Miracle-dz/UniFAR-FTUs huggingface dataset:
Poly(ADP‐ribosyl)ation inhibitors: Promising drug candidates for a wide variety of pathophysiologic conditions

Poly(ADP‐ribose) polymerases are involved in many aspects of regulation of cellular functions. Using NAD+ as a substrate, they catalyse the covalent transfer of ADP‐ribose units onto several acceptor proteins to form a branched ADP‐ribose polymer. The best characterised and first discovered member of this multiprotein family is PARP‐1. Its catalytic activity is markedly stimulated upon binding to DNA strand interruptions, and the resulting polymer is thought to function in chromatin relaxation as well as in signalling the presence of damage to DNA repair complexes and in regulating enzyme activities. Moderate activation of PARP‐1 facilitates the efficient repair of DNA damage arising from monofunctional alkylating agents, reactive oxygen species or ionising radiation, but severe genotoxic stress leads to rapid energy consumption and subsequently to necrotic cell death. The latter aspect of PARP‐1 activity has been implicated in the pathogenesis of various clinical conditions such as shock, ischaemia‐reperfusion and diabetes. Inhibition of ADP‐ribose polymer formation has been shown to be effective, on the one hand, in the treatment of cancer in combination with alkylating agents by suppressing DNA repair and thus driving tumour cells into apoptosis, and on the other hand it appears to be a promising drug target for the treatment of pathologic conditions involving oxidative stress. In view of the existence of several members of the PARP family in mammalian cells, one has to be aware of possible side effects but also of a wide spectrum of potential clinical applications, which calls for the development of more specific inhibitors. © 2004 Wiley‐Liss, Inc.
A three‐protein inhibitor of polar septation during sporulation in Bacillus subtilis

We present evidence for a three‐protein inhibitor of polar division that locks in asymmetry after the formation of a polar septum during sporulation in Bacillus subtilis. Asymmetric division involves the formation of cytokinetic Z‐rings near both poles of the developing cell. Next, a septum is formed at one of the two polar Z‐rings, thereby generating a small, forespore cell and a mother cell. Gene expression under the control of the mother‐cell transcription factor σE is needed to block cytokinesis at the pole distal to the newly formed septum. We report that this block in polar cytokinesis is mediated partly by σE‐directed transcription of spoIID, spoIIM and spoIIP, sporulation genes that were known to be involved in the subsequent process of forespore engulfment. We find that a spoIID, spoIIM and spoIIP triple mutant substantially mimicked the bipolar division phenotype of a σE mutant and that cells engineered to produce SpoIID, SpoIIM and SpoIIP prematurely were inhibited in septum formation at both poles. Consistent with the hypothesis that SpoIID, SpoIIM and SpoIIP function at both poles of the sporangium, a GFP–SpoIIM fusion localized to the membrane that surrounds the engulfed forespore and to the potential division site at the distal pole.
Eye Salvage with Combination of Intravitreal and Intracameral Melphalan Injection for Recurrent Retinoblastoma with Anterior Chamber Involvement: Report of a Case

Aims: Herein we report successful eye salvage following combined intravitreal and intracameral administration of melphalan for anterior chamber recurrence of retinoblastoma. Methods: A 12-month-old boy was referred with a sporadic bilateral retinoblastoma staged as group D and V in the right eye and group E and V in the left eye. Treatment initially involved 6 cycles of 3 drugs followed by focal treatments. The left eye was enucleated. Three months after the end of systemic chemotherapy, multiple recurrent lesions were noted in the ciliary body and the anterior chamber. A series of intravitreal (IVT) and intracameral (IC) injections of melphalan combined with a 7th cycle of systemic chemotherapy was performed. The therapeutic schedule alternated: week A an IVT of melphalan (30 μg/0.1 mL) for a total of 4 versus week B IC injections of melphalan (15 μg/0.05 mL) 4 IC in total. Each injection was preceded by an anterior chamber. Cryotherapy to the injection punctures was systematically performed. Results: Rapidly, iris and ciliary body nodules regressed completely based on clinical and ultrasound biomicroscopic examinations. After 3 years of follow-up, the patient has shown no evidence of recurrence. Conclusion: In our patient, combined IVT and IC administration of melphalan proved highly efficacious in eradicating the ciliary body and anterior chamber disease and salvage of his one remaining functional eye.
Identifying connections in a fractured rock aquifer using ADFTs

