gebhart/patrepeval huggingface dataset:
Stimulated Raman photoacoustic imaging (2010)

Achieving label-free, molecular-specific imaging with high spatial resolution in deep tissue is often considered the grand challenge of optical imaging. To accomplish this goal, significant optical scattering in tissues has to be overcome while achieving molecular specificity without resorting to extrinsic labeling. We demonstrate the feasibility of developing such an optical imaging modality by combining the molecularly specific stimulated Raman excitation with the photoacoustic detection. By employing two ultrashort excitation laser pulses, separated in frequency by the vibrational frequency of a targeted molecule, only the specific vibrational level of the target molecules in the illuminated tissue volume is excited. This targeted optical absorption generates ultrasonic waves (referred to as stimulated Raman photoacoustic waves) which are detected using a traditional ultrasonic transducer to form an image following the design of the established photoacoustic microscopy.
High‐grade serous carcinomas arise in the mouse oviduct via defects linked to the human disease (2017)

Recent studies have suggested that the most common and lethal type of 'ovarian' cancer, i.e. high-grade serous carcinoma (HGSC), usually arises from epithelium on the fallopian tube fimbriae, and not from the ovarian surface epithelium. We have developed Ovgp1-iCreER<sup>T2</sup> mice in which the Ovgp1 promoter controls expression of tamoxifen-regulated Cre recombinase in oviductal epithelium - the murine equivalent of human fallopian tube epithelium (FTE). We employed Ovgp1-iCreER<sup>T2</sup> mice to show that FTE-specific inactivation of several different combinations of tumour suppressor genes that are recurrently mutated in human HGSCs - namely Brca1, Trp53, Rb1, and Nf1 - results in serous tubal intraepithelial carcinomas (STICs) that progress to HGSC or carcinosarcoma, and to widespread metastatic disease in a subset of mice. The cancer phenotype is highly penetrant and more rapid in mice carrying engineered alleles of all four tumour suppressor genes. Brca1, Trp53 and Pten inactivation in the oviduct also results in STICs and HGSCs, and is associated with diffuse epithelial hyperplasia and mucinous metaplasia, which are not observed in mice with intact Pten. Oviductal tumours arise earlier in these mice than in those with Brca1, Trp53, Rb1 and Nf1 inactivation. Tumour initiation and/or progression in mice lacking conditional Pten alleles probably require the acquisition of additional defects, a notion supported by our identification of loss of the wild-type Rb1 allele in the tumours of mice carrying only one floxed Rb1 allele. Collectively, the models closely recapitulate the heterogeneity and histological, genetic and biological features of human HGSC. These models should prove useful for studying the pathobiology and genetics of HGSC in vivo, and for testing new approaches for prevention, early detection, and treatment. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Genetic and Physiological Aspects of Resistance to 5-Fluoropyrimidines in Saccharomyces cerevisiae (1970)

