gebhart/patrepeval huggingface dataset:
A clinical evaluation of the effects of an aromatic retinoid (Tigason), combination of retinoid and PUVA, and PUVA alone in severe psoriasis (1981)

Eighty ambulatory adult patients with severe psoriasis were included in our 14-week study to compare the clinical effects of treatment with an aromatic retinoid (Tigason), combination treatment with aromatic retinoid plus PUVA (RePUVA), and PUVA alone. RePUVA was given by two different modifications: either 4 weeks of pretreatment with retinoid followed by 6 weeks of PUVA treatment, or 10 weeks of retinoid treatment with concomitant PUVA treatment during the last 6 weeks. The latter modification of RePUVA proved to be significantly more effective than the other treatments (P less than 0.01) as regards complete remission. With respect to the number of patients with good or excellent improvement (75-100% improvement) there was no marked difference between RePUVA and PUVA treatments. Retinoid alone proved to be the least effective, showing, however, a good to excellent result in 65% of patients. Besides the increase in efficacy, another advantage achieved by RePUVA was a highly significant (P less than 0.001) reduction of total UVA doses to about one third as compared to PUVA therapy.
Engineered Commensal Bacteria Reprogram Intestinal Cells Into Glucose-Responsive Insulin-Secreting Cells for the Treatment of Diabetes (2015)

The inactive full-length form of GLP-1(1-37) stimulates conversion of both rat and human intestinal epithelial cells into insulin-secreting cells. We investigated whether oral administration of human commensal bacteria engineered to secrete GLP-1(1-37) could ameliorate hyperglycemia in a rat model of diabetes by reprogramming intestinal cells into glucose-responsive insulin-secreting cells. Diabetic rats were fed daily with human lactobacilli engineered to secrete GLP-1(1-37). Diabetic rats fed GLP-1-secreting bacteria showed significant increases in insulin levels and, additionally, were significantly more glucose tolerant than those fed the parent bacterial strain. These rats developed insulin-producing cells within the upper intestine in numbers sufficient to replace ∼25-33% of the insulin capacity of nondiabetic healthy rats. Intestinal tissues in rats with reprogrammed cells expressed MafA, PDX-1, and FoxA2. HNF-6 expression was observed only in crypt epithelia expressing insulin and not in epithelia located higher on the villous axis. Staining for other cell markers in rats treated with GLP-1(1-37)-secreting bacteria suggested that normal function was not inhibited by the close physical proximity of reprogrammed cells. These results provide evidence of the potential for a safe and effective nonabsorbed oral treatment for diabetes and support the concept of engineered commensal bacterial signaling to mediate enteric cell function in vivo.
KRAS mutation testing in colorectal cancer: the model for molecular pathology testing in the future (2016)

Somatic mutations in the KRAS gene often occur in colorectal cancer (CRC) and are predictive for poor response to EGFR blockade therapy. Over the past decade, routine detection of KRAS mutations has been employed in many diagnostic centers using a range of methodological approaches including Sanger sequencing, pyrosequencing, high-resolution melt analysis and more recently, next-generation sequencing approaches. This article highlights the clinical relevance of KRAS-mutated CRCs, examines advantages and disadvantages of various detection methods and highlights the considerations that are critical for an accurate, rapid and efficient workflow to detect KRAS and other RAS mutations in CRC presently and in the future.
Serving a Useful Purpose? Dilemmas of Caring (1998)

One of drives behind this study was the expanding role of congregations in welfare provision in Britain and the need, therefore, to understand congregations as organizations. The case studies demonstrated the numerous ways in which congregations were contributing to social welfare. They also indicated the nature of the organizational challenges faced by congregations as they expanded their caring activities.
Quantification of Staphylococcal‐Collagen Binding Interactions in Whole Blood by Use of a Confocal Microscopy Shear‐Adhesion Assay (2003)

