Miracle-dz/UniFAR-FTUs huggingface dataset:
Frequent Substitution Polymorphisms in African Green Monkey CCR5 Cluster at Critical Sites for Infections by Simian Immunodeficiency Virus SIVagm, Implying Ancient Virus-Host Coevolution

ABSTRACT In contrast to humans, several primate species are believed to have harbored simian immunodeficiency viruses (SIVs) since ancient times. In particular, the geographically dispersed species of African green monkeys (AGMs) are all infected with highly diversified SIVagm viruses at high prevalences (greater than 50% of sexually mature individuals) without evident diseases, implying that the progenitor monkeys were infected prior to their dispersal. If this is correct, AGMs would be expected to have accumulated frequent resistance-conferring polymorphisms in host genes that are important for SIV replication. Accordingly, we analyzed the coding sequences of the CCR5 coreceptors from 26 AGMs (52 alleles) in distinct populations of the four species. These samples contained 29 nonsynonymous coding changes and only 15 synonymous nucleotide substitutions, implying intense functional selection. Moreover, 24 of the resulting amino acid substitutions were tightly clustered in the CCR5 amino terminus (D13N in the vervets and Y14N in the tantalus species) or in the first extracellular loop (Q93R and Q93K in all species). The Y14N substitution was extremely frequent in the 12 wild-born African tantalus, with 7 monkeys being homozygous for this substitution and 4 being heterozygous. Although two of these heterozygotes and the only wild-type homozygote were naturally infected with SIVagm, none of the Y14N homozygotes were naturally infected. A focal infectivity assay for SIVagm indicated that all five tested SIVagms efficiently use CCR5 as a coreceptor and that they also use CXCR6 (STRL33/Bonzo) and GPR15 (BOB) with lower efficiencies but not CXCR4. Interestingly, the D13N, Y14N, Q93R, and Q93K substitutions in AGM CCR5 all strongly inhibited infections by the SIVagm isolates in vitro. The Y14N substitution eliminates a tyrosine sulfation site that is important for infections and results in partial N-linked glycosylation (i.e., 60% efficiency) at this position. Nevertheless, the CCR5(Y14N) component that lacks an N-linked oligosaccharide binds the chemokine MIP-lβ with a normal affinity and is fully active in signal transduction. Similarly, D13N and Q93R substitutions did not interfere with signal transduction. Thus, the common substitution polymorphisms in AGM CCR5 strongly inhibit SIVagm infections while substantially preserving chemokine signaling. In contrast, polymorphisms of human CCR5 are relatively infrequent, and the amino acid substitutions are randomly situated and generally without effects on coreceptor function. These results support an ancient coevolution of AGMs and SIVagm viruses and establish AGMs as a highly informative model for learning about host proteins that play critical roles in immunodeficiency virus infections.
Limited Enforcement, Financial Intermediation, and Economic Development: A Quantitative Assessment

We present a model of economic development where the importance of financial differences caused by limited enforcement can be measured. Economies where enforcement is poor direct less capital to the production sector and employ less efficient technologies. Calibrated simulations reveal that the resulting effect on output is large. Furthermore, the model correctly predicts that the average scale of production should rise with the quality of enforcement. Finally, we find that the importance of limited enforcement rises with the importance of capital in production.
Twice-ramanujan sparsifiers

We prove that every graph has a spectral sparsifier with a number of edges linear in its number of vertices. As linear-sized spectral sparsifiers of complete graphs are expanders, our sparsifiers of arbitrary graphs can be viewed as generalizations of expander graphs. In particular, we prove that for every d > 1 and every undirected, weighted graph G = (V,E,w) on n vertices, there exists a weighted graph H=(V,F,~{w}) with at most ⌈d(n-1)⌉ edges such that for every x ∈ R<sup>V</sup>, [x<sup>T</sup> L<sub>G</sub> x ≤ x<sup>T</sup> L<sub>H</sub> x ≤ ((d+1+2√d)/(d+1-2√d)) • x<sup>T</sup> L<sub>G</sub> x] where L<sub>G</sub> and L<sub>H</sub> are the Laplacian matrices of G and H, respectively. Thus, H approximates G spectrally at least as well as a Ramanujan expander with dn/2 edges approximates the complete graph. We give an elementary deterministic polynomial time algorithm for constructing H.
Relationship of QRS Amplitude Changes During Exercise to Left Ventricular Function and Volumes and the Diagnosis of Coronary Artery Disease

