gebhart/patrepeval huggingface dataset:
MET Kinase Inhibitor SGX523 Synergizes with Epidermal Growth Factor Receptor Inhibitor Erlotinib in a Hepatocyte Growth Factor–Dependent Fashion to Suppress Carcinoma Growth (2010)

The hepatocyte growth factor (HGF)-MET pathway supports several hallmark cancer traits, and it is frequently activated in a broad spectrum of human cancers (http://www.vai.org/met/). With the development of many cancer drugs targeting this pathway, there is a need for relevant in vivo model systems for preclinical evaluation of drug efficacy. Here, we show that production of the human HGF ligand in transgenic severe combined immunodeficient mice (hHGF(tg)-SCID mice) enhances the growth of many MET-expressing human carcinoma xenografts, including those derived from lung, breast, kidney, colon, stomach, and pancreas. In this model, the MET-specific small-molecule kinase inhibitor SGX523 partially inhibits the HGF-dependent growth of lung, breast, and pancreatic tumors. However, much greater growth suppression is achieved by combinatorial inhibition with the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib. Together, these results validate the hHGF(tg)-SCID mouse model for in vivo determination of MET sensitivity to drug inhibition. Our findings also indicate that simultaneously targeting the MET and EGFR pathways can provide synergistic inhibitory effects for the treatment of cancers in which both pathways are activated.
Oxcarbazepine: Clinical Development Program (1994)

Oxcarbazepine (OCBZ, Trileptal) is registered in several countries and has been well received by patients and physicians. However, newer standards in many other countries require additional data before registration can be achieved. For this reason, Ciba has implemented further clinical studies. OCBZ has a chemical structure that is closely related to carbamazepine (CBZ). In humans, OCBZ is not oxidatively metabolized, therefore causing little, if any, induction of hepatic enzymes. Because of this, and because of low protein-binding properties, OCBZ causes markedly fewer interactions with concomitant medications than most marketed antiepileptic drugs. OCBZ has been shown to have significantly fewer limiting side effects (described as side effects leading to discontinuation of treatment) than CBZ, while showing comparable efficacy. Many patients who are hypersensitive to CBZ can be treated with OCBZ. The usually administered dosage of OCBZ is approximately 50% higher than that of CBZ. However, better tolerability of OCBZ makes it possible to give higher dosages. The plasma concentration half-life of the active metabolite (monohydroxy derivative; MHD) makes it possible to administer OCBZ twice daily. No changes in dosage are necessary in patients with impaired renal function unless creatinine clearance is below 30 ml/min. In patients with such severely reduced creatinine clearance, the dose of OCBZ should be halved. Specific questions e.g., such as whether OCBZ causes hepatic enzyme induction at higher doses and the effect of OCBZ on intrinsic sex hormones, will be answered in future studies. In addition, the tolerability and pharmacokinetics of OCBZ in specific target populations such as the elderly, children, and hepatically impaired patients will be addressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Omnistereo: panoramic stereo imaging (2001)

An omnistereo panorama consists of a pair of panoramic images, where one panorama is for the left eye and another panorama is for the right eye. The panoramic stereo pair provides a stereo sensation up to a full 360 degrees. Omnistereo panoramas can be constructed by mosaicing images from a single rotating camera. This approach also enables the control of stereo disparity, giving larger baselines for faraway scenes, and a smaller baseline for closer scenes. Capturing panoramic omnistereo images with a rotating camera makes it impossible to capture dynamic scenes at video rates and limits omnistereo imaging to stationary scenes. We present two possibilities for capturing omnistereo panoramas using optics without any moving parts. A special mirror is introduced such that viewing the scene through this mirror creates the same rays as those used with the rotating cameras. The lens used for omnistereo panorama is also introduced, together with the design of the mirror. Omnistereo panoramas can also be rendered by computer graphics methods to represent virtual environments.
Hydrolytic stability of helical RNA: a selective advantage for the natural 3',5'-bond. (1976)

