gebhart/patrepeval huggingface dataset:
The immune score as a new possible approach for the classification of cancer (2012)

The outcome prediction in cancer is usually achieved by evaluating tissue samples obtained during surgical removal of the primary tumor focusing on their histopathological characteristics. Tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N), and evidence for metastases (M). However, this classification provides limited prognostic information in estimating the outcome in cancer and does not predict response to therapy. It is recognized that cancer outcomes can vary significantly among patients within the same stage. Recently, many reports suggest that cancer development is controlled by the host's immune system underlying the importance of including immunological biomarkers for the prediction of prognosis and response to therapy. Data collected from large cohorts of human cancers demonstrated that the immune-classification has a prognostic value that may be superior to the AJCC/UICC TNM-classification. Thus, it is imperative to begin incorporating immune scoring as a prognostic factor and to introduce this parameter as a marker to classify cancers, as part of the routine diagnostic and prognostic assessment of tumors. At the same time, the inherent complexity of quantitative immunohistochemistry, in conjunction with variable assay protocols across laboratories, the different immune cell types analyzed, different region selection criteria, and variable ways to quantify immune infiltration underscore the urgent need to reach assay harmonization. In an effort to promote the immunoscore in routine clinical settings worldwide, the Society for Immunotherapy of Cancer (SITC), the European Academy of Tumor Immunology, the Cancer and Inflammation Program, the National Cancer Institute, National Institutes of Health, USA and "La Fondazione Melanoma" will jointly initiate a task force on Immunoscoring as a New Possible Approach for the Classification of Cancer that will take place in Naples, Italy, February 13th, 2012. The expected outcome will include a concept manuscript that will be distributed to all interested participants for their contribution before publication outlining the goal and strategy to achieve this effort; a preliminary summary to be presented during the "Workshop on Tumor Microenvironment" prior to the SITC annual meeting on October 24th - 25th 2012 in Bethesda, Maryland, USA and finally a "Workshop on Immune Scoring" to be held in Naples in December of 2012 leading to the preparation of a summary document providing recommendations for the harmonization and implementation of the Immune Score as a new component for the classification of cancer.
Carbonic Anhydrase Inhibitors: Inhibition of Isozymes I, II And IV with Heterocyclic Mercaptans, Sulfenamides, Sulfonamides and their Metal Complexes (1998)

A series of sulfenamides, sulfonamides and sulfonamide metal complexes have been prepared starting from 4,5-disubstituted-3-mercapto-1,2,4-triazole derivatives. The heterocyclic mercaptans were oxidized to the corresponding sulfenamides by hypochlorite in the presence of ammonia. The sulfonamides were obtained by oxidation of sulfenamides with potassium permanganate. The Zn(II) and Cu(II) complexes of the new heterocyclic sulfonamides have been prepared via the sodium salt of the ligand. Inhibition of three carbonic anhydrase (CA) isozymes, hCA I, hCA II and bCA IV (h = human, b = bovine) with the prepared compounds has been investigated. Mercaptans were generally less inhibitory than sulfenamides, which in turn behaved as weaker inhibitors than the sulfonamides. The strongest inhibitors were the Zn(II) and Cu(II) complexes of the heterocyclic sulfonamides. Susceptibility to inhibition was generally: hCA II > bCA IV > hCA I. Although none of the obtained simple inhibitors (mercaptans, sulfenamides, sulfonamides) possessed antiglaucoma action when administered directly into the eye in experimental animals, the Zn(II) and Cu(II) complexes of some sulfonamides acted as more efficient intraocular pressure lowering agents as compared to the clinical drug dorzolamide. This constitutes an encouraging result for obtaining novel antiglaucoma drugs from this class of CA inhibitors.
Evasion of Early Cellular Response Mechanisms following Low Level Radiation-induced DNA Damage (2004)

