Miracle-dz/UniFAR-FTUs huggingface dataset:
Blood pressure lowering in acute phase of stroke: latest evidence and clinical implications

Persistent controversy exists as to whether there are worthwhile beneficial effects of early, rapid lowering of elevated blood pressure (BP) in acute stroke. Elevated BP or ‘hypertension’ (i.e. systolic >140 mmHg) is common in stroke, especially in patients with pre-existing hypertension and large strokes, due to variable ‘autonomic stress’ and raised intracranial pressure. While positive associations between BP levels and poor outcomes are evident across a range of studies, very low BP levels and large reductions in BP have also been shown to predict death and dependence, more so for ischaemic stroke (IS) than intracerebral haemorrhage (ICH). Accumulating evidence indicates that early BP lowering can reduce haematoma expansion in ICH, but there is uncertainty over whether this translates into improved clinical outcomes, particularly since such an effect was not evident from haemostatic therapy in clinical trials. Guidelines generally recommend control of high systolic BP (>180 mmHg), but recent evidence indicates that even more modest elevation (>140 mmHg) increases risks of cerebral oedema and haemorrhagic transformation following thrombolysis in IS. Thus, any potential benefits of rapid BP lowering in acute stroke, particularly in IS, must be balanced against the potential risks of worsening cerebral ischaemia from altered autoregulation/perfusion. This paper explores current knowledge regarding the management of hypertension in acute stroke and introduces ongoing clinical trials aimed at resolving such a critical issue in the care of patients with acute stroke.
Using of Web Objects method in agile web software projects

Paper describes an implementation of Web Objects (WO) methods for measurement of software development results. The method is applied to a data-set of 2 projects obtained by Faculty of Science and Education, University of Mostar, focused on Web application projects. The projects are done by internal agile team during 2013 year. The ultimate goal of this approach is using of WO for early estimation in agile projects.
Calcium antagonist and antiperoxidant properties of some hindered phenols

1 The calcium antagonist and antioxidant activities of certain synthetic and natural phenols, related to BHA (2‐t‐butyl‐4‐methoxyphenol), were evaluated in rat ileal longitudinal muscle and in lipid peroxidation models respectively. 2 Compounds with a phenol or a phenol derivative moiety, with the exception of 2,2′‐dihydroxy‐3,‐3′‐di‐t‐butyl‐5,5′‐dimethoxydiphenyl (di‐BHA), inhibited in a concentration‐dependent manner the BaCl2‐induced contraction of muscle incubated in a Ca2+‐free medium. Calculated pIC50 (m) values ranged between 3.32 (probucol) and 4.96 [3,5‐di‐t‐butyl‐4‐hydroxyanisole (di‐t‐BHA)], with intermediate activity shown by khellin < gossypol < quercetin < 3‐t‐butylanisole < BHA < nordihydroguaiaretic acid (NDGA) < 2,6‐di‐t‐butyl‐4‐methylphenol (BHT) and papaverine. 3 The Ca2+ channel activator Bay K 8644 overcame the inhibition sustained by nifedipine, BHA and BHT, while only partially reversing that of papaverine. 4 BHA, BHT, nifedipine and papaverine also inhibited in a concentration‐dependent fashion CaCl2 contractions of muscle depolarized by a K+‐rich medium. This inhibition appeared to be inversely affected by the Ca2+‐concentration used. 5 The inhibitory effects of nifedipine, papaverine, BHA and BHT were no longer present when muscle contraction was elicited in skinned fibres by 5 μm Ca2+ or 500 μm Ba2+, suggesting a plasmalemmal involvement of target sites in spasmolysis. 6 Comparative antioxidant capability was assessed in two peroxyl radical scavenging assay systems. These were based either on the oxidation of linoleic acid initiated by a heat labile azo compound or on lipid peroxidation of rat liver microsomes promoted by Fe2+ ions. Across both model systems, di‐t‐BHA, NDGA, BHT, di‐BHA, BHA and quercetin ranked as the most potent inhibitors of lipid oxidation, with calculated pIC50 (m) values ranging between 7.4 and 5.7. 7 Of the 32 compounds studied only 15 phenolic derivatives exhibited both antispasmogenic and antioxidant activity. Within this subgroup a linear and significant correlation was found between antispasmogenic activity and antioxidation. These bifunctional compounds were characterized by the presence of at least one hydroxyl group on the aromatic ring and a highly lipophilic area in the molecule. 8 Di‐t‐BHA is proposed as a lead reference compound for future synthesis of new antioxidants combining two potentially useful properties in the prevention of tissue damage after ischaemia‐reperfusion injury.
Drug “Diffusion” within the Brain a

