Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of Encephalitogenic T Cells with Recombinant TCR Ligands1

We have previously described recombinant MHC class II β1 and α1 domains loaded with free antigenic peptides with potent inhibitory activity on encephalitogenic T cells. We have now produced single-chain constructs in which the peptide Ag is genetically encoded within the same exon as the linked β1 and α1 domains, overcoming the problem of displacement of peptide Ag from the peptide binding cleft. We here describe clinical effects of recombinant TCR ligands (RTLs) comprised of the rat RT1.B β1α1 domains covalently linked to the 72–89 peptide of guinea pig myelin basic protein (RTL-201), to the corresponding 72–89 peptide from rat myelin basic protein (RTL-200), or to cardiac myosin peptide CM-2 (RTL-203). Only RTL-201 possessed the ability to prevent and treat active or passive experimental autoimmune encephalomyelitis. Amelioration of experimental autoimmune encephalomyelitis was associated with a selective inhibition of proliferation response and cytokine production by Ag-stimulated lymph node T cells and a drastic reduction in the number of encephalitogenic and recruited inflammatory cells infiltrating the CNS. The exquisitely selective inhibition could be observed between molecules that differ by a single methyl group (the single amino acid residue difference between RTL-200 (threonine) and RTL-201 (serine) at position 80 of the myelin basic protein peptide). These novel RTLs provide a platform for developing potent and selective human diagnostic and therapeutic agents for treatment of autoimmune disease.
Phosphoinositide Hydrolysis and Insulin Release From Isolated Perifused Rat Islets: Studies With Glucose

The ability of glucose to promote the hydrolysis of pre I a be led [2-3H]inositol-containing phosphoinositides (PI) was assessed by measuring the efflux of 3H in response to glucose and the accumulation of labeled inositol phosphates. The inclusion of nonradioactive inositol (1 mM) in the perifusion medium dramatically improved our ability to monitor glucose-induced increases in 3H efflux. Efflux studies with this method revealed the following. 1) 3H efflux is significantly greater at 7 than at 2.75 mM glucose, and this parallels a small but significant increase in insulin secretion. 2) D-manno-Heptulose reduces 3H efflux with 7 mM glucose to a level approximating that seen in the presence of 2.75 mM glucose and has no effect on 3H efflux with 2.75 mM glucose. 3) In the presence of 20 mM glucose plus 1 mM inositol, 3H efflux is rapid and biphasic, a response that parallels the timing and amplitude of the biphasic pattern of insulin secretion. Direct measurements of labeled inositol and inositol phosphate levels in islets revealed the following. 4) After 50 min of perifusion with 2.75 or 7 mM glucose, labeled inositol phosphates were significantly greater with 7 mM glucose. 5) In response to 20 mM glucose alone, islet levels of free inositol, inositol monophosphate (IP,), and inositol bisphosphate (IP2) increased. 6) In response to 20 mM glucose plus 1 mM cold inositol, islet levels of free inositol increased, whereas islet levels of IP1, IP2, and inositol trisphosphate (IP3) were reduced compared with values obtained with 20 mM glucose alone. 7) In response to perifusion with 20 mM glucose, IP3 accumulation was biphasic in nature, and this response precedes the biphasic pattern of both insulin output and 3H efflux by several minutes. These results suggest that PI hydrolysis in islets is tightly regulated by the ambient glucose level and that second-messenger signals generated by activation of this pathway may contribute to the biphasic pattern of glucose-induced insulin secretion.
Conflict of interest in orthopaedic research. An association between findings and funding in scientific presentations.