DNA damage that is not repaired with high fidelity can lead to chromosomal aberrations or mitotic cell death. To date, it is unclear what factors control the ultimate fate of a cell receiving low levels of DNA damage (i.e. survival at the risk of increased mutation or cell death). We investigated whether DNA damage could be introduced into human cells at a level and frequency that could evade detection by cellular sensors of DNA damage. To achieve this, we exposed cells to equivalent doses of ionizing radiation delivered at either a high dose rate (HDR) or a continuous low dose rate (LDR). We observed reduced activation of the DNA damage sensor ataxia-telangiectasia mutated (ATM) and its downstream target histone H2A variant (H2AX) following LDR compared with HDR exposures in both cancerous and normal human cells. This lack of DNA damage signaling was associated with increased amounts of cell killing following LDR exposures. Increased killing by LDR radiation has been previously termed the "inverse dose rate effect," an effect for which no clear molecular processes have been described. These LDR effects could be abrogated by the preactivation of ATM or simulated in HDR-treated cells by inhibiting ATM function. These data are the first to demonstrate that DNA damage introduced at a reduced rate does not activate the DNA damage sensor ATM and that failure to activate ATM-associated repair pathways contributes to the increased lethality of continuous LDR radiation exposures. This inactivation may reflect one strategy by which cells avoid accumulating mutations as a result of error-prone DNA repair and may have a broad range of implications for carcinogenesis and, potentially, the clinical treatment of solid tumors.
Correspondence re: B. H. Joshi et al., interleukin-13 receptor alpha chain: a novel tumor-associated transmembrane protein in primary explants of human malignant gliomas. Cancer Res., 60: 1168-1172, 2000. (2001)

I would like to address several issues with regard to an article by Joshi et al. [(1)][1] published recently in Cancer Research: ( a ) the report cites the number of normal brain tissues evaluated for the capacity to bind radiolabeled IL [1][2] -13 as assessed by autoradiography in error. Our group
Telomerase activity in normal and malignant hematopoietic cells. (1995)

Bone marrow and peripheral blood leukocytes from 19 leukemia patients were found to contain telomerase activity detectable by a PCR-based assay. Telomerase was also detectable in nonmalignant bone marrow and peripheral blood leukocytes from normal donors, including fractions enriched for granulocytes, T lymphocytes, and monocytes/B cells. Semiquantitative comparison revealed considerable overlap between telomerase activities in samples from normal subjects and leukemia patients, confounding evaluation of the role of telomerase in this disease. These data indicate that human telomerase is not restricted to immortal cells and suggest that the somatic expression of this enzyme may be more widespread than was previously inferred from the decline of human telomeres.
Immunomodulation by neutrophil myeloperoxidase and hydrogen peroxide: differential susceptibility of human lymphocyte functions. (1986)

The coexistence of activated polymorphonuclear leukocytes and lymphocytes in tumor masses and inflammatory tissues suggests the possibility of interaction between secreted neutrophil products and nearby lymphocytes. To test this hypothesis, we examined the effects of neutrophil myeloperoxidase and H2O2 on lymphocytes. Human peripheral blood mononuclear leukocytes were exposed to myeloperoxidase, an H2O2-generating system (glucose + glucose oxidase), and a halide, and were then tested for functional activities. Natural killer activity against K562 cells, lymphocyte proliferation in response to mitogens, and generation of immunoglobulin-secreting cells were all susceptible to oxidative injury by myeloperoxidase and H2O2. The degree as well as the mechanism of suppression was dependent on the glucose oxidase concentration (i.e., the rate of H2O2 delivery). At low H2O2 flux, myeloperoxidase was essential for induction of lymphocyte suppression; as the rate of H2O2 generation increased, suppression became myeloperoxidase-independent and was mediated by H2O2 alone. Various lymphocyte functions were differentially susceptible to oxidative injury by myeloperoxidase and H2O2. The proliferative response to poke-weed mitogen was the least sensitive, whereas antibody formation was the most sensitive. Proliferative responses to concanavalin A and phytohemagglutinin as well as natural killer activity displayed intermediate degrees of susceptibility. In all assays, lymphocyte viability was greater than 90%. Removal of monocytes from mononuclear leukocytes by adherence to glass increased susceptibility of lymphocytes to oxidative injury. Monocytes in proportions within the range present in peripheral blood mononuclear leukocytes protected lymphocyte functions against oxidative injury by myeloperoxidase and H2O2. This study demonstrates a differential susceptibility of various immune functions to oxidative injury by the neutrophil products myeloperoxidase and H2O2, and shows, in addition, that monocytes can modulate these interactions.
Mapping of the C3d receptor (CR2)-binding site and a neoantigenic site in the C3d domain of the third component of complement. (1985)

