gebhart/patrepeval huggingface dataset:
Quantitative determination of polar and ionic compounds in petroleum fractions by atmospheric pressure chemical ionization and electrospray ionization mass spectrometry (2002)

The capabilities of atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) methods for quantitative analysis of polar and ionic compounds in petroleum fractions have been examined. The requirements of the analysis for sensitivity, linear dynamic range, and structural characterization have been discussed. ESI was found to be approximately two orders of magnitude more sensitive than APCI and is most suitable for the detection of analytes in weak concentrations. Equivalent relative linear dynamic ranges were observed by the two methods (at least three orders of magnitude). For the relatively high analyte concentrations examined here (e.g., 1-100 ppm or higher), the absolute area counts increased linearly with the analyte amount only in APCI, making this method more attractive for quantitative liquid chromatography/mass spectrometry (LC/MS) applications. Nevertheless, a wider range of ionic compounds can be detected by ESI than by APCI.
Biodegradation of cyclic and substituted linear oligomers of poly(3-hydroxybutyrate) (1995)

Cyclic oligo(3-hydroxybutyrate), oligo(3-HB), was synthesized and purified, resulting in oligolides that contained three to seven (R)-3-hydroxybutyrate units (triolides up to heptolides). In addition, linear 3-HB octamers obtained as either tert-butyl or methyl esters were substituted with different end groups at the hydroxy end. The hydroxy terminus was replaced by either a benzyloxy, trifluoroacetoxy, crotonyloxy (S)-3-hydroxybutyryloxy, or fluorenylmethylcarbonyloxy (FMOC) group. P(3-HB) hairpin loops occurred on the surface of certain regions of the polymer, especially of lamellar crystallites. Cyclic 3-HB oligomers provide a model system for these loops. It is assumed that they provide attachment points for the depolymerizing enzymes. All of the (R)-oligolides tested were degraded except the (R)-triolide. Triolides were not degraded, suggesting that enzymatic attack was prevented presumably by steric hindrance on the rigid ring system. Unsubstituted linear octamers were degraded. Biodegradation was prevented when the hydroxy terminus was protected by the FMOC group, but was not dependent on a free hydroxy terminal group; all other protecting groups did not prevent degradation. Substitution of the carboxy end of a methyl or tert-butyl ester group did not influence biodegradation.
Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors. (1996)

Estimates of body fat, maximal aerobic capacity, and women's use of oral contraceptives explain about one-third of the variation in Si in a population-based sample of young healthy Caucasians.
Activation of globin gene expression by cDNAs from induced K562 cells. Evidence for involvement of ferritin in globin gene expression. (1991)

We have isolated non-globin cDNA clones specific for erythroid differentiation from K562 human erythroleukemia cells and have identified those that may regulate globin gene transcription. A cDNA library was constructed from K562 cells induced by hemin for production of embryonic and fetal hemoglobins and screened against cDNA from uninduced K562 cells. Full-length clones specific for induced K562 cells were ligated into a eukaryotic expression vector and transfected into HeLa cells to allow for production of the corresponding coded polypeptide. The ability to increase epsilon- or gamma-globin promoter activity was identified using cotransfection with a second vector containing a globin gene promoter fused to a reporter gene. Six of the induced K562-specific clones exhibited the ability to increase the levels of the reporter genes, bacterial chloramphenicol acetyltransferase and human growth hormone. Sequencing analyses of these clones indicated that five were homologous to ferritin heavy and light chains and one had no homology with known DNA or protein sequences. The ferritin light chain cDNA had the greatest effect on globin gene promoter activation, increasing the gamma-globin promoter activity by 6-8-fold. The activation of the globin gene promoter in the absence of globin gene translation suggests that ferritin (or iron) may have a direct role in globin gene transcription. The subtractive library cloning strategy has enabled us to isolate cDNA clones that activate specific gene promoter without the requirement of direct DNA binding. This approach may allow further identification of the genes encoding proteins that are involved in the control of erythropoiesis.
Penicillin anaphylaxis: a review of sensitization, treatment, and prevention. (1992)