Preliminary studies have suggested that QRS-amplitude changes due to exercise-induced alterations in ventricular volume and function can improve the diagnostic value of the exercise test. To evaluate this, electrocardiographic data and equilibrium radionuclide angiographic images were recorded simultaneously in 18 normal subjects and 60 coronary artery disease patients at rest and during supine bicycle exercise. In 24 of the 60 coronary artery disease patients, left ventricular volumes were also calculated. The measured QRS amplitudes were the R waves in V5, X, Y and Z, the Q wave in Z and the sum of amplitudes of R waves in X and Y and the Q wave in Z (2iR). The mean left ventricular ejection fraction increased significantly from rest to peak exercise in the normal subjects; however, the mean left ventricular ejection fraction and mean volumes did not change significantly in the coronary patients. There was no significant difference in the mean QRS-amplitude changes during exercise between the coronary artery disease patients and the normal subjects in any of the measured leads. The sensitivity and specificity of exercise-induced QRS-amplitude changes for coronary disease were lower than ST-segment changes. For ST-segment changes, the sensitivity was 57% and specificity was 100%; the best sensitivity and specificity for QRS amplitude occurred in RZ, 48% and 67%, respectively. When ejection fraction was related to 2R at rest and peak exercise for both normal subjects and coronary patients the correlations were fair (0.50, 0.51 respectively); however, the correlation between the magnitude of 2R and ejection fraction change from rest to peak exercise was poor and did not improve with any other measured QRS amplitudes or by separating normal subjects from coronary patients with and without previous myocardial infarction. There were also poor correlations between end-diastolic and endsystolic volumes to QRS amplitudes at rest, peak exercise and their magnitude of change from rest to peak exercise. Thus, R-wave amplitude changes during exercise testing have little diagnostic value and are not related to exercise-induced changes in left ventricular function or volumes.
Gaucher Disease‐Induced Pluripotent Stem Cells Display Decreased Erythroid Potential and Aberrant Myelopoiesis

Gaucher disease (GD) is the most common lysosomal storage disease resulting from mutations in the lysosomal enzyme glucocerebrosidase (GCase). The hematopoietic abnormalities in GD include the presence of characteristic Gaucher macrophages that infiltrate patient tissues and cytopenias. At present, it is not clear whether these cytopenias are secondary to the pathological activity of Gaucher cells or a direct effect of GCase deficiency on hematopoietic development. To address this question, we differentiated induced pluripotent stem cells (iPSCs) derived from patients with types 1, 2, and 3 GD to CD34+/CD45+/CD43+/CD143+ hematopoietic progenitor cells (HPCs) and examined their developmental potential. The formation of GD‐HPCs was unaffected. However, these progenitors demonstrated a skewed lineage commitment, with increased myeloid differentiation and decreased erythroid differentiation and maturation. Interestingly, myeloid colony‐formation assays revealed that GD‐HPCs, but not control‐HPCs, gave rise to adherent, macrophage‐like cells, another indication of abnormal myelopoiesis. The extent of these hematologic abnormalities correlated with the severity of the GCase mutations. All the phenotypic abnormalities of GD‐HPCs observed were reversed by incubation with recombinant GCase, indicating that these developmental defects were caused by the mutated GCase. Our results show that GCase deficiency directly impairs hematopoietic development. Additionally, our results suggest that aberrant myelopoiesis might contribute to the pathological properties of Gaucher macrophages, which are central to GD manifestations. The hematopoietic developmental defects we observed reflect hematologic abnormalities in patients with GD, demonstrating the utility of GD‐iPSCs for modeling this disease.
Impact of proximity to comprehensive sickle cell center on utilization of healthcare services among children with sickle cell disease

