gebhart/patrepeval huggingface dataset:
Noninvasive in vivo optical detection of biofilm in the human middle ear (2012)

Otitis media (OM), a middle-ear infection, is the most common childhood illness treated by pediatricians. If inadequately treated, OM can result in long-term chronic problems persisting into adulthood. Children with chronic OM or recurrent OM often have conductive hearing loss and communication difficulties and require surgical treatment. Tympanostomy tube insertion, the placement of a small drainage tube in the tympanic membrane (TM), is the most common surgical procedure performed in children under general anesthesia. Recent clinical studies have shown evidence of a direct correspondence between chronic OM and the presence of a bacterial biofilm within the middle ear. Biofilms are typically very thin and cannot be recognized using a regular otoscope. Here we report the use of optical coherent ranging techniques to noninvasively assess the middle ear to detect and quantify biofilm microstructure. This study involves adults with chronic OM, which is generally accepted as a biofilm-related disease. Based on more than 18,537 optical ranging scans and 742 images from 13 clinically infected patients and 7 normal controls using clinical findings as the gold standard, all middle ears with chronic OM showed evidence of biofilms, and all normal ears did not. Information on the presence of a biofilm, along with its structure and response to antibiotic treatment, will not only provide a better fundamental understanding of biofilm formation, growth, and eradication in the middle ear, but also may provide much-needed quantifiable data to enable early detection and quantitative longitudinal treatment monitoring of middle-ear biofilms responsible for chronic OM.
Antisense-induced exon skipping and synthesis of dystrophin in the mdx mouse (2000)

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease arising from defects in the dystrophin gene, typically nonsense or frameshift mutations, that preclude the synthesis of a functional protein. A milder, allelic version of the disease, Becker muscular dystrophy, generally arises from in-frame deletions that allow synthesis of a shorter but still semifunctional protein. Therapies to introduce functional dystrophin into dystrophic tissue through either cell or gene replacement have not been successful to date. We report an alternative approach where 2′-O-methyl antisense oligoribonucleotides have been used to modify processing of the dystrophin pre-mRNA in the mdx mouse model of DMD. By targeting 2′-O-methyl antisense oligoribonucleotides to block motifs involved in normal dystrophin pre-mRNA splicing, we induced excision of exon 23, and the mdx nonsense mutation, without disrupting the reading frame. Exon 23 skipping was first optimized in vitro in transfected H-2K(b)-tsA58 mdx myoblasts and then induced in vivo. Immunohistochemical staining demonstrated the synthesis and correct subsarcolemmal localization of dystrophin and γ-sarcoglycan in the mdx mouse after intramuscular delivery of antisense oligoribonucleotide:liposome complexes. This approach should reduce the severity of DMD by allowing a dystrophic gene transcript to be modified, such that it can be translated into a Becker-dystrophin-like protein.
Approximate Doubling of Numbers of Neurons in Postnatal Human Cerebral Cortex and in 35 Specific Cytoarchitectural Areas from Birth to 72 Months (1999)

From 1939 to 1967, J.L. Conel quantitatively studied the microscopic features of the developing human cerebral cortex and published the findings in eight volumes. We have constructed a database using his neuroanatomical measurements (neuronal packing density, myelinated large fiber density, large proximal dendrite density, somal breadth and height, and total cortical and cortical layer thickness) at the eight age periods (0 [term birth], 1, 3, 6, 15, 24, 48, and 72 postnatal months) he studied. In this report, we examine changes in neuron numbers over the eight age-points for 35 von Economo areas for which Conel gave appropriate data. From birth to 3 months postnatal age, total cortical neuron number increases 23-30%, then falls to within 3.5% of the birth value at 24 months, supporting our previous work showing that the observed decrease in the number of neurons per column of cortex under a 1-mm2 cortical surface from birth to 15 months is almost entirely due to cortical surface expansion. The present study also shows a 60-78% increase in total cortical neuron number above the birth value from postnatal ages 24 to 72 months. The generalization, to humans at least, of the finding of no postnatal neurogenesis in rhesus macaques, a species belonging to a superfamily that diverged from that of Homo sapiens more than 25 million years ago, is not warranted until explicitly proven for humans. The data of the present study support the existence of substantial postnatal neurogenesis in humans for the 35 cortical areas studied.
Selective thyromimetics. Cardiac-sparing thyroid hormone analogs containing 3'-arylmethyl substituents (1989)

