Miracle-dz/UniFAR-FTUs huggingface dataset:
Does Uric Acid Have a Pathogenetic Role in Graft Dysfunction and Hypertension in Renal Transplant Recipients?

Background. Uric acid (UA) may play a pathogenetic role in hypertension and kidney disease. We explored the prevalence of hyperuricemia and the relationship of UA to graft function and hypertension in prevalent renal transplant recipients (RTR). Methods. Baseline and follow-up data were collected on 90 RTR (mean age 51 yrs, 53% male, median transplant duration 7 years). Graft function was estimated using MDRD Study Equation 7. Results. At baseline, 70% RTR had hyperuricemia (UA >7.0 mg/dl (0.42mmol/L) in men and >6.0 mg/dl (0.36 mmol/L) in women) compared to 80% after 2.2 years (P=0.06). UA was not associated with blood pressure (BP) level but was higher in RTR with a history of hypertension compared to those without (8.6±1.8 vs. 7.3±2.2 mg/dl, [0.51±0.11 vs. 0.43±0.13 mmol/L], P=0.003) and in RTR on ≥3 antihypertensive medications compared to those taking less (9.1±1.6 vs. 7.6±1.8 mg/dL, [0.54±0.1 vs. 0.45±0.11 mmol/L], P<0.001). A history of hypertension was independently predictive of UA (&bgr; 0.06, [95% CI 0.02 to 0.10], P=0.007) in addition to sex, cyclosporine dose, prednisolone dose, estimated glomerular filtration rate (eGFRMDRD) and beta-blocker therapy. UA was independently predictive of follow-up eGFRMDRD (&bgr; −22.2 [95% CI −41.2 to −3.2], P=0.02) but did not predict change in eGFRMDRD over time. UA was independently associated with requirement for antihypertensive therapy (&bgr; 0.34, [95% CI 1.05 to 1.90], P=0.02). Conclusions. Hyperuricemia is common in RTR and is associated with need for antihypertensive therapy and level of graft function.
Novel androgen receptor gene mutations in Australian patients with complete androgen insensitivity syndrome

We have identified androgen receptor (AR) gene mutations in eight Australian subjects with complete androgen insensitivity syndrome (AIS). Four individuals, from three families, have novel mutations that introduce premature termination codons. Two siblings have the nonsense mutation Glu681X, and another subject has the nonsense mutation p.Ser884X. The other subject has a CA insertion at codon 829 (c.2847_2848insCA), causing a frameshift mutation that introduces four nonsense amino acids prior to a Stop codon. All the termination codons occur in the ligand binding domain, and cause reduced androgen binding in patient genital skin fibroblasts. Four further patients have missense mutations. One subject has two different mutations, p.Ala645Asp in the hinge region of the receptor, and p.Arg752Gln in the ligand binding domain. Both these mutations have previously been reported in patients with AIS, but the combination of these two mutations in one subject is unique. Another subject has a novel c.2533G>C transversion at the first nucleotide in exon 5, introducing the amino acid change p.Gly724Ala at a highly conserved residue in the ligand binding domain. Androgen binding is normal in fibroblasts from this subject, although other point mutations at this amino acid totally abolish binding. Two other subjects have mutations previously described as causing AIS, namely p.Arg779Trp and p.Val889Met substitutions in the ligand binding domain of the receptor. The p.Arg779Trp mutation is associated with the detection of a truncated AR protein in this patient's fibroblasts, suggesting the mutation renders the receptor susceptible to proteolysis. © 2004 Wiley‐Liss, Inc.
Long-Term Clinical Comparison of Procedural End Points After Pulmonary Vein Isolation in Paroxysmal Atrial Fibrillation: Elimination of Nonpulmonary Vein Triggers Versus Noninducibility