1. The rates and the ways different materials move from ventricular fluid into and through the caudate nucleus vary rather broadly. 2. The major mechanism of solute flow from ventricular CSF into and through the caudate nucleus appears to be simple diffusion. 3. Among solutes that pass across the BBB from brain to blood at very low rates, those that distribute mainly or exclusively in the extracellular space (e.g., sucrose, EDTA, and sodium) "diffuse" most rapidly into the caudate nucleus. 4. Among solutes which efflux across the BBB at very low rates, the apparent rate of diffusion within the caudate nucleus is the least for those that are readily taken up and accumulated by brain cells (e.g., AIB). 5. Solutes that move moderately to rapidly across the BBB from brain to blood only penetrate distances of several mm or less into the caudate before they are completely cleared from the tissue by the cerebral circulation. 6. In most instances the slopes of the tissue concentration profiles within the caudate nucleus during and after ventriculocisternal perfusion are fairly steep and are complex functions of parameters such as the effective tissue diffusion coefficient (Dt) and the transcapillary efflux rate constant (Ko), each of which are, in turn, dependent on separate sets of variables (e.g., the rate of cellular uptake for Dt and the rate of blood flow for ko). 7. The distribution process and kinetics may be much different in CNS areas adjacent to the subarachnoid space than in the caudate nucleus because of convective flow of subarachnoidal CSF through the perivascular spaces of the penetrating and emerging blood vessels and the arterioles and venules.
GZ‐793A, a lobelane analog, interacts with the vesicular monoamine transporter‐2 to inhibit the effect of methamphetamine

(R)‐3‐[2,6‐cis‐Di(4‐methoxyphenethyl)piperidin‐1‐yl]propane‐1,2‐diol (GZ‐793A) inhibits methamphetamine‐evoked dopamine release from striatal slices and methamphetamine self‐administration in rats. GZ‐793A potently and selectively inhibits dopamine uptake at the vesicular monoamine transporter‐2 (VMAT2). This study determined GZ‐793A's ability to evoke [3H]dopamine release and inhibit methamphetamine‐evoked [3H]dopamine release from isolated striatal synaptic vesicles. Results show GZ‐793A concentration‐dependent [3H]dopamine release; nonlinear regression revealed a two‐site model of interaction with VMAT2 (High‐ and Low‐EC50 = 15.5 nM and 29.3 μM, respectively). Tetrabenazine and reserpine completely inhibited GZ‐793A‐evoked [3H]dopamine release, however, only at the High‐affinity site. Low concentrations of GZ‐793A that interact with the extravesicular dopamine uptake site and the High‐affinity intravesicular DA release site also inhibited methamphetamine‐evoked [3H]dopamine release from synaptic vesicles. A rightward shift in the methamphetamine concentration‐response was evident with increasing concentrations of GZ‐793A, and the Schild regression slope was 0.49 ± 0.08, consistent with surmountable allosteric inhibition. These results support a hypothetical model of GZ‐793A interaction at more than one site on the VMAT2 protein, which explains its potent inhibition of dopamine uptake, dopamine release via a High‐affinity tetrabenazine‐ and reserpine‐sensitive site, dopamine release via a Low‐affinity tetrabenazine‐ and reserpine‐insensitive site, and a low‐affinity interaction with the dihydrotetrabenazine binding site on VMAT2. GZ‐793A inhibition of the effects of methamphetamine supports its potential as a therapeutic agent for the treatment of methamphetamine abuse.
Antiherpesvirus activity of 9-(4-hydroxy-3-hydroxymethylbut-1-yl) guanine (BRL 39123) in animals

