gebhart/patrepeval huggingface dataset:
The role of DNA damage in the resistance of human chronic myeloid leukemia cells to cyclophosphamide analogues. (1994)

We examined 4-hydroperoxycyclophosphamide (4HC) and phosphorodiamidic mustard (PM)-mediated cytotoxicity and DNA interstrand cross-link (ISC) induction in a 4HC-resistant subline, B5-180(3), that was derived from the subcloned human myeloid leukemia cell line KBM-7/B5. Based on the ratio of the 50% inhibitory concentration values, B5-180(3) cells were approximately 35-fold resistant to 4HC compared with the parental cells. 4HC-induced ISC levels (as measured by alkaline elution) were approximately 9-fold lower in the 4HC-resistant line than the parent line. To determine whether the approximately 9-fold reduction of initial 4HC-induced ISCs was related to elevated aldehyde dehydrogenase (ADH), we examined PM-mediated cytotoxicity and ISC induction in the two cell lines. Unlike 4HC, the cytotoxicity of PM is independent of ADH activity. B5-180(3) cells were between 5- and 7-fold resistant to the cytotoxic effects of PM and were only slightly (approximately 1.3-fold) resistant to PM-mediated ISC induction. Furthermore, when cells were exposed to 4HC in the presence of 40 micrograms/ml cyanamide, an efficient inhibitor of ADH, the resistance index based on the 50% inhibitory concentration values was decreased to approximately 8. Elevated ADH can therefore explain most of the decrease in 4HC-induced ISCs, with elevated GSH levels probably accounting for the remaining small increment of resistance. Thus, decreased levels of ISC induction can account for a factor of approximately 9 of the total approximately 35-fold resistance to 4HC. The remaining increment of resistance to 4HC, as well as the cross-resistance to PM, appears to relate to an enhanced ability of the resistant subline to tolerate drug-induced ISCs. Thus, multiple factors appear to be involved in the resistance of these cells to the cytotoxic and DNA-damaging effects of 4HC, with elevated ADH and temporal factors (related to the processing of DNA damage) being the most important of these.
Identification of the Iron-Responsive Genes of Neisseria gonorrhoeae by Microarray Analysis in Defined Medium (2005)

To ensure survival, most bacteria must acquire iron, a resource that is sequestered by mammalian hosts. Pathogenic bacteria have therefore evolved intricate systems to sense iron limitation and regulate gene expression appropriately. We used a pan-Neisseria microarray to examine genes regulated in Neisseria gonorrhoeae in response to iron availability in defined medium. Overall, 203 genes varied in expression, 109 up-regulated and 94 down-regulated by iron deprivation. In iron-replete medium, genes essential to rapid bacterial growth were preferentially expressed, while iron transport functions, and predominantly genes of unknown function, were expressed in low-iron medium. Of those TonB-dependent proteins encoded in the FA1090 genome with unknown ligand specificity, expression of three was not controlled by iron availability, suggesting that these receptors may not be high-affinity transporters for iron-containing ligands. Approximately 30% of the operons regulated by iron appeared to be directly under control of Fur. Our data suggest a regulatory cascade where Fur indirectly controls gene expression by affecting the transcription of three secondary regulators. Our data also suggest that a second MerR-like regulator may be directly responding to iron availability and controlling transcription independent of the Fur protein. Comparison of our data with those recently published for Neisseria meningitidis revealed that only a small portion of genes were found to be similarly regulated in these closely related pathogens, while a large number of genes derepressed during iron starvation were unique to each organism.
Redirecting T Cells (2011)

The pursuit of tumor-reactive T cells as a cancer therapy has continued unabated since the discovery of the graft-versus-leukemia effect in patients undergoing allogeneic hematopoietic stem-cell transplantation.1 Some successes have been noted: the adoptive transfer of Epstein–Barr virus (EBV)–specific T cells can prevent and treat post-transplantation lymphomas,2 and the adoptive transfer of in vitro activated and expanded autologous tumor-infiltrating lymphocytes after systemic depletion of lymphocytes induces durable complete remissions in some heavily pretreated patients with metastatic melanoma.3 Therapy with tumor-infiltrating lymphocytes is difficult and expensive, and it has benefited only patients with melanoma. Redirecting T cells by gene transfer of . . .
Detailed characterization of a homozygously deleted region corresponding to a candidate tumor suppressor locus at 21q11‐21 in human lung cancer (2008)

