gebhart/patrepeval huggingface dataset:
Geometry of interaction of metal ions with histidine residues in protein structures (1990)

An analysis of the geometry and the orientation of metal ions bound to histidine residues in proteins is presented. Cations are found to lie in the imidazole plane along the lone pair on the nitrogen atom. Out of the two tautomeric forms of the imidazole ring, the NE2-protonated form is normally preferred. However, when bound to a metal ion the ND1-protonated form is predominant and NE2 is the ligand atom. When the metal coordination is through ND1, steric interactions shift the side chain torsional angle, chi 2 from its preferred value of 90 or 270 degrees. The orientation of histidine residues is usually stabilized through hydrogen bonding; ND1-protonated form of a helical residue can form a hydrogen bond with the carbonyl oxygen atom in the preceding turn of the helix. A considerable number of ligands are found in helices and beta-sheets. A helical residue bound to a heme group is usually found near the C-terminus of the helix. Two ligand groups four residues apart in a helix, or two residues apart in a beta-strand are used in many proteins to bind metal ions.
Completely explosive ultracompact high-voltage nanosecond pulse-generating system (2006)

A conventional pulsed power technology has been combined with an explosive pulsed power technology to produce an autonomous high-voltage power supply. The power supply contained an explosive-driven high-voltage primary power source and a power-conditioning stage. The ultracompact explosive-driven primary power source was based on the physical effect of shock-wave depolarization of high-energy Pb(Zr52Ti48)O3 ferroelectric material. The volume of the energy-carrying ferroelectric elements in the shock-wave ferroelectric generators (SWFEGs) varied from 1.2 to 2.6cm3. The power-conditioning stage was based on the spiral vector inversion generator (VIG). The SWFEG-VIG system demonstrated successful operation and good performance. The amplitude of the output voltage pulse of the SWFEG-VIG system exceeded 90kV, with a rise time of 5.2ns.
Polysaccharide‐g‐polystyrene copolymers by persulfate initiation: Preparation and properties (1983)

Liquid Chromatograph (Table Four Waters p-Styragel columns were used (lo5, lo4, lo3, and 500 A) with an injection volume of 200 pL and a flow rate of 1 mL/min. Polystyrene standards were used. Standard deviation (a) on nu and an measurement was 11,400 and 19,300, respectively. The higher value of u form,, is due to the sensitivity of n,, to small fluctuations in the baseline and
Frutas y verduras como agentes preventivos en la dieta. I. Actividad antioxidante (2001)

Epidemiological studies have established that high consumption of fruit and vegetable is associated with lower incidence and mortality rates of cancer. Oxidative DNA damage is considered an important mechanism underlying many cancers. Therefore, by reducing the amount of oxidative DNA damage one could reduce the risk of developing cancer. In this report, free radical scavengers, antioxidant protective systems, B-carotene, vitamins E and C and selenium have been reviewed as antioxidants and chemopreventive agents in fruits and vegetables.
Analysis of nuclear and mitochondrial DNA alterations in thyroid and renal oncocytic tumors (1994)

The search for mitochondrial DNA (mtDNA) defects in oncocytic neoplasms has been the subject of several recent studies. We have performed qualitative and quantitative analysis of nuclear and mitochondrial DNAs in a series of 19 renal and 12 thyroid oncocytic tumors to identify specific alterations that might predict the clinical and biological behavior of these tumors. Allelic losses were seen in 2 of 19 renal tumors and 5 of 12 thyroid tumors. Among all loci (3p, 3q, 9q, 10q, 11p, 17p, and 17q) that showed losses, losses at 10q (one renal tumor and three thyroid tumors) were significantly higher (P < 0.05) than expected. Analysis of the COX I region previously reported to be altered in oncocytomas and the delta-loop region of mtDNA showed no detectable abnormalities in the restriction pattern in 10 renal and five thyroid tumors. PCR analysis of the commonly deleted 4,977-bp region failed to detect an increased frequency of mtDNA deletions in tumors compared to the controls. In addition, segmental amplification of the complete mtDNA from a renal oncocytoma using nine sets of primers revealed no gross alteration in mtDNA. Oncocytic tumors showed a mean 5-fold increase in mitochondrial DNA, which was significant (P < 0.001) when compared to corresponding controls. The relative increase in the cellular content of mtDNA may be associated with alterations in the normal coordinated interaction between the nuclear and mitochondrial genomes. Allelic deletions at 10q may be significant in the biology of oncocytic tumors, and their impact on the clinical behavior of these tumors warrants further investigation.
Prostatic Cancer: An overview (1990)