Dodecaadenylic acid containing a single 2', 5'-linkage at a defined position was formed by the coupling of two hexamers on a poly(U) template at 2 degrees. The rate of hydrolysis of this dodecamer was compared with that of a dodecamer that contained only the natural 3', 5'-linkages. At 40 degrees, in 1 M aqueous ethylenediamine at pH 8 in the absence of poly(U), both dodecamers hydrolyzed at comparable rates, but the addition of two equivalents of poly(U) caused a 7-fold increase in the initial rate of hydrolysis of the oligomer containing the 2', 5'-bond, and a 5-fold decrease in the initial rate of hydrolysis of the natural oligomer. When the oligomers are fully constrained in helical form, the ratio of the rates of cleavage of one 2', 5'-bond to one 3', 5'-bond under these conditions is probably about 900:1. The use of the 3', 5'-bond, in combination with a right-handed helix, appears to have had a large selective advantage over the use of the 2', 5'-bond for the storage of genetic information.
Expression of human cathepsin D in Xenopus oocytes: phosphorylation and intracellular targeting. (1987)

We have obtained expression of a cDNA clone for human cathepsin D in Xenopus laevis oocytes. Biosynthetic studies with [35S]methionine labeling demonstrated that most of the cathepsin D remained intracellular and underwent proteolytic cleavage, converting a precursor of Mr 47,000 D to a mature form of Mr 39,000 D with processing intermediates of Mr 43,000-41,000 D. greater than 90% of the cathepsin D synthesized by oocytes bound to a mannose 6-phosphate (Man-6-P) receptor affinity column, indicating the presence of phosphomannosyl residues. An analysis of [2-3H]mannose-labeled oligosaccharides directly demonstrated phosphomannosyl residues on cathepsin D. Sucrose-gradient fractionation, performed to define the membranous compartments that cathepsin D traversed during its biosynthesis, demonstrated that cathepsin D is targeted to a subpopulation of yolk platelets, the oocyte equivalent of a lysosome. Xenopus oocytes were able to endocytose lysosomal enzymes from the medium and this uptake was inhibited by Man-6-P, thus demonstrating the presence of Man-6-P receptors in these cells. Therefore, the entire Man-6-P dependent pathway for targeting of lysosomal enzymes is present in the oocytes. Xenopus oocytes should be a useful system for examining signals responsible for the specific targeting of lysosomal enzymes to lysosomes.
Soft Thermal Sensor with Mechanical Adaptability (2016)

A soft thermal sensor with mechanical adaptability is fabricated by the combination of single-wall carbon nanotubes with carboxyl groups and self-healing polymers. This study demonstrates that this soft sensor has excellent thermal response and mechanical adaptability. It shows tremendous promise for improving the service life of soft artificial-intelligence robots and protecting thermally sensitive electronics from the risk of damage by high temperature.
Proving properties of rule-based systems (2002)

A deductive method is applied to the validation of rule-based systems. A number of validation tasks, including the detection of errors or anomalies, the proof of termination, the verification of properties, and the generation of test cases, are all translated into conjectures. If the conjectures in an appropriate system theory are proved, the corresponding validation task is accomplished. The method applies to nonmonotonic rule systems, which may delete elements from working memory, as well as monotonic ones, which do not. Validation conjectures are proved or disproved in a new theorem-proving system, SNARK, which has facilities for reasoning in first-order theories with mathematical induction. The system has already been applied to establish properties of a number of simple rule-based systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. (1998)

The interstitial cells of Cajal (ICC) form a complex cell network within the gastrointestinal tract wall where they function as a pacemaker system. Expression of the kit proto-oncogene is essential for the development of this system. The aim of our study was to examine the hypothesis that gastrointestinal stromal tumors differentiate toward cells with an ICC phenotype. Ultrastructurally, 58 stromal tumors were characterized and found to share many features with ICC. Seventy-eight stromal tumors were immunophenotyped, particularly with regard to the kit receptor. All 78 tumors revealed strong, homogeneous immunoreactivity for the kit receptor as did ICC of adjacent and control gastrointestinal walls. Focal hyperplasia and hypertrophy of kit receptor positive cells were also observed in the gastrointestinal wall adjacent to the tumors. CD34 immunoreactivity observed in interstitial cells surrounding Auerbach's ganglia suggests that a subpopulation of ICC is CD34 positive and may explain why 56 of 78 stromal tumors were CD34 positive. Thirty control tumors, including gastrointestinal leiomyomas and leiomyosarcomas, were all negative for the kit receptor. We conclude that gastrointestinal stromal tumors show striking morphological and immunophenotypic similarities with ICC and that they may originate from stem cells that differentiate toward a pacemaker cell phenotype. We propose that the noncommittal name "gastrointestinal stromal tumor" be replaced by gastrointestinal pacemaker cell tumor.
Application of the thin film permalloy magnetoresistive sensors in electrical measurements (1984)