Introduction of specific arylmethyl groups at the 3'-position of the thyroid hormone 3,3',5-triiodo-L-thyronine (T3), and its known hormonally active derivatives, gives liver-selective, cardiac-sparing thyromimetics, with potential utility as plasma cholesterol lowering agents. Selectivity-conferring 3'-substituents include substituted benzyl, e.g. p-hydroxybenzyl, and heterocyclic methyl, e.g. 2-oxo-1,2-dihydropyrid-5-ylmethyl and 6-oxo-1,6-dihydropyridazin-3-ylmethyl. Correlations between in vivo and in vitro receptor binding affinities show that liver/heart selectivity does not depend on receptor recognition but on penetration or access to receptors in vivo. QSAR studies of the binding data of a series of 20 3'-arylmethyl T3 analogues show that electronegative groups at the para position increase both receptor binding and selectivity in vivo. However, increasing 3'-arylmethyl hydrophobicity increases receptor binding but reduces selectivity. Substitution at ortho and meta positions reduces both binding and selectivity. Replacement of the 3,5-iodo groups by halogen or methyl maintains selectivity, with 3,5-dibromo analogues in particular having increased potency combined with oral bioavailability. Diphenyl thioether derivatives also have improved potency but are less orally active. At the 1-position, the D enantiomer retains selectivity, but removal of the alpha-amino group to give a propionic acid results in loss of selective thyromimetic activity.
Flexural Strength of Sand‐Reinforced Ice (1991)

By reinforcing ice with readily available alluvium, an economic building material for remote Arctic locations may be obtained. Three‐point bending tests are performed on ice reinforced with sand (∼80% sand by weight) at three test temperatures (-5°, -10°, and -20°C). All samples fail in a brittle manner. Accordingly, a Weibull analysis of the results is performed. The test results show that both the mean bending strength and the Weibull modulus increase with decreasing temperature. This behavior may be explained by considering the variations of both unfrozen water content of the samples and the fracture toughness of the ice matrix with temperature. A simple model, based on failure arising from the propagation of flaws within the ice matrix, is presented, and it shows good agreement with the experimental results. Further work is needed to refine the model to account quantitatively for the variation of unfrozen water content with temperature.
Peptides with antimicrobial activity from four different families isolated from the skins of the North American frogs Rana luteiventris, Rana berlandieri and Rana pipiens (2000)

The skins of frogs of the genus Rana synthesize a complex array of antimicrobial peptides that may be grouped into eight families on the basis of structural similarity. A total of 24 peptides with differential growth-inhibitory activity towards the Gram-positive bacterium Staphylococcus aureus, the Gram-negative bacterium Escherichia coli and the yeast Candida albicans were isolated from extracts of the skins of three closely related North American frogs, Rana luteiventris (spotted frog), Rana berlandieri (Rio Grande leopard frog) and Rana pipiens (Northern leopard frog). Structural characterization of the antimicrobial peptides demonstrated that they belonged to four of the known families: the brevinin-1 family, first identified in skin of the Asian frog Rana porosa brevipoda; the esculentin-2 family, first identified in the European frog Rana esculenta; the ranatuerin-2 family, first identified in the North American bullfrog Rana catesbeiana; and the temporin family, first identified in the European frog Rana temporaria. Peptides belonging to the brevinin-2, ranalexin, esculentin-1 and ranatuerin-1 families were not identified in the extracts. Despite the close phylogenetic relationship between the various species of Ranid frogs, the distribution and amino-acid sequences of the antimicrobial peptides produced by each species are highly variable and species-specific, suggesting that they may be valuable in taxonomic classification and molecular phylogenetic analysis.
Value of Golgi protein 73 monoclonal antibody in diagnosis of hepatocellular carcinoma. (2011)