Penicillin and its derivatives are the commonest cause of drug-induced anaphylaxis, accounting for some 500 deaths per year in the United States. Penicillins are, however, sometimes withheld unnecessarily in patients who give spurious histories of penicillin allergy. A properly performed skin test will detect patients at risk of serious anaphylaxis. Many physicians do not fully appreciate the value of penicillin skin testing, however, and this has contributed to the withholding of penicillin and the use of other, often more expensive medications. Skin testing with a mixture of benzylpenicilloyl polylysine (major determinant) and a minor determinant mixture detects all patients at risk of major anaphylaxis. Of patients who test negative with these reagents, 1% to 4% will have non-life-threatening urticarial reactions. Skin testing is most useful in patients with a vague or inconsistent history of penicillin allergy for whom alternative antibiotics would not be effective or convenient. Aztreonam is the only semisynthetic penicillin that may safely be used in penicillin-allergic patients. Desensitization may be attempted in the patient with a positive skin test for whom there is no alternative to a penicillin-type drug.
Nuclear Cloning and Epigenetic Reprogramming of the Genome (2001)

Cloning of mammals by nuclear transfer (NT) results in gestational or neonatal failure with at most a few percent of manipulated embryos resulting in live births. Many of those that survive to term succumb to a variety of abnormalities that are likely due to inappropriate epigenetic reprogramming. Cloned embryos derived from donors, such as embryonic stem cells, that may require little or no reprogramming of early developmental genes develop substantially better beyond implantation than NT clones derived from somatic cells. Although recent experiments have demonstrated normal reprogramming of telomere length and X chromosome inactivation, epigenetic information established during gametogenesis, such as gametic imprints, cannot be restored after nuclear transfer. Survival of cloned animals to birth and beyond, despite substantial transcriptional dysregulation, is consistent with mammalian development being rather tolerant to epigenetic abnormalities, with lethality resulting only beyond a threshold of faulty gene reprogramming encompassing multiple loci.
(Ba, Sr)TiO3 Films Prepared by Liquid Source Chemical Vapor Deposition on Ru Electrodes (1996)

Electrical properties of (Ba, Sr)TiO 3 [BST] films have been investigated on RuO 2 /Ru and Ru electrodes instead of Pt, because they are easy to be etched. BST films were deposited at a substrate temperature of T s =420° C and a reactor pressure of P =1.5 Torr by employing a two-step liquid source chemical vapor deposition (CVD) process. BST films on RuO 2 /Ru were electrically shorted, which was considered to be caused by surface roughening during BST film deposition and/or post-annealing. In the case of Ru electrodes, an equivalent SiO 2 thickness of t eq =0.50 nm (a dielectric constant of ε r =190), a leakage current of J L =4.6×10 -8 A/cm 2 at +1.1 V, and a dielectric loss of tan δ=0.018 were achieved at a total film thickness of 250 Å, by restricting Ru surface oxidation and its surface roughening. Moreover, BST film deposition on Ru storage nodes, 0.24 µ m wide, 0.6 µ m deep, 0.15 µ m high, and each spaced by 0.3–0.14 µ m, verified that the storage capacitance can be successfully increased by using sidewalls of the storage node, without a significant increase in the leakage current.
Epigenetic biomarkers in the blood of patients with urological malignancies (2015)

In the era of personalized medicine, there is an urgent need for non-invasive biomarkers to optimize the individual treatment of cancer patients. Epigenetic alterations, including DNA methylation and non-coding RNAs, are a hallmark of malignant tumors. The detection of many of these epigenetic conditions is feasible in bodily fluids, that is, blood plasma and serum, and may therefore be used for liquid biopsy. In this review, we summarize and discuss the current state of research on circulating epigenetic alterations (DNA methylation, miRNA and long non-coding RNA) in serum and plasma of patients with bladder cancer, prostate cancer, renal cell carcinoma and testicular germ cell cancer.
Inactivation of the Retinoblastoma Susceptibility Gene in Human Breast Cancers (1988)

