gebhart/patrepeval huggingface dataset:
Expression of COX-2 and PGE synthase and synthesis of PGE2 in endometrial adenocarcinoma: a possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors (2001)

This study was designed to investigate the possible role of cyclo-oxygenase-2 (COX-2) and prostaglandin E(2)(PGE(2)) in endometrial adenocarcinoma. COX-2 RNA expression was confirmed in various grades of adenocarcinoma by ribonuclease protection assay. COX-2 and microsomal glutathione-dependent prostaglandin E synthase (mPGES) expression and PGE(2)synthesis were localised to the neoplastic epithelial cells and endothelial cells. In order to establish whether PGE(2)has an autocrine/paracrine effect in adenocarcinomas, we investigated the expression of 2 subtypes of PGE(2)receptors, namely EP2 and EP4, by real time quantitative PCR. Expression of EP2 and EP4 receptors was detected in adenocarcinomas from all grades of differentiation and was significantly higher than that detected in normal secretory phase endometrium (P< 0.01). The fold induction of expression in adenocarcinoma compared with normal secretory phase endometrium was 28.0 +/- 7.4 and 52.5 +/- 10.1 for EP2 and EP4 receptors respectively. Immunohistochemistry localised the site of expression of EP4 receptor in neoplastic epithelial cells and in the endothelium of carcinomas of all grades of differentiation. Finally, the functionality of the EP2/EP4 receptors was assessed by investigating cAMP generation following in vitro culture of adenocarcinoma tissue in the presence or absence of 300 nM PGE(2). cAMP production in response to PGE(2)was significantly higher in carcinoma tissue than that detected in normal secretory phase endometrium (3.42 +/- 0.46 vs 1.15 +/- 0.05 respectively; P< 0.001). In conclusion, these data suggest that PGE(2)may regulate neoplastic cell function in an autocrine/paracrine manner via the EP2/EP4 receptors.
Review article: prebiotics in the gastrointestinal tract (2006)

It is still early days for prebiotics, but they offer the potential to modify the gut microbial balance in such a way as to bring direct health benefits cheaply and safely.
Targeting tumor vasculature and cancer cells in orthotopic breast tumor by fractionated photosensitizer dosing photodynamic therapy. (2002)

Photodynamic therapy (PDT) is a locally administered therapy currently being investigated in various clinical and preclinical settings. Tumor-host interaction is an important determinant of tumor biology and response to treatments. Here we report for the first time the effects of PDT on an orthotopic, murine mammary tumor model. PDT utilizes two individually nontoxic components: (a) the localization in the target site of a photosensitizing drug; and (b) the activation of the photosensitizer by light of an appropriate wavelength and energy. PDT after a single dose of the photosensitizer MV6401 induced drug dose-dependent, long-term blood flow shut down and tumor growth delay in the MCaIV tumor, grown in the mammary fat pad. The plasma half-life of MV6401 was approximately 20 min, and the drug was confined to the vascular compartment shortly after administration. However, it accumulated in the interstitial compartment at 2-6 h after the administration. Two equal MV6401 doses injected 4 h and 15 min before the light administration allowed the photosensitizer to localize in both vascular and tumor cell compartments. The fractionated drug dose PDT more effectively induced tumor growth delay than the same total dose given as a single dose either at 4 h or at 15 min before light administration. The long-term effect of the fractionated drug PDT on blood flow was also more extensive than single-dose PDT. Fractionated photosensitizer dosing PDT offers a new strategy to optimize PDT therapy.
Female Sexual Dysfunction and Hormonal Status in Multiple Sclerosis Patients (2011)

