gebhart/patrepeval huggingface dataset:
Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients (2008)

The impact of KRAS mutations on cetuximab sensitivity in epidermal growth factor receptor fluorescence in situ hybridisation-positive (EGFR FISH+) metastatic colorectal cancer patients (mCRC) has not been previously investigated. In the present study, we analysed KRAS, BRAF, PI3KCA, MET, and IGF1R in 85 mCRC treated with cetuximab-based therapy in whom EGFR status was known. KRAS mutations (52.5%) negatively affected response only in EGFR FISH+ patients. EGFR FISH+/KRAS mutated had a significantly lower response rate (P=0.04) than EGFR FISH+/KRAS wild type patients. Four EGFR FISH+ patients with KRAS mutations responded to cetuximab therapy. BRAF was mutated in 5.0% of patients and none responded to the therapy. PI3KCA mutations (17.7%) were not associated to cetuximab sensitivity. Patients overexpressing IGF1R (74.3%) had significantly longer survival than patients with low IGF1R expression (P=0.006), with no difference in response rate. IGF1R gene amplification was not detected, and only two (2.6%) patients, both responders, had MET gene amplification. In conclusion, KRAS mutations are associated with cetuximab failure in EGFR FISH+ mCRC, even if it does not preclude response. The rarity of MET and IGF1R gene amplification suggests a marginal role in primary resistance. The potential prognostic implication of IGF1R expression merits further evaluation.
Cellular and Molecular Neurosurgery: Pathways from Concept to Reality-Part I: Target Disorders and Concept Approaches to Gene Therapy of the Central Nervous System (1997)

Recent advances in cellular and molecular biology and better understanding of genetic and biochemical bases of different central nervous system (CNS) disorders have made gene therapy of the CNS a realistic goal. Concept approaches for gene therapy of CNS disorders are reviewed and include the following: 1) gene replacement with a single normal allele to correct the inherited global neurodegenerative disorders, such as enzyme deficiencies; 2) brain repair to restore the function of a particular subset of cells that were lost because of a neurodegenerative process; 3) gene therapy of brain tumors; and 4) gene therapy of stroke. Techniques of viral vector-mediated CNS transfer of a therapeutic gene, transplantation of genetically modified cells, fetal embryonic implantation and/or implantation of genetically engineered neural progenitor cells, and production of a specific enzyme, neurotransmitter, and/or growth factor are discussed with respect to the therapeutic potential for global and localized CNS neurodegenerative disorders and stroke. Transfection of the CNS tumor cells with the drug susceptibility ("suicide") gene and/or "toxic" gene and antisense strategies and a concept of adoptive immunotherapy of brain tumors are also discussed. Other approaches, such as transfer of drug-resistant genes and monoclonal antibody gene transfer, are briefly discussed. In addition to summarizing current principles of gene therapy for several groups of CNS disorders, the issues that remain to be resolved in clinical reality, such as delivery of the genetic material and regulation of the cellular expression of the transgene, and the negatives associated with the concepts of gene therapy, such as transient gene expression, toxicity of viral proteins, drawbacks of antisense therapy, and the problem of immune response to the transfected protein, have been also identified.
Recombinant Listeria monocytogenes as a tumor therapeutic (2001)

