gebhart/patrepeval huggingface dataset:
ABX-EGF in combination with paclitaxel and carboplatin for advanced non-small cell lung cancer (NSCLC) (2004)

7083 Background: ABX-EGF is a high-affinity, fully human, IgG2 monoclonal antibody directed against epidermal growth factor receptor (EGFr). This is a report of results from part 1 of a 2-part, phase 2 trial to evaluate the efficacy, safety, and pharmacokinetics (PK) of ABX-EGF in combination with paclitaxel and carboplatin for advanced NSCLC. Methods: In this open-label, sequential, dose-escalation design in pts with NSCLC (stage IIIb or IV) and EGFr expression of 2+ or 3+ in >=10% of tumor cells, pts received weekly IV ABX-EGF in combination with standard paclitaxel and carboplatin every 3 weeks for up to 6 cycles; pts with response or stable disease could receive extended ABX-EGF therapy. Responses (RECIST) were evaluated at week 6 with confirmation >=3 weeks later. The PK of ABX-EGF and paclitaxel were evaluated at weeks 0 and 3. Results: Nineteen pts (5 men/14 women; mean [SD] age 52.2 [11.9] years) were enrolled into 3 ABX-EGF cohorts: 1.0 mg/kg (n=6), 2.0 mg/kg (n=7), and 2.5 mg/kg (n=6). One pt (5%) had a confirmed complete response (1.0 mg/kg) and 4 pts (21%) had partial responses (2 at 2.0 mg/kg and 2 at 2.5 mg/kg) by investigator assessment. The most common adverse event (AE) was skin rash (89% overall; 83%, 100%, and 83% in the 1.0, 2.0, and 2.5 mg/kg groups). The incidence of grade 3 skin rash did not appear to increase with dose (17% at 1.0 mg/kg, 29% at 2.0 mg/kg, and 0% at 2.5 mg/kg). Four pts (1 at 1.0 mg/kg and 3 at 2.0 mg/kg) had ABX-EGF dosing interrupted or reduced because of skin toxicities. The PK of ABX-EGF appeared to be dose dependent. PK results for paclitaxel were similar to that reported in the literature. Conclusions: ABX-EGF is well tolerated in combination with paclitaxel and carboplatin for advanced NSCLC. Part 2 of the study continues to accrue patients to further assess clinical activity in this setting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Inc. Amgen Amgen Amgen Amgen
Identification of a region of frequent loss of heterozygosity at 11q24 in colorectal cancer. (1999)

Loss of heterozygosity (LOH) at 11q23-qter occurs frequently in ovarian and other cancers, but for colorectal cancer, the evidence is conflicting. Seven polymorphic loci were analyzed between D11S897 and D11S969 in 50 colorectal tumors. Two distinct LOH regions were detected, suggesting possible sites for tumor-suppressor genes involved in colorectal neoplasia: a large centromeric region between D11S897 and D11S925, and a telomeric 4.9-Mb region between D11S912 and D11S969. There was no correlation with clinicopathological features. This analysis describes a region of LOH in the region 11q23.3-24.3 for the first time in colorectal cancer and provides complementary evidence for the ongoing effort to identify the gene(s) involved.
Glycoprotein lib peptide 656–667 mimics the fibrinogen γ chain 402–411 binding site on platelet integrin GPIIb/IIIa (1993)

The human integrin glycoprotein IIb/IIIa complex plays a central role in haemostasis as an inducible receptor for fibrinogen and other adhesive proteins at the platelet plasma membrane. Current evidence indicates that the ligand-binding domain of GPIIb/IIIa is discontinuous and placed at the subunit interface. Here we show that a synthetic peptide containing the polypeptide stretch GPIIb 656-667, which is hidden within the resting platelet GPIIb/IIIa heterodimer but becomes exposed following platelet activation with thrombin, binds to soluble fibrinogen (n = 2.3 +/- 1.3; Kd = 2 +/- 0.8 x 10(-5) M). This interaction is Ca(2+)-independent and can be partially inhibited with synthetic fibrinogen gamma-chain peptide 400-411 but not with GRGDS. In addition, peptide GPIIb 656-667 inhibits in a dose-dependent manner the aggregation of activated platelets (IC50 = 170 microM). Altogether, our results indicate that the GPIIb 656-667 region may form part of the inducible fibrinogen binding site and may not overlap with the integrin RGD-recognition domain.
Lack of Multiplication of Ecotropic Murine C-Type Viruses in Mouse Teratocarcinoma Primitive Cells: Brief Communication2 (1977)

