tbuckley/cabot-search huggingface dataset:
SEPARABLE POPULATIONS OF ACTIVATED THYMUS-DERIVED LYMPHOCYTES IDENTIFIED IN TWO ASSAYS FOR CELL-MEDIATED IMMUNITY TO MURINE TUMOR ALLOGRAFTS
Authors: Robert E. Tigelaar, R. M. Gorczynski
Journal: The Journal of Experimental Medicine (1974)

The immune response of C57BL mice to a DBA/2 tumor allograft has been assessed in two assays of cell-mediated immunity, the in vitro lysis of 51Cr-labeled target cells and the antigen-mediated inhibition of macrophage migration. Both assays were shown to be measuring a T-cell-mediated reaction. Three types of experiments suggested that distinct subpopulations of T cells mediate these reactions. The tissue distributions of these activities was distinctive; both activities were present in spleens from i.p. immunized mice, but only macrophage migration inhibition activity was found in the peripheral lymph nodes (PLN) of such mice. Adoptive transfer of immune spleen cells into irradiated syngeneic recipients revealed that while a substantial amount of migration inhibition activity could subsequently be found in PLN, cytotoxic activity was found predominantly in the spleens of these adoptive hosts. Velocity sedimentation analysis of immune cells 14 days after i.p. immunization indicated that while the majority of cytotoxic activity was associated with small and medium lymphocytes, the majority of migration inhibition activity was associated with medium and large lymphocytes. In addition, normal spleen cells were fractionated by velocity sedimentation immediately before allosensitization in vitro. Subsequent analysis of the sensitized fractions revealed that the activity profiles for cytotoxicity and macrophage migration inhibition were not coincident. The implications of these observations are discussed.
Proinflammatory Pathways: The Modulation by Flavonoids
Authors: Daniela Ribeiro, Marisa Freitas, José L. F. C. Lima, Eduarda Fernandes
Journal: Medicinal Research Reviews (2015)

