Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Cysteine Proteinases by Autolytic Digestion is Mediated by CBP2/Hsp47

CBP2/Hsp47 is a glycoprotein normally limited to the ER-Golgi where it is first associated with procollagen chains at a very early point during translation of nascent chains and later with properly folded procollagen. Although CBP2/Hsp47 is regarded as a molecular chaperone belonging to the serpin superfamily, this protein does not appear to inhibit serine proteinases. Here we demonstrate that CBP2/Hsp47 functions in a manner similar to other serpin superfamily members by cross class inhibiting cysteine proteinases. A CBP2/Hsp47 to cathepsin L inactivation stoichiometery of ~1.5 revealed concurrent cleavage of CBP2/Hsp47 with proteinase inactivation. Cleavage of the CBP2/Hsp47 was shown to occur outside the P 1 --P 1 ' at the P 16 --P 15 and P 2 '--P 3 ' bonds. In addition, the proteinase bands in SDS/PAGE diminished on reaction of the enzyme with CBP2/Hsp47. These results sustain a mechanism advocated by Björk et al. (1998), in which cysteine proteinases assault a peptide bond in the reactive site loop of serpins, (CBP2/Hsp47) adjacent to the P 1 --P 1 ' bonds involved in serine proteinase inhibition. The reaction proceeds with the substrate pathway dominating in the cysteine proteinase reaction. In these complexes the cysteine proteinases, papain and cathepsin L, are rendered more susceptible to proteolysis and are degraded by active enzyme. These properties help explain the mechanism by which CBP2/Hsp47 increases the fidelity of collagen production. Moreover, if CBP2/Hsp47 is shown to involve the multiplexin subclass of collagens, it may further provide a mechanism by which the motogen and angiogenic properties during development and/or neoplasia are regulated.
Baseline Prevalence and Emergence of Protease Inhibitor Resistance Mutations following Treatment in Chronic HCV Genotype-1-Infected Individuals

Background The HCV NS3/4A serine protease inhibitors (PIs) boceprevir (BOC), telaprevir (TVR) and simeprevir (SMV) are approved for treatment of chronic hepatitis C infection in combination with pegylated interferon and ribavirin. The present study investigated the prevalence of HCV NS3 drug resistance mutations (DRMs) associated with HCV genotype-1-infected individuals at baseline and in viral breakthrough following BOC and TVR treatment. Methods HCV genotype-1-infected individuals were enrolled in a multicentre, prospective outcomes study. The HCV NS3 viral protease was analysed for DRMs at baseline (n=164) and at viral breakthrough (n=18) following BOC/ TVR treatment. Results Viral NS3 protease subtype analysis showed 65.2% (107/164) were HCV subtype-1a and 34.8% (57/164) were HCV subtype-1b infections. Naturally occurring PI DRMs in NS3 (V36L, T54S, V55A, Q80K/R and I132V) were identified in 57.3% (94/164) cases at baseline. The NS3 Q80K polymorphism was found in 43/107 (40.2%) of HCV subtype-1a and exclusively in clade 1 (43/82; 52.4%) versus clade 2 viruses (0/25; 0%, P<10-6). The pretreatment I132V variant was found in 78.9% (45/57) of subtype-1b. Of 18 patients who had viral breakthrough, the majority was subtype-1a (77.8%, 14/18). BOC/TVR-associated DRMs were detected in 94.4% (17/18), of which 64.7% (11/17) emerged on-treatment. Conclusions To ensure the most appropriate direct-acting antiviral-based treatment regimen is employed, baseline reporting of clade and resistance mutations for HCV sub-type-1a using nucleotide sequence-based analysis is warranted prior to commencement of therapy.
The Role of Strategic Uncertainty in Area‐Wide Pest Management Decisions of Florida Citrus Growers

