Miracle-dz/UniFAR-FTUs huggingface dataset:
Orexinergic theta rhythm in the rat hippocampal formation: In vitro and in vivo findings

Previous in vivo data suggested that orexin neuropeptides (ORXA and ORXB) synthetized in hypothalamic neurons were involved in the mechanism of generation of the hippocampal formation theta rhythm. Surprisingly, this suggestion has never been directly proved by experiments using intraseptal or intrahippocampal administration of orexins. In this study, involving the use of in vitro hippocampal formation slices and in vivo model of anesthetized rat, we provide the first convergent electropharmacological evidence that in the presence of both ORXA and ORXB the hippocampal formation neuronal network is capable of producing oscillations in the theta band. This effect of orexin peptides was antagonized by selective blockers of orexin receptors (OX1R and OX2R), SB 334867 and TCS OX2 29, respectively. These results provide evidence for a novel, orexinergic mechanism responsible for the production of theta rhythm in the hippocampal formation neuronal network. © 2015 Wiley Periodicals, Inc.
Activation of Asparaginyl Endopeptidase Leads to Tau Hyperphosphorylation in Alzheimer Disease*

Background: Abnormal hyperphosphorylation of the microtubule-associated protein Tau is a hallmark of Alzheimer disease. Results: Acidosis of the brain activates and translocates asparaginyl endopeptidase from neuronal lysosomes to the cytoplasm where it leads to Tau hyperphosphorylation by inhibition of protein phosphatase 2A through cleavage of its inhibitor 2 into two active fragments. Conclusion: Activated asparaginyl endopeptidase causes Tau pathology. Significance: Brain acidosis can trigger Tau hyperphosphorylation. Neurofibrillary pathology of abnormally hyperphosphorylated Tau is a key lesion of Alzheimer disease and other tauopathies, and its density in the brain directly correlates with dementia. The phosphorylation of Tau is regulated by protein phosphatase 2A, which in turn is regulated by inhibitor 2, I2PP2A. In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2PP2A is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). Both I2NTF and I2CTF are known to bind to the catalytic subunit of protein phosphatase 2A and inhibit its activity. Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2PP2A translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I2PP2A, except when I2PP2A was mutated at the cleavage site Asn-175 to Gln. Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2PP2A, inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I2PP2A-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target.
Public holidays, tourism, and economic growth

In this article, a mechanism supporting the existence of an inverted u-shaped relation between the number of public holidays and the growth of an economy is presented. The nonlinear relationship is originated by two forces within a Schumpeterian economy: On the one hand, as the number of public holidays grows, the total number of workers searching for innovation increases; on the other hand, as the number of days of recreation increases, the number of working days producing innovations decreases. The combination of these two forces generates the inverted u-shaped relationship. The hypothesized mechanism suggests the existence of an optimal number of public holidays for an economy.
The platelet‐specific alloantigen PlA1 (HPA‐1a): a comparison of flow cytometric immunophenotyping and genotyping using polymerase chain reaction and restriction fragment length polymorphism in a Swedish blood donor population

BACKGROUND: There is an increasing interest in the development of rapid and reliable techniques for platelet alloantigen typing. STUDY DESIGN AND METHODS: By use of standardized flow cytometry and a specific human alloantiserum, 236 Swedish blood donors were immunophenotyped for the platelet‐specific alloantigen, PlA1 (HPA‐1a). RESULTS: Ten individuals (4.2%) had low fluorescence intensities and were considered PlA1‐ negative (HPA‐1a‐negative); all of them also demonstrated a PlA2/PlA2 (HPA‐1b/1b) genotype in a polymerase chain reaction and restriction fragment length polymorphism (PCR‐RFLP) assay of the underlying DNA polymorphism. The remaining population had clear positive fluorescence and was regarded as PlA1‐positive (HPA‐1a‐positive). The fluorescence distribution histogram among PlA1‐positive (HPA‐1a‐positive) individuals was dome‐shaped, and those individuals who were homozygous for PlA1 (HPA‐1a) could not be distinguished from those who were heterozygous. This finding was further substantiated by PCR‐RFLP analysis of the PlA1/PlA2 (HPA‐1a/1b) genotype; a heterozygous genotype was found among those having a medium fluorescence intensity as well as among those having a strong fluorescence intensity. CONCLUSION: Flow cytometry is a valuable tool for large‐scale detection of PlA1 (HPA‐ 1a). However, flow cytometry based on only one antiserum cannot distinguish between homozygous and heterozygous carriers of PlA1 (HPA‐ 1a). For zygosity testing and when platelets are difficult to obtain, the PCR‐RFLP technique is the assay of choice.
Sensitivity of new-generation computed tomography in subarachnoid hemorrhage.

