Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationship between optical coherence tomography, pattern electroretinogram and automated perimetry in eyes with temporal hemianopia from chiasmal compression.

PURPOSE To evaluate the relationship between pattern electroretinogram (PERG) amplitude, macular and retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT), and visual field (VF) loss on standard automated perimetry (SAP) in eyes with temporal hemianopia from chiasmal compression. METHODS Forty-one eyes from 41 patients with permanent temporal VF defects from chiasmal compression and 41 healthy subjects underwent transient full-field and hemifield (temporal or nasal) stimulation PERG, SAP and time domain-OCT macular and RNFL thickness measurements. Comparisons were made using Student's t-test. Deviation from normal VF sensitivity for the central 18 degrees of VF was expressed in 1/Lambert units. Correlations between measurements were verified by linear regression analysis. RESULTS PERG and OCT measurements were significantly lower in eyes with temporal hemianopia than in normal eyes. A significant correlation was found between VF sensitivity loss and full-field or nasal, but not temporal, hemifield PERG amplitude. Likewise a significant correlation was found between VF sensitivity loss and most OCT parameters. No significant correlation was observed between OCT and PERG parameters, except for nasal hemifield amplitude. A significant correlation was observed between several macular and RNFL thickness parameters. CONCLUSIONS In patients with chiasmal compression, PERG amplitude and OCT thickness measurements were significant related to VF loss, but not to each other. OCT and PERG quantify neuronal loss differently, but both technologies are useful in understanding structure-function relationship in patients with chiasmal compression. (ClinicalTrials.gov number, NCT00553761).
Molecular mechanisms and genomic maps of DNA excision repair in Escherichia coli and humans

Nucleotide excision repair is a major DNA repair mechanism in all cellular organisms. In this repair system, the DNA damage is removed by concerted dual incisions bracketing the damage and at a precise distance from the damage. Here, we review the basic mechanisms of excision repair in Escherichia coli and humans and the recent genome-wide mapping of DNA damage and repair in these organisms at single-nucleotide resolution.
Generation of cytochrome P450 3A4-overexpressing HepG2 cell clones for standardization of hepatocellular testosterone 6β-hydroxylation activity

Detoxification of xenobiotics including drugs is catalyzed by liver phase I and phase II enzymes. There are three main families of phase I cytochrome P450 (CYP450) monoxygenases that introduce polar groups on drugs. These phase I metabolites can then be further conjugated by transferases during phase II reaction. Liver biotransformation can also lead to toxic drug metabolites, the most common cause of drug failure during clinical investigation. CYP3A4 is considered to be the most important enzyme in drug metabolism. Drug development relies on the use of human liver cells in order to investigate drug metabolism and potential toxicity. With primary human liver cells as the gold standard several problems have to be solved, i.e. scarcity of functional human liver tissue, donor variation of CYP activity and rapid dedifferentiation processes during primary cell cultivation. These features make it difficult to use primary human liver cells as standard to measure CYP activity. To avoid problems with primary human liver cells, many attempts have been undertaken to establish liver carcinoma cell lines, non-transformed proliferating human liver cell systems and induced pluripotent stem cell-derived hepatocytes. Due to different problems with these surrogate systems, the one cell line that could be used as convenient standard cell system to benchmark CYP3A4 enzyme activity has not been established yet. Based on the widely used hepatocellular carcinoma cell line HepG2 and a lentiviral vector system, we generated cell clones for stable CYP3A4 overexpression. Here we present data on a new HepG2 cell clone (clone 9) showing higher than 10,000-fold overexpression of CYP3A4 compared to HepG2 parental cells. As measured by conversion of testosterone into 6 -hydroxytestosterone, we found an enzyme activity of about 600 pmol per minute per mg total cellular protein, which ranges at the upper end reported for primary human liver cells. This enzyme activity appeared to be kept stable in clone 9 cells, because there was no influence detectable when cells were treated with 5-azacytidine, a drug that interferes with epigenetic silencing processes. Prototypic CYP3A4 inducer rifampicin led to significant increase of CYP3A4 testosterone hydroxylase activity in HepG2 clone 9 cells. Altogether, HepG2 clone 9 strongly and stably overexpressed CYP3A4 leading to a physiological enzyme activity, which apparently was unaffected by epigenetic processes. Thus, HepG2 clone 9 could be a useful reference cell clone for CYP3A4 enzyme activity.
Analytical method development and validation for simultaneous determination and quantification of Ethinyl Estradiol and Gestodene in combined tablet dosage form by RP-HPLC

