gebhart/patrepeval huggingface dataset:
Abstract 2012: Ultra-deep sequencing of circulating free DNA to identify predictive, mutated HSP90 clients in the GALAXY TrialTM (NCT01348126): a randomized phase IIB/III study of ganetespib (STA-9090) in combination with docetaxel versus docetaxel alone in subjects wit (2013)

Abstract Background: Non-small cell lung cancer is a mosaic, comprising several distinct molecular subtypes driven by somatic mutations in so-called cancer genes. Several of these oncogenic mutations confer dependence on HSP90 e.g. EML4-ALK, BRAF, KRAS, KIT. Inhibition of Hsp90 induces apoptosis and can exploit this dependence. Ganetespib (G) is an Hsp90 inhibitor with single agent activity in molecularly defined disease, including EML4-ALK rearrangement, KRAS mutations, HER2 amplification and BRAF mutations. Circulating free DNA (cfDNA) is present at low levels in plasma of healthy individuals allowing detection of somatic mutations by deep sequencing. The aim of this work was to determine the mutational spectrum of patients enrolled into the GALAXY trial using this liquid biopsy strategy. Methods: We performed a prospective exploratory analysis to identify plasma-borne somatic mutations as predictors of clinical outcome with G in GALAXY, a randomized trial, comparing G + docetaxel (D), to D alone in 2nd line advanced NSCLC patients. Plasma samples were collected from approximately 200 patients with adenocarcinoma at baseline prior to initiation of treatment, and during cycles 1 and 2. cfDNA samples were evaluated using the Ion AmpliSeq™ Cancer Panel on the Ion Torrent |PGM platform to survey 739 amplicons in 46 cancer genes at up to 6000x depth. Results: CfDNA targeted sequence analysis of the first 38 patients revealed multiple concurrent mutations in client proteins including the HSP90 client proteins BRAF, PDGFR and KIT, demonstrating the feasibility of this method. Sequencing of a larger cohort is underway. Longitudinal sampling of plasma has been conducted to monitor temporal evolution of the penetrance of mutations. Summary: Ultra-deep re-sequencing of multiple somatic mutations in circulating cfDNA is feasible, and can potentially enable identification of G sensitive subgroups. This represents a new approach to biomarker discovery in the context of phase II trials. Citation Format: Dean Anthony Fennell, L. Miguel Martins, Iman El-Hariry, Vojo Vukovic, Florentina Teofilovici, Vienna L. Reichert, Jacqui Shaw. Ultra-deep sequencing of circulating free DNA to identify predictive, mutated HSP90 clients in the GALAXY TrialTM (NCT01348126): a randomized phase IIB/III study of ganetespib (STA-9090) in combination with docetaxel versus docetaxel alone in subjects wit [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2012. doi:10.1158/1538-7445.AM2013-2012
Neurophysiological assessment of spinal cord stimulation in failed back surgery syndrome (2010)

Despite good clinical results, the mechanisms of action of spinal cord stimulation (SCS) for the treatment of chronic refractory neuropathic pain have not yet been elucidated. In the present study, the effects of SCS were assessed on various neurophysiological parameters in a series of 20 patients, successfully treated by SCS for mostly unilateral, drug-resistant lower limb pain due to failed back surgery syndrome. Plantar sympathetic skin response (SSR), F-wave and somatosensory-evoked potentials (P40-SEP) to tibial nerve stimulation, H-reflex of soleus muscle, and nociceptive flexion (RIII) reflex to sural nerve stimulation were recorded at the painful lower limb. The study included two recording sets while SCS was switched 'ON' or 'OFF' for 1h. Significant changes in 'ON' condition were as follows: SSR amplitude, H-reflex threshold, and RIII-reflex threshold and latency were increased, whereas SSR latency, F-wave latency, H-reflex amplitude, P40-SEP amplitude, and RIII-reflex area were reduced. Analgesia induced by SCS mainly correlated with RIII attenuation, supporting a real analgesic efficacy of the procedure. This study showed that SCS is able to inhibit both nociceptive (RIII-reflex) and non-nociceptive (P40-SEP, H-reflex) myelinated sensory afferents at segmental spinal or supraspinal level, and to increase cholinergic sympathetic skin activities (SSR facilitation). Complex modulating effects can be produced by SCS on various neural circuits, including a broad inhibition of both noxious and innocuous sensory information processing.
Vagus nerve stimulation: A new approach to reduce heart failure. (2010)

