Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroprotective possibilities for Huntington’s disease

Huntington’s disease (HD) is a devastating genetic disorder. Despite the absence of effective therapy, there has been an explosion in interest for developing treatment strategies aimed at lessening or preventing the neuronal death that occurs in this disease. In large part, the renewed interest in neuroprotective strategies has been spurred by our increasing understanding of the genetic and molecular events that drive the underlying neuropathology of HD. This escalating understanding of the biological underpinnings of HD is derived from several convergent sources represented by investigators with clinical, genetic, molecular, physiological and neurobehavioural backgrounds. The diversity of data being generated has, in turn, produced a unique time in HD research where an impressive number of potential therapeutics are coming to the forefront. This review outlines several of these possibilities including the use of intracerebrally delivered neurotrophic factors, pharmacologically altering cellular energy production, the use of antiglutamatergic drugs, the use of caspase inhibitors and inhibitors of protein aggregation. This review also touches on the interesting possibility of whether or not the neurodegeneration in HD is at least partially reversible in nature. All of these possibilities are highlighted in the context that HD is a neurodegenerative disorder in which genetic detection provides a clear and unequivocal opportunity for neuroprotection.
Time course of left ventricular remodeling after stentless aortic valve replacement.

BACKGROUND Stentless aortic valves are associated with a significant decrease in left ventricular hypertrophy. This study examined the time course and factors affecting left ventricular mass regression (LVMR) after aortic valve replacement (AVR) with Cryolife O'Brien (CLOB) (Cryolife International, Atlanta, Ga) stentless valves. METHODS Between 1993 and 2000, 130 consecutive patients underwent AVR with CLOB. Mean age was 71.3 +/- 6.3 years. Sixty-four (49.2%) were male. Mean body surface area (BSA) was 1.7 +/- 0.2 m(2). Mean valve size implanted was 23.6 +/- 2.0 mm. All patients were monitored with serial echocardiograms; the first study was performed preoperatively, and subsequent controls were at 6 months, 1, 2, 3, 4, 5, 6, and 7 years, respectively. Left ventricular mass was calculated by the Devereux formula and indexed by BSA. RESULTS Analysis of variance showed a significant reduction in the left ventricular mass index (LVMI) over time (P < .001). Most LVMRs occurred within the first 6 months, and after 1 year LVMI had decreased by 37.5% with further, but not statistically significant, reductions at later examinations. We found that baseline BSA > 1.75 m(2), male sex, arterial blood pressure > or = 150 mm Hg, left ventricular ejection fraction < or = 35%, New York Heart Association functional class > or = III, non-sinus rhythm, and prevalent aortic incompetence to be factors influencing LVMR. LVMR was not related to postoperative effective orifice area < or = 0.85 cm/m(2) and prosthetic size. CONCLUSIONS AVR with a CLOB valve is followed by a significant LVMR that occurs soon after surgery. It is influenced by several patient-related factors: most of them can be predicted preoperatively.
Performance evaluation of genetic algorithms for flowshop scheduling problems

The aim of this paper is to evaluate the performance of genetic algorithms for the flowshop scheduling problem with an objective of minimizing the makespan. First we examine various genetic operators for the scheduling problem. Next we compare genetic algorithms with other search algorithms such as local search, taboo search and simulated annealing. By computer simulations, it is shown that genetic algorithms are a bit inferior to the others. Finally, we show two hybrid genetic algorithms: genetic local search and genetic simulated annealing. Their high performance is demonstrated by computer simulations. <<ETX>>
Detection and location of partial discharges in power transformers using acoustic and electromagnetic signals

The measurement of partial discharges (PD) is a non-destructive and sensitive diagnostic tool for the condition assessment of insulating systems. Two major tasks of PD measurements may be distinguished, (i) PD detection, hence providing evidence and the type of the PD and (ii) the location of the PD. The question "Where is the PD source? " is amongst others tremendously important for scheduling and starting maintenance/repair actions cost and time efficiently or to perform a risk analysis. Here the possibility to geometrically localize the flaw, by means of arrival times of acoustic PD signals, gets an extremely interesting option. Precise acoustic arrival times are consequently essential to accurately locate PD in a power transformer. The averaging of acoustic PD signals helps to enhance the acoustic sensitivity. The acoustic detection limit is lowered significantly and the determination of the arrival times is made possible for weaker PD. Supplementary steps, like automatic objective arrival time determination or additional wavelet-based de-noising further improve the overall location accuracy. A new location approach works with pseudo-times and allows for the use of robust direct solvers instead of the previously used iterative algorithms.
Immunomagnetic separation of adult human olfactory neural progenitors

