gebhart/patrepeval huggingface dataset:
Maleylacetate reductase of Pseudomonas sp. strain B13: specificity of substrate conversion and halide elimination (1995)

Maleylacetate reductase (EC 1.3.1.32) plays a major role in the degradation of chloroaromatic compounds by channelling maleylacetate and some chlorinated derivatives into the 3-oxoadipate pathway. Several substituted maleylacetates were prepared in situ by alkaline or enzymatic hydrolysis of dienelactones as the precursor. The conversion of these methyl-, chloro-, fluoro-, and bromo-substituted maleylacetates by malelacetate reductase from 3-chlorobenzoate-grown cells of Pseudomonas sp. strain B13 was studied. Two moles of NADH per mole of substrate was consumed for the conversion of maleylacetates which contain a halogen substituent in the 2 position. In contrast, only 1 mol of NADH was necessary to convert 1 mol of substrates without a halogen substituent in the 2 position. The conversion of 2-fluoro-, 2-chloro-, 2,3-dichloro-, 2,5-dichloro-, 2,3,5-trichloro-, 2-bromo-, 2,3-dibromo-, 2,5-dibromo-, 2-bromo-5-chloro-, 2-chloro-3-methyl-, and 2-chloro-5-methylmaleylacetate was accompanied by the elimination of halide from the 2 position and the temporary occurrence of the corresponding dehalogenated maleylacetate as an intermediate consuming the second mole equivalent of NADH. The properties of the halogen substituents influenced the affinity to the enzyme in the following manner. Km values increased with increasing van der Waals radii and with decreasing electronegativity of the halogen substituents (i.e., low steric hindrance and high electronegativity positively influenced the binding). The Km values obtained with 2-methyl-,3-methyl-, and 5-methylmaleylacetate showed that a methyl substituent negatively affected the affinity in the following order: 2 position >/ = 3 position >> 5 position. A reaction mechanism explaining the exclusive elimination of halogen substituents from the 2 position is proposed.
Initial genomic scan of the NIMH genetics initiative bipolar pedigrees: Chromosomes 3, 5, 15, 16, 17, and 22 (1997)

As part of the four-center NIMH Genetics Initiative on Bipolar Disorder we carried out a genomic scan of chromosomes 3, 5, 15, 16, 17, and 22. Genotyping was performed on a set of 540 DNAs from 97 families, enriched for affected relative pairs and parents where available. We report here the results of the initial 74 markers that have been typed on this set of DNAs. The average distance between markers (θ) was 12.3 cM. Nonparametric analysis of excess allele sharing among affected sibling pairs used the SIBPAL program of the S.A.G.E. package to test three hierarchical models of affected status. D16S2619 gave some evidence of linkage to bipolar disorder, with P = 0.006 for Model II (in which bipolar 1, bipolar 2 and schizoaffective-bipolar type individuals are considered affected). Nearby markers also showed increased allele sharing. A second interesting region was toward the telomere of chromosome 5q, where D5S1456 and nearby markers showed increased allele sharing; for D5S1456, P = 0.05, 0.015 and 0.008 as the models of affected status become more broad. MOD score analysis also supported the possible presence of a susceptibility locus in this region of chromosome 5. A pair of adjacent markers on chromosome 3, D3S2405 and D3S3038, showed a modest increased allele sharing in the broad model. Several isolated markers had excess allele sharing at the P < 0.05 level under a single model. D15S217 showed a MOD score of 2.37 (P < 0.025). Multipoint analysis flagged the region of chromosome 22 around D22S533 as the most interesting. Thus, several regions showed modest evidence for linkage to bipolar disorder in this initial genomic scan of these chromosomes, including broad regions near previous reports of possible linkage. Am. J. Med. Genet. 74:238–246, 1997. © Wiley-Liss, Inc.
Plasma Epstein-Barr Viral Deoxyribonucleic Acid Quantitation Complements Tumor-Node-Metastasis Staging Prognostication in Nasopharyngeal Carcinoma (2006)