Naturally arising tumor antigens can be categorized into four groups, shared tumor antigens, tissue-specific tumor antigens, mutated self antigens and antigens of tumor-associated viruses. Recombinant Listeria monocytogenes (rLm) has been demonstrated in animal models to induce a potent anti-tumor immune response by targeting an artificial tumor antigen to the immune system. In order to examine the ability of rLm to induce immune responses to actual tumor antigens two systems were developed. The first utilized the E7 gene derived from the human papillomavirus (HPV) and expressed in the majority of human cervical cancers to investigate the ability of rLm strains to induce immunity to a naturally occurring virally derived tumor antigen. The second system targeted the tumor antigen, P815A, to examine if rLm strains expressing a shared tumor antigen could overcome potential tolerance to these “self” proteins. To test the ability of rLm to induce immunity to the E7 antigen two rLm strains were constructed. One, Lm-E7, expressed and secreted the E7 gene product from a single chromosomally integrated gene. The second, Lm-LLO-E7, expressed and secreted a fusion protein comprised of a non-hemolytic listeriolysin O joined at the C-terminus to E7 and encoded by an episomal expression system. In spite of the induction of measurable E7 specific CTL responses, Lm-E7 had little effect on the growth of the E7 expressing tumor line, TC-1. Lm-E7 failed to induce a sufficient CD4+ T help response, and the depletion of CD4+ cells actually improved the effectiveness of Lm-E7 treatment. In contrast, Lm-LLO-E7 induced complete regression of established TC-1 tumors that was dependent on CD8+, CD4+ cells and the cytokine IFN-γ. The second model system tested the capabilities of rLm to secrete the shared tumor antigen P815A and the influence that an rLm strain secreting this protein had on established tumors of the antigen positive P815 tumor line. The results demonstrate that hydrophobic domains within a recombinant antigen can block secretion of the antigen by the rLm strain. Also, a P815A secreting rLm strain induced only weak immunity to P815A, insufficient to control P815 tumor growth.
Insulin Acutely Increases Fibrinogen Production in Individuals With Type 2 Diabetes but Not in Individuals Without Diabetes (2003)

Fibrinogen is an acute-phase reactant and an independent cardiovascular risk factor. Insulin without amino acid replacement acutely suppressed fibrinogen production in nondiabetic and type 1 diabetic individuals. Fibrinogen production and plasma concentration increase in insulin-resistant type 2 diabetes. It is not known whether altered response to insulin contributes to hyperfibrinogenemia in type 2 diabetes. Fibrinogen fractional (FSR) and absolute (ASR) synthesis rates were measured using a leucine isotopic model in type 2 diabetic men (n = 7; age = 51 +/- 3 years; BMI = 26.7 +/- 1 kg/m(2)) compared with matched nondiabetic subjects under basal conditions and following a 4-h euglycemic-, euaminoacidemic-hyperinsulinemic clamp. Basal fibrinogen concentration (+35%, P < 0.05) and ASR (+35%, P < 0.05) were greater in the diabetic subjects. Following clamp, fibrinogen FSR and ASR were unchanged in the control subjects. In contrast, fibrinogen FSR and ASR increased by 41 and 43%, respectively (P < 0.05), in the diabetic subjects. Thus, fibrinogen production is acutely increased by insulin when euglycemia and euaminoacidemia are maintained in type 2 diabetic individuals but not in nondiabetic individuals. Enhanced fibrinogen production by insulin is likely to be a key alteration contributing to hyperfibrinogenemia and therefore cardiovascular risk in type 2 diabetes. Unchanged fibrinogen production in nondiabetic individuals suggests a role of plasma amino acids in regulating fibrinogen production in humans.
Microemulsion Additives Enable Optimized Formation Damage Repair and Prevention (2005)

A new microemulsion additive has been developed that is effective in remediating damaged wells and is highly effective in fluid recovery and relative permeability enhancement when applied in drilling and stimulation treatments at dilute concentrations. The microemulsion is a unique blend of biodegradable solvent, surfactant, co-solvent and water. The nanometer-sized structures are modeled after Veronoi structures which when dispersed in the base treating fluid of water or oil permit a greater ease of entry into a damaged area of the reservoir or fracture system. The structures maximize surface energy interaction by expanding to twelve times their individual surface areas to allow maximum contact efficiency at low concentrations (0.1–0.5%). Higher loadings on the order of 2% can be applied in the removal of water blocks and polymer damage. Lab data are shown for the microemulsion in speeding the cleanup of injected fluids in tight gas cores. Further tests show that the microemulsion additive results in lower pressures to displace frac fluids from propped fractures resulting in lower damage and higher production rates. This reduced pressure is also evident in pumping operations where friction is lowered by 10–15% when the microemulsion is added to fracturing fluids. Field examples are shown for remediation and fracture treating of coals, shales and sandstone reservoirs, where productivity is increased by 20–50% depending on the treatment parameters. Drilling examples are shown in horizontal drilling where wells cleanup without the aid of workover rigs where offsets typically require weeks of workover.
Catalytic carbon-carbon bond cleavage and carbon-element bond formation give new life for polyolefins as biodegradable surfactants (2021)

