gebhart/patrepeval huggingface dataset:
Interaction of a Curcumin Analogue Dimethoxycurcumin with DNA (2011)

Dimethoxycurcumin (Dimc), a synthetic analogue of curcumin, that has been reported to exhibit better in vivo stability and anti-tumour activity, was investigated for its interaction with DNA, employing spectroscopic methods based on absorption, fluorescence, circular dichroism (CD), ethidium bromide (EtBr) competitive binding assay, 4'-6-diamidino-2-phenylindole (DAPI) displacement assay and fluorescence resonance energy transfer (FRET) assay. The mean binding constant for its interaction with calf thymus DNA (ct-DNA) was estimated to be 4.4±0.8 × 10(4) m(-1) . The studies using CD revealed that Dimc did not cause unwinding of the ct-DNA helix or induce major conformational changes. The EtBr and DAPI assays indicated that Dimc is not an intercalator but a minor groove binder. FRET assay also confirmed that Dimc interacts with DNA strands. Furthermore, viscosity measurements of ct-DNA solutions in the presence of Dimc supported these spectroscopic observations. Addition of Dimc to MCF-7 cells showed nuclear localization as visualized by confocal microscopy. In conclusion, the present studies addressed the mode of interaction of Dimc with biomolecules, which may have implications in developing Dimc as a DNA-targeted drug.
Poly(n-butyl acrylate-co-carbon monoxide-co-ethylene) Characterization by High-Temperature Two-Dimensional NMR at 750 MHz (2004)

Poly(n-butyl acrylate-co-carbon monoxide-co-ethylene) samples with varying monomer compositions and degrees of branching (g‘) were characterized using 750 MHz two-dimensional (2D) pulsed-field gradient (PFG) NMR spectroscopy. The NMR experiments were performed in solution at 100 °C to ensure sample homogeneity and sufficient mobility of the ethylene-based terpolymer. Since the 1H and 13C NMR spectra of the terpolymer samples were complex, 2D-1H/13C-heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond correlation (HMBC) experiments were conducted. The distinctive resonances of the ketone and ester carbonyl groups facilitated spectral assignments, such that chain-end resonances were apparent and the effects of short-chain-branching reactions and monomer sequence distributions were readily observed.
Chemical and physical characterization of oil shale combustion emissions in Estonia (2021)

In this study, oil shale combustion emission measurements were conducted in a 60 kWth Circulating Fluidized Bed combustion test facility located in a laboratory-type environment. A comprehensive set of instruments including a nitrate-ion-based Chemical Ionization Atmospheric Pressure interface Time-of-Flight Mass Spectrometer, a Soot-Particle Aerosol Mass Spectrometer, and a Potential Aerosol Mass (PAM) chamber was utilized to investigate the chemical composition and concentrations of primary and secondary emissions in oil shale combustion. In addition, the size distribution of particles (2.5–414 nm) as well as concentration and composition of gaseous precursors were characterized. Altogether 12 different experiments were conducted. Primary emissions were studied in seven experiments and aged emissions using PAM chamber in five experiments. Combustion temperatures and solid fuel circulation rates varied between different experiments, and it was found that the burning conditions had a large impact on gaseous and particulate emissions. The majority of the combustion particles were below 10 nm in size during good burning whereas in poor burning conditions the emitted particles were larger and size distributions with 2–3 particle modes were detected. The main submicron particle chemical component was particulate organic matter (POM), followed by sulfate, chloride, nitrate, and ammonium. The secondary particulate matter formed in the PAM chamber was mostly POM and the concentration of POM was many orders of magnitude higher in aged aerosol compared to primary emissions. A significant amount of aromatic volatile organic compounds (VOCs) was measured as well. VOCs have the potential to go through gas-to-particle conversion during the oxidation process, explaining the observed high concentrations of aged POM. During good combustion, when VOC emissions were lower, over 80% of SO2 was oxidized either to gaseous H2SO4 (37%) or particulate sulfate (46%) in the PAM chamber, which mimic the atmospheric processes taken place in the ambient air after few days of emission.
Proteins and Their Derived Peptides as Carriers in a Conjugate Vaccine for Streptococcus pneumoniae : Self-Heat Shock Protein 60 and Tetanus Toxoid (2003)

