gebhart/patrepeval huggingface dataset:
Phase III, Randomized Study of Gemcitabine and Oxaliplatin Versus Gemcitabine (fixed-dose rate infusion) Compared With Gemcitabine (30-minute infusion) in Patients With Pancreatic Carcinoma E6201: A Trial of the Eastern Cooperative Oncology Group (2009)

Neither GEM FDR nor GEMOX resulted in substantially improved survival or symptom benefit over standard GEM in patients with advanced pancreatic cancer.
Tafazzin Protein Expression Is Associated with Tumorigenesis and Radiation Response in Rectal Cancer: A Study of Swedish Clinical Trial on Preoperative Radiotherapy (2014)

Strong expression of TAZ protein seems to be related to rectal cancer development and RT response, it can be a predictive biomarker of distant recurrence in patients with preoperative RT.
Reciprocal regulation of autophagy and dNTP pools in human cancer cells (2014)

Ribonucleotide reductase (RNR) plays a critical role in catalyzing the biosynthesis and maintaining the intracellular concentration of 4 deoxyribonucleoside triphosphates (dNTPs). Unbalanced or deficient dNTP pools cause serious genotoxic consequences. Autophagy is the process by which cytoplasmic constituents are degraded in lysosomes to maintain cellular homeostasis and bioenergetics. However, the role of autophagy in regulating dNTP pools is not well understood. Herein, we reported that starvation- or rapamycin-induced autophagy was accompanied by a decrease in RNR activity and dNTP pools in human cancer cells. Furthermore, downregulation of the small subunit of RNR (RRM2) by siRNA or treatment with the RNR inhibitor hydroxyurea substantially induced autophagy. Conversely, cancer cells with abundant endogenous intracellular dNTPs or treated with dNTP precursors were less responsive to autophagy induction by rapamycin, suggesting that autophagy and dNTP pool levels are regulated through a negative feedback loop. Lastly, treatment with si-RRM2 caused an increase in MAP1LC3B, ATG5, BECN1, and ATG12 transcript abundance in xenografted Tu212 tumors in vivo. Together, our results revealed a previously unrecognized reciprocal regulation between dNTP pools and autophagy in cancer cells.
Synthesis and Self-Assembling Properties of Polymerizable Organogelators (2002)

In this paper we report the development of a family of polymerizable urea derivatives that are gelators for organic solvents. The design involves amino-acid-based urea derivatives containing methacrylate functional groups. Several of the bis-ureas show excellent gelation properties in a variety of organic solvents at very low concentrations (1.5 mM). The self-assembling properties of these compounds were studied by X-ray powder diffraction, optical microscopy, and electronic microscopy. The molecules self-assemble into fibrous aggregates as indicated by scanning electron microscopy. Depending on the nature of the monomeric unit, the structure of the aggregates ranges from small to large fibers and planar sheets. In polar solvents, the molecules exhibit multilamellar packing modes. The organogels can be polymerized by photoirradiation leading to significant increases in stability as indicated by changes in phase-transition temperature. The morphology of the aggregates was seen to maintain a similar structure both before and after irradiation. This method provides a novel type of polymer with designed self-assembling architecture and also affords to a route to stabilized polymer gels.
Targeting malignant B cells with an immunotoxin against ROR1 (2012)

The selective cell surface expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) has made ROR1 a novel and promising target for therapeutic monoclonal antibodies (mAbs). Four mouse mAbs generated by hybridoma technology exhibited specific binding to human ROR1. Epitope mapping studies showed that two mAbs (2A2 and 2D11) recognized N-terminal epitopes in the extracellular region of ROR1 and the other two (1A1 and 1A7) recognized C-terminal epitopes. A ROR1- immunotoxin (BT-1) consisting of truncated Pseudomonas exotoxin A (PE38) and the VH and VL fragments of 2A2-IgG was made recombinantly. Both 2A2-IgG and BT-1 showed dose-dependent and selective binding to primary CLL and MCL cells and MCL cell lines. Kinetic analyses revealed 0.12-nM (2A2-IgG) to 65-nM (BT-1) avidity/affinity to hROR1, depicting bivalent and monovalent interactions, respectively. After binding to cell surface ROR1, 2A2-IgG and BT-1 were partially internalized by primary CLL cells and MCL cell lines, and BT-1 induced profound apoptosis of ROR1-expressing MCL cell lines in vitro (EC 50 = 16 pM-16 nM), but did not affect ROR1-negative cell lines. Our data suggest that ROR1-immunotoxins such as BT-1 could serve as targeted therapeutic agents for ROR1-expressing B cell malignancies and other cancers.
Clinical and immunological assessment of Mycobacterium vaccae (SRL172) with chemotherapy in patients with malignant mesothelioma (2002)