Autonomic imbalance with increased adrenergic and reduced parasympathetic activity is involved in the development and progress of heart failure (HF). Experimental data have demonstrated that stimulation of the vagus nerve is able to reverse ventricular remodeling of the failing heart. There is also evidence that increasing parasympathetic activity may stimulate the production of nitric oxide, and reduce the devastating inflammatory process involved in HF. Vagus nerve stimulation (VNS) has been successfully applied for many years to treat drug resistant epilepsy. The first study of right vagus stimulation in patients with advance HF has proven the feasibility and safety of this new approach. Long term follow-up of increased vagal tone over 12 months with a specially designed stimulating system (CardioFit, BioControl, Yehud, Israel) has demonstrated that symptoms of HF can be significantly diminished, left ventricular ejection fraction increased, and ventricular volumes reduced. These recently published data are very promising and may offer another approach for patients with advanced HF already treated with optimal medical therapy. A prospective randomized trial with a larger patient cohort is needed to confirm these beneficial results of VNS.
Brain tumor demarcation using optical spectroscopy; an <italic>in vitro</italic> study (2000)

Optical spectroscopy for brain tumor demarcation was investigated in this study. Fluorescence and diffuse reflectance spectra were measured from normal and tumorous human brain tissues in vitro. A fluorescence peak was consistently observed around 460 nm (+/- 10 nm) emission from both normal and tumorous brain tissues using 337 nm excitation. Intensity of this fluorescence peak (F460) from normal brain tissues was greater than that from primary brain tumorous tissues. In addition, diffuse reflectance (Rd) between 650 and 800 nm from white matter was significantly stronger than that from primary and secondary brain tumors. A good separation between gray matter and brain tumors was found using the ratio of F460 and Rd at 460 nm (Rd460). Two empirical discrimination algorithms based on F460, Rd625, and F460/Rd460 were developed. These algorithms yielded an average sensitivity and specificity of 96% and 93%, respectively.
Efficacy of (S)‐1‐(3‐hydroxy‐2‐phosphonylmethoxypropyl)cytosine and 9‐(1,3‐dihydroxy‐2‐propoxymethyl)guanine for the treatment of murine cytomegalovirus infection in severe combined immunodeficiency mice (1992)

Mice with severe combined immunodeficiency (SCID) inoculated intraperitoneally with murine cytomegalovirus (MCMV) develop a wasting syndrome at 3-4 days and die at 6-9 days after the infection. 9-(1,3-Dihydroxy-2-propoxymethyl)guanine (DHPG, ganciclovir) and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) were compared for their efficacy against MCMV-induced disease and mortality in SCID mice. Under all treatment conditions, i.e., administration of the test compounds for 5 consecutive days starting on the day of infection (day 0), for 5 consecutive days starting on day 4 after the infection, 2 periods of 3 consecutive days starting on day 0 and day 9 after infection, or as a single dose on day 3 before infection, HPMPC proved far superior to ganciclovir in delaying the onset of the disease and increasing the lifespan of the MCMV-infected mice.
Bio‐inspired Synthesis of Protein‐Encapsulated CoPt Nanoparticles (2005)

Abstract The 24 subunit heat‐shock protein from Methanococcus jannaschii has been genetically altered to display a dodecapeptide on the interior surface that has a strong binding affinity to the L1 0 phase of CoPt (CP_Hsp). Reaction of Co II and Pt II salts at 65 °C under reducing conditions results in the formation of a stable CoPt mineral encapsulated within the protein cage. Metallic particles commensurate in size with the interior dimensions of the protein cage (6.5 ± 1.3 nm) have been imaged by transmission electron microscopy and are shown to be surrounded by the intact protein cage. Magnetic measurements performed on the encapsulated nanoparticles exhibit room‐temperature hysteresis on the order of 150 G (1 G = 10 –4 T) prior to annealing and 610 G after annealing at 650 °C.
Aperture filling of phase-locked laser arrays (1987)

Arrays of lasers that are locked together with the same phase produce far-field patterns with a significant amount of the energy residing in the sidelobes. We describe a technique that channels the majority of the sidelobe energy into the desired central lobe.
The role of substrate-binding groups in the mechanism of aspartate-β-semialdehyde dehydrogenase (2004)

