Miracle-dz/UniFAR-FTUs huggingface dataset:
Natural History of Impaired Glucose Tolerance: Follow‐up at Joslin Clinic

The goal of this study was to examine follow‐up data on the offspring of two parents with NIDDM who have IGT to identify predictors of progression to NIDDM. The study group consisted of 80 individuals with IGT (WHO criteria), 28 of whom had IGT at baseline, and 52 who developed it during follow‐up. Both an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were performed at baseline. After a median follow‐up interval of 8 years, 35 % had progressed to NIDDM, 37% had reverted to normal glucose tolerance, and 29% still had IGT. Those who progressed were younger and more obese than non‐progressors. Glucose and insulin values from the OGTT that established the diagnosis of IGT were analysed by multiple logistic regression to determine which time points best discriminated between progressors and non‐progressors. High insulin, but not glucose, values at 0 and 120 min distinguished progressors from non‐progressors. Values at other sample times that were significantly different (p < 0.05) in progressors were: higher glucose values at 30, 45, and 60 min and higher insulin values at 90 and 180 min. Multiple logistic regression analysis of Bergman's minimal model parameters obtained from the IVGTTs performed at baseline demonstrated that, once JGf is established, low acute phase insulin secretion as well as low insulin sensitivity are significant predictors of progression to NIDDM.
Development of CW doppler radar prototyping environment used for vehicle recognition and parameter estimation

This paper deals mainly with the development of prototyping tools for continuous wave 24GHz Doppler radar (DR) DSP modules. The modules are planned to be used for land-based vehicles and they are oriented on the wide range of devices from a simple velocity estimator and a vehicle counter to a vehicle shape recognizer. The prototyping software includes Matlab/Simulink, SolidWorks and Altera Quartus packages, the hardware - DR Front-end, Altera/Terasic FPGA development kits, a PC with sound card and video camera. Self-made software tools are briefly described. These tools have been used for the acquisition of real DR signals, video capturing of vehicle, testing of DR signal processing algorithms, simulation of DR behaviour in the context of urban traffic and comparison of experimental data with simulation results.
Entoptic foveal avascular zone measurement and diabetic retinopathy.

BACKGROUND Entoptic visualization of the foveal avascular zone (FAZ) provides a noninvasive method for measurement of the FAZ. To determine if repeatability of measurement with this technique is good enough to monitor changes in diabetic retinopathy, we quantify (1) the repeatability of entoptic FAZ measurement in healthy subjects and (2) the relationship between measured FAZ diameter and the severity of retinopathy. METHODS (1) To determine FAZ measurement repeatability, 10 healthy adults entoptically measured their FAZ diameters in 11 separate testing sessions. (2) In a separate experiment, 53 patients with varying levels of diabetic retinopathy and 21 control subjects used a vascular entoptoscope to measure their FAZ diameters. RESULTS The disease-related increase in FAZ diameter is large (approximately 400 microm) compared to the repeatability of the entoptic measurement within a subject (SD approximately 35 microm). CONCLUSION Entoptic measurements have the repeatability necessary to reliably monitor increases in FAZ diameter of the magnitude of those induced by diabetes.
Data mining, neural nets, trees — Problems 2 and 3 of Genetic Analysis Workshop 15

Genome‐wide association studies using thousands to hundreds of thousands of single nucleotide polymorphism (SNP) markers and region‐wide association studies using a dense panel of SNPs are already in use to identify disease susceptibility genes and to predict disease risk in individuals. Because these tasks become increasingly important, three different data sets were provided for the Genetic Analysis Workshop 15, thus allowing examination of various novel and existing data mining methods for both classification and identification of disease susceptibility genes, gene by gene or gene by environment interaction. The approach most often applied in this presentation group was random forests because of its simplicity, elegance, and robustness. It was used for prediction and for screening for interesting SNPs in a first step. The logistic tree with unbiased selection approach appeared to be an interesting alternative to efficiently select interesting SNPs. Machine learning, specifically ensemble methods, might be useful as pre‐screening tools for large‐scale association studies because they can be less prone to overfitting, can be less computer processor time intensive, can easily include pair‐wise and higher‐order interactions compared with standard statistical approaches and can also have a high capability for classification. However, improved implementations that are able to deal with hundreds of thousands of SNPs at a time are required. Genet. Epidemiol. 31(Suppl. 1):S51–S60, 2007. © 2007 Wiley‐Liss, Inc.
Small Interfering RNA Targeting Heme Oxygenase-1 Enhances Ischemia-Reperfusion-induced Lung Apoptosis*

