gebhart/patrepeval huggingface dataset:
Applications of Mathematics to Medical Problems (1925)

In the majority of the processes with which one is concerned in the study of the medical sciences, one has to deal with assemblages of individuals, be they living or be they dead, which become affected according to some characteristic. They may meet and exchange ideas, the meeting may result in the transference of some infectious disease, and so forth. The life of each individual consists of a train of such incidents, one following the other. From another point of view each member of the human community consists of an assemblage of cells. These cells react and interact amongst each other, and each individual lives a life which may be again considered as a succession of events, one following the other. If one thinks of these individuals, be they human beings or be they cells, as moving in all sorts of dimensions, reversibly or irreversibly, continuously or discontinuously, by unit stages or per saltum , then the method of their movement becomes a study in kinetics, and can be approached by the methods ordinarily adopted in the study of such systems.
Occurrence of Oxygen-Sensitive, NADP+-Dependent Pyruvate Dehydrogenase in Mitochondria of Euglena gracilis (1984)

Pyruvate dehydrogenase found in mitochondria of Euglena gracilis was active on NADP+ but not NAD+, and FAD and methyl viologen also served as electron acceptors. For 2-oxoglutarate dehydrogenase both NAD+ and NADP+ were utilized and the ratio of its activity on NAD+ and NADP+ was about 1:5. The activity of pyruvate dehydrogenase was inhibited by pyruvate in aerobiosis, while not in anaerobiosis.
Functionally important residues at a subunit interface site in the RecA protein from Escherichia coli. (1994)

Assembly of RecA subunits into long, helical oligomers is required for its roles in recombinational DNA repair and homologous genetic recombination. The crystal structure of RecA reveals an extensive network of amino acid residues that lie at the subunit boundaries. We have introduced a large set of substitutions at 5 clustered residues, which are shown in the crystal structure to make specific contacts with positions in the neighboring monomer. We find that 3 of the 5 residues are important for RecA function (Lys216, Phe217, and Arg222), whereas the other 2 (Asn213 and Tyr218) are not. The patterns of functionally allowed substitutions provide insight into the chemical and steric constraints required at these positions.
A new method of phase synchronization for GPS signals based bistatic radar (2012)

The phase synchronization is one of the key technologies for bistatic radar. Traditionally, it is used to be synchronized by sampling, analyzing and modifying the phase signal in the windowed FFT spectrum. But, the sync-error can be introduced by sampling the asynchronous signals. In this paper, we use a new method called All-Phase FFT. By the way of All-Phase FFT Analysis, the initial phase can be measured. At first we describe how this new method is developed. Then, we use MATLAB to do some simulations. The simulation result is a comparison of FFT and All-phase FFT. The simulation shows that this method can measure the phase difference precisely for matching the phase synchronization requirements of bistatic radar. All-Phase FFT is a good method that can develop signal processing ability in bistatic radar.
Chemo- and Regioselective Nucleophilic Reactions of (Bromomethyl)methylmaleic Anhydride: Synthesis of a-Quinoxalinyl- and a-Benzothiazinylacrylic Acids (1999)

The (bromomethyl)methylmaleic anhydride (2) on reaction with ophenylenediamine and o-aminothiophenol underwent chemo-and regioselective ring opening followed by intramolecular Michael type addition and 1,4- elimination reactions to furnish kinetically controlled products aquinoxalinylacrylic acid (5) and a-benzothiazinylacrylic acid (6) in good yields.The nucleophilic reactions of symmetrical and unsymmetrical cyclic anhydrides have been fully i n ~e s t i ~a t e d ' .~ as a elegant strategy for the synthesis of several structurally interesting and biologically important heterocyclic systems.It has been well established that the dimethylmaleic anhydride (1) on reaction with primary m i n e yields the corresponding imide2 and on reaction with o-phenylenediamine (0-PDA), first the corresponding imide and then pyrrolobenzimidazole via intramolecular conden~ation,~ while on reaction with o-aminothiophenol (0-ATP) yields benzothiazinylpropionic acid via ring opening
A fast silicon photoconductor-based liquid crystal light valve (1979)

A fast response, photoactivated liquid crystal light valve was developed for applications in real time optical data processing and large screen displays. The new device features high resolution and sensitivity.
Regulation of Cre recombinase activity by the synthetic steroid RU 486 (1996)

