gebhart/patrepeval huggingface dataset:
Experiments on Transfer of Cutaneous Sensitivity to Simple Compounds (1942)

In the course of experiments to passively transfer skin sensitiveness to simple compounds an attempt was made to induce sensitivity by injecting peritoneal exudates from sensitized animals. Guinea pigs were rendered sensitive to picryl chloride in the manner previously described, using conjugates (guinea pig stromata treated with picryl chloride) in conjunction with intraperitoneal injections of killed tubercle bacilli. To produce exudates, killed tubercle bacilli (or tuberculin) were injected intraperitoneally about 3 weeks from the beginning of the treatment, when substantial tuberculin hyper-sensitivity was established.On injecting such exudates intraperitoneally into normal animals, the recipients in most of the experiments were seen to develop sensitivity to picryl chloride; when then a drop of an oil solution of the substance was put on the skin, erythematous reactions, mostly of high color, were apparent on the next day. The phenomenon was found to be due not to the clarified fluid but to the sediment obtained upon centrifugation. Among the possible explanations, an active sensitization through residual antigenic material in the peritoneal exudates seems rather improbable because a transfer was possible also with the exudate of animals in which the injection of dead tubercle bacilli and picryl stromata was made under the skin of the neck (using as a vehicle "Aquaphor" (Duke Laboratories) and paraffin oil, according to a method devised by Freund). This is further supported by the appearance of the sensitivity after a short interval, namely, 2 days after injection of sufficient material, and fading of the reactivity within a few days. Finally, there is preliminary evidence that moderate heating sufficient to kill the exudate cells abolishes the effect. Consequently one would be inclined to assume that the sensitivity is produced by an activity in the recipient of the surviving cells, if not by antibodies carried by these.
The mechanism of carbohydrate-mediated complement activation by the serum mannan-binding protein. (1990)

Serum mannan-binding protein (S-MBP), a lectin specific for mannose and N-acetylglucosamine, was documented to activate complement through the classical pathway. In this study, we examined the mechanism that initiates this activation. By a passive hemolysis test using sheep erythrocytes coated with yeast mannan, the activation of complement by human S-MBP was shown to proceed in the absence of C1q. The following binding studies using 125I-labeled C1r2s2 and C1s indicated that the activated form of C1r2s2 bound to S-MBP located on the surface of the cells with high affinity. The binding of C1s to the cell-bound S-MBP require the presence of C1r, suggesting that C1r2s2 binds to S-MBP through C1r. The activation of C1s from a proenzyme to a protease was mediated by cell-bound S-MBP in the presence of C1r and the activated protease remained associated with the cells and was not released into the medium. The activation of complement with S-MBP was a solid phase event and did not proceed in a fluid phase. On the basis of these results, it was concluded that S-MBP is responsible for the initiation of carbohydrate-mediated complement activation as C1q does in immune complex-mediated complement activation.
Long-Term R-Values and Thermal Testing Requirements for Rigid Insulating Foams (1990)

This paper presents the results of two experimental studies. The first was a continuation of a 5-year aging study on foil-faced polyisocyanurate thermal insulation boards. These boards were retested in the guarded hot box and represent 11-year aged data. The results indicated excellent agreement with the plateaued R-values established on the 5-year aged samples. The second effort is an ongoing correlation study between the large-scale guarded hot box and small-scale heat flow meter tests using permeable faced polyisocyanurate foam thermal insulation boards. Thicknesses tested ranged from 2.5 to 8.1 cm (1 to 3.2 in.). The results to date show that, in general, with proper sampling of large-scale boards, good agreement can be expected between guarded hot box and heat flow meter test results.
A Human Interleukin-12/23 Monoclonal Antibody for the Treatment of Psoriasis (2007)