Heme oxygenase-1 (HO-1) is emerging as an important cytoprotective enzyme system in a variety of injury models. To optimize future therapeutic applications of HO-1, it is necessary to delineate the precise functions and mechanisms as well as modes of externally regulating HO-1 expression. Investigations have been limited by difficulties with the generation of HO-1 null mice and the lack of specific HO-1 inhibitors. Lung ischemia-reperfusion (I-R) injury is the inciting event in acute lung failure following transplantation, surgery, and shock. To study the function of HO-1 in I-R-induced lung injury, we designed small interfering RNA (siRNA) sequences that effectively suppress HO-1 expression both in vitro and in vivo in an organ-specific manner. In this study we show that there is enhanced apoptosis, via increased Fas expression and caspase 3 activity, in the presence of HO-1 siRNA in endothelial cells and mouse lung during I-R injury, whereas HO-1 overexpression attenuates apoptosis. To the best of our knowledge, we are the first to demonstrate that lung-specific siRNA delivery can be achieved by intranasal administration without the need for viral vectors or transfection agents in vivo, thereby obviating potential concerns for toxicity if siRNA technology is to have clinical application in the future.
Platelet-derived growth factor (PDGF)-dependent association of phospholipase C-gamma with the PDGF receptor signaling complex

We investigated the interaction of phospholipase C-gamma (PLC-gamma) with wild-type and mutant forms of the platelet-derived growth factor (PDGF) beta-receptor both in vivo and in vitro. After PDGF treatment of CHO cell lines expressing wild-type or either of two mutant (delta Ki and Y825F) PDGF receptors, PLC-gamma became tyrosine phosphorylated and associated with the receptor proteins. The receptor association and tyrosine phosphorylation of PLC-gamma correlated with the ability of these receptors to mediate ligand-induced phosphatidylinositol turnover. However, both the delta Ki and Y825F mutant receptors were deficient in transmitting mitogenic signals, suggesting that the PDGF-induced tyrosine phosphorylation and receptor association of PLC-gamma are not sufficient to account for the growth-stimulatory activity of PDGF. Wild-type and delta Ki mutant PDGF receptor proteins expressed with recombinant baculovirus vectors also associated in vitro with mammalian PLC-gamma. However, baculovirus-expressed c-fms, v-fms, c-src, and Raf-1 proteins failed to associate with PLC-gamma under similar conditions. Phosphatase treatment of the baculovirus-expressed PDGF receptor greatly decreased its association with PLC-gamma. This requirement for receptor phosphorylation was also observed in vivo, where PLC-gamma could not associate with a mutant PDGF receptor (K602A) defective in autophosphorylation. PLC-gamma also coimmunoprecipitated with two other putative receptor substrates, the serine-threonine kinase Raf-1 and the 85-kilodalton phosphatidylinositol-3' kinase, presumably through its association with the ligand-activated receptor. Furthermore, baculovirus-expressed Raf-1 phosphorylated purified PLC-gamma in vitro at sites which showed increased serine phosphorylation in vivo in response to PDGF. These results suggest that PDGF directly influences PLC activity by inducing the association of PLC-gamma with a receptor signaling complex, resulting in increased tyrosine and serine phosphorylation of PLC-gamma.
A Victorian Leviathan: Mudie's Select Library

PUBLISHERS ADVERTISEMENTS of newly issued fiction in the middle and late years of the nineteenth century frequently proclaimed to interested readers, "Popular New Novels, at all the libraries, each in three volumes, crown octavo," or "This day, at all libraries, in three volumes. ," thus revealing the importance of these great lending organizations in book distribution and, by implication, the dominance in the fiction lists at the libraries of the novel in three volumes. In other words, novels were announced not for sale, but as available to the public through lending organizations; their form was commonly not one volume, but three. Their cost, usually discreetly ignored in the advertisements, was a guineaand-a-half for the three volumes, a cost which effectively priced them out of the market for individual buyers. Readers who wanted recent novels were thus driven to the powerful circulating libraries, which exerted a significant influence in the Victorian literary milieu. To clarify the position of the libraries, their operation, and their connection with the three-decker novel, two aspects of their history should be examined. First, a survey of the libraries will focus on an account of the single most important firm-Mudie's Select Library-indicate its organization and operation, and briefly glance at what was virtually its only rival, W. H. Smith and Sons. '
Spatial arrangement of gene products of the P1 operon in the membrane of Mycoplasma pneumoniae