We elicit a measure of strategic uncertainty from growers by using an experimental game grounded on the theory of global games. This allows us to achieve the following: propose a mechanism for measuring strategic uncertainty aversion; compare growers' risk aversion to their strategic uncertainty aversion; explore how growers' strategic uncertainty aversion is affected by changes in group size and coordination requirement; and relate a strategic uncertainty aversion measure to growers' actual decisions to participate in an area&#8208;wide pest management program. In our experimental setting, we found that when the coordination requirement for a successful outcome is low, most growers see the strategic uncertainty posed by human interaction as more favorable in terms of expected payoffs relative to a game against nature. In contrast, when the coordination requirement is high, most growers expect lower payoffs and choose to coordinate less. We also found evidence that growers' strong beliefs about neighbors not coordinating negatively impacted their choices to coordinate. Our measure of strategic uncertainty was also found to influence the likelihood of growers to actually coordinate sprays. Our findings help explain why participation in area&#8208;wide pest management to control the vector of citrus greening across Florida has not been as widespread as expected; the strategic uncertainty involved in relying on neighbors has made many growers choose self&#8208;reliance in spraying despite the lower payoff.
Relationship between plasma iohexol clearance and urinary exogenous creatinine clearance in dogs.

The objective of this study was to determine if plasma iohexol clearance, computed by a 1-compartment model defined by 3 plasma samples. was an accurate measure of glomerular filtration rate (GFR) in dogs. Twenty-two adult Beagle dogs of both genders were studied. Ten dogs had intact kidneys, and 12 dogs had surgically reduced renal mass. A bolus injection of iohexol was made, and blood was obtained for plasma iohexol assay after 120, 180, and 240 minutes. Plasma was analyzed for iohexol concentration by means of 3 assay methods: chemical, high-performance liquid chromatography (HPLC), and inductively coupled plasma emission spectroscopy (ICP). Urinary clearance of exogenous creatinine was used to measure GFR for three 30-minute periods occurring between 150 and 240 minutes after iohexol injection. Plasma clearance of iohexol and renal clearance of creatinine were compared by linear regression analysis and by limits of agreement techniques. Plasma iohexol clearance and urinary exogenous creatinine clearance were significantly correlated (chemical R2 = .90; HPLC R2 = .96; and ICP R2 = .96). The 1-compartment iohexol clearance:exogenous creatinine clearance ratios were 1.04 +/- 0.17, 1.05 +/- 0.14, and 1.10 +/- 0.15 for the chemical, HPLC, and ICP methods of assay, respectively, indicating that plasma iohexol clearance slightly overestimated GFR. Assuming a +/- 2 standard deviation interval for error, corrected plasma iohexol clearance measured GFR with +/-34% accuracy for the chemical, +/-26% accuracy for the HPLC, and +/-27% accuracy for the ICP method. These results indicate that plasma iohexol clearance should have utility for detection of renal dysfunction earlier in the course of progressive renal disease than is possible with measurement of plasma creatinine or urea concentrations.
Maternal deaths in rural Gambia

Abstract The objective of this study was to determine causes and contributing factors to maternal deaths in a poor rural setting. We included all maternal deaths (N =42), identified from January to September 2002, in a remote area of The Gambia. To gain a comprehensive picture of medical causes and contributing factors a combination of audit procedure and verbal autopsy was applied. The results showed that anaemia (n =12) was the leading cause of death followed by haemorrhage (n =10), eclampsia (n =8) and obstructed labour (n =8). Placental abruption accounted for 9 of the 10 haemorrhage cases. Substandard obstetric care was identified for the majority of deaths. Substantial inadequacies were revealed at the hospital, characterized by operational difficulties and an uncoordinated emergency preparedness, including malfunction of the blood transfusion service, failure to obtain operative delivery, poor birth monitoring and lack of trained personnel, electricity, medical equipment and drugs. Substandard primary care and logistic difficulties within the referral process further complicated the situation. Delay in seeking care by the cases themselves played a less important role. It was concluded that interventions, addressing the profound deficiencies within the health care system and increasing access to emergency obstetric care, are warranted to reduce maternal deaths in a poor setting such as rural Gambia.
Use of Local Community Hospital Data for Surveillance of Antimicrobial Resistance

We sought to determine whether antimicrobial susceptibility data from a nonteaching community hospital could be used to detect statistically significant local increases in resistance among Streptococcus pneumoniae over a 5-year period. Minimum inhibitory concentrations (MICs) of penicillin and ceftriaxone from 1997-1998 were compared with those from 2000-2001. MICs of penicillin and ceftriaxone for organisms collected in a nonteaching community hospital in central Illinois were used for analysis. The hospital has 224 beds and a catchment area of approximately 40 miles. There were significant increases in MICs of penicillin and ceftriaxone between 1997-1998 and 2000-2001. The MIC of penicillin increased from 0.042 to 0.121 μg/mL (P = .001; 95% confidence interval, -1.713 to -0.388), and the MIC of ceftriaxone increased from 0.028 to 0. 071μg/mL (P = .005; 95% confidence interval, -1.353 to -0.188). There were no significant changes in the percentage of S. pneumoniae isolates that were resistant, intermediate, or susceptible to penicillin and ceftriaxone. MIC data from a community hospital can be used to detect local increases in the rate of resistance before antibiogram data show significant changes. This information is important for demonstrating to physicians the need to review local antibiotic use in the attempt to slow the development of resistant organisms in the community.
Effect of Macro-economic Variables on Economic Growth of Pakistan