BACKGROUND Financial conflict of interest has been associated with an increased likelihood that authors will report positive study outcomes. The purpose of this study was to investigate the association between types of declared conflict of interest and reported study outcomes in orthopaedic research. METHODS The abstracts of all podium presentations given at the 2001 and 2002 Annual Meetings of the American Academy of Orthopaedic Surgeons were analyzed by three orthopaedic surgeons with advanced training in clinical epidemiology. The findings reported in each abstract were graded as positive, negative, neutral, or not applicable. Self-reported conflict of interest was recorded and classified. RESULTS Conflicts of interest were reported in 40.8% (212) of 519 abstracts. The interobserver reliability of the grading of the study findings was acceptable (intraclass correlation coefficient, 0.725). Rates of conflict of interest related to royalties, stock options, or consultant or employee status varied significantly by subspecialty field (p < 0.001). The overall rate of positive study findings was 84.0% (436 of the 519 abstracts). Positive findings were more common in studies authored by individuals with a conflict of interest related to royalties (98.4% [sixty of sixty-one] compared with 88.0% [381 of 433] for studies authored by individuals without a conflict of interest related to royalties; relative risk = 1.1 [95% confidence interval = 1.0 to 1.1]; p = 0.02), in studies authored by individuals with a conflict of interest related to stock options (100.0% [twenty-nine of twenty-nine] compared with 84.7% [394 of 465]; relative risk = 1.2 [95% confidence interval = 1.0 to 1.3]; p = 0.04), and in studies authored by individuals with a conflict of interest related to consultant or employee status (97.8% [ninety-one of ninety-three] compared with 89.0% [357 of 401]; relative risk = 1.1 [95% confidence interval = 1.0 to 1.2]; p = 0.01). Positive findings were not more common in studies authored by individuals with a conflict of interest related to research or institutional funding (93.5% [143 of 153] compared with 91.8% [313 of 341]; relative risk = 1.0 [95% confidence interval = 0.95 to 1.5]; p = 0.65). In the multivariate analysis, the factors that remained significant predictors of positive outcomes were royalties (p = 0.002) and consultant or employee status (p = 0.038). CONCLUSIONS Self-reported conflicts of interest are common in orthopaedic research, particularly in the subspecialty fields of adult reconstruction of the knee, adult reconstruction of the hip, and spine. Presentations authored by individuals with a conflict of interest related to royalties, stock options, or consulting or employee status were significantly more likely to describe positive findings. While there may be distinct benefits associated with industry support of orthopaedic research, safeguards must be established to maintain public trust in the medical research establishment.
Skeletal muscle‐specific immunotoxin for the treatment of focal muscle spasm

Intramuscular injection of botulinum toxin type A (BTX) is used to treat many disorders characterized by muscular spasms. The utility of BTX, however, is limited by its short duration of action, the development of resistance after repeated injections, and cross-reactivity with autonomic neurons. To overcome these limitations, we engineered an immunotoxin (ITX) to damage skeletal muscle fibers selectively by chemically linking a monoclonal antibody against the nicotinic acetylcholine receptor to the toxin rich In vitro, the ITX was 20,000—fold more toxic to myotubes than myoblasts, consistent with the degree of acetylcholine receptor expression. The gastrocnemius muscles of 30 rats were unilaterally injected with a series of protein toxins at various concentrations and examined histopathologically 7 and 30 days later. ITX produced destructive myopathic changes at a dose 300—fold less than the maximum tolerated dose. Assessment of rat muscle strength after unilateral gastrocnemius injections showed that ITX was more effective and had a longer duration of action than BTX. ITXs may have potential for the treatment of involuntary muscle spasms.
ANALYSIS OF INTRATHECAL INTERLEUKIN‐6 AS A POTENTIAL PREDICTIVE FACTOR FOR VASOSPASM IN SUBARACHNOID HEMORRHAGE

OBJECTIVEInflammatory response seems to be one of the relevant pathophysiological aspects for developing vasospasm in subarachnoid hemorrhage. The probable diagnostic value of intrathecal proinflammatory markers is still unclear and is assessed in this study. METHODSWe analyzed daily clinical data and laboratory tests of the cerebrospinal fluid (CSF) of 64 patients with mostly poor-grade subarachnoid hemorrhage during a period of 14 days. Special attention was given to the relationship between the development of vasospasm and the time course of the intrathecal interleukin (IL)-6 concentrations in CSF (IL-6CSF). The potential power of IL-6CSF for predicting vasospasm was studied. RESULTSVasospasm developed in 28.1% of the patients, with a mean onset of 6.4 days after bleeding, and was detected by conventional methods. Patients with vasospasm demonstrated statistically significant higher median values of IL-6CSF on Days 4 and 5 (P < 0.05). Most importantly, the increase of IL-6CSF preceded the conventional signs of vasospasm. A cut-off value of IL-6CSF of at least 2000 pg/ml on Day 4 yielded an 11.72-fold higher relative risk (95% confidence interval, 2.93–46.60) of developing vasospasm, predicting vasospasm with a sensitivity of 88.9% and a specificity of 78.3%. We found a statistically significant correlation between IL-6CSF and delayed cerebral ischemia for Day 7 (P = 0.03). However, there was no correlation with IL-6CSF on any other day and outcome. CONCLUSIONIL-6CSF seems to be a reliable early marker for predicting vasospasm after subarachnoid hemorrhage on Days 4 and 5 before clinical onset.
Treatment initiation with zidovudine-containing potent antiretroviral therapy impairs CD4 cell count recovery but not clinical efficacy