The frequent presence of loss of heterozygosity (LOH) at 21q21 in lung cancer suggests the existence of putative tumor suppressor genes in this genomic region. Furthermore, the identification of a homozygous deletion in this region has lent further support for its potential involvement in pathogenesis. In the present study, extensive screening of a large panel of lung cancer cell lines resulted in the identification of a homozygous deletion at 21q21.1 in the large cell lung carcinoma cell line Calu-6. Subsequent detailed characterization allowed us to narrow down the extent of the shortest region of overlap of homozygous deletions at 21q21.1 to 3.4 Mbp. Together with existing information showing a relationship with the shortest region of overlap and LOH in lung cancer, the overlapping 1.8-Mbp region was suggested to be a prime candidate for a genomic region that may harbor putative tumor suppressor genes. We found frequent downregulation of two coding genes, SAMSN1 and USP25, as well as of three miRNA genes, miR-99a, let-7c, and miR-125b-2, which reside in the commonly deleted region in human lung cancer. In addition, initial attempts were made to investigate their potential alterations and functional involvements in the development of lung cancer.
An approach to long-range electron transfer mechanisms in metalloproteins: In situ scanning tunneling microscopy with submolecular resolution (1999)

In situ scanning tunneling microscopy (STM) of redox molecules, in aqueous solution, shows interesting analogies and differences compared with interfacial electrochemical electron transfer (ET) and ET in homogeneous solution. This is because the redox level represents a deep indentation in the tunnel barrier, with possible temporary electronic population. Particular perspectives are that both the bias voltage and the overvoltage relative to a reference electrode can be controlled, reflected in spectroscopic features when the potential variation brings the redox level to cross the Fermi levels of the substrate and tip. The blue copper protein azurin adsorbs on gold(111) via a surface disulfide group. Well resolved in situ STM images show arrays of molecules on the triangular gold(111) terraces. This points to the feasibility of in situ STM of redox metalloproteins directly in their natural aqueous medium. Each structure also shows a central brighter contrast in the constant current mode, indicative of 2- to 4-fold current enhancement compared with the peripheral parts. This supports the notion of tunneling via the redox level of the copper atom and of in situ STM as a new approach to long-range electron tunneling in metalloproteins.
Oracle8 Tuning (1997)

From the Publisher:
In today's world of mission-critical database systems, microseconds mean money. High-level performance tuning skills are in great demand. Oracle8 Tuning is packed full of these career-enhancing skills and carries the official endorsement of Oracle Corporation. Using actual application and technique examples from companies with precisely tuned and customized Oracle Server environments, four of the Oracle community's most respected experts show you how to become proactive in your Oracle tuning efforts; customize an Oracle database to fit your organization's mission-critical demands; use Oracle8's new tools and networking capabilities to create a smarter, more efficient database system; address the performance issues of all platforms, including Microsoft's Windows NT and Hewlett-Packard's HP/UX; tune I/O, memory, CPU power, security, and more for maximum performance; tailor your system with Oracle tools, such as Oracle Enterprise Manager, PL/SQL, and the Performance Pack; and Maintain optimal performance levels with tried-and-true tips on troubleshooting.
Autophagy regulates myeloid cell differentiation by p62/SQSTM1-mediated degradation of PML-RARα oncoprotein (2011)

PML-RARα oncoprotein is a fusion protein of promyelocytic leukemia (PML) and the retinoic acid receptor-α (RARα) and causes acute promyelocytic leukemias (APL). A hallmark of all-trans retinoic acid (ATRA) responses in APL is PML-RARα degradation which promotes cell differentiation. Here, we demonstrated that autophagy is a crucial regulator of PML-RARα degradation. Inhibition of autophagy by short hairpin (sh) RNA that target essential autophagy genes such as Atg1, Atg5 and PI3KC3 and by autophagy inhibitors (e.g. 3-methyladenine), blocked PML-RARα degradation and subsequently granulocytic differentiation of human myeloid leukemic cells. In contrast, rapamycin, the mTOR kinase inhibitor, enhanced autophagy and promoted ATRA-induced PML-RARα degradation and myeloid cell differentiation. Moreover, PML-RARα co-immunoprecipitated with ubiquitin-binding adaptor protein p62/SQSTM1, which is degraded through autophagy. Furthermore, knockdown of p62/SQSTM1 inhibited ATRA-induced PML-RARα degradation and myeloid cell differentiation. The identification of PML-RARα as a target of autophagy provides new insight into the mechanism of action of ATRA and its specificity for APL.
Efficient Syntheses of β-Cyanosugars Using Glycosyl Iodides Derived from Per-O-silylated Mono- and Disaccharides (2001)