Reliable study results are scarce in prostate cancer for several reasons. The treated tumors represent a wide variety of natural history and therapeutic response. One assumes to select 'soft' or minimally toxic treatment for patients with good prognostic factors while aggressive treatment is reserved for infaust prognosis. Stage, grade and prognostic factors may influence the indication and choice of treatment. Better treatment selection will depend on the outcome of actual ongoing randomized trials, the development of new drugs or existing drugs in new indications and, above all, basic studies on the growth potential and invasiveness of the prostate cancer cell. Defining the correct treatment for the right cancer in the right patient is our clinical challenge for the next decade.
A novel putative tyrosine kinase receptor with oncogenic potential. (1991)

We have detected transforming activity by a tumorigenicity assay using NIH3T3 cells transfected with DNA from a chronic myeloproliferative disorder patient. Here, we report the cDNA cloning of the corresponding oncogene, designated UFO, in allusion to the as yet unidentified function of its protein. Nucleotide sequence analysis of a 3116bp cDNA clone revealed a 2682-bp-long open reading frame capable of directing the synthesis of a 894 amino acid polypeptide. The predicted UFO protein exhibits characteristic features of a transmembrane receptor with associated tyrosine kinase activity. The UFO proto-oncogene maps to human chromosome 19q13.1 and is transcribed into two 5.0 kb and 3.2 kb mRNAs in human bone marrow and human tumor cell lines. The UFO locus is evolutionarily conserved between vertebrate species. A 4.0 kb mRNA of the murine UFO homolog is expressed in a variety of different mouse tissues. We thus have identified a novel element of the complex signaling network involved in the control of cell proliferation and differentiation.
Evaluation of TruCount Absolute-Count Tubes for Determining CD4 and CD8 Cell Numbers in Human Immunodeficiency Virus-Positive Adults (2000)

A single-platform technology that uses an internal bead standard and three-color flow cytometry to determine CD4 and CD8 absolute counts was evaluated for reproducibility and agreement. Values obtained using TruCount absolute-count tubes were compared to those obtained using a two-color predicate methodology. Sixty specimens from human immunodeficiency virus type 1-infected donors were shipped to five laboratories. Each site also analyzed replicates of 14 human immunodeficiency virus type 1-infected local specimens at 6 h and again at 24 h. The interlaboratory variability was significantly less with TruCount (median difference in percent coefficient of variation [%CV] between the two methods was -8% and -3% for CD4 and CD8, respectively) than with the predicate method. Intralaboratory variability was smaller, with a median difference in %CV of -1% for both CD4 and CD8 with 6-h samples and -2% and -3% for CD4 and CD8, respectively, with 24-h samples. Use of TruCount for shipped samples resulted in a median CD4 count change of 7 cells (50th estimated percentile) when all laboratories and CD4 strata were combined. For on-site samples, the median CD4 count change was 10 CD4 cells for 6-h samples and 2 CD4 cells for 24-h samples. Individual site biases occurred in both directions and cancelled each other when the data were combined for all laboratories. Thus, the combined data showed a smaller change in median CD4 count than what may have occurred at an individual site. In summary, the use of TruCount decreased both the inter- and intralaboratory variability in determining absolute CD4 and CD8 counts.
Case Studies of an Infant, a Toddler, and an Adolescent Treated With a Negative Pressure Wound Treatment System (2004)