The present paper describes a simple isocratic reve rse phase HPLC method for the simultaneous determin ation and Quantification of Gestodene and Ethinyl Estradiol i n Pharmaceutical dosage forms. The Seperation and e stimation was achieved with normal C 18(250 x4.6mm,5μ) columns using a mixture of acetonit rile,methanol and water(35:15:50) as the mobile phase at a flow rate of 2.0 ml/min and detection was carried out at 210 nm.The seperation was achieved within 18 mins and retentio n of Gestodene and Ethinyl Estradiol is 10.5 and 7. 4 mins respectively. The developed method was validated an d linearity of the proposed method was in the range of 1.8811. 33mg/mL(r-0.9994) for Gestodene, 0.755-4.531 mg/ mL (0.99973) for Ethinyl Estradiol. The proposed me thod was suitable for simultaneous Determination and Qua ntification of Gestodene and Ethinyl Estradiol in c ombined pharmaceutical dosage forms.
Comparison of four markers of intestinal permeability in control subjects and patients with coeliac disease.

BACKGROUND Controversy surrounds the issue of intestinal permeability in patients with coeliac disease, polyethylene glycol 400 indicating reduced and di-/mono-saccharide urine excretion ratios and 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) indicating increased permeability. METHODS We assessed the suitability of polyethylene glycol 400, L-rhamnose, lactulose, and 51Cr-EDTA as markers of intestinal permeability by assessing urine excretions after simultaneous intravenous instillation of these markers and after oral administration in normals and patients with coeliac disease. RESULTS After intravenous administration the 24-h urine excretion of polyethylene glycol 400, L-rhamnose, lactulose, and 51Cr-EDTA was 40%, 72%, 93%, and 97%, respectively. There was no significant difference between controls and patients with coeliac disease. Oral administration of the markers in an iso- and hyper-osmolar test solution demonstrates reduced permeation due to an osmotic retention effect of lactulose. In contrast, hyperosmolar glycerol increases permeation of all markers except L-rhamnose. Timing of urines and altering osmolarity is important for the behavior of individual markers but does not enhance the discrimination between controls and patients when the differential urine excretion of lactulose/L-rhamnose is used. The sensitivity of the urine excretion ratio of lactulose/L-rhamnose was comparable to that of 51Cr-EDTA used by itself. Whereas lactulose/L-rhamnose and 51Cr-EDTA showed increased intestinal permeability in coeliac disease, the permeation of polyethylene glycol was reduced. Permeation of the markers did not correlate significantly with jejunal histology. CONCLUSIONS Correlations of marker permeation rates with test dose osmolarity in controls and patients with coeliac disease shows a variable lack of conformity, suggesting that the markers may permeate the intestine by different routes, which are affected to a different extent in coeliac disease.
The cell polarity protein ASIP/PAR‐3 directly associates with junctional adhesion molecule (JAM)