Our self-prepared monoclonal antibody can effectively detect GP73 serum level in HCC patients, and has higher sensitivity and specificity than AFP. It may be superior to the currently used GP73 polyclonal antibody. The results lay the foundation for the further development of ELISA methods by using this monoclonal antibody.
A new use for intracellular antibody expression: inactivation of human immunodeficiency virus type 1. (1993)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
A Micropump-Driven High-Speed MEMS Gas Chromatography System (2007)

We report (1) the integration of the first functioning MEMS gas chromatography system ( μGC) featuring a micropump, a micro-column, and a micro-chemiresistor sensor array; and (2) experimental demonstration of the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">state-of-the-art</i> multi-vapor gas separation and detection. In particular, we report the best GC analysis data from the first micropump-driven μGC system to date: the separation and detection of 11 volatile organic compounds (VOC)'s within only 78 seconds while consuming only 15.1 mW of power within a small volume of 0.5 cc. We also report the use of temperature programming (TP) of the separation column for fast analysis, which shortened the analysis time from 78 seconds to 24 seconds while maintaining gas analysis resolution.
From today's INTRAnet of things to a future INTERnet of things: a wireless- and mobility-related view (2010)

In this article, we present the current status of the Internet of Things, and discuss how the current situation of many "Intranets" of Things should evolve into a much more integrated and heterogeneous system. We also summarize what in our opinion are the main wirelessand mobility-related technical challenges that lie ahead, and outline some initial ideas on how such challenges can be addressed in order to facilitate the IoT's development and acceptance in the next few years. We also describe a case study on the IoT protocol architecture.
RNase cleavage-based methods for mutation/SNP detection, past and present (2001)

Mutation detection based on ribonuclease cleavage of basepair mismatches in single-stranded RNA probes hybridized to DNA targets was first described over 15 years ago. The original methods relied on RNase A for mismatch cleavage; however, this enzyme fails to cleave many mismatches and has other drawbacks. More recently, a new method for RNase-cleavage-based mutation scanning has been developed, which takes advantage of the ability of RNase 1 and RNase T1 to cleave mismatches in duplex RNA targets, when these enzymes are used in conjunction with nucleic acid intercalating dyes. The method, called NIRCA, is relatively low-cost in terms of materials and equipment required. It is being used to detect mutations and SNPs in a wide variety of genes involved in human genetic disease and cancer, as well as in disease-related viral and bacterial genes. This review describes historical and recently developed RNase cleavage-based methods for mutation/SNP scanning. Hum Mutat 18:190–204, 2001. © 2001 Wiley-Liss, Inc.
SFCHECK: a unified set of procedures for evaluating the quality of macromolecular structure-factor data and their agreement with the atomic model (1999)

In this paper we present SFCHECK, a stand-alone software package that features a unified set of procedures for evaluating the structure-factor data obtained from X-ray diffraction experiments and for assessing the agreement of the atomic coordinates with these data. The evaluation is performed completely automatically, and produces a concise PostScript pictorial output similar to that of PROCHECK [Laskowski, MacArthur, Moss & Thornton (1993). J. Appl. Cryst. 26, 283–291], greatly facilitating visual inspection of the results. The required inputs are the structure-factor amplitudes and the atomic coordinates. Having those, the program summarizes relevant information on the deposited structure factors and evaluates their quality using criteria such as data completeness, structure-factor uncertainty and the optical resolution computed from the Patterson origin peak. The dependence of various parameters on the nominal resolution (d spacing) is also given. To evaluate the global agreement of the atomic model with the experimental data, the program recomputes the R factor, the correlation coefficient between observed and calculated structure-factor amplitudes and Rfree (when appropriate). In addition, it gives several estimates of the average error in the atomic coordinates. The local agreement between the model and the electron-density map is evaluated on a per-residue basis, considering separately the macromolecule backbone and side-chain atoms, as well as solvent atoms and heterogroups. Among the criteria are the normalized average atomic displacement, the local density correlation coefficient and the polymer chain connectivity. The possibility of computing these criteria using the omit-map procedure is also provided. The described software should be a valuable tool in monitoring the refinement procedure and in assessing structures deposited in databases.
Characterization of Spherical Molybdenum Powders Prepared by RF Plasma Processing (2012)