Mutants resistant to 5-fluorouracil, 5-fluorocytosine, and 5-fluorouridine were selected in yeast, and the mechanisms of their resistance were investigated. The investigated mutations map in seven different loci. (i) A mutation at the locus FUI 1 gives specifically resistance to 5-fluorouridine. (ii) Two loci are involved in a specific 5-fluorocytosine resistance: a mutation at locus FCY 1 produces a loss of cytosine deaminase activity; a mutation at locus FCY 2 results in the loss of the activity of a cytosine-specific permease. (iii) A mutation at the locus FUR 4 gives a simultaneous resistance to 5-fluorouracil and to 5-fluorouridine by loss in the activity of the uracil-specific permease. (iv) We found three types of mutants in the locus FUR 1. One is dominant and weakly resistant to 5-fluorouracil, 5-fluorocytosine, and 5-fluorouridine. The two others are recessive and are unable to catalyze one of the steps involved in uracil transformation into uridine 5'-monophosphate; this block-age explains their strong resistance to 5-fluorouracil and 5-fluorocytosine. Of these two mutants, one is resistant to 5-fluorouridine and the other is not. (v) Mutations at locus FUR 2 give resistance to 5-fluorouracil, 5-fluorocytosine, and 5-fluorouridine. These mutations are dominant and lead to a loss in the feedback regulation of the aspartic transcarbamylase activity by uridine triphosphate. (vi) The mutants FUR 3 are resistant to 5-fluorocytosine and 5-fluorouridine. They are dominant and physiologically related to the mutants of the locus FUR 1 but their mechanism of resistance is not understood.
2,4-Diaminothieno[2,3-d]pyrimidines as antifolates and antimalarials. 1. Synthesis of 2,4-diamino-5,6,4,8-tetrahydrothianaphtheno[2,3-d]pyrimidines and related compounds (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT2,4-Diaminothieno[2,3-d]pyrimidines as antifolates and antimalarials. 1. Synthesis of 2,4-diamino-5,6,4,8-tetrahydrothianaphtheno[2,3-d]pyrimidines and related compoundsA. Rosowsky, M. Chaykovsky, K. K. N. Chen, M. Lin, and E. J. ModestCite this: J. Med. Chem. 1973, 16, 3, 185–188Publication Date (Print):March 1, 1973Publication History Published online1 May 2002Published inissue 1 March 1973https://pubs.acs.org/doi/10.1021/jm00261a002https://doi.org/10.1021/jm00261a002research-articleACS PublicationsRequest reuse permissionsArticle Views263Altmetric-Citations45LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Electronic and steric tuning of chiral diene ligands for rhodium-catalyzed asymmetric arylation of imines (2009)

Rhodium-catalyzed asymmetric arylation of imines using electronically and sterically-modified chiral diene ligands gave the corresponding diarylmethylamines in high yield and with high enantioselectivity using just 0.3 mol% of catalyst.
A Clinical Trial of the Effects of Dietary Patterns on Blood Pressure (1997)

A diet rich in fruits, vegetables, and low-fat dairy foods and with reduced saturated and total fat can substantially lower blood pressure. This diet offers an additional nutritional approach to preventing and treating hypertension.
[True pancreatic cysts in adults]. (1995)

True or congenital cysts of the pancreas in adults are extremely rare entities. We describe two cases of true cysts located in the head of the pancreas, which presented with symptoms of epigastric pain, palpable mass and jaundice. CT scan was useful to demonstrate the location and extent of the lesion and its relation with neighbouring structures, but failed to determine the nature of the cyst. Diagnosis was obtained by the histological study of the cystic wall at surgery.
Trait-Associated SNPs Are More Likely to Be eQTLs: Annotation to Enhance Discovery from GWAS (2010)

Although genome-wide association studies (GWAS) of complex traits have yielded more reproducible associations than had been discovered using any other approach, the loci characterized to date do not account for much of the heritability to such traits and, in general, have not led to improved understanding of the biology underlying complex phenotypes. Using a web site we developed to serve results of expression quantitative trait locus (eQTL) studies in lymphoblastoid cell lines from HapMap samples (http://www.scandb.org), we show that single nucleotide polymorphisms (SNPs) associated with complex traits (from http://www.genome.gov/gwastudies/) are significantly more likely to be eQTLs than minor-allele-frequency-matched SNPs chosen from high-throughput GWAS platforms. These findings are robust across a range of thresholds for establishing eQTLs (p-values from 10(-4)-10(-8)), and a broad spectrum of human complex traits. Analyses of GWAS data from the Wellcome Trust studies confirm that annotating SNPs with a score reflecting the strength of the evidence that the SNP is an eQTL can improve the ability to discover true associations and clarify the nature of the mechanism driving the associations. Our results showing that trait-associated SNPs are more likely to be eQTLs and that application of this information can enhance discovery of trait-associated SNPs for complex phenotypes raise the possibility that we can utilize this information both to increase the heritability explained by identifiable genetic factors and to gain a better understanding of the biology underlying complex traits.
Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: a twin and family history study of autism. (1995)

The use of the family history method to examine the pattern of recurrence risks for complex disorders such as autism is not straightforward. Problems such as uncertain phenotypic definition, unreliable measurement with increased error rates for more distant relatives, and selection due to reduced fertility all complicate the estimation of risk ratios. Using data from a recent family history study of autism, and a similar study of twins, this paper shows how a latent-class approach can be used to tackle these problems. New findings are presented supporting a multiple-locus model of inheritance, with three loci giving the best fit.
Humoral Autoimmunity and Transplant Vasculopathy: When Allo is Not Enough (2010)

