gebhart/patrepeval huggingface dataset:
Prolonged survival in a patient with BRCA2 associated metastatic pancreatic cancer after exposure to camptothecin: a case report and review of literature (2009)

Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 have been proven to predict a drastically increased lifetime risk of breast and ovarian cancers in the individuals who carry them. A number of studies have shown that the third most common cancer associated with these mutations is pancreatic cancer. There is evidence of in vivo therapeutic response to the cross-linking agents; such as mitomycin C (MMC) in BRCA2 mutated pancreatic cell lines. We present the 'first patient' who achieved a prolonged survival on irinotecan, a topoisomerase I poison, administered alone and then in combination with cetuximab. Our patient presented at the age of 71 years with a dual diagnosis of prostate carcinoma and pancreatic carcinoma on the background of a significant family history of cancer. On genetic testing, he was found to have the common Ashkenazi Jewish BRCA2 mutation, 6174delT. To date, he has received 22 cycles of docetaxel, capecitabine, and gemcitibine followed by single agent irinotecan every 3 weeks for 27 cycles, and then weekly cetuximab was added to the regimen at cycle 28. His disease then remained stable for an additional 13 months. He did not have mutated KRAS. MMC and oxaliplatin was then introduced upon progression. His current treatment is MMC plus irinotecan as oxaliplatin was removed because of a hypersensitivity reaction. This patient is stable with an Eastern Cooperative Oncology Group performance status of 0, four and a half years (56 months) after his initial diagnosis. DNA topoisomerases are nuclear enzymes responsible for the regulation of DNA topology. They are involved in basic DNA transactions during replication, transcription, and recombination. BRCA2-deficient human cells are deficient in the repair of double-strand breaks and DNA cross-links through homologous recombination. Active poisons of topoisomerase I include derivatives of camptothecin. Our case is the first clinical piece of evidence that demonstrates an increased sensitivity to camptothecin-11 and a reduced topoisomerase I relaxation activity in BRCA2 associated pancreatic cancer. This case shows that patients with metastatic pancreatic carcinoma and BRCA2 mutations may have disease that is biologically more chemosensitive and consequently prolong survival despite prognostically unfavorable disease.
Adding a Hydrogen Bond May Not Help: Naphthyridinone vs Quinoline Inhibitors of Macrophage Migration Inhibitory Factor (2017)

Coordination of the ammonium group of Lys32 in the active site of human macrophage migration inhibitory factor (MIF) using a 1,7-naphthyridin-8-one instead of a quinoline is investigated. Both gas- and aqueous-phase DFT calculations for model systems indicate potential benefits for the added hydrogen bond with the lactam carbonyl group, while FEP results are neutral. Three crystal structures are reported for complexes of MIF with <b>3a</b>, <b>4a</b>, and <b>4b</b>, which show that the desired hydrogen bond is formed with O-N distances of 2.8-3.0 Å. Compound <b>4b</b> is the most potent new MIF inhibitor with <i>K</i><sub>i</sub> and <i>K</i><sub>d</sub> values of 90 and 94 nM; it also has excellent aqueous solubility, 288 μg/mL. Consistent with the FEP results, the naphthyridinones are found to have similar potency as related quinolines in spite of the additional protein-ligand hydrogen bond.
Conjugation and Evaluation of Small Hydrophobic Molecules to Triazole-Linked siRNAs (2014)

Short interfering RNAs (siRNAs) have tremendous potential as a new class of next-generation therapeutics; however, their progress is lagging due to issues related to stability, biodistribution, and cell-membrane permeability. To overcome these issues, there is widespread interest in chemically modifying siRNAs. In this study, siRNAs that contain a triazole-backbone unit with pyrimidine-modified hydrophobic substituents were synthesized and examined for their gene-silencing activity. In our study, we generated a library of siRNAs that target both a plasmid reporter system and an endogenous gene target, bcl-2. Our results indicate that these unique modifications are well tolerated within the RNA interference pathway. In addition, a cholesterol-modified triazole-linked siRNA targeting the exogenous target firefly luciferase was capable of gene-silencing at levels greater than 80% in the absence of a carrier complex.
Large-Scale Separation of Metallic and Semiconducting Single-Walled Carbon Nanotubes (2005)

