gebhart/patrepeval huggingface dataset:
Establishment of a tumor-specific immunotherapy model utilizing TNP-reactive helper T cell activity and its application to the autochthonous tumor system. (1984)

Preinduction of potent hapten-reactive helper T cell activity and subsequent immunization with hapten-coupled syngeneic tumor cells result in enhanced induction of tumor-specific immunity through T-T cell collaboration between anti-hapten helper T cells and tumor-specific effector T cells. On the basis of this augmenting mechanism, a tumor-specific immunotherapy protocol was established in which a growing tumor regresses by utilizing a potent trinitrophenyl (TNP)-helper T cell activity. C3H/He mice were allowed to generate the amplified (more potent) TNP-helper T cell activity by skin painting with trinitrochlorobenzene (TNCB) after pretreatment with cyclophosphamide. Five weeks later, the mice were inoculated intradermally with syngeneic transplantable X5563 tumor cells. When TNCB was injected into X5563 tumor mass, an appreciable number of growing tumors, in the only group of C3H/He mice in which the amplified TNP-helper T cell activity had been generated were observed to regress (regressor mice). These regressor mice were shown to have acquired tumor-specific T cell-mediated immunity. Such immunity was more potent than that acquired in mice whose tumor was simply removed by surgical resection. These results indicate that in situ TNP haptenation of the tumor cells in TNP-primed mice can induce the enhanced tumor-specific immunity leading to the regression of a growing tumor. Most importantly, the present study further investigates the applicability of this TNP immunotherapy protocol to an autochthonous tumor system. The results demonstrate that an appreciable percent of growing methylcholanthrene-induced autochthonous tumors regressed by the above TNP immunotherapy protocol. Thus, the present model provides an effective maneuver for tumor-specific immunotherapy in syngeneic transplantable as well as autochthonous tumor systems.
Update on the management of advanced breast cancer. (1999)

Recent trials comparing single-agent vs combination therapy in metastatic breast cancer suggest that it may be time to reconsider the belief that combination chemotherapy is the gold standard of treatment. Based on the limited randomized trial data available to date, high-dose chemotherapy with stem-cell rescue should not be viewed as "state-of-the art" treatment for metastatic disease and should be used only in the context of clinical trials. Recent trials have explored the optimal dosing and scheduling of the taxanes, as well as the possible role of these agents in combination regimens. Capecitabine (Xeloda), a new oral fluoropyrimidine, appears to be comparable in efficacy to CMF (cyclophosphamide, methotrexate, and fluorouracil), and preclinical data suggest possible synergy between this agent and the taxanes. Other promising agents under study include liposome-encapsulated doxorubicin (TLCD-99), an immunoconjugate linking a chimeric human/mouse monoclonal antibody to doxorubicin molecules; MTA (LY231514), a multitargeted antifolate; and marimistat, a broad-spectrum matrix metalloproteinase inhibitor. Tamoxifen (Nolvadex) remains the most important hormonal agent, but new antiestrogens and selective estrogen receptor modulators (SERMs) may provide alternatives. The potential role of new aromatase inhibitors as first-line hormonal agents requires further study. Finally, the possible synergy between trastuzumab (Herceptin), a recombinant humanized monoclonal antibody to the HER-2/neu protein, and paclitaxel (Taxol) is being studied in two clinical trials.
Optical microscopy, multinuclear NMR (2H,14N and35Cl) and X-ray studies of dodecyl-and hexadecyl-trimethylammonium chloride/water mesophases (1990)