The impact of comprehensive care on utilization of healthcare services by children with sickle cell disease (SCD) has not been fully evaluated. We compared the medical care utilization and mortality in children less than 20 years of age with SCD in four regions in the state of Tennessee with and without a comprehensive sickle cell center (CSCC).
Fluid regimens for colostomy irrigation: a systematic review

Background Various techniques for managing faecal evacuation have been proposed; however, colostomy irrigation is favoured as it leads to better patient outcomes. Alternative fluid regimens for colostomy irrigation have been suggested to achieve effective evacuation. Aim The objective of this review was to summarise the best available evidence on the most effective fluid regimen for colostomy irrigation. Search strategy Trials were identified by electronic searches of CINAHL, PubMed, MEDLINE, Current Contents, the Cochrane Library and EMBASE. Unpublished articles and references lists from included studies were also searched. Selection criteria Randomised controlled trials and before‐and‐after studies investigating any fluid regimen for colostomy irrigation were eligible for inclusion. Outcomes measured included fluid inflow time, total wash‐out time, haemodynamic changes during irrigation, cramps, leakage episodes, quality of life and level of satisfaction. Data collection and analysis Trial selection, quality appraisal and data extraction were carried out independently by two reviewers. Differences in opinion were resolved by discussion. Main results The systematic literature search strategy identified two cross‐over trials that compared water with another fluid regimen. Owing to the differences in irrigating solutions used, the results were not pooled for analysis. Both the polyethylene glycol electrolyte solution and glyceryl trinitrate performed significantly better than water. Conclusion There is some evidence to support the effectiveness of fluid regimens other than water, such as polyethylene glycol electrolyte and glyceryl trinitrate, for colostomy irrigation. Further well‐designed clinical trials are required to establish solid evidence on the effectiveness of other irrigating solutions that might enhance colonic irrigation.
The Effects of Feedback on Targeting Performance in Visually Stressed Conditions

In most graphical user interfaces, a substantial part of the user’s interaction involves targeting screen objects with the mouse cursor. Targeting tasks with small targets are visually demanding, and can cause users difficulty in some circumstances. These circumstances can arise either if the user has a visual disability or if factors such as fatigue or glare diminish visual acuity. One way of reducing the sensory demands of targeting is to add redundant feedback to the interface that indicates when the user has successfully acquired a target. Under optimal viewing conditions, such feedback has not significantly improved targeting performance. However, we hypothesized that targeting feedback would be more beneficial in a visually stressed situation. We carried out an experiment in which normally sighted participants in a reduced-acuity environment carried out targeting tasks with a mouse. We found that people were able to select targets significantly faster when they were given targeting feedback, and that they made significantly fewer errors. People also greatly preferred interfaces with feedback to those with none. The results suggest that redundant targeting feedback can improve the usability of graphical interfaces, both for low-vision users and also for normally sighted users in visually stressed environments.
Simian Varicella Virus Expresses a Latency-Associated Transcript That Is Antisense to Open Reading Frame 61 (ICP0) mRNA in Neural Ganglia of Latently Infected Monkeys

ABSTRACT Simian varicella virus (SVV) and varicella-zoster virus (VZV) are closely related alphaherpesviruses that cause varicella (chickenpox) in nonhuman primates and humans, respectively. After resolution of the primary disease, SVV and VZV establish latent infection of neural ganglia and may later reactivate to cause a secondary disease (herpes zoster). This study investigated SVV gene expression in neural ganglia derived from latently infected vervet monkeys. SVV transcripts were detected in neural ganglia, but not in liver or lung tissues, of latently infected animals. A transcript mapping to open reading frame (ORF) 61 (herpes simplex virus type 1 [HSV-1] ICP0 homolog) was consistently detected in latently infected trigeminal, cervical, and lumbar ganglia by reverse transcriptase PCR. Further analysis confirmed that this SVV latency-associated transcript (LAT) was oriented antisense to the gene 61 mRNA. SVV ORF 21 transcripts were also detected in 42% of neural ganglia during latency. In contrast, SVV ORF 28, 29, 31, 62, and 63 transcripts were not detected in ganglia, liver, or lung tissues of latently infected animals. The results demonstrate that viral gene expression is limited during SVV latency and that a LAT antisense to an ICP0 homolog is expressed. In this regard, SVV gene expression during latency is similar to that of HSV-1 and other neurotropic animal alphaherpesviruses but differs from that reported for VZV.
Review on Sphaeranthus indicus Linn. (Koṭṭaikkarantai)