Olfactory neuroepithelium (ONe) has lifelong regenerative capacity owing to the presence of mitotically active progenitors. The accessibility of ONe makes it a unique source of progenitors for cell replacement strategies in the CNS. We have established lines of neurosphere forming cells (NSFCs) from adult postmortem ONe and patients undergoing nasal sinus surgery by endoscopic biopsy. These heterogeneous lines are composed primarily of an immature neuronally restricted and a small glial restricted subpopulation. More homogeneous subpopulations of the NSFCs are essential for detailed study of factors influencing their lineage restriction. Immunomagnetic bead separation using an antibody against tyrosine kinase (Trk) receptors (Trk-pan, which recognizes Trk-A, B, C) resulted in viable, enriched positive and negative subpopulations that could be analyzed immunocytochemically. The positive cells remained positive for the first week after which the number of Trk-pan expressing cells decreased. The negative subpopulation began to express Trk-pan immunoreactivity after five days in vitro. Both subpopulations reverted to the heterogeneous composition after two weeks. Furthermore, most NSFCs were positive for Trk-B, a few for Trk-A, while no reactivity was observed for Trk-C. Because NSFCs produce brain derived neurotrophic factor (BDNF) and express Trk B, the specific receptor for BDNF, it is likely that population dynamics are under a paracrine and/or autocrine regulatory mechanism. Lineage restriction analysis demonstrated that the isolated subpopulation had a restriction potential equivalent to the original heterogeneous population. These studies characterize further the NSFCs and support the future potential therapeutic use of ONe-derived progenitors for CNS injury and neurodegenerative disorders.
The Disulfide Bond Structure of Plasmodium Apical Membrane Antigen-1*

Apical membrane antigen-1 (AMA-1) of Plasmodium falciparum is one of the leading asexual blood stage antigens being considered for inclusion in a malaria vaccine. The ability of this molecule to induce a protective immune response has been shown to be dependent upon a conformation stabilized by disulfide bonds. In this study we have utilized the reversed-phase high performance liquid chromatography of dithiothreitol-reduced and nonreduced tryptic digests of Plasmodium chabaudi AMA-1 secreted from baculovirus-infected insect cells, in conjunction with N-terminal sequencing and electrospray-ionization mass spectrometry, to identify and assign disulfide-linked peptides. All 16 cysteine residues that are conserved in all known sequences of AMA-1 are incorporated into intramolecular disulfide bonds. Six of the eight bonds have been assigned unequivocally, whereas the two unassigned disulfide bonds connect two Cys-Xaa-Cys sequences separated by 14 residues. The eight disulfide bonds fall into three nonoverlapping groups that define three possible subdomains within the AMA-1 ectodomain. Although the pattern of disulfide bonds within subdomain III has not been fully elucidated, one of only two possible linkage patterns closely resembles the cystine knot motif found in growth factors. Sites of amino acid substitutions in AMA-1 that are well separated in the primary sequence are clustered by the disulfide bonds in subdomains II and III. These findings are consistent with the conclusion that these amino acid substitutions are defining conformational disulfide bond-dependent epitopes that are recognized by protective immune responses.
The associations of suicide attempts in adolescents.

OBJECTIVE Suicide completion has increased in the United States among 15- to 24-year-olds from 4.5 per 100 000 (1950) to 13.2 per 100 000 (1990). Suicide attempts have been found to be associated with depression, substance use, overall number of life stressors, gender, and impulsive behaviors. We hypothesized that suicide attempt is associated with many other health risk behaviors. DESIGN To evaluate this hypothesis, we analyzed the data from the 1993 Massachusetts Youth Risk Behavior Survey from a representative sample of students in grades 9 through 12 in public and private high schools. We examined the relationships between ever attempting suicide and engaging in other health risk or problem behaviors (eg, sexual activity, substance use, violence, and seat belt nonuse). RESULTS The 3054 students were distributed among the 9th to 12th grades; 50.7% were female, 77.7% white, 6.7% black, 5.9% Hispanic, 4. 6% Asian, . 8% Native American, and 4.4% other; and the mean age was 16 +/- 1.2 years. Based on logistic regression analysis, ever attempting suicide was associated with physical fights in the past 12 months (odds ratio [OR] = 1.3[95% confidence interval (CI), 1. 22-1.44]), regular cigarette use in the past 30 days (2.0[1.41-2. 97]), female gender (3.2[2.21-4.71]), lack of seat belt use (1.3[1. 21-1.34]), gun carrying in the past 30 days (1.4[1.12-1.70]), substance use before last sexual activity (1.4[1.09-1.84]), Native American or other (2.4[1.21-4.71]), and lifetime use of other drugs (1.2[1.04-1.40]). The full model correctly assigned 92% of the youth. There were small differences in models for males, females, and sexually active youth. Same gender sexual experiences for sexually active youth did not significantly improve the model (partial r = .0, OR = .87 [95% CI, .33-2.30]) and fewer (88%) of the youth were correctly assigned by the model. CONCLUSIONS Ever attempting suicide is associated with other problem behaviors. This research proposes an empirical model of the relationship between suicide attempts and other health risk behaviors. Identifying which adolescents are at risk for suicide attempts from the presence of accompanying risk behaviors will help clinicians to evaluate suicide risk when other problem behaviors are identified, thus enabling the design of possible prevention strategies.
Radioimmunotherapy targeting of HER2/neu oncoprotein on ovarian tumor using lead-212-DOTA-AE1.