Objective:Zidovudine-containing antiretroviral therapy has been associated with a lower rise in absolute CD4 cell counts in several randomized trials. We examined the predictive factors for this phenomenon and assessed its impact on clinical progression during treatment in a large patient cohort. Design:An analysis of data from the Swiss HIV Cohort Study. Methods:All 2177 treatment-naive adults who began potent antiretroviral therapy (ART) between September 1995 and September 2004 were included. Exclusion criteria were previous ART and treatment duration of less than 3 months. Follow-up was censored in the case of a treatment switch or stop. Results:A total of 1312 patients initiated zidovudine-containing ART and 865 started ART without zidovudine. Except for slightly higher absolute CD4 cell counts in the zidovudine group, prognostic characteristics at baseline and viral suppression during treatment did not differ. During an observation time of 2343 and 1486 patient-years, the CD4 cell count increased by a median of 221 versus 286 cells/μl at 2 years and 290 versus 379 cells/μl at 4 years in the zidovudine versus no zidovudine group; however, the rise in the percentage of CD4 cells was similar in both groups. The zidovudine group had a significantly slower rise in total lymphocytes and haemoglobin. In multivariable Cox models, the hazard for new HIV-associated clinical events was not affected by zidovudine-containing ART. Conclusion:Over 4 years, zidovudine led to a smaller increase in absolute, but not percentage, CD4 cell counts. The effect can be explained as a slower rise in total lymphocytes and has no impact on clinical efficacy.
Functional anatomy of chemical senses in the alert monkey revealed by positron emission tomography

Functional imaging technique using positron emission tomography (PET) has made it possible to localize functional brain regions in the human brain by detecting changes in regional cerebral blood flow (rCBF). Performing PET studies in the monkey will aid in integrating monkey electrophysiological research with human PET studies. We examined changes in rCBF during olfactory or combined olfactory and gustatory (flavour) stimulation using PET in the alert rhesus monkey. Olfactory or flavour stimulation with acetic acid or apple increased rCBF in the prepyriform area, substantia innominata and amygdala. Besides these areas, flavour stimulation increased rCBF in the anterior insula and frontal operculum, orbitofrontal cortex, inferior frontal gyrus and cerebellum. Apple odour or flavour stimuli increased rCBF in the inferior occipital gyrus in addition to the above areas. These findings suggest that the increases of rCBF in response to neural activities in the primary olfactory and gustatory cortices are detectable by the use of PET. In addition, regions activated by apple stimuli suggest that higher brain function might be detected with PET in the alert monkey.
Root caries risk indicators: a systematic review of risk models.