Sphaeranthus indicus Linn. is from the aroma family Asteraceae. It is also known with other synonyms such as Munditika, Mundi, Shravana, Bhikshu, Tapodhana, Mahashravani, Shravanahva, Shravanashirshaka. It is abundantly distributed in damp areas in plains and also as a weed in the rice fields. In the Indian system of medicine, the plant as a whole plant or its different anatomical parts viz., leaf, stem, bark, root, flower and seed are widely used for curing many diseases. The plant is bitter, stomachic, restorative, alterative, pectoral, demulcent and externally soothing. The whole plant and its anatomical parts have been reported with different types of secondary metabolites which include eudesmanolides, sesquiterpenoids, sesquiterpene lactones, sesquiterpene acids, flavone glycosides, flavonoid C-glycosides, isoflavone glycoside, sterols, sterol glycoside, alkaloid, peptide alkaloids, amino acids and sugars. The essential oils obtained from the flowers and whole plants were analyzed by different authors and reported the presence of many monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons and oxygenated sesquiterpenes. The whole plants, its isolated secondary metabolites and different anatomical parts have been reported for ovicidal, antifeedant, anthelmintic, antimicrobial, antiviral, macrofilaricidal, larvicidal, analgesic, antipyretic, hepatoprotective, antitussive, wound healing, bronchodilatory, mast cell stabilizing activity, anxiolytic, neuroleptic, immunomodulatory, anti-diabetic, antihyperlipidemic and antioxidant, antioxidant, central nervous system depressant, anti-arthritic, nephroprotective, anticonvulsant activities and many other activities. It is also effective on psoriasis. In the present paper, the plant is reviewed for its phytochemical and pharmacological reports in detail.
Computational Prediction and Molecular Characterization of an Oomycete Effector and the Cognate Arabidopsis Resistance Gene

Hyaloperonospora arabidopsidis (Hpa) is an obligate biotroph oomycete pathogen of the model plant Arabidopsis thaliana and contains a large set of effector proteins that are translocated to the host to exert virulence functions or trigger immune responses. These effectors are characterized by conserved amino-terminal translocation sequences and highly divergent carboxyl-terminal functional domains. The availability of the Hpa genome sequence allowed the computational prediction of effectors and the development of effector delivery systems enabled validation of the predicted effectors in Arabidopsis. In this study, we identified a novel effector ATR39-1 by computational methods, which was found to trigger a resistance response in the Arabidopsis ecotype Weiningen (Wei-0). The allelic variant of this effector, ATR39-2, is not recognized, and two amino acid residues were identified and shown to be critical for this loss of recognition. The resistance protein responsible for recognition of the ATR39-1 effector in Arabidopsis is RPP39 and was identified by map-based cloning. RPP39 is a member of the CC-NBS-LRR family of resistance proteins and requires the signaling gene NDR1 for full activity. Recognition of ATR39-1 in Wei-0 does not inhibit growth of Hpa strains expressing the effector, suggesting complex mechanisms of pathogen evasion of recognition, and is similar to what has been shown in several other cases of plant-oomycete interactions. Identification of this resistance gene/effector pair adds to our knowledge of plant resistance mechanisms and provides the basis for further functional analyses.
Performance analysis of square arranged antenna array with SC and MRC receiver over Nakagami fading channel

In this paper, the performance of using a square array of four antennas for selection combining (SC) and maximal-ratio combining (MRC) of Nakagami correlated signals is investigated. The closed form of average output signal-to-noise ratio and bit error rate (BER) for SC with arbitrary four correlated branches is derived; the expression of BER with MRC is also derived by utilizing the characteristic function method. Two models for the angle of arrival (AOA), i.e., uniform and truncated Gaussian, are considered in the system performance evaluation. The effects of correlation coefficients and fading factor on the system performance are investigated through numerical examples, which show that the uniformly distributed AOA system outperforms the truncated Gaussian-distributed counterpart with small angular spread. The degradation of system performance in the presence of one-antenna failure is also investigated.
Chiral sulfoxidations catalyzed by rat liver cytochromes P-450.