The reversible dephosphorylation of beta-aspartyl phosphate to L-aspartate-beta-semialdehyde (ASA) in the aspartate biosynthetic pathway is catalyzed by aspartate-beta-semialdehyde dehydrogenase (ASADH). The product of this reaction is a key intermediate in the biosynthesis of diaminopimelic acid, an integral component of bacterial cell walls and a metabolic precursor of lysine and also a precursor in the biosynthesis of threonine, isoleucine and methionine. The structures of selected Haemophilus influenzae ASADH mutants were determined in order to evaluate the residues that are proposed to interact with the substrates ASA or phosphate. The substrate Km values are not altered by replacement of either an active-site arginine (Arg270) with a lysine or a putative phosphate-binding group (Lys246) with an arginine. However, the interaction of phosphate with the enzyme is adversely affected by replacement of Arg103 with lysine and is significantly altered when a neutral leucine is substituted at this position. A conservative Glu243 to aspartate mutant does not alter either ASA or phosphate binding, but instead results in an eightfold increase in the Km for the coenzyme NADP. Each of the mutations is shown to cause specific subtle active-site structural alterations and each of these changes results in decreases in catalytic efficiency ranging from significant (approximately 3% native activity) to substantial (<0.1% native activity).
Drug design for neuroscience (1993)

Neurotransmitter receptors as pharmacological targets in Alzheimer's disease - design of drugs on a rational basis, Povi Krogsgaard-Larsen the design and synthesis of BMY 21502 - a potential memory and cognition enhancing agent, Ronald J. Mattson and Joseph P. Yevich muscarinic agonists for the central nervous system, Raymond Baker and Angus M. MacLeod novel organic reactions in the search for anxioselective anxiolytics at the benzodiazepine receptor, Weijiang Zhang and James M. Cook design of orally active dopamine autoreceptor agonists, Lawrence D. Wise and Juan C. Jaen 3 Beta-[substituted phenyl]tropan-2-carboxylic acid ester analogues of cocaine - synthesis, biochemical and pharmacological properties, F. Ivy Carroll et al serotonin receptors, agents and actions, Jeffrey L. Herndon and Richard A. Glennon studies of a novel series of thiazole-containing 5-HT3 receptor antagonists, Terry Rosen et al conformationally constrained acidic amino acids as probes of glutamate receptors and transporters, Richard Bridges and Richard Chamberlin L-2-[carboxycyclopropyl]glycines - conformationally constrained L-glutamate analogues, Yasufumi Ohfune and Heruhiko Shinozaki design and synthesis of conformationally constrained acidic amino acids as NMDA receptor antagonists, Paul L. Ornstein modulation of the NMDA receptor complex - design and synthesis of competitive NMDA antagonists and PCP-site ligands, Christopher F. Bigge et al glycine-site N-methyl-D-aspartate receptor antagonists, Paul D. Leeson synthetic inositol 1,4,5-triphosphate affinity-chromatography - fishing out novel ins(1,4,5)P3- recognizable proteins, Schoichiro Ozaki et al chemical approaches to brain-targeting of biologically active compounds, Marcus E. Brewster.
Characterization of follistatin-related gene as a negative regulatory factor for activin family members during mouse heart development (2007)

Follistatin-related gene (FLRG) encodes a secretory glycoprotein that has characteristic cysteine-rich follistatin domains. FLRG protein binds to and neutralizes several transforming growth factor-beta (TGF-beta) superfamily members, including myostatin (MSTN), which is a potent negative regulator of skeletal muscle mass. We have previously reported that FLRG was abundantly expressed in fetal and adult mouse heart. In this study, we analyzed the expression of FLRG mRNA during mouse heart development. FLRG mRNA was continuously expressed in the embryonic heart, whereas it was very low in skeletal muscles. By contrast, MSTN mRNA was highly expressed in embryonic skeletal muscles, whereas the expression of MSTN mRNA was rather low in the heart. In situ hybridization and immunohistochemical analysis revealed that FLRG expressed in smooth muscle of the aorta and pulmonary artery, valve leaflets of mitral and tricuspid valves, and cardiac muscles in the ventricle of mouse embryonic heart. However, MSTN was expressed in very limited areas, such as valve leaflets of pulmonary and aortic valves, the top of the ventricular and atrial septa. Interestingly, the expression of MSTN was complementary to that of FLRG, especially in the valvular apparatus. Biochemical analyses with surface plasmon resonance biosensor and reporter assays demonstrated that FLRG hardly dissociates from MSTN and activin once it bound to them, and efficiently inhibits these activities. Our results suggest that FLRG could function as a negative regulator of activin family members including MSTN during heart development.
Electroabsorption in GaAs/AlGaAs coupled quantum well waveguides (1987)