Abstract Inflammation is a natural, carefully orchestrated response of the organism to tissue damage, involving various signaling systems and the recruitment of inflammatory cells. These cells are stimulated to release a myriad of mediators that amplify the inflammatory response and recruit additional cells. These mediators present numerous redundancies of functions, allowing a broad and effective inflammatory response, but simultaneously make the understanding of inflammation pathways much difficult. The extent of the inflammatory response is usually self‐limited, although it depends on the balance between the pro‐ and anti‐inflammatory signals. When that equilibrium is dislocated, a more widespread inflammatory response may take place. Flavonoids have been shown to be possible alternatives to the traditionally molecules used as anti‐inflammatory agents. In fact, the biological activities of flavonoids include the modulation of the diverse phases of inflammatory processes, from the gene transcription and expression to the inhibition of the enzymatic activities and the scavenging of the reactive species. In the present review, the inflammatory network is widely revised and the flavonoids’ broad spectrum of action in many of the analyzed inflammatory pathways is revised. This kind of integrated revision is original in the field, providing the reader the simultaneous comprehension of the inflammatory process and the potential beneficial activities of flavonoids.
Long-term outcome prediction by clinicopathological risk classification algorithms in node-negative breast cancer—comparison between Adjuvant!, St Gallen, and a novel risk algorithm used in the prospective randomized Node-Negative-Breast Cancer-3 (NNBC-3) trial
Authors: M. Schmidt, A. Victor, D. Bratzel, D. Boehm, C. Cotarelo, A. Lebrecht, W. Siggelkow, J.G. Hengstler, A. Elsäßer, M. Gehrmann, H.-A. Lehr, H. Koelbl, G. von Minckwitz, N. Harbeck, C. Thomssen
Journal: Annals of Oncology (2008)
Detection of Human Papillomavirus (HPV) 16-Specific CD4+ T-cell Immunity in Patients with Persistent HPV16-Induced Vulvar Intraepithelial Neoplasia in Relation to Clinical Impact of Imiquimod Treatment
Authors: Mariëtte I.E. van Poelgeest, Manon van Seters, Marc van Beurden, Kitty M.C. Kwappenberg, Claudia Heijmans-Antonissen, Jan W. Drijfhout, Cornelis J.M. Melief, Gemma G. Kenter, Theo J.M. Helmerhorst, Rienk Offringa, Sjoerd H. van der Burg
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Topical application of the immune response modifier imiquimod is an alternative approach for the treatment of human papillomavirus (HPV)–positive vulvar intraepithelial neoplasia (VIN) and aims at the immunologic eradication of HPV-infected cells. We have charted HPV16-specific immunity in 29 patients with high-grade VIN and examined its role in the clinical effect of imiquimod treatment. Experimental Design: The magnitude and cytokine polarization of the HPV16 E2-, E6-, and E7-specific CD4+ T-cell response was charted in 20 of 29 patients by proliferation and cytokine bead array. The relation between HPV16-specific type 1 T-cell immunity and imiquimod treatment was examined in a group of 17 of 29 patients. Results: HPV16-specific proliferative responses were found in 11 of the 20 patients. In eight of these patients, T-cell reactivity was associated with IFNγ production. Fifteen of the women treated with imiquimod were HPV16+, of whom eight displayed HPV16 E2- and E6-specific T-cell immunity before treatment. Imiquimod neither enhanced nor induced such immunity in any of the subjects. Objective clinical responses (complete remission or &amp;gt;75% regression) were observed in 11 of the 15 patients. Of these 11 responders, eight patients displayed HPV16-specific type 1 CD4+ T-cell immunity, whereas three lacked reactivity. Notably, the four patients without an objective clinical response also lacked HPV16-specific type 1 T-cell immunity. Conclusions: HPV16-specific IFNγ-associated CD4+ T-cell immunity, although not essential for imiquimod-induced regression of VIN lesions, may increase the likelihood of a strong clinical response (P = 0.03).
The Three-Month Effect of Mobile Internet-Based Cognitive Therapy on the Course of Depressive Symptoms in Remitted Recurrently Depressed Patients: Results of a Randomized Controlled Trial
Authors: Gemma Kok, Huibert Burger, Heleen Riper, Pim Cuijpers, Jack Dekker, Harm van Marwijk, Filip Smit, Aaron Beck, Claudi L.H. Bockting
Journal: Psychotherapy and Psychosomatics (2015)

Background: Internet-based cognitive therapy with monitoring via text messages (mobile CT), in addition to treatment as usual (TAU), might offer a cost-effective way to treat recurrent depression. Method: Remitted patients with at least 2 previous episodes of depression were randomized to mobile CT in addition to TAU (n = 126) or TAU only (n = 113). A linear mixed model was used to examine the effect of the treatment condition on a 3-month course of depressive symptoms after remission. Both an intention-to-treat analysis (n = 239) and a completer analysis (n = 193) were used. Depressive symptoms were assessed using the Inventory of Depressive Symptomatology (IDS-SR30) at baseline and 1.5 and 3 months after randomization. Results: Residual depressive symptoms showed a small but statistically significant decrease in the intention-to-treat group over 3 months in the mobile CT group relative to the TAU group (difference: -1.60 points on the IDS-SR30 per month, 95% CI = -2.64 to -0.56, p = 0.003). The effect of the treatment condition on the depressive symptomatology at the 3-month follow-up was small to moderate (Cohen's d = 0.44). All analyses among completers (≥5 modules) showed more pronounced treatment effects. Adjustment for unequally distributed variables did not markedly affect the results. Conclusions: Residual depressive symptoms after remission showed a more favorable course over 3 months in the mobile CT group compared to the TAU group. These results are a first indication that mobile CT in addition to TAU is effective in treating recurrently depressed patients in remission. However, demonstration of its long-term effectiveness and replication remains necessary. © 2015 S. Karger AG, Basel.
INTEGRATION OF T CELL RECEPTOR–DEPENDENT SIGNALING PATHWAYS BY ADAPTER PROTEINS
Authors: James L. Clements, Nancy J. Boerth, Jong Ran Lee, Gary A. Koretzky
Journal: Annual Review of Immunology (1999)

