gebhart/patrepeval huggingface dataset:
Adeno-Associated Virus Vector Gene Expression Occurs in Nondividing Cells in the Absence of Vector DNA Integration (1994)

Adeno-associated virus type 2 (AAV2)-based vectors are capable of stable expression in the airway epithelium and may be useful for gene therapy for human diseases, such as cystic fibrosis. Certain virus vectors, such as retroviruses, require active cell division for integration and expression, but this has not been formally evaluated in the case of AAV2. The cystic fibrosis bronchial epithelial cell line, IB3-1, which can be transduced by AAV2 vectors, was shown to undergo a decrease in DNA synthesis to undetectable levels when grown to confluence. Cultures in which < 0.1% of cells were dividing could still be efficiently transduced with AAV-lacZ or AAV-neo vectors, with a linear dose response, up to 91% with a multiplicity of 3,000 vector particles per cell. The fate of vector DNA in nondividing target cells was investigated by Southern blotting of both low molecular weight, nonintegrated DNA and high molecular weight, genomic DNA fractions. Detectable levels of vector DNA were only seen in the nonintegrated state. These results indicate that AAV2-based vectors, unlike retrovirus vectors, do not require active cell division or integration for expression to occur and thus possess a unique profile of biologic properties.
Disposable Diet Packet for Feeding and Oviposition of Lygus hesperus (Hemiptera: Miridae)1 (1982)

A disposable, heat-sealed packet has been developed for use in feeding and oviposition of the Debolt Lygus diet for laboratory rearing of Lygus hesperus Knight. An individual packet is formed by heat sealing the edges of a piece of Parafilm (10 by 10 cm) with a piece of polyethelene plastic (10 by 14 cm) film on three sides. The packet is partially filled with diet, and the remaining edge is then heat sealed to form a disposable packet of diet. The packets can be used for feeding nymphs and adults and also can be used for adult oviposition.
Wnt‐5a signaling is correlated with infiltrative activity in human glioma by inducing cellular migration and MMP‐2 (2010)

Wnts are secreted ligands that consist of 19 members in humans, regulate cell proliferation, differentiation, motility and fate in many stages including the embryonic stage and tumorigenesis. Wnts bind to cell surface receptors named Frizzleds and LRPs, and transduce their signals through β-catenin-dependent and -independent intracellular pathways. Gliomas are one of the most common intracranial tumors. Gliomas exhibit a progression associated with widespread infiltration into surrounding neuronal tissues. However, the molecular mechanisms that stimulate the invasion of glioma cells are not fully understood. We established two cell lines from human glioma cases and analyzed the expression of all Wnt and Frizzled members in these cell lines and other well-known glioma cell lines by real-time PCR study. The mRNA of Wnt-5a and -7b and Frizzled-2, -6 and -7 were overexpressed in glioma cells. The elevation of Wnt-5a expression was most remarkable. Although Wnt-5a is reported to have oncogenic and antioncogenic activity in several cancers, the role of Wnt-5a signaling in human glioma cells remains unclear. Immunohistochemical study also revealed high expression of Wnt-5a in 26 (79%) of 33 human glioma cases. The positivity of Wnt-5a expression was correlated with the clinical grade. Knockdown of Wnt-5a expression suppressed migration, invasion and expression of matrix metalloproteinase-2 of glioma cells. Reciprocally, treatment with purified Wnt-5a ligand resulted in stimulation of cell migration and invasion. MMP-2 inhibitor suppressed the Wnt-5a-dependent invasion of U251 cells. These results suggested that Wnt-5a is not only a prognostic factor but also a therapeutic target molecule in gliomas for preventing tumor cell infiltration.
Atheroprotective immunization with MDA-modified apo B-100 peptide sequences is associated with activation of Th2 specific antibody expression (2005)

Immunization with MDA apo B-100 fragments induce a shift from Th1 to a Th2 specific oxidized LDL antibody expression, but without a concomitant downregulation of plaque IFN-gamma expression.
Preliminary evaluation of collagen as a component in the thermally- induced 'weld' (1991)