In bloodborne staphylococcal infections, bacteria and platelets often combine, forming thrombi on the subendothelium, where collagen is exposed. In this process, the collagen serves as a potential binding surface for Staphylococcus aureus. However, the extent and importance of S. aureus-collagen binding interactions in the development of infected thrombi is uncertain. We quantified S. aureus adhesion to collagen in a whole-blood suspension under defined physiologically relevant fluid shear conditions. S. aureus-collagen binding interactions, mediated by both the S. aureus collagen adhesin (CNA) and protein A-von Willebrand factor (vWf), were evaluated using mutant strains and antibody-blocking techniques. The position of adherent bacteria (at the collagen surface or above the surface in the platelet aggregate) was measured using confocal laser microscopy. Results demonstrated significant CNA-collagen interactions and protein A-vWf-collagen binding interactions under physiological shear conditions. We conclude that collagen binding interactions are important in the development of infected thrombi.
Blue-Fluorescent Antibodies (2000)

The forte of catalytic antibodies has resided in the control of the ground-state reaction coordinate. A principle and method are now described in which antibodies can direct the outcome of photophysical and photochemical events that take place on excited-state potential energy surfaces. The key component is a chemically reactive optical sensor that provides a direct report of the dynamic interplay between protein and ligand at the active site. To illustrate the concept, we used a trans-stilbene hapten to elicit a panel of monoclonal antibodies that displayed a range of fluorescent spectral behavior when bound to a trans-stilbene substrate. Several antibodies yielded a blue fluorescence indicative of an excited-state complex or "exciplex" between trans-stilbene and the antibody. The antibodies controlled the isomerization coordinate of trans-stilbene and dynamically coupled this manifold with an active-site residue. A step was taken toward the use of antibody-based photochemical sensors for diagnostic and clinical applications.
Optimal Design of Microarray Immunoassays to Compensate for Kinetic Limitations (2006)

In this report we examine the limitations of existing microarray immunoassays and investigate how best to optimize them using theoretical and experimental approaches. Derived from DNA technology, microarray immunoassays present a major technological challenge with much greater physicochemical complexity. A key physicochemical limitation of the current generation of microarray immunoassays is a strong dependence of antibody microspot kinetics on the mass flux to the spot as was reported by us previously. In this report we analyze, theoretically and experimentally, the effects of microarray design parameters (incubation vessel geometry, incubation time, stirring, spot size, antibody-binding site density, etc.) on microspot reaction kinetics and sensitivity. Using a two-compartment model, the quantitative descriptors of the microspot reaction were determined for different incubation and microarray design conditions. This analysis revealed profound mass transport limitations in the observed kinetics, which may be slowed down as much as hundreds of times compared with the solution kinetics. The data obtained were considered with relevance to microspot assay diffusional and adsorptive processes, enabling us to validate some of the underlying principles of the antibody microspot reaction mechanism and provide guidelines for optimal microspot immunoassay design. For an assay optimized to maximize the reaction velocity on a spot, we demonstrate sensitivities in the am and low fm ranges for a system containing a representative sample of antigen-antibody pairs. In addition, a separate panel of low abundance cytokines in blood plasma was detected with remarkably high signal-to-noise ratios.
Why there are complementary learning systems in the hippocampus and neocortex: Insights from the successes and failures of connectionist models of learning and memory. (1995)

Damage to the hippocampal system disrupts recent memory but leaves remote memory intact. The account presented here suggests that memories are first stored via synaptic changes in the hippocampal system, that these changes support reinstatement of recent memories in the neocortex, that neocortical synapses change a little on each reinstatement, and that remote memory is based on accumulated neocortical changes. Models that learn via changes to connections help explain this organization. These models discover the structure in ensembles of items if learning of each item is gradual and interleaved with learning about other items. This suggests that the neocortex learns slowly to discover the structure in ensembles of experiences. The hippocampal system permits rapid learning of new items without disrupting this structure, and reinstatement of new memories interleaves them with others to integrate them into structured neocortical memory systems.
Medium chain triglycerides dose‐dependently prevent liver pathology in a rat model of nonalcoholic fatty liver disease (2013)