Pretherapy circulating EBV DNA load is an independent prognostic factor to International Union Against Cancer (UICC) staging in NPC. Combined interpretation of EBV DNA data with UICC staging data leads to alteration of risk definition of patient subsets, with improved risk discrimination in early-stage disease. Validation studies are awaited.
Regulation ofN-Arginine Dibasic Convertase Activity by Amines:  Putative Role of a Novel Acidic Domain as an Amine Binding Site (1998)

Peptide sequence analysis and cDNA cloning indicate that a previously described mouse arginine-specific dibasic cleaving enzyme (dynorphin converting enzyme) [Csuhai et al. (1995) Biochemistry 34, 12411] is the homologue of N-arginine dibasic convertase (NRDc) isolated from rat testis [Chesneau et al. (1994) J. Biol. Chem. 269, 2056]. A mouse NRDc cDNA exhibited 98% amino acid identity with the rat cDNA. However, within a 74 residue acidic stretch, this identity drops to 82%. Likewise, the corresponding acidic stretch of human NRDc is only 73% identical with that of rat NRDc. To reconcile previously observed kinetic differences between rat and mouse NRDc, the hydrolysis of peptide substrates by the rat, human, and mouse enzymes was compared using phosphate and Tris as buffers. Although the three NRDc's behaved similarly, Tris had a pronounced effect on the kinetics of peptide hydrolysis. With BAM-8, alpha-neoendorphin, and dynorphin B as substrates, Tris increased KM up to 40-fold with little change in Vmax, while with dynorphin A or somatostatin 28 as substrate, Tris caused a decrease in KM of up to 100 fold, again with only a modest change in Vmax. Other amines, including the polyamines putrescine, spermidine, and spermine, all affected NRD convertase activity. It is proposed that amines bind to the acidic stretch found in NRDc, and that quantitative differences in the sensitivity to amines between the rat, mouse, and human enzymes can be at least partially accounted for by differences in their acidic stretch. The role of polyamines as physiological modulators of N-arginine dibasic convertase is considered.
2001 Volvo Award Winner in Clinical Studies: Lumbar Fusion Versus Nonsurgical Treatment for Chronic Low Back Pain (2001)

Lumbar fusion in a well-informed and selected group of patients with severe CLBP can diminish pain and decrease disability more efficiently than commonly used nonsurgical treatment.
Possible use of glucocorticoid receptor antagonists in the treatment of major depression: preliminary results using RU 486. (1993)

The rationale for the use of anti-glucocorticoids in the treatment of major depression has been reviewed. Four patients with chronic severe depression who were resistant to conventional therapies were given RU 486 (200 mg/day) for periods up to eight weeks. Substantial levels of RU 486 were achieved within the first few days, and the levels fell gradually over the week after the treatment was discontinued. In three cases, treatment was stopped before the eight weeks were completed: in one case because of the appearance of a rash, in the others because of side-effects, which, in retrospect, were likely unrelated to the drug. The mean scores on the Hamilton Rating Scale for Depression of three patients decreased. Levels of adrenocorticotrophin, dehydroepiandrosterone and cortisol rose during treatment. These preliminary results suggest that glucocorticoid antagonists may be effective in the treatment of major depression and merit further exploration.
Osteoarticular and intercalary allograft transplantation in the management of malignant tumors of bone (1982)

Since 1971, the Orthopaedic Service at the Massachusetts General Hospital has treated 106 patients with malignant or aggressive bone tumors by wide resection and replacement with frozen cadaveric allograft. Sixty-one of these patients have been followed for over two years (mean, 4.5 years), allowing a comprehensive end-results analysis. In 45 patients, mostly with giant-cell tumors of chondrosarcomas, the resection involved the articular end of a long bone and the replacement not only included bone, but glycerolized (to prevent freezing injury) and articular cartilage. Ten of the segments were intercalary (bone alone) and six involved a combination of bone and metallic joint prosthesis. Patients were graded as excellent, good, fair, or failure, depending principally on functional capacity. End-results analysis in this group showed that five of the 61 patients had either a local recurrence (2) and/or distant metastases (3); in five additional patients the limb was amputated or the implant removed, primarily because of infection (total failure rate, 16.5%). Forty-five (73.8%) had successful transplants (graded excellent or good) and were able to live essentially normal lives. Six of the patients (10%) required a brace or cane but three of these patients were able to return to preoperative work activities. Although the operations were arduous and difficult, and despite a high infection rate (13%) and occasional pathologic fractures (10%), the results compare favorably with other techniques used to restore the skeleton following massive segmental resection. In long-term follow-up, the data suggest that if no complication ensue in the first two years, the results are generally quite good and the grafts show no evidence of progressive deterioration with time.
Phighting the Phisher: Using Web Bugs and Honeytokens to Investigate the Source of Phishing Attacks (2007)