The C3d domain of C3 contains the site that binds to the C3d receptor (CR2) which is expressed on B lymphocytes. It also contains a neoantigenic determinant that is recognized by monoclonal antibody (mAb) 130 and is expressed when C3b is cleaved to iC3b and subsequently to C3dg or C3d. mAb 130 inhibits the binding of C3d to CR2. In this study, the locations of the CR2-binding site and of the neoantigen recognized by mAb 130 within the C3d domain were investigated. Treatment of human C3d with CNBr generated two major fragments with Mrs of 12,500 and 8600. Binding studies showed that only the Mr 8600 fragment was capable of binding to both CR2 and mAb 130. Amino-terminal sequence analysis of the Mr 8600 fragment and comparison with the amino acid sequence derived from human C3 cDNA [de Bruijn, M. H. L. & Fey, G. H. (1985) Proc. Natl. Acad. Sci. USA 82, 708-712] placed it between residues 1199 and 1274 of the C3 sequence. Several peptides were synthesized according to the derived C3 sequence of amino acid residues 1209-1236. Based on their differential binding to CR2 and mAb 130, we localized the CR2-binding site and mAb 130 neoantigenic site, respectively, to residues 1227-1232 and 1217-1232 of the C3 sequence.
Nanoscale Drug Delivery Systems for Enhanced Drug Penetration into Solid Tumors: Current Progress and Opportunities (2012)

Poor penetration of anticancer drags into solid tumors significantly limits their efficacy. This phenomenon has long been observed for small-molecule chemotherapeutics, and it can be even more pronounced for nanoscale therapies. Nanoparticles have enormous potential for the treatment of cancer due to their wide applicability as drug delivery and imaging vehicles and their size-dependent accumulation into solid tumors by the enhanced permeability and retention (EPR) effect. Further, synthetic nanoparticles can be engineered to overcome barriers to drag delivery. Despite their promise for the treatment of cancer, relatively little work has been done to study and improve their ability to diffuse into solid tumors following passive accumulation in the tumor vasculature. In this review, we present the complex issues governing efficient penetration of nanoscale therapies into solid tumors. The current methods available to researchers to study nanoparticle penetration into malignant tumors are described, and the most recent works studying the penetration of nanoscale materials into solid tumors are summarized. We conclude with an overview of the important nanoparticle design parameters governing their tumor penetration, as well as by highlighting critical directions in this field.
Childhood Sexual Abuse, Body Image, and Disordered Eating: A Structural Modeling Analysis (2003)

ABSTRACT Based on previous literature, we proposed and tested a model of the relationships between child sexual abuse (CSA), body image, dieting, and bulimic behavior. The model specified that body image functioned as a mediator between CSA and eating disturbance. Multiple measures of each of the constructs of interest were collected from a sample of 222 college age women, and the data were analyzed using structural equation modeling. Both the measurement model and the proposed structural model demonstrated an adequate fit. As with previous research, results support a model in which body image strongly affects dieting behavior, which in turn directly affects bulimic behavior. The results did not appear to support the proposed mediational model involving the hypothesized indirect effect of CSA on eating pathology. There was, however, a small direct relationship between CSA and bulimic behavior and a moderate relationship between CSA and posttraumatic symptomatology.
Theory and design of high order sound field microphones using spherical microphone array (2002)