For several decades, allograft rejection was believed to be mediated almost exclusively by cellular immune responses, but it is now realized that humoral responses also play a major role. Although directed typically against donor human leukocyte antigen, it is becoming increasingly evident that the antibody response can also target autoantigens that are shared between donor and recipient and that this autoantibody may contribute to graft rejection. Many aspects of transplant-induced humoral autoimmunity remain poorly understood and key questions persist; not least what triggers the response and how autoantibody causes graft damage. Here, we collate results from recent clinical and experimental studies in transplantation and autoimmune diseases to propose answers to these questions.
A Comparison of TiO<SUB>2</SUB> and ZnO Nanoparticles as Photosensitizers in Photodynamic Therapy for Cancer (2014)

The TiO2 and ZnO nanoparticles are the most promising next-generation photodynamic therapy (PDT) photosensitizers. This paper reports a one-to-one comparison of TiO2 and ZnO nanoparticles as photosensitizers in photodynamic therapy of cancer. After incubating SMMC-7721 hepatocarcinoma cells with TiO2 and ZnO nanoparticles, we irradiated the cells with ultraviolet (UV) light and formation of intracellular reactive oxygen species (ROS) was monitored using the dichloro-dihydro-fluorescein diacetate (DCFH-DA) method. The cytotoxicities of ZnO and TiO2 nanoparticles as photosensitizers in cancer PDT were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, the mRNA and protein expression levels of apoptosis-related gene, including Bax, Bcl-2, and Caspase 3 were examined using RT-PCR and Western blot to elucidate the possible molecular mechanisms involved. Our results demonstrated that both TiO2 and ZnO nanoparticles could generate ROS within the tumor cells after irradiation, which in turn could attack the cancer cells. The caspase-dependent apoptosis was thus induced, resulting in anticancer activity. When the therapeutic effects were compared, no differences between the TiO2 and ZnO nanoparticles were observed for PDT. Either TiO2 or ZnO nanoparticles can therefore be used in the near future as alternative photosensitizers in targeted tumor PDT when light is directly focused on the lesion.
A novel 6 bp insertion in exon 7 associated with an unusual phenotype in a family with Fabry disease (2003)

A male patient presented with oligosymptomatic Fabry disease (end stage renal failure and non-obstructive cardiomyopathy) at around 30 years of age. His leukocyte alpha-galactosidase activity (alpha-gal) was 2.6% of controls. A 50-year-old sister had similar cardiac symptoms and her asymptomatic heterozygous daughter (33 years) had normal enzyme activity. All three patients carried a novel, 6bp insertion on exon 7 of the AGAL gene. The majority of male Fabry patients carrying mutations in exon 7 have residual alpha-gal below 1% and suffer from neuropathic pain. Comparable oligosymptomatic phenotypes in Caucasian patients carry a common mutation on exon 6 (R301Q) and have a significantly later onset. The course of the disease is likely to be altered by recombinant enzyme therapy in the future. Therefore, a thorough documentation of phenotypes, residual activities and underlying genotypes is of current interest.
Measurement of the absolute penetration depth and surface resistance of superconductors and normal metals with the variable spacing parallel plate resonator (2000)

The variable spacing parallel plate resonator (VSPPR) is a microwave transmission line resonator with a continuously variable thickness of the dielectric spacer between the superconducting or metallic plates, filled by cryogenic liquid or vacuum. We measure the dielectric spacer thickness dependencies of the resonator frequency and quality factor, and fit them to theoretical forms, in order to extract the absolute values of penetration depth, λ, and surface resistance, Rs. A cryogenic micropositioning setup is developed to vary the spacer thickness from 0 to 100 μm with a resolution of 8.5 nm, and to maintain parallelism of the resonator plates. Measurement of ac capacitance between the plates is utilized to directly determine the separation between the resonator plates and to reduce the effect of their tilt and nonflatness on the accuracy of the measured Rs and λ. Because the operating temperature is fixed (77 K), the result for a superconductor is independent of an a priori model for the penetration depth versus temperature. This technique can also be employed as a surface impedance standard for characterization of high temperature superconducting films for microwave applications.
Development and Application of Two Multiplex Real-Time PCR Assays for the Detection of Mycobacterium ulcerans in Clinical and Environmental Samples (2007)