This paper presents a summary of research findings for a new reacitve phishing investigative technique using Web bugs and honeytokens. Phishing has become a rampant problem in today 's society and has cost financial institutions millions of dollars per year. Today's reactive techniques against phishing usually involve methods that simply minimize the damage rather than attempting to actually track down a phisher. Our research objective is to track down a phisher to the IP address of the phisher's workstation rather than innocent machines used as intermediaries. By using Web bugs and honeytokens on the fake Web site forms the phisher presents, one can log accesses to the honeytokens by the phisher when the attacker views the results of the forms. Research results to date are presented in this paper
Abstract 2804: Expression of miR-17-92 enhances antitumor activity of T cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts (2014)

Abstract Background Expression of miR-17-92 confers type-1 phenotype and enhanced survival of T-cells. We have previously reported that miR-17-92 is down-regulated in T-cells derived from glioblastoma (GBM) patients. We hypothesized that transgene-derived co-expression of miR17-92 and chimeric antigen receptor (CAR) in T-cells improves the efficacy of adoptive transfer therapy against GBM. Methods We constructed novel lentiviral vectors for miR-17-92 (FG12-EF1a-miR-17/92) and a CAR consisting of epidermal growth factor receptor variant III (EGFRvIII)-specific single-chain variable fragment (scFv) coupled to the T-cell receptor CD3ζ chain signaling module and co-stimulatory motifs of CD137 (4-1BB) and CD28 in tandem (pELNS-3C10-CAR). Human T-cells were transduced with these lentiviral vectors and their anti-tumor effects were evaluated both in vitro and in vivo. Results In addition to antigen-specific and potent cytotoxic activities against U87 GBM cells stably expressing EGFRvIII (U87-EGFRvIII), CAR-transduced T-cells (CAR-T-cells) co-transduced with miR-17-92 exhibited improved survival in the presence of temozolomide (TMZ) compared with CAR-T-cells without miR-17-92 co-transduction. In mice bearing intracranial U87-EGFRvIII xenografts, CAR-T-cells with or without transgene-derived miR-17-92 expression demonstrated similar levels of potent therapeutic effects without demonstrating any uncontrolled growth of CAR-T-cells. However, when these mice were re-challenged with U87-EGFRvIII cells in the brains, mice receiving co-transduced CAR-T-cells exhibited improved protection compared with mice treated with CAR-T-cells without miR-17-92 co-transduction. Conclusion These results warrant development of novel CAR-T-cell strategies by incorporation of miR-17-92 to improve the therapeutic potency, especially in patients with GBM. Citation Format: Masasuke Ohno, Takayuki Ohkuri, Akemi Kosaka, Carl H. June, Atsushi Natsume, Hideho Okada. Expression of miR-17-92 enhances antitumor activity of T cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2804. doi:10.1158/1538-7445.AM2014-2804
Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C (2007)

In patients with chronic hepatitis C and steatosis, CTGF may promote fibrosis independently of inflammation. CTGF may link steatosis and fibrosis via increased leptin levels.
Mild hypothermia and Mg++ protect against irreversible damage during CNS ischemia. (1984)

Spinal cord ischemia was produced in rabbits by temporary occlusion of the abdominal aorta just distal to the renal arteries; and recovery, or failure to recover, was assessed by examining the rabbits for permanent loss of sensory and motor function in the hind limbs. A temperature reduction of 3 degrees C during the period of circulatory impairment caused a doubling of the duration of ischemia that could be reversibly sustained. Intravenous administration of 5 mmoles/kg of MgCl2 before the ischemia (a dose sufficient to produce neuromuscular blockade) caused a 50% increase in the tolerable duration. The combination of the 3 degrees C reduction in temperature and the elevated Mg++ increased by about 3 fold the duration of ischemia that could be sustained before irreversible damage occurred. These results may have implications for the care of patients subjected to marginal degrees of CNS ischemia.
Genomic Cis-Regulatory Logic: Experimental and Computational Analysis of a Sea Urchin Gene (1998)