This study demonstrates the therapeutic efficacy of an interleukin-12/23 monoclonal antibody in psoriasis and provides further evidence of a role of the interleukin-12/23 p40 cytokines in the pathophysiology of psoriasis. Larger studies are needed to determine whether serious adverse events might limit the clinical usefulness of this new therapeutic target. (ClinicalTrials.gov number, NCT00320216 [ClinicalTrials.gov].).
Comprehensive molecular characterization of clear cell renal cell carcinoma (2012)

Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.
NOTES (2011)

A summary is not available for this content so a preview has been provided. Please use the Get access link above for information on how to access this content.
Role of Fatty Acid De Novo Biosynthesis in Polyhydroxyalkanoic Acid (PHA) and Rhamnolipid Synthesis by Pseudomonads: Establishment of the Transacylase (PhaG)-Mediated Pathway for PHA Biosynthesis in Escherichia coli (2001)

Since Pseudomonas aeruginosa is capable of biosynthesis of polyhydroxyalkanoic acid (PHA) and rhamnolipids, which contain lipid moieties that are derived from fatty acid biosynthesis, we investigated various fab mutants from P. aeruginosa with respect to biosynthesis of PHAs and rhamnolipids. All isogenic fabA, fabB, fabI, rhlG, and phaG mutants from P. aeruginosa showed decreased PHA accumulation and rhamnolipid production. In the phaG (encoding transacylase) mutant rhamnolipid production was only slightly decreased. Expression of phaG from Pseudomonas putida and expression of the beta-ketoacyl reductase gene rhlG from P. aeruginosa in these mutants indicated that PhaG catalyzes diversion of intermediates of fatty acid de novo biosynthesis towards PHA biosynthesis, whereas RhlG catalyzes diversion towards rhamnolipid biosynthesis. These data suggested that both biosynthesis pathways are competitive. In order to investigate whether PhaG is the only linking enzyme between fatty acid de novo biosynthesis and PHA biosynthesis, we generated five Tn5 mutants of P. putida strongly impaired in PHA production from gluconate. All mutants were complemented by the phaG gene from P. putida, indicating that the transacylase-mediated PHA biosynthesis route represents the only metabolic link between fatty acid de novo biosynthesis and PHA biosynthesis in this bacterium. The transacylase-mediated PHA biosynthesis route from gluconate was established in recombinant E. coli, coexpressing the class II PHA synthase gene phaC1 together with the phaG gene from P. putida, only when fatty acid de novo biosynthesis was partially inhibited by triclosan. The accumulated PHA contributed to 2 to 3% of cellular dry weight.
Antibody–Drug Conjugates for Tumor Targeting—Novel Conjugation Chemistries and the Promise of non-IgG Binding Proteins (2015)

Antibody-drug conjugates (ADCs) have emerged as a promising class of anticancer agents, combining the specificity of antibodies for tumor targeting and the destructive potential of highly potent drugs as payload. An essential component of these immunoconjugates is a bifunctional linker capable of reacting with the antibody and the payload to assemble a functional entity. Linker design is fundamental, as it must provide high stability in the circulation to prevent premature drug release, but be capable of releasing the active drug inside the target cell upon receptor-mediated endocytosis. Although ADCs have demonstrated an increased therapeutic window, compared to conventional chemotherapy in recent clinical trials, therapeutic success rates are still far from optimal. To explore other regimes of half-life variation and drug conjugation stoichiometries, it is necessary to investigate additional binding proteins which offer access to a wide range of formats, all with molecularly defined drug conjugation. Here, we delineate recent progress with site-specific and biorthogonal conjugation chemistries, and discuss alternative, biophysically more stable protein scaffolds like Designed Ankyrin Repeat Proteins (DARPins), which may provide such additional engineering opportunities for drug conjugates with improved pharmacological performance.
Neutrophil Elastase Enhances Sputum Solubilization in Cystic Fibrosis Patients Receiving DNase Therapy (2011)

