gebhart/patrepeval huggingface dataset:
Recombinant alpha-interferon enhances tumor targeting of an antimelanoma monoclonal antibody in vivo. (1990)

To determine whether recombinant human alpha-interferon (rIFN alpha A) could enhance tumor uptake of an antimelanoma monoclonal antibody (Mab) 96.5 in vivo, groups of nude mice bearing P97 antigen-positive human melanoma subcutaneous xenografts were given i.m. injections of normal saline or rIFN alpha A daily for 10 days. On day 7, mice received either 5 micrograms of 111In-labeled Mab 96.5 or irrelevant 111In-labeled subclass-matched or non-subclass-matched control Mabs. Animals were killed 72 h later and the percent injected dose per gram (%ID/g) in tumor and normal organs was determined. There was a significant (p less than 0.001) increase in 96.5 in tumors of IFN-treated mice compared to saline-treated mice and mice receiving irrelevant Mabs. There was also a significantly increased uptake of 96.5 in blood, heart, lung, kidney, and muscle of IFN-treated vs. control mice (p less than 0.05). This finding was most likely due to increased antigen shedding since significant differences in %ID/g were not observed between IFN-treated and control mice bearing antigen-negative tumors. Furthermore, P97 content in tumor and tissues of IFN-treated mice bearing melanoma xenografts was significantly higher than in mice without tumors. In summary, IFN enhanced targeting of 96.5 via an antigen-specific mechanism. These data confirm and extend previous studies in other tumor systems, and suggest that clinical trials of Mabs plus IFN might be useful in overcoming poor Mab localization that occurs as a result of antigenic heterogeneity in humans.
Effect of Probiotics on Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2016)

It has been reported that gut probiotics play a major role in the bidirectional communication between the gut and the brain. Probiotics may be essential to people with depression, which remains a global health challenge, as depression is a metabolic brain disorder. However, the efficacy of probiotics for depression is controversial. This study aimed to systematically review the existing evidence on the effect of probiotics-based interventions on depression. Randomized, controlled trials, identified through screening multiple databases and grey literature, were included in the meta-analysis. The meta-analysis was performed using Review Manager 5.3 software using a fixed-effects model. The meta-analysis showed that probiotics significantly decreased the depression scale score (MD (depressive disorder) = -0.30, 95% CI (-0.51--0.09), p = 0.005) in the subjects. Probiotics had an effect on both the healthy population (MD = -0.25, 95% CI (-0.47--0.03), p = 0.03) and patients with major depressive disorder (MDD) (MD = -0.73, 95% CI (-1.37--0.09), p = 0.03). Probiotics had an effect on the population aged under 60 (MD = -0.43, 95% CI (-0.72--0.13), p = 0.005), while it had no effect on people aged over 65 (MD = -0.18, 95% CI (-0.47-0.11), p = 0.22). This is the first systematic review and meta-analysis with the goal of determining the effect of probiotics on depression. We found that probiotics were associated with a significant reduction in depression, underscoring the need for additional research on this potential preventive strategy for depression.
Stereospecific method to (E) and (Z) terminal fluoroolefins and its application to the synthesis of 2'-deoxy-2'-fluoromethylenenucleosides as potential inhibitors of ribonucleoside diphosphate reductase (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereospecific method to (E) and (Z) terminal fluoroolefins and its application to the synthesis of 2'-deoxy-2'-fluoromethylenenucleosides as potential inhibitors of ribonucleoside diphosphate reductaseJames R. McCarthy, Donald P. Matthews, David M. Stemerick, Edward W. Huber, Philippe Bey, Bruce J. Lippert, Ronald D. Snyder, and Prasad S. SunkaraCite this: J. Am. Chem. Soc. 1991, 113, 19, 7439–7440Publication Date (Print):September 1, 1991Publication History Published online1 May 2002Published inissue 1 September 1991https://doi.org/10.1021/ja00019a061RIGHTS & PERMISSIONSArticle Views650Altmetric-Citations175LEARN 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 (302 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Mechanical Design and Analysis for a Scanning Fiber Endoscope (2001)

