gebhart/patrepeval huggingface dataset:
Potential of the Akt inhibitor LY294005 to antagonize the efficacy of Cisplatin against HCT116 tumor cells in a DNA mismatch repair-dependent manner (2006)

Human colorectal adenocarcinoma sublines either deficient (HCT116+ch2) or proficient (HCT116+ch3) in the function of MLH1, one of five proteins crucial to DNA mismatch repair (MMR), were used to investigate whether the Akt-specific inhibitor LY294005 could not only increase the efficacy of platinum drugs in HCT116 cells in general but also increase the efficacy of the cisplatinum compounds Cisplatin and Lipoplatin specifically in MLH1-deficient, Cisplatin- and Lipoplatin-resistant HCT116 cells. We report that, under the conditions it increased the efficacy of Docetaxel and did not affect that of 6-thioguanine, LY294005 decreased the sensitivity of both sublines to Cisplatin, Lipoplatin, Oxaliplatin, and Lipoxal. Notably, the LY294005-imposed decrease was significantly higher in the MLH1-proficient than in the MLH1-deficient subline with Cisplatin and Lipoplatin, whereas it was nearly the same in both sublines with Oxaliplatin and Lipoxal. These LY294005-imposed changes in drug sensitivity, i.e. increase with Docetaxel and decreases with platinum compounds, were not associated with the concomitant abrogation in the levels of phospho-Aktser473. Analogous changes in drug sensitivity were also observed with the PI3-kinase inhibitor LY294002, but these changes were associated with complete abrogation of phospho-Aktser473. These observations suggest a possible relationship between MMR-mediated cisplatinum DNA damage signaling and the Akt signaling pathway, e.g. a common target for both pathways. A possibly novel property of Akt in aggravating drug sensitivity may also be proposed.
Bone Morphogenetic Proteins Induce Gremlin, a Protein That Limits Their Activity in Osteoblasts (2000)

Bone morphogenetic proteins (BMP) induce the differentiation of cells of the osteoblastic lineage and enhance the function of the osteoblast. Growth factor activity is regulated by binding proteins, and we previously showed that BMPs induce noggin, a glycoprotein that binds and blocks BMP action. Recently, additional BMP antagonists, such as gremlin, have been described, but there is no information about their expression or function in osteoblasts. We tested for the expression of gremlin and studied its induction by BMPs in cultures of osteoblast-enriched cells from 22-day-old fetal rat calvariae (Ob cells). BMP-2 caused a time- and dose-dependent increase in gremlin messenger RNA and polypeptide levels, as determined by Northern and Western blot analyses. The effects of BMP-2 on gremlin transcripts were independent of new protein synthesis. BMP-2 increased the rate of gremlin transcription as determined by nuclear run-on assays. Fibroblast growth factor-2 and platelet-derived growth factor BB also induced gremlin, but other hormones and growth factors had no effect. Gremlin prevented the stimulatory effects of BMP-2 on DNA, collagen, noncollagen protein synthesis, and alkaline phosphatase activity in Ob cells. In conclusion, BMPs induce gremlin transcription in Ob cells, a mechanism that probably limits BMP action in osteoblasts.
Detection of aneuploidies by paralogous sequence quantification (2004)

Our data suggests that PSQ is a robust, easy to interpret, and easy to set up method for the diagnosis of common aneuploidies, and can be performed in less than 48 h, representing a competitive alternative for widespread use in diagnostic laboratories.
In situ analysis of corrosion inhibitors using a portable mass spectrometer with paper spray ionization (2013)

Paper spray (PS) ambient ionization is implemented using a portable mass spectrometer and applied to the detection of alkyl quaternary ammonium salts in a complex oil matrix. These salts are commonly used as active components in the formulation of corrosion inhibitors. They were identified in oil and confirmed by their fragmentation patterns recorded using tandem mass spectrometry (MS/MS). The cations of alkyl and benzyl-substituted quaternary ammonium salts showed characteristic neutral losses of CnH2n (n carbon number of the longest chain) and C7H8, respectively. Individual quaternary ammonium compounds were detected at low concentrations (<1 ng μL(-1)) and over a dynamic range of ∼5 pg μL(-1) to 500 pg μL(-1) (ppb). Direct detection of these compounds in complex oil samples without prior sample preparation or pre-concentration was also demonstrated using a home-built miniature mass spectrometer at levels below 1 ng μL(-1).
FVD: a high-performance virtual machine image format for cloud (2011)