Fractured rock aquifers are difficult to characterize because of their extremely heterogeneous nature. Developing an understanding of fracture network hydraulic properties in these aquifers is difficult and time consuming, and field testing techniques for determining the location and connectivity of fractures in these aquifers are limited. In the Clare Valley, South Australia, well interference is an important issue for a major viticultural area that uses a fractured aquifer. Five fracture sets exist in the aquifer, all dipping >25°. In this setting, we evaluate the ability of steady‐state asymmetric dipole‐flow tests (ADFTs) to determine the connections between a test well and a set of piezometers. The procedure involves dividing a test well into two chambers using a single packer and pumping fluid from the upper chamber to the lower chamber. By conducting a series of tests at different packer elevations, an “input” signal is generated in fracture zones connected to the test well. By monitoring the “output” response of the hydraulic dipole field at piezometers, the connectivity of the fractures between the test well and piezometers can be determined. Results indicate the test well used in this study is connected in a complex three‐dimensional geometry, with drawdown occurring above and below areas of potentiometric buildup. The ADFT method demonstrates that the aquifer evaluated in this study cannot be modeled effectively on the well scale using continuum flow models.
The Coagulation Disorder of Orthotopic Hepatic Transplantation

Orthotopic hepatic transplantation, which encompasses the excision of a diseased liver, an anhepatic interval and the arrival of a new liver taken from a cadaver, dramatically interferes with the normal hemostatic balance. Changes in thrombocytes, blood coagulation and fibrinolysis invariably occur, and bleeding and thrombosis may arise and seriously endanger the recipient's chance of survival. So far, there has been limited opportunity to investigate the acute coagulation disorder of orthotopic hepatic transplantation in human recipients. Useful additional information has been gained, however, from studies in animals, and has helped to clarify some of the underlying mechanisms. Still, conflicting findings have been reported and much of the present understanding still is based on speculation. This article is divided into two parts. In the first, coagulation data in clinical and experimental liver transplantation accumulated over the last 14 years are reviewed and discussed. In the second part, coagulation findings in a new series of 10 human liver recipients are presented. In these patients, further evidence of heparin as a critical factor in abnormal bleeding was obtained.
The Impact of Paying Interest on Reserves in the Presence of Government Deficit Financing

This paper re-examines the impact that paying interest on reserves has on price level indeterminacy, price level volatility, and overall economic well-being. Unlike previous papers which examined these issues, the model developed in this paper allows the return on reserves to equal the return on government securities, which is less than the prevailing return on storage. Equally important, this model also considers how deficit financing changes the impact that paying interest on reserves has on the economy. I show that the number of steady state equilibria is equal to, or greater than, the number that arise when no interest is paid on reserves. Consequently, the level of economic indeterminacy is equal to or greater than in an economy without interest payments. When the level of indeterminacy is the same, then economic volatility is reduced with the introduction of interest payments. However, when greater indeterminacy in the interest-on-reserves economy exists, then there also exists greater volatility. In addition, paying interest on reserves can be welfare enhancing under certain conditions. When it is not, an appropriate expansionary open market operation can sometimes, although not always, offset the welfare losses associated with interest payments. Finally, under a narrow set of conditions, unpleasant monetarist arithmetic may also obtain.
Nucleotide sequence of a variant protein A of Staphylococcus aureus suggests molecular heterogeneity among strains

Protein A is a cell wall linked protein of Staphylococcus aureus that binds mammalian IgG. Although protein A displays high size heterogeneity among strains, cloning and sequencing of its gene from two strains had not shown a large difference in size. Here we report a third protein A gene sequence that shows a size variation relative to these two, due to deletions on both one IgG binding domain and a cell wall binding domain (region X). By analysis of the three sequences we were able to delineate a hypothetic model for region X domain evolution and discussed the origin of genetic variability within and without strains.
An equalizer-adaptation logic for a 25-Gb/s wireline receiver in 28-nm CMOS

