Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural analysis of the varicella-zoster virus gp98-gp62 complex: posttranslational addition of N-linked and O-linked oligosaccharide moieties

Varicella-zoster virus specifies the formation of several glycoproteins, including the preponderant gp98-gp62 glycoprotein complex in the outer membranes of virus-infected cells. These viral glycoproteins are recognized and precipitated by a previously described monoclonal antibody designated monoclone 3B3. When an immunoblot analysis was performed, only gp98 was reactive with monoclone 3B3 antibody; likewise, titration in the presence of increased concentrations of sodium dodecyl sulfate during antigen-antibody incubations caused selective precipitation of gp98 but not gp62. Further structural analyses of gp98 were performed by using the glycosidases endo-beta-N-acetylglucosaminidase H (endoglycosidase H) and neuraminidase and two inhibitors of glycosylation (tunicamycin and monensin). In addition to gp98, antibody 3B3 reacted with several intermediate products, including gp90, gp88, gp81, and a nonglycosylated polypeptide, p73. Since gp98 was completely resistant to digestion with endoglycosidase H, it contained only complex carbohydrate moieties; conversely, gp81 contained mainly high-mannose residues. Polypeptide p73 was immunodetected in the presence of tunicamycin and designated as a nascent recipient of N-linked sugars, whereas gp88 was considered to contain O-linked oligosaccharides because its synthesis was not affected by tunicamycin. The ionophore monensin inhibited production of mature gp98, but other intermediate forms, including gp90, were detected. Since the latter product was similar in molecular weight to the desialated form of gp98, one effect of monensin treatment of varicella-zoster virus-infected cells was to block the addition of N-acetylneuraminic acid. Monensin also blocked insertion of gp98 into the plasma membrane and, as determined by electron microscopy, inhibited envelopment of the nucleocapsid and its transport within the cytoplasm. On the basis of this study, we reached the following conclusions: the primary antibody 3B3-binding epitope is located on gp98, gp98 is a mature product of viral glycoprotein processing, gp98 contains both N-linked and O-linked oligosaccharide side chains, gp90 is the desialated penultimate form of gp98, gp88 is an O-linked intermediate of gp98, gp81 is the high-mannose intermediate of gp98, and p73 is the unglycosylated precursor of gp98.
A Performance and Area Efficient ASIP for Higher-Order DPA-Resistant AES

Masking is a common method used in embedded systems to prevent differential power analysis (DPA) attack. However, first-order masking cannot prevent higher-order DPA attacks. To enhance security, higher-order masking should be implemented. Hardware accelerator based higher-order masking has higher performance, but it consumes large area. General purpose processor (GPP) based higher-order masking is area-efficient, but it is unable to meet performance requirements. To handle this problem, we propose a novel high-order DPA-resistant ASIP. We develop three performance and area-efficient methods to extend the instruction set for a 32-bit LEON3 processor, with the goal of reducing execution cycles and code sizes. First, we reorder the execution sequence of SubBytes and ShiftRows. We partition new critical pathłthe masked SubBytes followed by the masked MixColumns, and transform computations from GF(28) to GF(24)2 that efficiently reduces the area. We reused our previous technique, which moved the map and the inverse map functions outside the AES round. Second, we develop an algorithm to search for an optimal transformation matrix of the map function to reduce the critical path of the masked MixColumns. Third, we reuse first-order masked SubBytes for higher-order masked SubBytes to optimize area without compromising performance. The experimental results show that our third-order masking design reduces around 8/9 execution cycles of GPP based reference design and reduces 70.5% area of hardware accelerator based reference design. We have realized a highly secure ASIP with third-order masking that dramatically reduces execution cycles from 197-470 K to only 3.3 K compared with state-of-the-art software implementations.
Association of the status of interstitial cells of Cajal and electrogastrogram parameters, gastric emptying and symptoms in patients with gastroparesis