Catalytic methods that introduce functional groups via carbon-carbon bond cleavage steps have typically been limited to moieties activated by strain or by directing groups, with few transformations engaging the bonds of only sp(3)-hybridized carbon atoms in saturated hydrocarbons. Here, we report the conversion of catenated carbon chains in polyolefins, which currently represent >50% of discarded plastics, into shorter aliphatic alkylaluminum species via a sequence of zirconation via C-H bond activation, beta-alkyl elimination for carbon-carbon bond cleavage, and heterobimetallic alkyl group exchange for carbon-aluminum bond formation. The versatility of aliphatic alkylaluminum species is exemplified by their subsequent conversion into high-value fatty acids or alcohols, which have applications as biodegradable surfactants and detergents. A technoeconomic analysis indicates that fatty alcohols produced from discarded polyolefins are cost competitive with conventional syntheses. Thus, this process could ameliorate economic and environmental challenges of the plastic-waste crisis.
Signature-Based Small Molecule Screening Identifies Cytosine Arabinoside as an EWS/FLI Modulator in Ewing Sarcoma (2007)

We demonstrate that a gene expression-based approach to small-molecule library screening can identify, for rapid clinical testing, candidate drugs that modulate previously intractable targets. Furthermore, this is a generic approach that can, in principle, be applied to the identification of modulators of any tumor-associated oncoprotein in the rare pediatric malignancies, but also in the more common adult cancers.
NASCArrays: a repository for microarray data generated by NASC's transcriptomics service (2003)

NASC operates an Affymetrix 'GeneChip' (microarray) service for the Arabidopsis thaliana community. All data produced by the service are publicly available through our microarray data base 'NASCArrays' published at http://affymetrix. arabidopsis.info. The data are accessible through text searching and a series of data mining tools. All data are annotated with sample preparation details, and the original Affymetrix data are available for download. The database aims to be MIAME supportive and provide a coordinated resource for re searchers interested in the transcriptome of Arabidopsis. Using this database, data produced will be shared with other databases worldwide.
Developmental Validation of a Single-Tube Amplification of the 13 CODIS STR Loci, D2S1338, D19S433, and Amelogenin: The AmpFℓSTR® Identifiler® PCR Amplification Kit (2004)

Analysis of length polymorphism at short tandem repeat (STR) loci utilizing the polymerase chain reaction (PCR) process has proven to be an ideal assay for human identification purposes. The short length of STR loci coupled with the amplification of target sequence through PCR allows for a robust, sensitive, and specific assay for highly polymorphic markers. A multiplex containing fifteen STR loci plus the gender-determining locus Amelogenin was developed to provide a single amplification/detection of all CODIS (Combined DNA Index System) STR loci (CSF1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, TH01, TPOX, and vWA) as well as two internationally-accepted STRs (D2S1338 and D19S433). By incorporating five-dye fragment analysis technology and non-nucleotide linkers, previously optimized AmpFlSTR kit primer sequences have been maintained. This kit has been developed in accordance with the standards of the forensic community as defined by the DNA Advisory Board. Validation studies were performed to include developmental validation, and the results support the use of the AmpFlSTR Identifiler PCR Amplification Kit for human identity and parentage testing.
A Novel Δ3,Δ2-Enoyl-CoA Isomerase Involved in the Biosynthesis of the Cyclohexanecarboxylic Acid-Derived Moiety of the Polyketide Ansatrienin A, (2000)