ABSTRACT A simple thermodynamic approach to tissue 'welding' was studied. Freshbovine tendon (67% type I collagen) was sectioned into disk shaped pieces, pairs ofwhich were inserted between bowed glass coverslips and wrapped in aluminum foil.The packets were heated in a waterbath according to two protocols. In group I,packets were tested for four minutes at temperatures between 55-65°C, in 1 °Cintervals. In group II, the packets were kept at 62°C for 4 minutes while the rate ofcooling was altered. The force necessary to separate the tendon disks was thenmeasured. The optimal temperature for tissue bonding (group I) was 62°C (598gm/in2). Stress values below 250 gm/in2 could be achieved without heat application and were considered non-welds. Group II showed that the faster the sample cools, thestronger the bond. Several conclusions can be postulated. The narrow temperature region necessary for tissue 'welding' strongly suggests that melting of type I collagen fibrilsis involved. Bonding presumably occurs at 62°C by allowing a-strands from thecollagen super-helix molecule to form new, random connections. Group II resultssuggest that trans-incisional reannealing of unraveled helices does not play a role intissue bonding. Rapid cooling allows less time for extended helix reformation; same-side a-helix reannealing may inhibit effective welds by reducing sites for trans-
An evidential reasoning approach to distributed multiple-hypothesis detection (1987)

A distributed detection system consisting of n local detectors and a fusion center is considered. The local detectors send their inferences with regard to a set of M candidate hypotheses to the fusion center where the final decision is made. Unlike conventional detectors which produce single-hypothesis hard decisions, each local detector produces a "subset" of the M hypotheses and a discrete confidence level associated with that subset. The fusion center then employs Dempster's combining rule for evidence aggregation. The optimum confidence-based partitioning of local decision space with respect to the system performance is studied. For the M=3 case, it is shown that the presented system greatly outperforms the one where each local detector provides a single-hypothesis hard decision.
Non-rigid image registration: theory and practice (2004)

Image registration is an important enabling technology in medical image analysis. The current emphasis is on development and validation of application-specific non-rigid techniques, but there is already a plethora of techniques and terminology in use. In this paper we discuss the current state of the art of non-rigid registration to put on-going research in context and to highlight current and future clinical applications that might benefit from this technology. The philosophy and motivation underlying non-rigid registration is discussed and a guide to common terminology is presented. The core components of registration systems are described and outstanding issues of validity and validation are confronted.
GENE EXPRESSION ANALYSIS IN HUMAN RENAL ALLOGRAFT BIOPSY SAMPLES USING HIGH-DENSITY OLIGOARRAY TECHNOLOGY1 (2001)

High-density oligoarray technology is useful for screening gene expression in transplanted tissues undergoing acute rejection. Because this method does not rely on a priori knowledge of which genes are involved in acute rejection, it is likely to yield novel insights into the mechanisms and diagnosis of rejection.
Derivatization Solid-Phase Microextraction Gas Chromatographic--Mass Spectrometric Determination of Organic Acids in Tobacco (1997)

Isovaleric, valeric, hexanoic, benzoic, phenylacetic, 3-methylvaleric, heptanoic, octanoic, and nonanoic acids are converted to their methyl esters and quantitated for flue-cured tobacco grades of increasing stalk position using derivatization headspace solid-phase microextraction (SPME) with selected ion monitoring mode mass spectrometry. Qualitative analysis of the headspace of tobacco derivatized with methanolic hydrochloric acid using a 65-µm Carbowax-divinylbenzene SPME fiber indicates selectivity for relatively nonpolar volatile and semivolatile organic acid methyl esters. By contrast, direct exposure of an 85-µm polyacrylate SPME fiber to derivatives followed by GC—MS analysis provides the capability to evaluate significantly more polar organic acid methyl esters such as malic acid dimethylester and citric acid trimethylester.
Effects of successful cardioversion of persistent atrial fibrillation on right ventricular refractoriness and repolarization (2005)

Restoration of sinus rhythm in persistent AF patients is followed by significant effects on ventricular refractoriness and repolarization related to cycle length change. No AF related ventricular electrophysiological alterations were found.
Assessment and Optimizations of Candida albicans In Vitro Biofilm Assays (2017)