The genomic regulatory network that controls gene expression ultimately determines form and function in each species. The operational nature of the regulatory programming specified in cis-regulatory DNA sequence was determined from a detailed functional analysis of a sea urchin control element that directs the expression of a gene in the endoderm during development. Spatial expression and repression, and the changing rate of transcription of this gene, are mediated by a complex and extended cis-regulatory system. The system may be typical of developmental cis-regulatory apparatus. All of its activities are integrated in the proximal element, which contains seven target sites for DNA binding proteins. A quantitative computational model of this regulatory element was constructed that explicitly reveals the logical interrelations hard-wired into the DNA.
A comparative study of neural network to artificial noses (2006)

Artificial neural networks have been used to classify odor patterns and are showing promising results. In this paper we present four different models of neural networks to implement pattern recognition system in artificial noses. The models investigated are the multi-layer perceptrons, two different implementations of the radial basis function networks and the probabilistic neural network. All the models were tested with and without temporal processing. A complex data base with nine different classes was used in this paper
Species and Strain-specific Typing of Cryptosporidium Parasites in Clinical and Environmental Samples (1998)

Cryptosporidiosis has recently attracted attention as an emerging waterborne and foodborne disease as well as an opportunistic infection in HIV infected individuals. The lack of genetic information, however, has resulted in confusion in the taxonomy of Cryptosporidium parasites and in the development of molecular tools for the identification and typing of oocysts in environmental samples. Phylogenetic analysis of the small subunit ribosomal RNA (SSU rRNA) gene has shown that the genus Cryptosporidium comprises several distinct species. Our data show the presence of at least four species: C. parvum, C. muris, C. baileyi and C. serpentis (C. meleagridis, C. nasorum and C. felis were not studied). Within each species, there is some sequence variation. Thus, various genotypes (genotype 1, genotype 2, guinea pig genotype, monkey genotype and koala genotype, etc.) of C. parvum differ from each other in six regions of the SSU rRNA gene. Information on polymorphism in Cryptosporidium parasites has been used in the development of species and strain-specific diagnostic tools. Use of these tools in the characterization of oocysts in various samples indicates that C. parvum genotype 1 is the strain responsible for most human Cryptosporidium infections. In contrast, genotype 2 is probably one of the major sources for environmental contamination, and has been found in most oysters examined from Chesapeake Bay that may serve as biologic monitors of estuarine waters.
Design and optimization of a linker for fusion protein construction (2009)

Bivalent, bispecific single-chain antibody fusion protein construction appears to be a promising tool for tumor therapy. One of its drawbacks is that the function and activity of the fusion proteins have varied affinity and/or anti-tumor activity compared with the original molecules from which they are derived. A more optimized linker for fusion proteins would confer more favorable biological activities upon bispecific single-chain antibodies. Thus, it is critical to design and optimize an inter-peptide linker. With different functional domains and optimized linkers, fusion proteins provide a solid base for targeted immune therapy for malignancies. In this paper, we review the inter-peptide linker studies and the design of an optimized linker using genetic algorithms. The spatial structure of the fusion protein can be predicted by using genetic and bioinformatics research. Based on current research, the future focus will be on different correlation models to perform simulations of spatial structures and drug molecule design.
Partial purification and characterization of a renotropic fraction from ovine pituitaries. (1982)