We present an adaptation scheme for a wireline-receiver equalizer composed of a feed-forward equalizer (FFE) and a decision-feedback equalizer (DFE), where the FFE is a cascaded connection of a high-frequency equalizer (HFEQ) and a low-frequency equalizer (LFEQ). The HFEQ is adjusted by using the conventional filter-pattern method. For the LFEQ adjustment, we used a modified filter-pattern method where the pattern matching is performed based on the mark ratio (i.e., the probability of `1'), to enhance the gain of the parameter-adjusting feedback loop. The adaptation is performed in the background, i.e., while data is being received.
BIOME SHIFTS IN SIBERIAN ARCTIC TUNDRA : EVIDENCE FROM FIVE DECADES OF SPACE-BASED EARTH OBSERVATION

Increasing abundance of tall, canopy-forming shrubs is one of the primary changes expected in the Arctic tundra biome with recent climate warming, but virtually all evidence for shrub increase comes from North America. Here we demonstrate a novel technique for assessing changes in the extent of tall shrublands in northwest Siberian tundra since the 1960s, using satellite imagery dating to the early Space Age. First, we directly quantified changes in tall shrub cover by comparing high-resolution satellite imagery from the 1960s and recent years for five ~60 km 2 study areas. We then determined temporal trends in the Normalized Difference Vegetation Index (NDVI)—a spectral metric of the abundance of green vegetation—for these sites for 19842012, using imagery from Landsat satellites. We found that Landsat pixels with strong, positive NDVI trends tended to correspond to areas which have developed new shrub cover since the 1960s. We exploited the sensitivity of Landsat NDVI time-series to changes in tundra vegetation to estimate recent changes in shrubland extent for six much larger (~1,000 km 2 ) study areas. We conclude that alder abundance has increased at all eleven sites distributed across this large and littlestudied region, and that high potential exists for future shrub increase.
Blood or Urine Measurement of Human Chorionic Gonadotropin for Detection of Ectopic Pregnancy? A Comparative Study of Quantitative and Qualitative Methods in Both Fluids

One hundred seventy-five patients with features of ectopic pregnancy were studied, of whom 95 were subsequently shown to have an ectopic pregnancy. Paired blood and urine samples were assayed for human chorionic gonadotropin (hCG) by two radioimmunoassays, one immunoradiometric assay for intact hCG and an immunoradiometric assay for free beta subunit that also detects the “beta core” of hCG in urine. Qualitative testing was also performed using the Tandem Icon method of immunoconcentration on a membrane. The quantitative results for intact hCG showed an approximately unitary relationship between concentrations in both fluids, with a close correlation (r=0.84, gradient=1.01). The qualitative tests for hCG in both serum and urine were positive in all patients with ectopic pregnancy. The Tandem Icon is equally useful in blood and urine, whereas quantitative assays are more reliable in the blood. Quantitation of urinary hCG is not recommended because of the variable dilution of the glycoprotein in this fluid.
Precise Relative Positioning of Vehicles with On-the-Fly Carrier Phase Resolution and Tracking

Forward collision warning systems, lane change assistants, and cooperative adaptive cruise control are examples of safety relevant applications that rely on accurate relative positioning between vehicles. Current solutions estimate the position of an in-front driving vehicle by measuring the distance with a radar sensor, a laser scanner, or a camera system. The perception range of these sensors can be extended by the exchange of GNSS information between the vehicles using an intervehicle communication link. One possibility is to transmit GNSS pseudorange and carrier phase measurements and compute a highly accurate baseline vector that represents the relative position between two vehicles. Solving for the unknown integer ambiguity is specially challenging for low-cost single-frequency receivers. Using the well-known LAMBDA (Least-squares AMBiguity Decorrelation Adjustment) algorithm, in this paper, we present a method for tracking the ambiguity vector solution, which is able to detect and recover from cycle slips and cope with changing satellite constellations. In several test runs performed in real-world open-sky environments with two vehicles, the performance of the proposed Ambiguity Tracker approach is evaluated. The experiments revealed that it is in fact possible to track the position of another vehicle with subcentimeter accuracy over longer periods of time with low-cost single-frequency receivers.
Characterization of a Pattern Recognition Protein, a Masquerade-Like Protein, in the Freshwater Crayfish Pacifastacus leniusculus1