Mycobacterium ulcerans is a slow-growing environmental bacterium that causes a severe skin disease known as Buruli ulcer. PCR has become a reliable and rapid method for the diagnosis of M. ulcerans infection in humans and has been used for the detection of M. ulcerans in the environment. This paper describes the development of a TaqMan assay targeting IS2404 multiplexed with an internal positive control to monitor inhibition with a detection limit of less than 1 genome equivalent of DNA. The assay improves the turnaround time for diagnosis and replaces conventional gel-based PCR as the routine method for laboratory confirmation of M. ulcerans infection in Victoria, Australia. Following analysis of 415 clinical specimens, the new test demonstrated 100% sensitivity and specificity compared with culture. Another multiplex TaqMan assay targeting IS2606 and the ketoreductase-B domain of the M. ulcerans mycolactone polyketide synthase genes was designed to augment the specificity of the IS2404 PCR for the analysis of a variety of environmental samples. Assaying for these three targets enabled the detection of M. ulcerans DNA in soil, sediment, and mosquito extracts collected from an area of endemicity for Buruli ulcer in Victoria with a high degree of confidence. Final confirmation was obtained by the detection and sequencing of variable-number tandem repeat (VNTR) locus 9, which matched the VNTR locus 9 sequence obtained from the clinical isolates in this region. This suite of new methods is enabling rapid progress in the understanding of the ecology of this important human pathogen.
Identification of Chimpanzee Fab Fragments by Repertoire Cloning and Production of a Full-Length Humanized Immunoglobulin G1 Antibody That Is Highly Efficient for Neutralization of Dengue Type 4 Virus (2004)

ABSTRACT A safe and effective dengue vaccine is still not available. Passive immunization with monoclonal antibodies from humans or nonhuman primates represents an attractive alternative for the prevention of dengue virus infection. Fab monoclonal antibodies to dengue type 4 virus (DENV-4) were recovered by repertoire cloning of bone marrow mRNAs from an immune chimpanzee and analyzed for antigen binding specificity, V H and V L sequences, and neutralizing activity against DENV-4 in vitro. Fabs 5A7, 3C1, 3E4, and 7G4 were isolated from a library constructed from a chimpanzee following intrahepatic transfection with infectious DENV-4 RNA. Fabs 5H2 and 5D9, which had nearly identical V H sequences but varied in their V L sequences, were recovered from a library constructed from the same chimpanzee after superinfection with a mixture of DENV-1, DENV-2, and DENV-3. In radioimmunoprecipitation, Fab 5A7 precipitated only DENV-4 prM, and Fabs 3E4, 7G4, 5D9, and 5H2 precipitated DENV-4 E but little or no prM. Fab 3E4 and Fab 7G4 competed with each other for binding to DENV-4 in an enzyme-linked immunosorbent assay, as did Fab 3C1 and Fab 5A7. Fab 5H2 recognized an epitope on DENV-4 that was separate from the epitope(s) recognized by other Fabs. Both Fab 5H2 and Fab 5D9 neutralized DENV-4 efficiently with a titer of 0.24 to 0.58 μg/ml by plaque reduction neutralization test (PRNT), whereas DENV-4-neutralizing activity of other Fabs was low or not detected. Fab 5H2 was converted to full-length immunoglobulin G1 (IgG1) by combining it with human sequences. The humanized chimpanzee antibody IgG1 5H2 produced in CHO cells neutralized DENV-4 strains from different geographical origins at a similar 50% plaque reduction (PRNT 50 ) titer of 0.03 to 0.05 μg/ml. The DENV-4 binding affinities were 0.42 nM for Fab 5H2 and 0.24 nM for full-length IgG1 5H2. Monoclonal antibody IgG1 5H2 may prove valuable for passive immunoprophylaxis against dengue virus in humans.
Automatic Landmark Generation for Point Distribution Models (1994)