Abstract There is a need for smaller, more flexible, optical imaging tools for use in minimally invasive diagnostic and therapeutic procedures [1]. Towards this end, a novel technique of image acquisition has been developed based upon the controlled vibration of a waveguide and detection of light backscattered from the waveguide onto an object [2]. The anticipated result of this research is the creation of an optical scanner capable of operating at high frequency, with a large field-of-view (FOV) in a 1 mm diameter enclosure. The mechanics of this system have been explored for use in near-field scanning optical microscopy applications [3], and are now examined for use in a scanning fiber endoscope. Discussed in this report are the vibration characteristics of two possible waveguide geometries: a cylindrical and a tapered optical fiber.
Analysis of Immunological Nonresponsiveness to the 19-Kilodalton Fragment of Merozoite Surface Protein 1 ofPlasmodium yoelii: Rescue by Chemical Conjugation to Diphtheria Toxoid (DT) and Enhancement of Immunogenicity by Prior DT Vaccination (2003)

The Plasmodium merozoite surface protein 1 (MSP1) is a leading vaccine candidate for protecting against the blood stage of malaria. Previous studies have shown that the 19-kDa carboxyl terminus of this protein is able to induce protective immunity in some monkey and mouse strains. We show that immunization with the recombinant Plasmodium yoelii 19-kDa fragment of MSP1 (MSP1(19)) expressed in Saccharomyces cerevisiae (yMSP1(19)) can induce protective antibodies in several inbred mouse strains and one outbred mouse strain. However, mice expressing the H-2(s) major histocompatibility complex haplotype are unable to generate yMSP1(19)-specific antibodies. While synthetic peptides derived from MSP1(19) are immunogenic in B10.S mice, they cannot function as helper epitopes, and immunization with yMSP1(19) does not induce T cells that recognize the recombinant protein or synthetic peptides corresponding to its sequence. Nonresponsiveness could be overcome by using chemical linkers to conjugate yMSP1(19) to diphtheria toxoid (DT), resulting in immunogens capable of inducing protective yMSP1(19)-specific antibodies in both MSP1(19)-responsive and otherwise nonresponsive mouse strains. The ability of sera from mice immunized with the conjugate to inhibit binding of a protective monoclonal antibody (MAb 302) to yMSP1(19) correlated strongly with a delay in the prepatent period. Chemical conjugation of yMSP1(19) to DT may be a preferred method to enhance immunogenicity, as carrier priming experiments demonstrated that an existing immune response to DT enhanced a subsequent antibody response to yMSP1(19) after vaccination with yMSP1(19)-DT. These results have important implications for the development of a malaria vaccine to protect a population with diverse HLAs.
An Experimental Study Comparing Percutaneous Discectomy with Chemonucleolysis (1993)

The aim of this study was to assess the macroscopic and microscopic reaction of the intervertebral disc to discectomy with the Automated Nucleotome (Surgical Dynamics, San Leandro, CA), and to compare this with simple trephining of the annulus and with chemonucleolysis. In eight adult sheep, two of four adjacent lumbar discs were randomly incised using the trephine of the Automated Nucleotome, while the remaining levels underwent nuclear excision with the Automated Nucleotome probe. Another four sheep underwent chemonucleolysis at three adjacent lumbar levels. All animals were killed at 6 weeks. The discs that had undergone trephining alone and those treated with the Automated Nucleotome probe had almost identical radiographic and macroscopic changes and showed similarities on microscopic examination. Macroscopically, these discs did not differ from control levels, whereas those treated with chymopapain showed marked changes with a reduction of both nuclear and annular volume. The results of this study suggest that any therapeutic effect of percutaneous discectomy with the Automated Nucleotome is likely to be attributable to the perforation of the annulus alone with the removal of small amounts of nuclear material contributing little, or nothing, to the claimed benefits of the procedure.
A Review on Chemical-Induced Inflammatory Bowel Disease Models in Rodents (2014)