Background: Pulmonary vein isolation (PVI) is effective for maintenance of sinus rhythm in 50% to 75% of patients with paroxysmal atrial fibrillation, and it is not uncommon for patients to require additional ablation after PVI. We prospectively evaluated the relative effectiveness of 2 post-PVI ablation strategies in paroxysmal atrial fibrillation. Methods and Results: A total of 500 patients (mean age, 55.7±11.0 years; 74.6% male) were randomly assigned to undergo ablation by 2 different strategies after PVI: (1) elimination of non-PV triggers (group A, n=250) or (2) stepwise substrate modification including complex fractionated atrial electrogram or linear ablation until noninducibility of atrial tachyarrhythmia was achieved (group B, n=250). During a median follow-up of 26.0 months, 75 (32.2%) patients experienced at least 1 episode of recurrent atrial tachyarrhythmia after the single procedure in group A compared with 105 (43.8%) patients in group B (P value in log-rank test of Kaplan–Meier analysis: 0.012). Competing risk analysis showed that the cumulative incidence of atrial tachycardia was significantly higher in group B compared with group A (P=0.007). With the exception of total ablation time, there were no significant differences in fluoroscopic time or procedure-related complications between the 2 groups. Conclusions: Elimination of triggers as an end point of ablation in patients with paroxysmal atrial fibrillation decreased long-term recurrence of atrial tachyarrhythmia compared with a noninducibility approach achieved by additional empirical ablation. The post-PVI trigger test is thus a better end point of ablation for paroxysmal atrial fibrillation.
Phasic spike patterning in rat supraoptic neurones in vivo and in vitro

In vivo, most vasopressin cells of the hypothalamic supraoptic nucleus fire action potentials in a ‘phasic’ pattern when the systemic osmotic pressure is elevated, while most oxytocin cells fire continuously. The phasic firing pattern is believed to arise as a consequence of intrinsic activity‐dependent changes in membrane potential, and these have been extensively studied in vitro. Here we analysed the discharge patterning of supraoptic nucleus neurones in vivo, to infer the characteristics of the post‐spike sequence of hyperpolarization and depolarization from the observed spike patterning. We then compared patterning in phasic cells in vivo and in vitro, and we found systematic differences in the interspike interval distributions, and in other statistical parameters that characterized activity patterns within bursts. Analysis of hazard functions (probability of spike initiation as a function of time since the preceding spike) revealed that phasic firing in vitro appears consistent with a regenerative process arising from a relatively slow, late depolarizing afterpotential that approaches or exceeds spike threshold. By contrast, in vivo activity appears to be dominated by stochastic rather than deterministic mechanisms, and appears consistent with a relatively early and fast depolarizing afterpotential that modulates the probability that random synaptic input exceeds spike threshold. Despite superficial similarities in the phasic firing patterns observed in vivo and in vitro, there are thus fundamental differences in the underlying mechanisms.
Detection of Vibrio cholerae O1 in the aquatic environment by fluorescent-monoclonal antibody and culture methods

Vibrio cholerae O1 in plankton samples collected from ponds and rivers between February 1987 and January 1990 in Matlab, Bangladesh, was detected by the fluorescent-monoclonal antibody (FA) technique. Samples were collected at sites which were monitored fortnightly (fixed sites) as well as at sites that were part of a case-control study. FA results were compared with those obtained by conventional culture methods (CM). A total of 876 samples were collected; V. cholerae O1 was detected in 563 samples (64.27%) by the FA method and in 3 samples (0.34%) by CM. Of the fixed-site plankton samples, 439 (63.62%) were positive by FA and none were positive by CM. Of the 93 case sites sampled on the day after the occurrence of a case of cholera, 73 (78.49%) were positive for V. cholerae O1 by FA and 3 (3.2%) were positive by CM. In comparison, of the 93 first-day sample collections at control sites at the time a case of cholera occurred, only 51 (54.83%) were positive by FA and none were positive by CM. From the data, it is concluded that V. cholerae O1 is present throughout the year in the ponds and rivers of Bangladesh that were examined in this study and that V. cholerae can be detected by FA but not always by CM. The FA procedure was found to be very useful in detecting V. cholerae in plankton, with which it was associated and often occurred in large numbers in the nonculturable stage. Thus, studies investigating the significance of the role of environmental factors in the epidemiology of cholera can be performed effectively by using FA. Such studies are in progress.
Association of smoking and other risk factors with Fuchs' endothelial corneal dystrophy severity and corneal thickness.