In the applications of single-walled carbon nanotubes (SWNTs), it is extremely important to separate semiconducting and metallic SWNTs. Although several methods have been reported for the separation, only low yields have been achieved at great expense. We show a separation method involving a dispersion-centrifugation process in a tetrahydrofuran solution of amine, which makes metallic SWNTs highly concentrated to 87% in a simple way.
The DIMINUTO gene of Arabidopsis is involved in regulating cell elongation. (1995)

We have isolated a recessive mutation named diminuto (dim) from T-DNA transformed lines of Arabidopsis thaliana. Under normal growth conditions, the dim mutant has very short hypocotyls, petioles, stems, and roots because of the reduced size of cells along the longitudinal axes of these organs. In addition, dim results in the development of open cotyledons and primary leaves in dark-grown seedlings. The gene for DIM was cloned by T-DNA tagging. DIM encodes a novel protein of 561 amino acids that possesses bipartite sequence domains characteristic of nuclear localization signals. Molecular and physiological studies indicate that the loss-of-function mutant allele does not abolish the response of seedlings to light or phytohormones, although the inhibitory effect of light on hypocotyl elongation is greater in the mutant than in wild type. Moreover, the dim mutation affects the expression of a beta-tubulin gene, TUB1, which is thought to be important for plant cell growth. Our results suggest that the DIM gene product plays a critical role in the general process of plant cell elongation.
Use of Core/Shell Structured Nanoparticles for Biomedical Applications (2008)

Nanoparticles have found wide spread application in varied fields of engineering. Recently, core/shell nanostructures have been found to have improved properties when compared to their other alternatives are patented. These core/shell structures also interest researchers in the field of biomedical engineering and some potential applications have been identified. The classification of core/shell nanoparticles, the synthesis of these structures and their applications in the field of biomedical engineering are discussed in this article. The future work points at the possibilities of improvement and the material that might be preferred for specific applications. Keywords: Core/shell, nanoparticles, biomedical applications, nanoparticles synthesis
A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA) (2019)

ClinicaltTrials.gov Identifier: NCT02203695 Date of Registration: 06/16/2014. Date of First Participant Enrollment: 04/16/2015.
Fine specificity of cytotoxic T lymphocytes primed in vivo either with virus or synthetic lipopeptide vaccine or primed in vitro with peptide. (1991)

Standard synthetic peptide preparations contain numerous peptidic byproducts in small amounts, which may be efficiently recognized by cytotoxic T lymphocytes (CTL). Recognition patterns of such peptide mixtures by CTL may serve as a kind of fingerprint for CTL fine specificity. Three types of H-2Db-restricted CTL were compared in this way. CTL primed in vivo either with A/PR/8/34 influenza virus or with a synthetic lipopeptide vaccine prepared from influenza nucleoprotein (NP) peptide 365-380 showed identical fine specificity. Both recognize virus-infected cells. In contrast, CTL primed in vitro with NP 365-380 had a different fine specificity and they did not recognize virus-infected cells. Most significantly, the two in vivo primed CTL types efficiently recognized the natural viral nonapeptide NP 366-374 presented by virus-infected H-2b cells, whereas the in vitro primed CTL failed to do so.
The Way Computer Graphics Works (1997)

Mandatory Basics. Hardware Basics. Graphic Primitives. 3D Vectors and Transforms. Modeling. The Whole Scene (Lights, Camera, Action!). Rendering (Converting a Scene to Pixels). Animation. Saving the Pixels (Image File Issues). Where to Go From Here. Glindex.
Stabilizing effect of various organic solvents on protein. (1978)

The rate of denaturation of hemaglobin and other proteins by mechanical shaking is strongly affected by organic solvents. A group pf solvents,including alcohols and ketones, was found to stabilize proteins at low concentrations, although these same organic solvents denatured proteins at high concentrations. The stabilizing effect of alcohols increased with increasing chain lenghts. The second group of solvents, including toluene and chloroform, showed only a destabilizing effect, while the third group of solvents such as formamide and pentane had no effect over a wide range of concentrations. Organic solvents may be used to protect or denature a specific protein in solutions containing various proteins.
Synthesis of a functional F0 sector of the Escherichia coli H+-ATPase does not require synthesis of the alpha or beta subunits of F1 (1986)