The spatial arrangement of three P1 operon-encoded proteins--attachment protein P1 (ORF5 gene product) and the ORF6-derived proteins of 40 and 90 kDa--in the membrane of Mycoplasma pneumoniae M129 was investigated by nearest-neighbor analysis. For these studies, the homobivalent, thiol-cleavable, and nonmembrane-permeating cross-linking reagent 3,3'-dithiobis(sulfosuccinimidylpropionate) (DTSSP) was used. The cross-linked proteins were isolated by immunoprecipitation with antibodies directed against fusion proteins of selected regions of the 40-kDa, the 90-kDa, or the P1 protein. The individual components of the immunoprecipitated protein complexes were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, autoradiography, and immunoblot analysis. This study showed that the P1 protein, the ORF6 gene product, and an unidentified 30-kDa protein were linked to each other in the intact bacterial membrane by the reagent DTSSP, indicating that these proteins are located at a maximal distance of 12 A (1 A = 0.1 nm) on the tip structure of M. pneumoniae.
Near hexagonal close-packed optical fiber array for parallel optical interconnection

In conventional optical fiber based two-dimensional (2-D) parallel optical interconnection (POI), optical fiber arrays are aligned to 2-D light sources and detectors using precisely fabricated hole-plate or stacked V-groove plates. All these structures have problems in making positioning components and assembly with high accuracy. For polymer optical fibers with large diameter, the whole dimension of the array will be too large if they are positioned using V-grooves or hole-plate. This paper proposes a 2-D near hexagonal close-packed (NHCP) optical fiber array for 2-D POI. NHCP array has a cross-sectional profile of near-hexagonal lattice and with fibers precisely positioned at each node of lattice. Compared with perfect HCP lattice, NHCP lattice is slightly stretched in one dimension and still have all fibers with nonuniform diameter packed tightly with high packing fraction. The position of fibers in NHCP array is very important when aligned to 2-D light sources and detectors. This paper deduce the analytically expression for the probability distribution of fiber position which is related to variance of fiber diameter and structure parameters of NHCP array, and verified it by computer simulation. Experiment samples of NHCP array have been made showing that NHCP array is easy to be fabricated.
Overexpression of Cyclin A Inhibits Augmentation of Recombinant Adeno-Associated Virus Transduction by the Adenovirus E4orf6 Protein

ABSTRACT The 34-kDa product of adenovirus E4 region open reading frame 6 (E4orf6) dramatically enhances transduction by recombinant adeno-associated virus vectors (rAAV). This is achieved by promoting the conversion of incoming single-stranded viral genomes into transcriptionally competent duplex molecules. The molecular mechanism for enhancing second-strand synthesis is not fully understood. In this study, we analyzed the cellular consequences of E4orf6 expression and the requirements for efficient rAAV transduction mediated by E4orf6. Expression of E4orf6 in 293 cells led to an inhibition of cell cycle progression and an accumulation of cells in S phase. This was preceded by specific degradation of cyclin A and p53, while the levels of other proteins involved in cell cycle control remained unchanged. In addition, the kinase activity of cdc2 was inhibited. We further showed that p53 expression is not necessary or inhibitory for augmentation of rAAV transduction by E4orf6. However, overexpression of cyclin A inhibited E4orf6-mediated enhancement of rAAV transduction. A cyclin A mutant incapable of recruiting protein substrates for cdk2 was unable to inhibit E4orf6-mediated augmentation. In addition, we created an E4orf6 mutant that is selectively defective in rAAV augmentation of transduction. Based on these findings, we suggest that cyclin A degradation represents a viral mechanism to disrupt cell cycle progression, resulting in enhanced viral transduction. Understanding the cellular pathways used during transduction will increase the utility of rAAV vectors in a wide range of gene therapy applications.
Entorhinal cortex in temporal lobe epilepsy