Spherical molybdenum powders were synthesized by (RF) plasma with irregular molybdenum powders. The powder characteristics and spheroidization efficiency of the feeding rate for obtain the spherical molybdenum powders were studied. The phase composition and morphological properties of the powders were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM). As a result, the fine spherical powders composed of pure molybdenum with favorable dispersity and its surface became smooth. The spheroidization efficiency of synthesized powders was almost 100 % at feeding rate of 5g/min. LMS analysis indicated that the as-prepared powder had narrow particle size distribution and the spheroidization efficiency of the sample decreases gradually as increasing of the feeding rate. The RF plasma spheroidization of molybdenum powder is an ideal route synthesis of well- spherical molybdenum powders used as near net-shape technology and powder metallurgy.
Temporal Generative Adversarial Nets with Singular Value Clipping (2016)

In this paper, we propose a generative model, Temporal Generative Adversarial Nets (TGAN), which can learn a semantic representation of unlabeled videos, and is capable of generating videos. Unlike existing Generative Adversarial Nets (GAN)-based methods that generate videos with a single generator consisting of 3D deconvolutional layers, our model exploits two different types of generators: a temporal generator and an image generator. The temporal generator takes a single latent variable as input and outputs a set of latent variables, each of which corresponds to an image frame in a video. The image generator transforms a set of such latent variables into a video. To deal with instability in training of GAN with such advanced networks, we adopt a recently proposed model, Wasserstein GAN, and propose a novel method to train it stably in an end-to-end manner. The experimental results demonstrate the effectiveness of our methods.
Prostatic intraepithelial neoplasia in mice expressing an androgen receptor transgene in prostate epithelium (2001)

Prostate cancer (PCa) is an androgen dependent disease that can be treated by androgen ablation therapy, and clinical trials are under way to prevent PCa through the reduction of androgen receptor (AR) activity. However, there are no animal models of AR-mediated prostatic neoplasia, and it remains unclear whether the AR is a positive or negative regulator of cell growth in normal prostate secretory epithelium. To assess the direct effects of the AR in prostate epithelium, a murine AR transgene regulated by the rat probasin promoter (Pb) was used to generate transgenic mice expressing increased levels of AR protein in prostate secretory epithelium. The prostates in younger (<1 year) Pb-mAR transgenic mice were histologically normal, but Ki-67 immunostaining revealed marked increases in epithelial proliferation in ventral prostate and dorsolateral prostate. Older (>1 year) transgenic mice developed focal areas of intraepithelial neoplasia strongly resembling human high-grade prostatic intraepithelial neoplasia (PIN), a precursor to PCa. These results demonstrate that the AR is a positive regulator of cell growth in normal prostate epithelium and provide a model system of AR-stimulated PIN that can be used for assessing preventative hormonal therapies and for identifying secondary transforming events relevant to human PCa.
Optochemical Control of Deoxyoligonucleotide Function via a Nucleobase-Caging Approach (2013)