The establishment and maintenance of cellular polarity are critical for the development of multicellular organisms. PAR (partitioning‐defective) proteins were identified in Caenorhabditis elegans as determinants of asymmetric cell division and polarized cell growth. Recently, vertebrate orthologues of two of these proteins, ASIP/PAR‐3 and PAR‐6, were found to form a signalling complex with the small GTPases Cdc42/Rac1 and with atypical protein kinase C (PKC). Here we show that ASIP/PAR‐3 associates with the tight‐junction‐associated protein junctional adhesion molecule (JAM) in vitro and in vivo. No binding was observed with claudin‐1, ‐4 or ‐5. In fibroblasts and CHO cells overexpressing JAM, endogenous ASIP is recruited to JAM at sites of cell–cell contact. Over expression of truncated JAM lacking the extracellular part disrupts ASIP/PAR‐3 localization at intercellular junctions and delays ASIP/PAR‐3 recruitment to newly formed cell junctions. During junction formation, JAM appears early in primordial forms of junctions. Our data suggest that the ASIP/PAR‐3–aPKC complex is tethered to tight junctions via its association with JAM, indicating a potential role for JAM in the generation of cell polarity in epithelial cells.
A Cross-sectional Descriptive Study to Estimate the Prevalence of Early Initiation and Exclusive Breast Feeding in the Rural Health Training Centre of a Medical College in Tamilnadu, Southern India

Introduction: The World Health Organization and the National guidelines on infant and young child feeding recommend the practice of exclusive breastfeeding of infants for the first 6 months after their birth. The objective of this study was to estimate the prevalence of the early initiation of and exclusive breast feeding. Method: A cross sectional, descriptive study was done. 79 infants and children who attended the under five clinic in the Rural Health Training Centre (RHTC), Pulipakkam Village, were chosen for the study by convenient sampling. This study was conducted by interviewing 79 mothers of the children in the ages of 0–24 months, who attended the under five clinic of RHTC, Pulipakkam. The data was collected by using a pre tested, structured questionnaire to obtain the information on the breast feeding and the hygienic feeding practices among mothers. The statistical analysis was done by the authors by using the SPSS, version 16. The significance in the differences were evaluated by using the Chi square test and the relationship between the variables were evaluated by using Kendall’s tau correlation. A p value of <0.05 was considered as statistically significant. Results: The prevalence of the early Initiation of breast feeding was 97.5% and the prevalence of exclusive breast feeding in the study population was 68%. Inadequate exclusive breast feeding and the lack of hygienic feeding practices among the mothers were significantly associated with an increased incidence of upper and lower respiratory tract infections and gastro intestinal infections in the infants and the children. Conclusion: The education of the antenatal mothers on the benefits of breast feeding and hygienic feeding practices and making all hospitals baby friendly have to be focused on, in order to achieve 80% exclusive breast feeding as per the national guidelines on infant and young child feeding. We need
Cyclic activation of endplate acetylcholine receptors

Significance The binding of agonists to receptors is an essential event in cell signaling. We propose a general mechanism for agonist binding based on a model allosteric protein, the neuromuscular acetylcholine receptor. Binding constants were measured for different agonists, to both resting and active individual target sites. The results confirm a cyclic activation mechanism. Agonist binding requires diffusion and a local conformational change, with receptor activation accelerating the latter so that association becomes nearly diffusion-limited. At each site, receptor activation approximately doubles the agonist-binding energy. These results indicate that binding (“affinity”) and activation (“efficacy”), long considered to be independent processes, are linked obligatorily. We speculate that cyclic activation and coupling between activation and binding are fundamental aspects of receptor operation. Agonists turn on receptors because they have a higher affinity for active versus resting conformations of the protein. Activation can occur by either of two pathways that connect to form a cycle: Agonists bind to resting receptors that then become active, or resting receptors activate and then bind agonists. We used mutations to construct endplate acetylcholine receptors (AChRs) having only one functional neurotransmitter-binding site and single-channel electrophysiology to measure independently binding constants for four different agonists, to both resting and active conformations of each site. For all agonists and sites, the total free energy change in each pathway was the same, confirming the activation cycle without external energy. Other results show that (i) there is no cooperativity between sites; (ii) agonist association is slower than diffusion in resting receptors but nearly diffusional in active receptors; (iii) whereas resting affinity is determined mainly by agonist association, active affinity is determined mainly by agonist dissociation; and (iv) at each site and for all agonists, receptor activation approximately doubles the agonist-binding free energy. We discuss a two-step mechanism for binding that involves diffusion and a local conformational change (“catch”) that is modulated by receptor activation. The results suggest that binding to a resting site and the switch to high affinity are both integral parts of a single allosteric transition. We hypothesize that catch ensures proper signal recognition in complex chemical environments and that binding site compaction is a determinant of both resting and active affinity.
A Review of Design Principles for Community-based Natural Resource Management