The main purpose of this study explores the effect of macroeconomic variables on the economy of Pakistan. This study contributes to the existing literature by investigate the empirical methods for estimation the impact of macroeconomic variables (inflation, interest rate, export and exchange rate) on the growth of economy. Used the time series data of 50 years during the period of 1968-2017 for the analysis. Data collected from the websites of World Bank and state bank of Pakistan. The findings of this study indicated that inflation is negative and insignificantly effected on growth, while interest and exchange rate is negative but significant and export has positive and significant impact on the growth of economy. The results suggested that the government should tight the policies and control the other factors which can badly affect the economic growth of Pakistan. Interest rate, exports exchange rate should also be controlled according to the development of economy. Keywords: Economic growth; inflation; interest rate; exports; exchange rate; Pakistan
Surface Tension, Glutathione Content and Redox Ratio of the Tracheal Aspirate Fluid of Premature Infants with IRDS

Objective: Determination of the surface tension (ST), the total glutathione (GL) content and the ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH) in the tracheal aspirate (TA) of newborn infants with IRDS. Methods: The ST of the TA was determined by monitoring the fluid level pulsated in a capillary glass tube by means of a digitalized videocomputerized picture analysis program, a technique developed in our laboratory. The concentrations of GSSG and total GL in the TA were determined enzymatically with glutathione reductase. All results of laboratory tests were referred to the total phospholipid (PL) concentration. Patients, Experimental Material: TA samples were collected from 32 intubated premature and newborn infants admitted to the NICU with IRDS during the first 2 weeks of their lives. Control samples were obtained from 11 children prior to elective surgery. Results: The ST relative to the PL content (surface tension index, STI) was significantly lower in the newborns with IRDS than in the control group, and the concentration of GSH in the TA was also markedly decreased in all IRDS infants studied. The concentration of GSSG and the ratio of GSSG to GSH were significantly higher in the severe cases and in those with an unfavourable prognosis. Surfactant treatment had a protective effect against oxidative stress, it induced a decrease in both the GSSG concentration and in the GL redox ratio (GSSG/GSH) in the TA. There was a close correlation between the GSH content and the STI value of the samples studied. Conclusion: Oxidation and consequent depletion of GSH in the TA may be an aggravating factor in the development of the insufficient surface activity in intubated newborns with IRDS.
Favorable long-term survival after reduced-intensity allogeneic transplantation for multiple-relapse aggressive non-Hodgkin's lymphoma.

PURPOSE The role of allogeneic transplantation with reduced-intensity conditioning in diffuse large B-cell lymphoma (DLBCL) is currently unclear, with relatively little published data. We report the outcome of reduced-intensity transplantation (RIT) in a cohort of 48 consecutive patients with relapsed/refractory DLBCL (30 patients with de novo disease and 18 patients with transformed follicular lymphoma) who underwent transplantation with an alemtuzumab-containing regimen, with a median follow-up of 52 months. PATIENTS AND METHODS Patients had experienced treatment failure with a median of five lines of prior therapy, including autologous transplantation in 69%, and 17% of patients were chemotherapy refractory at transplantation. Median age was 46 years, and 38% of patients had matched/mismatched unrelated donors. Conditioning was with alemtuzumab, fludarabine, and melphalan, and additional graft-versus-host disease (GVHD) prophylaxis was with cyclosporine. RESULTS All patients were successfully engrafted. Only 17% of patients developed grade 2 to 4 acute GVHD, with 13% experiencing extensive chronic GVHD. Four-year estimated nonrelapse mortality was 32%, and relapse risk was 33%. Twelve patients received donor lymphocyte infusions +/- chemoimmunotherapy for relapse, and five patients obtained durable remissions, giving current progression-free survival (PFS) and overall survival (OS) rates at 4 years of 48% and 47%, respectively. Patients who had chemotherapy-sensitive disease before RIT had current PFS and OS rates at 4 years of 55% and 54%, respectively. Chemotherapy-refractory patients had a poor outcome. CONCLUSION The encouraging survival rates with extended follow-up suggest a role for RIT in chemotherapy-sensitive relapsed DLBCL, even in patients who have previously experienced treatment failure with autologous transplantation. Future studies will be required to determine whether any subset of patients with relapsed DLBCL should be considered for RIT versus autologous transplantation.
The use of a vasodilator, felodipine, as an adjuvant to long-term oxygen treatment in COLD patients.