The uncB, E, F, and H genes of the Escherichia coli unc operon were cloned behind the lac promoter of plasmid pUC9, generating plasmid pBP101. These unc loci code, respectively, for the chi, omega, and psi subunits of the F0 sector and the delta subunit of the F1 sector of the H+-ATP synthase complex. Induction of expression of the four unc genes by the addition of isopropyl-beta-D-thiogalactoside resulted in inhibition of growth. During isopropyl-beta-D-thiogalactoside induction, the three subunits of F0 were integrated into the cytoplasmic membrane with a resultant increase in H+ permeability. A functional F0 was formed from plasmid pBP101 in a genetic background lacking all eight of the unc structural genes coding the F1F0 complex. In the unc deletion background, a reasonable correlation was observed between the amount of F0 incorporated into the membrane and the function measured, i.e., high-affinity binding of F1 and rate of F0-mediated H+ translocation. This correlation indicates that most or all of the F0 assembled in the membrane is active. Although the F0 assembled under these conditions binds F1, only partial restoration of NADH-dependent or ATP-dependent quenching of quinacrine fluorescence was observed with these membranes. Proteolysis of a fraction of the psi subunit may account for this partial deficiency. The experiments described demonstrate that a functional F0 can be assembled in vivo in E. coli strains lacking genes for the alpha, beta, gamma, and epsilon subunits of F1.
Rings of Single-Walled Carbon Nanotubes:  Molecular-Template Directed Assembly and Monte Carlo Modeling (2007)

Rings of single-walled carbon nanotubes (SWNTs) were assembled by dip-pen nanolithography (DPN) generated molecular templates consisting of COOH-terminated monolayers in circular patterns surrounded by passivating CH3-terminated SAMs. Experimental data and atomic-level Monte Carlo simulations show that SWNTs assemble into rings with radii as small as 100 nm at the edge of the COOH templates. This directed assembly is strongly length-dependent; only when the length of a SWNT is longer than half of the circumference of the circle does the SWNT bend to precisely follow the interface of the COOH-terminated monolayer. The theoretical modeling shows that the strain energy of each SWNT is balanced by the energy difference between the van der Waals interactions of the tube with COOH and CH3 templates to produce the resulting ring structure.
Induction of CD8+ T Cells to an HIV-1 Antigen through a Prime Boost Regimen with Heterologous E1-Deleted Adenoviral Vaccine Carriers (2003)

E1-deleted adenoviral recombinants most commonly based on the human serotype 5 (AdHu5) have been shown thus far to induce unsurpassed transgene product-specific CD8(+) T cell responses. A large percentage of the adult human population carries neutralizing Abs due to natural exposures to AdHu5 virus. To circumvent reduction of the efficacy of adenovirus (Ad) vector-based vaccines by neutralizing Abs to the vaccine carrier, we developed E1-deleted adenoviral vaccine carriers based on simian serotypes. One of these carriers, termed AdC68, expressing a codon-optimized truncated form of gag of HIV-1 was shown previously to induce a potent transgene product-specific CD8(+) T cell response in mice. We constructed a second chimpanzee adenovirus vaccine vector, termed AdC6, also expressing the truncated gag of HIV-1. This vector, which belongs to a different serotype than the AdC68 virus, induces high frequencies of gag-specific CD8(+) T cells in mice including those pre-exposed to AdHu5 virus. Generation of an additional E1-deleted adenoviral vector of chimpanzee origin allows for sequential booster immunizations with heterologous vaccine carriers. In this study, we show that such heterologous prime boost regimens based on E1-deleted adenoviral vectors of different serotypes expressing the same transgene product are highly efficient in increasing the transgene product-specific CD8(+) T cell response. They are equivalent to sequential vaccinations with an E1-deleted Ad vector followed by booster immunization with a poxvirus vector and they surpass regimens based on DNA vaccine prime followed by a recombinant adenoviral vector boost.
Neuroprotective Actions of Flavonoids (2011)