OBJECTIVE To identify risk indicators that are associated with root caries incidence in published predictive risk models. METHODS Abstracts (n = 472) identified from a MEDLINE, EMBASE, and Cochrane registry search were screened independently by two investigators to exclude articles not in English (n = 39), published prior to 1970 (none), or containing no information on either root caries incidence, risk indicators, or risk models (n = 209). A full-article duplicate review of the remaining articles (n = 224) selected those reporting predictive risk models based on original/primary longitudinal root caries incidence studies. The quality of the included articles was assessed based both on selected criteria of methodological standards for observational studies and on the statistical quality of the modeling strategy. Data from these included studies were extracted and compiled into evidence tables, with information about the cohort location, incidence period, sample size, age of the study participants, risk indicators included in the model, root caries incidence, modeling strategy, significant risk indicators/predictors, and parameter estimates and statistical findings. RESULTS Thirteen articles were selected for data extraction. The overall quality of the included articles was poor to moderate. Root caries incidence ranged from 12% to 77% (mean ± SD = 45 ± 17%); follow-up time of the published studies was ≤ 10 years (range = 9; median = 3); sample size ranged from 23-723 (mean ± SD = 264 ± 203; median = 261); person-years ranged from 23 to 1540 (mean ± SD = 760 ± 556; median = 746). Variables most frequently tested and significantly associated with root caries incidence were (times tested; % significant; directionality): baseline root caries (12; 58%; positive); number of teeth (7; 71%; three times positive, twice negative), and plaque index (4; 100%; positive). Ninety-two other clinical and nonclinical variables were tested: 27 were tested three times or more and were significant between 9% and 100% of the times tested; and 65 were tested but never significant. CONCLUSIONS The root caries incidence indicators/predictors most frequently reported were root caries prevalence at baseline, number of teeth, and plaque index. This finding can guide targeted root caries prevention. There was substantial variation among published models of root caries risk in terms of variable selection, sample size, cohort location, assessment methods, incidence periods, association directionality, and analytical techniques. Future studies should emphasize variables frequently tested and often significant, and validate existing models in independent databases.
The potential role of heparin in assisted conception.

BACKGROUND Heparan sulphates play key roles in conception and early pregnancy events. The role of heparin, a structural analogue, and its application to assisted conception, is largely unknown. METHODS Relevant studies were identified by searching PubMed 1966-November 2007 and Google Scholar without limitations. Sensitive search strategies were combined with relevant medical subject headings and text words. RESULTS The similarities of heparin and heparan, the haemostatic changes induced by ovarian stimulation and the risk of thrombosis, the contribution of thrombophilia to pregnancy and infertility outcomes, early embryo-maternal dialogue and how these various aspects of assisted conception may be modified by heparin are reviewed. CONCLUSIONS Heparin can alter the haemostatic response to controlled ovarian stimulation and modify the risk of thrombosis. It can also modulate many of the fundamental physiological processes required for blastocyst apposition, adherence and implantation and as well as trophoblast differentiation and invasion due to its similarities with heparan sulphates and has the potential to improve pregnancy rates and outcomes.
Tactophonics: your favourite thing wants to sing

Description of a project, inspired by the theory of affordance, exploring the issues of visceral expression and audience engagement in the realm of computer performance. Describes interaction design research techniques in novel application, used to engage and gain insight into the culture and mindset of the improvising musician. This research leads to the design and implementation of a prototype system that allows musicians to play an object of their choice as a musical instrument.
Serologic mapping and biochemical characterization of the carcinoembryonic antigen epitopes using fourteen distinct monoclonal antibodies

A series of 14 monoclonal anti‐carcinoembryonic antigen (CEA, Mr 180,000) antibodies (MAbs) that show a strong degree of selective reactivity for human colon carcinomas versus normal adult tissues were used to construct a serological map of the CEA molecule. The MAbs were generated using extracts of colon carcinomas as immunogen and are thus given a COL designation. None of the 14 COL‐MAbs tested were reactive with purified non‐specific cross‐reacting antigen (NCA, Mr 55,000) from normal lung, although some showed reactivity to human granulocytes. All the COL‐MAbs tested were reactive with normal fecal antigen‐2 (NFA‐2, Mr170,000); however, many of the COL‐MAbs demonstrated a higher affinity constant to CEA than to NFA‐2. Cross‐competition radioimmunoassays classified the 14 COL‐MAbs into 5 groups. The chemical nature of the COL‐binding domains was tested using chemically or enzymatically treated CEA; all reacted with periodate‐treated CEA and deglycosy‐lated CEA, indicating that the COL‐reactive epitopes appear to be of a proteinaceous nature. Heat treatment, reduction, alkylation, pepsin digestion or pronase treatment of CEA, however, gave differential results with respect to COL binding. Antibody titration experiments were carried out to define differential reactivities to colorectal carcinoma versus NCA‐containing granulocyte extracts; these results were compared with results obtained using several anti‐CEA MAbs that have been used in clinical trials. Granulocyte binding and biochemical studies showed that the COL MAbs may distinguish as many as 7 to 10 CEA epitopes.
The market integration process under different regulatory regimes: evidence from the European car sector