The side chain of the antifungal polyketide ansatrienin A produced by Streptomyces collinus contains a cyclohexanecarboxylic acid (CHC) derived moiety. This CHC in the coenzyme A activated form (CHC-CoA) is derived from shikimic acid via a pathway in which the penultimate step is the isomerization of 2-cyclohexenylcarbonyl-CoA to 1-cyclohexenylcarbonyl-CoA. We have purified a 28 kDa 2-cyclohexenylcarbonyl-CoA isomerase (ChcB) from S. collinus and cloned and sequenced the corresponding chcB gene. The predicted amino acid sequence of ChcB showed moderate sequence identity to members of the hydratase/isomerase superfamily of enzymes. The recombinant ChcB was overexpressed in Escherichia coli and purified to homogeneity using metal chelate chromatography. Kinetic analysis demonstrated that recombinant ChcB had wide substrate specificity and could catalyze a double bond isomerization using 2-cyclohexenylcarbonyl-CoA (K(m) 116 +/- 68 microM, k(cat)( )()3.7 +/- 1.0 min(-)(1)), trans-3-hexenyl-CoA (K(m) 39 +/- 10 microM, k(cat)( )()12.8 +/- 1 min(-)(1)), and vinylacetyl-CoA (K(m) 156 +/- 34 microM, k(cat)( )()29 +/- 3 min(-)(1)) as substrates. ChcB activity in cell extracts of S. collinus SP1, an insertionally disrupted chcB mutant, was shown to decrease by more than 99% (as compared to the wild-type strain) using all three of these substrates. The S. collinus SP1 strain, unlike the wild-type strain, could not produce omega-cyclohexyl fatty acids but was still able to grow efficiently on methyl oleate as a sole carbon source. These observations demonstrate that the S. collinus ChcB is required for catalyzing the isomerization of 2-cyclohexenylcarbonyl-CoA to 1-cyclohexenylcarbonyl-CoA during CHC-CoA biosynthesis but not for degradation of unsaturated fatty acids. The chcB gene does not appear to be associated with the ansatrienin biosynthetic gene cluster, which has previously been shown to contain at least one gene known to be essential for CHC-CoA biosynthesis. This finding represents a notable exception to the general rule regarding the clustering of polyketide biosynthetic pathway genes.
In vivo molecular imaging by LAESI MS (2008)

ADVERTISEMENT RETURN TO ISSUEPREVRESEARCH PROFILENEXTIn vivo molecular imaging by LAESI MSChristine PiggeeCite this: Anal. Chem. 2008, 80, 13, 4783Publication Date (Web):July 1, 2008Publication History Published online1 July 2008Published inissue 1 July 2008https://pubs.acs.org/doi/10.1021/ac086126chttps://doi.org/10.1021/ac086126cnewsACS Publications. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views481Altmetric-Citations5LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (159 KB) Get e-Alertsclose SUBJECTS:Molecular imaging Get e-Alerts
A Theory of Communicating Sequential Processes (1984)

A mathematical model for communicating sequential processes is given, and a number of its interesting and useful properties are stated and proved. The possibilities of nondetermimsm are fully taken into account.
CATCH-919 Hand: Design of a 9-actuator 19-DOF Anthropomorphic Robotic Hand (2018)

To achieve human-like dexterity for anthropomorphic robotic hands, it is essential to understand the biomechanics and control strategies of the human hand, in order to reduce the number of actuators being used without loosing hand flexibility. To this end, in this article, we propose a new interpretation about the working mechanism of the metacarpal (MCP) joint's extension and the underlying control strategies of the human hand, based on which we further propose a highly flexible finger design to achieve independent movements of interphalangeal (IP) joints and MCP joint. Besides, we consider the hyperextension of fingertip into our design which helps robotic finger present compliant and adaptive posture for touching and pinching. In addition, human thumb muscle functions are reconstructed in the proposed robotic hand design, by replacing 9 human muscle tendons with 3 cables in the proposed task-oriented design, realizing all 33 static and stable grasping postures. Videos are available at https://sites.google.com/view/szwd
Effects of a Prostaglandin DP Receptor Agonist, AL-6598, on Aqueous Humor Dynamics in a Nonhuman Primate Model of Glaucoma (2006)

This study examines, in 11 cynomolgus monkeys with unilateral laser-induced glaucoma, the ocular hypotensive mechanism of action of AL-6598, partial agonist at the DP and EP prostanoid receptors. In a crossover fashion, both eyes of each monkey were dosed twice daily with 25 microL of either AL-6598 0.01% or vehicle for 2 days and on the morning of the 3rd day. Measurements were made on day 3 of each treatment. Alternative treatments were separated by at least 2 weeks. Intraocular pressures (IOPs) were measured by pneumatonometry and aqueous flow and outflow facility by fluorophotometry. Uveoscleral outflow was calculated mathematically. In the normotensive eyes, compared to vehicle treatment, AL-6598 decreased IOP from 22.5 +/- 0.7 to 18.7 +/- 0.9 mmHg (P = 0.006), increased uveoscleral outflow from 0.47 +/- 0.17 to 1.22 +/- 0.17 microL/min (P = 0.03), and increased aqueous flow from 1.49 +/- 0.10 to 1.93 +/- 0.13 microL/min (P = 0.01). No measurement in AL-6598-treated hypertensive eyes was significantly different from vehicle treatment. It is concluded that AL-6598 reduces IOP by increasing uveoscleral outflow in normotensive eyes of ketamine-sedated monkeys, despite an increase in aqueous flow. This effect is different from that of PGD(2), which decreases aqueous flow, and of the selective DP receptor agonist, BW245C, which increases both outflow facility and uveoscleral outflow in addition to decreasing aqueous flow.
Small Macrocycles As Highly Active Integrin α2β1 Antagonists (2014)

