gebhart/patrepeval huggingface dataset:
The Future of Targeted Therapy: Combining Novel Agents (2002)

The anti-HER2 monoclonal antibody Herceptin demonstrates significant clinical benefits in patients with HER2-positive metastatic breast cancer (MBC). However, the combination of Herceptin plus anthracyclines, although efficacious, demonstrated a higher than expected incidence of cardiotoxicity. Therefore, studies are currently investigating Herceptin in combination with alternative anthracyclines, such as epirubicin and liposomal doxorubicin. Investigators are also beginning to examine the potential of Herceptin plus hormonal therapy, a combination that will delay the need to use cytotoxic chemotherapy. Furthermore, a plethora of novel agents have been developed that target the processes of tumorigenesis, including HER1 tyrosine-kinase inhibitors, farnesyl-transferase inhibitors, and cyclooxygenase 2 (COX2) inhibitors. Preclinical data demonstrate that the combination of Herceptin with these agents can produce at least additive effects and therefore a rationale exists to investigate these regimens in the clinical setting. As a result of the targeted nature of these agents, it is anticipated that such strategies will have favorable safety profiles. It is possible that through the development and use of biological anticancer agents, such as Herceptin, future anticancer regimens may be specifically tailored to each patient based on their molecular characteristics.
The selective addition of water to CC bonds; enzymes are the best chemists (2011)

Water is the liquid of life. Nature has therefore evolved countless enzymes that catalyse the addition of water to C=C bonds, isolated or conjugated. These reactions are regio- and enantioselective, they are part of primary metabolism as well as the secondary metabolism. The enzymes that catalyse these reactions (hydratases or hydro-lyases) are applied industrially in selected cases. However, they are not generally used in the laboratory although they outperform all currently available catalytic chemical methodologies. This feature article highlights the potential that hydratases have for chemistry compared to the acid catalysed addition of water.
Syndecan-4 signals cooperatively with integrins in a Rhodependent manner in the assembly of focal adhesions and actin stress fibers (1999)

The assembly of focal adhesions and actin stress fibers by cells plated on fibronectin depends on adhesion-mediated signals involving both integrins and cell-surface heparan sulfate proteoglycans. These two cell-surface receptors interact with different domains of fibronectin. To attempt to identify the heparan sulfate proteoglycans involved, we used fibronectin-null (FN-/-) mouse fibroblasts to eliminate the contribution of endogenous fibronectin during the analysis. FN-/- fibroblasts plated on the cell-binding domain of fibronectin or on antibodies directed against mouse beta1 integrin chains attach but fail to spread and do not form focal adhesions or actin stress fibers. When such cells are treated with antibodies directed against the ectodomain of mouse syndecan-4, they spread fully and assemble focal adhesions and actin stress fibers indistinguishable from those seen in cells plated on intact fibronectin. These results identify syndecan-4 as a heparan sulfate proteoglycan involved in the assembly process. The antibody-stimulated assembly of focal adhesions and actin stress fibers in cells plated on the cell-binding domain of fibronectin can be blocked with C3 exotransferase, an inhibitor of the small GTP-binding protein Rho. Treatment of cells with lysophosphatidic acid, which activates Rho, results in full spreading and assembly of focal adhesions and actin stress fibers in fibroblasts plated on the cell-binding domain of fibronectin. We conclude that syndecan-4 and integrins can act cooperatively in generating signals for cell spreading and for the assembly of focal adhesions and actin stress fibers. We conclude further that these joint signals are regulated in a Rho-dependent manner.
Combined Cyclodialysis and Cataract Surgery (1998)

Combining cyclodialysis with small incision cataract surgery has been successful in a high percentage of cases in the author's experience. It has become the procedure of first choice for patients with cataracts and glaucoma.
Enhancement of oxygen and methane solubility in 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide using carbon dioxide (2005)

The presence of CO(2) increases the solubility of O(2) and CH(4) in 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide at 25 degrees C and pressures to 13 bar.
Propagation of fetal human RPE cells: Preservation of original culture morphology after serial passage (1990)