Abstract Our goal was to investigate associations between the status of interstitial cells of Cajal (ICC) and electrogastrogram (EGG) parameters, gastric emptying and symptoms in a large cohort of patients with gastroparesis. Forty‐one patients with refractory gastroparesis who were referred for gastric electrical stimulation (GES) underwent full thickness gastric (antrum) biopsy during the surgery to place the GES device. The biopsy samples were stained with c‐kit and scored for the presence of ICC based on criteria obtained from 10 controls. All patients underwent EGG recordings, a 4‐h standardized scintigraphic gastric emptying study and symptom assessment prior to the surgery. Based on antral biopsy, 15 patients (36%) had almost no ICC (ICC− group) and 26 patients had adequate cell numbers (ICC+ group). EGG recordings in the ICC− group displayed significantly less normal slow waves than in the ICC+ group both in the fasting and fed states. Tachygastria in the ICC− group was significantly more than in the ICC+ group both in the fasting (32 ± 8%vs 11 ± 2%) and fed states (27 ± 9%vs 12 ± 2%). There was no statistical difference in gastric emptying, symptom severity of gastroparesis, aetiology, age and gender between the two groups. Severely depleted ICC occurs in up to 36% of gastroparetic patients and significantly correlates with an abnormal EGG. Severely depleted ICC does not correlate with the severity of gastroparesis as assessed by gastric emptying or symptom status but did result in a poorer symptomatic response to GES. These data suggest that the EGG may have a role for predicting ICC status during clinical evaluation of gastroparetic patients.
Specific Alterations of Endothelial Signal Transduction Pathways of Porcine Epicardial Coronary Arteries in Left Ventricular Hypertrophy

Coronary endothelial dysfunction in left ventricular hypertrophy (LVH) can reduce myocardial perfusion and result in an impaired global LV function. The objective of this study was to characterize the specific alterations of endothelial signal transduction of coronary arteries in a swine LVH model. Aortic banding was performed 3 cm above the coronary ostia. Vascular reactivity studies were performed to assess the nitric oxide (NO) and the EDHF-mediated relaxations. There was a significant increase in LV/body weight ratio associated with an increased in LV diastolic and end-diastolic pressure and decrease in dP/dT (P < 0.05), with no significant difference in coronary pressures 60 days after pressure-overload LVH. There was a significant decrease in endothelium-dependent relaxations to serotonin (5-HT) and to bradykinin (BK) (P < 0.05 for both) from LVH animals. There was no significant decrease of relaxations in the presence of BK and Nω-l-arginine (EDHF pathway). Plasma NOx levels decreased significantly from 1.8% ± 0.2% to 1.2% ± 0.1% (P < 0.05 versus control). Chronic pressure-overload LVH is associated with an endothelial dysfunction involving both Gi and Gq protein–mediated relaxations in coronary arteries as well as the EDHF pathway.
Calcium spikes and calcium plateaux evoked by differential polarization in dendrites of turtle motoneurones in vitro.

1. The ability of dendrites in turtle motoneurones to support calcium spikes and calcium plateaux was investigated using differential polarization by applied electric fields. 2. Electric fields were generated by passing current through transverse slices of the turtle spinal cord between two plate electrodes. The linear extracellular voltage gradient generated by the field implied that the tissue was ohmic and homogeneous. 3. The transmembrane potential at the cell body of motoneurones was measured as the voltage difference between an intracellular and an extracellular microelectrode. 4. In normal medium an applied field induced synaptic activity as well as intrinsic polarization of motoneurones. Synaptic activity was suppressed by tetrodotoxin (TTX, 1 microM). 5. In the presence of TTX and tetraethylammonium (TEA, 1‐5 mM), applied fields evoked multicomponent Ca2+ spikes in both the soma‐hyperpolarizing and soma‐depolarizing direction of the field. The different components of Ca2+ spikes were discrete and additive. High amplitude components had higher threshold and faster time course and were followed by larger after‐hyperpolarizations, than low amplitude components. The frequency of field‐evoked regenerative responses was relatively insensitive to somatic bias current. 6. TTX‐resistant Ca(2+)‐mediated plateau potentials promoted by apamin were evoked by differential polarization in both the soma‐depolarizing and soma‐hyperpolarizing direction. 7. It is concluded that Ca2+ channels responsible for Ca2+ spikes and Ca2+ plateaux are present in dendrites of spinal motoneurones of the turtle.
The Failure of Retrograde Autologous Priming of the Cardiopulmonary Bypass Circuit to Reduce Blood Use After Cardiac Surgical Procedures