The antiviral activity of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123) was assessed in several animal models of herpes simplex virus (HSV) infection. BRL 39123 was as active as acyclovir (ACV) when applied topically to guinea pigs with a cutaneous HSV type 1 (HSV-1) infection and was also active topically in an HSV-2 genital infection. Before systemic administration to infected animals, BRL 39123 and ACV were administered orally and subcutaneously to mice, and the blood was assayed for each compound by high-pressure liquid chromatography. When given systemically to mice infected cutaneously with HSV-1, BRL 39123 was as active as ACV. In mice infected intranasally with HSV-1 or HSV-2, single daily subcutaneous doses of BRL 39123 were more effective than equivalent treatment with ACV, reflecting the more persistent activity seen in cell culture and a more stable triphosphate within the infected cell. When the compounds were supplied in drinking water for this infection, BRL 39123 and ACV had similar potencies against HSV-1, although ACV was more active against an HSV-2 infection than BRL 39123 was. In mice infected intraperitoneally with HSV-1, BRL 39123 was 10-fold more potent than ACV and a single dose of BRL 39123 reduced virus replication within the peritoneal cavity more effectively than 3 doses of ACV given 1, 5, and 20 h after infection. Although BRL 39123 failed to eradicate the virus from mice latently infected with HSV-1, treatment initiated 5 h after infection of the ear pinna reduced the numbers of mice that developed latent infections.
Eisosomes provide membrane reservoirs for rapid expansion of the yeast plasma membrane

ABSTRACT Cell surface area rapidly increases during mechanical and hypoosmotic stresses. Such expansion of the plasma membrane requires ‘membrane reservoirs' that provide surface area and buffer membrane tension, but the sources of this membrane remain poorly understood. In principle, the flattening of invaginations and buds within the plasma membrane could provide this additional surface area, as recently shown for caveolae in animal cells. Here, we used microfluidics to study the rapid expansion of the yeast plasma membrane in protoplasts, which lack the rigid cell wall. To survive hypoosmotic stress, yeast cell protoplasts required eisosomes, protein-based structures that generate long invaginations at the plasma membrane. Both budding yeast and fission yeast protoplasts lacking eisosomes were unable to expand like wild-type protoplasts during hypoosmotic stress, and subsequently lysed. By performing quantitative fluorescence microscopy on single protoplasts, we also found that eisosomes disassembled as surface area increased. During this process, invaginations generated by eisosomes at the plasma membrane became flattened, as visualized by scanning electron microscopy. We propose that eisosomes serve as tension-dependent membrane reservoirs for expansion of yeast cells in an analogous manner to caveolae in animal cells. Highlighted Article: During membrane stretching in yeast protoplasts, eisosomes disassemble to release membrane invaginations and to facilitate surface area expansion.
Two amino acid residues confer type specificity to a neutralizing, conformationally dependent epitope on human papillomavirus type 11

Characterization of virus binding by neutralizing antibodies is important both in understanding early events in viral infectivity and in development of vaccines. Neutralizing monoclonal antibodies (MAbs) to human papillomavirus type 11 (HPV11) have been described, but mapping the binding site has been difficult because of the conformational nature of key type-specific neutralization epitopes on the L1 coat protein. We have determined those residues of the L1 protein of HPV11 which confer type specificity to the binding of HPV11-neutralizing MAbs. Binding of three HPV11-specific neutralizing MAbs could be redirected to HPV6 L1 virus-like particles in which as few as two substitutions of corresponding amino acid residues from HPV11 L1 have been made, thus demonstrating the importance of these residues to MAb binding through the transfer of a conformationally dependent epitope. In addition, a fourth neutralizing MAb could be distinguished from the other neutralizing MAbs in terms of the amino acid residues which affect binding, suggesting the possibility that it neutralizes HPV11 through a different mechanism.
Cyclosporine Abrogates De Novo Generation of Tregs Independently of IL‐2