A major problem in sound field reconstruction systems is how to record the higher order (> 1) harmonic components of a given sound field. Spherical harmonics analysis is used to establish theory and design of a higher order recording system, which comprises an array of small microphones arranged in a spherical configuration and associated signal processing. This result has implications to the advancement of future sound field reconstruction systems. An example of a third order system for operation over a 10∶1 frequency range of 340 Hz to 3.4 kHz is given.
Booster vaccination against pertussis in Chinese children at six years of age using reduced antigen content diphtheria-tetanus-acellular pertussis vaccine (Boostrix™) (2010)

Pertussis continues to circulate in Chinese communities and older children, adolescents and adults are sources of infection for unprotected infants. Two studies conducted in Jiangsu Province in the People's Republic of China assessed the immunogenicity, reactogenicity and safety of Boostrix(), a combined reduced antigen content diphtheria-tetanus-acellular pertussis vaccine (dTpa) when administered as a booster dose to children 6 to 8 years of age. Immunogenicity was assessed before and one month after vaccination in a subset. Reactogenicity was assessed over a 4-day follow-up using diary cards. A total of 690 Chinese subjects were enrolled. Boostrix() was well tolerated. One month after the booster dose, 100% of dTpa recipients had seroprotective antibody concentrations against diphtheria and tetanus. The percentage of subjects with a response against pertussis antigens (using locally defined cut-offs) was 91.9% for pertussis toxoid, 98.8% for filamentous hemagglutinin, and 100% for pertactin. The exploratory analysis showed no statistically significant differences between dTpa or diphtheria-tetanus vaccine in terms of the percentage of subjects with seroprotective antibodies against diphtheria or tetanus. These studies demonstrate that Boostrix() is well tolerated and immunogenic when administered as a booster dose to 6 to 8 year old Chinese children previously immunized with a combined diphtheria-tetanus-pertussis vaccine. Introduction of dTpa into the routine Chinese immunization schedule would provide booster vaccination against pertussis without the addition of further injections into the Chinese vaccination schedule and is likely to promote improved pertussis control in older children.
A New Rigorous Approach for Modelling and Refining Concurrent Behaviour in JSD Specifications. (1992)

Reevaluation of routine exchange nailing as the recommended treatment for aseptic femoral delayed union or nonunion may be required. A significant number of patients who undergo reamed exchange nailing will require additional procedures to achieve fracture healing.
In Vivo Endoscopic Optical Coherence Tomography of the Human Gastrointestinal Tract - Toward Optical Biopsy (2000)

The newly developed portable OCT equipment and flexible fiberoptic probe makes OCT a promising method for endoscopic "optical biopsy".
Marked Interspecies Variations Concerning the Interactions of Camptothecin with Serum Albumins: A Frequency-Domain Fluorescence Spectroscopic Study (1994)

Camptothecin, an anticancer agent reknown for its novel mechanism of action and outstanding murine in vivo activity, has to date displayed only modest therapeutic utility against human cancers. The drug contains an delta-lactone ring moiety which, at pH7.4, hydrolyzes to yield a biologically inactive carboxylate form. Comparison of drug stability in both plasma and purified serum albumin samples revealed that ring opening occurred to a much greater extent in human samples versus those of other species. Multifrequency phase-modulation spectroscopic analyses of the intrinsic fluorescence emissions of the two drug forms revealed a physical explanation for the extensive ring opening observed in the presence of human serum albumin (HSA): the protein exhibited a marked 200-fold binding preference for the carboxylate (K = 1.2 x 10(6) M-1) relative to the lactone (K approximately 5.5 x 10(3) M-1). Serum albumins from other species were found to bind camptothecin carboxylate not nearly as tightly as HSA. Due to the unique capacity of human albumin to bind camptothecin carboxylate, resulting in extensive conversion of the drug to its biologically inactive form, it appears that the success of the agent in eradicating cancer in animal models may be inherently more difficult to duplicate in man.
Patch clamp recording of the responses to three bitter stimuli in mouse taste cells. (1999)