Fast Virtual Disk (FVD) is a new virtual machine (VM) image format and the corresponding block device driver developed for QEMU. QEMU does I/O emulation for multiple hypervisors, including KVM, Xen-HVM, and VirtualBox. FVD is a holistic solution for both Cloud and non-Cloud environments. Its feature set includes flexible configurability, storage thin provisioning without a host file system, compact image, internal snapshot, encryption, copy-on-write, copy-on-read, and adaptive prefetching. The last two features enable instant VM creation and instant VM migration, even if the VM image is stored on direct-attached storage. As its name indicates, FVD is fast. Experiments show that the throughput of FVD is 249% higher than that of QCOW2 when using the Post-Mark benchmark to create files.
Mechanisms and Products of Photosensitized Degradation of Nucleic Acids and Related Model Compounds (1983)

Abstract The mechanisms and products of photosensitized and singlet oxygen oxidation of nucleic acid model compounds have been investigated using kinetics analysis and product isolation and identification. A competitive kinetics analysis is presented as a simple yet quantitative method for the determination of the role of singlet oxygen in homogeneous chemical reactions. This method is compared to other techniques that have been used in the past including determination of the solvent isotope effect and the effect of singlet oxygen quenchers and variations in oxygen and substrate concentration. The results of competitive kinetics experiments indicate that the photooxidation of dGuo (2′‐deoxyguanosine) at pH 7–10 in buffered aqueous solution sensitized by Rose Bengal, Methylene Blue, Thionine or several other dyes proceeds predominantly by a pathway requiring intermediate formation of singlet oxygen. In contrast, dGuo photooxidation under the same conditions sensitized by flavin or pterin derivatives proceeds predominantly by pathways that do not involve singlet oxygen. Most of the primary products of dGuo photooxidation are very unstable and consequently are difficult, if not impossible, to isolate and characterize. However, two compounds have now been isolated that correspond to the addition of a single molecule of oxygen to the purine ring of guanine with the purine ring system still intact. Some of the products formed in the singlet oxygen oxidation of 2′‐deoxyguanosine appear to be different than some of the products formed in flavin photosensitized reactions in agreement with kinetic results that indicate that the flavin sensitized reactions proceed by mechanisms that do not involve intermediacy of singlet oxygen. If the unique nature of the products of 2′‐deoxyguanosine oxidation by singlet oxygen can be firmly established it may be possible to detect singlet oxygen reactions in vivo by product analysis.
Transformation of isolated mammalian mitochondria by bacterial conjugation (2005)

We have developed a method for transferring exogenous DNA molecules into isolated mammalian mitochondria using bacterial conjugation. In general, we accomplish this by (i) inserting an origin of DNA transfer (oriT) sequence into a DNA construct, (ii) transforming the construct into an appropriate Escherichia coli strain and then (iii) introducing the mobilizable DNA into mitochondria through conjugation. We tested this approach by transferring plasmid DNA containing a T7 promoter sequence into mitochondria that we had engineered to contain T7 RNA polymerase. After conjugation between E.coli and mitochondria, we detected robust levels of T7 transcription from the DNA constructs that had been transferred into the mitochondria. This approach for engineering DNA constructs in vitro and subsequent transfer into mitochondria by conjugation offers an attractive experimental system for studying many aspects of vertebrate mitochondrial gene expression and is a potential route for transforming mitochondrial networks within mammalian cells.
Thermally Assisted Adiabatic Quantum Computation (2008)