Ulcerative colitis and Crohn's disease are a set of chronic, idiopathic, immunological and relapsing inflammatory disorders of the gastrointestinal tract referred to as inflammatory bowel disorder (IBD). Although the etiological factors involved in the perpetuation of IBD remain uncertain, development of various animal models provides new insights to unveil the onset and the progression of IBD. Various chemical-induced colitis models are widely used on laboratory scale. Furthermore, these models closely mimic morphological, histopathological and symptomatical features of human IBD. Among the chemical-induced colitis models, trinitrobenzene sulfonic acid (TNBS)-induced colitis, oxazolone induced-colitis and dextran sulphate sodium (DSS)-induced colitis models are most widely used. TNBS elicits Th-1 driven immune response, whereas oxazolone predominantly exhibits immune response of Th-2 phenotype. DSS-induced colitis model also induces changes in Th-1/Th-2 cytokine profile. The present review discusses the methodology and rationale of using various chemical-induced colitis models for evaluating the pathogenesis of IBD.
The IL‐17 pathway as a major therapeutic target in autoimmune diseases (2010)

Th17 cells are a subset of T helper cells that have been recently found to play important functions in host defense and the pathogenesis of various human autoimmune and inflammatory diseases. Th17 cells produce IL-17A, IL-17F, IL-22, and IL-21, of which IL-17A and IL-17F mediate many of the downstream pathologic functions of these cells. IL-17A and IL-17F signal through IL-17RA and IL-17RC heterodimeric receptors that are mainly expressed on tissue epithelial cells and fibroblasts. While IL-17A and IL-17F are important for host defense against many extracellular pathogens, they can also cause excessive tissue damage and exacerbate proinflammatory responses during autoimmunity. The IL-17 pathway, therefore, is a primary therapeutic target downstream of Th17 cells.
Multi-core data streaming architecture for ray tracing (2007)

Ray tracing is a computer graphics technique to generate photo-realistic images. All though it can generate precise and realistic images, it requires a large amount of computation. The intersection test between rays and objects is one of the dominant factors of the ray tracing speed. We propose a new parallel processing architecture, named R PL S, for accelerating the ray tracing computation. R PL S boosts the speed of the intersection test by using a new algorithm based on ray-casting through planes, data streaming architecture offers highly efficient data provision in a multi-core environment. We estimate the performance of a future SoC implementation of R PL S by software simulation, and show 600 times speedup over a conventional CPU implementation.
Uses and Abuses of Tumor Markers in the Diagnosis, Monitoring, and Treatment of Primary and Metastatic Breast Cancer (2006)

Although breast cancer incidence continues to increase, mortality has been decreasing, principally as a result of earlier detection and improvements in adjuvant systemic therapy. Nonetheless, because antineo-plastic agents are associated with substantial morbidity and occasional mortality, efforts to individualize treatment strategies are desirable. In addition to classic histopathologic diagnosis, molecular and cellular tumor markers may help in establishing prognosis or prediction of benefit. Recommendations for routine use of tumor markers in breast cancer have been conservative. Although several studies have been reported, few are of sufficiently high level of evidence to permit solid conclusions. Three key issues in tumor marker evaluation are utility, magnitude, and reliability. Poorly conceived study designs cloud the issue of how the marker might be used. Reliance on p-values rather than the size of the differences in outcome between patients who are positive and those who are negative for the factor obscures the importance. Technical issues result in poor reproducibility and interpretability of assays. Analytical issues lead to poorly defined cutoff values for marker levels. Poor patient selection leads to difficulty interpreting results because of confounders such as differences in treatment regimens. This review focuses on these issues, with an emphasis on currently accepted tumor markers. Finally, new tumor marker reporting recommendations are discussed, the adoption of which may lead to improved design and publication of tumor marker studies in the future.
Rejection of Mouse Renal Cell Carcinoma Elicited by Local Secretion of Interleukin‐2 (1996)