Mutational inactivation of the retinoblastoma susceptibility (RB) gene, a recessive cancer gene, has been implicated in the genesis of retinoblastoma and certain other human neoplasms. This gene is now shown to be inactivated in two of nine human breast cancer cell lines examined. The RB gene of one cell line had a homozygous internal duplication of a 5-kilobase region containing exons 5 and 6. The RB messenger RNA transcript was correspondingly lengthened, and its translation was probably terminated prematurely due to a shifted reading frame. The other cell line had a homozygous deletion of the RB gene that removed the entire gene beyond exon 2. The RB gene product, pp110RB, was not detectable in either cell line by immuno-precipitation with specific antibodies. These findings are significant in relation to proposed genetic mechanisms of breast cancer formation.
State of the art: antiretroviral and prophylactic treatments in HIV/AIDS. (1999)

HIV results in a continual and progressive pathological attack on the human immune system. This attack on the immune system can be altered with combination antiretroviral agents that interrupt the HIV life-cycle. There are three classes of approved antiretroviral agents: nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors. The progressive deterioration of the patient's immune system by HIV infection increases the likelihood of developing opportunistic infections. Primary measures that can be taken to prevent the development of opportunistic infections are preventing exposure to the microorganisms in the environment and maintaining a competent immune system using antiretroviral therapy through prophylactic agents specific to opportunistic infections.
Controlled morphology of biologically derived metal nanopatterns (1997)

We report the ability to control the morphology of nanometer thick Ti oxide films that were created via a parallel nanofabrication process using a two-dimensional protein crystal as a template. Atomic force microscopy was used to examine the evolution of these structures from a periodic array of nanometer-scale dots (nanodots) to a screen containing a periodic array of nanometer-scale holes (nanoscreen) as the film thickness was increased. A Monte Carlo solid-on-solid simulation was then developed to explain the thickness dependence of the morphology as the metal film self-organizes into these nanopatterns.
Plasma Concentrations of Interleukin-6 and Abdominal Aortic Diameter Among Subjects Without Aortic Dilatation (1999)

Previous studies suggest that cytokine-induced tissue inflammation may participate in the pathogenesis of abdominal aortic aneurysms. Serum inflammatory markers may reflect arterial inflammation in asymptomatic phases of the aneurysmal disease. We studied 120 outpatients (62 men; age, 65+/-9 years) by ultrasound evaluation of the abdominal aorta to evaluate the association of circulating levels of interleukin-6 (IL-6) with abdominal aortic diameter in subjects with normal aortic size. Aortic diameter was measured at the infrarenal level and indexed for body surface area. Seven patients with abdominal aortic dilatation (indexed aortic diameter, >1.3 cm/m2) were also identified. Plasma concentrations of IL-6, serum amyloid A (SAA), C-reactive protein (CRP), total homocysteine, and lipids were measured. Among the 113 subjects without aortic dilatation, indexed aortic diameter was positively associated with serum levels of IL-6 (P<0.01), SAA (P<0.01), and total homocysteine (P=0.01). IL-6 levels increased in a stepwise fashion among dichotomized groups of aortic size (low and high aortic diameters) and peaked in patients with aortic dilatation (2.3+/-1.2 versus 2. 7+/-0.9 versus 3.2+/-0.9 pg/mL, respectively; P for trend=0.039). None of the serum lipid measurements correlated with abdominal aortic diameter. Although CRP levels were associated with SAA levels (r=0.60; P<0.001), associations between CRP and aortic diameter were nonsignificant. In multivariate analysis, levels of IL-6 (P=0.02), SAA (P=0.001), and total homocysteine (P<0.001) were independent correlates of indexed aortic diameter. In conclusion, circulating levels of IL-6, SAA, and total homocysteine may reflect processes involved in the early phases of abdominal aortic aneurysm formation, before dilation of the abdominal aorta is established. These data support a role for chronic inflammation in the progression of asymptomatic aortic disease.
Solving structures of protein complexes by molecular replacement withPhaser (2006)

Molecular replacement (MR) generally becomes more difficult as the number of components in the asymmetric unit requiring separate MR models (i.e. the dimensionality of the search) increases. When the proportion of the total scattering contributed by each search component is small, the signal in the search for each component in isolation is weak or non-existent. Maximum-likelihood MR functions enable complex asymmetric units to be built up from individual components with a ;tree search with pruning' approach. This method, as implemented in the automated search procedure of the program Phaser, has been very successful in solving many previously intractable MR problems. However, there are a number of cases in which the automated search procedure of Phaser is suboptimal or encounters difficulties. These include cases where there are a large number of copies of the same component in the asymmetric unit or where the components of the asymmetric unit have greatly varying B factors. Two case studies are presented to illustrate how Phaser can be used to best advantage in the standard ;automated MR' mode and two case studies are used to show how to modify the automated search strategy for problematic cases.
3D models of the lips for realistic speech animation (2002)