Hemodilution during cardiopulmonary bypass (CPB) is a primary risk factor for blood transfusion in cardiac surgical patients. Priming of the CPB circuit with the patients’ own blood (retrograde autologous priming, RAP) is a technique used to limit hemodilution and reduce transfusion requirements. We designed this study to examine the impact of RAP on perioperative blood product use. Using a retrospective cohort study design, the medical records of all patients undergoing CPB (excluding circulatory arrest cases) by a single surgeon were examined. Data were collected over a 24-mo period when RAP was routinely used as a blood conservation strategy (RAP group, n = 257). This group was compared with a cohort of patients during the 24 mo immediately preceding the introduction of RAP into clinical practice (no RAP group, n = 288). A small, statistically insignificant reduction in the percentage of patients receiving packed red blood cells was observed in the RAP group (44% versus 51% no RAP, P = 0.083). No differences were found between the groups in the number of units of packed red blood cells, platelets, or fresh frozen plasma transfused throughout the perioperative period. These results suggest that overall, RAP does not offer a clinically important benefit as a blood conservation technique.
Effect of Fibular Plate Fixation on Rotational Stability of Simulated Distal Tibial Fractures Treated with Intramedullary Nailing

Background: The effect of an intact fibula on rotational stability after a distal tibial fracture has, to the best of our knowledge, not been clearly defined. We designed a cadaver study to clarify our clinical impression that fixation of the fibula with a plate increases rotational stability of distal tibial fractures fixed with a Russell-Taylor intramedullary nail.Methods: Seven matched pairs of embalmed human cadaveric legs and sixteen fresh-frozen human cadaveric legs, including one matched pair, were tested. To simulate fractures, 5-mm transverse segmental defects were created at the same level in the tibia and fibula, 7 cm proximal to the ankle joint in each bone. The tibia was stabilized with a 9-mm Russell-Taylor intramedullary nail that was statically locked with two proximal and two distal screws. Each specimen was tested without fibular fixation as well as with fibular fixation with a six-hole semitubular plate. A biaxial mechanical testing machine was used in torque control mode with an initial axial load of 53 to 71 N applied to the tibial condyle. Angular displacement was measured in 0.56-N-m torque increments to a maximal torque of 4.52 N-m (40 in-lb). Results: Initially, significantly less displacement (p ⩽ 0.05) was produced in the specimens with fibular plate fixation than in those without fibular plate fixation. The difference in angular displacement between the specimens treated with and without plate fixation was established at the first torque data point measured but did not increase as the torque was increased. No significant difference in the rotational stiffness was found between the specimens treated with and without plate fixation after measurement of the second torque data point (between 1.68 and 4.48 N-m). Conclusions: Fibular plate fixation increased the initial rotational stability after distal tibial fracture compared with that provided by tibial intramedullary nailing alone. However, there was no difference in rotational structural stiffness between the specimens treated with and without plate fixation as applied torque was increased.Clinical Relevance: In patients with ipsilateral distal tibial and fibular fractures who are treated with Russell-Taylor intramedullary nailing of the tibia, rotational stability of the tibial fracture can be increased by plate-and-screw fixation of the fibula, which may reduce the risk of valgus malunion.
Mechanism of primary graft non‐function in a rat model for fatty liver transplantation