To determine if there was a beneficial effect of dietary medium chain triglycerides (MCT) on nonalcoholic fatty liver disease (NAFLD), male rats were isocalorically overfed diets containing 10–70% total energy as corn oil or a 70% fat diet in which corn oil was replaced with increasing concentrations of saturated fat (18:82, beef tallow:MCT oil) from 20–65% for 21 d using total enteral nutrition (TEN). As dietary content of corn oil increased, hepatic steatosis and serum ALTs were elevated (P&lt;0.05). This was accompanied by greater expression of cytochrome P450 enzyme CYP2E1 (P&lt;0.05) and higher concentrations of polyunsaturated 18:2 and 20:4 fatty acids (FA) in the hepatic lipid fractions (P&lt;0.05). Increasing the proportion of MCT‐enriched saturated fat resulted in a dose‐dependent reduction in steatosis and necrosis without affecting CYP2E1 induction. There was no incorporation of C8–C10 FAs into liver lipids, but increasing dietary MCT reduced liver lipid 18:2 and 20:4 concentrations; reduced membrane susceptibility to radical attack; stimulated FA beta‐and omega‐oxidation as a result of activation of peroxisomal proliferator activated receptor (PPAR)alpha and appeared to increase mitochondrial respiration through complex III. These data suggest that dietary MCT could be utilized as a potential treatment for NAFLD. Supported in part by USDA, ARS‐CRIS 6251–51000‐005–004S.
Imaging artefacts in atomic force microscopy with carbon nanotube tips (2005)

Dynamic atomic force microscopy (dynamic AFM) with carbon nanotube tips has been suggested as an enabling tool for high precision nanometrology of critical dimension features of semiconductor surfaces.We investigate the performance of oscillating AFM microcantilevers with multi-walled carbon nanotube (multi-walled CNT) tips interacting with high aspect ratio structures while in the attractive regime of dynamic AFM.We present experimental results on SiO 2 gratings and tungsten nanorods, which show two distinct imaging artefacts, namely the formation of divots and large ringing artefacts that are inherent to CNT AFM probe operation.Through meticulous adjustment of operating parameters, the connection of these artefacts to CNT bending, adhesion, and stiction is described qualitatively and explained.
Expression of stem cell factor and its receptor by human neuroblastoma cells and tumors (1995)

Bone marrow (BM) is a frequent site of metastasis in children with neuroblastoma (NB). Nonhematopoietic cell lines of the same neuroectodermal origin produce both stem cell factor (SCF) and its receptor, the product of the c-kit protooncogene (c-kit). Because recombinant SCF is likely to be soon clinically tested to accelerate BM recovery after high-dose chemotherapy, a treatment administered to children with disseminated NB, we addressed the question of whether SCF/c-kit complex could play a role in the proliferation and metastasis of NB cells. Northern blot analysis showed SCF mRNA transcripts in 7 of 8 (88%) NB cell lines and c-kit in 1 (13%). Neither c-kit nor SCF could be detected by Western blotting in cell extracts or by surface immunofluorescence and flow cytometry. Soluble SCF protein was detected by enzyme immunoassay at low concentrations in the cell supernatants in the same 7 NB cell lines. Treatment of 4 NB cell lines by SCF +/- cytokines relevant to BM physiology did not induce c-kit antigenic expression or modulate 3H-thymidine uptake. Likewise, the latter was not changed by incubating the cells with anti-c-kit neutralizing antibodies. Immunohistochemical analysis showed weak diffuse or focal staining for SCF and c-kit in few primary or metastatic tumor samples, only once simultaneously. We conclude that NB cell lines usually produce low levels of soluble SCF but do not express c-kit and that both proteins are rarely detected in NB tumors. The SCF/c-kit complex appears to be unlikely to stimulate NB growth or metastasis; thus, recombinant SCF could be safely administered to children with NB.
Static Charge Development on Explosives . (1991)