To create a strategy for inducible gene targeting we developed a Cre-lox recombination system which responds to the synthetic steroid RU 486. Several fusions between Cre recombinase and the hormone binding domain (HBD) of a mutated human progesterone receptor, which binds RU 486 but not progesterone, were constructed. When tested in transient expression assays recombination activities of all fusion proteins were responsive to RU 486, but not to the endogenous steroid progesterone. However, the observed induction of recombination activity by the synthetic steroid varied between the different fusion proteins. The fusion with the highest activity in the presence of RU 486 combined with low background activity in the absence of the steroid was tested after stable expression in fibroblast and embryonal stem (ES) cells. We could demonstrate that its recombination activity was highly dependent on RU 486. Since the RU 486 doses required to activate recombination were considerably lower than doses displaying anti-progesterone effects in mice, this system could be used as a valuable tool for inducible gene targeting.
Influenza vaccination in patients with rheumatic diseases. Safety and efficacy. (1979)

The safety and efficacy of influenza vaccination were studied in 32 healthy volunteers and in 62 patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, degenerative joint disease, and other rheumatic diseases. These individuals, none of whom was acutely ill, were examined at the time of immunization and one week, three weeks, and four months later. Flare-ups of rheumatic disease following immunization were infrequent and usually minor. Seroconversion to A/New Jersey/76 developed in 62% to 87% of all individuals and to A/Victoria/75 in 62% to 69%. Antibody responses to A/New Jersey/76 were significantly lower in young patients taking glucocorticoids compared to those not taking glucocorticoids. The antibody responses to A/New Jersey/76 and A/Victoria/75 in patients with SLE were not different from normal responses. Administration of these vaccines was safe in these patients with stable disease and induced antibody responses in most individuals.
HIV-1 Tat Peptide Binding to TAR RNA by Electrospray Ionization Mass Spectrometry (1997)

Electrospray ionization mass spectrometry (ESI-MS) has been used to study the noncovalent complexes formed from the interaction between HIV-1 Tat peptide and Tat protein with TAR RNA. Both positive ion and negative ion ESI mass spectra showed a maximum stoichiometry of 3:1 between Tat peptide and TAR RNA. However, the higher order complexes only occurred at high relative concentrations of Tat peptide. The 1:1 Tat peptide-TAR RNA complex is believed to involve only specific interactions, whereas the higher order complexes involve nonspecific interactions. Relative binding affinities between Tat peptide and TAR RNA and its various mutants (TAR missing the three-nucleotide bulge, TAR with a poly(ethylene glycol) linker in the bulge region, and TAR with a poly(ethylene glycol) linker in the loop region) can be differentiated by competitive binding experiments and ESI-MS measurements. The gas phase mass spectrometry experiments are consistent with solution phase studies, as they show that mutations in the bulge region reduce TAR RNA affinity to Tat peptide.
Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. (1989)

Mesalazine coated with Eudragit L is a safe, logical alternative to sulphasalazine.
Generation and Accumulation of Immunosuppressive Adenosine by Human CD4+CD25highFOXP3+ Regulatory T Cells (2009)

Naturally occurring regulatory T cells (nTreg) are crucial for maintaining tolerance to self and thus preventing autoimmune diseases and allograft rejections. In cancer, Treg down-regulate antitumor responses by several distinct mechanisms. This study analyzes the role the adenosinergic pathway plays in suppressive activities of human nTreg. Human CD4(+)CD25(high)FOXP3(+) Treg overexpress CD39 and CD73, ectonucleotidases sequentially converting ATP into AMP and adenosine, which then binds to A(2a) receptors on effector T cells, suppressing their functions. CD4(+)CD39(+) and CD4(+)CD25(high) T cells express low levels of adenosine deaminase (ADA), the enzyme responsible for adenosine breakdown, and of CD26, a surface-bound glycoprotein associated with ADA. In contrast, T effector cells are enriched in CD26/ADA but express low levels of CD39 and CD73. Inhibitors of ectonucleotidase activity (e.g. ARL67156) and antagonists of the A(2a) receptor (e.g. ZM241385) blocked Treg-mediated immunosuppression. The inhibition of ADA activity on effector T cells enhanced Treg-mediated immunosuppression. Thus, human nTreg characterized by the presence of CD39 and the low expression of CD26/ADA are responsible for the generation of adenosine, which plays a major role in Treg-mediated immunosuppression. The data suggest that the adenosinergic pathway represents a potential therapeutic target for regulation of immunosuppression in a broad variety of human diseases.
Studies on the Syntheses of Pyrimidine Derivatives. II (1956)