▪ Abstract The initiation of biochemical signal transduction following ligation of surface receptors with intrinsic cytoplasmic tyrosine kinase activity is common for many cell types. T lymphocytes also require activation of tyrosine kinases following T cell receptor (TCR) ligation for maximal stimulation. However, the TCR has no intrinsic tyrosine kinase activity. Instead, the TCR must rely on cytoplasmic tyrosine kinases that localize to the TCR complex and initiate TCR-mediated signaling events. Although much has been learned regarding how these cytosolic tyrosine kinases are activated and recruited to the TCR complex, relatively little is understood about how these initial events are translated into transcriptional activation of genes that regulate cytokine production, cell proliferation, and cell death. Recently, it has become clear that the class of intracellular molecules known collectively as adapter proteins, molecules with modular domains capable of recruiting additional proteins but that exhibit no intrinsic enzymatic activity, serve to couple proximal biochemical events initiated by TCR ligation with more distal signaling pathways.
Treating exercise oscillatory ventilation in heart failure: the detail that may matter
Authors: Marco Guazzi
Journal: European Respiratory Journal (2012)

Over the last 15 yrs, cardiologists have had to face a progressive recognition that abnormalities in the ventilatory response to exercise are relevant features of the heart failure syndrome [1]. Prior pathophysiology studies have defined the mechanistic role of the lung (impaired perfusion and increased minute ventilation ( V ′E)) [2] and of the periphery (increased chemo/metaboreflex sensitivity) [3] as determinants of the inefficient ventilatory response and early exercise termination.

A wealth of literature has indeed brought evidence that, whatever the predominant substrate, the increase in V ′E relative to carbon dioxide production ( V ′CO2), primarily measured as the slope of this relationship, is a powerful indicator of disease severity [1, 4] that extends beyond peak oxygen uptake ( V ′O2), since its prognostic power is retained even when peak V ′O2 is near the normal range [5]. The consistency of these observations has substantially contributed to broadening the use of exercise gas exchange analysis for the clinical assessment and estimation of prognosis for the wide spectrum of heart failure populations [6].

As ventilation inefficiency has become an established matter of interest for heart failure specialists, further details have emerged as part of the picture, the most remarkable being exertional oscillatory ventilation (EOV) [7–12], a phenomenon originally described as anecdotal [13–15], and now considered a marker of disease severity even stronger than …
CGAL: computing genome assembly likelihoods
Authors: Atif Rahman, Lior Pachter
Journal: Genome biology (2013)

Assembly algorithms have been extensively benchmarked using simulated data so that results can be compared to ground truth. However, in de novo assembly, only crude metrics such as contig number and size are typically used to evaluate assembly quality. We present CGAL, a novel likelihood-based approach to assembly assessment in the absence of a ground truth. We show that likelihood is more accurate than other metrics currently used for evaluating assemblies, and describe its application to the optimization and comparison of assembly algorithms. Our methods are implemented in software that is freely available at http://bio.math.berkeley.edu/cgal/ .
Biofabricated Nanoparticle Coating for Liver‐Cell Targeting
Authors: Cheng Zhang, Xue Qu, Jinyang Li, Hua Hong, Jianbo Li, Jie Ren, Gregory F. Payne, Changsheng Liu
Journal: Advanced Healthcare Materials (2015)

Biology routinely uses noncovalent interactions to perform complex functions that range from the molecular recognition of ligand–receptor binding to the reversible self‐assembly/disassembly of hierarchical nanostructures (e.g., virus particles). Potentially, biological materials that offer such recognition and reversible self‐assembly functionality can be applied to nanomedicine. Here, polysaccharides with the multifunctional polysaccharide‐binding protein Concanavalin A (Con A) are coupled to create a functional nanoparticle coating. This coating is self‐assembled in a layer‐by‐layer format by sequentially contacting a nanoparticle with Con A and the polysaccharide glycogen. In the final assembly step, a galactomannan targeting ligand is self‐assembled into the coating. Evidence indicates that the mannose residues of the galactomannan backbone are responsible for assembly into the coating by Con A binding, while the galactose side chain residues are responsible for targeting to the liver‐specific asialoglycoprotein receptor (ASGP‐R). Binding to ASGP‐R induces endocytic uptake, while the low endosomal pH triggers disassembly of the coating and release of the nanoparticle‐entrapped drug. In vitro cell studies indicate that the coating confers liver‐cell‐specific function for both nanoparticle uptake and drug delivery. These studies extend the use of Con A to sugar‐mediated and organ‐specific targeting, and further illustrate the potential of biologically based fabrication for generating functional materials.
Caring for sex workers
Authors: Michael L Rekart
Journal: BMJ (2015)