PURPOSE We investigated effects of smoking and other risk factors on the development of advanced Fuchs' endothelial corneal dystrophy (FECD) and on central corneal thickness (CCT). METHODS Eyes from Caucasian probands, affected and unaffected family members, and unrelated controls matched for age from the FECD Genetics Multi-Center Study (n = 2044 subjects) were examined. Univariate and multivariate models, adjusted for family correlations, were used to determine the effect of smoking, sex, diabetes, and age on FECD case/control status and CCT. RESULTS In a multivariate model, sex and smoking were associated significantly with advanced FECD (grades 4-6) development (P = 0.016 and P = 0.047, respectively). Female sex increased odds by 34%. Smoking increased odds by 30%. In a multivariate model, diabetes was associated with an increase of 9.1 μm in average CCT (P = 0.021). Female sex was associated significantly with a decrease in average CCT by 6.9 μm (P = 0.015). Smoking had no significant effect on CCT in any model. As shown previously, advanced FECD was associated with large increases in CCT (31.4-94.2 μm). CONCLUSIONS Smoking was associated with an increased risk of advanced FECD and self-reported diabetes was associated with increased CCT. Further study of the impact of smoking and diabetes on FECD development and changes in corneal thickness is warranted.
Assessment of DNA damage and its modulation by dietary and genetic factors in smokers using the Comet assay: a biomarker model

Abstract Methods are needed to assess exposure to genotoxins in humans and to improve understanding of dietary cancer prevention. The Comet assay was used to detect smoking-related exposures and dietary modulations in target tissues. Buccal scrapings, blood and faeces were collected from 38 healthy male volunteers (smokers and non-smokers) during a dietary intervention study with bread supplemented with prebiotics±antioxidants. GSTM1-genotype was determined with PCR. Buccal and peripheral lymphocytes were analysed for DNA damage using the Comet assay. Genotoxicity of faecal water (FW) was assayed in human colon HT29 clone 19A cells. ‘Tail intensity’ (TI) was used as a quantitative indicator of DNA damage in the Comet assay. Intervention with bread reduced DNA damage in lymphocytes of smokers (8.3±1.7% TI versus 10.2±4.1% TI, n=19), but not of non-smokers (8.6±2.8% TI versus 8.3±2.7% TI, n=15). Faecal water genotoxicity was reduced only in non-smokers (9.4±2.9% TI versus 18.9±13.1% TI, n=15) but not in smokers (15.5±10.7% TI versus 20.4±14.1% TI, n=13). The Comet assay was efficient in the detection of both smoking-related exposure (buccal cells) and efficacy of dietary intervention (faecal samples). Smokers and non-smokers profited differently from the intervention with prebiotic bread±antioxidants. Stratification of data by genotype enhanced specificity/sensitivity of the intervention effects and contributed important information on the role of susceptibility.
Circuit weight training and cardiac morphology: a trial with magnetic resonance imaging

Background: Aerobic training (AT) and circuit weight training (CWT) improve peak oxygen uptake (VO2peak). During CWT the circulatory system is exposed to higher pressure, which could induce left ventricle morphological adaptations, possibly distinct from those derived from aerobic training. Objective: To compare the effects of aerobic training and CWT upon morphological and functional cardiac adaptations detected by magnetic resonance imaging. Methods: Twenty healthy sedentary individuals were randomly assigned to participate in a 12-week programme of aerobic training (n = 6), CWR (n = 7) or no intervention (n = 7, controls). Training programmes consisted of 36 sessions, 35 min each, 3 times per week, at 70% of maximal heart rate, and CWT included series of resistance exercises performed at 60% of 1 maximal repetition. Cardiopulmonary exercise testing and cardiac magnetic resonance imaging were performed before and after the intervention. Results: There was a similar improvement in VO2peak following aerobic training (mean (SD) increment: 12 (4)%) and CWT (12 (4)%), while there was no change in the control group. Aerobic training (12 (6)%) and CWT (16 (5)%) improved strength in the lower limbs, and only CWT resulted in improvement of 13 (4)% in the strength of the upper limbs. However, there were no detectable changes in left ventricular mass, end-diastolic volume, stroke volume or ejection fraction. Conclusion: In previously sedentary individuals, short-term CWT and aerobic training induce similar improvement in functional capacity without any adaptation in cardiac morphology detectable by cardiac magnetic resonance imaging.
Radiosurgery as palliation for brain metastases: a retrospective review of 72 patients harboring multiple lesions at presentation.