We induced T cell help for vaccination against Streptococcus pneumoniae (Pn) using self and foreign peptides and their source proteins conjugated to the capsular polysaccharide (CPS) of type 4 Pn; the carriers were self-heat shock protein 60 (HSP60) and tetanus toxoid (TT). We measured the production of IgG Abs to the CPS and the carriers, and tested resistance to challenge with highly lethal amounts of Pn injected i.p. (LD(50) x 10(3)-10(6)). We now report that vaccination protects old and young mice from bacterial challenge; however, there were significant differences in vaccine efficacy based on the carrier. Self-HSP60 peptide p458m was more effective than the whole HSP60 molecule and was equally effective compared with TT. Both p458m and TT were more protective than the TT-derived peptide p30 after a single vaccination. However, peptide p30 was effective in more MHC genotypes than was p458m. Unlike other vaccines, protection conferred by p458m was not related to the amount of anti-CPS Ab: mice that produced very little Ab were still protected from highly lethal doses of bacteria (LD(50) x 10(5)-10(6)). Furthermore, unlike the other carriers, there was no Ab response to the p458m carrier. Thus, peptides, self as well as foreign, can provide T cell help that differs functionally from that provided by the whole parent protein.
Epidemiology of Pancreatic Cancer (2023)

Adenocarcinoma of the pancreas is the most common histologic subtype and makes up 90% of pancreatic cancers. The global incidence of pancreatic cancer has more than doubled over the past 25 years due to population aging as well as increases in the prevalence of key pancreatic cancer risk factors. In this chapter we provide an overview of risk factors and detail their association with pancreatic cancer.
The cross-sectional image guided Ilizarov frame positioning for the surgery planning of lower extremity deformity correction (2002)

A Windows based interactive graphical computer program is developed to provide a vision of positioning the Ilizarov frames for lower extremity deformity correction surgery. The program retrieves the preoperative planning data created from the authors' LegPerfect/sup TM/ program and plots the planning results on the screen. At the same time, it loads a pre-obtained cross-sectional image at the level of selected ring position. The selected ring is overlaid on this image centered on the approximated bone axis. The user can work on this graphical environment to move the ring on top of the cross-sectional image and install the wires on the ring. Together with the authors' preoperative planning program, this program can give better vision on how to accomplish optimal ring and wire positioning.
Investigations on the role of insulin and scorpion antivenom in scorpion envenoming syndrome (2003)

Acute myocardiopathy in alloxan treated experimental dogs and rabbits was induced by subcutaneous (SQ) injection of scorpion venom from Mesobuthus tamulus concanesis, Pocock. Envenoming resulted in an initial transient hypertension (180-320 mm Hg.) followed by hypotension. Simultaneous administration of venom and species-specific scorpion antivenom (SAV) prevented hypertension and hypotension. Hypotension did not occur when SAV was given 60 min after envenoming. Blood glucose, triglycerides, cholesterol, amylase, insulin, glucagon, cortisol, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count, red blood cell (RBC) count, hemoglobin (Hb), 2,3-diphosphoglycerate (2,3-DPG), and glutathione levels were increased 60 and 90 min after envenoming. Total white blood cell (WBC) count was reduced 60 min and increased 90 min after envenoming. Simultaneous administration of venom and SAV did not alter Hb, MCHC, and packed cell volume (PCV) levels, or ECG, and cardiovascular, biochemical, metabolic, and hormonal changes. Hematological parameters were reversed when SAV was given 30 and 60 min after envenoming. PCV, Hb, and MCHC values returned to normal 120 min after SAV. Alloxan-treated dogs showed increased blood glucose, cholesterol, glucagon, cortisol levels; reduced glycogen content of liver, cardiac and skeletal muscles; and reduced insulin levels and insulin/ glucagon ratio (I/G ratio). Envenoming in the alloxan pre-treated dogs further increased these levels and reduced tissue glycogen content, insulin levels, and I/G ratio. Administration of 4 U of insulin to alloxan pre-treated envenomed rabbits caused a biochemical and clinical improvement and increased glycogen content of all tissues in comparison with the values from those administered with SAV to alloxan pre-treated envenomed animals. SAV administration to envenomed alloxan pre-treated rabbits did not cause clinical or biochemical improvement. Severe scorpion envenoming causes an autonomic storm with a massive release of catecholamines and other counter-regulatory hormones; changes in insulin secretion resulting in fuel energy deficits producing multi-system-organ-failure (MSOF); and death. Administration of either insulin or SAV (through the release of insulin) appears to be the physiological basis for the control of the metabolic support to control the adverse effects triggered by counter-regulatory hormones.
Bone marrow transplantation in patients aged 45 years and older (1986)