By heating 6-(5-bromo-2-pyrimidinyl) aminohexanoic acid and thiourea in aqueous solution, it was derived to 6-(5-isothiouronyl-2-pyrimidinyl) aminohexanoic acid and application of sodium malonaldehyde to its hydrochloride in aqueous solution, with piperidine as the condensation agent, afforded 6-[5-(5-nitro-2-pyrimidinyl)thio-2-pyrimidinyl] aminohexanoic acid. This compound submitted to permanganate oxidation and the corresponding 5-(5-nitro-2-pyrimidinyl) sulfonyl compound was obtained. Its reduction with stannous chloride and conc. hydrochloric acid yielded the 5-amino compound.Diazotization of 6-(5-amino-2-pyrimidinyl) aminohexanoic acid by the usual method afforded 6-(5-hydroxy-2-pyrimidinyl) aminohexanoic acid. In a similar manner, 5-bromo and 5-chloro compounds were obtained, besides two kinds of crystals; one of white needles whose molecular formula agreed with C10H15O2N4Cl⋅HCl and the other of white rhomboprisms agreeing with C10H15O2N4Br⋅HBr.Both underwent condensation with anisaldehyde to form a hydrazone compound, so that they were determined as 6-[1-(5-chloro-2-pyrimidinyl) -hydrazino] hexanoic acid and its 5-bromo compound.
Transcriptional mechanisms of type I collagen gene expression are differentially regulated by interleukin-1 beta, tumor necrosis factor alpha, and transforming growth factor beta in Ito cells. (1992)

Regulation of the procollagen type I (Pro alpha 1) gene in cultured Ito cells by diverse cytokines was studied. Specifically, we have examined the effect of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and transforming growth factor beta (TGF beta) on collagen biosynthesis, levels of Pro alpha 1 (I) mRNA, and rate of transcription of Pro alpha 1 (I) gene. TGF beta stimulated procollagen synthesis at least 2-fold at every concentration tested (5-20 ng/ml), whereas TNF alpha inhibited it at the same concentrations. In contrast to what occurs in dermal fibroblasts, IL-1 beta (5-20 units/ml) preferentially inhibited procollagen production as measured by [3H]proline incorporation. A similar pattern was obtained when total protein synthesis was analyzed by [25S]methionine radiolabeling. Interestingly, while TGF beta-treated cells exhibited greater than 3-fold increase in steady-state levels of Pro alpha 1 (I) mRNA, the treatment with IL-1 had no effect on procollagen mRNA levels. TNF alpha treatment resulted in a 2-fold decrease in the amount of collagen mRNA. The treatment with combinations of cytokines indicated that collagen gene expression in Ito cells is differentially regulated by these cytokines. Furthermore, nuclear run-off transcription experiments were performed. The results obtained suggest that TGF beta regulates increasing collagen type I gene expression at transcriptional levels, and TNF alpha inhibits the transcriptional rate of Pro alpha 1 (I) gene. It is noteworthy that IL-1 beta acts on collagen type I gene regulation by a separate mechanism at a posttranscriptional level.
SonoWand, an Ultrasound-based Neuronavigation System (2000)

The SonoWand system enables neuronavigation through direct use of intraoperative three-dimensional ultrasound. Further research will be necessary to explore the potential clinical value and the limitations of this technology.
Elimination of the Hydrolytic Water Molecule in a Class A β-Lactamase Mutant:  Crystal Structure and Kinetics, (1996)