OBJECT The purpose of this study was to determine the outcome of palliative gamma knife radiosurgery (GKS) in a group of poor-risk patients with multiple brain metastases. METHODS The medical records of 72 patients with multiple brain metastases treated with GKS between October 1993 and November 9, 2001, were reviewed retrospectively. All patients presented with more than 10 lesions. There were 26 men and 46 women. The median age was 60 years (range 24-84 years). There were 39 patients with lung cancer, 18 with breast cancer, nine with metastatic melanomas, two with metastatic renal cell carcinomas, and four with other primary tumors. A total of 147 treatment sessions were required to treat 1304 sites in 72 patients. A mean of 10.4 isocenters per treatment was used. The mean tumor volume was 1.7 cm3. All patients had extracranial disease. The variables included in this study were the patient's Karnofsky Performance Scale score, age, sex, the radiation dose, initial number of lesions, and tumor volume and histopathology. CONCLUSIONS Radiosurgery can be a powerful tool in the palliative management of advanced metastatic disease even in patients presenting with multiple brain metastases. A median of two outpatient treatments was required, allowing the advanced cancer patient to avoid protracted fractionated radiotherapy and to undergo other therapeutic treatment with an acceptable quality of life.
Crystallographic Studies of the Interaction of Cyclodextrin Glycosyltransferase from Bacillus circulans Strain 251 with Natural Substrates and Products (*)

Asp-229, Glu-257, and Asp-328 constitute the catalytic residues in cyclodextrin glycosyl transferase from Bacillus circulans strain 251. Via site-directed mutagenesis constructed D229N, E257Q, and D328N mutant proteins showed a 4,000-60,000-fold reduction of cyclization activity. A D229N/E257Q double mutant showed a 700,000-fold reduction and was crystallized for use in soaking experiments with α-cyclodextrin. Crystal structures were determined of wild type CGTase soaked at elevated pH with α-cyclodextrin (resolution, 2.1 Å) and maltoheptaose (2.4 Å). In addition, structures at cryogenic temperature were solved of the unliganded enzyme (2.2 Å) and of the D229N/E257Q mutant after soaking with α-cyclodextrin (2.6 Å). In the crystals soaked in α-cyclodextrin and maltoheptaose, a maltotetraose molecule is observed to bind in the active site. Residue 229 is at hydrogen bonding distance from the C-6 hydroxyl group of the sugar, which after cleavage will contain the new reducing end. In the D229N/E257Q double mutant structure, two α-cyclodextrins are observed to replace two maltoses at the E-domain, thus providing structural information on product inhibition via binding to the enzyme's raw starch binding domain.
Accuracy-controlled convergence criterion for full wave simulation

Full wave electromagnetic (EM) simulations frequently encounter low-frequency breakdown: for decoupling of electric and magnetic fields in low frequency, the impedance matrix degenerates into near singular matrix and causes convergence problems. The iterative algorithms are currently the primary solvers of matrix equation for massive EM simulation. For absence of constraint between simulation accuracy and the convergence condition for iterative solver, excessively rigorous convergence condition has to be applied to ensure simulation accuracy, as a result, this way leads to over convergence, i.e., converge at unnecessarily high accuracy and simulation time doubly increases. By theoretically analyzing the impedance matrix, connection between simulation accuracy and the relative residual error which serves as the convergence condition in iterative solvers is established, and an accuracy-controlled convergence criterion is proposed. Numerical experiments are included to demonstrate that this convergence criterion effectively avoids the occurrence of over convergence yet insures simulation accuracy; therefore the simulation efficiency is visibly promoted.
Effect of Cardiac Resynchronization Therapy on Endothelium‐Dependent Vasodilatation in the Cutaneous Microvasculature