Ecotropic murine C-type viruses did not multiply in strain 129 mouse primitive teratocarcinoma cells cultivated in vitro. In contrast they replicated in differentiated cell lines derived from the same tumor.
Boolean implication networks derived from large scale, whole genome microarray datasets (2008)

We describe a method for extracting Boolean implications (if-then relationships) in very large amounts of gene expression microarray data. A meta-analysis of data from thousands of microarrays for humans, mice, and fruit flies finds millions of implication relationships between genes that would be missed by other methods. These relationships capture gender differences, tissue differences, development, and differentiation. New relationships are discovered that are preserved across all three species.
Exploiting the properties of carbon nanotubes for nanolithography (1998)

Carbon nanotube tips are explored in fabricating oxide nanostructures on silicon surfaces with an atomic force microscope. Nanotubes can write nanostructures at speeds up to 0.5 mm/s over large surface areas, and present a solution to the long-standing tip-wear problem. Experimental and theoretical work find that nanotube tips are impervious to high compressive and lateral forces and breakdown in high electric fields. A “cleaving” method is developed to reproducibly obtain dome-closed multi-walled nanotube tips with suitable length. Nanotube materials could become key elements for future miniaturization applications.
Interactive graph cuts for optimal boundary & region segmentation of objects in N-D images (2002)

In this paper we describe a new technique for general purpose interactive segmentation of N-dimensional images. The user marks certain pixels as "object" or "background" to provide hard constraints for segmentation. Additional soft constraints incorporate both boundary and region information. Graph cuts are used to find the globally optimal segmentation of the N-dimensional image. The obtained solution gives the best balance of boundary and region properties among all segmentations satisfying the constraints. The topology of our segmentation is unrestricted and both "object" and "background" segments may consist of several isolated parts. Some experimental results are presented in the context of photo/video editing and medical image segmentation. We also demonstrate an interesting Gestalt example. A fast implementation of our segmentation method is possible via a new max-flow algorithm.
Simulation optimization using soft computing (2001)

To date, most of the research in simulation optimization has been focused on single response optimization on the continuous space of input parameters. However, the optimization of more complex systems does not fit this framework. Decision makers often face the problem of optimizing multiple performance measures of systems with both continuous and discrete input parameters. Previously acquired knowledge of the system by experts is seldomincorporated into the simulation optimization engine. Furthermore, when the goals of the system design are stated in natural language or vague terms, current techniques are unable to deal with this situation. For these reasons, we define and study the fuzzy single response simulation optimization (FSO) and fuzzy multiple response simulation optimization (FMSO) problems.\n\nThe primary objective of this research is to develop an efficient and robust method for simulation optimization of complex systems with multiple vague goals. This method uses a fuzzy controller to incorporate existing knowledge to generate high quality approximate Pareto optimal solutions in a minimum number of simulation runs.\n\nFor comparison purposes, we also propose an evolutionary method for solving the FMSO problem. Extensive computational experiments on the design of a flow line manufacturing system (in terms of tandem queues with blocking) have been conducted. Both methods are able to generate high quality solutions in terms of Zitzlerand Thiele's 'dominated space' metric. Both methods are also able to generate an even sample of the Pareto front. However, the fuzzy controlled method is more efficient, requiring fewer simulation runs than the evolutionary method to achieve the same solution quality.\n\nTo accommodate the complexity of natural language, this research also provides a new Bezier curve-based mechanism to elicit knowledge and express complex vague concepts. To date, this is perhaps the most flexible and efficient mechanism for both automatic and interactive generation of membership functions for convex fuzzy sets.
A dynamin-like protein (ADL2b), rather than FtsZ, is involved in Arabidopsis mitochondrial division (2002)