Eight patients with chronic obstructive lung disease (COLD) and pulmonary hypertension were given an infusion of a calcium antagonist, felodipine, during ongoing, long-term oxygen treatment (LTOT). The effects on central haemodynamics and ventilation-perfusion matching were studied. At rest pulmonary and systemic vascular resistances (PVR and SVR) were reduced by 18% (NS) and 26% (p less than 0.05), respectively. Cardiac output increased by 23%. There was a tendency to increased perfusion of low alveolar ventilation-perfusion ratio (VA/Q) areas (VA/Q less than 0.1) and to increased shunt compared to pretreatment values. Arterial oxygen tension (PaO2) fell by 0.7 kPa (p less than 0.001) but total oxygen transport increased by 23% (p less than 0.001). After treatment with oral felodipine (7.5-15 mg.day-1) for a mean time of 14 wks, PVR and SVR were reduced by 16% (p less than 0.05) and 7% (NS), respectively, as compared to pretreatment values at rest. Cardiac output rose by 13%. The VA/Q ratios and the PaO2 returned towards pretreatment values. The total oxygen transport increased by 11% (p less than 0.05) at rest and increased by 19% (p less than 0.05) during exercise as compared to the pretreatment value. The positive effect on central haemodynamics indicates that felodipine may be a valuable adjunct to ongoing LTOT.
Chronic active disease pattern predicts early damage in juvenile systemic lupus erythematosus

Objective The objective of this article is to assess disease activity patterns and their relationship to damage, death and growth failure in a cohort of juvenile lupus. Methods Chronic active, relapsing-remitting and long quiescent activity patterns were retrospectively classified according to longitudinal scores of both the Modified SLEDAI-2K and ECLAM. The Pediatric SLICC/ACR Damage Index (Ped-SDI) was scored at the last visit in patients followed more than six months. Survival analysis was performed considering death, damage and growth failure, and stratified according to disease activity patterns. Cox model analysis identified predictors for damage and growth failure among onset clinical variables. Results Thirty-seven patients with 11 years mean age at diagnosis and 3.2 years mean follow-up were studied. According to the Modified SLEDAI-2K, activity pattern was 67.5% relapsing-remitting, 29.8% chronic active and 2.7% long quiescent and by ECLAM, 45.9%, 48.7% and 5.4%, respectively. The five-year survival was 90%. Damage accrued in 62.5% and growth failure in 31.3%. Chronic active cases progressed to damage earlier than relapsing-remitting (log-rank test, p < 0.05). Damage was associated with disease duration (p < 0.0001), thrombocytopenia (p < 0.05) and alopecia (p < 0.004). Growth failure was associated with disease duration (p < 0.007) and renal failure (p < 0.007). Conclusion Damage was observed in nearly two-thirds of patients, and occurred earlier in the chronic active pattern. Disease duration, thrombocytopenia and alopecia at onset predicted damage.
Matrix sparsification for coded matrix multiplication

Coded computation is a framework for providing redundancy in distributed computing systems to make them robust to slower nodes, or stragglers. In a recent work of Lee et al., the authors propose a coded computation scheme for distributedly computing A x x in the presence of stragglers. The proposed algorithm first encodes the data matrix A to obtain an encoded matrix F. It then computes F x x using distributed processors, waits for some subset of the processors to finish their computations, and decodes A x x from the partial computation results. In another recent work, Dutta et al. explore a new tradeoff between the sparsity of the encoded matrix F and the number of processors to wait to compute A x x. They show that one can introduce a large number of zeros into F to reduce the computational overheads while maintaining the number of processors to wait relatively low. Hence, one can potentially further speed up the distributed computation. In this work, motivated by this observation, we study the sparsity of the encoded matrix for coded computation. Our goal is to characterize the fundamental limits on the sparsity level. We first show that the Short-Dot scheme is optimal if an Maximum Distance Separable (MDS) matrix is fixed. Further, by also designing this MDS matrix, we propose a new encoding scheme that can achieve a strictly larger sparsity than the existing schemes. We also provide an information-theoretic upper bound on the sparsity.
Lead Effects on Corn Mitochondrial Respiration