Aims: Cardiac resynchronization therapy (CRT) improves hemodynamic parameters, exercise capacity, symptoms, functional status, and prognosis among patients with chronic heart failure (CHF). The role of the vascular endothelium in these improvements is largely unknown. In this study, we aimed to investigate whether the endothelium‐dependent reactivity of the peripheral microcirculation improves in CHF patients during the first 2 months of CRT.
The Yin-Yang of DNA Damage Response: Roles in Tumorigenesis and Cellular Senescence

Senescent cells are relatively stable, lacking proliferation capacity yet retaining metabolic activity. In contrast, cancer cells are rather invasive and devastating, with uncontrolled proliferative capacity and resistance to cell death signals. Although tumorigenesis and cellular senescence are seemingly opposite pathological events, they are actually driven by a unified mechanism: DNA damage. Integrity of the DNA damage response (DDR) network can impose a tumorigenesis barrier by navigating abnormal cells to cellular senescence. Compromise of DDR, possibly due to the inactivation of DDR components, may prevent cellular senescence but at the expense of tumor formation. Here we provide an overview of the fundamental role of DDR in tumorigenesis and cellular senescence, under the light of the Yin-Yang concept of Chinese philosophy. Emphasis is placed on discussing DDR outcome in the light of in vivo models. This information is critical as it can help make better decisions for clinical treatments of cancer patients.
Mechanisms That Shape Human Antibody Repertoire Development in Mice Transgenic for Human Ig H and L Chain Loci

To determine the impact of the milieu on the development of the human B cell repertoire, we carried out a comprehensive analysis of productive and nonproductive Ig gene rearrangements from transgenic mice engineered to express single copies of the unrearranged human H chain and L chain Ig gene loci. By examining the nonproductive repertoire as an indication of the immediate product of the rearrangement machinery without an impact of selection, we discovered that the distribution of human rearrangements arising in the mouse was generally comparable to that seen in humans. However, differences between the distribution of nonproductive and productive rearrangements that reflect the impact of selection suggested species-specific selection played a role in shaping the respective repertoires. Although expression of some VH genes was similar in mouse and human (IGHV3-23, IGHV3-30, and IGHV4-59), other genes behaved differently (IGHV3-33, IGHV3-48, IGHV4-31, IGHV4-34, and IGHV1-18). Gene selection differences were also noted in L chains. Notably, nonproductive human VH rearrangements in the transgenic mice expressed shorter CDRH3 with less N addition. Even the CDRH3s in the productive rearrangements were shorter in length than those of the normal human productive repertoire. Amino acids in the CDRH3s in both species showed positive selection of tyrosines and glycines, and negative selection of leucines. The data indicate that the environment in which B cells develop can affect the expressed Ig repertoire by exerting influences on the distribution of expressed VH and VL genes and by influencing the amino acid composition of the Ag binding site.
Ultra low power 2-tier 3D stacked sub-threshold H.264 intra frame encoder

Digital circuits used in sensor networks require longer battery life and do not demand a fast frequency of operation. Sub-threshold circuits for such applications are an attractive option. Three dimensional ICs (3DICs) on the other hand is an emerging technology which helps in miniaturization and reduction in interconnects, resulting in power saving and performance improvement. Several works on sub-threshold circuits and TSV based 3DICs have been studied independently but none have studied the impact of 3D stacking of sub-threshold circuits. We design and study an ultra-low power 2-tier 3D sub-threshold implementation of H.264 intra frame encoder that encodes video frames. The encoder consumes 0. 73μW power at 16.13 KHz clock frequency for a typical application of encoding a Common Image Format (CIF) frame. The motivation is to assess the feasibility of the use of extreme low power video encoders in image sensor based sensor networks. Low power operation is highly beneficial to such unattended sensor networks by extending their battery life. Sub-threshold design helps us in this respect while 3D stacking minimizes footprint area, helps in off-chip to on-chip memory integration and improves timing performance.