Three pediatric case studies (infant, toddler, and adolescent) using negative pressure wound treatment system (NPWS) in a children's hospital are described. Each child had complex surgical wounds and different goals for the therapy. The infant had an ulcerating labial hemangioma surgically removed, and the NPWS was used to expedite granulation tissue in preparation for a split-thickness skin graft. The critically ill toddler required abdominal fasciotomies for compartment syndrome, and the NPWS was applied to reduce interstitial abdominal edema and manage the excessive wound drainage. The adolescent initially had surgery to correct a pectus excavatum; when the sternal wound became infected and required debridement, the NPWS was used to expedite wound healing. The results of the NPWS were positive. Although this therapy has been used more commonly in adults, these case studies demonstrate its efficacy in several different types of wounds and age groups of children. The wound, ostomy, continence nurse should include the NPWS in his or her treatment differential as a valuable option for pediatric patients.
GCP5 and GCP6: Two New Members of the Human γ-Tubulin Complex (2001)

The gamma-tubulin complex is a large multiprotein complex that is required for microtubule nucleation at the centrosome. Here we report the purification and characterization of the human gamma-tubulin complex and the identification of its subunits. The human gamma-tubulin complex is a ring of ~25 nm, has a subunit structure similar to that reported for gamma-tubulin complexes from other species, and is able to nucleate microtubule polymerization in vitro. Mass spectrometry analysis of the human gamma-tubulin complex components confirmed the presence of four previously identified components (gamma-tubulin and gamma-tubulin complex proteins [GCPs] 2, 3, and 4) and led to the identification of two new components, GCP5 and GCP6. Sequence analysis revealed that the GCPs share five regions of sequence similarity and define a novel protein superfamily that is conserved in metazoans. GCP5 and GCP6, like other components of the gamma-tubulin complex, localize to the centrosome and associate with microtubules, suggesting that the entire gamma-tubulin complex takes part in both of these interactions. Stoichiometry experiments revealed that there is a single copy of GCP5 and multiple copies of gamma-tubulin, GCP2, GCP3, and GCP4 within the gamma-tubulin complex. Thus, the gamma-tubulin complex is conserved in structure and function, suggesting that the mechanism of microtubule nucleation is conserved.
Isolation of Immune Cells from Primary Tumors (2012)

Tumors create a unique immunosuppressive microenvironment (tumor microenvironment, TME) whereby leukocytes are recruited into the tumor by various chemokines and growth factors. However, once in the TME, these cells lose the ability to promote anti-tumor immunity and begin to support tumor growth and down-regulate anti-tumor immune responses. Studies on tumor-associated leukocytes have mainly focused on cells isolated from tumor-draining lymph nodes or spleen due to the inherent difficulties in obtaining sufficient cell numbers and purity from the primary tumor. While identifying the mechanisms of cell activation and trafficking through the lymphatic system of tumor bearing mice is important and may give insight to the kinetics of immune responses to cancer, in our experience, many leukocytes, including dendritic cells (DCs), in tumor-draining lymph nodes have a different phenotype than those that infiltrate tumors. Furthermore, we have previously demonstrated that adoptively-transferred T cells isolated from the tumor-draining lymph nodes are not tolerized and are capable of responding to secondary stimulation in vitro unlike T cells isolated from the TME, which are tolerized and incapable of proliferation or cytokine production. Interestingly, we have shown that changing the tumor microenvironment, such as providing CD4(+) T helper cells via adoptive transfer, promotes CD8(+) T cells to maintain pro-inflammatory effector functions. The results from each of the previously mentioned studies demonstrate the importance of measuring cellular responses from TME-infiltrating immune cells as opposed to cells that remain in the periphery. To study the function of immune cells which infiltrate tumors using the Miltenyi Biotech isolation system, we have modified and optimized this antibody-based isolation procedure to obtain highly enriched populations of antigen presenting cells and tumor antigen-specific cytotoxic T lymphocytes. The protocol includes a detailed dissection of murine prostate tissue from a spontaneous prostate tumor model (TRansgenic Adenocarcinoma of the Mouse Prostate -TRAMP) and a subcutaneous melanoma (B16) tumor model followed by subsequent purification of various leukocyte populations.
Syntheses of the naturally occurring naphtho[2,3-b]pyran-5,10-quinones α-caryopterone, dihydro-α-caryopterone, and O-methyldihydro-α-caryopterone (1976)