Many factors have been suggested to contribute to sexual dysfunction (SD) in multiple sclerosis (MS) patients, but the research on their impact on sexual functioning (SF) and sexual quality of life (SQoL) remains scant.The aim of this study was to investigate correlates of SF and SQoL in MS patients, as well as possible gender differences.204 MS patients were interviewed, completed the questionnaires, and underwent neurological assessment.Primary outcome measures included the International Index of Erectile Function, the Female Sexual Function Questionnaire, the Sexual Quality of Life Questionnaire, the Beck Depression Inventory, and the Expanded Disability Status Scale.The course and duration of the disease did not predict patients' SF. Negative correlations were found for brainstem symptoms with orgasmic function and overall satisfaction in men and between cognitive functioning and the partner domain in women. Interestingly, brainstem symptoms correlated positively with the arousal domain in women. More than half (52.1%) of patients fulfilled Beck Depression Inventory criteria for depression, and these patients showed more SD than nondepressive individuals. The strongest negative correlations with depressive symptoms were found for desire, erectile function, and overall satisfaction with sexual life in men and for orgasm and sexual enjoyment in women. Deterioration in particular domains of SF was clearly related with diminished SQoL. The main gender difference was a strong influence of decreased desire on SQoL in women and no such correlation in men. Negative assessment of the relationship with partner significantly affected all domains of SF and SQoL in MS women and the desire domain in MS men.Several correlates of SF in MS patients were found. The role of brainstem symptoms needs further investigation. Clinicians should pay close attention to depressive symptoms and relationship factors in MS patients who suffer from SD. Lew‐Starowicz M and Rola R. Correlates of sexual function in male and female patients with multiple sclerosis. J Sex Med 2014;11:2172–2180.
The Masking Game: Design of Activatable Antibodies and Mimetics for Selective Therapeutics and Cell Control (2021)

The high selectivity and affinity of antibody binding have made antibodies all-pervasive tools in therapy, diagnosis, and basic science. A plethora of chemogenetic approaches has been devised to make antibodies responsive to stimuli ranging from light to enzymatic activity, temperature, pH, ions, and effector molecules. Within a single decade, the field of activatable antibodies has yielded marketed therapeutics capable of engaging antigens that could not be targeted with traditional antibodies, as well as new tools to control intracellular protein location and investigate biological processes. Many opportunities remain untapped, waiting for more efficient and generally applicable masking strategies to be developed at the interface between chemistry and biotechnology.
A Cancer Vaccine Induces Expansion of NY-ESO-1-Specific Regulatory T Cells in Patients with Advanced Melanoma (2012)

Cancer vaccines are designed to expand tumor antigen-specific T cells with effector function. However, they may also inadvertently expand regulatory T cells (Treg), which could seriously hamper clinical efficacy. To address this possibility, we developed a novel assay to detect antigen-specific Treg based on down-regulation of surface CD3 following TCR engagement, and used this approach to screen for Treg specific to the NY-ESO-1 tumor antigen in melanoma patients treated with the NY-ESO-1/ISCOMATRIX™ cancer vaccine. All patients tested had Treg (CD25(bright) FoxP3(+) CD127(neg)) specific for at least one NY-ESO-1 epitope in the blood. Strikingly, comparison with pre-treatment samples revealed that many of these responses were induced or boosted by vaccination. The most frequently detected response was toward the HLA-DP4-restricted NY-ESO-1(157-170) epitope, which is also recognized by effector T cells. Notably, functional Treg specific for an HLA-DR-restricted epitope within the NY-ESO-1(115-132) peptide were also identified at high frequency in tumor tissue, suggesting that NY-ESO-1-specific Treg may suppress local anti-tumor immune responses. Together, our data provide compelling evidence for the ability of a cancer vaccine to expand tumor antigen-specific Treg in the setting of advanced cancer, a finding which should be given serious consideration in the design of future cancer vaccine clinical trials.
Emergent behavior of regional heterogeneity in the lung and its effects on respiratory impedance (2011)

The ability to maintain adequate gas exchange depends on the relatively homogeneous distribution of inhaled gas throughout the lung. Structural alterations associated with many respiratory diseases may significantly depress this function during tidal breathing. These alterations frequently occur in a heterogeneous manner due to complex, emergent interactions among the many constitutive elements of the airways and parenchyma, resulting in unique signature changes in the mechanical impedance spectrum of the lungs and total respiratory system as measured by forced oscillations techniques (FOT). When such impedance spectra are characterized by appropriate inverse models, one may obtain functional insight into derangements in global respiratory mechanics. In this review, we provide an overview of the impact of structural heterogeneity with respect to dynamic lung function. Recent studies linking functional impedance measurements to the structural heterogeneity observed in acute lung injury, asthma, and chronic obstructive pulmonary disease are highlighted, as well as current approaches for the modeling and interpretation of impedance. Finally, we discuss the potential diagnostic role of FOT in the context of therapeutic interventions.
Enzymatic characterization of beta-D-galactoside alpha 2,3-trans-sialidase from Trypanosoma cruzi (1993)