The chirality of sulfoxidation catalyzed by two cytochrome P-450 isozymes purified from phenobarbital-induced rat liver was studied by using 4-tolyl ethyl sulfide as a substrate. Both P-450 isoenzymes, termed PB-1 and PB-4, when reconstituted with purified rat liver NADPH-cytochrome P-450 reductase and cytochrome b5, generated 4-tolyl ethyl sulfoxide which was predominantly in the S-(-) configuration. In the case of isozyme PB-1, the sulfoxide was 79 +/- 1% S and was formed with a turnover of 41 min-1; with isoenzyme PB-4, sulfoxide, 84 +/- 1%, S, was formed at 31 min-1. In addition, PB-1-1 catalyzed oxygen transfer to the p-methyl group of the sulfide substrates to yield the (ethylthio)benzyl alcohol with a turnover of 6.8 min-1, corresponding to a sulfur:carbon oxygenation partition ratio of 6:1. Isozyme PB-4 was approximately 80-fold less efficient at catalyzing this carbon hydroxylation, giving a sulfur:carbon ratio of approximately 375:1. In the absence of cytochrome b5, turnover numbers were reduced to approximately 15% and 67% of the above values for PB-1 and PB-4, respectively, with no change in sulfoxide chirality. This fact, and the lack of improvement in chirality upon inclusion of scavengers for reactive oxygen species, suggests that the approximately 79-84% chirality observed for the sulfoxide product reflects an intrinsic lack of complete stereospecificity in these cytochrome P-450 catalyzed reactions. The enantiomeric composition of 4-tolyl ethyl sulfoxide generated in rat liver microsomal incubations was shown to reflect the relative contribution of cytochrome P-450 isozymes, which generate the S-(-) enantiomer preferentially, and of the flavin adenine dinucleotide (FAD) containing monooxygenase (EC 1.14.13.8), which as we have shown catalyzes (R)-(+)-sulfoxide formation [Light, D. R. , Waxman, D. J. & Walsh, C. (1982) Biochemistry (preceding paper in this issue)]. Thus, the chirality of microsome-catalyzed sulfoxidation is shown to be modulated by factors which alter the relative participation of these by factors which alter the relative participation of these two liver monooxygenases, such as phenobarbital induction, inclusion of inhibitors or activators (metyrapone and n-octylamine), and variation in sulfide substrate concentration.
Incident diabetes associated with antipsychotic use in the United Kingdom general practice research database.

BACKGROUND Recent reports suggest an association between antipsychotic use and development or exacerbation of diabetes. This study evaluated the risk of incident diabetes associated with the use of atypical and conventional antipsychotics. METHOD This nested case-control study included all patients in the U.K. General Practice Research Database treated with antipsychotic drugs between January 1994 and December 1998. The main outcome measures were the odds ratios of current (within prior 6 months) or recent (7 to 12 months) antipsychotic exposure among those with (N = 424) compared with those without incident diabetes (N = 1522). RESULTS The adjusted odds ratio for current use of any antipsychotic drug compared with no use in the past year among those with diabetes was 1.7 (95% confidence interval [CI] = 1.3 to 2.3). The adjusted odds ratio for current use of atypical and conventional antipsychotic drugs compared with no use in the past year among those with diabetes was 4.7 (95% CI = 1.5 to 14.9) and 1.7 (95% CI = 1.2 to 2.3), respectively. The adjusted odds ratio for recent use of conventional antipsychotic drugs compared with no use in the past year among those with diabetes was 1.0 (95% CI = 0.6 to 1.6). The odds ratio for recent atypical antipsychotic drug use could not be calculated because no study subjects had this exposure. CONCLUSION This study showed an increased risk of incident diabetes among current users of atypical and conventional antipsychotic medications. These results were independent of other established risk factors. The larger association observed for atypical antipsychotic users should be regarded as preliminary given the small number of incident diabetes cases in this group.