<i>Candida albicans</i> biofilms have a significant medical impact due to their rapid growth on implanted medical devices, their resistance to antifungal drugs, and their ability to seed disseminated infections. Biofilm assays performed <i>in vitro</i> allow for rapid, high-throughput screening of gene deletion libraries or antifungal compounds and typically serve as precursors to <i>in vivo</i> studies. Here, we compile and discuss the protocols for several recently published <i>C. albicans</i><i>in vitro</i> biofilm assays. We also describe improved versions of these protocols as well as novel <i>in vitro</i> assays. Finally, we consider some of the advantages and disadvantages of these different types of assays.
The Role of ATF4 Stabilization and Autophagy in Resistance of Breast Cancer Cells Treated with Bortezomib (2009)

The ubiquitin-proteasome system plays a key regulatory role in cellular homeostasis. The inhibition of the 26S proteasome by Bortezomib leads to the accumulation of misfolded proteins, resulting in endoplasmic reticulum stress followed by a coordinated cellular response called unfolded protein response (UPR). Endoplasmic reticulum stress is also a potent inducer of macroautophagy. Bortezomib is a selective and potent inhibitor of the 26S proteasome and is approved for the treatment of multiple myeloma. Clinical trials with Bortezomib have shown promising results for some types of cancers, but not for some others, including those of the breast. In this study, we show that Bortezomib induces the UPR and autophagy in MCF7 breast cancer cells. Surprisingly, Bortezomib did not induce phosphorylation of PERK, a key initial step of the UPR. We show that induction of autophagy by Bortezomib is dependent on the proteasomal stabilisation of ATF4 and up-regulation of LC3B by ATF4. We show that ATF4 and LC3B play a critical role in activating autophagy and protecting cells from Bortezomib-induced cell death. Our experiments also reveal that HDAC6 knockdown results in decreased LC3B protein and reduced autophagy. Our work shows that the induction of autophagy through ATF4 may be an important resistance mechanism to Bortezomib treatment in breast cancer, and targeting autophagy may represent a novel approach to sensitize breast cancers to Bortezomib.
Construction of a Family of Cys2His2 Zinc Binding Sites in the Hydrophobic Core of Thioredoxin by Structure-Based Design (1998)

A semi-automated, rational design strategy has been used to introduce a family of seven single, mononuclear Cys2His2 zinc sites at various locations in the hydrophobic core of Escherichia colithioredoxin, a protein that is normally devoid of metal centers. The electronic absorption spectra of the CoII complexes show that five of these designed proteins bind metal with the intended tetrahedral geometry. The designed sites differ in their metal-binding constants and effects on protein stability. Since these designs are constructed within the same host protein framework, comparison of their behavior allows a qualitative evaluation of dominant factors that contribute to metal-binding and metal-mediated protein stabilization. Metal-binding constants are dominated by steric interactions between the buried, designed coordination sphere and the surrounding protein matrix. Metal-mediated stability is the consequence of differential binding to the native and unfolded states. Increased interactions with the unfolded state decrease the stabilizing effect of metal binding. The affinity for the unfolded state is dependent on the placement of the primary coordination sphere residues within the linear protein sequence. These results indicate that a protein fold can have a remarkably broad potential for accommodating metal-mediated cross-links and suggest strategies for engineering protein stability by constructing metal sites that maximize metal binding to the native state and minimize binding to the unfolded state.
Effect of lactic acid supplementation on pancreaticsecretion in pigs after weaning (1998)