Thin film magnetoresistive magnetic field sensor may be used in the design of measurement converters. Two basic function modules - a multiplier and a direct current transformer - have been described. Using the modules following converters have been constructed and investigated: one- and threephase power converter, watt-hour meter, direct current transformer, adder and contactless current converter. Main advantages of these converters are: design simplicity, small geometric dimensions and relatively low errors - of the order of 0.5%.
An Inertial Measurement System for Hand and Finger Tracking (2011)

The primary Human Computer Interfaces (HCI) today are the keyboard and mouse. These interfaces do not facilitate a fluid flow of thought and intent from the operator to the computer. A computer mouse provides only 2 Degrees of Freedom (2DOF). Touch interfaces also provide 2DOF, but with multiple points, making the touch interface far more expressive. The hand has 6 Degrees of Freedom (6DOF)by itself. Combined with the motion of the fingers, the hand has the potential to represent a vast array of differing gestures. Hand gestures must be captured before they can be used as a HCI. Fortunately, advances in device manufacturing now make it possible to build a complete Inertial Measurement Unit (IMU) the size of a fingernail. This thesis documents the design and development of a glove out tted with six IMUs. The IMUs are used to track the finger and hand positions. The glove employs a controller board for capturing IMU data and interfacing with the host computer. Python™ software on the host computer captures data from the glove. MATLAB™ is used to perform IMU calculations of the incoming data. The calculated data drives a 3D visualization of the glove rendered in Panda3D™. Future work using the glove would include improved IMU algorithms and development of gesture pattern recognition.
Pathophysiology of bone metastases: how this knowledge may lead to therapeutic intervention. (2004)

Bone metastases are common in many advanced cancers and are a clinically relevant source of skeletal morbidity. The bone mineral matrix contains numerous growth factors that are released during normal bone remodeling, providing a fertile microenvironment for tumor cell colonization and proliferation. Tumor cells then release a variety of growth factors that promote bone resorption and increase the risk of skeletal complications. Bisphosphonates are potent inhibitors of osteoclast activity that have demonstrated efficacy in the treatment of bone metastases. Bisphosphonates bind avidly to the bone matrix, are released during bone resorption, and are subsequently internalized by osteoclasts, where they interfere with biochemical pathways and induce osteoclast apoptosis. Bisphosphonates also antagonize osteoclastogenesis and promote the differentiation of osteoblasts. As a result, bisphosphonates inhibit tumor-induced osteolysis and reduce skeletal morbidity. Furthermore, preclinical studies suggest that bisphosphonates possess antitumor activity and can inhibit proliferation and induce apoptosis of tumor cell lines. In addition, zoledronic acid, a new-generation bisphosphonate, appears to inhibit tumor cell invasion of the extracellular matrix. These data suggest that zoledronic acid and other bisphosphonates may play a role in the reduction of skeletal tumor burden and the prevention of bone metastasis.
ChemInform Abstract: STUDIES ON ANTIVIRAL SUBSTANCES. IX. SYNTHESIS AND ANTIVIRAL ACTIVITY OF 1‐ACYL‐2‐HALO‐3‐FORMYLINDOLE THIOSEMICARBAZONES (1979)

Abstract Die durch Acylierung von Indolinon mittels entsprechender Säureanhydride erhaltenen 1‐Acyl‐indolinone (I) reagieren nach Vilsmeyer zu den Formyl‐indolen (II), die zu den Thiosemicarbazonen (III) umgesetzt werden können.
Photoacoustic Point Source (2001)