Abstract The liquid crystal phases occurring with the cationic surfactants dodecyltrimethyl ammonium chloride (C12TAC) and hexadecyltrimethyl ammonium chloride (C16TAC) in water have been examined using differential scanning calorimetry, low-angle X-ray diffraction and, in particular, multinuclear magnetic resonance spectroscopy. The dependence of water (2H2O), chloride (35Cl), and surfactant (14N) quadrupole splittings (δ) on composition in the hexagonal and lamellar phase has been determined. For C12TAC, from the 14N δ values, the location and ordering of the NMe3 + was found to be almost independent of composition for the H1 phase, whereas at the higher surfactant concentration within the Lα phase the order increased gradually. Within the H1 phase the 35Cl δ values are highly sensitive to composition and temperature. This implies that the chloride ions reside between the head groups at the highest water concentrations and are squeezed out as temperature or surfactant concentration increases. Water 2H δ values show a maximum as a function of composition allowing an estimate of 4·3 bound water molecules per surfactant for the H1 phase and > 2 bound for the Lα phase to be made. For C16 TAC X-ray diffraction data shows that the gel phase occurring below 40°C has an interdigited monolayer structure. At temperatures above the gel phase, H1 and Lα phases occur, these being separated by V1 or intermediate phases. Broadly, similar NMR quadrupole splittings to those found for C12 TAC were measured for the H1 and Lα phases of C16 TAC. Only 2H δ measurements could be made on the gel phase. The values are generally larger than those for the Lα phase, indicating an increase in water ordering because of the increased order of the surfactant layer.
The Effects of Storage on Fresh Human Osteochondral Allografts (2004)

Historically, fresh human osteochondral allografts have been stored in lactated Ringer's solution at 4 degrees C and then transplanted as quickly as possible, generally within 2 to 5 days, to ensure delivery of a high level of viable chondrocytes. Recently, allograft distribution companies have begun to provide fresh osteochondral allografts that are stored in a proprietary culture medium usually for at least 2 weeks before delivery to the surgeon for implantation. The effects of such storage on human cartilage have not been well-defined. In the current study the effects of storage in lactated Ringer's solution and in culture media were assessed. After 7 days of storage in lactated Ringer's solution, a significant decline in chondrocyte viability and metabolic activity was seen. Culture media provided significantly better preservation of the cartilage with viability and metabolic activity remaining essentially unchanged from baseline for as many as 14 days. The biochemical and biomechanical properties of the extracellular matrix remained stable with storage in both solutions with time. These data suggest that osteochondral allografts stored under traditional conditions in lactated Ringer's solution should continue to be implanted as quickly as possible and certainly within 7 days of donor death. If kept in culture media, the storage duration may be extended to approximately 2 weeks.
Normal T-Cell Turnover in Sooty Mangabeys Harboring Active Simian Immunodeficiency Virus Infection (2000)

Sooty mangabeys naturally infected with simian immunodeficiency virus (SIV) remain healthy though they harbor viral loads comparable to those in rhesus macaques that progress to AIDS. To assess the immunologic basis of disease resistance in mangabeys, we compared the effect of SIV infection on T-cell regeneration in both monkey species. Measurement of the proliferation marker Ki-67 by flow cytometry showed that mangabeys harbored proliferating T cells at a level of 3 to 4% in peripheral blood irrespective of their infection status. In contrast, rhesus macaques demonstrated a naturally high fraction of proliferating T cells (7%) that increased two- to threefold following SIV infection. Ki-67(+) T cells were predominantly CD45RA(-), indicating increased proliferation of memory cells in macaques. Quantitation of an episomal DNA product of T-cell receptor alpha rearrangement (termed alpha1 circle) showed that the concentration of recent thymic emigrants in blood decreased with age over a 2-log unit range in both monkey species, consistent with age-related thymic involution. SIV infection caused a limited decrease of alpha1 circle numbers in mangabeys as well as in macaques. Dilution of alpha1 circles by T-cell proliferation likely contributed to this decrease, since alpha1 circle numbers and Ki-67(+) fractions correlated negatively. These findings are compatible with immune exhaustion mediated by abnormal T-cell proliferation, rather than with early thymic failure, in SIV-infected macaques. Normal T-cell turnover in SIV-infected mangabeys provides an explanation for the long-term maintenance of a functional immune system in these hosts.
Increased beta-cell proliferation and reduced mass before diabetes onset in the nonobese diabetic mouse. (1999)