The effect of lactic acid supplementation to the starter diet, on pancreatic secretion in pigs after weaning was studied in three crossbred piglets (Duroc, Danish Landrace and Yorkshire). The pigs were weaned at 28 days of age, and adapted to live in metabolic cages for one week, after which the piglets were surgically fitted with a pancreatic duct catheter and a duodenal T-cannula for chronic collection of the pancreatic juice. Studies were then carried out over a period of three weeks, during which the piglets were fed three times a day (at 08.00, 15.00, and 22.00 h). During period I , the piglets were fed with a standard weaner diet (control), during period II with a standard weaner diet supplemented with 2.5 % lactic acid period (lactic acid) and during period III with a standard wea ner diet (control). Beginning four days after surgery, samples of pancreatic juice were taken hourly from 08.00 to 16.00 h. During period II , when lactic acid was added to the feed, the mean for all measured parameters of pancreatic secretion, except bicarbonate, increased in comparison to their values during period I . However this increase was only significant for volume and protein content. In contrast, during period III , when lactic acid was removed, there were no statistically significant changes in any of the measured parameters of pancreatic secretion compared to their values in period II. Our data strongly indicate that dietary supplementation with lactic acid stimulates pancre atic secretion in piglets after weaning.
Maxout Networks (2013)

We consider the problem of designing models to leverage a recently introduced approximate model averaging technique called dropout. We define a simple new model called maxout (so named because its output is the max of a set of inputs, and because it is a natural companion to dropout) designed to both facilitate optimization by dropout and improve the accuracy of dropout's fast approximate model averaging technique. We empirically verify that the model successfully accomplishes both of these tasks. We use maxout and dropout to demonstrate state of the art classification performance on four benchmark datasets: MNIST, CIFAR-10, CIFAR-100, and SVHN.
Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases (2016)

While certain logistical obstacles limit the clinical applications of MSC conditioned medium such as the volume required for treatment, the therapeutic application of MSC extracellular vesicles remains promising, primarily due to ability of extracellular vesicles to maintain the functional phenotype of the parent cell. However, utilization of MSC extracellular vesicles will require large-scale production and standardization concerning identification, characterization and quantification.
Association of 70-Gene Signature Assay Findings With Physicians’ Treatment Guidance for Patients With Early Breast Cancer Classified as Intermediate Risk by the 21-Gene Assay (2017)

The 70-GS provides clinically actionable information regarding patients classified as intermediate risk by the 21-GA and was associated with a change in treatment decision in 282 of these patients (33.6%). Chemotherapy was added or withheld by the treating physician based on the results of the 70-GS test. Physicians reported more confidence with their treatment recommendation after receiving 70-GS results.
p63 expression in benign and malignant breast lesions. (2004)

The p63 gene encodes six protein isoforms. The transactivating isoforms have similar actions with p53, while the N-isoforms inhibit transcription activation by p53 and transactivating isoforms. p63 is expressed in stratified epithelia and in basal cells of the prostate and salivary glands. In mammary epithelium p63 has been shown to be expressed only in the myoepithelial layer. In the present study we investigated the immunohistochemical expression of p63, in benign and malignant breast lesions, and compared it with known myoepithelial cell markers. Our material consisted of 140 benign and 126 malignant breast lesions. We used the antibodies anti-p63, anti-alpha-smooth muscle actin, anti-S-100 protein and anti-cytokeratin 14. In all benign lesions, p63 immunoreactivity was noted in the myoepithelial cell layer surrounding the luminal epithelial cells. A less continuous peripheral rim of myoepithelial cells was also highlighted with p63-staining in all situ carcinomas. All invasive breast carcinomas were devoided of peripheral p63 staining. Interestingly, strong nuclear p63 immunoreactivity was noted in a small fraction (5-15%) of epithelial cells in all cases of papillomatosis, in 62.5% of in situ ductal papillary-type carcinomas and in 33.3% of invasive papillary carcinomas. Comparable staining was observed with S-100. The stromal cells were unreactive to p63. Our findings suggest that p63 is a sensitive and specific myoepithelial marker, and may be included in immunohistochemical panels aiming to identify myoepithelial cells in problematic breast lesions. Regarding papillary neoplasms, it is possible that tumor cells acquire and exhibit at least in part a myoepithelial differentiation program.
Genotoxicity testing of Maillard reaction products. (1989)