[reaction: see text] Reported herein is a general method for the efficient syntheses of a variety of beta-cyano glycosides through the activation of per-O-trimethylsilyl glycosides with TMSI to form alpha-glycosyl iodides, which undergo S(N)2-type displacement when treated with tetrabutylammonium cyanide. The cyanoglycosides were reduced under mild conditions using NaBH(4) in the presence of catalytic CoCl(2)(H(2)O)(6) in THF/H(2)O to give the corresponding aminomethyl glycosides.
Dysfunctional Tear Syndrome (2006)

Panelist opinion relied on symptoms and signs (not tests) for selection of treatment strategies. Therapy is chosen to match disease severity and presence versus absence of lid margin disease or tear distribution and clearance disturbances.
Flying focal spot (FFS) in cone-beam CT (2005)

In the beginning of 2004 medical spiral-CT scanners that acquire up to 64 slices simultaneously became available. Most manufacturers use a straightforward acquisition principle, namely an X-ray focus rotating on a circular path and an opposing cylindrical detector whose rotational center coincides with the X-ray focus. The 64-slice scanner available to us, a Somatom Sensation 64 spiral cone-beam CT scanner (Siemens, Medical Solutions, Forchheim, Germany), makes use of a flying focal spot that allows for view-by-view deflections of the focal spot in the rotation direction (/spl alpha/FFS) and in the z-direction (zFFS). The FFS feature doubles the sampling density in the channel direction and in the longitudinal direction. Up to four detector readings contribute to one view (projection). A significant reduction of in-plane aliasing and of aliasing in the z-direction can be expected. Especially the latter is of importance to spiral CT scans where aliasing is known to produce so-called windmill artifacts. We have derived and analyzed the optimal focal spot deflection values /spl part//spl alpha/ and /spl part/z as they would ideally occur in our scanner. Based upon these we show how image reconstruction can be performed in general. A simulation study showing reconstructions of mathematical phantoms further provides evidence that image quality can be significantly improved with the FFS. Aliasing artifacts, that manifest as streaks emerging from high-contrast objects, and windmill artifacts are reduced by almost an order of magnitude with the FFS compared to a simulation without FFS.
Nanoscale silicon wires synthesized using simple physical evaporation (1998)

We report the large-scale synthesis of silicon nanowires (SiNWs) using a simple but effective approach. High purity SiNWs of uniform diameters around 15 nm were obtained by sublimating a hot-pressed silicon powder target at 1200 °C in a flowing carrier gas environment. The SiNWs emit stable blue light which seems unrelated to quantum confinement, but related to an amorphous overcoating layer of silicon oxide. Our approach can be used, in principle, as a general method for synthesis of other one-dimensional semiconducting, or conducting nanowires.
Percent Change in Wound Area of Diabetic Foot Ulcers Over a 4-Week Period Is a Robust Predictor of Complete Healing in a 12-Week Prospective Trial (2003)

The percent change in foot ulcer area after 4 weeks of observation is a robust predictor of healing at 12 weeks. This simple tool may serve as a pivotal clinical decision point in the care of diabetic foot ulcers for early identification of patients who may not respond to standard care and may need additional treatment.
SERS Detection of Dopamine Using Label-Free Acridine Red as Molecular Probe in Reduced Graphene Oxide/Silver Nanotriangle Sol Substrate (2015)

The reduced graphene oxide/silver nanotriangle (rGO/AgNT) composite sol was prepared by the reduction of silver ions with sodium borohydride in the presence of H2O2 and sodium citrate. In the nanosol substrate, the molecular probe of acridine red (AR) exhibited a weak surface-enhanced Raman scattering (SERS) peak at 1506 cm(-1) due to its interaction with the rGO of rGO/AgNT. Upon addition of dopamine (DA), the competitive adsorption between DA and AR with the rGO took place, and the AR molecules were adsorbed on the AgNT aggregates with a strong SERS peak at 1506 cm(-1) that caused the SERS peak increase. The increased SERS intensity is linear to the DA concentration in the range of 2.5-500 μmol/L. This new analytical system was investigated by SERS, fluorescence, absorption, transmission electron microscope (TEM), and scanning electron microscope (SEM) techniques, and a SERS quantitative analysis method for DA was established, using AR as a label-free molecular probe.
CD4+T cell recognition of MHC class II-restricted epitopes from NY-ESO-1 presented by a prevalent HLA DP4 allele: Association with NY-ESO-1 antibody production (2001)