We study the effect of a thermal environment on adiabatic quantum computation using the Bloch-Redfield formalism. We show that in certain cases the environment can enhance the performance in two different ways: (i) by introducing a time scale for thermal mixing near the anticrossing that is smaller than the adiabatic time scale, and (ii) by relaxation after the anticrossing. The former can enhance the scaling of computation when the environment is super-Ohmic, while the latter can only provide a prefactor enhancement. We apply our method to the case of adiabatic Grover search and show that performance better than classical is possible with a super-Ohmic environment, with no a priori knowledge of the energy spectrum.
Impact of Endogenous Bile Salts on the Thermodynamics of Supersaturated Active Pharmaceutical Ingredient Solutions (2017)

A variety of formulation strategies have been developed to mitigate the inadequate aqueous solubility of certain therapeutic agents. Among these, achieving supersaturation in vivo is a promising approach to improve the extent of oral absorption. Because of the thermodynamic instability of supersaturated solutions, inhibitors are needed to kinetically hinder crystallization. In addition to commonly used polymeric additives, bile salts, naturally present in the gastrointestinal tract, have been shown to exhibit crystallization inhibition properties. However, the impact of bile salts on solution thermodynamics is not well understood, although this knowledge is essential in order to explore the mechanism of crystallization inhibition. To better describe solution thermodynamics in the presence of bile salts, a side-by-side diffusion cell was used to evaluate solute flux for solutions of telaprevir in the absence and presence of the six most abundant bile salts in human intestinal fluid at various solute concentrations; flux measurements provide information about the solute thermodynamic activity and hence can provide an improved measurement of supersaturation in complex solutions. Trihydroxy bile salts had minimal impact on solution phase boundaries as well as solute flux, while micellar dihydroxy bile salts solubilized telaprevir leading to reduced solute flux across the membrane. An inconsistency between the concentration-based supersaturation ratio and that based on solute thermodynamic activity (the fundamental driving force for crystallization) was noted, suggesting that the activity-based supersaturation should be determined to better interpret any modification in crystallization kinetics in the presence of these additives. These findings indicate that bile salts are not interchangeable from a thermodynamic perspective and provide a foundation for further studies evaluating the mechanism of crystallization inhibition.
The Role of HMGB1 in the Pathogenesis of Inflammatory and Autoimmune Diseases (2014)

High-mobility group box 1 (HMGB1) protein is a highly abundant protein that can promote the pathogenesis of inflammatory and autoimmune diseases once it is in an extracellular location. This translocation can occur with immune cell activation as well as cell death, with the conditions for release associated with the expression of different isoforms. These isoforms result from post-translational modifications, with the redox states of three cysteines at positions 23, 45 and 106 critical for activity. Depending on the redox states of these residues, HMGB1 can induce cytokine production via toll-like receptor 4 (TLR4) or promote chemotaxis by binding the chemokine CXCL12 for stimulation via CXCR4. Fully oxidized HMGB1 is inactive. During the course of inflammatory disease, HMGB1 can therefore play a dynamic role depending on its redox state. As a mechanism to generate alarmins, cell death is an important source of HMGB1, although each major cell death form (necrosis, apoptosis, pyroptosis and NETosis) can lead to different isoforms of HMGB1 and variable levels of association of HMGB1 with nucleosomes. The association of HMGB1 with nucleosomes may contribute to the pathogenesis of systemic lupus erythematosus by producing nuclear material whose immunological properties are enhanced by the presence of an alarmin. Since HMGB1 levels in blood or tissue are elevated in many inflammatory and autoimmune diseases, this molecule can serve as a unique biomarker as well as represent a target of novel therapies to block its various activities.
Characterization of chromosomal integration sites for heterologous gene expression in Saccharomyces cerevisiae (2009)

The construction of mitotically stable yeast strains for heterologous gene or pathway expression often requires chromosomal integration. However, transcription levels vary between different chromosome regions. We therefore characterized 20 different integration sites of the Sacchromyces cerevisiae genome by inserting lacZ as a reporter gene under the control of two different promoters and determining expression levels through enzyme activity measurement. An up to 8.7-fold difference was detected between the sites conferring lowest and highest expression, respectively. This opens the opportunity for modulating gene expression levels while retaining promoter and culture conditions.
Conceptus Influences the Distribution of Uterine Leukocytes During Early Porcine Pregnancy1 (2002)