Cystic fibrosis patients suffer from chronic lung infection and inflammation due to the secretion of viscous sputum. Sputum viscosity is caused by extracellular DNA, some of which originates from the release of neutrophil extracellular traps (NETs). During NET formation neutrophil elastase (NE) partially processes histones to decondense chromatin. NE is abundant in CF sputum and is thought to contribute to tissue damage. Exogenous nucleases are a palliative treatment in CF as they promote sputum solubilization. We show that in a process reminiscent of NET formation, NE enhances sputum solubilization by cleaving histones to enhance the access of exogenous nucleases to DNA. In addition, we find that in Cf sputum NE is predominantly bound to DNA, which is known to downregulate its proteolytic activity and may restrict host tissue damage. The beneficial role of NE in CF sputum solubilization may have important implications for the development of CF therapies targeting NE.
Deformable part models are convolutional neural networks (2015)

Deformable part models (DPMs) and convolutional neural networks (CNNs) are two widely used tools for visual recognition. They are typically viewed as distinct approaches: DPMs are graphical models (Markov random fields), while CNNs are “black-box” non-linear classifiers. In this paper, we show that a DPM can be formulated as a CNN, thus providing a synthesis of the two ideas. Our construction involves unrolling the DPM inference algorithm and mapping each step to an equivalent CNN layer. From this perspective, it is natural to replace the standard image features used in DPMs with a learned feature extractor. We call the resulting model a DeepPyramid DPM and experimentally validate it on PASCAL VOC object detection. We find that DeepPyramid DPMs significantly outperform DPMs based on histograms of oriented gradients features (HOG) and slightly outperforms a comparable version of the recently introduced R-CNN detection system, while running significantly faster.
Bulky Diarylammonium Arenesulfonates as Selective Esterification Catalysts (2005)

More environmentally benign alternatives to current chemical processes, especially large-scale, fundamental reactions such as ester condensations, are highly desirable for many reactions. Bulky diarylammonium pentafluorobenzenesulfonates and tosylates serve as extremely active dehydration catalysts for the ester condensation reaction of carboxylic acids with equimolar amounts of sterically demanding alcohols and acid-sensitive alcohols. Typically, the esterification reaction is performed in heptane by heating at 80 degrees C in the presence of 1 mol % of the catalyst without removing water. Esterification with primary alcohols proceeds without solvents even at room temperature. Furthermore, 4-(N-mesitylamino)polystyrene resin-bound pentafluorobenzenesulfonate can be recycled more than 10 times without activity loss.
REVIEW ARTICLE: Fetomaternal Immunotolerance (2008)

Implantation of mammalian conceptus in uterine cavity is the result of evolutionary adaptation, through high level of physiological procedures to ensure its success. However the majority of pregnancy losses occur before or during implantation. It is expected that exploring and defining the molecular and physiological road map during the crucial time of implantation will enable us to decode and effectively treat fertility defects. Immunological, hormonal and molecular factors participate in the feto-maternal cross talk during implantation and designate the effectiveness of the process. The atypical expression of major histocompatibility complex and other protein-antigens, such as Fas/FasL and petformin in human trophoblast, the modified function of cellular constituents of the feto-maternal interface, as well as the specific role of some hormones and cytokines, represent substantive parameters of feto-maternal immunotolerance during implantation.
HLA-C and HLA-E reduce antibody-dependent natural killer cell-mediated cytotoxicity of HIV-infected primary T cell blasts (2004)

These studies indicate that the presence of HLA-C and HLA-E molecules on HIV-infected cells may facilitate evasion of NK-mediated killing of antibody-coated HIV-infected cells.
Retrovirus-mediated gene transfer of beta-nerve growth factor into mouse pituitary line AtT-20. (1988)