The title compounds have been prepared by appropriate alkylation of 3-hydroxy-5-methoxy-1,4-napthoquinone, obtained from the adduct (6) derived by addition of 1-methoxycyclohexa-1,3-diene (4) to 2-methoxy-1,4-benzoquinone (5).
A recombineering based approach for high-throughput conditional knockout targeting vector construction (2007)

Functional analysis of mammalian genes in vivo is primarily achieved through analysing knockout mice. Now that the sequencing of several mammalian genomes has been completed, understanding functions of all the genes represents the next major challenge in the post-genome era. Generation of knockout mutant mice has currently been achieved by many research groups but only by making individual knockouts, one by one. New technological advances and the refinements of existing technologies are critical for genome-wide targeted mutagenesis in the mouse. We describe here new recombineering reagents and protocols that enable recombineering to be carried out in a 96-well format. Consequently, we are able to construct 96 conditional knockout targeting vectors simultaneously. Our new recombineering system makes it a reality to generate large numbers of precisely engineered DNA constructs for functional genomics studies.
Prostate cancer management: (2) an update on locally advanced and metastatic disease (2003)

Just under half of men with prostate cancer present with locally advanced or metastatic disease. A multidisciplinary approach is required to improve survival, minimise complications, and provide adequate palliation. Radiotherapy remains the mainstay of treatment for pelvic disease control and encouraging results have been reported with androgen ablation as adjuvant therapy. In metastatic disease androgen ablation is usually first line, although ultimately most tumours become hormone refractory, requiring second or third line treatments. Localised or systemic radiotherapy may be used for palliation in metastatic disease. With the advent of more potent bisphosphonates the common bony complications associated with metastases may be reduced. This, the second review of prostate cancer, explores the various treatments available to the multidisciplinary team.
Distribution of orexin receptor mRNA in the rat brain (1998)

The expression pattern of mRNA encoding two orexin receptors (OX1R and OX2R) in the rat brain was examined. OX1R and OX2R exhibited marked differential distribution. Within the hypothalamus, OX1R mRNA is most abundant in the ventromedial hypothalamic nucleus whereas OX2R is predominantly expressed in the paraventricular nucleus. High levels of OX1R mRNA were also detected in tenia tecta, the hippocampal formation, dorsal raphe, and locus coeruleus. OX2R mRNA is mainly expressed in cerebral cortex, nucleus accumbens, subthalamic and paraventricular thalamic nuclei, anterior pretectal nucleus. The presence of orexin receptor mRNA in the hypothalamus is in support of its proposed role in feeding regulation. Broad central distribution of orexin receptors may indicate additional functions for orexins.
An eight-subunit COP9 signalosome with an intact JAMM motif is required for fungal fruit body formation (2007)

Fruit body formation in filamentous fungi is a complex and yet hardly understood process. We show here that protein turnover control is crucial for Aspergillus nidulans development. Deletion of genes encoding COP9 signalosome (CSN) subunits 1, 2, 4, or 5 resulted in identical blocks in fruit body formation. The CSN multiprotein complex controls ubiquitin-dependent protein degradation in eukaryotes. Six CSN subunits interacted in a yeast two-hybrid analysis, and the complete eight-subunit CSN was recruited by a functional tandem affinity purification tag fusion of subunit 5 (CsnE). The tagged CsnE was unable to recruit any CSN subunit in a strain deleted for subunit 1 or subunit 4. Mutations in the JAMM metalloprotease core of CsnE resulted in mutant phenotypes identical to those of csn deletion strains. We propose that a correctly assembled CSN including a functional JAMM links protein turnover to fungal sexual development.
The Stroke Data Bank: design, methods, and baseline characteristics. (1988)

The National Institute of Neurological and Communicative Disorders and Stroke initiated the Stroke Data Bank, which is a multicenter project to prospectively collect data on the clinical course and sequelae of stroke. Additional objectives were to provide information that would enable a standard diagnostic clinical evaluation, to identify prognostic factors, and to provide planning data for future studies. A brief description of the structure and methods precede the baseline characterization of 1,805 patients enrolled in the Stroke Data Bank between July 1983 and June 1986. Two thirds of these patients were admitted within 24 hours after stroke onset. Medical history, neurologic history, and hospitalization summaries are presented separately for the following stroke subtypes: infarction, unknown cause; embolism from cardiac source; infarction due to atherosclerosis; lacune; parenchymatous or intracerebral hemorrhage; subarachnoid hemorrhage; and other. The utility and limitations of these data are discussed.
Improved Catalytic Properties of Halohydrin Dehalogenase by Modification of the Halide-Binding Site (2005)