OBJECTIVE To determine the sensitivity of the initial new-generation CT (NGCT) scan interpretation for detection of acute nontraumatic subarachnoid hemorrhage (SAH) and to decide whether lumbar puncture (LP) should follow a "normal" NGCT scan. METHODS A retrospective chart review was performed of patients admitted between March 1988 and July 1994 with proven SAH. Exclusion criteria were age < 2 years, diagnosis other than acute SAH, history of head trauma within 24 hours before symptom onset, NGCT scan not done before diagnosis, and records not available. Patients were placed into two groups: symptom duration < 24 hours (group 1) and > 24 hours (group 2) prior to CT scan. The resolution of each NGCT scanner was recorded. An NGCT scanner was defined as a third-generation scanner or more recent. RESULTS Of 349 SAH patients, 181 met inclusion criteria. The sensitivity of NGCT scans for SAH was 93.1% for the group 1 patients (n = 144) and 83.8% for the group 2 patients (n = 37). The overall sensitivity was 91.2%. All the patients who had SAH not detected by NGCT scans were diagnosed by LP. There was no significant relationship between NGCT scanner resolution and sensitivity for SAH. CONCLUSION Initial interpretation of NGCT scans to detect SAH does not approach 100% sensitivity. A "normal" NGCT scan does not reliably exclude the need for LP in patients who have symptoms suggestive of SAH.
18F-FLT PET in hematologic disorders: a novel technique to analyze the bone marrow compartment.

UNLABELLED Few diagnostic procedures are available to determine the degree of bone marrow cellularity and the numbers of cycling cells in patients with bone marrow disorders. Noninvasive imaging of the bone marrow compartment may be helpful. The PET tracer 3'-fluoro-3'-deoxy-L-thymidine (18F-FLT) has been developed recently. 18F-FLT uptake is related to the rate of DNA synthesis and increases with higher proliferation rates in many types of cancer. Background uptake of 18F-FLT in bone marrow is common. 18F-FLT PET might, therefore, visualize the high cycling activity of hematopoietic cells in the bone marrow compartment. Therefore, we investigated the feasibility of visualization and quantification of the activity of the bone marrow compartment with 18F-FLT PET to distinguish different hematologic disorders. METHODS Clinical and laboratory data of 18 patients with myelodysplasia (MDS), chronic myeloproliferative disorders, myelofibrosis, aplastic anemia, or multiple myeloma were correlated with the results of 18F-FLT PET using visual analysis and the standardized uptake value (SUV). Findings were compared with those of healthy control subjects (n = 14). RESULTS With SUV and visual analysis, a distinction could be made between MDS (n = 9), chronic myeloproliferative disorders (n = 3), and myelofibrosis (n = 3) compared with healthy control subjects. A significant increase in 18F-FLT uptake was observed in all of the studied patients with MDS and myeloproliferative disorders. In contrast, patients with myelofibrosis and aplastic anemia (n = 1) demonstrated a decline in bone marrow 18F-FLT uptake compared with healthy control subjects. Comparable results were observed in osteolytic lesions of patients with multiple myeloma (n = 2). CONCLUSION 18F-FLT PET can be used to visualize the proliferative activity of the bone marrow compartment and may be helpful to distinguish separate hematologic disorders.
Alternating zinc fingers in the human male associated protein ZFY: 2D NMR structure of an even finger and implications for "jumping-linker" DNA recognition.

ZFY, a sex-related Zn-finger protein encoded by the human Y chromosome, is distinguished from the general class of Zn-finger proteins by the presence of a two-finger repeat. Whereas odd-numbered domains and linkers fit a general consensus, even-numbered domains and linkers exhibit systematic differences. Because this alternation may have fundamental implications for the mechanism of protein-DNA recognition, we have undertaken biochemical and structural studies of fragments of ZFY. We describe here the solution structure of a representative nonconsensus (even-numbered) Zn finger based on 2D NMR studies of a 30-residue peptide. Structural modeling by distance geometry and simulated annealing (DG/SA) demonstrates that this peptide folds as a miniglobular domain containing a C-terminal beta--hairpin and N-terminal alpha-helix (beta beta alpha motif). These features are similar to (but not identical with) those previously described in consensus-type Zn fingers (derived from ADR1 and Xfin); the similarities suggest that even and odd ZFY domains bind DNA by a common mechanism. A model of the protein-DNA complex (designated the "jumping-linker" model) is presented and discussed in terms of the ZFY two-finger repeat. In this model every other linker is proposed to cross the minor groove by means of a putative finger/linker submotif HX4HX3-hydrophobic residue-X3. Analogous use of a hydrophobic residue in a linker that spans the minor groove has recently been described in crystallographic and 3D NMR studies of homeodomain-DNA complexes. The proposed model of ZFY is supported in part by the hydroxyl radical footprint of the TFIIIA-DNA complex [Churchill, M.E. A. , Tullius, T.D. , & Klug, A. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 5528-5532].
Algorithm design for optimal power flow, security-constrained unit commitment, and demand response in energy systems