In 1990, Elinor Ostrom proposed eight design principles, positing them to characterize robust institutions for managing common-pool resources such as forests or fisheries. Since then, many studies have explicitly or implicitly evaluated these design principles. We analyzed 91 such studies to evaluate the principles empirically and to consider what theoretical issues have arisen since their introduction. We found that the principles are well supported empirically and that several important theoretical issues warrant discussion. We provide a reformulation of the design principles, drawing from commonalities found in the studies.
Attitudes of African Americans Toward Return of Results From Exome and Whole Genome Sequencing

Exome sequencing and whole genome sequencing (ES/WGS) present patients and research participants with the opportunity to benefit from a broad scope of genetic results of clinical and personal utility. Yet, this potential for benefit also risks disenfranchising populations such as African Americans (AAs) that are already underrepresented in genetic research and utilize genetic tests at lower rates than other populations. Understanding a diverse range of perspectives on consenting for ES/WGS and receiving ES/WGS results is necessary to ensure parity in genomic health care and research. We conducted a series of 13 focus groups (n = 76) to investigate if and how attitudes toward participation in ES/WGS research and return of results from ES/WGS differ between self‐described AAs and non‐AAs. The majority of both AAs and non‐AAs were willing to participate in WGS studies and receive individual genetic results, but the fraction not interested in either was higher in AAs. This is due in part to different expectations of health benefits from ES/WGS and how results should be managed. Our results underscore the need to develop and test culturally tailored strategies for returning ES/WGS results to AAs. © 2013 Wiley Periodicals, Inc.
Genetic and temporal patterns of multiple parasitism by brown-headed cowbirds (Molothrus ater) on song sparrows (Melospiza melodia)

Identifying the factors used by an avian brood parasite to select host nests is important in understanding the determinates of individual reproductive success, yet such factors are poorly known for most parasitic species. Insights into these factors may come from understanding the conditions under which female parasites lay more than one egg per host nest (multiple parasitism). Using genetic techniques we examined patterns of multiple parasitism on a preferred host, the song sparrow (Melospiza melodia), to determine some basic patterns of multiple parasitism. Multiple parasitism involved equal frequencies of the same female parasitizing the same nest again and two or more females parasitizing the same nest. The frequency of multiple parasitism increased as the season progressed. We also documented a high frequency of parasitism that was not synchronized with host laying. These laying patterns may be the result of cowbirds "making the best of a bad situation" or of suboptimal host choice by inexperienced, .
Teardrop superior mesenteric vein: CT sign for unresectable carcinoma of the pancreas.

OBJECTIVE Our objective was to investigate whether a tethered, teardrop-shaped superior mesenteric vein (SMV) is a reliable CT indicator of unresectable adenocarcinoma of the head of the pancreas. MATERIALS AND METHODS CT scans of 92 patients with high suspicion for pancreatic head adenocarcinoma were retrospectively reviewed by two radiologists who were unfamiliar with the patients' outcomes. The reviewers were asked to assess whether the teardrop SMV sign was present or not; agreement was reached by consensus. Teardrop SMV was considered absent in patients with an obstructed vessel. RESULTS Of 92 patients, 30 had a normal pancreas without a teardrop SMV. A mass in the head of the pancreas was seen in all 62 patients with cancer. Of these 62 patients, 30 (seven with teardrop SMV) were deemed to have inoperable disease by standard CT or clinical criteria. The remaining 32 patients underwent surgery; only 15 of these 32 had successful pancreatoduodenectomies. No patient with resectable tumor had an unequivocal teardrop SMV sign. In 17 patients (13 with teardrop SMV), resection of the tumor could not be accomplished because of vascular encasement (n = 12) or metastasis (n = 5). Added to conventional signs, teardrop SMV significantly increased CT's sensitivity (from 60% to 91%) and accuracy (from 79% to 95%) without significantly changing its specificity (from 100% to 98%) for resectability of pancreatic head cancer. CONCLUSION The teardrop SMV is a reliable sign for predicting unresectability of adenocarcinoma of the head of the pancreas and can significantly contribute to preoperative planning.
Solution blow spinning: A new method to produce micro- and nanofibers from polymer solutions