Expression of the biologically active beta-subunit of mouse nerve growth factor (beta-NGF) was conferred onto cultured AtT-20 mouse pituitary cells via a replication-defective retroviral vector. The retroviral LTR promoter was used for expression of a cDNA for beta-NGF corresponding to the shorter mRNA species produced by most tissues that receive sympathetic innervation. The vector included the TU5 gene conferring resistance to the neomycin analogue G418 under the control of an SV40 early promoter. AtT-20 cells, which produce essentially no endogenous beta-NGF, were infected and then cloned under G418 selection. Clones were evaluated for release into the medium of biologically active beta-NGF using a bioassay for neurite extension from PC-12 cells. The biological activity was equivalent to 1 to 10 ng of beta-NGF per mg cell protein over 24 hours. Immune precipitation and SDS/polyacrylamide gel electrophoresis of labelled proteins in the medium showed that the major form of immunoreactive beta-NGF secreted from cells comigrated with authentic mature beta-NGF, apparent Mr 13,000. Release of this beta-NGF from cells was stimulated by addition of 1 mM-8-bromocyclic AMP or 10 nM-corticotropin releasing factor, suggesting that at least some of the processed factor is stored in secretory vesicles. These studies, together with those on other cultured cells, which produce beta-NGF and lack secretory granules, e.g. L cells, suggest that the beta-NGF precursor synthesized from the shorter mRNA species can be processed and secreted through either the regulated or constitutive route. This retroviral vector provides a potential means of conferring beta-NGF expression onto a number of different cell types in culture and in vivo.
TCR β-chain variable region-driven selection and massive expansion of HLA-class I-restricted antitumor CTL lines from HLA-A*0201+ melanoma patients (1997)

Recognition of a given melanoma Ag involves a limited array of T cell clones bearing a structurally defined TCR. The aim of this study was to verify whether this information can be used to isolate and expand such anti-tumor effectors from fresh lymphocyte populations. We found that one to three different TCR beta-chain variable (TCRBV) regions were significantly expanded in 4-wk mixed lymphocyte-tumor cultures (MLTC) from six HLA-A*0201+ melanoma patients, and that the T cells expressing the expanded TCRBV regions were involved in HLA class I-restricted lysis of the tumor. T cell activation by mAbs to MLTC-selected TCRBV region and CD28 resulted in large scale expansion (1-10 x 10(9) cells) of T cell lines, highly enriched for the expression of a single TCRBV region and for CD8+ T cells. The TCRBV-driven selection was equally effective when applied to patients' or healthy donors' lymphocytes, and the T cell lines isolated from melanoma patients exerted HLA class I-restricted lysis of the autologous tumor. MLTC and TCRBV-selected lines recognized allogeneic melanomas sharing HLA-A and -B alleles with the autologous tumor, but only two of the HLA-A2-restricted lines were directed to a known peptide from melanoma-associated Ags. Single-strand conformation polymorphism analysis indicated a polyclonal composition of both MLTC and TCRBV-selected lines, but expansion of clonotypes with identical CDR3 length was observed only in the MLTC lines. Thus, TCRBV-driven selection can be exploited to obtain large scale expansion of antitumor CTL lines from melanoma patients.
The HLJ1 -targeting drug screening identified Chinese herb andrographolide that can suppress tumour growth and invasion in non-small-cell lung cancer (2013)

HLJ1 is a novel tumour suppressor and is a potential druggable target for non-small-cell lung cancer (NSCLC). In this report, using a promoter-containing enhancer region as the HLJ1-targeting drug-screening platform, we identified several herbal compounds from a Chinese herbal bank with the capacity to enhance HLJ1 promoter activity and suppress tumour growth and invasion of NSCLC. Among the herbal drugs identified, the andrographolide (from Andrographis paniculata [Burm. f.] Nees.) most significantly induced HLJ1 expression and suppressed tumorigenesis both in vitro and in vivo. The andrographolide upregulates HLJ1 via JunB activation, which modulates AP-2α binding at the MMP-2 promoter and represses the expression of MMP-2. In addition, silencing of HLJ1 partially reverses the inhibition of cancer-cell invasion by andrographolide. Microarray transcriptomic analysis was performed to comprehensively depict the andrographolide-regulated signalling pathways. We showed that andrographolide can affect 939 genes (analysis of variance, false discovery rate < 0.05) that are dominantly involved in the cell cycle, apoptosis and adhesion-related biological signalling, including mitogen-activated protein kinase, focal adhesion and tight junction pathways, indicating the diverse effects of andrographolide on anticancer invasion and proliferation. In conclusion, the HLJ1-targeting drug-screening platform is useful for screening of novel anticancer compounds. Using this platform, we identified andrographolide is a promising new anticancer agent that could suppress tumour growth and invasion in NSCLC.
Multifocal optical-resolution photoacoustic microscopy in vivo (2011)