The experimental evidences accumulated during last years point out a relevant role of oxidative stress in neurodegeneration. As anti-cellular oxidative stress agents flavonoids can act either as direct chemical antioxidants, the classic view of flavonoids as antioxidants, or as modulators of enzymes and metabolic and signaling pathways leading to an overshot of reactive oxygen species (ROS) formation, a more recently emerging concept. Flavonoids, a large family of natural antioxidants, undergo a significant hepatic metabolism leading to flavonoid-derived metabolites that are also bioactive as antioxidant agents. The development of more efficient flavonoid's based anti-oxidative stress therapies should also take into account their bioavailability in the brain using alternate administration protocols, and also that the major ROS triggering the cellular oxidative stress are not the same for all neurodegenerative insults and diseases. On these grounds, we have reviewed the reports on neuroprotection by different classes of flavonoids on cellular cultures and model animals. In addition, as they are now becoming valuable pharmacological drugs, due to their low toxicity, the reported adverse effects of flavonoids in model experimental animals and humans are briefly discussed.
Influence of daptomycin on staphylococcal abscesses and experimental tobramycin nephrotoxicity (1989)

The antibacterial efficacies of daptomycin and vancomycin were compared in male Fischer rats with subcutaneous abscesses caused by either methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant S. aureus (MRSA). The influence of daptomycin on tobramycin nephrotoxicity was also assessed. MSSA or MRSA abscesses were treated with subcutaneous daptomycin (10 mg/kg every 12 h), vancomycin (125 mg/kg every 12 h), or diluent (every 12 h) for 5 to 10 days. Rats in both antibiotic treatment groups had lower abscess bacterial counts than did controls at days 5 and 10 (P less than 0.0025). The daptomycin treatment groups had lower abscess bacterial counts than did the vancomycin treatment groups for MSSA at day 5 (P less than 0.0025) and day 10 (P less than 0.025) and for MRSA at day 10 (P less than 0.0025). Nephrotoxicity treatment groups included animals treated for 3, 7, 10, 14, and 17 days with subcutaneous diluent (every 12 h), daptomycin (20 mg/kg every 12 h), tobramycin (40 mg/kg every 12 h), and the combination of daptomycin and tobramycin. Compared with controls, animals treated with daptomycin alone exhibited no detectable nephrotoxicity. Rats given tobramycin alone developed functional and histopathologic abnormalities from days 7 through 17. Animals treated with daptomycin and tobramycin for 14 days had a lower mean concentration of creatinine in serum (P less than 0.005), higher mean creatinine clearance values (P less than 0.05), and less cortical tubular cell regeneration (P less than 0.05) than did rats treated with tobramycin alone. In rats with staphylococcal subcutaneous abscesses, daptomycin was superior to vancomycin in treating both MSSA and MRSA. Daptomycin alone caused no detectable renal injury, and in rats given daptomycin combined with tombramycin, there was less histologic and functional renal injury than in animals given tobramycin alone.
Role of TNFα in pulmonary pathophysiology (2006)

Tumor necrosis factor alpha (TNFalpha) is the most widely studied pleiotropic cytokine of the TNF superfamily. In pathophysiological conditions, generation of TNFalpha at high levels leads to the development of inflammatory responses that are hallmarks of many diseases. Of the various pulmonary diseases, TNFalpha is implicated in asthma, chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In addition to its underlying role in the inflammatory events, there is increasing evidence for involvement of TNFalpha in the cytotoxicity. Thus, pharmacological agents that can either suppress the production of TNFalpha or block its biological actions may have potential therapeutic value against a wide variety of diseases. Despite some immunological side effects, anti-TNFalpha therapeutic strategies represent an important breakthrough in the treatment of inflammatory diseases and may have a role in pulmonary diseases characterized by inflammation and cell death.
Role of Ras signaling in erythroid differentiation of mouse fetal liver cells: functional analysis by a flow cytometry–based novel culture system (2003)

Ras signaling plays an important role in erythropoiesis. Its function has been extensively studied in erythroid and nonerythroid cell lines as well as in primary erythroblasts, but inconclusive results using conventional erythroid colony-forming unit (CFU-E) assays have been obtained concerning the role of Ras signaling in erythroid differentiation. Here we describe a novel culture system that supports terminal fetal liver erythroblast proliferation and differentiation and that closely recapitulates erythroid development in vivo. Erythroid differentiation is monitored step by step and quantitatively by a flow cytometry analysis; this analysis distinguishes CD71 and TER119 double-stained erythroblasts into different stages of differentiation. To study the role of Ras signaling in erythroid differentiation, different H-ras proteins were expressed in CFU-E progenitors and early erythroblasts with the use of a bicistronic retroviral system, and their effects on CFU-E colony formation and erythroid differentiation were analyzed. Only oncogenic H-ras, not dominant-negative H-ras, reduced CFU-E colony formation. Analysis of infected erythroblasts in our newly developed system showed that oncogenic H-ras blocks terminal erythroid differentiation, but not through promoting apoptosis of terminally differentiated erythroid cells. Rather, oncogenic H-ras promotes abnormal proliferation of CFU-E progenitors and early erythroblasts and supports their erythropoietin (Epo)-independent growth.
Do carotenoids play a photoprotective role in the cytoplasm of Haematococcus lacustris (Chlorophyta)? (1991)