Starting from clinical candidates Firategrast, Valategrast, and AJM-300, a series of novel macrocyclic platelet collagen receptor α2β1 antagonists were developed. The amino acid derived low molecular weight 14-18-membered macrocycles turned out to be highly active toward integrin α2β1 with IC50s in the low nanomolar range. The conformation of the macrocycles was found to be highly important for the activity, and an X-ray crystal structure was obtained to clarify this. Subsequent docking into the metal-ion-dependent adhesion site (MIDAS) of a β1 unit revealed a binding model indicating key binding features. Macrocycle 38 was selected for further in vitro and in vivo profiling.
Torsional Carbon Nanotube Artificial Muscles (2011)

Rotary motors of conventional design can be rather complex and are therefore difficult to miniaturize; previous carbon nanotube artificial muscles provide contraction and bending, but not rotation. We show that an electrolyte-filled twist-spun carbon nanotube yarn, much thinner than a human hair, functions as a torsional artificial muscle in a simple three-electrode electrochemical system, providing a reversible 15,000° rotation and 590 revolutions per minute. A hydrostatic actuation mechanism, as seen in muscular hydrostats in nature, explains the simultaneous occurrence of lengthwise contraction and torsional rotation during the yarn volume increase caused by electrochemical double-layer charge injection. The use of a torsional yarn muscle as a mixer for a fluidic chip is demonstrated.
A phase I/II safety and efficacy study of intratumoral light-activated drug therapy using talaporfin sodium in patients with inoperable hepatocellular carcinoma (2009)

e15684 Background: Light Infusion Therapy™ (Litx™) consists of the light-activated drug, talaporfin sodium (LS11®; mono-L-aspartyl chlorin e6), activated by a single-use, disposable device with an array of light-emitting diodes (LEDs). We evaluated talaporfin in combination with the light source in a phase 1/2 safety and efficacy trial in patients with hepatocellular carcinoma (HCC). To the best of our knowledge, this is the first clinical study of light-activated drug therapy in patients with HCC. Methods: Patients had confirmed primary HCC, 1–3 liver lesions, an ECOG score of 0–2, and a life expectancy of at least 16 weeks. Prior treatment failure with locally ablative techniques was allowed. The light-activated drug used in the study was talaporfin, a semi-synthesized, water-soluble chlorin e6 derivative. The LED device used in this study was a 1.5 mm diameter linear array of LEDs with a 25 mm emitting length at a wavelength of 664 nm. Patients underwent image-guided percutaneous placement of 1–4 LED device(s) using either local anesthesia or conscious sedation. The LED devices were used in single lesions or in multiple lesions. Following intratumoral placement of the LED devices, patients received talaporfin at 1 mg/kg IV bolus. Delivery of light energy commenced 15 min to 1 hr following drug administration with a total illumination time of 2.8 hrs. Results: The enrolled study group consisted of 8 patients. All 8 patients completed the week 4 assessment and were evaluated for tumor response. One (12.5%) out of 8 patients in this study was reported to have a complete response at week 4. Five patients (62.5%) were reported to have stable disease, and another 2 patients (25%) showed progressive disease. During the study, 7 patients reported a total of 16 treatment-related adverse events. There were no treatment-related adverse events that were greater than grade 2. At 1 year post treatment, all patients were alive. Conclusions: The results from this phase 2 study demonstrated that the therapy was safe for the treatment of HCC. A subsequent randomized controlled phase 3 pivotal trial is nearing completion and is designed to prove efficacy in patients with inoperable HCC. [Table: see text]