Although ultrasound arrays have been exploited in photoacoustic imaging to improve imaging speed, ultrasound-array-based optical-resolution photoacoustic microscopy (OR-PAM) has never been achieved previously to our knowledge. Here we present our development of multifocal OR-PAM using a microlens array for optical illumination and an ultrasound array for photoacoustic detection. Our system is capable of imaging hemoglobin concentration and oxygenation in individual microvessels in vivo at high speed. Compared with a single focus, multiple foci reduce the scanning load and increase the imaging speed significantly. The current multifocal system can acquire 1000 × 500 × 200 voxels at ~10 μm lateral resolution within 4 min.
PULLOUT STRENGTH OF SUTURE ANCHORS USED IN ROTATOR CUFF REPAIR (2003)

We found that pullout strength of suture anchors correlates well with bone mineral density of the tuberosities. Higher loads to failure were found in regions in the proximal part of the tuberosities. Placement of anchors in these regions may prevent anchor loosening, formation of a tendon-bone gap, and failure of the rotator cuff repair.
Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer (2013)

The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS, BRAF). Attempts to fill this gap are emerging. The Cancer Genome Atlas (TGCA) reported two main CRC groups, based on the incidence and spectrum of mutated genes, and another paper reported an EMT expression signature defined subgroup. We performed a prior free analysis of CRC heterogeneity on 1113 CRC gene expression profiles and confronted our findings to established molecular determinants and clinical, histopathological and survival data. Unsupervised clustering based on gene modules allowed us to distinguish at least five different gene expression CRC subtypes, which we call surface crypt-like, lower crypt-like, CIMP-H-like, mesenchymal and mixed. A gene set enrichment analysis combined with literature search of gene module members identified distinct biological motifs in different subtypes. The subtypes, which were not derived based on outcome, nonetheless showed differences in prognosis. Known gene copy number variations and mutations in key cancer-associated genes differed between subtypes, but the subtypes provided molecular information beyond that contained in these variables. Morphological features significantly differed between subtypes. The objective existence of the subtypes and their clinical and molecular characteristics were validated in an independent set of 720 CRC expression profiles. Our subtypes provide a novel perspective on the heterogeneity of CRC. The proposed subtypes should be further explored retrospectively on existing clinical trial datasets and, when sufficiently robust, be prospectively assessed for clinical relevance in terms of prognosis and treatment response predictive capacity. Original microarray data were uploaded to the ArrayExpress database (http://www.ebi.ac.uk/arrayexpress/) under Accession Nos E-MTAB-990 and E-MTAB-1026.
Overexpression of Her-2/Neu may be an Indicator of Poor Prognosis in Prostate Cancer (1993)

Previous reports have shown that Her-2/neu oncogene expression in human breast cancer and ovarian cancer may be associated with poorer prognosis. We report the expression of Her-2/neu on fresh samples of known prostatic adenocarcinoma but not on those of benign prostatic hypertrophy. Using a monoclonal antibody (TA1) directed against human Her-2/neu oncogene product and an immunohistochemical staining method, no Her-2/neu expression was noted with benign prostatic hypertrophy (15 samples). With prostatic adenocarcinoma samples, a subset (9 of 25) showed overexpression of Her-2/neu. Such overexpression is correlated with higher histological grade, higher stage of disease, and high S phase and aneuploidy on flow cytometric analysis. These findings suggest that Her-2/neu may be a prognostic marker in prostate cancer as well.