Background: The entorhinal cortex (EC) is a distinct anatomic and functional region of the anterior parahippocampal gyrus, which plays a role in seizure generation and propagation in temporal lobe epilepsy (TLE). In tissue resected from TLE patients, cell loss in the EC has been described. Objectives: To develop a standardized protocol for identifying the anatomic boundaries of the EC using high-resolution MRI and to examine morphologic changes of the EC in TLE. Methods: We performed T1-weighted MRIs in 20 patients (7 males) with TLE (mean age 34 years) and 18 normal controls (mean age 26 years). Eleven patients had a left and 9 a right epileptic focus as defined by history, video-EEG, and surgical outcome. The volumes of the EC, the hippocampus, and the amygdala were measured using a standardized MRI protocol. Analysis of variance (ANOVA) was used to examine the effect of seizure focus lateralization and hemisphere on these volumes. An asymmetry ratio [A (%) = 100 × (R−L)/(R+L)/2] was also compared between groups using ANOVA. Results: In normal controls the volume of the right EC was 1,247 ± 127 mm3 (mean ± standard deviation), and that of the left EC was 1,215 ± 135 mm3 (p > 0.05). We found a bilateral reduction in the volume of the EC in TLE patients compared with controls (p < 0.05). Examination of the asymmetry ratios showed that the reduction in volume of the EC was greater ipsilateral to the epileptic focus (p < 0.05). The volumes of the hippocampus and the amygdala were smaller on the side of the focus in TLE patients compared with controls (p < 0.05). Conclusions: With a standardized protocol for the quantitative assessment of the EC, patients with unilateral TLE show bilateral reduction in the volume of the EC. However, this reduction is more severe ipsilateral to the epileptic focus.
Endogenous PMN sialidase activity exposes activation epitope on CD11b/CD18 which enhances its binding interaction with ICAM‐1

Diapedesis is a dynamic, highly regulated process by which leukocytes are recruited to inflammatory sites. We reported previously that removal of sialyl residues from PMNs enables these cells to become more adherent to EC monolayers and that sialidase activity within intracellular compartments of resting PMNs translocates to the plasma membrane following activation. We did not identify which surface adhesion molecules were targeted by endogenous sialidase. Upon activation, β2 integrin (CD11b/CD18) on the PMN surface undergoes conformational change, which allows it to bind more tightly to the ICAM‐1 and ICAM‐2 on the EC surface. Removal of sialyl residues from CD18 and CD11b, by exogenous neuraminidase or mobilization of PMN sialidase, unmasked activation epitopes, as detected by flow cytometry and enhanced binding to ICAM‐1. One sialidase isoform, Neu1, colocalized with CD18 on confocal microscopy. Using an autoperfused microflow chamber, desialylation of immobilized ICAM‐1 enhanced leukocyte arrest in vivo. Further, treatment with a sialidase inhibitor in vivo reversed endotoxin‐induced binding of leukocytes to ICAM‐1, thereby suggesting a role for leukocyte sialidase in the cellular arrest. These data suggest that PMN sialidase could be a physiologic source of the enzymatic activity that removes sialyl residues on β2 integrin and ICAM‐1, resulting in their enhanced interaction. Thus, PMN sialidase may be an important regulator of the recruitment of these cells to inflamed sites.
LPA1 is essential for lymphatic vessel development in zebrafish

Lysophosphatidic acid (LPA) has long been implicated in regulating vascular development via endothelial cell‐expressed G protein‐coupled receptors. However, because of a lack of notable vascular defects reported in LPA receptor knockout mouse studies, the regulation of vasculature by LPA receptors in vivo is still uncertain. Using zebrafish as a model, we studied the gene expression patterns and functions of an LPA receptor, LPA1, during embryonic development, in particular, vascular formation. Whole‐mount in situ hybridization experiments revealed that zebrafish lpa1 (zlpa1) was ubiquitously expressed early in development, and its expression domains were later localized to the head region and the vicinity of the dorsal aorta. The expression of zlpa1 surrounding the dorsal aorta suggests its role in vasculature development. Knocking down of zLPA1 by injecting morpholino (MO) oligonucleotides at 0.625–1.25 ng per embryo resulted in the absence of thoracic duct and edema in pericardial sac and trunk in a dose‐dependent manner. These zlpa1‐MO‐resulted defects could be specifically rescued by ectopic expression of zlpa1. In addition, overexpression of vegf‐c, a well‐known lymphangiogenic factor, also partially ameliorated the inhibition of thoracic duct development. Taken together, these results demonstrate that LPA1 is necessary for lymphatic vessel formation during embryonic development in zebrafish. —Lee, S. ‐J., Chan, T. ‐H. , Chen, T. ‐C. , Liao, B. ‐O. , Hwang, P.‐P., Lee, H. LPA1 is essential for lymphatic vessel development in zebrafish. FASEB J. 22, 3706–3715 (2008)
Hyperosmotic stress response by strains of bakers' yeasts in high sugar concentration medium