The substrate specificity, physico-chemical, and kinetic properties of the trans-sialidase from Trypanosoma cruzi have been investigated. The enzyme demonstrates activity towards a wide range of saccharide, glycolipid, and glycoprotein acceptors which terminate with a beta-linked galactose residue, and synthesizes exclusively an alpha 2-3 sialosidic linkage. Oligosaccharides which terminate in Gal beta 1-4(Fuc alpha 1-3)GlcNAc, Gal beta 1-3(Fuc alpha 1-4)GlcNAc, or Gal alpha 1- are not acceptor-substrates. The enzyme utilizes alpha 2,3-linked sialic acid when the donor species is an oligosaccharide and can also transfer, at a low rate, sialic acid from synthetic alpha-sialosides such as p-nitrophenyl-alpha-N-acetylneuraminic acid, but NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)Glc is not a donor-substrate. The trans-sialidase has an apparent pH optimum of 7.9 and a temperature optimum of 13 degrees C. The kinetic properties of the enzyme suggest that the trans-sialylation reaction may occur via a rapid equilibrium random or steady-state ordered mechanism. A method for immobilizing the enzyme is described together with examples of its use for the synthesis of oligosaccharide and glycoprotein precursors of sialyl-Lewis and sialyl-Lewis.
EKG Guided Placement of Subclavian CVP Catheters Using J-Wire (1986)

In an attempt to improve the accuracy of central venous pressure (CVP) catheter tip location, 84 consecutive cardiac surgery patients in sinus rhythm were studied prospectively with respect to subclavian insertion of a CVP catheter using a guidewire technique. The presence of cardiac arrhythmia was used as an index of right atrial (RA) location of the guidewire tip, before threading the catheter over the guidewire. Correct catheter tip location (superior vena cava [SVC] or RA) was achieved in 100% of patients (N = 78) with premature atrial contractions (PACs) related to guidewire insertion. This fell to 50% (N = 4) if no arrhythmias were noted from the guidewire. Ventricular arrhythmias were noted in two of 84 patients (2.4%). Other problems related to the use of this technique are discussed.
Poly(ortho esters)From Concept to Reality (2004)

The development of poly(ortho esters) dates back to the early 1970s, and during that time, four distinct families were developed. These polymers can be prepared by a transesterification reaction or by the addition of polyols to diketene acetals, and it is the latter method that has proven to be preferred one. The latest polymer, now under intense development, incorporates a latent acid segment in the polymer backbone that takes advantage of the acid-labile nature of the ortho ester linkages and allows control over erosion rates. By use of diols having selected chain flexibility, polymers that range from hard, brittle materials to materials that have a gel-like consistency at room temperature can be obtained. Drug release from solid materials will be illustrated with 5-fluorouacil and bovine serum albumin, and drug release from gel-like materials will be illustrated with mepivacaine, now in Phase II clinical trials as a delivery system to treat post-operative pain. A brief summary of preclinical toxicology studies is also presented.
Clostridium difficile colitis associated with chronic renal failure (1998)

CDAD carries a high mortality in nephrology patients, especially those with established CRF. The diagnosis may be missed if a careful antibiotic history is not taken, including agents received prior to admission. Rational antibiotic prescribing and adherence to infection control measures are vital to reduce the incidence of this serious condition.
Branching morphogenesis independent of mesenchymal–epithelial contact in the developing kidney (1999)

