclei induced by this exposure contained one or more kinetochores; i.e., they were not composed of acentric chromatin. By deleting kinetochore-positive micronuclei from the analysis, and by reconstructing micronucleus frequencies based on the fraction of cells that had divided following radiation exposure, a direct comparison between micronuclei and acentric chromosome fragments was made. On that basis, the probability of an acentric fragment becoming a visible micronucleus in either daughter cell of a dividing pair was estimated to be about 0.6. The distribution of acentric fragments among mitotic cells conformed to Poisson expectation, while the distribution of micronuclei among daughter cells was significantly overdispersed. The phenomenon of overdispersion is discussed in connection with proposed cellular processes that effect a nonrandom segregation of acentric fragments.
Medical Imaging of Intervertebral Disc Degeneration: Current Status of Imaging

Study Design. The author reviewed literature and reports on spine imaging, selected key articles in which novel imaging strategies were described, and prepared a review of currently developing imaging strategies in intervertebral disc degeneration. Objectives. To provide a review of imaging in intervertebral disc degeneration that covers the current methodology briefly and describs developing techniques in detail. Summary of Background Data. Computed tomography and magnetic resonance imaging provide excellent anatomic images of the spine. However, anatomic imaging of the spine does not reliably identify the source of pain in patients with intervertebral disc degeneration. Many functional imaging techniques are suited to the study of the spine. Some of these techniques will improve our understanding of intervertebral disc degeneration and clinical symptomatology. Methods. The author selected reports in the current literature for further review and attempted to describe succinctly the material in the reports that are most relevant to spine imaging. Results. New and potentially useful imaging strategies for spine imaging include dynamic computed tomography, dynamic magnetic resonance imaging, functional magnetic resonance imaging, diffusion imaging, and magnetic resonance spectroscopy. Conclusions. Technological advances in magnetic resonance imaging and computed tomography imaging continue to offer more opportunities to investigate and diagnose back pain and intervertebral disc degeneration.
The Administrative State and its Constitutional Legitimacy: An Analysis of the USA Patriot Act of 2001 in the Context of Rohr’s Constitutional Framework of the Administrative State

American Public Administration has identified more closely with management than with governance. Therefore, its constitutional legitimacy is often questioned. Many of the current scholars emphasize the importance of the legitimacy of the administrative state from a constitutional perspective. John Rohr has authored both the pioneering and the standard setting work in this area. Rohr attempts to legitimate the administrative state in terms of a comprehensive constitutional perspective based on the founding of the American Republic. This study examines Rohr’s constitutional philosophy of the administrative state and testes its usefulness to public administrators. The study looked at the administrative agencies created by the USA Patriot Act of 2001 and their compatibility with Rohr’s constitutional framework. The major research question posed: Is the USA Patriot Act of 2001 legitimate within Rohr’s framework of the administrative state? Specifically, does the USA Patriot Act create and empower executive agencies beyond the pale of separation of powers as developed by Rohr? This study has utilized an interpretive methodology situated within the qualitative method of inquiry. Methodologically, the first part of this study attempts to comprehend the history of the administrative state and its legitimacy