Recently, the FtsZ protein, which is known as a key component in bacterial cell division, was reported to be involved in mitochondrial division in algae. In yeast and animals, however, mitochondrial fission depends on the dynamin-like proteins Dnm1p and Drp1, respectively, whereas in green plants, no potential mitochondrial division genes have been identified. BLAST searches of the nuclear and mitochondrial genome sequences of Arabidopsis thaliana did not find any obvious homologue of the alpha-proteobacterial-type ftsZ genes. To determine whether mitochondrial division of higher plants depends on a dynamin-like protein, we cloned a cDNA for ADL2b, an Arabidopsis homologue of Dnm1p, and tested its subcellular localization and its dominant-negative effect on mitochondrial division. The fusion protein of green fluorescent protein and ADL2b was observed as punctate structures localized at the tips and at the constriction sites of mitochondria in live plant cells. Cells expressing dominant-negative mutant ADL2b proteins (K56A and T77F) showed a significant fusion, aggregation, and/or tubulation of mitochondria. We propose that mitochondrial division in higher plants is conducted by dynamin-like proteins similar to ADL2b in Arabidopsis. The evolutional points of loss of mitochondrial FtsZ and the functional acquisition of dynamin-like proteins in mitochondrial division are discussed.
Immunoadsorption: Strategies for Antigen Elution and Production of Reusable Adsorbents (1992)

Immunoadsorption is a powerful and generalizable method for protein purification that exploits the fine specificity of antigen-antibody interactions. In spite of its potential utility, the more widespread process scale use of immunoadsorption has been limited by the high cost of the antibody and the lack of gentle elution schemes that completely preserve the activity of both the immunoadsorbent and the eluted product. In this report, we review common chemical elution strategies such as pH, ionic strength, chaotropic salts, denaturants, and organic solvents as well as physical techniques such as pressure, electrokinetics, and temperature. In general, selection of elution strategies has largely been an empirical art, balancing stability of the immunoadsorbent and the eluted product and efficiency. The limitations of the available choices demonstrate that more attention must be placed on the antibody. Techniques which assist in the identification or creation of new antibodies with improved binding properties and resistance to degradation, e.g., screening and/or rational protein engineering, are also discussed.
Intrinsic cardiac origin of human cardiosphere-derived cells (2011)

Cardiosphere-derived cells are of endogenous cardiac origin, with no detectable contribution from extra-cardiac seeding.
The adipocyte specific transcription factor C/EBPalpha modulates human ob gene expression. (1996)

The ob gene product, leptin, apparently exclusively expressed in adipose tissue, is a signaling factor regulating body weight homeostasis and energy balance. ob gene expression is increased in obese rodents and regulated by feeding, insulin, and glucocorticoids, which supports the concept that ob gene expression is under hormonal control, which is expected for a key factor controlling body weight homeostasis and energy balance. In humans, ob mRNA expression is increased in gross obesity; however, the effects of the above factors on human ob expression are unknown. We describe the structure of the human ob gene and initial functional analysis of its promoter. The human ob gene's three exons cover approximately 15 kb of genomic DNA. The entire coding region is contained in exons 2 and 3, which are separated by a 2-kb intron. The first small 30-bp untranslated exon is located >10.5 kb upstream of the initiator ATG codon. Three kilobases of DNA upstream of the transcription start site has been cloned and characterized. Only 217 bp of 5' sequence are required for basal adipose tissue-specific expression of the ob gene as well as enhanced expression by C/EBPalpha. Mutation of the single C/EBPalpha site in this region abolished inducibility of the promoter by C/EBPalpha in cotransfection assays. The gene structure will facilitate our analysis of ob mutations in human obesity, whereas knowledge of sequence elements and factors regulating ob gene expression should be of major importance in the prevention and treatment of obesity.
Galectin‐3 deficiency protects pancreatic islet cells from cytokine‐triggered apoptosis in vitro (2013)