Two site-directed mutant enzymes of the class A beta-lactamase from Staphylococcus aureus PC1 were produced with the goal of blocking the site that in the native enzyme is occupied by the proposed hydrolytic water molecule. The crystal structures of these two mutant enzymes, N170Q and N170M, have been determined and refined at 2.2 and 2.0 A, respectively. They reveal that the side chain of Gln 170 displaces the water molecule, whereas that of Met170 does not. In both cases, the catalytic rates with benzylpenicillin are reduced by 10(4) compared with the native enzyme. With nitrocefin, the N170Q mutant enzyme exhibits an approximately 800-fold reduced rate compared with the native enzyme and in addition, a fast initial burst with stoichiometry of 1 mol of degraded nitrocefin/mol of enzyme. Stopped-flow kinetic experiments establish that the rate constant of the burst is 250 s-1, a value comparable with the rate of acylation of the native enzyme. Two structurally based mechanisms that explain the kinetic properties of the N170Q beta-lactamase are proposed, both invoking a deacylation-impaired enzyme due to the elimination of the hydrolytic water molecule. The catalytic rate of the N170M mutant enzyme with nitrocefin is reduced by approximately 50-fold compared with the native enzyme, and the slow progressive inhibition that is revealed indicates that the hydrolysis proceeds via a branched pathway mechanism. This is consistent with the structural data that show that the water site is preserved and that Met170 occupies part of the space that is required for substrate binding. The short contacts between the substrate and the enzyme may lead to structure perturbation and inactivation.
Oocyte-Specific Expression of Mouse Zp-2: Developmental Regulation of the Zona Pellucida Genes (1990)

The zona pellucida surrounds all mammalian oocytes and plays a vital role at fertilization and in early development. The genes that code for two of the mouse zona proteins (ZP2 and ZP3) represent a developmentally regulated set of genes whose expression serves as markers of mouse oocyte growth and differentiation. We previously characterized the single-copy Zp-3 gene and showed that its expression is oocyte specific and restricted to a narrow window of oocyte development. We now define the Zp-2 gene transcript and show that it is coordinately expressed with Zp-3 only during the 2-week growth phase of oogenesis that occurs prior to ovulation. Like Zp-3, the expression of Zp-2 is restricted to oocytes, and, although not detectable in resting oocytes, both ZP2 and ZP3 transcripts accumulate to become very abundant messengers in 50-microns-diameter oocytes. Ovulated eggs contain ZP2 and ZP3 transcripts which are 200 nucleotides shorter than those found in growing oocytes and have an abundance of less than 5% of the peak levels. In an attempt to understand the molecular details associated with the developmentally regulated, tissue-specific gene expression of the zona genes, the Zp-2 genetic locus has been characterized and its 5' flanking sequences have been compared with those of Zp-3. Both genes contain three short (8- to 12-base-pair) DNA sequences of 80 to 88% identity located within 250 base pairs of their transcription start sites.
Production of granulocyte colony-stimulating factor at the materno-foetal interface in human pregnancy. (1992)

A bioassay specific for human granulocyte colony-stimulating factor (G-CSF) was developed and used to measure G-CSF production in human pregnancy tissues. G-CSF was secreted by both foetal chorionic villous and maternal decidual tissues taken in the first trimester and at term. The level of G-CSF production by placental tissue was 6750 (1250-10,000) units of bioactivity per g of tissue in 48 hr in the first trimester and 104 (83-190) U/g at term. Bioactive G-CSF was also secreted by decidual tissue, more in the first trimester than at term. ELISA immunoassays measured 75 (10-820) ng/g/48 hr of G-CSF antigen from first trimester placenta, 15 (10-50) ng/g from first trimester decidua and less than 2 ng/g from term placenta. RNA isolated from decidual and chorionic villous tissue or from cells purified by flow cytometry, contained G-CSF mRNA in both tissues. In decidua, mRNA for G-CSF was confined to the macrophages, and cytotrophoblast from term amniochorion contained no detectable G-CSF mRNA. No G-CSF, measured as bioactivity or as mRNA, was detectable in choriocarcinoma cell lines.
Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma. (1999)

Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA) is a genetically engineered monoclonal antibody for the treatment of non-Hodgkin's lymphoma. This chimeric mouse/human, immunoglobulin GI kappa anti-CD20 antibody mediates complement-dependent cell lysis and antibody-dependent cellular cytotoxicity. It also has been shown to sensitize chemoresistant human lymphoma cell lines and to induce apoptosis. It was approved by the Food and Drug Administration on November 26, 1997, for the indication of relapsed or refractory, CD-20 positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma Rituximab is the first monoclonal antibody approved for the treatment of cancer and the first single agent approved specifically for therapy of a lymphoma. The recommended dose is rituximab 375 mg/m2 intravenously weekly x4 infusions. Treatment is well tolerated and outpatient therapy is feasible. Adverse events are mostly grades I and 2, occurring primarily with the first infusion. In a phase II single-agent clinical trial, the overall response rate was 50%, with a median time to progression in responders of 10.2 months. In a larger multicenter trial involving 166 patients, the overall response rate was 48% with 6% complete and 42% partial responses. Median time to progression for responders was 13.2 months and median duration of response was 11.6 months. A 40% response rate has been observed on re-treatment with rituximab. Activity also has been seen in patients with bulky disease. Combination studies have been performed with interferon, cyclophosphamide/doxorubicin/vincristine/prednisone, and radioimmunotherapy. Rituximab, the first monoclonal antibody approved for the treatment of cancer, is safe and effective in treating patients with relapsed or refractory, CD-20 positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma.
Mailbox Names for Common Services, Roles and Functions (1997)

This specification enumerates and describes Internet mail addresses
(mailbox name @ host reference) to be used when contacting personnel
at an organization. [STANDARDS-TRACK]
Propeptide of a precursor to a plant vacuolar protein required for vacuolar targeting. (1991)

Sporamin is a protein without glycans that accumulates in large quantities in the vacuoles of the tuberous root of the sweet potato. It is synthesized as a prepro precursor with an N-terminal extension composed of a 21-amino-acid signal peptide and a 16-amino-acid propeptide. A total of 48 base pairs, corresponding to the nucleotide sequence that encodes the propeptide, was deleted from a cDNA clone for sporamin. This delta pro mutant sequence, as well as the sequence of the wild-type sporamin cDNA, was placed downstream from the promoter of the 35S transcript from cauliflower mosaic virus and introduced into the genome of suspension-cultured tobacco cells by Agrobacterium-mediated transformation. In contrast to the vacuolar localization of sporamin in cells that expressed the wild-type precursor, sporamin was secreted into the culture medium from cells in which the delta pro precursor was expressed. The secreted form of sporamin was shorter by two amino acids at its N terminus than authentic sporamin; it migrated anomalously during electrophoresis on SDS/polyacrylamide gel as a result of the presence of intramolecular disulfide bridges, as does authentic sporamin. The kinetics of secretion of sporamin from the cell were similar to those of proteins normally secreted by the host tobacco cells. These results indicate that the propeptide of the precursor to sporamin is required for correct targeting of sporamin to the vacuole and that proteins can be secreted from plant cells by a bulk-flow default pathway in the absence of a functional sorting signal.
Regulation of the activity of IFN-gamma promoter elements during Th cell differentiation. (1998)

Before they can deliver their effector functions, CD4+ Th cells must differentiate into Th1 or Th2 subsets. We have prepared reporter transgenic mice that express the luciferase gene under the control of proximal (prox.IFN-gamma) and distal (dist.IFN-gamma) regulatory elements from the IFN-gamma promoter to permit investigation of mechanisms that regulate IFN-gamma gene transcription during Th cell differentiation. Precursor Th cells (pTh) contain high levels of cAMP response element binding protein-activation transcription factor-1 (CREB-ATF1) proteins that bind these promoter elements from the IFN-gamma gene, and these cells fail to express promoter activity. Restimulated effector Th (eTh) cells have reduced levels of CREB-ATF1 proteins, their nuclear extracts exhibit reduced CREB-ATF1 binding and greater Jun and Jun-ATF2 binding to dist.IFN-gamma), and eTh cells express promoter activity. CREB directly competes with effector T cell nuclear proteins for dist.IFN-gamma binding, and overexpression of CREB inhibits both prox.IFN-gamma- and dist.IFN-gamma-directed transcription in Jurkat T cells. IL-12-stimulated Thl differentiation increases dist.IFN-gamma activity in restimulated eTh1 cells; eTh1 nuclear extracts form increased levels of Jun-ATF2-dist.IFN-gamma complexes. Taken together, these data suggest that both de-repression and trans-activation contribute to the induction of IFN-gamma gene transcription during Th1 differentiation.