A novel GaAs/AlGaAs coupled quantum well structure, consisting of two 46 Å wells separated by a 11.5 Å barrier, was embedded in a leaky waveguide. Polarization anisotropy and quantum-confined Stark effect absorption changes are observed, and a 14:1 modulator is demonstrated operating at the peak of the first light-hole transition. Although the lowest energy transitions behave as predicted by tunneling resonance calculations, higher energy states exhibit unusual behavior due to valence-band mixing.
Design properties of hydrogel tissue-engineering scaffolds (2011)

This article summarizes the recent progress in the design and synthesis of hydrogels as tissue-engineering scaffolds. Hydrogels are attractive scaffolding materials owing to their highly swollen network structure, ability to encapsulate cells and bioactive molecules, and efficient mass transfer. Various polymers, including natural, synthetic and natural/synthetic hybrid polymers, have been used to make hydrogels via chemical or physical crosslinking. Recently, bioactive synthetic hydrogels have emerged as promising scaffolds because they can provide molecularly tailored biofunctions and adjustable mechanical properties, as well as an extracellular matrix-like microenvironment for cell growth and tissue formation. This article addresses various strategies that have been explored to design synthetic hydrogels with extracellular matrix-mimetic bioactive properties, such as cell adhesion, proteolytic degradation and growth factor-binding.
Evidence for the location of the receptor-binding site of human erythropoietin at the carboxyl-terminal domain (1991)

Five different peptides (P1: 84′95; P2: 152′166; P3: 52′63; P4: 7′23; P5: 110′123) homologous to relatively hydrophilic regions of human erythropoietin (huEpo) have been synthesized to identify biologically active domains of the hormone. All peptides were able to induce high titers of peptide-specific antibodies in rabbits. Antisera from rabbits induced by recombinant huEpo (rhuEpo) contained a relatively high amount of antibodies preferentially directed against three peptides (P2, P4, and P5), of which P4 comprised the amino-terminal region, P2 the carboxyl-terminus, and P5 an interior region previously described as the receptor-binding site. The same three peptides were able to induce rhuEpo-specific antibodies, whereas P1 and P3 lacked this activity. Only peptide-P2-induced antisera inhibited the biologic activity of rhuEpo in a cell proliferation assay, indicating that the carboxyl-terminal region of the molecule is essentially involved in the biologic function of rhuEpo.
High-Efficiency Green Organic Light-Emitting Devices Utilizing Phosphorescent Bis-cyclometalated Alkynylgold(III) Complexes (2010)

A new phosphorescent material of cyclometalated alkynylgold(III) complex, [Au(2,5-F(2)C(6)H(3)-C∧N∧C)(C≡C-C(6)H(4)N(C(6)H(5))(2)-p)] (1) (2,5-F(2)C(6)H(3)-HC∧N∧CH = 2,6-diphenyl-4-(2,5-difluorophenyl)pyridine), has been synthesized, characterized, and its device performance investigated. This luminescent gold(III) complex was found to exhibit rich PL and EL properties and has been utilized as phosphorescent dopants of OLEDs. At an optimized dopant concentration of 4%, a device with a maximum external quantum efficiency (EQE) of 11.5%, corresponding to a current efficiency of 37.4 cd/A and a power efficiency of 26.2 lm/W, has been obtained. Such a high EQE is comparable to that of Ir(ppy)(3)-based devices. The present work suggests that the alkynylgold(III) complex is a promising phosphorescent material in terms of both efficiency and thermal stability, with the additional advantages of its relatively inexpensive cost and low toxicity.
Location-based augmented reality on mobile phones (2010)