#### The bottom line Sex workers are adults who receive money or goods for sexual services, either regularly or occasionally,1 including female, male, and transgendered sex workers.2 3 Youths under 18 years who sell sex are sexually exploited and not included in the definition. Caring for sex workers seeking health services requires knowledge, flexibility, open mindedness, and, above all, a non-judgmental attitude. Practitioners can be directly involved in curing communicable diseases, preventing chronic conditions, and helping patients through a sometimes difficult period. Sex workers are at higher risk of many conditions (box 1), but they may also have ongoing chronic disease issues. This article provides an evidence based review (see box 2 for details of data search) of the specific health needs of sex workers, aimed at non-specialist hospital doctors, general practitioners, and candidates for postgraduate examinations globally. #### Box 1: Health issues for sex workers
The Effect of Food on the Pharmacokinetics of S-1 after Single Oral Administration to Patients with Solid Tumors
Authors: Godefridus J. Peters, Paul Noordhuis, Cornelis J. van Groeningen, Giuseppe Giaccone, Ulbe Holwerda, Daphne Voorn, Ad Schrijvers, Jan H. Schornagel, Jos H. Beijnen, Pierre Fumoleau, Jan H. M. Schellens
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose is to determine the effect of food on the bioavailability of S-1, an oral formulation of the 5-fluorouracil (5FU) prodrug Ftorafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), a dihydropyrimidine dehydrogenase inhibitor, and oxonic acid (an inhibitor of 5FU phosphoribosylation in normal gut mucosa) in a molar ratio of 1:0.4:1. Experimental Design: Eighteen patients received a single dose of S-1 of 35 mg/m2 with (535–885 kcal) or without food in a crossover study design: in arm A without breakfast on day −7 and with breakfast on day 0 and in arm B the reversed sequence. Blood samples were taken before and after S-1 administration. This food effect was evaluated according to the Food and Drug Administration guidelines using log-transformed data. Results: Pharmacokinetic parameters for 5FU without breakfast were as follows: Tmax, 107 min; Cmax, 1.60 μm; area under the plasma concentration-time curve (AUC) 441 μm × min; and T1/2, 104 min. Fasting decreased Tmax of FT, 5FU, CDHP, and oxonic acid significantly (P &amp;lt; 0.006) and increased the Cmax (P &amp;lt; 0.013). The food/fast ratio for the AUC of FT was not different, which for 5FU was 0.84 (P = 0.041), for CDHP was 0.89 (P = 0.191), for oxonic acid was 0.48 (P &amp;lt; 0.0005), and for cyanuric acid, the breakdown product of oxonic acid, was 5.1 (P = 0.019). Accumulation of uracil, indicative for dihydropyrimidine dehydrogenase inhibition, was not affected, as well as the T1/2 of FT, 5FU, CDHP, and oxonic acid. Evaluation of the log-transformed data demonstrated that the 90% confidence interval for the food/fast ratio for the Cmax and AUC of FT, 5FU, CDHP, and uracil were within 70–143% and 80–125%, respectively, indicating no food effect. Only for oxonic acid and cyanuric acid were these values outside this interval. Conclusions: Food intake affected only the pharmacokinetics of the S-1 constituent oxonic acid but not of FT, CDHP, and 5FU. Because oxonic acid is included to protect against gastrointestinal toxicity, this observation might affect the gastrointestinal toxicity and thus the efficacy of S-1.
The RASSF3 Candidate Tumor Suppressor Induces Apoptosis and G1–S Cell-Cycle Arrest via p53
Authors: Takumi Kudo, Mitsunobu Ikeda, Misa Nishikawa, Zeyu Yang, Kikuo Ohno, Kentaro Nakagawa, Yutaka Hata
Journal: Cancer Research (2012)