It has been previously established that hypophysectomy leads to renal atrophy in rats and that a crude pituitary-derived fraction is effective in restoring kidney weight to the level expected for intact animals of the same body weight. This paper reports that considerable purification of the crude renotropic fraction from ovine pituitaries has been achieved and that the purified fraction is capable of restoring kidney weights of hypophysectomized castrated rats to normal values. For example, after five daily subcutaneous injections (135 micrograms/day) there were significant increases in dry kidney weight and total renal protein and DNA. The pituitary-derived fraction was devoid of somatotropin, contained only trace amounts of corticotropin, gamma-lipotropin, vasopressin, and prolactin, and had only low levels of thyrotropin and follitropin. Daily injections of prolactin, thyrotropin, and follitropin in doses of 20 micrograms each failed to stimulate renal growth in hypophysectomized rats. Thus, it seems highly unlikely that these factors are responsible for the observed renal hyperplasia after treatment with the pituitary fraction. The purified renotropic fraction had an isoelectric pH between 8 and 9. On polyacrylamide gel electrophoresis in the presence of detergent and a reducing agent, the renotropic fraction exhibited two major bands and one minor band with mobilities that corresponded to those of a standard lutropin preparation. The renotropic fraction exhibited considerable crossreactivity with an antiserum directed against the lutropin alpha subunit, suggesting the presence of the common glycoprotein hormone subunit. Moreover, the purified fraction stimulated steroid production by Leydig tumor cells in vitro. It is noteworthy, however, that standard ovine lutropin at 135 micrograms/day failed to exhibit renotropic activity in hypophysectomized castrated rats, although effects were noted at twice that dose. It appears that the renotropic activity represents a pituitary substance that can be separated from lutropin only with difficulty.
Functional differences between two Fc receptor ITAM signaling motifs (1995)

Most Ig receptors exist as multi-subunit complexes with a unique ligand binding alpha chain and a common signaling FcR gamma-chain. The myeloid Fc gamma RIIa (CD32) appears unique among FcR because both ligand-binding and signaling capacity are found in the alpha chain. Within the cytoplasmic tails of Fc gamma RIIa and FcR gamma-chain similar, but not identical, activatory motifs (ITAMs) have been defined, in which tyrosines play an important role. Previously, Fc gamma RIIa-ITAM was shown to be critical for both proximal and distal activatory functions in IIA1.6 B-cell transfectants. Triggering of interleukin-2 (IL-2) release and antigen presentation was absent in Fc gamma RIIa, but not in FcR gamma-chain receptor complexes. We now assessed the capacity of Fc gamma RIIa wild-type and Fc gamma RIIa/gamma chimeric molecules to trigger IL-2 production and antigen presentation by B cells. Both of these functions could solely be triggered by receptors containing the FcRIIa was capable of functional interaction with FcR gamma-chain, thus reconstituting the capacity to trigger IL-2 release and antigen presentation. These data document qualitative differences between Fc receptor ITAMs.
Lung dosimetry for radioiodine treatment planning in the case of diffuse lung metastases. (2006)

MCNP4b-based, patient-specific 3D dosimetry is feasible and important in the dosimetry of thyroid cancer patients with avid lung metastases that exhibit prolonged retention in the lungs.
Interpolyelectrolyte Complexes of Conjugated Copolymers and DNA:  Platforms for Multicolor Biosensors (2004)

Interchain interactions modulate the frequency of emission from a cationic water-soluble conjugated polymer. The polymer, PFPB, is obtained by a Suzuki copolymerization of p-phenylenebisboronic acid with a 95:5 mixture of 2,7-dibromo-9,9-bis(6'-bromohexyl)fluorene and 4,7-dibromo-2,1,3-benzothiadiazole, followed by quarternization of the pendant groups by addition of NMe3. The structure of PFPB contains 5% of the 2,1,3-benzothiadiazole (BT) chromophore within a cationic poly(fluorene-co-phenylene) polymer chain. The emission of PFPB is blue under dilute conditions (<1 x 10-6 M in repeat units) and green at higher concentrations. Energy transfer to dye-labeled ss-DNA is more efficient, relative to the parent polymer poly(9,9-bis(6'-N,N,N,-trimethylammonium)hexyl)fluorene-co-alt-1,4-phenylene) dibromide (PFP), as a result of improved spectral overlap. By using a peptide nucleic acid (PNA-C*) labeled with a red-emitting chromophore one can obtain three different emission colors, depending on the nature of the substrate under interrogation. If no ss-DNA is present, the solution emits blue. With a ss-DNA that is noncomplementary to PNA-C*, green emission is observed. Red emission occurs upon addition of ss-DNA complementary to the PNA sequence.