Four strains of bakers' yeast were analysed for their hyperosmotic responses when in media that mimic conditions occurring in bread doughs. Two of the strains produced strong fermentative activity in medium with low osmotic stress, but produced considerably less ethanol in high sucrose concentration medium. Two other strains produced more similar fermentation activities across the range of media tested. The strains that were inhibited by high sucrose concentration were unable to produce significant amounts of glycerol under hyperosmotic conditions. By contrast, the yeasts that were not inhibited significantly by high sucrose produced a considerable amount of glycerol. The strains that produced significant glycerol exhibited efficient expression of the glycerol‐3‐phosphate dehydrogenase gene GPD1. These novel data on the molecular responses of industrially relevant strains of bakers' yeasts are prerequisite to designing strategies for improving the performance of industrial yeasts in high sugar concentration media.
Nicotine Augments the Beneficial Effects of Mesenchymal Stem Cell-based Therapy in Rat Model of Multiple Sclerosis

ABSTRACT Experimental autoimmune encephalomyelitis (EAE) in rats through immunization with guinea pig spinal cord homogenate (GPSCH) produces a chronic disease with a relapsing pattern such as multiple sclerosis (MS) in humans. In previous studies, the immunomodulatory benefits of mesenchymal stem cells (MSCs) and nicotine have already been determined. Thus, this research was conducted to assess the additional benefits of the combination therapy of MSCs and nicotine in a rat model of MS. EAE was induced by GPSCH and complete Freund’s adjuvant (CFA) in female Wistar rats. The therapies were initiated at day 12 post-immunization (p.i.), when the rats developed a neurological disability score. The symptoms were recorded daily until day 33, when the rats were sacrificed. Finally, the splenocytes were evaluated by Enzyme-linked immunosorbent assay (ELISA) for cytokine production. The therapeutic treatment in the EAE rats with a combination of MSCs and nicotine exhibited a more desirable outcome, causing the regression of the average mean clinical score and neuropathological features to be more favorable than the treatment with either therapy alone. The combination therapy led to a significant reduction in the cumulative disease disability from day 21. For the EAE rats treated with nicotine and MSCs, this period was started from day 22 and 28 p.i. , respectively. Besides the increase in the levels of IL-10, the combined therapy significantly reduced the splenocytes production of pro-inflammatory IL-17 as well as TNF-α more profoundly than either of the medications alone. In conclusion, the combination of MSCs and nicotine can be suggested as a promising strategy for further MS therapeutics improvement.
Prevalence of tooth transposition. A meta-analysis.

OBJECTIVE To synthesize currently existing data and investigate the prevalence of tooth transposition as well as its relation to gender, dental arch, and quadrant occurrence. MATERIALS AND METHODS Several electronic databases were searched in order to identify the potentially relevant studies. Initially, 591 papers were retrieved. After applying specific inclusion and exclusion criteria, nine studies were eligible for inclusion in this evaluation. Meta-analysis was performed by determining the event rate and the 95% confidence intervals estimated by the random effect model. RESULTS Analysis of the data of the primary studies revealed that tooth transposition has a mean prevalence of 0.33%. This prevalence seems to be the same between the two genders. However, tooth transposition appears more frequently in the maxilla than in the mandible and more unilaterally than bilaterally. CONCLUSION Tooth transposition is a rare phenomenon that affects various populations, including across genders, in a similar manner. Some maxillary predisposition exists, and its unilateral occurrence is higher than that of bilateral.