To determine whether loss of beta-cell mass and function in the NOD mouse occurs gradually, beginning after the onset of insulitis, or abruptly, just before the onset of overt diabetes, beta-cell mass and rates of beta-cell proliferation and insulin secretory responses from the perfused pancreas were measured in NOD and control NOD/Scid mice at 8-9, 13, and 18 weeks of age. Of the NOD mice, 11 and 70% had diabetes (fasting blood glucose >8.3 mmol/l) at 13 and 18 weeks of age, respectively. Beta-cell mass in 8-week-old NOD mice was 69% of control mice (P>0.05), but the rate of 5-bromo-2-deoxyuridine uptake was greater, suggesting a compensatory proliferative response to ongoing autoimmune beta-cell destruction. Despite an increase in the rate of beta-cell proliferation, beta-cell mass was significantly reduced by 42% in 13-week-old nondiabetic NOD mice and by 73% in 18-week-old diabetic NOD mice. Insulin secretory responses to glucose and arginine demonstrated reductions of similar magnitude. In 18-week-old diabetic NOD mice, insulin secretion was reduced to a greater degree than beta-cell mass, suggesting the presence of beta-cell dysfunction in addition to reduced mass. These results suggest that in the NOD mouse, beta-cell destruction begins soon after the onset of insulitis. Despite a compensatory beta-cell proliferative response, beta-cell mass progressively falls and is significantly reduced by 13 weeks despite normal blood glucose concentrations. Diabetes may be present when residual beta-cell mass represents 30% of control levels.
High expression of FER tyrosine kinase predicts poor prognosis in clear cell renal cell carcinoma (2012)

FER tyrosine kinase (FER) has been demonstrated to play a critical role in tumorigenesis and metastasis; however, its potential value as a novel prognostic marker for clear cell renal cell carcinoma (ccRCC) remains unclear. In 48 paired samples of ccRCCs and normal adjacent tissues (ADTs), real-time PCR was used to evaluate the expression of FER mRNA. The expression of FER protein was assessed in 87 ADTs and 206 samples of ccRCC using immunohistochemical methods. Statistical analysis was used to examine the correlations between the expression levels of FER and the clinical characteristics of ccRCC patients. A significant difference was identified between ccRCC tissues and ADTs in the mRNA levels of FER. Immunohistochemistry analyses revealed higher expression of FER protein in 87 ccRCC samples compared to the paired ADTs. In addition, FER protein expression in 206 ccRCC samples was significantly correlated with tumor size, T stage, N classification, metastasis, recurrence and Fuhrman grade, while associations with age and gender were not identifed. The Kaplan-Meier survival analysis showed that patients with high FER levels had a poorer survival outcome compared with those with lower levels. The log-rank test demonstrated that the cumulative survival rates were significantly different between the two groups. The Cox regression analysis indicated that FER expression, N stage and distant metastasis were independent prognostic factors for overall survival of ccRCC patients. Our results indicate that overexpression of FER in tumor tissues predicts a poor prognosis of patients with ccRCC, and FER may serve as a novel prognostic marker for ccRCC.
Rapid determination and quantitation of the accessibility to native RNAs by antisense oligodeoxynucleotides in murine cell extracts (1998)

A major concern for antisense experiments is the prediction of effective oligonucleotide binding sites. We have developed a system to carry out oligodeoxyribonucleotide-RNA and ribozyme-RNA binding experiments in cell extracts to create a protein environment known to directly influence the structure of the mRNA. In these experiments the native, endogenous mRNA is probed using oligodeoxyribonucleotides (ODNs) to identify RNase H-accessible sites. The resulting RNase H-mediated cleavages in the cell extracts were quantified using RT-PCR with fluorescein and rhodaminetagged primers to generate fluorescent products that are analyzed and quantified on an automated DNA sequencer. As a model substrate for testing this system, we have targeted the murine DNA methyltransferase (MTase) mRNA. An ODN binding site in native MTase mRNA was identified that was cleaved by endogenous RNase H with an efficiency of 85% in the extracts. The ODN that was most effective in the cell extracts was also found to provide the best activity in vivo , resulting in a 75-85% reduction of the MTase mRNA. These data support the use of cell extracts and native transcripts to identify antisense and perhaps ribozyme target sites.
Fiber-optic near-infrared reflectance sensor for detection of organics in soils (1995)