A multifunctional masquerade-like protein has been isolated, purified, and characterized from hemocytes of the freshwater crayfish, Pacifastacus leniusculus. It was isolated by its Escherichia coli binding property, and it binds to formaldehyde-treated Gram-negative bacteria as well as to yeast, Saccharomyces cerevisiae, whereas it does not bind to formaldehyde-fixed Gram-positive bacteria. The intact masquerade (mas)-like protein is present in crayfish hemocytes as a heterodimer composed of two subunits with molecular masses of 134 and 129 kDa. Under reducing conditions the molecular masses of the intact proteins are not changed. After binding to bacteria or yeast cell walls, the mas-like protein is processed by a proteolytic enzyme. The 134 kDa of the processed protein yields four subunits of 65, 47, 33, and 29 kDa, and the 129-kDa protein results in four subunits of 63, 47, 33, and 29 kDa in 10% SDS-PAGE under reducing conditions. The 33-kDa protein could be purified by immunoaffinity chromatography using an Ab to the C-terminal part of the mas-like protein. This subunit of the mas-like protein has cell adhesion activity, whereas the two intact proteins, 134 and 129 kDa, have binding activity to LPSs, glucans, Gram-negative bacteria, and yeast. E. coli coated with the mas-like protein were more rapidly cleared in crayfish than only E. coli, suggesting this protein is an opsonin. Therefore, the cell adhesion and opsonic activities of the mas-like protein suggest that it plays a role as an innate immune protein.
Opposing Roles for TRAF1 in the Alternative versus Classical NF-κB Pathway in T Cells*

Background: The T cell costimulatory molecule 4-1BB signals through TRAF1 and TRAF2. Results: TRAF1−/− T cells show hyperproliferation due to enhanced alternative NF-κB activation but have impaired classical NF-κB activation. Conclusion: TRAF1 enhances 4-1BB induced classical NF-κB activation but restricts alternative NF-κB activation in the absence of costimulation. Significance: This explains the contrasting roles attributed to TRAF1. T cells lacking TRAF1 hyperproliferate in response to T cell receptor signaling but have impaired signaling downstream of specific TNFR family members such as 4-1BB. Here we resolve this paradox by showing that while TRAF1 is required for maximal activation of the classical NF-κB pathway downstream of 4-1BB in primary T cells, TRAF1 also restricts the constitutive activation of NIK in anti-CD3-activated T cells. Activation of the alternative NF-κB pathway is restricted in unstimulated cells by a cIAP1/2:TRAF2:TRAF3:NIK complex. Using knockdown of NIK by siRNA we show that in activated CD8 T cells TRAF1 is also involved in this process and that constitutive activation of the alternative NF-κB pathway is responsible for costimulation independent hyperproliferation and excess cytokine production in TRAF1-deficient CD8 T cells compared with WT CD8 T cells. The T cell costimulatory molecule 4-1BB critically regulates the survival of activated and memory CD8 T cells. We demonstrate that stimulation through 4-1BB induces cIAP1-dependent TRAF3 degradation and activation of the alternative NF-κB pathway. We also show that while both TRAF1 and cIAP1 have non-redundant roles in suppressing the alternative NF-κB pathway in T cells activated in the absence of costimulation, activation of the classical NF-κB pathway downstream of 4-1BB requires TRAF1, whereas cIAP1 plays a redundant role with cIAP2. Collectively these results demonstrate that TRAF1 plays a critical role in regulating T cell activation both through restricting the costimulation independent activation of NIK in activated T cells and by promoting the 4-1BB-induced classical NF-κB pathway.
Evidence for occurrence of the ESAT-6 protein in Mycobacterium tuberculosis and virulent Mycobacterium bovis and for its absence in Mycobacterium bovis BCG