Centrally located secondary carotenoids, mainly astaxanthin, disperse towards the periphery of Haematococcuslacustris (Chlorophyta)cells under light induction, and move back towards the centre after illumination is discontinued. Absorption spectra and HPLC analysis of the extracted pigments show no major quantitative or qualitative changes during this migration, indicating that the dispersion effect is due to relocation of the existing pigments under the influence of light. Red akinetes (non-motile cells filled with secondary carotenoids) are found to be more resistant to photoinhibition than green akinetes. A possible photoprotective role for the secondary carotenoids is therefore suggested.
Analytical Assessment of Simplified Transient Fuel Tests for Vehicle Transient Fuel Compensation (2005)

&lt;div class="htmlview paragraph"&gt;Good air/fuel ratio (A/F) control is essential to high quality combustion performance, drivability and emissions in internal combustion engine powered vehicles. Cold start and transient fuel wall wetting effects cause significant A/F control challenges in port fuel injected (PFI) engines. Transient fuel compensation (TFC) strategies are used to help control the A/F during cold starts and transient load and RPM conditions for good vehicle performance, but developing optimum TFC strategies and calibrations in a vehicle with many competing effects is very difficult. Thus, simplified transient tests such as fuel or throttle perturbation tests are often used to develop and validate new strategies or calibrations for use in vehicle. This paper will illustrate the use of a validated physical model to analytically assess the value of fuel and throttle perturbation tests for developing a TFC calibration for vehicle use.&lt;/div&gt;
Ku70 Is Required for DNA Repair but Not for T Cell Antigen Receptor Gene Recombination In Vivo (1997)

Ku is a complex of two proteins, Ku70 and Ku80, and functions as a heterodimer to bind DNA double-strand breaks (DSB) and activate DNA-dependent protein kinase. The role of the Ku70 subunit in DNA DSB repair, hypersensitivity to ionizing radiation, and V(D)J recombination was examined in mice that lack Ku70 (Ku70(-/-)). Like Ku80(-/-) mice, Ku70(-/-) mice showed a profound deficiency in DNA DSB repair and were proportional dwarfs. Surprisingly, in contrast to Ku80(-/-) mice in which both T and B lymphocyte development were arrested at an early stage, lack of Ku70 was compatible with T cell receptor gene recombination and the development of mature CD4+CD8- and CD4-CD8+ T cells. Our data shows, for the first time, that Ku70 plays an essential role in DNA DSB repair, but is not required for TCR V(D)J recombination. These results suggest that distinct but overlapping repair pathways may mediate DNA DSB repair and V(D)J recombination.
Chromosome instability in colorectal tumor cells is associated with defects in microtubule plus-end attachments caused by a dominant mutation in APC (2003)

The attachment of microtubule plus ends to kinetochores and to the cell cortex is essential for the fidelity of chromosome segregation. Here, we characterize the causes underlying the high rates of chromosome instability (CIN+) observed in colorectal tumor cells. We show that CIN+ tumor cells exhibit inefficient microtubule plus-end attachments during mitosis, accompanied by impairment of chromosome alignment in metaphase. The mitotic abnormalities associated with CIN+ tumor cells correlated with status of adenomatous polyposis coli (APC). Importantly, we have shown that a single truncating mutation in APC, similar to mutations found in tumor cells, acts dominantly to interfere with microtubule plus-end attachments and to cause a dramatic increase in mitotic abnormalities. We propose that APC functions to modulate microtubule plus-end attachments during mitosis, and that a single mutant APC allele predisposes cells to increased mitotic abnormalities, which may contribute to tumor progression.