Abstract We established a fatty liver model in rat suitable for the model of human liver with steatosis by cholesterol enriched chow, and investigated the mechanism of primary graft non‐function in fatty liver transplantation (LTx) using this model. Grafts with steatosis caused primary graft dysfunction after LTx following even short cold preservation; however, no significant difference was recognized in mitochondrial function of the graft during preservation. Morphological findings were not different at 1 h after reperfusion between non‐steatotic and steatotic livers. Focal necrosis of hepatocytes was seen and the sinusoidal endothelial cells were injured 24 h after reperfusion. In addition, the fluidity of the plasma membrane decreased in fatty liver. Our results indicate that deterioration of sinusoidal endothelial cells after reperfusion causes graft dysfunction in LTx of steatotic liver.
Multiple Domains of the Co-chaperone Hop Are Important for Hsp70 Binding*

The Hop/Sti1 co-chaperone binds to both Hsp70 and Hsp90. Biochemical and co-crystallographic studies have suggested that the EEVD-containing C terminus of Hsp70 or Hsp90 binds specifically to one of the Hop tetratricopeptide repeat domains, TPR1 or TPR2a, respectively. Mutational analyses of Hsp70 and Hop were undertaken to better characterize interactions between the C terminus of Hsp70 and Hop domains. Surprisingly, truncation of EEVD plus as many as 34 additional amino acids from the Hsp70 C terminus did not reduce the ability of Hsp70 mutants to co-immunoprecipitate with Hop, although further truncation eliminated Hop binding. Hop point mutations targeting a carboxylate clamp position in TPR1 disrupted Hsp70 binding, as was expected; however, similar point mutations in TPR2a or TPR2b also inhibited Hsp70 binding in some settings. Using a yeast-based in vivo assay for Hop function, wild type Hop and TPR2b mutants could fully complement deletion of Sti1p; TPR1 and TPR2a point mutants could partially restore activity. Conformations of Hop and Hop mutants were probed by limited proteolysis. The TPR1 mutant digested in a similar manner to wild type; however, TPR2a and TPR2b mutants each displayed greater resistance to chymotryptic digestion. All point mutants retained an ability to dimerize, and none appeared to be grossly misfolded. These results raise questions about current models for Hop/Hsp70 interaction.
Women Directors, Family Ownership and Earnings Management in Malaysia

Purpose - The purpose of this paper is to determine whether the representation of women on the boards (WOMBDs) and audit committees is associated with a reduction in the practice of earnings management and whether women are associated with income reducing (conservative) rather than income-increasing (aggressive) earnings management. The authors further argue that family ownership moderates the relationship between the presence of WOMBDs and audit committees and earnings management. Design/methodology/approach - The study uses non-finance firms listed on Bursa Malaysia over a period of four years, i.e. from 2008 until 2011. Findings - The evidence reveals that the presence of WOMBD or audit committee is not associated with a propensity for earnings management. In addition, the evidence also reveals that family ownership does not interact either with WOMBD or with women on the audit committee (WOMAC) to influence the propensity for earnings management. Nevertheless, the additional analyses show that, while women on boards are not associated with income-decreasing accruals, the presence of women on audit committees leads to income-reducing earnings management. The evidence further reveals that family ownership does not interact with either WOMBD or WOMAC to influence income-decreasing earnings management. Originality/value - This study extends prior research on the role of women directors and women audit committee members on earnings management focussing on family ownership. Further, the study also examines the direction of earnings management as opposed to the most prior studies, which mainly focus on the propensity of earnings management.
Factor V Leiden in an Urartian, Dating Back to 1000 BC

Factor V Leiden (FVL) is the most common monogenic disorder that causes activated protein C (APC) resistance, creating hyper-coagulation. The mutation shows an uneven geographic distribution, significantly high in European populations. The mutation is believed to have originated approximately 20 000 years ago probably from a geographic region close to Anatolia. This fact makes it noteworthy to search for the mutation in ancient populations that once lived in this area. One of these civilizations, Urartu was centered around Van Lake in Eastern Turkey. The archeological remains from the excavations of the region are dated back to 1000 BC. Teeth, taken from the excavations of Van Yoncatepe fortress, were taken into DNA analysis considering all the precautions for ancient DNA analysis. Multiplex STR (Short Tandem Repeats) analysis were performed both to determine the gender of the samples and to conclude that the samples are preserved from modern DNA contamination. After getting an 80% amplification success for amelogenin, a melting curve analysis using lightcycler was performed to determine the FVL genotype of each sample. Of the 60 samples, 1 gave a positive amplification result for FV gene and was found to be heterozygous. To date, the age of this mutation was estimated based on statistical calculations using haplotype frequencies; here for the first time, we report FVL in an ancient population of 3000 years.
Serological markers of autoimmunity in pregnant women with polycystic ovary syndrome: a pilot study