We investigate the photoacoustic effect generated by heat deposition at a point in space in an inviscid fluid. Delta-function and long Gaussian optical pulses are used as sources in the wave equation for the displacement potential to determine the fluid motion. The linear sound-generation mechanism gives bipolar photoacoustic waves, whereas the nonlinear mechanism produces asymmetric tripolar waves. The salient features of the photoacoustic point source are that rapid heat deposition and nonlinear thermal expansion dominate the production of ultrasound.
Multimeric connexin interactions prior to the trans-Golgi network (2001)

Cells that express multiple connexins have the capacity to form heteromeric (mixed) gap junction hemichannels. We used a dominant negative connexin construct, consisting of bacterial beta-galactosidase fused to the C terminus of connexin43 (Cx43/beta-gal), to examine connexin compatibility in NIH 3T3 cells. Cx43/beta-gal is retained in a perinuclear compartment and inhibits Cx43 transport to the cell surface. The intracellular connexin pool induced by Cx43/beta-gal colocalized with a medial Golgi apparatus marker and was readily disassembled by treatment with brefeldin A. This was unexpected, since previous studies indicated that Cx43 assembly into hexameric hemichannels occurs in the trans-Golgi network (TGN) and is sensitive to brefeldin A. Further analysis by sucrose gradient fractionation showed that Cx43 and Cx43/beta-gal were assembled into a subhexameric complex. Cx43/beta-gal also specifically interacted with Cx46, but not Cx32, consistent with the ability of Cx43/beta-gal to simultaneously inhibit multiple connexins. We confirmed that interactions between Cx43/beta-gal and Cx46 reflect the ability of Cx43 and Cx46 to form heteromeric complexes, using HeLa and alveolar epithelial cells, which express both connexins. In contrast, ROS osteoblastic cells, which differentially sort Cx43 and Cx46, did not form Cx43/Cx46 heteromers. Thus, cells have the capacity to regulate whether or not compatible connexins intermix.
Trop2 and its overexpression in cancers: regulation and clinical/ therapeutic implications (2014)

Trop2 is a transmembrane glycoprotein encoded by the Tacstd2 gene. It is an intracellular calcium signal transducer that is differentially expressed in many cancers. It signals cells for self-renewal, proliferation, invasion, and survival. It has stem cell-like qualities. Trop2 is expressed in many normal tissues, though in contrast, it is overexpressed in many cancers and the overexpression of Trop2 is of prognostic significance. Several ligands have been proposed that interact with Trop2. Trop2 signals the cells via different pathways and it is transcriptionally regulated by a complex network of several transcription factors. Trop2 expression in cancer cells has been correlated with drug resistance. Several strategies target Trop2 on cancer cells that include antibodies, antibody fusion proteins, chemical inhibitors, nanoparticles, etc. The in vitro studies and pre-clinical studies, using these various therapeutic treatments, have resulted in significant inhibition of tumor cell growth both in vitro and in vivo in mice. A clinical study is underway using IMMU-132 (hrS7 linked to SN38) in patients with epithelial cancers. This review describes briefly the various characteristics of cancer cells overexpressing Trop2 and the potential application of Trop2 as both a prognostic biomarker and as a therapeutic target to reverse resistance.
The PSIPRED protein structure prediction server (2000)

Freely available to non-commercial users at http://globin.bio.warwick.ac.uk/psipred/
Specific Secondary Genetic Alterations in Mantle Cell Lymphoma Provide Prognostic Information Independent of the Gene Expression–Based Proliferation Signature (2007)

Cyclin D1-positive and -negative MCLs share the same secondary genetic aberrations, supporting the concept that they correspond to the same genetic entity. The integration of genetic information on chromosome 3q and 9q alterations into a proliferation signature-based model may improve the ability to predict survival in patients with MCL.
Beckwith–Wiedemann syndrome (2005)

Beckwith-Wiedemann syndrome (BWS) is a clinically heterogeneous overgrowth syndrome associated with an increased risk for embryonal tumor development. BWS provides an ideal model system to study epigenetic mechanisms. This condition is caused by a variety of genetic or epigenetic alterations within two domains of imprinted growth regulatory genes on human chromosome 11p15. Molecular studies of BWS have provided important data with respect to epigenotype/genotype-phenotype correlations; for example, alterations of Domain 1 are associated with the highest risk for tumor development, specifically Wilms' tumor. Further, the elucidation of the molecular basis for monozygotic twinning in BWS defined a critical period for imprint maintenance during pre-implantation embryonic development. In the future, such molecular studies in BWS will permit enhanced medical management and targeted genetic counseling.
Real-time implementation of an efficient RLS algorithm based on IIR filter for acoustic echo cancellation (2008)