Since the development of short-term genotoxicity tests such as the Ames assay, the mutagenicity of Maillard reaction products has been tested extensively. Some products have exhibited strong activity. For example, one of the earliest studies demonstrated some mutagenic activity in a dichloromethane extract of a D-glucose/ammonia Maillard model system. Many researchers have attempted to pinpoint the principal chemical(s) of mutagenicity of the Maillard products using various sugar-amino acid browning model systems over last two decades. However, no mutagenic individual Maillard product has been isolated and identified. Nitrite has been also used as a reactant in browning reaction model systems, primarily to investigate the formation of potentially mutagenic or carcinogenic N-nitroso compounds. Recently some potent mutagens isolated from pyrolyzed amino acids or proteins have begun to receive attention as Maillard reaction products.
Protein Dynamics Control the Progression and Efficiency of the Catalytic Reaction Cycle of the Escherichia coli DNA-Repair Enzyme AlkB (2014)

A central goal of enzymology is to understand the physicochemical mechanisms that enable proteins to catalyze complex chemical reactions with high efficiency. Recent methodological advances enable the contribution of protein dynamics to enzyme efficiency to be explored more deeply. Here, we utilize enzymological and biophysical studies, including NMR measurements of conformational dynamics, to develop a quantitative mechanistic scheme for the DNA repair enzyme AlkB. Like other iron/2-oxoglutarate-dependent dioxygenases, AlkB employs a two-step mechanism in which oxidation of 2-oxoglutarate generates a highly reactive enzyme-bound oxyferryl intermediate that, in the case of AlkB, slowly hydroxylates an alkylated nucleobase. Our results demonstrate that a microsecond-to-millisecond time scale conformational transition facilitates the proper sequential order of substrate binding to AlkB. Mutations altering the dynamics of this transition allow generation of the oxyferryl intermediate but promote its premature quenching by solvent, which uncouples 2-oxoglutarate turnover from nucleobase oxidation. Therefore, efficient catalysis by AlkB depends upon the dynamics of a specific conformational transition, establishing another paradigm for the control of enzyme function by protein dynamics.
Fyn and Src Are Effectors of Oncogenic Epidermal Growth Factor Receptor Signaling in Glioblastoma Patients (2009)

Activating epidermal growth factor receptor (EGFR) mutations are common in many cancers including glioblastoma. However, clinical responses to EGFR inhibitors are infrequent and short-lived. We show that the Src family kinases (SFK) Fyn and Src are effectors of oncogenic EGFR signaling, enhancing invasion and tumor cell survival in vivo. Expression of a constitutively active EGFR mutant, EGFRvIII, resulted in activating phosphorylation and physical association with Src and Fyn, promoting tumor growth and motility. Gene silencing of Fyn and Src limited EGFR- and EGFRvIII-dependent tumor cell motility. The SFK inhibitor dasatinib inhibited invasion, promoted tumor regression, and induced apoptosis in vivo, significantly prolonging survival of an orthotopic glioblastoma model expressing endogenous EGFRvIII. Dasatinib enhanced the efficacy of an anti-EGFR monoclonal antibody (mAb 806) in vivo, further limiting tumor growth and extending survival. Examination of a large cohort of clinical samples showed frequent coactivation of EGFR and SFKs in glioblastoma patients. These results establish a mechanism linking EGFR signaling with Fyn and Src activation to promote tumor progression and invasion in vivo and provide rationale for combined anti-EGFR and anti-SFK targeted therapies.
Inhibition of Adipogenesis Through MAP Kinase-Mediated Phosphorylation of PPARγ (1996)

Adipocyte differentiation is an important component of obesity and other metabolic diseases. This process is strongly inhibited by many mitogens and oncogenes. Several growth factors that inhibit fat cell differentiation caused mitogen-activated protein (MAP) kinase-mediated phosphorylation of the dominant adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) and reduction of its transcriptional activity. Expression of PPARgamma with a nonphosphorylatable mutation at this site (serine-112) yielded cells with increased sensitivity to ligand-induced adipogenesis and resistance to inhibition of differentiation by mitogens. These results indicate that covalent modification of PPARgamma by serum and growth factors is a major regulator of the balance between cell growth and differentiation in the adipose cell lineage.