Recent work by Kang et al. brings new insight into the mechanism by which cyclosporine A (CsA) blocks tolerance induction (1). Previous studies demonstrated that CsA inhibits activation induced cell death (AICD) in alloreactive T cells as well as expansion of the Foxp3-expressing regulatory T cells (Tregs). Given the crucial role of IL-2 in both AICD and homeostasis of Tregs, the authors hypothesize that the CsA-induced inhibition of tolerance is IL-2 dependent. Indeed, providing a long-lasting form of IL-2 (IL-2/Fc) reversed the effects of CsA. Combined IL-2/Fc and CsA enhanced AICD of alloreactive T cells and dramatically augmented the suppressive capacities of Tregs (1). Therefore, the authors propose that this may be a promising therapeutic combination in human transplantation.
Different outcomes of synergy between song production and song perception in the same subspecies (Molothrus ater ater).

Here we report data requiring a reinterpretation of published results on the female cowbird's (Molothrus ater ater) ability to identify male song (King, A. P., and West, M. J. (1983). Female perception of cowbird song: A closed developmental program. Dev. Psychobiol. , 16:335-342). Previously we stated that naive females, given extensive social experience with males from a distant cowbird subspecies, showed the same degree of preference for native song as did naive females reared with local males: extensive experience with another subspecies produced no evidence of postnatal modifiability. The procedure used to probe for modifiability did not, however, expose the different groups of females to comparable levels of stimulation because the females differentially affected the behavior of their male companions. We must therefore amend our conclusion about the modifiability of females. In addition, we report data on populational differences within the M.a. ater subspecies in the female's ability to influence heterosubspecific males, but data that are consistent with the more general pattern of synergistic effects during song development.
A four-way all-metal-waveguide power divider for millimeter-wave/THz array application

A four-way all-metal-waveguide power divider has been developed for millimeter-wave/THz array application. The power divider was realized by an E-plane Y-junction and two H-plane T-junction structures. To concatenate the two H-plane T-junctions to the outputs of the E-plane Y-junction structure respectively, good phase and amplitude balance of all output ports are guaranteed by its structure symmetry. According to EM simulations, the simulated -20dB return loss bandwidth is from 94.1GHz to 104.1GHz, and good amplitude and phase balance are observed in the operating band. The proposed structure has the properties of high splitting efficiency, efficient heat sinking and high power capacity.
Antiendothelial cell antibodies in vasculitis and connective tissue disease

Antiendothelial cell antibodies (AECA) are a heterogeneous family of antibodies reacting with endothelial cell antigens. These antibodies are found in various diseases and recognise several antigen determinants. Different pathophysiological effects have been observed in in vitro experiments, which include direct or indirect cytotoxicity and endothelial cell apoptosis. Furthermore, some AECA activate endothelial cells, resulting in increased leucocyte adhesiveness, activation of coagulation and vascular thrombosis. In animal models, it has been shown that AECA could promote vascular damage. Neither the endothelial cell antigens nor their precise role in the pathogenecity of different diseases in which AECA are found is well characterised. Nowadays, it is not known whether AECA are an epiphenomenon accompanying vascular injury or whether they are pathogenic. It is controversial whether fluctuations in AECA titres are associated with disease activity during follow-up studies. This review summarises the present knowledge about AECA, AECA antigens and their potential role in the pathogenecity of vasculitis and connective tissue diseases.
Automated design of spacecraft power subsystems

This paper discusses the application of evolutionary computing to a dynamic space vehicle power subsystem resource and performance simulation in a parallel processing environment. Our objective is to demonstrate the feasibility, application and advantage of using evolutionary computation techniques for the early design search and optimization of space systems. With this approach, engineers specify several sets of conditional subsystem performance criteria to trade off subsystem goals of mass, cost, performance and risk. Once specified, the integrated evolutionary/simulation software will then automatically generate a design option for each criteria, selecting and sizing power elements based on the space system's anticipated performance in the simulated environment. Initial activity plans from two actual JPL missions, Mars exploration rovers (MER) and Deep Impact (DI) are used to test the software. Our results have shown human-competitive advantages by generating credible design concepts much faster than humans are able to and without the need for expert initial designs
Designing on-chip clock generators