A near infrared fiber-optic chemical sensor system using reflectance spectroscopic measurements has been assembled. This system was evaluated and found attractive for remote detection of organics in soils over distances of at least 30 meters.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The costs and limits of availability for replicated services (2001)

As raw system and network performance continues to improve at exponential rates, the utility of many services is increasingly limited by availability rather than performance. A key approach to improving availability involves replicating the service across multiple, wide-area sites. However, replication introduces well-known tradeoffs between service consistency and availability. Thus, this paper explores the benefits of dynamically trading consistency for availability using a continuous consistency model. In this model, applications specify a maximum deviation from strong consistency on a per-replica basis. In this paper, we: i) evaluate availability of a prototype replication system running across the Internet as a function of consistency level, consistency protocol, and failure characteristics, ii) demonstrate that simple optimizations to existing consistency protocols result in significant availability improvements (more than an order of magnitude in some scenarios), iii) use our experience with these optimizations to prove tight upper bounds on the availability of services, and iv) show that maximizing availability typically entails remaining as close to strong consistency as possible during times of good connectivity, resulting in a communication versus availability trade-off.
Changing Residue 338 in Human Factor IX from Arginine to Alanine Causes an Increase in Catalytic Activity (1998)

This study was designed to identify functionally important factor IX (FIX) residues. Using recombinant techniques and cell culture, we produced a mutant FIX with arginine at 338 changed to alanine (R338A-FIX). This molecule had approximately 3 times greater clotting activity than that of wild type FIX (wt-FIX) in the activated partial thromboplastin assay. R338A-FIX reacted normally with a panel of three FIX specific monoclonal antibodies and migrated on sodium dodecyl sulfate-polyacrylamide gels indistinguishably from wt-FIX. Using functional assays, we determined that R338A-FIXa's Kd for factor VIIIa (FVIIIa) was similar to that of wt-FIXa. Our kinetic analysis, using factor X as substrate, indicated that the mutation's major effects were a 3-fold increase in kcat and a 2-fold decrease in Km both manifested only in the presence of FVIIIa. R338A-FIXa's increased catalytic efficiency did not result from ablation of a thrombin sensitive site, reported to occur at arginine 338, since in our assays the thrombin inhibitor, hirudin, had no effect on activity of either wt-FIXa or R338A-FIXa. R338A-FIXa and wt-FIXa had equal activity, with or without FVIIIa, toward the synthetic substrate, methylsulfonyl-D-cyclohexylglycyl-arginine-p-nitroanilide. Interestingly, R338A-FIXa had reduced affinity for heparin. Therefore, we propose that R338A-FIXa's increased activity is not due to an allosteric effect on the active site, but that the Arg-338 residue is part of an exosite that binds both factor X and the mucopolysaccharide, heparin.
Diversity decay in opportunistic content sharing systems (2011)

As content that users access on their mobile devices becomes bulkier, opportunistic networking is becoming a potential complement to centralised and infrastructure based downloads. We study how users share items of mutual interest with each other with a simple model based on a `networked urn process'. We investigate the effect of different content sharing policies upon a multi-category set of items. We find that the process of sharing mutual interests inherently disproportionately reinforces category replication disparity, i.e., the most popular categories become proportionally even more numerous. These findings uncover a major hurdle in the creation of automatic opportunistic file sharing between users. Even if users altruistically sacrifice battery power and network resources to share content not relevant to them, overall, the system may not be able to fairly distribute items that belong to niche categories.
Formation mechanisms of Monochloropropanediol (MCPD) fatty acid diesters in refined palm (Elaeis guineensis) oil and related fractions (2011)