Although several pathways of bitter taste signal transduction have been proposed in taste cells, these mechanisms have not been elucidated in detail. To investigate the diversity of responses to bitter stimuli, we recorded the electrophysiological responses to quinine, denatonium and naringin using whole-cell patch clamp technique in isolated taste cells of C57BL/6J mice. Ten mM quinine induced depolarizing response under the current clamp mode, and inward current response under the voltage-clamp mode (holding potential -80 mV) using both K+ (with pseudo intracellular solution) and Cs+ (K+ was substituted by Cs+ in the pseudo intracellular solution) pipettes. However, when the K+ pipette was used, the membrane conductance was suppressed and activated in succession. On the other hand, the membrane conductance was only activated when the Cs+ pipette was used. Half to one mM denatonium induced depolarizing response under the current clamp mode, and outward current response under the voltage clamp mode with both pipettes. Using these pipettes, the membrane conductance was activated or suppressed in the individual case. Naringin-induced responses were not detected in these measurements. These electrophysiological recordings suggest that multiple transduction mechanisms are involved in bitter taste perception in mouse taste cells.
Three-Dimensional Display Of Nuclear Magnetic Resonance Images (1982)

We report on the results of a collaboration between two independent research projects. In one, we have been developing a software system for the detection and display of surfaces of organs and organ systems from three-dimensional reconstructions; in the other, we have been developing hardware and software for the three-dimensional reconstruction of objects using nuclear magnetic resonance zeugmatographic imaging. The merging of these two modalities gives us a truly powerful tool for three-dimensional visualization. This is demonstrated by frames from movies illustrating the external and internal three-dimensional structure of organs, such as the brain and the heart, produced by applying the display programs to the nuclear magnetic resonance reconstructions.
Correlations of Inflammatory Biomarkers With the Onset and Prognosis of Idiopathic Sudden Sensorineural Hearing Loss (2012)

Neutrophil counts above the reference range of a facility will be a useful indicator of poor prognosis of ISHL. Synchronism of different types of NF-κB activation pathways could be required to cause severe ISHL. An NKCA decrease, an acute neutrophil count increase, and an IL-6 increase can induce NF-κB activation in the cochlea and cause severe ISHL. Further epidemiologic surveys should be conducted to evaluate whether stressful life events increase the risk of severe ISHL onset.
Laboratory Synthesis and Characterization of Megamers: Core‐Shell Tecto(dendrimers) (2001)

This chapter has sections titled: Introduction General Comments Self-Assembly/Covalent Bond Formation Method Direct Covalent Bond Formation Method References
A randomised comparison of medical and hysteroscopic management in women consulting a gynaecologist for treatment of heavy menstrual loss (1997)

Medical treatment was less effective than transcervical resection of the endometrium, irrespective of previous treatment or type of medical management. Early hysteroscopic endometrial surgery should be considered by such woman with the choice made by the woman after a full discussion of the advantages and disadvantages of all the options.
Carbohydrate Arrays for Functional Studies of Carbohydrates (2004)

Carbohydrates, as components of glycoproteins, glycolipids and proteoglycans, play an important biological role as recognition markers through carbohydrate-protein interactions. For the most part, biophysical and biochemical methods have been used to analyze these biomolecular interactions. In contrast, less attention has been given to the development of high-throughput procedures to elucidate carbohydrate-protein recognition events. Recently, carbohydrate arrays were developed and employed as a novel high-throughput analytic tool for monitoring carbohydrate-protein interactions. This technique has been used to profile protein binding and enzymatic activity. The results have shown that carbohydrate binding to the corresponding lectins is highly selective and that the relative binding affinities are well correlated with those obtained from solution-based assays. In addition, this effort demonstrated that carbohydrate arrays could be also utilized to identify and characterize novel carbohydrate-binding proteins or carbohydrate-processing enzymes. Finally, the results of this investigation showed that lectin-carbohydrate binding affinities could be quantitatively assessed by determining IC50 values for soluble carbohydrates with the carbohydrate arrays. The results of these studies suggest that carbohydrate arrays have the potential of playing an important role in basic researches, the diagnoses of diseases and drug discovery.