The objectives of this study were to determine the toxicity of intratumoural/intrapleural SRL172 in addition to intradermal SRL172 and standard chemotherapy (mitomycin-C, vinblastine and cisplatin) in patients with malignant mesothelioma. Patients received chemotherapy (mitomycin-C: 8 mg m(-2), vinblastine: 6 mg m(-2), cisplatin 50 mg m(-2)) on a 3-weekly basis for up to six courses. IP SRL172 injections were given 3-weekly prior to chemotherapy and escalated in groups of three patients from 1 microg to 1 mg bacilli in 10-fold increments. Patients were also given ID SRL172 at a dose of 1 mg bacilli 4-weekly. Patients were assessed for toxicity after each course of chemotherapy and for response by CT imaging. Immuno-haematological parameters were analyzed pre-treatment and 1 month after completion of treatment. There was no dose limiting toxicity with IP SRL172 although there was greater toxicity at the highest dose (n=13). There were six out of 16 partial responses (37.5%). Haemato-immunological parameters, measured in seven patients pre and post-therapy, revealed that response rate correlated with a decrease in platelet count and there was an increase in activation of natural killer cells and a decrease in the percentage of IL-4 producing T cells in all tested patients post-treatment. SRL172 can be given safely into tumour deposits and the pleural cavity in patients with malignant mesothelioma and we have established the dose for phase II testing.
Object management system concepts (1984)

An office database should be a “total” information resource in that it should be capable of storing data of many arbitrary types. Users of such a system should be able to store conveniently their documents and graphics objects in the same logical storage space as their more traditional records-oriented data. This paper presents a data model that can be used to describe more effectively the objects that occur naturally in the office environment. This model exploits some of the richer semantics of office objects such as the containment of one object within another (e.g., reports contain chapters) and the version histories of objects and their constituent parts. This model forms the basis for our experimental object management system which is used to support the creation of new office application programs.
Medicinal Chemistry of Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibitors (2013)

Nicotinamide phoshophoribosyltransferase (NAMPT) plays a key role in the replenishment of the NAD pool in cells. This in turn makes this enzyme an important player in bioenergetics and in the regulation of NAD-using enzymes, such as PARPs and sirtuins. Furthermore, there is now ample evidence that NAMPT is secreted and has a role as a cytokine. An important role of either the intracellular or extracellular form of NAMPT has been shown in cancer, inflammation, and metabolic diseases. The first NAMPT inhibitors (FK866 and CHS828) have already entered clinical trials, and a surge in interest in the synthesis of novel molecules has occurred. The present review summarizes the recent progress in this field.
Concomitant Tumor Immunity to a Poorly Immunogenic Melanoma Is Prevented by Regulatory T Cells (2004)

Concomitant tumor immunity describes immune responses in a host with a progressive tumor that rejects the same tumor at a remote site. In this work, concomitant tumor immunity was investigated in mice bearing poorly immunogenic B16 melanoma. Progression of B16 tumors did not spontaneously elicit concomitant immunity. However, depletion of CD4(+) T cells in tumor-bearing mice resulted in CD8(+) T cell-mediated rejection of challenge tumors given on day 6. Concomitant immunity was also elicited by treatment with cyclophosphamide or DTA-1 monoclonal antibody against the glucocorticoid-induced tumor necrosis factor receptor. Immunity elicited by B16 melanoma cross-reacted with a distinct syngeneic melanoma, but not with nonmelanoma tumors. Furthermore, CD8(+) T cells from mice with concomitant immunity specifically responded to major histocompatibility complex class I-restricted epitopes of two melanocyte differentiation antigens. RAG1(-/-) mice adoptively transferred with CD8(+) and CD4(+) T cells lacking the CD4(+)CD25(+) compartment mounted robust concomitant immunity, which was suppressed by readdition of CD4(+)CD25(+) cells. Naturally occurring CD4(+)CD25(+) T cells efficiently suppressed concomitant immunity mediated by previously activated CD8(+) T cells, demonstrating that precursor regulatory T cells in naive hosts give rise to effective suppressors. These results show that regulatory T cells are the major regulators of concomitant tumor immunity against this weakly immunogenic tumor.
National Initiatives to Build Healthcare Information Infrastructures. (2010)

Significant sums of money are invested in information systems (IS) initiatives in the healthcare sector all over the world. Most countries have implemented Electronic Patient Record (EPR) systems, which are clinical IS that support documentation of examination, treatment, and care of patients. EPR systems are expected to raise the quality of care, reduce medical errors, cut waiting time and render the operation of healthcare more effective. Many of the expected benefits from EPR systems hinge on their ability to facilitate information sharing between healthcare providers. Consequently, many governments and healthcare providers have formulated national strategies to achieve a fully integrated information infrastructure building on interoperable EPR systems. In this paper we describe how the health authorities in Denmark have attempted to achieve interoperability through standardization of EPR systems in the so-called B-EPR initiative (i.e. Basic Structure for EPR).The initiative eventually failed and we argue that the main reason for this was too high ambitions along three dimensions: the geographical reach, the functional scope, and the temporal span. We argue that a critical look at the ambition level and associated strategies may contribute to formulating more modest targets. It is worthwhile to focus on defining strategies that specify how small and manageable initiatives can be extended and built on.
Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane. (1993)

A 16-residue peptide [(Ala-Glu-Ala-Glu-Ala-Lys-Ala-Lys)2] has a characteristic beta-sheet circular dichroism spectrum in water. Upon the addition of salt, the peptide spontaneously assembles to form a macroscopic membrane. The membrane does not dissolve in heat or in acidic or alkaline solutions, nor does it dissolve upon addition of guanidine hydrochloride, SDS/urea, or a variety of proteolytic enzymes. Scanning EM reveals a network of interwoven filaments approximately 10-20 nm in diameter. An important component of the stability is probably due to formation of complementary ionic bonds between glutamic and lysine side chains. This phenomenon may be a model for studying the insoluble peptides found in certain neurological disorders. It may also have implications for biomaterials and origin-of-life research.
Avoidance of sun exposure is a risk factor for all‐cause mortality: results from the Melanoma in Southern Sweden cohort (2014)

The results of this study provide observational evidence that avoiding sun exposure is a risk factor for all-cause mortality. Following sun exposure advice that is very restrictive in countries with low solar intensity might in fact be harmful to women's health.
Reconstruction of Damaged Corneas by Transplantation of Autologous Limbal Epithelial Cells (2000)

Transplantation of autologous limbal epithelial cells cultured on amniotic membrane is a simple and effective method of reconstructing the corneal surface and restoring useful vision in patients with unilateral deficiency of limbal epithelial cells.
A Helical Epitope in the C4 Domain of HIV Glycoprotein 120 (1995)

The fourth conserved domain of the human immunodeficiency virus type 1 (HIV-1) envelope, the C4 region of glycoprotein 120 (gp120), is an amphipathic stretch of amino acids that, based on mutational analyses, constitutes a major component of the CD4 binding region in gp120. In the absence of crystallographic and NMR data on C4 in intact gp120, we sought to gain insight into C4's conformation and accessibility in gp120 by taking an immunochemical approach. In this study, a peptomer composed of a repeat peptide of C4 amino acids 419-436 from gp120 of HIV-1MN was synthesized for use as a conformationally constrained immunogen. Circular dichroism studies disclosed that the polymerized peptide, peptomer-(419-436), in 0.01 M Na2HPO4 buffer, pH 7.4, at 25 degrees C contained a dominant alpha-helical structure (53 +/- 1%) compared with 2 +/- 4% alpha-helical content for the monomeric peptide-(419-436). The peptomer in Ribi's adjuvant induced the production of rabbit antibodies that recognized recombinant and native gp120 but, consistent with the literature, the C4 peptide having no conformational constraints did not. The experimental results show that only those antibodies formed against a helical immunogen from C4 will recognize recombinant and native gp120, and, therefore, the results support the notion that C4 is an alpha-helix in gp120.
Inhibitors of P-Glycoprotein-Mediated Daunomycin Transport in Rat Liver Canalicular Membrane Vesicles (1996)

P-glycoprotein (P-gp), the multidrug resistance (MDR) gene product, is exclusively located on the canalicular membrane of hepatocytes. Recent studies using isolated rat canalicular liver plasma membrane (cLPM) vesicles indicate that daunomycin (DNM) is a substrate for the ATP-dependent P-gp efflux system in the rat liver. The isoforms of P-gp present in cLPM and in cancer cell lines differ in that the major form present in the liver represents the gene product of mdr2 in mice (MDR3 in humans; class III) while the isoform of P-gp in cancer cells is the gene product of mdr1 in mice (MDR1 in humans, class I). The objective of this study was to examine the inhibitory effects of various organic compounds, most of which have been studied previously in MDR cancer cells, on P-gp-mediated [3H]DNM uptake into cLPM. Also, the stereospecificity of P-gp for its substrates was investigated by comparing the inhibitory effects of the enantiomers and the racemic mixtures of verapamil and propranolol. DNM exhibited ATP-dependent active transport into rat liver cLPM with a Km of 26.8 +/- 13.4 microM and a Vmax of 4.9 +/- 0.8 nmol/45 s/mg of protein (n = 4). ADP, AMP, and a nonhydrolyzable ATP analogue did not increase DNM transport over the control value. Thirty-one potential inhibitors were examined; only acridine orange, doxorubicin, verapamil, propranolol, phosphatidylcholine, beta-estradiol glucuronide, and DNM itself showed statistically significant inhibition of [3H]DNM uptake into cLPM. These results suggest that only a limited number of substrates bind to or are transported across the hepatic canalicular membrane via P-gp. Phosphatidylcholine, a substrate for the gene product of the class III P-gp gene, produced significant inhibition of [3H]DNM transport (30.6% at a 10-fold-higher substrate concentration), suggesting that transport may be mediated, at least in part, by this P-gp gene product. There were no statistically significant differences in the inhibitory effects of the enantiomers and racemate of verapamil on [3H]DNM transport into cLPM, but the enantiomers of propranolol exhibited stereospecific inhibition of DNM transport. (R)-(+)-Propranolol produced a statistically significant inhibition of [3H]DNM transport similar to that observed with the racemic mixture, while (S)(-)-propranolol showed no inhibition. These findings suggest that bile canalicular P-gp may exhibit stereospecificity of binding or transport for its substrates.
Use of C6-deficient rats to evaluate the mechanism of hyperacute rejection of discordant cardiac xenografts. (1993)

C plays a critical role in the hyperacute rejection (HAR) of discordant xenografts (Xg), but the relative contribution of early vs late C components is unknown. In this study, genetic differences in C6 activity were correlated with HAR of guinea pig cardiac Xg by the rat. Seven rat strains were tested for C activity. Six strains (PVG.R1 (R1), PVG.1A (1A), DA, W/F, F344, LEW) had readily detectable C activity in the total and alternative pathways. Some PVG rats also had adequate C activity [PVG (C+)] but others [PVG (C-)] had a profound C6 deficiency. All rats with adequate C activity (n = 35) rejected cardiac Xg between 15 and 80 min. PVG (C+) (n = 6) rats also rejected cardiac Xg hyperacutely (26 +/- 12 min), whereas PVG (C-) (n = 16) rats, which had high preformed IgM natural antibody titers, rejected cardiac Xg in 1 to 2 days (2678 +/- 542 min). Transfer of serum from R1 rats to PVG (C-) recipients with vigorously beating Xg caused HAR of cardiac Xg within 116 +/- 75 min. Transfer of fresh PVG (C-) serum or heat-inactivated R1 serum did not induce HAR. HAR was characterized by intravascular platelet aggregation and interstitial hemorrhage, whereas Xg transplanted to PVG (C-) recipients had patent vessels at 30 min but were heavily infiltrated by granulocytes and monocytes at 2 days. These findings indicate that a deficiency in C6 prevents HAR but allows an accelerated acute rejection that may be mediated by the generation of vasoactive and chemotactic C3a and C5a.
Increased N-Myristoyltransferase Activity Observed in Rat and Human Colonic Tumors (1995)