3D models of the lips have been developed in the framework of an audio visual articulatory speech synthesizer. Unlike most of the regions of the human face, the lips are essentially characterized by their border contours. The internal and external contours of the vermilion zone can be fitted by means of algebraic equations. The coefficients of these equations must be controlled so that the lip shape can be adapted to speaker dependent conformations and to any speech "gesture". To reach this goal, a 3D model of the lips has been based on a geometrical analysis of the natural lips of a French speaker. Our lip model was developed by adjusting a set of continuous functions best fitting the contours of 22 reference lip shapes. Only five parameters are necessary to predict all the equations of the contours of the lip model. From this model, a volumetric model based on implicit surfaces was also developed to take into account lip contact.
SGDB: a database of synthetic genes re-designed for optimizing protein over-expression (2006)

Here we present the Synthetic Gene Database (SGDB): a relational database that houses sequences and associated experimental information on synthetic (artificially engineered) genes from all peer-reviewed studies published to date. At present, the database comprises information from more than 200 published experiments. This resource not only provides reference material to guide experimentalists in designing new genes that improve protein expression, but also offers a dataset for analysis by bioinformaticians who seek to test ideas regarding the underlying factors that influence gene expression. The SGDB was built under MySQL database management system. We also offer an XML schema for standardized data description of synthetic genes. Users can access the database at http://www.evolvingcode.net/codon/sgdb/index.php, or batch downloads all information through XML files. Moreover, users may visually compare the coding sequences of a synthetic gene and its natural counterpart with an integrated web tool at http://www.evolvingcode.net/codon/sgdb/aligner.php, and discuss questions, findings and related information on an associated e-forum at http://www.evolvingcode.net/forum/viewforum.php?f=27.
Altering Antibody–Drug Conjugate Binding to the Neonatal Fc Receptor Impacts Efficacy and Tolerability (2016)

Antibody-drug conjugates (ADC) rely on the target-binding specificity of an antibody to selectively deliver potent drugs to cancer cells. IgG antibody half-life is regulated by neonatal Fc receptor (FcRn) binding. Histidine 435 of human IgG was mutated to alanine (H435A) to explore the effect of FcRn binding on the pharmacokinetics, efficacy, and tolerability of two separate maytansine-based ADC pairs with noncleavable linkers, (c-DM1 and c-H435A-DM1) and (7v-Cys-may and 7v-H435A-Cys-may). The in vitro cell-killing potency of each pair of ADCs was similar, demonstrating that H435A showed no measurable impact on ADC bioactivity. The H435A mutant antibodies showed no detectable binding to human or mouse FcRn in vitro, whereas their counterpart wild-type IgG ADCs were found to bind to FcRn at pH = 6.0. In xenograft bearing SCID mice expressing mouse FcRn, the AUC of 7v-Cys-may was 1.6-fold higher than that of 7v-H435A-may, yet the observed efficacy was similar. More severe thrombocytopenia was observed with 7v-H435A-Cys-may as compared to 7v-Cys-may at multiple dose levels. The AUC of c-DM1 was approximately 3-fold higher than that of c-H435A-DM1 in 786-0 xenograft bearing SCID mice, which led to a 3-fold difference in efficacy by dose. Murine FcRn knockout, human FcRn transgenic line 32 SCID animals bearing 786-0 xenografts showed an amplified exposure difference between c-DM1 and c-H435A-DM1 as compared to murine FcRn expressing SCID mice, leading to a 10-fold higher dose required for efficacy despite a 6-fold higher AUC of the c-H435A-DM1. The accelerated clearance observed for the noncleavable maytansine ADCs with the H435A FcRn mutation led to reduced efficacy at equivalent doses and exacerbation of clinical pathology parameters (decreased tolerability) at equivalent doses. The results show that reduced ADC clearance mediated by FcRn modulation can improve therapeutic index.
Effect of permeation enhancers on the release of ketoprofen through transdermal drug delivery systems. (1996)