Increasing age has been reported to be a poor prognostic factor for survival after bone marrow transplantation. We evaluated causes of death and frequency and type of complications after marrow grafting in 24 syngeneic and 39 allogeneic recipients who were 45 to 68 years old at the time of transplant. Most patients were in an advanced stage of hematologic malignancy. Among patients given syngeneic transplants, actuarial disease-free survival at 7 years is 20%. The major causes of death were relapse of leukemia and idiopathic interstitial pneumonia. Among allogeneic recipients, 9 (23%) are currently alive, and actuarial disease-free survival at 7 years is 11%. Cytomegalovirus pneumonia and septicemia were the most frequent causes of death. Patients over 50 years of age had the poorest survival rate (1/13), but many of these were transplanted in an advanced stage of their disease. However, among 12 patients transplanted while in remission or at an early stage of their disease, 5 are surviving 65 to 1,160 days after transplantation, with an actuarial survival rate of 22% at 3 years. This is in contrast to those who received their transplant in relapse: 2 out of 20 patients (10%) became long-term survivors, with a probability of survival of 15% at 3 years. The actuarial incidence of grade II through IV acute graft-v-host disease (GVHD) was 30% for allogeneic recipients 45 to 50 years of age. This was not significantly different from the incidence in younger patients. In patients 51 to 62 years of age, the actuarial incidence of acute GVHD was 79%; however, this group included three partially HLA-mismatched transplants. Ten of 15 patients surviving at least 3 months developed chronic GVHD. These results suggest that marrow transplantation is feasible and should be considered in patients over 45 years, especially if recipients are in good clinical condition and are at an early stage of their disease, such as the chronic phase of chronic myelogenous leukemia and preleukemia. For patients more than 50 years of age, allogeneic marrow grafting cannot presently be considered first-line therapy.
Findings from the phase I clinical trials of CX-4945, an orally available inhibitor of CK2. (2011)

3087 Background: CK2 protein kinase is an attractive target for anticancer therapy because it is essential to the survival and maintenance of the cancer phenotype, it is overexpressed in cancer cells, and it supports multiple oncogenic signaling pathways. CX-4945 is a first-in-class, orally available, small molecule with highly selective inhibition of CK2. Methods: Two phase I clinical studies with CX-4945 were conducted in patients with advanced solid tumors in successive escalating dose cohorts. CX-4945 was administered orally on two different dosing schedules; twice daily or four times daily, for the first 3 consecutive weeks of a 4 week cycle. Therapy was continued until the patient showed signs of intolerance to CX-4945, or evidence of disease progression. All patients studied provided blood samples for pharmacokinetic and pharmacodynamic analyses, including the biomarker measurements of IL-6 and IL-8 levels, phosphoproteins to assess the inhibition of CK2 protein kinase in peripheral blood mononuclear cells, and downstream inhibition of the Akt signaling pathway. Results: Forty-three patients received oral doses with CX-4945 in these phase I studies. The maximum tolerated doses (MTDs) were determined for both dosing schedules, and the drug was deemed generally well tolerated. Diarrhea and hypokalemia are the dose limiting toxicities (DLTs), and these toxicities are reversible with drug discontinuation, antidiarrheal use, and potassium supplementation. The pharmacokinetics of CX-4945 were linear and dose dependent, and evidence of biomarker responses in the inhibition of CK2 and Akt pathways were observed in a drug exposure-related manner. No complete or partial RECIST responses were seen, but stable disease for at least 6 months was evident in 15% of treated patients. Conclusions: These studies established that CX-4945 can be orally administered safely on two different dosing schedules. The pharmacokinetics of CX-4945 were dose dependent, and drug exposure related inhibition of the CK2 and Akt pathways were observed. Disease stabilization was evident with CX-4945 as a single agent. Combination phase Ib/II studies in a number of different cancers are planned.
INCIDENCE RATES OF DISLOCATION, PULMONARY EMBOLISM, AND DEEP INFECTION DURING THE FIRST SIX MONTHS AFTER ELECTIVE TOTAL HIP REPLACEMENT (2003)

Prognostic study, Level II-1 (retrospective study). See p. 2 for complete description of levels of evidence.
[1,2,4]Triazolo[3,4- b ]benzothiazole scaffold as versatile nicotinamide mimic allowing nanomolar inhibition of different PARP enzymes (2022)