Point Distribution Models (PDMs) are statistically derived flexible templates which are trained on sets of examples of the object(s) to be modelled. They require that each example is represented by a set of points (landmaiks) and that each landmark represents the same location on each of the examples. Generating the landmarks from 2D boundaries or 3D surfaces has previously been a manual process. Here, we describe a method for automatically generating PDMs from a training set of pixel- lated boundaries in 2D. The algorithm is a two-stage process in which a pair-wise corresponder is first used to establish an approximate set of landmarks on each of the example boundaries; in the second phase the landmarks are refined using an iterative non-linear optimisation scheme to generate a more compact PDM. We present results for two objects - the right hand and a chamber of the heart. The mo- dels generated using the automatically placed landmarks are shown to be better than those derived from landmarks located manually.
Activity Based Video Content Trajectory Representation and Segmentation (2004)

A novel approach is developed to segment continuous CCTV recordings according to the activities captured in the scene. This approach differs from previous approaches which are mostly based on shot change detection and shot grouping. Video content is represented by constructing a cumulative multi-event histogram over time. An on-line segmentation algorithm is then proposed to detect breakpoints in the video content, which is more robust to noise and computationally much more efficient compared to existing on-line segmentation algorithms. Its performance is compared to that of two off-line algorithms on surveillance videos monitoring an aircraft ramp area. Our experiments demonstrate that this activity based video content representation is superior to a colour histogram based representation for surveillance video segmentation.
IL-6 Signaling in Psoriasis Prevents Immune Suppression by Regulatory T Cells (2009)

T memory/effector cells (Tmem/eff) isolated from psoriatic patients are chronically activated and poorly suppressed by regulatory T cells (Treg). The proinflammatory cytokine IL-6, which signals through Stat3, allows escape of Tmem/eff cells from Treg-mediated suppression in a murine system. We show here that IL-6 protein is markedly elevated and most highly expressed by CD31(+) endothelial cells and CD11c(+) dermal dendritic cells (DCs) in lesional psoriatic skin. We hypothesized that exposure to high IL-6 in lesional tissue may lead to the dampened Treg function observed in psoriasis patients. Indeed, we found that IL-6, but not other Stat3-activating cytokines, was necessary and sufficient to reverse human T cell suppression by Treg in an in vitro model using activated DCs as a source of IL-6. IL-6Ralpha and gp130 expression was significantly elevated in psoriatic effector T cells compared with normal controls. Overall, IL-6Ralpha expression on Treg exceeded that of effector T cells, and both populations phosphorylated Stat3 in response to IL-6. Phosphorylation of Stat3 in T cells contributes to Th17 differentiation and we identify cells within lesional tissue that coexpress CD3, IL-17, and IL-6, indicating that Th17 cells are present in vivo within the psoriatic Tmem/eff population and contribute to IL-6-mediated resistance to Treg suppression. Taken together, T lymphocytes trafficking into lesional psoriatic skin encounter high IL-6 from endothelial cells, DCs, and Th17 cells, enabling cutaneous T cell escape from Treg suppression and Th17 participation in inflammation. Targeting IL-6 signaling pathways in psoriasis may rebalance Treg/T effector activity and ameliorate disease.
Repulsive guidance molecule B (RGMB) plays negative roles in breast cancer by coordinating BMP signaling (2012)

Repulsive guidance molecules (RGMs) coordinate axon formation and iron homestasis. These molecules are also known as co-receptors of bone morphogenetic proteins (BMPs). However, the role played by RGMs in breast cancer remains unclear. The present study investigated the impact of RGMB on functions of breast cancer cells and corresponding mechanisms. RGMB was knocked down in breast cancer cells by way of an anti-RGMB ribozyme transgene. Knockdown of RGMB resulted in enhanced capacities of proliferation, adhesion, and migration in breast cancer cells. Further investigations demonstrated RGMB knockdown resulted in a reduced expression and activity of Caspase-3, accompanied with better survival in RGMB knockdown cells under serum starvation, which might be induced by its repression on MAPK JNK pathway. Up-regulations of Snai1, Twist, FAK, and Paxillin via enhanced Smad dependent sigaling led to increased capacities of adhesion and migration. Our current data firstly revealed that RGMB may act as a negative regulator in breast cancer through BMP signaling.