Halohydrin dehalogenase (HheC) from Agrobacterium radiobacter AD1 catalyzes the dehalogenation of vicinal haloalcohols by an intramolecular substitution reaction, resulting in the formation of the corresponding epoxide, a halide ion, and a proton. Halide release is rate-limiting during the catalytic cycle of the conversion of (R)-p-nitro-2-bromo-1-phenylethanol by the enzyme. The recent elucidation of the X-ray structure of HheC showed that hydrogen bonds between the OH group of Tyr187 and between the Odelta1 atom of Asn176 and Nepsilon1 atom of Trp249 could play a role in stabilizing the conformation of the halide-binding site. The possibility that these hydrogen bonds are important for halide binding and release was studied using site-directed mutagenesis. Steady-state kinetic studies revealed that mutant Y187F, which has lost both hydrogen bonds, has a higher catalytic activity (k(cat)) with two of the three tested substrates compared to the wild-type enzyme. Mutant W249F also shows an enhanced k(cat) value with these two substrates, as well as a remarkable increase in enantiopreference for (R)-p-nitro-2-bromo-1-phenylethanol. In case of a mutation at position 176 (N176A and N176D), a 1000-fold lower catalytic efficiency (k(cat)/K(m)) was obtained, which is mainly due to an increase of the K(m) value of the enzyme. Pre-steady-state kinetic studies showed that a burst of product formation precedes the steady state, indicating that halide release is still rate-limiting for mutants Y187F and W249F. Stopped-flow fluorescence experiments revealed that the rate of halide release is 5.6-fold higher for the Y187F mutant than for the wild-type enzyme and even higher for the W249F enzyme. Taken together, these results show that the disruption of two hydrogen bonds around the halide-binding site increases the rate of halide release and can enhance the overall catalytic activity of HheC.
Transepithelial corneal collagen crosslinking: Bilateral study (2011)

Transepithelial CXL treatment appeared to halt keratoconus progression, with a statistically significant improvement in visual and topographic parameters. The treatment was safe and well tolerated. Its noninvasive nature makes it potentially useful in cases in which epithelial debridement is ideally avoided, such as pediatric cases, uncooperative patients, and thin corneas with thicknesses nearing 380 μm.
Effect of Ring Size or an Additional Heteroatom on the Potency and Selectivity of Bicyclic Benzylamine-Type Inhibitors of PhenylethanolamineN-Methyltransferase1a (1996)

In the search for potent and selective inhibitors of the enzyme phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28), we examined the effect of ring size or an additional heteroatom in the conformationally-restricted benzylamine-type PNMT inhibitors. Based on semiempirical calculations (MNDO) and molecular modeling studies, PNMT-inhibitory activity of these compounds seemed to be dependent on (a) the torsion angle between the plane of the aromatic ring and the endo N atom lone pair ( tau 2 angle), with the optimal value of tau 2 being about - 75 degrees, and (b) the amount of steric bulk about the 3-position of 1,2,3,4-tetrahydroisoquinoline (5, THIQ). 2,3,4,5-Tetrahydro-1H-2-benzazepine (6) was found to have the highest selectivity (PNMT Ki = 3.34 microM, alpha 2 Ki = 11 microM, selectivity = 3.2) as compared to other homologues of THIQ (PNMT Ki = 9.67 microM, alpha 2 Ki = 0.35 microM, selectivity = 0.036). The higher PNMT-inhibitory activity of 6 was attributed to favorable steric interactions of the puckered methylene groups in the putative bioactive conformation of 6 at the PNMT active site, whereas unfavorable interactions of these puckered methylene groups at the alpha 2-adrenoceptor were thought to be the cause of reduced alpha 2 affinity of 6. No further enhancement of the selectivity of the benzazepine ring system could be obtained via introduction of a second heteroatom (N, O, S) at the 5-position in this ring system.