Whether mesenchymal-epithelial interactions leading to branching morphogenesis in developing epithelial tissues such as the kidney require direct cell-cell contact or are due to soluble mediators elaborated by the inducing tissue has been the subject of much debate. Here we demonstrate that ureteric bud (UB) epithelium, from which the kidney collecting system and upper urinary tract are derived, can undergo impressive three-dimensional branching morphogenesis when cultured in the appropriate extracellular matrix context in the absence of direct contact with mesenchymal tissue, indicating that the program for branching morphogenesis is inherent to the UB. Both a soluble factor in BSN cell-conditioned medium (BSN-CM) derived from an immortalized cell line thought to originate in the early metanephric mesenchyme and glial cell line-derived neurotrophic factor (GDNF) were required for early and later events in branching morphogenesis. In the absence of BSN-CM, the isolated UB did not survive; a similar result was obtained in the presence of neutralizing antibodies against glial cell line-derived neurotrophic factor. Preliminary analysis of key activity present in BSN-CM indicates that it is a heat-sensitive, heparin-binding factor with a probable molecular mass greater than 100 kDa. When the in vitro cultured UB was recombined with freshly isolated metanephric mesenchyme, nephric units were induced in the mesenchyme, and the UB branches underwent elongation. Our data suggest that, although UB branching morphogenesis per se does not require direct mesenchymal contact, such contact may play a key role in regulating branch elongation and establishing the pattern of branching. The results also suggest an approach to in vitro engineering of nephron.
Time Reversal Imaging by Adaptive Interference Canceling (2007)

We develop the time reversal adaptive interference canceler (TRAIC) time reversal beamformer (TRBF), a new algorithm to detect and locate targets in rich scattering environments. It utilizes time reversal in two stages: (1) Anti-focusing: TRAIC time reverses and then reshapes the clutter backscatter to mitigate the clutter response; (2) Focusing: TRBF time reverses the residual backscatter to focus the radar image on the target. Laboratory experiments with electromagnetic radar data in a highly cluttered environment confirm the superiority of TRAIC-TRBF over conventional direct subtraction (DS) beamform imaging.
Defining the nociceptive flexion reflex (NFR) threshold in human participants: A comparison of different scoring criteria (2006)

Despite the widespread use of the nociceptive flexion reflex (NFR) paradigm in clinical and experimental pain research, there is currently no consensus on how best to define NFR threshold. Accordingly, the present studies were designed to assess the accuracy and reliability of different NFR threshold scoring criteria. Study 1 compared 13 scoring criteria in their accuracy for identifying the presence of the NFR, then generated empirically derived cut-points for the best criteria, and examined the test-retest reliability of NFR thresholds derived from these cut-points. Study 2 evaluated the replicability of these findings in an independent sample. Results from the two studies suggested that standardized peak (NFR Interval Peak z score) and mean (NFR Interval z score) biceps femoris electromyogram (EMG) activity were accurate and reliable criteria for defining NFR threshold. Acknowledging that cut-points may need to be adjusted for different research designs, graphs depicting sensitivity and specificity across a range of cut-points have been provided to facilitate researcher's decision-making. It is hoped that the results of these studies will promote a standard NFR threshold assessment methodology, and further encourage the application of the NFR paradigm in the investigation of mechanisms and characteristics of both painful and non-painful diseases.
The chemokine network in cancer - much more than directing cell movement (2004)

Cytokine and chemokine gradients are central to the directed movement of cells in both homeostatic and pathological processes. Most cancers have a complex chemokine network which can influence immune responses to the tumor, direct the extent and cellular composition of the leukocyte infiltrate and also play a role in angiogenesis. Tumor cells can also hijack the chemokine system and gain expression of certain chemokine receptors and respond to specific chemokine gradients. Chemokine receptor expression and activation on malignant cells may be central to the growth, survival and migration of cancer cells from the primary tumor. Chemokine receptors, both CC and CXC have been detected on malignant cells and the relevant ligands are sometimes expressed at the tumor site and at sites of tumor spread, suggesting a role for the chemokine family in malignant growth and metastasis.
A comparative study of JPEG2000, AVC/H.264, and HD photo (2007)

In this paper, we report a study evaluating rate-distortion performance between JPEG 2000, AVC/H.264 High 4:4:4 Intra and HD Photo. A set of ten high definition color images with different spatial resolutions has been used. Both the PSNR and the perceptual MSSIM index were considered as distortion metrics. Results show that, for the material used to carry out the experiments, the overall performance, in terms of compression efficiency, are quite comparable for the three coding approaches, within an average range of ±10% in bitrate variations, and outperforming the conventional JPEG.
MBE‐VLS growth of GaAs nanowires on (111)Si substrate (2008)