Beta cell apoptosis is a hallmark of diabetes. Since we have previously shown that galectin-3 deficient (LGALS3(-/-) ) mice are relatively resistant to diabetes induction, the aim of this study was to examine whether beta cell apoptosis depends on the presence of galectin-3 and to delineate the underlying mechanism. Deficiency of galectin-3, either hereditary or induced through application of chemical inhibitors, β-lactose or TD139, supported survival and function of islet beta cells compromised by TNF-α + IFN-γ + IL-1β stimulus. Similarly, inhibition of galectin-3 by β-lactose or TD139 reduced cytokine-triggered apoptosis of beta cells, leading to conclusion that endogenous galectin-3 propagates beta apoptosis in the presence of an inflammatory milieu. Exploring apoptosis-related molecules expression in primary islet cells before and after treatment with cytokines we found that galectin-3 ablation affected the expression of major components of mitochondrial apoptotic pathway, such as BAX, caspase-9, Apaf, SMAC, caspase-3, and AIF. In contrast, anti-apoptotic molecules Bcl-2 and Bcl-XL were up-regulated in LGALS3(-/-) islet cells when compared to wild-type (WT) counterparts (C57BL/6), resulting in increased ratio of anti-apoptotic versus pro-apoptotic molecules. However, Fas-triggered apoptotic pathway as well as extracellular signal-regulated kinase 1/2 (ERK1/2) was not influenced by LGALS-3 deletion. All together, these results point to an important role of endogenous galectin-3 in beta cell apoptosis in the inflammatory milieu that occurs during diabetes pathogenesis and implicates impairment of mitochondrial apoptotic pathway as a key event in protection from beta cell apoptosis in the absence of galectin-3.
Identification of Candidate Gammaherpesvirus 68 Genes Required for Virus Replication by Signature-Tagged Transposon Mutagenesis (2004)

Current methods for determining the role of a given gene product in the gammaherpesvirus 68 (gammaHV68) life cycle require generation of a specific mutation by either homologous recombination in mammalian cells or bacterial artificial chromosome-mediated mutagenesis in Escherichia coli. The mutant virus is then compared to wild-type virus, and the role of the gene in the viral life cycle is deduced from its phenotype. This process is both time-consuming and labor intensive. Here we present the use of random, transposon-mediated signature-tagged mutagenesis for the identification of candidate viral genes involved in virus replication. Pools of viral mutants, each containing a random insertion of a transposon, were generated with a transposon donor library in which each transposon contains a unique sequence identifier. These pools were transfected into mammalian cells, and the ability of each mutant to replicate was assessed by comparing the presence of virus in the output pool to that present in the input pool of viral genomes. With this approach we could rapidly screen up to 96 individual mutants simultaneously. The location of the transposon insertion was determined by sequencing individual clones with a common primer specific for the transposon end. Here we present the characterization of 53 distinct viral mutants that correspond to insertions in 29 open reading frames within the gammaHV68 genome. To confirm the results of the signature-tagged mutagenesis screen, we quantitated the ability of each mutant to replicate compared to wild-type gammaHV68. From these analyses we identified 16 gammaHV68 open reading frames that, when disrupted by transposon insertions, score as essential for virus replication, and six other open reading frames whose disruption led to significant attenuation of virus replication. In addition, transposon insertion in five other gammaHV68 open reading frames did not affect virus replication. Notably, all but one of the candidate essential replication genes identified in this screen have been shown to be essential for the replication of at least one other herpesvirus.
Gene discovery in the wood-forming tissues of poplar: Analysis of 5,692 expressed sequence tags (1998)

A rapidly growing area of genome research is the generation of expressed sequence tags (ESTs) in which large numbers of randomly selected cDNA clones are partially sequenced. The collection of ESTs reflects the level and complexity of gene expression in the sampled tissue. To date, the majority of plant ESTs are from nonwoody plants such as Arabidopsis, Brassica, maize, and rice. Here, we present a large-scale production of ESTs from the wood-forming tissues of two poplars, Populus tremula L. x tremuloides Michx. and Populus trichocarpa 'Trichobel.' The 5,692 ESTs analyzed represented a total of 3,719 unique transcripts for the two cDNA libraries. Putative functions could be assigned to 2,245 of these transcripts that corresponded to 820 protein functions. Of specific interest to forest biotechnology are the 4% of ESTs involved in various processes of cell wall formation, such as lignin and cellulose synthesis, 5% similar to developmental regulators and members of known signal transduction pathways, and 2% involved in hormone biosynthesis. An additional 12% of the ESTs showed no significant similarity to any other DNA or protein sequences in existing databases. The absence of these sequences from public databases may indicate a specific role for these proteins in wood formation. The cDNA libraries and the accompanying database are valuable resources for forest research directed toward understanding the genetic control of wood formation and future endeavors to modify wood and fiber properties for industrial use.
Synthesis of CuInS2, CuInSe2, and Cu(InxGa1-x)Se2(CIGS) Nanocrystal “Inks” for Printable Photovoltaics (2008)