NY-ESO-1 is a tumor-specific shared antigen with distinctive immunogenicity. Both CD8(+) T cells and class-switched Ab responses have been detected from patients with cancer. In this study, a CD4(+) T cell line was generated from peripheral blood mononuclear cells of a melanoma patient and was shown to recognize NY-ESO-1 peptides presented by HLA-DP4, a dominant MHC class II allele expressed in 43--70% of Caucasians. The ESO p157--170 peptide containing the core region of DP4-restricted T cell epitope was present in a number of tumor cell lines tested and found to be recognized by both CD4(+) T cells as well as HLA-A2-restricted CD8(+) T cells. Thus, the ESO p157--170 epitope represents a potential candidate for cancer vaccines aimed at generating both CD4(+) and CD8(+) T cell responses. More importantly, 16 of 17 melanoma patients who developed Ab against NY-ESO-1 were found to be HLA-DP4-positive. CD4(+) T cells specific for the NY-ESO-1 epitopes were generated from 5 of 6 melanoma patients with NY-ESO-1 Ab. In contrast, no specific DP4-restricted T cells were generated from two patients without detectable NY-ESO-1 Ab. These results suggested that NY-ESO-1-specific DP4-restricted CD4(+) T cells were closely associated with NY-ESO-1 Ab observed in melanoma patients and might play an important role in providing help for activating B cells for NY-ESO-1-specific Ab production.
Chemically crosslinked high‐density polyethylene (1969)

Abstract Chemical crosslinking of high‐density polyethylene was studied. The amount of gel produced by a given peroxide concentration depends on the molecular weight of the polymer. More scission reactions, during the crosslinking process, occur in low‐density than in high‐density polyethylene crosslinked with Varox and Luperox 130 peroxides. The rheological behavior of partially crosslinked polyethylene is useful and convenient for quality control, for characterization, and for studies on the various mechanisms associated with the crosslinking process.
Two Novel Proteins Activate Superoxide Generation by the NADPH Oxidase NOX1 (2003)

NOX1, an NADPH oxidase expressed predominantly in colon epithelium, shows a high degree of similarity to the phagocyte NADPH oxidase. However, superoxide generation by NOX1 has been difficult to demonstrate. Here we show that NOX1 generates superoxide when co-expressed with the p47(phox) and p67(phox) subunits of the phagocyte NADPH oxidase but not when expressed by itself. Since p47(phox) and p67(phox) are restricted mainly to myeloid cells, we searched for their homologues and identified two novel cDNAs. The mRNAs of both homologues were found predominantly in colon epithelium. Differences between the homologues and the phagocyte NADPH oxidase subunits included the lack of the autoinhibitory domain and the protein kinase C phosphorylation sites in the p47(phox) homologue as well as the absence of the first Src homology 3 domain and the presence of a hydrophobic stretch in the p67(phox) homologue. Co-expression of NOX1 with the two novel proteins led to stimulus-independent high level superoxide generation. Stimulus dependence of NOX1 was restored when p47(phox) was used to replace its homologue. In conclusion, NOX1 is a superoxide-generating enzyme that is activated by two novel proteins, which we propose to name NOXO1 (NOX organizer 1) and NOXA1 (NOX activator 1).
The Addition of the BTK Inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma (2016)

Combining CTL019 with ibrutinib represents a rational way to incorporate two of the most recent therapies in MCL. Our findings pave the way to a two-pronged therapeutic strategy in patients with MCL and other types of B-cell lymphoma. Clin Cancer Res; 22(11); 2684-96. ©2016 AACR.
All-trans-retinol is a ligand for the retinoic acid receptors. (1993)