Background. Gestational diabetes mellitus (GDM) is highly prevalent in women with polycystic ovary syndrome (PCOS). Women with GDM have considerable risk for developing both type 1 and type 2 diabetes. Aim. To evaluate the prevalence of anti-GAD65 and anti-IA2 auto-antibodies in Chilean pregnant women with GDM, normal pregnancy (NP) and with PCOS (PPCOS) to establish whether in PCOS women GDM is partially induced by auto-antibodies. Methods. Women with singleton pregnancies matched by age and gestational age were included: 50 GDM, 59 NP and 50 PPCOS. During gestational weeks 22–28, a 2-h, 75 g oral glucose tolerance test was performed, with measurement of glucose, insulin, lipids and auto-antibodies. Results. A highly prevalence of anti-GAD65 antibodies (12%) was observed in women with GDM. PPCOS and NP women showed a similar distribution of anti-GAD65 antibodies (2.0% and 1.7%, respectively). Anti-IA2 antibodies were present in 4.0% of women with GDM, in 1.7% of NP women and 2.0% PPCOS women. Conclusion. A highly prevalence of anti-GAD65 was observed in women with GDM which is in agreement with previous studies. Nevertheless, the frequency of these auto-antibodies was very low in NP and PPCOS women.
Regulation of fatty acid composition in Escherichia coli: a proposed common mechanism for changes induced by ethanol, chaotropic agents, and a reduction of growth temperature

Growth of Escherichia coli in the presence of ethanol and chaotropic salts resulted in the synthesis of lipids containing elevated levels of unsaturated fatty acids analogous to the effect of a reduction in growth temperature. Both ethanol and chaotropic agents acted at the level of fatty acid biosynthesis and altered lipid composition by decreasing the proportion of saturated acyl chains available for the synthesis of phospholipids. A reduction in temperature causes similar effects on fatty acid biosynthesis in vivo and in vitro. Ethanol, chaotropic salts, and a decrease in temperature all weaken hydrophobic interactions. Antichaotropic salts antagonized and effects of these treatments on fatty acid synthesis in vitro. These results are consistent with a common mechanism for the effects of chaotropic agents, temperature, and ethanol on fatty acid synthesis. The biosynthesis of saturated and unsaturated acyl chains may be regulated by the strength of hydrophobic interactions. Changes in the strength of hydrophobic interactions could alter enzyme structure, substrate structure, or the equilibrium between the soluble enzymes of fatty acid synthesis and their respective acyl carrier protein substrates.
HIV‐1 Tat protein promotes formation of more‐processive elongation complexes.

The Tat protein of HIV‐1 trans‐activates transcription in vitro in a cell‐free extract of HeLa nuclei. Quantitative analysis of the efficiency of elongation revealed that a majority of the elongation complexes generated by the HIV‐1 promoter were not highly processive and terminated within the first 500 nucleotides. Tat trans‐activation of transcription from the HIV‐1 promoter resulted from an increase in processive character of the elongation complexes. More specifically, the analysis suggests that there exist two classes of elongation complexes initiating from the HIV promoter: a less‐processive form and a more‐processive form. Addition of purified Tat protein was found to increase the abundance of the more‐processive class of elongation complex. The purine nucleoside analog, 5,6‐dichloro‐1‐beta‐D‐ribofuranosylbenzimidazole (DRB) inhibits transcription in this reaction by decreasing the efficiency of elongation. Surprisingly, stimulation of transcription elongation by Tat was preferentially inhibited by the addition of DRB.