Static charge development character of some of the important explosive crystals have been predicted on the basis of their crystal class and symmetry. Among the important mechanism of charge development, the piezoelectric and pyroelectric characters have been considered. Ammonium trinitrate, ammonium nitrate, m-dinitro-benzene, trinitro-toluene, styphnic acid, beeta-lead styphnate, 4,4'dinitro-dipheny1, a-hexamethylenetetranitramine, nitroguanidine, picric acid, dimethylnitramine, a-lead azide and beeta-lead azide are pyroelectric in nature, whereas pentaerythritol tetranitrate, picryliodide, hexamethylenetranitramine, tetranitromethane and trinitroethane are piezoelectric in nature.
Roles of Fc receptors in autoimmunity (2002)

The receptors for the Fc of immunoglobulins, Fc receptors (FcRs), link the humoral and cellular branches of the immune system, and they have important functions in the activation and down-modulation of immune responses. Balanced signalling through activating and inhibitory FcRs regulates the activity of various cells in the immune system. Recent work in animal models indicates that the development of many human autoimmune diseases might be caused by impairment of the FcR regulatory system. This review provides an overview of the mechanisms of FcR-based immune regulation and describes how autoimmune disease might result from its dysfunction.
Synthesis and Characterization of a Cobalamin−Colchicine Conjugate as a Novel Tumor-Targeted Cytotoxin (2004)

Colchicine was derivatized at C7 with p-alkoxyacetophenone and conjugated to cobalamin (vitamin B(12)) through an acid-labile hydrazone linker. The cobalamin moiety leads to preferential uptake of the cobalamin-colchicine prodrug by cancer cells, whereupon the hydrazone linker undergoes hydrolysis in the lysosome to unmask colchicine, which acts as a potent cytotoxin by stabilizing microtubules and causing cell death. The bioconjugate is stable in cell culture media and at neutral pH but undergoes hydrolysis with a half-life of 138 min at pH 4.5. The colchicine-cobalamin bioconjugate exhibits nanomolar LC(50) values against breast, brain, and melanoma cancer cell lines in culture. Attachment of colchicine to cobalamin is expected to increase the therapeutic index of the drug by limiting the side effects caused by the current nonselective administration of tubulin-targeted chemotherapeutic drugs.
Optical Coherence Tomography: An Emerging Technology for Biomedical Imaging and Optical Biopsy (2000)

Optical coherence tomography (OCT) is an emerging technology for performing high-resolution cross-sectional imaging. OCT is analogous to ultrasound imaging, except that it uses light instead of sound. OCT can provide cross-sectional images of tissue structure on the micron scale in situ and in real time. Using OCT in combination with catheters and endoscopes enables high-resolution intraluminal imaging of organ systems. OCT can function as a type of optical biopsy and is a powerful imaging technology for medical diagnostics because unlike conventional histopathology which requires removal of a tissue specimen and processing for microscopic examination, OCT can provide images of tissue in situ and in real time. OCT can be used where standard excisional biopsy is hazardous or impossible, to reduce sampling errors associated with excisional biopsy, and to guide interventional procedures. In this paper, we review OCT technology and describe its potential biomedical and clinical applications.
Parkinson's disease: insights from pathways (2010)

Parkinson's disease (PD) typically presents in sporadic fashion, but the identification of disease-causing mutations in monogenically inherited PD genes has provided crucial insight into the pathogenesis of this disorder. Mutations in autosomal recessively inherited genes, namely parkin, PINK1 and DJ-1, typically lead to early onset parkinsonism. At least two of these genes (PINK1 and parkin) appear to work in the same pathway related to maintenance of mitochondrial functional integrity under conditions of oxidative stress. Dominantly inherited mutations in leucine-rich repeat kinase 2 (LRRK2) and alpha-synuclein cause late onset PD, generally with Lewy bodies that are characteristic of sporadic PD and there is evidence that these two genes are also in a common pathway. There is also growing evidence from recently undertaken genome-wide association studies that naturally occurring sequence variants in alpha-synuclein and LRRK2, but also Tau, also confer an increased risk for late onset, sporadic PD. Collectively, these results highlight how understanding pathways for inherited PD are starting to impact ideas about the pathogenesis, some of which may also be relevant to the commoner sporadic disease.
Glycoprotein Biomarker Panel for Pancreatic Cancer Discovered by Quantitative Proteomics Analysis (2014)