Chalcopyrite copper indium sulfide (CuInS2) and copper indium gallium selenide (Cu(InxGa(1-x))-Se2; CIGS) nanocrystals ranging from approximately 5 to approximately 25 nm in diameter were synthesized by arrested precipitation in solution. The In/Ga ratio in the CIGS nanocrystals could be controlled by varying the In/Ga reactant ratio in the reaction, and the optical properties of the CulnS2 and CIGS nanocrystals correspond to those of the respective bulk materials. Using methods developed to produce uniform, crack-free micrometer-thick films, CulnSe2 nanocrystals were tested in prototype photovoltaic devices. As a proof-of-concept, the nanocrystal-based devices exhibited a reproducible photovoltaic response.
H2RM: A Hybrid Rough Set Reasoning Model for Prediction and Management of Diabetes Mellitus (2015)

Diabetes is a chronic disease characterized by high blood glucose level that results either from a deficiency of insulin produced by the body, or the body's resistance to the effects of insulin. Accurate and precise reasoning and prediction models greatly help physicians to improve diagnosis, prognosis and treatment procedures of different diseases. Though numerous models have been proposed to solve issues of diagnosis and management of diabetes, they have the following drawbacks: (1) restricted one type of diabetes; (2) lack understandability and explanatory power of the techniques and decision; (3) limited either to prediction purpose or management over the structured contents; and (4) lack competence for dimensionality and vagueness of patient's data. To overcome these issues, this paper proposes a novel hybrid rough set reasoning model (H2RM) that resolves problems of inaccurate prediction and management of type-1 diabetes mellitus (T1DM) and type-2 diabetes mellitus (T2DM). For verification of the proposed model, experimental data from fifty patients, acquired from a local hospital in semi-structured format, is used. First, the data is transformed into structured format and then used for mining prediction rules. Rough set theory (RST) based techniques and algorithms are used to mine the prediction rules. During the online execution phase of the model, these rules are used to predict T1DM and T2DM for new patients. Furthermore, the proposed model assists physicians to manage diabetes using knowledge extracted from online diabetes guidelines. Correlation-based trend analysis techniques are used to manage diabetic observations. Experimental results demonstrate that the proposed model outperforms the existing methods with 95.9% average and balanced accuracies.
Core Excitation Spectroscopy of Phenyl- and Methyl-Substituted Silanol, Disiloxane, and Disilane Compounds:  Evidence for π-Delocalization across the Si−CphenylBond (1997)

The Si 1s and 2p solid state photoabsorption (total electron yield) spectra of triphenylsilanol, hexaphenyldisiloxane, and hexaphenyldisilane and the Si 1s spectra (total ion yield) of gaseous trimethylsilanol, hexamethyldisiloxane, hexamethyldisilane, and trimethylmethoxysilane have been recorded using synchrotron radiation. These spectra are compared to inner shell electron energy loss spectra of gaseous triphenylsilanol, hexaphenyldisilane, trimethylmethoxysilane, hexamethyldisiloxane, and hexamethyldisilane in the Si 2p and C 1s regions, measured under scattering conditions where electric dipole transitions dominate (2.5 keV residual energy, θ ≤ 2°). Comparison of the Si 1s and Si 2p spectra of the Ph3Si−X and Me3Si−X species shows there are low-lying transitions at Si which occur exclusively in the Ph3Si−X species. These transitions are attributed to (Si 1s-1,π*Si-Ph) and (Si 2p-1,π*Si-Ph) states in which the core excited electron is delocalized across the Si−C(phenyl) bond into the π* levels of the phenyl ring. Extended Hückel and ab initio molecular orbital calculations of the core excitation spectra support this interpretation. Transitions characteristic of Si−Si and Si−O bonds are also identified.
HIV-1 protease inhibitors: synthesis and biological evaluation of glycopeptidemimetics. (1993)

A series of glycopeptidemimetics based on the hydroxyethylene Phe-Phe isostere have been synthesized and evaluated for their ability to inhibit the enzyme HIV-1 protease. Incorporation of carbohydrate moieties at the P'2-position and elimination of P'3 amino acid in our lead compound 1, provided inhibitors with only nanomolar potencies (400-800 nM). However, incorporation of a carbohydrate moiety at the P'3-position with branched chain amino acid at the P'2-position, resulted in inhibitors with subnanomolar potencies. Within this series, compound 21 was the most potent inhibitor (IC50 value 0.17 nM). This compound has also shown to block the spread of HIV-1 in T-lymphoid cells at an inhibitor concentration of 200 nM.