We introduced the interleukin-2 (IL-2) gene into mouse renal cell carcinoma (RenCa) in order to examine the mechanism of tumor rejection. IL-2 gene-transfected RenCa (RenCa/IL-2Hi) exhibited marked retardation of tumor growth when implanted in a syngeneic host. Growth retardation of RenCa/IL-2Hi was also observed in athymic nude mice even after depletion of natural killer (NK) cells by treatment with anti-asialo GM1 antibody. Histological analysis of RenCa/IL-2Hi tumors disclosed non-specific inflammatory changes in syngeneic hosts. Co-injection of Bacillus Calmette Guerin with RenCa/IL-2Hi considerably enhanced the anti-tumor effects. Taken together, these findings strongly suggest that in situ IL-2 production leads to tumor rejection through non-specific inflammatory responses without participation of T cells and NK cells. On the other hand, the syngeneic mice that had rejected RenCa/IL-2Hi acquired immunity against parental RenCa, suggesting possible participation of memory T cells in the second rejection of the tumor.
A sindbis virus mRNA polynucleotide vector achieves prolonged and high level heterologous gene expressionin vivo (1995)

The direct Intramuscular delivery of naked plasmld DNA has been demonstrated to allow expression of encoded heterologous genes in the target myocytes. The method has been employed to elicit Immunization based upon delivery of antigen encoding plasmld DNA. For application In the context of achieving anti-tumor immunization against antigenic transforming oncoproteins, delivery of plasmld DNAs encoding these molecules would create significant potential safety hazards. As an alternative to DNA polynucleotide vectors, we explored the utility of mRNA vehicles for Inducing foreign gene expression in muscle cells In vivo . Synthetic reporter-gene encoding mRNA transcripts were derived for this analysis. The sindbis virus vector was also used to derive luciferase mRNA transcripts which possessed self-replication capacity. In these studies, It could be shown that the replicative vector was capable of directing significantly elevated levels of reporter gene expression In myocytes compared to a non-replicatlve mRNA species. In addition, the replicative species was capable of achieving significantly prolonged levels of In vivo gene expression compared to non-replicatlve mRNA. Both of these characteristics will make replicative mRNA vectors of utility for polynucleotide-based immunization protocols.
Band-Edge Electroabsorption in Quantum Well Structures: The Quantum-Confined Stark Effect (1984)

We present theory and extended experimental results for the large shift in optical absorption in GaAs-AlGaAs quantum well structures with electric field perpendicular to the layers. In contrast to the Stark effect on atoms or on excitons in bulk semiconductors, the exciton resonances remain resolved even for shifts much larger than the zero-field binding energy and fields &gt; 50 times the classical ionization field. The model explains these results as a consequence of the quantum confinement of carriers.
High-conductivity graphene nanocomposite via facile, covalent linkage of gold nanoparticles to graphene oxide (2012)

Graphene and its derivative, graphene oxide (GO) have been substantively used as the main framework for dispersing or building nanoarchitectures because of their excellent properties in electronics and catalysis. The requirement to obtain superior graphene-metal hybrid nanomaterials has led us to explore a facile way to design 4-aminobenzenethiol/1-hexanethiolate-protected gold nanoparticles (aAuNPs)-functionalized graphene oxide composite (aAuNPs-GO) in solution. We demonstrate that when aAuNPs with amino groups are exposed to GO, well-dispersed coverage of Au nanoparticles are mainly observed on the edge of GO sheet. In contrast, when 1-hexanethiolate-protected gold nanoparticles (hAuNPs) without amino groups are exposed to GO, hAuNPs simply aggregate on the surface of GO. This indicates that amino groups located on the surface of Au nanoparticles are an essential prerequisite for attachment of nearly monodispersed aAuNPs. The strategy described here for the fabrication of aAuNPs-GO provides a straightforward approach to develop graphene-based nanocomposites with undamaged sheets structure and good solubility and also improve the conductivity of GO sheets evidently.
Recent developments in the pharmacological treatment of Parkinson?s disease (2003)