Pregnancy in humans and rodents is associated with dramatic changes in leukocyte populations within the uterus. In these species, recruitment of leukocytes, mostly natural killer (NK) lymphocytes, accompanies decidualization of endometrial stroma even in the absence of pregnancy. In the pig, a nondecidualizing species, the predominant lymphocytes in the pregnant uterus are T and/or NK cells, but their distribution relative to embryonic attachment sites has not been reported. The objective of this study was to compare the abundance of leukocytes in porcine endometrium in contact with trophoblast with that between attachment sites during the early postattachment period. Uteri were recovered on Days 15-17 (n = 4), 18 and 19 (n = 4), 21 and 22 (n = 5), and 25-27 (n = 2) of gestation and from cycling pigs during the luteal phase (Day 15; n = 3). Leukocytes were identified in uterus obtained at versus between attachment sites using an antibody reactive with all leukocytes (CD44). In all pregnant animals, leukocytes were diffusely scattered throughout the endometrial stroma but were rare or absent in the luminal epithelium. Leukocyte density was approximately 3-fold greater in endometrium in contact with conceptuses than in endometrium between attachment sites throughout the early postattachment period. Leukocyte density during the luteal phase was similar to that between attachment sites, suggesting that leukocyte recruitment was a localized response to the embryo. The ability of an individual porcine conceptus to recruit maternal leukocytes to the adjacent stroma may be a vital step in early placental development and embryo survival.
Continuous control with deep reinforcement learning (2015)

We adapt the ideas underlying the success of Deep Q-Learning to the continuous action domain. We present an actor-critic, model-free algorithm based on the deterministic policy gradient that can operate over continuous action spaces. Using the same learning algorithm, network architecture and hyper-parameters, our algorithm robustly solves more than 20 simulated physics tasks, including classic problems such as cartpole swing-up, dexterous manipulation, legged locomotion and car driving. Our algorithm is able to find policies whose performance is competitive with those found by a planning algorithm with full access to the dynamics of the domain and its derivatives. We further demonstrate that for many of the tasks the algorithm can learn policies end-to-end: directly from raw pixel inputs.
Security of web browser scripting languages: vulnerabilities, attacks, and remedies (1998)

While conducting a security analysis of JavaScript and VBScript, the most popular scripting languages on the Web, we found some serious #aws. Motivated by this outcome, we propose steps towards a sound de#nition and design of a security framework for scripting languages on the Web. We show that if such a security framework had been integrated into the respective scripting languages from the very beginning, the probability of preventing the multiple security #aws, that we and other research groups identi#ed, would have been greatly increased.
Cabozantinib: an Active Novel Multikinase Inhibitor in Renal Cell Carcinoma (2017)

Clear cell renal cell carcinoma (RCC) is characterized by inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. VHL loss drives tumor angiogenesis and accounts for the clinical activity of VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs), the first-line standard of care for advanced RCC. Within the last year, three new second-line treatments have received FDA approval for use after anti-angiogenic therapy: the immune checkpoint inhibitor nivolumab, the TKI cabozantinib, and the combination of the TKI lenvatinib and the mTOR inhibitor everolimus. Cabozantinib inhibits VEGFRs, MET, and AXL, kinases that promote tumorigenesis, angiogenesis, metastasis, and drug resistance. Compared with everolimus, cabozantinib has shown statistically significant improvements in the three key efficacy endpoints of overall survival, progression-free survival, and objective response rate in patients with RCC who were previously treated with a VEGFR TKI. Herein, we summarize the translational research and clinical development that led to approval of cabozantinib as second-line therapy in RCC.
Oxygen-Modified Poly(4-dicyanomethylene-4H-cyclopenta[2,1-b;3,4-b‘]dithiophene):  A Tunable Low Band Gap Polymer (1999)