Oxidation of exogenous nicotinamide-adenine dinucleotide and succinate by corn mitochondria was measured as a function of lead chloride concentration. Lead chloride (50 to 62 micromoles per liter) stimulated oxidation of exogenous reduced nicotinamide-adenine dinucleotide by 174 to 640 percent depending on the reaction mediums, whereas lead chloride (12.5 micromoles per liter) inhibited succinate oxidation by more than 80 percent. When inorganic phosphate was included in reaction mediums the subsequent addition of lead was without effect due to the low solubility of lead phosphate. If addition of lead was followed by addition of phosphate the inhibition of succinate oxidation by lead was released, but there was no reduction in the stimulation of oxidation of reduced nicotinamide-adenine dinucleotide by lead. The effects of lead on plant growth might be accentuated under conditions of phosphate deficiency.
Chronic cocaine disruption of estrous cyclicity in the rat: dose-dependent effects.

The effects of cocaine on cyclic reproductive function in females remain largely unknown. In this study, we sought to define the range of doses of cocaine effective in disrupting estrous cyclicity and inhibiting ovulation. Estrous cyclicity was monitored daily by vaginal cytology. Group 1 consisted of rats receiving no treatment. Group 2 consisted of rats injected daily with saline s.c. Groups 3 to 6 consisted of rats injected with 1, 5, 10 and 20 mg/kg/day of cocaine HCl s.c. , respectively. Group 7 consisted of rats that were food-restricted to allow weight gains comparable to those of group 6. Our results indicate a dose-dependent effect of cocaine on estrous cyclicity with an estimated IC50 of 8.5 mg/kg/day (i.e., the dose of cocaine required to inhibit the number of proestrus: estrus events per 3-week period of analysis by 50%). Over 50% of the rats with cycle disruption on 10 mg/kg/day of cocaine, but almost none of those with cycle disruption on 20 mg/kg/day, returned to normal cyclic patterns after cessation of cocaine treatment. Serum luteinizing hormone levels were reduced 53 and 74% by 10 and 20 mg/kg/day of cocaine, respectively, with an IC50 of 8.9 mg/kg/day. In contrast, cocaine had no significant effect at any of the tested dosages on serum follicle-stimulating hormone or prolactin levels. Ovulation rates were significantly reduced at both 10 and 20 mg/kg/day of cocaine (IC50 = 11 mg/kg/day of cocaine). (ABSTRACT TRUNCATED AT 250 WORDS)
Human coronavirus OC43 interacts with major histocompatibility complex class I molecules at the cell surface to establish infection.

Human coronaviruses have been associated with common colds, diarrhea and enterocolitis, and have been implicated in multiple sclerosis. HLA class I molecules may play a critical role as receptor for OC43 because monoclonal antibody (mAb)W6/32 to HLA-A, -B and -C specificities completely blocks infectivity in human rhabdomyosarcoma (RD) cells. The role of HLA class 1 antigen as the virus receptor was examined using HLA-A3.1 stably transfected human plasma cells and untransfected HMY.C1R cells which do not express HLA-A and -B molecules. When the cells (5 x 10(6)) were infected at a multiplicity of one, the HLA.A3 transfected cells produced 10(8) PFU of virus whereas no replication occurred in the HMY.C1R cells mAb W6/32 reduced the virus yield by 99.9%. Cell membranes from HMY.C1R, HMY.A3 cells and chicken erythrocytes were biotinylated as live cells. Immunoprecipitation with polyclonal antiviral antibody to detect binding of biotinylated cell membranes to virus revealed that biotinylated HMY.A3 membranes coprecipitated with virus-antibody complexes when the immunoprecipitates were electrophoresed on SDS-PAGE gel, electroblotted and stained with Avidin-horseradish peroxidase. The results provide direct evidence that OC43 virus can recognize HLA class I as receptor on the cell surface.