A solution blow spinning technique was developed using elements of both electrospinning and melt blowing technologies as an alternative method for making non-woven webs of micro- and nanofibers with diameters comparable with those made by the electrospinning process with the advantage of having a fiber production rate (measured by the polymer injection rate) several times higher. The diameters of fibers produced ranged from 40 nm for poly(lactic acid) to several micrometers for poly(methyl methacrylate). This solution blow spinning method uses a syringe pump to deliver a polymer solution to an apparatus consisting of concentric nozzles whereby the polymer solution is pumped through the inner nozzle while a constant, high velocity gas flow is sustained through the outer nozzle. Analysis of the process showed that pressure difference and shearing at the gas/solution interface jettisoned multiple strands of polymer solution towards a collector. During flight, the solvent component of the strands rapidly evaporates forming a web of micro and nanofibers. The effect of injection rate, gas flow pressure, polymer concentration, working distance, and protrusion distance of the inner nozzle was investigated. Polymer type and concentration had a greater effect on fiber diameter than the other parameters tested. Injection rate, gas flow pressure, and working distance affected fiber production rate and/or fiber morphology. Fibers were easily formed into yarns of micro- and nanofibers or non-woven films that could be applied directly onto biological tissue or collected in sheets on a rotating drum. Indeed, virtually any type of target could be used for fiber collection.
A Systematic Review of Sources of Variability and Uncertainty in eDNA Data for Environmental Monitoring

Environmental DNA (eDNA) is becoming a standard tool in environmental monitoring that aims to quantify spatiotemporal variation for the measurement and prediction of ecosystem change. eDNA surveys have complex workflows encompassing multiple decision-making steps in which uncertainties can accumulate due to field sampling design, molecular biology lab work, and bioinformatics analyses. We conducted a quantitative review of studies published prior to December 2017 (n = 431) that had sampled eDNA from a variety of ecosystems and that had explicitly accounted for variability and uncertainty associated with eDNA workflows, either in their study design (e.g., replication) or data analysis (e.g., statistically modeling the spatiotemporal variation). We recorded differences among research studies in their spatial and temporal study design, the detected scales of natural variation in the study taxa, and how researchers measured and addressed the multiple sources of variability and uncertainty associated with the eDNA workflow. We show that relatively few studies used eDNA to understand temporal variation in biodiversity compared to spatial variation, and fewer described how uncertainties were addressed. We recommend increasing the number of temporal studies and to account for both natural variation and sources of uncertainty, such as imperfect detection, when undertaking eDNA surveys. Of studies that quantified spatiotemporal variation, this review identified gaps in the scales over which researchers have observed these patterns. Increasing the number of long-term and broad-scale eDNA studies will improve understanding of how useful eDNA is at scales relevant for monitoring the effects of environmental changes such as climatic shifts or land use change. Even where sources of spatiotemporal variation and uncertainty were accounted for, the effort in quantifying this variation differed among the different steps in the eDNA process, from field, to laboratory and bioinformatics procedures, depending on the type of community studied (micro- vs. macro-organism communities). We recommend more consistent experimental and modeling methods, accounting for spatiotemporal variation, and uncertainty in eDNA collection, and analysis, and incorporation of prior knowledge of sources of variability via Bayesian modeling approaches to account for uncertainties such as imperfect detection, to generate robust diversity estimates and increase the comparability of eDNA datasets for environmental monitoring across space and time.