En este trabajo investigamos el proceso de integracion del mercado europeo de automoviles analizando la evolucion en las divergencias del "Pricing-to-Market" a traves de distintos paises de destino de las exportaciones. El estudio toma en consideracion el comportamiento de precios de los exportares de Reino Unido durante el periodo 1999m1-2009m1. Los resultados preliminares indican la presencia de discriminacion internacional de precios como fuente de dispersion de precios en el area euro, lo que implica la presencia de segmentacion de mercados y divergencias significativas en las estructuras de mercado percibidas por las empresas exportadoras. No obstante, el analisis dinamico muestra que las divergencias en el "Pricing-to-Market" son inestables lo que implica variaciones relativas en las estructuras de mercado percibidas por los exportadores. Cuando en el analisis incluimos informacion estadistica a partir de la implantacion completa de las Exenciones en Bloque (1400/2002), obtenemos convergencia en el comportamiento de precios a traves de los paises. Este resultado contrasta claramente con la evidencia obtenida a partir de algunos productos de control y el periodo anterior. Los resultados son consistentes con que la liberalizacion del sistema de distribucion haya jugado un papel relevante en el proceso de integracion del mercado.
A Review on Recent Development of Spacecraft Attitude Fault Tolerant Control System

Motivated by several accidents, attitude control of a spacecraft subject to faults/failures has gained considerable attention in a wider range of aerospace engineering and academic communities. This paper is concerned with industrial practices and theoretical approaches for fault tolerant control (FTC) and fault detection and diagnosis (FDD) in spacecraft attitude control system. An overview on recent development of spacecraft attitude FTC system design is presented. The basis of a FTC system is introduced. The existing engineering FTC techniques and theoretical methodologies, including their advantages and disadvantages, are discussed. Moreover, closely associated with the reliability-relevant issues, recent progress in attitude FTC design strategies is reviewed. A brief review of some open problems in the general area of spacecraft attitude control design subject to components faults/failures is further concluded.
Cytokine BAFF Gene Variation Is Associated with Survival of Patients with T-cell Lymphomas

Purpose: Cytokine BAFF is a potent molecule for the activation and survival of B cells, and it also plays an important role in T-cell function. Genetic polymorphism (rs9514828C>T) in BAFF has been associated with elevated BAFF transcription. We sought to determine whether rs9514828 is associated with T-cell lymphoma (TCL) survival. Experimental Design: BAFF rs9514828 genotypes and survival of TCL were analyzed in the discovery group including 150 patients, and the results were replicated in an independent validation group of 120 patients. Kaplan–Meier analysis was conducted to compare survival among different genotypes. Cox proportional hazard models were used to identify independent significant variables. Luciferase reporter gene assays were conducted to examine the function of rs9514828 variant. Results: We found that BAFF rs9514828 polymorphism was significantly associated with TCL survival. In pooled analysis of two independent groups, the favorable rs9514828 TC and TT genotypes had significantly better five-year survival rates compared with the CC genotype (47% and 53% vs. 22%, P = 2.27 × 10−5 for log-rank test). Multivariate Cox regression analysis showed that rs9514828 was an independent prognostic factor, with HRs for patient death being 0.48 [95% confidence interval (CI), 0.32–0.71] for the CT and 0.47 (95% CI, 0.23–0.93) for the TT genotypes. Reporter gene assays indicated that the rs9514828T allele had significantly higher promoter activity than the rs9514828C counterpart. Conclusion: These findings suggest that functional polymorphism in BAFF might be a genetic determinant for the survival of patients with TCL. Clin Cancer Res; 18(8); 2250–6. ©2012 AACR.
Amplification of cancer cell apoptosis in photodynamic therapy‐treated tumors by adjuvant ceramide analog LCL29

C6‐ceramide analog LCL29 was recently shown to improve the cure rates of mouse tumors treated by photodynamic therapy (PDT), but the mechanism underlying the therapeutic gain remains unclear. Since LCL29 is a pro‐apoptotic agent, the main objective of the present study was to determine how LCL29 affects cancer cell apoptosis in PDT‐treated tumors.