Competition of all-trans-retinol and all-trans-retinaldehyde with 3H-labeled all-trans-retinoic acid (RA) for binding to retinoic acid receptors (RARs) was examined in human neuroblastoma cell nuclear extracts. All-trans-retinol was 35-fold less potent than all-trans-RA, whereas all-trans-retinaldehyde was 500-fold less active in binding to the nuclear receptors. To confirm that all-trans-retinol binds to RARs, experiments were carried out with RARs alpha, beta, and gamma expressed as bacterial fusion proteins. All-trans-retinol was only 4- to 7-fold less potent than all-trans-RA in binding to all three RAR subtypes. The all-trans-retinol binding observed was not the result of metabolism of retinol to RA or some other active compound during the binding experiment. Retinyl acetate was virtually inactive in competition binding experiments, while very slight activity was observed with 13-cis-RA and all-trans-retinaldehyde. Significant competition occurred with 4-hydroxy-RA and 4-keto-RA, which were 15- to 40-fold less potent than all-trans-RA. The 9-cis isomer of RA was equipotent with all-trans-retinol in these studies. These results suggest that all-trans-retinol cannot be excluded as a physiologically significant ligand for RAR-mediated gene expression.
Preparation of intact monomeric collagen from rat tail tendon and skin and the structure of the nonhelical ends in solution. (1976)

Procedures for the preparation of soluble collagen from rat skin and tail tendon were reviewed and revised to permit the preparation of native monomeric collagen with intact nonhelical ends. The degree of intactness was estimated from the tyrosine content, which is present only in the nonhelical ends, and by mobility of the COOH-terminal cyanogen bromide peptide of the alpha1 chain on sodium dodecyl sulfate gels. The amount of covalently cross-linked polymeric material present was estimated by molecular sieve chromatography of denatured samples. Rapid purification in the cold was sufficient to prevent or greatly reduce proteolytic alteration. Fractionation by salt precipitation at acid pH was effective in reducing the content of polymeric material. Rat tail tendon yielded completely intact native collagen, but some high molecular weight aggregates remained. Collagen from the skin of lathyritic rats was easier to obtain free of aggregates, but contained about 1 less tyrosine residue per alpha1 chain even when isolated in the presence of enzyme inhibitors. Proton NMR spectra of denatured acidic solutions of these preparations showed that 4 to 5 tyrosine residues per alpha chain were present, confirming the chemical analysis. Spectra of the native molecule showed that about the same number of tyrosine residues per chain are in rapid motion, unlike residues in the helical portion of the molecule, a result which shows that the nonhelical ends of the native molecule are unstructured in acidic solution.
Anaerobic Oxidation of Toluene, Phenol, and p -Cresol by the Dissimilatory Iron-Reducing Organism, GS-15 (1990)

The dissimilatory Fe(III) reducer, GS-15, is the first microorganism known to couple the oxidation of aromatic compounds to the reduction of Fe(III) and the first example of a pure culture of any kind known to anaerobically oxidize an aromatic hydrocarbon, toluene. In this study, the metabolism of toluene, phenol, and p-cresol by GS-15 was investigated in more detail. GS-15 grew in an anaerobic medium with toluene as the sole electron donor and Fe(III) oxide as the electron acceptor. Growth coincided with Fe(III) reduction. [ring-C]toluene was oxidized to CO(2), and the stoichiometry of CO(2) production and Fe(III) reduction indicated that GS-15 completely oxidized toluene to carbon dioxide with Fe(III) as the electron acceptor. Magnetite was the primary iron end product during toluene oxidation. Phenol and p-cresol were also completely oxidized to carbon dioxide with Fe(III) as the sole electron acceptor, and GS-15 could obtain energy to support growth by oxidizing either of these compounds as the sole electron donor. p-Hydroxybenzoate was a transitory extracellular intermediate of phenol and p-cresol metabolism but not of toluene metabolism. GS-15 oxidized potential aromatic intermediates in the oxidation of toluene (benzylalcohol and benzaldehyde) and p-cresol (p-hydroxybenzylalcohol and p-hydroxybenzaldehyde). The metabolism described here provides a model for how aromatic hydrocarbons and phenols may be oxidized with the reduction of Fe(III) in contaminated aquifers and petroleum-containing sediments.
Registration of phase 3 crossover trials on ClinicalTrials.gov (2020)

The registration and reporting of randomized crossover trials must account for the paired nature of the design. Our observations and recommendations informed the development of guidelines for good reporting practices in the registration and reporting of randomized crossover trials.