Energy management is of prime importance for power system operators to enhance the use of the existing and new facilities, while maintaining a high level of reliability. In this thesis, we develop analytical models and efficient algorithms for energy management programs in transmission and distribution networks. First, we study the optimal power flow (OPF) in ac-dc grids, which is a non-convex optimization problem. We use convex relaxation techniques and transform the problem into a semidefinite program (SDP). We derive the sufficient conditions for zero relaxation gap and design an algorithm to obtain the global optimal solution. Subsequently, we study the security-constrained unit commitment (SCUC) problem in ac-dc grids with generation and load uncertainty. We introduce the concept of conditional value-at risk to limit the net power supply shortage. The SCUC is a nonlinear mixed-integer optimization problem. We use l1-norm approximation and convex relaxation techniques to transform the problem into an SDP. We develop an algorithm to determine a near-optimal solution. Next, we target the role of end-users in energy management activities. We study demand response programs for residential users and data centers. For residential users, we capture their coupled decision making in a demand response program with real-time pricing as a partially observable stochastic game. To make the problem tractable, we approximate the optimal scheduling policy of the residential users by the Markov perfect equilibrium (MPE) of a fully observable stochastic game with incomplete information. We develop an online load scheduling learning algorithm to determine the users’ MPE policy. Last but not least, we focus on the demand response
Public Attention, Governmental Bargaining, and Supranational Activism: Explaining European Integration in Response to Crises

Why and how do crises cause European integration? Going beyond case- and policy area-specific analyses, the present paper develops a general, liberal intergovernmentalist model of the crisis-integration link. The empirical process-tracing test of this model is performed on two diverse cases of crises: the BSE Crisis 1996–2002 and the Euro Crisis 2010–13. The original analysis of primary documents and newspaper articles reveals that, as theoretically expected, crises stir high public attention and thus turn policy change in the affected policy areas into a salient issue for governments. This opens a ‘window of opportunity’ for domestic actors to approach their governments with change proposals. Governmental cost–benefit calculations, the distribution of bargaining power at the EU level, as well as supranational activism then explain deeper European integration in response to a crisis. With these findings, the present paper contributes to a broader understanding of the mechanisms of European integration in exceptional times.
Using the Dallas Pain Questionnaire to Classify Individuals With Low Back Pain in a Working Population

Study Design. Individuals with low back pain were classified by cluster analysis of their responses to the Dallas Pain Questionnaire. These results enabled development of an alternative simple classification tool that yielded results close to those obtained by the cluster analysis. Objectives. To use the Dallas Pain Questionnaire to classify workers with low back pain, and to develop a practical classification tool for physicians. Summary of Background Data. The severity of low back pain is important information for patient management. Questionnaires exploring the multidimensional aspect of low back pain have been used to classify individuals with low back pain. The Dallas Pain Questionnaire is a short self-administered questionnaire that explores the functional and emotional aspects of chronic low back pain. It was tested in a population still at work using a simplified scoring system. Methods. The study included 765 persons with low back pain still at work who completed the self-administered questionnaire. Of these patients, 732 could be classified by cluster analysis according to their answers to the Dallas Pain Questionnaire. A classification tool was developed to categorize them. Using external variables, the groups thus formed were compared. Results. Respondents were classified into four classes: class 1 (minor disability), class 2 (intermediate disability), class 3 (disability for some physical activities), and class 4 (physical disability and emotional disturbance). External pain-related variables were clearly associated with increasing low back pain severity as measured by this classification tool. Conclusions. The Dallas Pain Questionnaire discriminated between different groups of persons with low back pain. The proposed classification uses a short, simple practical tool to assess different levels of low back pain.
The Use of Freeze-Dried Allograft Bone for Anterior Cervical Fusions

A consecutive series of 87 patients undergoing Smith–Robinson anterior cervical fusion were analyzed. Either freeze-dried tricortical iliac crest bone or tricortical autograft bone was used. Surgical technique was otherwise identical. Radiography showed delayed union at 3 months in 13% of patients with autograft and in 37% of patients with freeze-dried allograft. At 1 year, radiography showed nonunion in 8% of patients with autograft and in 22% of patients with allograft. One-level procedures had a delayed union rate of 7% for autograft and 21% for allograft. Nonunion in one-level procedures was 5% for both autograft and allograft. For two-level procedures, the nonunion rate was 17% for autograft and 63% for allograft. Graft collapse was more commonly seen with freeze-dried allograft (30%) than with autograft (5%). Relief of neck and arm pain, however, was similar in both groups.
Short‐term resistance training and the older adult: the effect of varied programmes for the enhancement of muscle strength and functional performance