Feasibility studies were performed to prepare membrane controlled transdermal drug delivery system of ketoprofen containing Carbopol 934p gels. The ability of permeation enhancers such as oleic acid, polyethylene glycol 400 and propylene glycol to provide improved performance has been investigated. The variables studied were drug loading, type of the permeation enhancers, and their concentration. Diffusion studies across Spectra/por 1 membranes were performed using Franz diffusion cells. The medium employed was pH 7.4 phosphate buffer. The permeation parameters such as flux, enhancement ratio, permeation and diffusion coefficients have been evaluated. The results indicated a zero or near zero-order release kinetics. The studies indicated that oleic acid in a concentration of 35% w/w provided the maximum permeation when the ketoprofen concentration in the patches was 5%. Corresponding values of flux,enhancement ratio, permeability and diffusion coefficients were 6.22 micrograms/cm2/h, 8.57, 1.09 x 10(-3) cm/h, and 3.13 x 10(-6) cm3/h respectively. Further, an increase in ketoprofen loading from 5 to 10% increased the permeation.
Arginines in the CDR of anti‐dsDNA autoantibodies facilitate cell internalization via electrostatic interactions (2008)

Internalization of autoantibodies against double-stranded DNA (anti-dsDNA) is crucial to the pathogenesis of systemic lupus erythematosus. Anti-dsDNA may bind to cell-surface targets in order to facilitate the subsequent cell penetration of the anti-dsDNA. In this study, we observed that the 9D7 monoclonal anti-dsDNA autoantibody (9D7 mAb) penetrates into Jurkat cells via a novel alternative pathway. Endocytosis inhibitors or a lipid-raft inhibitor did not significantly change the penetration of 9D7 mAb into the Jurkat cells. However, heparin sulfate, chondroitin sulfate B, decaarginine and chondroitinase ABC significantly suppressed the internalization and the 9D7 mAb inhibited the internalization of Tat-GFP. Moreover, the penetration of the 9D7 mAb was significantly reduced in proteoglycan-deficient cells (pgs A-745). Positively charged amino acids including arginine are commonly found in the CDR of the 9D7 mAb. Point mutations to the arginine residues in the CDR of the H chain of the recombinant 9D7 mAb significantly attenuated its DNA-binding and cell-penetration abilities. These findings indicate that cell penetration of anti-dsDNA is due to the electrostatic interactions of arginine residues in the CDR with the negatively charged sulfated polysaccharides on the cell surface.
BTK inhibition in myeloma: targeting the seed and the soil (2012)

In this issue of Blood , Tai and colleagues identify Bruton tyrosine kinase (BTK) inhibition as a new and effective strategy for the treatment of myeloma and the associated bone disease.[1][1]

Despite many recent advances in our understanding of the pathogenesis of multiple myeloma and the
High frequency capacitive single crystal silicon resonators and coupled resonator systems (2006)

The objective of the work presented in this thesis is to implement high-Q silicon capacitive micromechanical resonators operating in the HF, VHF and UHF frequency bands. Several variations of a fully silicon-based bulk micromachining fabrication process referred to as HARPSS have been developed, characterized and optimized to overcome most of the challenges facing application of such devices as manufacturable electronic components. Several micromechanical structures for implementation of high performance capacitive silicon resonators covering various frequency ranges have been developed under this work. Design criteria and electromechanical modeling of such devices is presented. &#13;\nUnder this work, HF and VHF resonators with quality factors in the tens of thousands and RF-compatible equivalent electrical impedances have been implemented successfully. Resonance frequencies in the GHz range with quality factors of a few thousands and lowest motional impedances reported for capacitive resonators to date have been achieved. Several resonator coupling techniques for implementation of higher order resonant systems with possibility of extension to highly selective bandpass filters have been investigated and practically demonstrated. Finally, a wafer-level vacuum sealing technique applicable to such resonators has been developed and its reliability and hermeticity is characterized.
Thalidomide Target Identified (2010)

Thalidomide binding to a component of an E3 ubiquitin ligase induces developmental defects in vertebrates.