Abstract The growth of a GaAs nanowire was attempted on a (111)Si substrate by molecular beam epitaxy adopting the vapour‐liquid‐solid method with Au colloids as the catalysts. The shape of the nanowire was of a hexagonal column of about 3 μm long. The growth rate of the wire was extremely high as compared to the previous reports. The diameter near the bottom of the wire was not equal to but larger than that measured at the top of the wire, which is attributed to the diffusion of the Ga precursors on the wire wall. It was found that the shape as well as size of the wire was sensitive to the growth conditions, and a long and thin nanowire was achieved at high V/III ratios. (© 2008 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Rotation–vibration spectra of icosahedral molecules. I. Icosahedral symmetry analysis and fine structure (1989)

Icosahedral symmetry analysis is developed for analyzing eigensolutions of rovibrational tensor Hamiltonians for molecules such as B12H12−2, C20H20, and C60. Simplified asymptotic formulas and procedures are developed for obtaining rotational spectral fine structure for high angular momentum. J=100 eigenlevels for sixth- and tenth-rank icosahedral tensors are discussed using different approximations and visualization schemes.
Neuronal uptake of tau/pS422 antibody and reduced progression of tau pathology in a mouse model of Alzheimer‘s disease (2014)

The severity of tau pathology in Alzheimer's disease brain correlates closely with disease progression. Tau immunotherapy has therefore been proposed as a new therapeutic approach to Alzheimer's disease and encouraging results have been obtained by active or passive immunization of tau transgenic mice. This work investigates the mechanism by which immunotherapy can impact tau pathology. We demonstrate the development of Alzheimer's disease-like tau pathology in a triple transgenic mouse model of Alzheimer's disease and show that tau/pS422 is present in membrane microdomains on the neuronal cell surface. Chronic, peripheral administration of anti-tau/pS422 antibody reduces the accumulation of tau pathology. The unequivocal presence of anti-tau/pS422 antibody inside neurons and in lysosomes is demonstrated. We propose that anti-tau/pS422 antibody binds to membrane-associated tau/pS422 and that the antigen-antibody complexes are cleared intracellularly, thereby offering one explanation for how tau immunotherapy can ameliorate neuronal tau pathology.
Methanocarba ring as a ribose modification in ligands of G protein-coupled purine and pyrimidine receptors: synthetic approaches (2012)

Adenosine receptors (ARs) and P2Y receptors for purine and pyrimidine nucleotides have widespread distribution and regulate countless physiological processes. Various synthetic ligands are in clinical trials for treatment of inflammatory diseases, pain, cancer, thrombosis, ischemia, and other conditions. The methanocarba (bicyclo[3.1.0]hexane) ring system as a rigid substitution for ribose, which maintains either a North (N) or South (S) conformation, tends to preserve or enhance the potency and/or selectivity for certain receptor subtypes. This review summarizes recent developments in the synthetic approaches to these biologically important nucleoside and nucleotide analogues.
In vivo and in vitro growth-inhibitory effect of bovine seminal ribonuclease on a system of rat thyroid epithelial transformed cells and tumors. (1992)

We investigated the antitumoral effect of bovine seminal RNase (BS-RNase) in vivo and in vitro on a model system of epithelial tumor- and metastasis-derived cells as well as on epithelial tumors derived from the same system. We found that while BS-RNase significantly inhibited the growth in vitro of the epithelial tumor-derived cells, its inhibitory effect was even more dramatic on the growth of metastasis-derived cells. BS-RNase exerted no appreciable growth inhibition on normal thyroid epithelial cells. When administered in vivo to rats bearing solid carcinomas, having the same thyroid origin, BS-RNase induced a drastic reduction in the tumor weight, with no detectable toxic effects on the treated animals. These data show, for the first time on a system of neoplastically transformed epithelial cells, that BS-RNase has a potent specific antitumoral activity.
Clue cells in predicting infections after abdominal hysterectomy. (1991)

Seventy women scheduled for abdominal hysterectomy were examined for the presence of clue cells in the vaginal discharge in an attempt to identify a possible risk group for development of postoperative infection. Seven of 20 women (35%) with clue cells developed vaginal cuff infections or wound infections, compared with four of 50 women (8%) without clue cells (P less than .01). Women with bacterial vaginosis, diagnosed by air-dried vaginal smears, are therefore at risk for postoperative infection.