Pancreatic cancer is a lethal disease where specific early detection biomarkers would be very valuable to improve outcomes in patients. Many previous studies have compared biosamples from pancreatic cancer patients with healthy controls to find potential biomarkers. However, a range of related disease conditions can influence the performance of these putative biomarkers, including pancreatitis and diabetes. In this study, quantitative proteomics methods were applied to discover potential serum glycoprotein biomarkers that distinguish pancreatic cancer from other pancreas related conditions (diabetes, cyst, chronic pancreatitis, obstructive jaundice) and healthy controls. Aleuria aurantia lectin (AAL) was used to extract fucosylated glycoproteins and then both TMT protein-level labeling and label-free quantitative analysis were performed to analyze glycoprotein differences from 179 serum samples across the six different conditions. A total of 243 and 354 serum proteins were identified and quantified by label-free and TMT protein-level quantitative strategies, respectively. Nineteen and 25 proteins were found to show significant differences in samples between the pancreatic cancer and other conditions using the label-free and TMT strategies, respectively, with 7 proteins considered significant in both methods. Significantly different glycoproteins were further validated by lectin-ELISA and ELISA assays. Four candidates were identified as potential markers with profiles found to be highly complementary with CA 19-9 (p < 0.001). Obstructive jaundice (OJ) was found to have a significant impact on the performance of every marker protein, including CA 19-9. The combination of α-1-antichymotrypsin (AACT), thrombospondin-1 (THBS1), and haptoglobin (HPT) outperformed CA 19-9 in distinguishing pancreatic cancer from normal controls (AUC = 0.95), diabetes (AUC = 0.89), cyst (AUC = 0.82), and chronic pancreatitis (AUC = 0.90). A marker panel of AACT, THBS1, HPT, and CA 19-9 showed a high diagnostic potential in distinguishing pancreatic cancer from other conditions with OJ (AUC = 0.92) or without OJ (AUC = 0.95).
Functional Mixed Metal–Organic Frameworks with Metalloligands (2011)

Immobilization of functional sites within metal-organic frameworks (MOFs) is very important for their ability to recognize small molecules and thus for their functional properties. The metalloligand approach has enabled us to rationally immobilize a variety of different functional sites such as open metal sites, catalytic active metal sites, photoactive metal sites, chiral pore environments, and pores of tunable sizes and curvatures into mixed metal-organic frameworks (M'MOFs). In this Minireview, we highlight some important functional M'MOFs with metalloligands for gas storage and separation, enantioselective separation, heterogeneous asymmetric catalysis, sensing, and as photoactive and nanoscale drug delivery and biomedical imaging materials.
Measuring and Modeling of Human Soft Tissue and Seat Interaction (1997)

&lt;div class="htmlview paragraph"&gt;Deformations of soft tissues and seat cushion foam are significant factors in determining the interface contours between the seat and the back of the thigh. This paper describes the measurement of forces, deformations, and contours of people's thighs and seat cushion materials. The goal of this work is to represent the human interactions with seats. A two-dimensional, plane strain finite element method was used to develop a contact model between the cross section of the human mid-thigh and flat surfaces, which can be a flat, rigid surface or a flat, foam cushion of various thicknesses and densities. Results of human and seat interactions for various subjects were measured, modeled, and compared. The present work showed a good agreement between experiments and models for various subjects and foam densities. The important results showed that the stiffness of the foam does not depend on the foam thickness.&lt;/div&gt;
Structural aspects of platinum anticancer drug interactions with DNA (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructural aspects of platinum anticancer drug interactions with DNASuzanne E. Sherman and Stephen J. LippardCite this: Chem. Rev. 1987, 87, 5, 1153–1181Publication Date (Print):October 1, 1987Publication History Published online1 May 2002Published inissue 1 October 1987https://doi.org/10.1021/cr00081a013Request reuse permissionsArticle Views3046Altmetric-Citations800LEARN 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 InReddit PDF (5 MB) Get e-Alertsclose Get e-Alerts