With recent improvements in semiconductor technology, the speed of state-of-the-art microprocessors has doubled roughly every other year. At such high speed, distributing clock signals across the system and making sure every component in the system is synchronized become very important issues. It is shown that one way to solve the inter-chip clock synchronization problem is to use an on-chip phase-locked loop (PLL) for clock generation. The PLL can generate an on-chip clock that is phase-locked to the off-chip clock. Since the buffer to the PLL is lightly loaded, the delay through it is much smaller than the delay through a conventional clock buffer. As a result, inter-chip clock skew is substantially reduced. The functional blocks of a PLL clock generator, including phase detectors, charge pumps, loop filters, and voltage-controlled oscillators (VCOs) are described. Frequency synthesis in VCO-based PLLs and problems associated with designing and simulating PLLs are discussed. <<ETX>>
Induction of Tissue Inhibitor of Metalloproteinase‐2 in Injured Rat Artery a

Arteries damaged by the passage of a balloon catheter become thicker. ' The vascular response to injury includes smooth muscle cell (SMC) proliferation and migration from the media into the intima, and it results in the formation of a neointima. The neointima is further enlarged in mass by the accumulation of matrix molecules synthesized by the SMCs. A shift in the balance of protease and protease inhibitors is probably necessary for vascular remodeling to occur. For example, a shift in favor of proteolysis might facilitate medial SMC movement by increasing the rate of degradation of the pericellular matrix. Recent studies from this laboratory showed an increased expression of the serine protease tissue-type plasminogen activator (t-PA) by migrating SMCs in the balloon-injured rat carotid artery. Furthermore, heparin, a known inhibitor of SMC migration and intimal thickening, inhibits t-PA expression by SMCS. ~ Matrix metalloproteinases (MMPs) are also expressed by SMCs and increased in injured vessels. The effect of these proteases is, to some extent, offset by the activity of the corresponding protease inhibitors. For example, the coordinated expression of extracellular MMPs and their inhibitors during transition of the mammary gland from a lactating phenotype to a nonlactating phenotype during involution was described in mice.3 Matrix accumulation in the forming neointima might be influenced as much by a decline in proteolytic activity as by an increase in matrix synthesis. In this study, we measured the expression of TIMP-2, a tissue inhibitor of the MMPs, in the injured artery to define better the role of proteases and their inhibitors in vascular remodeling.
Evaluating the impact of variation in automatically generated embodied object descriptions

The primary task for any system that aims to automatically generate human-readable output is choice: the input to the system is usually well-specified, but there can be a wide range of options for creating a presentation based on that input. When designing such a system, an important decision is to select which aspects of the output are hard-wired and which allow for dynamic variation. Supporting dynamic choice requires additional representation and processing effort in the system, so it is important to ensure that incorporating variation has a positive effect on the generated output. In this thesis, we concentrate on two types of output generated by a multimodal dialogue system: linguistic descriptions of objects drawn from a database, and conversational facial displays of an embodied talking head. In a series of experiments, we add different types of variation to one of these types of output. The impact of each implementation is then assessed through a user evaluation in which human judges compare outputs generated by the basic version of the system to those generated by the modified version; in some cases, we also use automated metrics to compare the versions of the generated output. This series of implementations and evaluations allows us to address three related issues. First, we explore the circumstances under which users perceive and appreciate variation in generated output. Second, we compare two methods of including variation into the output of a corpus-based generation system. Third, we compare human judgements of output quality to the predictions of a range of automated metrics. The results of the thesis are as follows. The judges generally preferred output that incorporated variation, except for a small number of cases where other aspects of the output obscured it or the variation was not marked. In general, the output of systems that chose the majority option was judged worse than that of systems that chose from a wider range of outputs. However, the results for non-verbal displays were mixed: users mildly preferred agent outputs where the facial displays were generated using stochastic techniques to those where a simple rule was used, but the stochastic facial displays decreased users’ ability to identify contextual tailoring in speech while the rule-based displays did not. Finally, automated metrics based on simple corpus similarity favour generation strategies that do not diverge far from the average corpus examples, which are exactly the strategies that human judges tend to dislike. Automated metrics that measure other properties of the generated output correspond more closely to users’ preferences.