Parkinson’s disease (PD) is a neurodegenerative disorder associated with the loss of dopaminergic neurons in the substantia nigra. The decline of dopamine leads to motor dysfunctions manifested as tremor, rigidity and bradykinesia. The pharmacological treatment of choice for the past 30 years has primarily been the dopamine precursor levodopa. Although it is the most effective treatment available, it is clear that other drugs are needed in order to sustain a therapeutic benefit and to alleviate fluctuations in mobility (i.e., motor fluctuations). Furthermore, there is some evidence that levodopa may hasten the occurrence of motor fluctuations and involuntary movements called dyskinesias. Hence, many clinicians delay the use of levodopa and employ the use of other symptomatic treatments including monoamine oxidase type B (MAO-B) inhibitors and dopamine agonists as first-line therapy in de novo patients. Regardless of treatment, the disease continues to progress as there is still no obvious means of altering disease progression (i.e., no neuroprotective therapy), to restore loss of dopamine (i.e., no restorative therapy) or prevent the disease (i.e. preventative therapy). With disease progression, polypharmacy is common and often employs a combination of antiparkinsonian agents. There have been some key advances in treatment with the advent of MAO-B inhibitors, dopamine agonists and catechol-O-methyltransferase inhibitors; however, the arsenal of drug treatment remains limited. As the mechanism of PD is further elucidated, novel drug treatments will continue to emerge in the areas of preventative, restorative or symptomatic therapy. Despite the purpose of treatment, the ideal pharmacological drug for PD will include the presence of a safe side-effect profile, a simple dosing schedule, the ability to provide symptomatic relief and the potential to alter disease progression. The purpose of this article is to examine upcoming antiparkinsonian drugs in clinical trials based on their pharmacology, safety and efficacy.
XELIRI or FOLFIRI as salvage therapy in advanced pancreatic cancer. (2010)

Fluoropyrimidine and irinotecan combination does not seem to have any role in the treatment of gemcitabine-resistant PA.
A phase I dose escalation (DE) and pharmacokinetics (PK) study of intravenous aflibercept (VEGF Trap) plus irinotecan, 5-fluorouracil, and leucovorin (I-LV5FU2) in patients with advanced solid tumors (STs) (2008)

3557 Background: Aflibercept (AF), a recombinant fusion molecule of the human VEGF receptor extracellular domains and the Fc portion of human IgG1, is a potent inhibitor of vascular endothelial growth factor. This study assessed the safety, dose limiting toxicities (DLTs)/recommended dose (RD) and PK of AF+I-LV5FU2. Methods: DE of AF followed by I-LV5FU2 (fixed standard dose) every 2 weeks (q2w) were explored. Results: 38 pts were enrolled (M/F: 18/20, median age 53 [19–77], ECOG PS 0/1: 24/13) including colorectal (23) and ovarian (5) cancers. Thirty six pts received prior chemotherapy (CT): median 3 [1–5]. A total of 404 cycles (median 10 [1–26]) of AF+I- LV5FU2 were administered across 4 AF dose levels (DL) ranging from 2.0 to 6.0 mg/kg. DLTs were: 2/12 pts at 4.0 (Grade (Gr) 3 proteinuria (PrU)>2wks including 1 pt with thrombotic microangiopathy), 2/10 pts at 5.0 (Gr 3 stomatitis and esophageal reflux) and 2/12 pts at 6.0 mg/kg (febrile neutropenia, Gr 3 stomatitis). The main AF-related Gr3–4 toxicities (% pts) were hypertension (32%) and PrU (11%). Moderate (Gr2) epistaxis (18%) and dysphonia (24%) were observed. Free and bound AF concentrations in combination with I-LV5FU2 are comparable to those observed with AF in monotherapy. AF had no influence on the PK of I-LV5FU2. Seven partial responses (synovial sarcoma, ovarian, pancreas and 4 colon cancers), 19 stable diseases were reported. AF 4.0 mg/kg was selected as the RD for feasibility based on PK analysis (excess of free AF at the end of the q2w dosing interval) and the absence of relationship between DE and clinical parameters (toxicity and activity). Conclusions: AF was safely combined with I-LV5FU2 with no evidence of exacerbation of CT-related toxicities. Class-effect toxicities related to AF were reported. Clear signs of activity were observed. Updated results will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis