gebhart/patrepeval huggingface dataset:
Azathioprine in the treatment of systemic lupus erythematosus. A controlled study (1971)

Abstract Sixteen patients with systemic lupus erythematosus have been observed for from 1 to 4 years while taking prednisone plus azathioprine in a dose of 2.5 mg/kg/day and compared to 19 patients with systemic lupus erythematosus managed with prednisone alone for a similar period. Patients receiving azathioprine showed a decreased mortality and morbidity, required less daily prednisone than the control group, exhibited no increased tendency to develop infection, had fewer exacerbations of their disease and maintained better renal function. Discontinuation of the azathioprine was associated with severe exacerbations of disease. The toxicity of azathioprine was minimal.
Monophosphoryl lipid A behaves as a T-cell-independent type 1 carrier for hapten-specific antibody responses in mice (1995)

It is known that the lipopolysaccharide (LPS) of gram-negative bacteria, in addition to being a potent adjuvant, is an effective carrier for covalently associated haptens. However, the toxic nature of most forms of LPS precludes their use as adjuvants or carriers for human vaccines. 4'-Monophosphoryl lipid A (MLA), a derivative of LPS with attenuated toxicity, is currently being tested in humans as an immunological adjuvant. In this study, MLA was tested for its ability to function as a carrier for a small hapten, the trinitrophenyl group (TNP). MLA was first modified by addition of 6-aminocaproic acid to the 6' position of the disaccharide backbone (Cap-MLA). TNP was then attached to Cap-MLA via the free amino group, yielding TNP-Cap-MLA. Immunization of normal mice with TNP-Cap-MLA resulted in high-titer anti-TNP responses of immunoglobulin M and all immunoglobulin G subclasses. Furthermore MLA, like other T-cell-independent type 1 (TI-1) carriers, induced responses in athymic and X-linked immunodeficient mice. In all cases, immunization with either MLA alone or TNP-Cap plus MLA failed to induce measurable anti-TNP antibodies of any isotype, indicating that covalent association of MLA and hapten was necessary for MLA's carrier activity to be manifested. These properties of MLA make it a potential candidate as a carrier for vaccine subunit components, such as small peptides, especially for situations in which T-cell help is impaired, as occurs following human immunodeficiency virus type 1 infection.
Wyner-Ziv coding of motion video (2003)

In current interframe video compression systems, the encoder performs predictive coding to exploit the similarities of successive frames. The Wyner-Ziv theorem on source coding with side information available only at the decoder suggests that an asymmetric video codec, where individual frames are encoded separately, but decoded conditionally (given temporally adjacent frames) could achieve similar efficiency. We report the first results on a Wyner-Ziv coding scheme for motion video that uses intraframe encoding, but interframe decoding.
CD154 on the surface of CD4+CD25+ regulatory t cells contributes to skin transplant tolerance (2003)

Neutralizing the function of CD154 on regulatory T cells upon antigen exposure induces heightened levels of suppressive activities and is likely a contributing factor to the long-lived therapeutic effects of anti-CD154 treatment.
The non‐enzymatic microbicidal activity of lysozymes (1999)

T4 lysozyme was thought to destroy bacteria by its muramidase activity. However, we demonstrate here that amphipathic helix stretches in the C-terminus of T4 lysozyme mediate its bactericidal and fungistatic activities. In heat-denatured T4 lysozyme, the enzymatic activity is completely abolished but unexpectedly, the antimicrobial functions remain preserved. Small synthetic peptides corresponding to amphipathic C-terminal domains of T4 lysozyme show a microbicidal activity. Its membrane disturbing activity was directly demonstrated for bacterial, fungal and plant cells but not in a hemolysis assay. Comparable results were obtained with hen egg white lysozyme. This opens up many new opportunities for optimization of lysozymes as antimicrobial agents in various applications by protein engineering.
Polarization Dependence of the Two-Photon Absorption of Tumbling Molecules with Application to Liquid 1-Chloronaphthalene and Benzene (1970)

The two-photon absorption cross section δ for photons of any polarization (linear, circular, or elliptical) is averaged over all orientations of the absorbing molecule. The result is given by 〈δ〉 = δFF + δGG + δHH, where δF, δG and δH are molecular parameters and F, G, and H are simple functions of the polarization vectors. It is shown how the δ's may be calculated from theory and also how they may be measured by experiment. Experiments using only linearly polarized light are insufficient to determine all three δ's; hence, circularly polarized light will play an essential role in this spectroscopy. For absorption of two linearly polarized photons with angle θ between their polarization vectors, the angular dependence is 〈δ〉 = A + Bcos2θ, where A and B are simple combinations of the δ's. We obtain two exact symmetry rules which permit allowed two-photon transitions of different symmetries to be distinguished. For transitions from totally symmetric ground states the rules are: (1) If the excited state transforms like xy, yz, or zx, then δF = 0. (2) If the excited state transforms like x2, y2, or z2, then δG = δH. In cases of near resonance, when a single intermediate state dominates the formula for the cross section, we show that δF = δH, and that linearly polarized light suffices for a complete investigation. These results are applied to liquid 1-chloronaphthalene. We find two allowed two-photon transitions which are assigned Bb11g (perpendicular nodes) at 37 700 cm−1 and A1g (total symmetry) at 42 600 cm−1. This is in reasonable agreement with theoretical predictions of other authors. We have also examined the region of the second excited singlet of benzene, near 6.2 eV. We were not able to detect any two-photon absorption, setting an upper limit of about 10−51 cm4·sec/photon·molecule on its 〈δ〉. This leads to an unequivocal assignment of B11u for this state according to calculations of Jortner. In an Appendix we examine the effect of “hot spots” in the laser beam on the observed cross sections. We show that the elimination of the hot spots is of some importance, contrary to a statement of other authors.
Kinetics of hairpin ribozyme cleavage in yeast. (1997)

Hairpin ribozymes catalyze a self-cleavage reaction that provides a simple model for quantitative analyses of intracellular mechanisms of RNA catalysis. Decay rates of chimeric mRNAs containing self-cleaving ribozymes give a direct measure of intracellular cleavage kinetics in yeast. Intracellular ribozyme-mediated cleavage occurs at similar rates and shows similar inhibition by ribozyme mutations as ribozyme-mediated reactions in vitro, but only when ribozymes are located in a favorable mRNA sequence context. The impact of cleavage on mRNA abundance is shown to depend directly on intrinsic mRNA stability. Surprisingly, cleavage products are no more labile than uncleaved mRNAs despite the loss of terminal cap structures or poly (A).
Resected RNA pseudoknots and their recognition by histidyl-tRNA synthetase (1998)

Duplexes constituted by closed or open RNA circles paired to single-stranded oligonucleotides terminating with 3'-CCAOH form resected pseudoknots that are substrates of yeast histidyl-tRNA synthetase. Design of this RNA fold is linked to the mimicry of the pseudoknotted amino acid accepting branch of the tRNA-like domain from brome mosaic virus, known to be charged by tyrosyl-tRNA synthetases, with RNA minihelices recapitulating accepting branches of canonical tRNAs. Prediction of the histidylation function of the new family of minimalist tRNA-like structures relates to the geometry of resected pseudoknots that allows proper presentation to histidyl-tRNA synthetase of analogues of the histidine identity determinants N-1 and N73 present in tRNAs. This geometry is such that the analogue of the major N-1 histidine determinant in the RNA circles faces the analogue of the discriminator N73 nucleotide in the accepting oligonucleotides. The combination of identity elements found in tRNAHis species from archaea, eubacteria, and organelles (G-1/C73) is the most efficient for determining histidylation of the duplexes. The inverse combination (C-1/G73) leads to the worst histidine acceptors with charging efficiencies reduced by 2-3 orders of magnitude. Altogether, these findings open new perspectives for understanding evolution of tRNA identity and serendipitous RNA functions.
The Autoimmune Regulator Directly Controls the Expression of Genes Critical for Thymic Epithelial Function (2007)

The autoimmune regulator (Aire) gene plays an essential role in negative selection of T cells and deletion of autoreactive T cells in the thymus. The defect in thymic selection in Aire(-/-) mice was attributed to the repressed expression of tissue-specific Ags in the thymic epithelial cells and defective Ag presentation; however, the molecular mechanism underlying these functions has been elusive. Using the chromatin immunoprecipitation technique, we demonstrate here that Aire binds in vivo to specific DNA sequence motifs and directly regulates thymic expression of genes important for thymic functions including expression of autoantigens, cytokines, transcription factors, and posttranslational modifiers. These results unambiguously established Aire as a key transcriptional regulator of the immune system.
Extracorporeal photopheresis in the treatment of AIDS-related complex: extended trial. (1993)

The objective of this study was to further evaluate the relative safety of extracorporeal photopheresis in the treatment of patients with AIDS-related complex. Twenty patients with AIDS-related complex, three from the initial report and 17 additional patients, were enrolled. The patient population had various risk factors. There were nine homosexuals, five heterosexual consorts of human immunodeficiency virus (HIV)-positive patients, four reformed i.v. drug abusers, and two hemophilia patients. The patients received monthly treatment with extracorporeal photopheresis. In 16 of the 19 patients, this study provides evidence of clinical stability over a longer period. The relative stability of beta 2-microglobulin and neopterin levels demonstrates that photopheresis therapy does not have an untoward effect on the degree of activation of the immune system with respect to induction of HIV replication. Antibody titers to the major viral antigens, envelope glycoproteins (gp) 120 and 41, reverse transcriptase enzyme gp 66/31 and 55, and the core protein p24 remained stable throughout the course of therapy. A subjective improvement was noted in the majority of patients. The evaluation of T-cell subsets revealed that the photopheresis treatment did not have a detrimental effect on CD3 and CD8 cells. Some decreases were noted in the CD4 cell counts but the decline may be less than is normally seen at corresponding stages of HIV infection. Skin test responsivity improved in 11 patients, remained unchanged in seven patients, and declined in two. The preliminary results suggest that in HIV disease, extracorporeal photopheresis is safe and warrants a prospective controlled trial.
The pyramid match kernel: discriminative classification with sets of image features (2005)

Discriminative learning is challenging when examples are sets of features, and the sets vary in cardinality and lack any sort of meaningful ordering. Kernel-based classification methods can learn complex decision boundaries, but a kernel over unordered set inputs must somehow solve for correspondences epsivnerally a computationally expensive task that becomes impractical for large set sizes. We present a new fast kernel function which maps unordered feature sets to multi-resolution histograms and computes a weighted histogram intersection in this space. This "pyramid match" computation is linear in the number of features, and it implicitly finds correspondences based on the finest resolution histogram cell where a matched pair first appears. Since the kernel does not penalize the presence of extra features, it is robust to clutter. We show the kernel function is positive-definite, making it valid for use in learning algorithms whose optimal solutions are guaranteed only for Mercer kernels. We demonstrate our algorithm on object recognition tasks and show it to be accurate and dramatically faster than current approaches
Strategies for calibrating a subcutaneous glucose sensor. (1989)

The calibration of the glucose sensor is a critical issue for the subcutaneous implantation of such devices, since it allows from the sensor output the estimation of the prevailing subcutaneous glucose concentration. This study has compared estimations of subcutaneous glucose concentration in rats, calculated from the sensor's signal by using calibration parameters (sensitivity coefficient and background current) determined either under in vitro or in vivo conditions. The in vitro calibration was performed in phosphate buffer at 37 degrees C. The in vivo parameters were calculated by comparing changes in the sensor output current to concomitant changes in blood glucose concentration, induced by intravenous insulin injection and glucose infusion. The apparent subcutaneous glucose concentration, calculated with in vitro parameters, remained much lower than the concomitant blood glucose levels throughout the experiments. By contrast, when it was calculated with the calibration parameters determined in vivo, either in the hypoglycemia or hyperglycemia range, the apparent subcutaneous glucose concentration well reflected blood glucose levels with a five min time lag. We conclude that it is the two-point in vivo calibration procedure which allows the calculation of an apparent subcutaneous glucose concentration best reflecting blood glucose levels.
Yeast Srp1p has homology to armadillo/plakoglobin/beta-catenin and participates in apparently multiple nuclear functions including the maintenance of the nucleolar structure. (1994)

SRP1, a suppressor of certain temperature-sensitive mutations in RNA polymerase I in Saccharomyces cerevisiae, encodes a protein that is associated with nuclear pores. By using a system of conditional SRP1 expression and by isolating temperature-sensitive srp1 mutants, we have demonstrated that Srp1p is essential for maintenance of the crescent-shaped nucleolar structure, RNA transcription, and the proper functions of microtubules as inferred from analysis of nuclear division/segregation and immunofluorescence microscopy of microtubules. Different mutant alleles showed significantly different phenotypes in relation to these apparently multiple functional roles of the protein. We have also found that eight imperfect 42-amino-acid tandem repeats present in Srp1p are similar to the 42-amino-acid repeats in armadillo/plakoglobin/beta-catenin proteins present in adhesive junction complexes of higher eukaryotes. We discuss this similarity in connection with the observed pleiotropic effects of srp1 mutations.
Nanoscale field effect transistor for biomolecular signal amplification (2007)

We report amplification of biomolecular recognition signal in lithographically defined silicon nanochannel devices. The devices are configured as field effect transistors (FET) in the reversed source-drain bias region. The measurement of the differential conductance of the nanowire channels in the FET allows sensitive detection of changes in the surface potential due to biomolecular binding. Narrower silicon channels demonstrate higher sensitivity to binding due to increased surface-to-volume ratio. The operation of the device in the negative source-drain region demonstrates signal amplification. The equivalence between protein binding and change in the surface potential is described.
Identification of MHC Class II-Restricted Peptide Ligands, Including a Glutamic Acid Decarboxylase 65 Sequence, that Stimulate Diabetogenic T Cells from Transgenic BDC2.5 Nonobese Diabetic Mice (2001)

Nonobese diabetic (NOD) mice spontaneously develop insulitis and destruction of pancreatic islet beta cells similar to type 1 diabetes mellitis in humans. Insulitis also occurs in the BDC2.5 TCR transgenic line of NOD mice that express the rearranged TCR alpha- and beta-chain genes of a diabetogenic NOD CD4 T cell clone. When activated with syngeneic islet cells in culture, BDC2.5 T cells adoptively transfer disease to NOD recipients, but the identity of the islet cell Ag responsible for pathogenicity is not known. To characterize the autoantigen(s) involved, BDC2.5 T cells were used to screen a combinatorial peptide library arranged in a positional scanning format. We identified more than 100 decapeptides that stimulate these T cells at nanomolar concentrations; they are then capable of transferring disease to NOD-scid mice. Surprisingly, some of the peptides include sequences similar (8 of 10 residues) to those found within the 528-539 fragment of glutamic acid decarboxylase 65. Although this 12-mer glutamic acid decarboxylase 65 fragment is only slightly stimulatory for BDC2.5 T cells (EC(50) > 100 microM), a larger 16-mer fragment, 526-541, shows activity in the low micromolar range (EC(50) = 2.3 microM). Finally, T cells from prediabetic NOD mice respond spontaneously to these peptide analogs in culture; this finding validates them as being related to a critical autoantigen involved in the etiology of spontaneous diabetes and indicates that their further characterization is important for a better understanding of underlying disease mechanisms.
Rapid diagnosis of scrub typhus by a passive hemagglutination assay using recombinant 56-kilodalton polypeptides (1993)

The genes encoding the 56-kDa polypeptides were amplified by polymerase chain reaction from the genomic DNAs of three serotypes of Rickettsia tsutsugamushi, Gilliam, Karp, and Boryong. The amplified products were cloned into expression vector pIH821, and the recombinant antigens were expressed in Escherichia coli as fusion proteins with maltose-binding protein. The recombinant 56-kDa polypeptides were purified by affinity chromatography for the sensitization of sheep erythrocytes. The recombinant 56-kDa polypeptides were evaluated with 89 serum specimens from health blood donors, 94 serum specimens from scrub typhus patients, and 31 serum specimens from patients with other febrile diseases by a passive hemagglutination assay (PHA). Among the scrub typhus patients diagnosed by indirect immunofluorescent-antibody testing, the antibodies to R. tsutsugamushi were detected in 93 patients (99%). One serum specimen from a healthy person showed a false-positive reaction by this method. The recombinant PHA showed no cross-reactions with sera obtained from other febrile patients with diseases such as murine typhus, hemorrhagic fever with renal syndrome, and leptospirosis. In conclusion, this recombinant PHA could be substituted for the conventional indirect immunofluorescent-antibody test and the immunoperoxidase test.
Biodegradable mitomycin C microspheres given intra-arterially for inoperable hepatic cancer. With particular reference to a comparison with continuous infusion of mitomycin C and 5-fluorouracil (1985)

Thirty-two patients with inoperable hepatic cancer underwent intra-arterial hepatic infusion using mitomycin C (MMC) and 5-fluorouracil (5-FU) or intra-arterial hepatic chemoembolization using heated albumin microspheres containing MMC with an average diameter 45 +/- 8 micron. Nineteen of the 32 patients received the MMC microsphere treatment and another 13 received the conventional infusion treatment, lasting for 3.4 months. The administered doses of MMC microspheres were 11.7 +/- 11.1 mg as MMC in the 12 with metastatic cancer and 6.9 +/- 2.1 mg as MMC in the 7 with hepatocellular cancer (HCC). On the contrary, the 13 patients who underwent conventional infusion had average doses of MMC 34.5 +/- 17.3 mg and of 5-FU 13.4 +/- 7.7 g, over 3.4 months. An objective tumor response was obtained in 13/19 (68.4%) under MMC microsphere chemoembolization, compared to 6/13 (46.2%) under the conventional infusion. The average level of CEA in the 12 with metastatic cancer, who underwent MMC microsphere therapy, dropped from 57.7 ng/ml to 16.5 ng/ml, while that in the 10 patients on conventional infusion dropped from 24.0 ng/ml to 17.4 ng/ml; that of alpha-fetoprotein dropped in all 7 with HCC on MMC microsphere chemoembolization, compared to a fall in 1/3 on conventional infusion. With the MMC microsphere treatment, 5 patients from colorectal cancer lived for 15.6 +/- 7.6 months, 2 are alive with a long life expectancy; and 7 patients from gastric or pancreatic cancer lived for only 9.3 +/- 3.3 months. In case of conventional infusion, 6 patients from colorectal cancer survived for 8.6 +/- 3.2 months; and 4 patients from gastric or gallbladder cancer survived for 6.0 +/- 1.0 months. The MMC microsphere treatment is superior at P = 0.059 in survival duration to the conventional infusion treatment. However, much the same survival occurred in 7 on MMC microsphere chemoembolization and 3 on continuous infusion.
ACTR-33. A PHASE I STUDY OF CONVECTION-ENHANCED DELIVERY OF LIPOSOMAL-IRINOTECAN USING REAL-TIME IMAGING WITH GADOLINIUM IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA (2016)

Local delivery into the central nervous system circumvents the challenges associated with the blood-brain barrier and minimizes systemic toxicity while achieving higher concentrations of therapeutics. Convection enhanced delivery (CED) utilizes fluid convection to distribute macromolecules into the interstitial spaces of brain parenchyma. CED a high-concentration version of liposomal irinotecan (nal-IRI-HC) has been optimized in animal models and showed promising anti-tumor activity. A major recent advance in the application of CED is the development of real time CED (RCD), which utilizes MRI to visualize the CED process with the aid of co-convected contrast agents and thus monitor infusions and ensure precise delivery. A phase I study is ongoing evaluating CED of nal-IRI-HC with real-time MRI for patients with recurrent high grade glioma (HGG). This 3+3 dose escalation trial employs dose levels of 20 mg, 40 mg, 60 mg, and 80 mg of nal-IRI-HC, given via up to 3 catheters surgically placed in an intra-tumoral location. Maximum total volume infused will be 1.0 ml for the two lowest dose groups, 1.5 ml for the third dose group, and 2.0 ml for the highest dose group. To date 7 patients have been enrolled and treated. Median progression free survival was 2.9 months. All radiographic progression was found to be outside the infusion area. One grade 3 adverse event was encountered. The median total volume of distribution (Vd) to volume infused (Vi) ratio was 1.6 - 2.0 for each infusion based on correlations between pre-infusion modeling of drug distribution and post-infusion imaging. Image-guided CED allows for real-time placement and adjustment of cannula and for real time visualization of therapeutics into the brains of patients with recurrent HGG. In this early phase trial, real time CED of nal-IRI-HC appears well tolerated and suggests larger volume infusions warrants clinical evaluation.