Monochloropropanediol (MCPD) fatty acid esters are process contaminants generated during the deodorisation of edible oils. In particular, MCPD diesters are found in higher abundance in refined palm oil than other edible oils. In the present study, a series of model reactions mimicking palm oil deodorisation has been conducted with pure acylglycerols in the presence or absence of either organic or inorganic chlorine-containing compounds. Results showed that the bulk of MCPD diesters are formed above 200°C through the reaction of organochlorines with triacylglycerols (TAG). Additional experiments confirmed that this reaction can be initiated during palm oil deodorisation by hydrogen chloride (HCl) gas evolved through the thermal degradation of organochlorines present in the oil. Therein, the majority of the ultimately produced MCPD diesters are the result of HCl reacting with TAG, via protonation, followed by the elimination of a fatty acid residue. Two possible MCPD diester formation mechanisms are highlighted, both of which involve acyloxonium ion reactive intermediates. Investigations with pure TAG regio-isomers showed that MCPD ester formation is regioselective and the sn-1(3) position of the glycerol backbone is favoured.
Comparison of azelastine nasal spray and oral ebastine in treating seasonal allergic rhinitis (1995)

The efficacy and safety of the nasally administered histamine H1 receptor blocking drug azelastine was investigated in a randomized comparative trial with ebastine. Patients were treated for 14 days and efficacy was assessed by the physician using a rating scale measuring 10 nasal and ocular symptoms of seasonal rhinitis (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Tolerability was measured on the basis of reported adverse events. Data from a total of 59 patients were included in the efficacy analysis. Both treatment groups had dramatic reductions in the physician's total symptom score following treatment. Mean scores in the azelastine group decreased from 12.4 pretreatment to 5.6, while the mean ebastine scores decreased from 13.6 to 6.6. There was no significant difference between the two groups (p = 0.86). Changes in individual rhinitis symptoms showed no differences between the two groups. The majority of patients in both treatment groups reported an initial relief of symptoms within 1 h of dosing. For seven patients treated with azelastine, the initial effect was already seen after 10 min (ebastine: two patients). Eight adverse events were reported in each treatment group; all were mild except one report of sedation in an ebastine patient, which was of moderate severity. Three patients reported somnolence during treatment with ebastine. A bitter taste was mentioned by four patients in the azelastine group, but neither somnolence nor sedation was reported with azelastine. In conclusion, the results of the study suggest that both azelastine and ebastine are effective treatments of the symptoms of seasonal allergic rhinitis. Both drugs were well tolerated.
Comparative genomics on mammalian Fgf6-Fgf23 locus (2005)

CCND2-C12orf5-FGF23-FGF6 locus at human chromosome 12p13.32 and CCND1-ORAOV1-FGF19-FGF4 locus at human chromosome 11q13.3 are paralogous regions (paralogons) within the human genome. FGF23 is the causative factor for tumor-induced osteomalacia (TIO), a paraneoplastic disorder characterized by hypophosphatemia and skeletal undermineralization, and also for autosomal dominant hypophosphatemic rickets (ADHR). Here, rat Fgf6 and Fgf23 complete coding sequences were determined by using bioinformatics. Rat Fgf6 and Fgf23 genes, consisting of three exons, were located within AC103292.6 rat genome sequence. Rat Fgf6 and Fgf23 genes were clustered in tail-to-head manner with an interval of about 52 kb. Human FGF6 and FGF23 genes were clustered in tail-to-head manner with an interval of about 54 kb. Intergenic conserved region (IGCR) within the FGF6-FGF23 gene cluster was identified based on the evolutionary conservation. Human FGF6-FGF23 IGCR (nucleotide position 111648-112242 of AC008012.8 genome sequence) and rat Fgf6-Fgf23 IGCR (nucleotide position 156318-156894 of AC103292.6 genome sequence) showed 77.6% total nucleotide identity. CP2, E47, CREB and PAX4 binding sites were conserved among human FGF6, rat Fgf6, and mouse Fgf6 promoters. GATA and E47 binding sites were conserved among human FGF23, rat Fgf23, and mouse Fgf23 promoters. Because mouse Fgf23 mRNA was expressed in dendritic cells and activated spleen, tumor infiltrating dendritic cells are candidate sources of FGF23 secretion in TIO patients. This is the first report on comparative genomics analyses on human FGF6-FGF23 gene cluster and rodents Fgf6-Fgf23 gene cluster.