RASSF3 is the smallest member of the RASSF family of proteins that function as tumor suppressors. Unlike other members of this important family, the mechanisms through which RASSF3 suppresses tumor formation remain unknown. Here, we show that RASSF3 expression induces p53-dependent apoptosis and its depletion attenuates DNA damage-induced apoptosis. We found that RASSF3-induced apoptosis depended upon p53 expression. Exogenous expression of RASSF3 induced G(1)-S arrest, which was also p53 dependent. In contrast, loss of RASSF3 promoted cell-cycle progression, abrogated UVB- and VP-16-induced G(1)-S arrest, decreased p53 protein and target gene expression, and prevented DNA repair. RASSF3 was shown to directly interact with and facilitate the ubiquitination of MDM2, the E3 ligase that targets p53 for degradation, thereby increasing p53 stabilization. Together, our findings show the tumor suppressor activity of RASSF3, which occurs through p53 stabilization and regulation of apoptosis and the cell cycle.
The kinematic theory: A new window to study and analyze simple and complex human movements
Authors: Réjean Plamondon
Journal: Behavioral and Brain Sciences (1997)

To cover as much as possible the various questions raised by the commentators, I have divided my Response into three major sections. In section R1, I reply to the major comments and remarks dealing with the basic hypothesis upon which the kinematic theory is built (Plamondon 1993b; 1993c; 1995a; 1995b). I focus on linearity, determinism, kinematics, and the biological significance of the model parameters. I conclude this section by showing how, from a practical point of view, the delta-lognormal law can be used to group similar data prior to proceeding with further statistical analysis. In section R2, I address the main comments and remarks dealing with the speed/accuracy tradeoffs. First, I focus on the origin of speed/accuracy tradeoffs and the effect of visual feedback. Then I clarify some terminology problems and mathematical misinterpretations prior to providing new support for the theory using the experiments and data referred to by some commentators. I devote section R3 to a generalization of the kinematic theory and to some potential applications. I first provide new explanations of some classical experiments; then I show how more complex movements can be analyzed using the delta-lognormal law. I focus on perturbed and oscillatory movements as well as on cursive script and signature analysis. I conclude this section and my Response by showing some possible applications to the study of movement learning in children as well as to the study of aging phenomena in movement control. I complete my Response by recalling some technical problems that still need further analysis. Throughout the text, I try to convince the reader that the kinematic theory provides a new window on old and new data in the field.
Effects of vitamin antioxidant supplementation on cell kinetics of patients with adenomatous polyps.
Authors: R J Cahill, K R O'Sullivan, P M Mathias, S Beattie, H Hamilton, C O'Morain
Journal: Gut (1993)

Colonic crypt cell proliferation is used as an indicator of risk of colorectal carcinoma. Subjects with adenomatous polyps and cancer have an increased cell proliferation and a shift of the proliferative zone towards the apex of the crypt. Epidemiological and in vitro studies have confirmed a link between vitamins A, E, C, beta-carotene, and colorectal cancer. In vitro bromodeoxyuridine immunohistochemical technique was used to assess the effect of daily oral supplementation with vitamin E (160 mg), vitamin C (750 mg), or beta-carotene (9 mg) on the colonic crypt cell proliferation in patients with adenomatous polyps (n = 40) compared with normal subjects with no colonic disease (n = 20). The patients were given supplementation for one month and colonic biopsy specimens were taken before and at the end of the trial. Patients with adenomatous polyps had a significantly higher mean labelling index per cent than controls (p &lt; 0.001). Vitamin C or beta-carotene supplementation, however, significantly reduced the total proliferation (p &lt; 0.005) whereas vitamin E supplementation had no effect on the colonic crypt cell proliferation. beta-carotene reduced cell proliferation at the base of the crypt only. Vitamin C reduced cell proliferation in all the crypt compartments from the apex to the base to those values seen in age and sex matched controls. These findings indicate that prolonged supplementation with vitamin C may reduce the recurrence of adenomatous polyps.