UNLABELLED The specificity, toxicity and efficacy of lead (212Pb) radioimmunotherapy were evaluated in nude mice bearing the SK-OV-3 human ovarian tumor cell line expressing the HER2/neu proto-oncogene. METHODS The therapeutic agent used was the tumor-specific anti-HER2/neu monoclonal antibody AE1 conjugated to 212Pb, 212Bi being the daughter and thus the source of the alpha-particle and beta emissions. A bifunctional derivative of tetraazacyclododecanetetraacetic acid (p-SCN-Bz-DOTA) was used to couple 212Pb to the anti-HER2/neu monoclonal antibody AE1. The chelating agent did not alter the binding affinity to its antigenic target or the pharmacokinetics and tissue distribution of the AE1 antibody. Toxicity and therapeutic efficacy of 212Pb-AE1 were evaluated in nude mouse ascites or solid tumor models, wherein SK-OV-3 cells were administered i.p. or s.c. , respectively. RESULTS The dose-limiting acute toxicity after i.v. administration of 212Pb-AE1 was bone marrow suppression, which was observed at doses above 25 microCi. Therefore, doses of 10 and 20 microCi were used in efficacy trials. The i.p. administration of 212Pb-AE1 3 days after i.p. tumor inoculation led to a significant (P2 = 0.015) prolongation of tumor-free survival. In a second model, i.v. treatment with 212Pb-AE1 3 days after s.c. tumor inoculation prevented subsequent tumor development in all animals treated with 10 or 20 microCi of 212Pb-AE1 (P2 = 0.002 compared to control groups). This efficacy in the adjuvant setting was antibody specific because treatments with equivalently labeled control antibody or unlabeled AE1 antibody or no treatment were less effective. The rate of growth of small (mean tumor volume, 15 mm3) SK-OV-3 tumors was modestly inhibited. However, tumor growth was not inhibited in mice bearing larger (mean tumor volume, 146 mm3) SK-OV-3 tumors by the administration of a single dose of 10 or 20 microCi of 212Pb-AE1. CONCLUSION Lead-212-AE1 as an intact radiolabeled monoclonal antibody may be of only modest value in the therapy of bulky solid tumors due to the short physical half-life of 212Pb and time required to achieve a useful tumor-to-normal tissue ratio of radionuclide after administration. However, the radiolabeled monoclonal antibody may be useful in therapy of tumors in the adjuvant setting. Furthermore, 212Pb may be of value in select situations, including treatment of leukemia, intercavitary therapy or strategies that target vascular endothelial cells of tumors.
A conceptual model of psychological contracts in construction projects

The strategic importance of relationship style contracting is recognised in the construction industry. Both public and private sector clients are stipulating more integrated and collaborative forms of procurement. Despite relationship and integrated contractual arrangement being available for some time, it is clear that construction firms have been slow to adopt them. Hence it is timely to examine how social exchanges, via unwritten agreement and behaviours, are being nurtured in construction projects. This paper adopted the concept of Psychological Contracts (PC) to describe unwritten agreement and behaviours. A conceptual model of the PC is developed and validated using the results from a questionnaire survey administered to construction professionals in Australia. The results uncovered the relationships that existed amongst relational conditions and relational benefits, the PC and the partners’ satisfaction. The results show that all the hypotheses in the conceptual model of the PC are supported, suggesting the PC model is important and may have an effect on project performance and relationship quality among contracting parties. A validated model of the PC in construction was then developed based on the correlations among each component. The managerial implications are that past relationships and relationship characteristics should be taken into account in the selection of procurement partners and the promise of future resources, support and tangible relational outcomes are also vital. It is important for contracting parties to pay attention to unwritten agreements (the PC) and behaviours when managing construction projects.
CEACAM2 positively regulates integrin αIIbβ3-mediated platelet functions

Abstract Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is an Ig-ITIM superfamily member that regulates integrin αIIbβ3 function. We hypothesized that its twin protein, CEACAM2, exerts a similar physiologic role in murine platelets. CEACAM2-deficient mice (Cc2−/−) displayed prolonged tail bleeding times and increased volume of blood loss. Cc2−/− platelets have moderate integrin αIIbβ3-mediated functional defects with impaired kinetics of platelet spreading on fibrinogen and type I collagen and delayed kinetics in the retraction of fibrin clots in vitro. This functional integrin αIIbβ3 defect could not be attributed to altered integrin αIIbβ3 expression. Cc2−/− platelets displayed normal ‘inside-out’ signaling properties as demonstrated by normal agonist-induced binding of soluble fluorescein isothiocyanate (FITC)-fibrinogen and JON/A antibody binding. This data provides direct evidence that disruption of CEACAM2 induces a moderate integrin αIIbβ3-mediated platelet function defect, and that CEACAM2 is essential to maintain a normal integrin αIIbβ3-mediated platelet function.
Can MM‐PBSA calculations predict the specificities of protein kinase inhibitors?

An application of the Molecular mechanics Poisson–Boltzmann surface area (MM‐PBSA) protocol to the prediction of protein kinase inhibitor selectivity is presented. Six different inhibitors are placed in equivalent orientations in each of six different receptors. Fully solvated molecular dynamics is then run for 1 ns on each of the 36 complexes, and the resulting trajectories scored, using the implicit solvent model. The results show some correlation with experimentally‐determined specificities; anomalies may be attributed to a variety of causes, including difficulties in quantifying induced fit penalties and variabilities in normal modes calculations. Decomposing interaction energies on a per‐residue basis yields more useful insights into the natures of the binding modes and suggests that the real value of such calculations lies in understanding interactions rather than outright prediction. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2007
Enantioselective synthesis of an all-syn four vicinal fluorine motif.

Alkanes bearing multiple vicinal fluorine atoms at adjacent stereocenters may be considered intermediate between alkanes and perfluoroalkanes, and as a class, their chemistry and behavior remain to be explored. We report here a stereoselective synthesis of an all-syn four vicinal fluorine motif as a single enantiomer. The four vicinal fluorine compound was amenable to single-crystal X-ray analysis, and the resulting structure displays gauche relationships between all four fluorines, consistent with the fluorine gauche effect, and CF.HC hydrogen bonding between adjacent fluoroalkyl chains.
Return Dispersion and Conditional Momentum Returns: International Evidence

The momentum premium is pervasive across international markets and different asset classes; however, the drivers of this premium are yet to be established. This paper contributes to the literature by examining the association between a leading economic indicator, namely return dispersion, and the momentum premium. This association is examined across four regional momentum strategies and a global momentum strategy. We document a strong association between return dispersion and the momentum premium using both ex-post and ex-ante empirical methods. This association is robust to the inclusion of a set of control variables and an alternate specification of return dispersion. We test a conditional momentum strategy that scales the unconditional momentum strategy by the level of return dispersion and find that the conditional momentum strategy outperforms the unconditional momentum strategy in all regions. The results presented in this paper document the dynamic association between risk and the momentum premium.
Magnetization Transfer Magnetic Resonance Imaging: A Clinical Review

Magnetic resonance imaging has traditionally used the T1 and T2 relaxation times and proton density (PD) of tissue water (hydrogen protons) to manipulate contrast. Magnetization transfer (MT) is a new form of tissue contrast based on the physical concept that tissues contain two or more separate populations of hydrogen protons: a highly mobile (free) hydrogen (water) pool, Hf, and an immobile (restricted) hydrogen pool, Hr, the latter being those protons bound to large macromolecular proteins and lipids, such as those found in such cellular membranes as myelin. Direct observation of the Hr magnetization pool is normally not possible because of its extremely short T2 time (<200 μs). But saturation of the restricted pool will have a detectable effect on the mobile (free) proton pool. Saturation of the restricted pool decreases the signal of the free pool by transferring the restricted pool's saturation. Exchange of magnetization between the free and restricted hydrogen protons is a substantial mechanism for spin-lattice (T1) relaxation in tissues and the physical basis of MT. Through an appropriately designed pulse sequence, magnetization transfer contrast (MTC) can be produced. MT contrast is different from T1, T2, and PD, and it likely reflects the structural integrity of the tissue being imaged. A variety of clinically important uses of MT have emerged. In this clinical review of the neuroradiological applications of MT, we briefly review the physics of MT, the appearance of normal brain with MT, and the use of MT as a method of contrast enhancement/background suppression and in tissue characterization, such as evaluation of multiple sclerosis and other white-matter lesions and tumors. The role of MT in small-vessel visualization on three-dimensional time-of-flight magnetic resonance angiography and in head and neck disease and newer applications of MT are also elaborated.
Why Are There so Many or so Few Parties?

Prior to the 2002 electoral reform, political parties in Russia’s regional legislative elections showed poor performance. Since December 2003, however, all regions have been obliged to elect no less than half of the members of their assemblies by proportional representation. As a result, party competition at the sub-national level became unavoidable. This study tests three kinds of hypotheses dealing with the institutional, sociological, and political factors in the fragmentation of party systems within Russia’s regions. The analysis demonstrates that political factors, especially the activity of the Kremlin and the heads of regional executives, have played the primary role in shaping regional party systems.