The reaction of n-doped poly(4-dicyanomethylene-4H-cyclopenta[2,1-b;3,4-b‘]dithiophene) with O2 at negative potentials (e.g., −0.60 V) produces changes in the polymer's electrochemistry, electronic spectrum, and conductivity profile that indicate a lowering of its band gap. Cyclic voltammetry of O2-modified films shows increased currents in the voltage region corresponding to the band gap, between the original onsets of n and p doping. The onset of electronic absorption shifts from 0.8 eV to lower energies with increasing reaction time. In situ conductivity measurements show that the intrinsic conductivity increases by as much as a factor of 100 (to ∼10-6 S cm-1), corresponding to a reduction of the band gap to ∼0.2 eV. Thus by controlling the reaction time with O2 the band gap of the polymer can be tuned over the range of <0.2 to 0.8 eV. Raman spectra suggest that electrochemically driven substitution of the polymer with hydroxyl groups at the β-positions of the thiophene rings is responsible for the lowering of the band gap.
The Cost–Utility of Adjuvant Chemotherapy Using Docetaxel and Cyclophosphamide Compared with Doxorubicin and Cyclophosphamide in Breast Cancer (2011)

Relative to ac, tc is a cost-effective adjuvant chemotherapy regimen, with a cost-effectiveness ratio well below commonly applied thresholds.
Potential Metal-Binding Domains in Nucleic Acid Binding Proteins (1986)

A systematic search for sequences that potentially could form metal-binding domains in proteins has been performed. Five classes of proteins involved in nucleic acid binding or gene regulation were found to contain such sequences. These observations suggest numerous experiments aimed at determining whether metal-binding domains are present in these proteins and, if present, what roles such domains play in the processes of nucleic acid binding and gene regulation.
Production and tumour‐binding characterization of a chimeric anti‐CEA Fab expressed in Eschericwa coli (1994)

A recombinant chimeric Fab (rcFab), with Fv derived from the monoclonal A5B7 antibody to carcinoembryonic antigen (CEA), and with human CHI and C kappa was cloned into pUC 19 and expressed in Escherichia coli. rcFab (10 to 12 mg per litre) was produced in bacterial culture fluid, and functional purified rcFab was isolated by affinity chromatography (using antibody to human C kappa) and size-exclusion gel filtration. The rcFab did not show reduced affinity for CEA, and reacted with human colorectal tumours showing a typical anti-CEA pattern by immunocytochemistry; it was also stable after iodination. Biodistribution studies in nude mice bearing human tumour xenografts showed no toxicity and good tumour localization. Therapeutic ratios at early time points were better than those obtained with whole murine antibody. The results demonstrate that bacterially produced anti-CEA Fab is of use for tumour targeting.
Dissociation of Escherichia coli heat-labile enterotoxin adjuvanticity from ADP-ribosyltransferase activity (1995)

The heat-labile enterotoxin (LT) of Escherichia coli is immunologically and physiochemically related to cholera enterotoxin. A number of studies have been performed to determine the relationship of the ADP-ribosylating enzymatic activity of these enterotoxins to toxicity and adjuvanticity. These studies have generally examined the effect of abolishing the ADP-ribosyltransferase activity of A1 by a variety of chemical or genetic manipulations. In every case, loss of enzymatic activity was associated with loss of biological activity and also with the ability of the molecules to function as oral adjuvants. Consequently, we explored an alternate approach to detoxification of LT without altering its adjuvanticity. Specifically, we generated a novel mutant form of LT by genetic modification of the proteolytically sensitive residues that join the A1 and A2 components of the A subunit. This mutant contains a single amino acid substitution within the disulfide subtended region joining A1 and A2. This mutant toxin, designated LT(R192G), is not sensitive to proteolytic activation, has negligible activity on mouse Y-1 adrenal tumor cells, and is devoid of ADP-ribosyltransferase activity. Nonetheless, LT(R192G) retains the ability to function as a mucosal adjuvant, increasing the serum immunoglobulin G (IgG) and mucosal IgA responses to coadministered antigen (OVA) beyond that achieved with administration of that antigen alone. Further, LT(R192G) prevented the induction of tolerance to coadministered antigen and did not induce tolerance against itself, as demonstrated by the presence of significant serum anti-LT IgG and mucosal anti-LT IgA antibodies in immunized mice.