The computational capability of mobile phones has been rapidly increasing, to the point where augmented reality has become feasible on cell phones. We present an approach to indoor localization and pose estimation in order to support augmented reality applications on a mobile phone platform. Using the embedded camera, the application localizes the device in a familiar environment and determines its orientation. Once the 6 DOF pose is determined, 3D virtual objects from a database can be projected into the image and displayed for the mobile user. Off-line data acquisition consists of acquiring images at different locations in the environment. The online pose estimation is done by a feature-based matching between the cell phone image and an image selected from the precomputed database using the phone's sensors (accelerometer and magnetometer). The application enables the user both to visualize virtual objects in the camera image and to localize the user in a familiar environment. We describe in detail the process of building the database and the pose estimation algorithm used on the mobile phone. We evaluate the algorithm performance as well as its accuracy in terms of reprojection distance of the 3D virtual objects in the cell phone image.
Compressive imaging for video representation and coding (2006)

Abstract. Compressive Sensing is an emerging field based on the revelation that a small group of nonadaptive linear projections of a compressible signal contains enough information for reconstruction and processing. In this paper, we propose algorithms and hardware to support a new theory of Compressive Imaging. Our approach is based on a new digital image/video camera that directly acquires random projections of the light field without first collecting the pixels/voxels. Our camera architecture employs a digital micromirror array to perform optical calculations of linear projections of an image onto pseudorandom binary patterns. Its hallmarks include the ability to obtain an image with a single detection element while measuring the image/video fewer times than the number of pixels/voxels; this can significantly reduce the computation required for video acquisition/encoding. Since our system relies on a single photon detector, it can also be adapted to image at wavelengths that are currently impossible with conventional CCD and CMOS imagers. We are currently testing a prototype design for the camera and include experimental results. Index Terms: camera, compressive sensing, imaging, incoherent projections, linear programming, random
Progestin Increases Gene Transcription and Messenger Ribonucleic Acid Stability of Fatty Acid Synthetase in Breast Cancer Cells (1989)

The cDNA clone (Pg8) corresponding to the 3'-end of fatty acid synthetase (FAS) mRNA is one of the few probes to study in cell lines the mechanism by which an endogenous gene is regulated by progestins. The steady-state level of FAS mRNA is known to be increased by the synthetic progestin R5020 in the human breast cancer cell line MCF7. We show here that it is also increased in another progesterone-receptor-positive cell line T47D but not in progesterone-receptor-negative cell lines BT20, MDA-MB231, and HBL100. In R5020-treated MCF7 cells, the FAS mRNA concentration increased with cell density. Protein synthesis inhibitors did not abolish progestin induction of FAS suggesting a primary effect of the hormone. In vitro nuclear run-on transcription assays showed that the FAS gene transcription rate was increased about 4-fold by progestin. This stimulation of transcription was detectable 30 min after addition of R5020 and was maximal after 4 h, but could not totally account for the total increase in the mRNA steady state level. Chase experiments in the presence of Actinomycin D or Cordycepin showed that progestin also increased the half-life of FAS mRNA from 6-9 h to 24-33 h. We conclude that progestin stimulates the FAS concentration both by increasing the transcription rate of the gene and by stabilizing the mRNA.
Architectural Changes in the TCR:CD3 Complex Induced by MHC:Peptide Ligation (2004)

A hallmark of T cell activation is the ligation-induced down-modulation of the TCR:CD3 complex. However, little is known about the molecular events that drive this process. The CD3 zeta-chain has been shown to play a unique role in regulating the assembly, transport, and cell surface expression of the TCR:CD3 complex. In this study we have investigated the relationship between CD3zeta and the TCRalphabetaCD3epsilondeltagamma complex after ligation by MHC:peptide complexes. Our results show that there is a significant increase in free surface CD3zeta, which is not associated with the TCR:CD3 complex, after T cell stimulation. This may reflect dissociation of CD3zeta from the TCRalphabetaCD3epsilondeltagamma complex or transport of intracellular CD3zeta directly to the cell surface. We also show that MHC:peptide ligation also results in exposure of the TCR-associated CD3zeta NH2 terminus, which is ordinarily buried in the complex. These observations appears to be dependent on Src family protein tyrosine kinases, which are known to be critical for efficient T cell activation. These data suggest a mechanism by which ligated TCR may be differentiated from unligated TCR and selectively down-modulated.