An efficient acoustic echo canceller has been proposed for hands-free communication systems which use a recursive least squares (RLS) algorithm. It also employ an infinite impulse response (IIR) filter based on output error method. The proposed IIR-RLS filter is more suitable for modeling real systems due to its pole-zero structure and it is required fewer number of filter coefficients to identify the time-varying echo path as compared to the traditional FIR-NLMS filter. However, with non-stationary long durations signals the proposed IIR-RLS filter suffers from instability problem. To avoid this problem, auto covariance matrix resetting was employed. Furthermore, the proposed system has been implemented in real-time in a real environment using National Instruments NI-PXI-1042Q controller system and data acquisition input card PXI-4472. Practical results, show that the proposed algorithm has the local minimum solutions and remain stable.
This Week's Citation Classic: Recalibrated Linkage Map of Escherichia coli K-12 (1982)

Barbara Bachmann's reflections on an article she co-authored. Bachmann, B. J., K. B. Low, and A. L. Taylor. Recalibrated linkage map of Escherichia coli K-12. Bacteriological Review 40: 116-167, 1976.
Farnesyltransferase inhibitor tipifarnib is well tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma (2004)

Patients with multiple myeloma (MM) with mutated RAS are less likely to respond to chemotherapy and have a shortened survival. Therefore, targeting RAS farnesylation may be a novel approach to treatment of MM. We evaluated the activity and tolerability of the farnesyltransferase (FTase) inhibitor tipifarnib (Zarnestra) in a phase 2 trial as well as its ability to inhibit protein farnesylation and oncogenic pathways in patients with relapsed MM. Forty-three patients (median age, 62 years [range, 33-82 years]) with a median of 4 (range, 1-6) chemotherapy regimens entered the study. Tipifarnib, 300 mg orally twice daily, was administered for 3 weeks every 4 weeks. The most common toxicity was fatigue occurring in 66% of patients. Other toxicities included diarrhea, nausea, neuropathy, anemia, and thrombocytopenia. Sixty-four percent of the patients had disease stabilization. Treatment with tipifarnib suppressed FTase (but not geranylgeranyltransferase I) in bone marrow and peripheral blood mononuclear cells and also inhibited the farnesylation of HDJ-2 in unfractionated mononuclear cells and purified myeloma cells. Inhibition of farnesylation did not correlate with disease stabilization. Finally, tipifarnib decreased the levels of phosphorylated Akt and STAT3 (signal transducer and activator of transcription 3) but not Erk1/2 (extracellular signal regulated kinase 1 and 2) in bone marrow cells. We conclude that tipifarnib is tolerable, can induce disease stabilization, and can inhibit farnesylation and oncogenic/tumor survival pathways.
Alkali Metal Reduction Potentials Measured in Chloroaluminate Ambient‐Temperature Molten Salts (1992)

Alkali metal electrochemical reductions at a mercury film electrode (MFE) were studied in (MEIC = 1‐methyl‐3‐ethylimidazolium chloride) molten salts buffered to a neutral composition with . The MFE was formed by mercury deposition on a 127‐μm iridium disk electrode. At the Ir‐MFE, the reduction potentials for the Li, Na, K, Rb, and Cs amalgams were observed at −1.16, −1.26, −1.62, −1.67, and −1.75 V (vs. Al/Al(III)), respectively. By comparison of the amalgam reduction potentials in the melts to aqueous data, the formal reduction potentials for the elemental alkali metals in the buffered neutral melts are calculated to be −2.14, −2.15, −2.71, −2.77, and −2.87 V (vs.Al/Al(III)), for Li, Na, K, Rb, and Cs, respectively. The solvation energies for the alkali metals in the chloroaluminate molten salts are calculated to be approximately 4 to 15% lower than aqueous solvation energies.