ESAT-6 is a secreted protein present in the short-term culture filtrate of Mycobacterium tuberculosis after growth on a synthetic Sauton medium. ESAT-6 has recently been demonstrated to induce strong T-cell responses in a mouse model of memory immunity after infection with M. tuberculosis. In Western blotting (immunoblotting), the monoclonal antibody HYB76-8, reacting with ESAT-6, gave a 6-kDa region was observed in filtrates from four of eight substrains of M. bovis BCG that produced high levels of MPB64, while no band occurred in the 6-kDa region with any of these BCG substrains. Southern blotting and PCR experiments with genomic mycobacterial DNA showed the presence of the esat-6 gene in reference strains and clinical isolates of M. tuberculosis as well as in virulent M. bovis. The esat-6 gene could not be demonstrated in any of the eight substrains of M. bovis BCG tested by these techniques. Two gene deletions that distinguish M. bovis BCG from virulent M. bovis have thus now been demonstrated. Deletion of mpb64 affects four of the eight substrains tested; deletion of esat-6 affects all of them. The reaction of HYB76-8 AT 26 kDa with four of the BCG substrains was demonstrated to result from cross-reactivity with MPB64. HYB76-8 was also shown to cross-react with the A, B, and C components of the antigen 85 complex and MPT51.
[Prevalence of hypertension in a disadvantaged population in Antilles: a major role for obesity?].

UNLABELLED The aim of this study was to evaluate the prevalence of hypertension and its management in a disadvantaged population, essentially composed of those receiving state subsidies and the unemployed. METHODS The PHAPPG study : Prevalence of Hypertension in a Population Précaire Guadeloupéenne (disadvantaged population in Guadeloupe) included 2420 consecutive people considered to be 'disadvantaged' seen in the two medical examination centres in Guadeloupe between November 2001 and November 2003. RESULTS The prevalence of obesity was considerable throughout the female population of Antilles (29%). It was recorded in 12% of men. The prevalence of hypertension in the population was 24.7% for men and 22.1% for women. Obesity was the main factor that could explain the higher prevalence of hypertension noted in Antilles, especially among 'disadvantaged' women. In effect, after correction for other risk factors and for age, this prevalence of hypertension was on average three times higher amongst the obese compared to subjects with normal weights. CONCLUSION The prevalence of hypertension is elevated in the population of Antilles, especially among the disadvantaged. Obesity is the key factor, upon which a primary prevention policy for hypertension could be based.
Asymmetric Corneal Flattening Effect After Small Incision Cataract Surgery.

PURPOSE To determine whether the flattening effect of corneal incisions differs between the right and left eye. METHODS A retrospective study of preoperative and postoperative corneal astigmatism was performed for patients who had bilateral cataract surgery by a right-handed surgeon. The change in corneal astigmatism was attributed to the 2.2-mm phacoemulsification incision, and the incisional flattening effect was calculated. The incisions were grouped by position on the eye and whether they were performed on the preoperative steep corneal meridian. RESULTS A total of 1,298 eyes of 649 patients were evaluated. The flattening effect of temporal 2.2-mm incisions performed on the preoperative corneal steep meridian was different for right eyes (0.53 diopters [D]) and left eyes (0.34 D) (P = .017). The flattening effect of superior 2.2-mm incisions performed on the preoperative corneal steep meridian was equivalent in the two eyes. CONCLUSIONS The flattening effect of a corneal incision may depend on whether it has been performed on the right or the left eye. [J Refract Surg. 2016;32(9):598-603. ].
Target Location and Visual Feedback as Variables Determining Accuracy of Aiming Movements

The accuracy of a long aiming movement was studied as a function of whether it was performed toward or away from the midline of the subject's body in the presence or absence of visual feedback. 30 right-handed, male university students (19—26 yr.) served as subjects. With movement distance and duration controlled, the mean percentage of error was 6 34% less for movements made toward the body's midline than for those performed away from the midline. The mean percentage of error was also 48% less in the presence of visual feedback than in its absence. However, contrary to our expectation, movements executed toward the body's midline were not appreciably less disrupted in the absence of visual feedback than movements performed away from the midline.