Synthetic oligonucleotides have been extensively applied tocontrol a wide range of biological processes such as gene expression, gene repair, DNA replication, and protein activity. Based on well-established sequence design rules that typically rely on Watson-Crick base pairing interactions researchers can readily program the function of these oligonucleotides. Therefore oligonucleotides provide a flexible platform for targeting a wide range of biological molecules, including DNA, RNA, and proteins. In addition, oligonucleotides are commonly used research tools in cell biology and developmental biology. However, a lack of conditional control methods has hampered the precise spatial and temporal regulation of oligonucleotide activity, which limits the application of these reagents to investigate complex biological questions. Nature controls biological function with a high level of spatial and temporal resolution and in order to elucidate the molecular mechanisms of biological processes, researchers need tools that allow for the perturbation of these processes with Nature's precision. Light represents an excellent external regulatory element since irradiation can be easily controlled spatially and temporally. Thus, researchers have developed several different methods to conditionally control oligonucleotide activity with light. One of the most versatile strategies is optochemical regulation through the installation and removal of photolabile caging groups on oligonucleotides. To produce switches that can control nucleic acid function with light, chemists introduce caging groups into the oligomer backbone or on specific nucleobases to block oligonucleotide function until the caging groups are removed by light exposure. In this Account, we focus on the application of caged nucleobases to the photoregulation of DNA function. Using this approach, we have both activated and deactivated gene expression optochemically at the transcriptional and translational level with spatial and temporal control. Specifically, we have used caged triplex-forming oligomers and DNA decoys to regulate transcription, and we have regulated translation with light-activated antisense agents. Moreover, we also discuss strategies that can trigger DNA enzymatic activity, DNA amplification, and DNA mutagenesis by light illumination. More recently, we have developed light-activated DNA logic operations, an advance that may lay the foundation for the optochemical control of complex DNA calculations.
Highly sensitive inhibition of hTERT mRNA expression and telomerase activity by DNA-signal-peptide conjugates (2005)

In the present study, we investigated the antisense properties of conjugate oligonucleotides (ODNs) inhibiting human telomerase activity. Conjugate oligonucleotides assembled with signal peptides, artificially designed peptides, amines and sugars were synthesized by solid phase fragment condensation (SPFC) in sufficient yields. Conjugate ODNs showed a high resistance to nuclease degradation and sufficient binding affinity to target RNA, comparatively rapid and sufficient intracellular delivery and specific localization controlled by signal peptides (nuclear localization signals, NLS; nuclear export signals, NES). ODN-NLS conjugates demonstrated high antisense inhibitory effects against human telomerase activity into the nucleus (e. g, phosphorothioate conjugate inhibited the telomerase activity over 95%), whereas ODN-NES conjugates inhibited target mRNA expression into the cytoplasm.
Type II NKT cell–mediated anergy induction in type I NKT cells prevents inflammatory liver disease (2007)

Because of the paucity of known self lipid-reactive ligands for NKT cells, interactions among distinct NKT cell subsets as well as immune consequences following recognition of self glycolipids have not previously been investigated. Here we examined cellular interactions and subsequent immune regulatory mechanism following recognition of sulfatide, a self-glycolipid ligand for a subset of CD1d-restricted type II NKT cells. Using glycolipid/CD1d tetramers and cytokine responses, we showed that activation of sulfatide-reactive type II NKT cells and plasmacytoid DCs caused IL-12- and MIP-2-dependent recruitment of type I, or invariant, NKT (iNKT) cells into mouse livers. These recruited iNKT cells were anergic and prevented concanavalin A-induced (ConA-induced) hepatitis by specifically blocking effector pathways, including the cytokine burst and neutrophil recruitment that follow ConA injection. Hepatic DCs from IL-12(+/+) mice, but not IL-12(-/-) mice, adoptively transferred anergy in recipients; thus, IL-12 secretion by DCs enables them to induce anergy in iNKT cells. Our data reveal what we believe to be a novel mechanism in which interactions among type II NKT cells and hepatic DCs result in regulation of iNKT cell activity that can be exploited for intervention in inflammatory diseases, including autoimmunity and asthma.