ABSTRACT Here we report [1,2,4]triazolo[3,4- b ]benzothiazole (TBT) as a new inhibitor scaffold, which competes with nicotinamide in the binding pocket of human poly- and mono-ADP-ribosylating enzymes. The binding mode was studied through analogs and their crystal structures with TNKS2, PARP2, PARP14 and PARP15. Based on the substitution pattern, we were able to identify The 3-amino derivatives 21 (OUL243) and 27 (OUL232), as inhibitors of mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP14 and PARP15 at nM potencies, with compound 27 being the most potent PARP10 inhibitor described to date with an IC 50 of 7.8 nM and the first PARP12 inhibitor ever reported. On the contrary, hydroxy derivative 16 (OUL245) inhibits poly-ARTs with a selectivity towards PARP2. The scaffold does not possess inherent cell toxicity and the inhibitors can enter cells and engage with the target protein. This, together with favorable ADME properties, demonstrates the potential of the TBT scaffold for future drug development efforts towards selective inhibitors against specific enzymes.
Abstract 2923: New insights into interactions of the androgen receptor with ELK1 and the platform antagonist KCI807 (2022)

Abstract Prostate cancer (PC) is generally dependent on the androgen signaling axis for growth. Advanced PC is managed by androgen deprivation therapy (ADT). However, the tumors frequently progress by restoring AR signaling that is either androgen-independent or hypersensitive to androgen, leading to castration resistant prostate cancer (CRPC). CRPC is also supported by hormone-independent actions of AR splice variants which lack the ligand binding domain. Additionally, ADT has many undesirable side effects on a variety of normal tissues that depend on androgen for non-growth related functions, including effects on the cardiovascular system, central nervous system (cognitive effects), bone and muscle. Therefore, a more strategic therapy approach would be to disrupt a functional arm of AR-signaling that is critical for PC/CRPC growth but not for the essential physiological roles of AR in normal tissues. Previous studies in this laboratory have identified ELK1 as an AR tethering protein essential for activation of a critical set of androgen/AR growth genes in various PC model cell line models, both in vitro and in vivo, including those resistant to castration and enzalutamide. It was also established that the N-terminal A/B domain of AR binds to ELK1 by co-opting the two ERK docking sites on ELK1 to constitutively activate genes enriched for cell growth functions in PC cells. A platform antagonist (KCI807) was discovered that bound to AR (Kd = 7x10-8 M), blocking its association with ELK1 and inhibiting PC/CRPC tumor growth. KCI807 has a limited target gene set (a subset of AR target genes) that is primarily and highly enriched for functions in cell cycle progression and mitosis. To further drug development, we must identify the ELK1 docking site recognition sites in AR and the KCI807 binding site. Using a variety of complimentary approaches, we have now mapped and validated the ELK1 docking site recognition sites in the AR A/B domain and also the binding site of KCI807 in AR. The two docking site recognition sites in the AR A/B domain for the two docking sites in ELK1 span amino acids 358-456 and amino acids 514-557. We have also developed a working model in which KCI807 binds in a cleft adjacent to the downstream ELK1-binding site, within the DBD, displacing an alpha helix which in turn disrupts ELK1 binding. Further structural and functional studies based on this knowledge will directly aid in design of next-generation antagonists to selectively target ELK1-dependent growth signaling by AR in PC/CRPC tumors. Citation Format: Claire L. Soave, Charles Ducker, Nathan Nicely, Yanfang Huang, Luke Pardy, Peter Shaw, Manohar Ratnam. New insights into interactions of the androgen receptor with ELK1 and the platform antagonist KCI807 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2923.
Chlorotrimethylsilane-Mediated Synthesis of Functionalized Fused Pyridines: Reaction of 3-Formylchromones with Electron-Rich Aminoheterocycles (2007)

The reaction of 3-formylchromones with aminoheterocycles was investigated. A simple and flexible general procedure for annulation of 5-(2-hydroxybenzoyl)pyridines was proposed. The best reaction conditions were found to be heating the reaction mixture in DMF in the presence of Me3SiCl as a promoter and water as scavenger.
Otitis Media (2002)