Although it is well recognized that resistance training is an efficient strategy to enhance physical performance in older adults, less is known about the most effective type of resistive exercise or the role of functional training. This study compared the effectiveness of three varied short‐term (8 weeks) training protocols on muscle strength and functional performance in older men and women aged 65–84 years. Participants underwent twice‐weekly high‐velocity varied‐resistance training (HV), twice weekly slow to moderate‐velocity constant‐resistance training (CT), combined once weekly high‐velocity varied‐resistance and once weekly gymnasium‐based functional training (CB) or no training (CO). Dynamic muscle strength (1RM) of six muscle groups was assessed using isotonic equipment and functional performance by a battery of tests. Following 8 weeks of training, whole‐body muscle strength increased (P<0·001) by 22·0 ± 12·5% (mean ± SD), 21·7 ± 11·0% and 26·1 ±14·4% in HV, CT and CB, respectively, compared to CO (−1·8 ± 7·2%). In between group comparisons, only the HV group displayed greater chair rise ability (P =0·010) than the CO group, while differences among groups approached significance for the fast 6‐m walk and the stair climb test (P = 0·017 and 0·041 respectively). Within groups, the HV group significantly improved in stair‐climbing and chair rise ability (P≤0·001) while CB improved in the fast 6‐m walk (P = 0·003) and CT improved their static balance, as assessed by the functional reach test (P<0·001). This study indicates that twice weekly high‐velocity resistance training is superior to strength and combined functional and resistance training for improving some power‐orientated functional tasks. Although other functional performance improvements were modest among the training protocols, short‐term combined once weekly resistance and once weekly functional training in older adults was as effective in enhancing muscle strength as twice‐weekly resistance training. These results have important implications for older adults who are unable or unwilling to frequently attend exercise facilities.
Impact of Dietary Tomato Juice on Changes in Pulmonary Oxidative Stress, Inflammation and Structure Induced by Neonatal Hyperoxia in Mice (Mus musculus)

Many preterm infants require hyperoxic gas for survival, although it can contribute to lung injury. Experimentally, neonatal hyperoxia leads to persistent alterations in lung structure and increases leukocytes in bronchoalveolar lavage fluid (BALF). These effects of hyperoxia on the lungs are considered to be caused, at least in part, by increased oxidative stress. Our objective was to determine if dietary supplementation with a known source of antioxidants (tomato juice, TJ) could protect the developing lung from injury caused by breathing hyperoxic gas. Neonatal mice (C57BL6/J) breathed either 65% O2 (hyperoxia) or room air from birth until postnatal day 7 (P7d); some underwent necropsy at P7d and others were raised in room air until adulthood (P56d). In subsets of both groups, drinking water was replaced with TJ (diluted 50:50 in water) from late gestation to necropsy. At P7d and P56d, we analyzed total antioxidant capacity (TAC), markers of oxidative stress (nitrotyrosine and heme oxygenase-1 expression), inflammation (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) expression), collagen (COL) and smooth muscle in the lungs; we also assessed lung structure. We quantified macrophages in lung tissue (at P7d) and leukocytes in BALF (at P56d). At P7d, TJ increased pulmonary TAC and COL1α1 expression and attenuated the hyperoxia-induced increase in nitrotyrosine and macrophage influx; however, changes in lung structure were not affected. At P56d, TJ increased TAC, decreased oxidative stress and reversed the hyperoxia-induced increase in bronchiolar smooth muscle. Additionally, TJ alone decreased IL-1β expression, but following hyperoxia TJ increased TNF-α expression and did not alter the hyperoxia-induced increase in leukocyte number. We conclude that TJ supplementation during and after neonatal exposure to hyperoxia protects the lung from some but not all aspects of hyperoxia-induced injury, but may also have adverse side-effects. The effects of TJ are likely due to elevation of circulating antioxidant concentrations.
Comparison of merger and acquisition (M&A) success in horizontal, vertical and conglomerate M&As: industry sector vs. services sector

ABSTRACT Due to the high failure rate of the merger and acquisition (M&A) strategy, this study raises the question of whether there is a difference between the types of M&A in relation to M&A success. The study presents a research model to examine how each of the types of M&As – horizontal, vertical and conglomerate – separately affect M&A success. The study compares between the industry sector and the services sector. The results show that horizontal M&As lead to integration success and synergy success in the industry sector, but in the services sector, it leads to a failure of the integration stage, and in the both sectors it hinders the profitability. Vertical M&As lead to a success only in relation to synergy in the services sector, while conglomerate M&As lead to integration success and synergy success in the both sectors, but without success in relation to the profitability in the both sectors.