This study demonstrates for the first time that N-myristoyltransferase activity is higher in colonic epithelial neoplasms than in normal-appearing colonic tissue and that an increase in N-myristoyltransferase activity appears at an early stage in colonic carcinogenesis.
Efficient erasure correcting codes (2001)

We introduce a simple erasure recovery algorithm for codes derived from cascades of sparse bipartite graphs and analyze the algorithm by analyzing a corresponding discrete-time random process. As a result, we obtain a simple criterion involving the fractions of nodes of different degrees on both sides of the graph which is necessary and sufficient for the decoding process to finish successfully with high probability. By carefully designing these graphs we can construct for any given rate R and any given real number /spl epsiv/ a family of linear codes of rate R which can be encoded in time proportional to ln(1//spl epsiv/) times their block length n. Furthermore, a codeword can be recovered with high probability from a portion of its entries of length (1+/spl epsiv/)Rn or more. The recovery algorithm also runs in time proportional to n ln(1//spl epsiv/). Our algorithms have been implemented and work well in practice; various implementation issues are discussed.
Acute stress delays brain mitochondrial permeability transition pore opening (2014)

Since emotional stress elicits brain activation, mitochondria should be a key component of stressed brain response. However, few studies have focused on mitochondria functioning in these conditions. In this work, we aimed to determine the effects of an acute restraint stress on rat brain mitochondrial functions, with a focus on permeability transition pore (PTP) functioning. Rats were divided into two groups, submitted or not to an acute 30-min restraint stress (Stress, S-group, vs. Control, C-group). Brain was removed immediately after stress. Mitochondrial respiration and enzymatic activities (complex I, complex II, hexokinase) were measured. Changes in PTP opening were assessed by the Ca(2+) retention capacity. Cell signaling pathways relevant to the coupling between mitochondria and cell function (adenosine monophosphate-activated protein kinase, phosphatidylinositol 3-kinase, glycogen synthase kinase 3 beta, MAPK, and cGMP/NO) were measured. The effect of glucocorticoids was also assessed in vitro. Stress delayed (43%) the opening of PTP and resulted in a mild inhibition of complex I respiratory chain. This inhibition was associated with significant stress-induced changes in adenosine monophosphate-activated protein kinase signaling pathway without changes in brain cGMP level. In contrast, glucocorticoids did not modify PTP opening. These data suggest a rapid adaptive mechanism of brain mitochondria in stressed conditions, with a special focus on PTP regulation. In a rat model of acute restraint stress, we observed substantial changes in brain mitochondria functioning. Stress significantly (i) delays (43%) the opening of permeability transition pore (PTP) by the calcium (Ca(2+) ), its main inductor and (ii) results in an inhibition of complex I in electron transport chain associated with change in AMPK signaling pathway. These data suggest an adaptive mechanism of brain mitochondria in stressed condition, with a special focus on PTP regulation.
The Pfam Protein Families Database (2000)

Pfam is a large collection of protein multiple sequence alignments and profile hidden Markov models. Pfam is available on the WWW in the UK at http://www.sanger.ac.uk/Software/Pfam/, in Sweden at http://www.cgr.ki.se/Pfam/ and in the US at http://pfam.wustl.edu/. The latest version (4.3) of Pfam contains 1815 families. These Pfam families match 63% of proteins in SWISS-PROT 37 and TrEMBL 9. For complete genomes Pfam currently matches up to half of the proteins. Genomic DNA can be directly searched against the Pfam library using the Wise2 package.
Donor neutralization in GaAs(Si) by atomic hydrogen (1985)

Hydrogen plasma exposure of n-type GaAs(Si) at 250 °C results in a decrease of the free-carrier concentration by several orders of magnitude. This neutralization effect has been demonstrated in silicon-doped layers grown by molecular beam epitaxy or formed by annealed implants as well as in bulk material. The same effect is produced electrochemically (H3PO4 electrolyte), whereas helium plasma exposure has no effect, thus confirming the role of hydrogen insertion. The hydrogen penetration depth into GaAs(Si) is inversely dependent on the Si concentration. Recovery of the electrical activity follows first order dissociation kinetics with a dissociation energy of 2.1 eV. Complete restoration of free-carrier concentration occurs by heating at 420 °C for less than 3 min. Extrapolated to low temperatures, these results imply many years of stability at 150 °C or below.