An otherwise healthy 17-month-old boy had a cold accompanied by two days of rhinorrhea, cough, and fever (temperature of up to 38.8°C). On day 5, he became fussy and woke up crying several times during the night. The following day he was afebrile, and a physical examination was normal except for findings of a slightly red left tympanic membrane with no middle-ear fluid and a bulging right tympanic membrane with white fluid behind it, obscuring the umbo. How should he be treated?
Evaluation of the Culture Method NIHSJ-02 Alternative to ISO 10272-1:2006 for the Detection of Campylobacter jejuni and Campylobacter coli in Chicken: Collaborative Study (2013)

For the surveillance of the prevalence of Campylobacter jejuni and Campylobacter coli in raw chicken products in Japan, a qualitative method, National Institute of Health Sciences Japan (NIHSJ)-02, was developed as an alternative to International Organization for Standardization (ISO) 10272-1:2006. In the NIHSJ-02 culture method, the enrichment step is carried out in a reduced volume of Preston broth at 42 +/- 1 degrees C to reduce cost and space, and to prevent the overgrowth of background bacteria. To evaluate the performance of NIHSJ-02, a collaborative study was conducted, and the results obtained by NIHSJ-02 were compared with those obtained using the reference method, ISO 10272-1:2006. Fifteen laboratories participated; each examined 48 minced chicken samples consisting of test samples uninoculated, inoculated with C. jejuni at a low or high level, and inoculated with C. coli at a low level. The average probabilities of detection by NIHSJ-02 across laboratories were 0.033, 0.222, 0.678, and 0.267 in samples uninoculated, inoculated with C. jejuni at a low and high level, and with C. coli at a low level, respectively. Those by ISO 10272-1:2006 were 0.051, 0.128, 0.551, and 0.090. Significantly higher probabilities of detection were determined by NIHSJ-02 compared to ISO 10272-1:2006, except for uninoculated samples. On the other hand, significantly lower frequency of occurrence of background bacteria was observed by NIHSJ-02 (43.1%) compared with ISO 10272-1:2006 (92.6%). NIHSJ-02 showed better performance than ISO 10272-1:2006 with regard to the selective detection of C. jejuni and C. coli in chicken.
Sequential Adriamycin and CMF in Metastatic Breast Cancer (1997)

PURPOSE: To evaluate the clinical activity of a sequential treatment with Adriamycin followed by CMF (cyclophosphamide, methotrexate, fluorouracil) and the relative therapeutic contribution of the two drug regimens given at full conventional doses in metastatic breast cancer. PATIENTS AND METHODS: From August 1990 to February 1993, 44 patients with advanced breast cancer previously untreated with chemotherapy entered the study. Treatment consisted of the intravenous administration of Adriamycin (75 mg/m&sup2; on day 1 every three weeks) for four cycles followed by intravenous CMF (cyclophosphamide, 600 mg/m&sup2;; methotrexate, 40 mg/m&sup2;; fluorouracil 600 mg/m&sup2;) on days 1 and 8 every four weeks for four total courses. RESULTS: In 41 evaluable patients, four cycles of full-dose Adriamycin were able to achieve an overall response rate of 75%, including 17% complete remissions. Four cycles of CMF administered after Adriamycin were able to increase tumor response in 64% of evaluable cases. At the end of the sequential treatment program, 78% of 41 patients achieved an objective remission and in 30% of them a clinical complete response was documented. Main side effects, i.e., leukopenia and gastrointestinal disturbances, were moderate and short-lasting. One patient died because of acute myocardial infarction. CONCLUSION: In untreated metastatic breast cancer patients, the sequential administration of Adriamycin and CMF is highly effective at the expense of a moderate toxicity profile that allows high-dose intensity of both drug regimens. CMF treatment after upfront Adriamycin is able to exert a further therapeutic advantage.
Impact of pump and signal wavelength on inhomogeneous characteristics of L-band EDFAs (2002)

Inhomogeneous gain saturation in C-band and L-band EDFAs is compared for the 980 nm and 1480 nm pump wavelength bands. Results demonstrate the manner in which pump wavelength and saturation signal wavelength affects the L-band inhomogeneous characteristic.
Dichroism in photoinduced infrared spectra of polyalkylthiophenes (1994)

Abstract The photoinduced infrared spectra of stretch‐oriented polyhexylthiophene and polyoctylthiophene are reported as a function of the polarization both of the pump light and of the probe IR beam. There is no change in the intensity of photoinduced IR absorption due to the polarization of the pump; however, the spectra show parallel dichroism when the probe is polarized. The experimental results are analyzed on the basis of the “effective conjugation coordinate” theory (ECC).