The permissive effects of extracellular matrix (ECM) on in vitro growth and differentiation of fetal human retinal pigment epithelial (RPE) cells have been studied. Factors which enhanced the effect of ECM to support cell division were also examined, including growth factors, culture media, and serum requirement. Under the specific culture conditions we have defined, it is possible to propagate these RPE cells at low density (less than 20 cells/mm2) with excellent growth properties for greater than 72 doublings (fourteen passages) in serial culture. Later-passaged cells maintained the morphological appearance of early-passaged cultures. ECM produced by bovine corneal endothelial cells was by far the most predominant factor in promoting rapid cell proliferation and viability over repeated passaging. Basic fibroblast growth factor (bFGF) exerted a substantial effect on the rate of cell division at different serum concentrations on plastic dishes. In addition, this factor showed profound synergistic effect when RPE cells were maintained on ECM, both in the preservation of cell morphology and also in long term viability. Other growth factors, such as epidermal growth factor (EGF) and transforming growth factor-beta (TGF-B), were also tested, but EGF effects were less prominent than those observed with bFGF, and TGF-B had an inhibitory effect at high concentrations. The ability to obtain a relatively large number of human RPE cells in vitro which preserve the appearance of early passage cells may provide useful opportunities to study the physiological properties and pathological alterations involving this important cell type.
Overlapping Expression and Redundant Activation of Mesenchymal Fibroblast Growth Factor (FGF) Receptors by Alternatively Spliced FGF-8 Ligands (1997)

FGF-8 is a member of the family of fibroblast growth factors and is expressed during vertebrate embryo development. Eight potential FGF-8 isoforms are generated by alternative splicing in mice, several of which are expressed during embryogenesis in epithelial locations. The significance of the multiple isoforms is currently unknown. In this report, we investigate the expression patterns and the specificity of the FGF-8 isoforms for known fibroblast growth factor (FGF) receptors. RNAs for seven of the eight potential isoforms are present at multiple sites of embryonic Fgf8 expression. None of the FGF-8 isoforms exhibited activity when assayed with BaF3 cells expressing the "b" splice forms of FGF receptors 1-3, which are mostly expressed in epithelial tissues. Mesenchymally expressed "c" splice forms of FGF receptors 2 and 3 and FGF receptor 4 were activated by several FGF-8 isoforms. These findings are consistent with the hypothesis that the multiple FGF-8 isoforms are functionally redundant and function to signal in paracrine (epithelial to mesenchymal) contexts.
Cyclophosphamide Allows for In vivo Dose Reduction of a Potent Oncolytic Virus (2005)

The success of cancer virotherapy depends on its efficacy versus toxicity profile in human clinical trials. Progress towards clinical trials can be hampered by the relatively elevated doses of oncolytic viruses administered in animal models to achieve an anticancer effect and by the even higher doses required in humans to approximate an animal bioequivalent dose. Such elevated doses of injected viral proteins may also lead to undesirable toxicities and are also very difficult to produce in a biotechnological setting. We report that a relatively potent herpes simplex virus type 1 oncolytic virus (rQNestin34.5) produces 45% survivors at a dose of 3 x 10(4) plaque-forming units (pfu) in a 9-day-old mouse model of human glioma. Unlike our previous findings with less potent oncolytic viruses, though, the preadministration of cyclophosphamide did not enhance this survival or affect oncolytic virus tumor distribution and tumor volume. However, when oncolytic virus doses were reduced (3 x 10(3) and 3 x 10(2) pfu), cyclophosphamide significantly enhanced both animal survival and oncolytic virus tumor distribution and also reduced tumor volumes. These findings thus show that cyclophosphamide allows for dose reduction of doses of a relatively potent oncolytic virus, a finding with implications for the development of clinical trials.
Development of an Electro-Optic Scanner for Potential Endoscope Application (2009)

Technological advancements in endoscopy design are in current development due to the increased demand for minimally invasive medical procedures. One such advancement is reducing the overall size of the endoscope system while maintaining the resolution and field-of-view (FOV). Reduction of size results in less tissue damage and trauma during operation as well as faster recovery times for patients. Additionally, areas that are inaccessible by today's endoscope designs will be possible to examine. Current endoscopes use either a bundle of optical fibers (optical waveguides) and/or one or more cameras having an array of detectors to capture an image. Thus, the diameter of these devices employed for remote imaging cannot be reduced to smaller than the image size. Even if one ignores additional optical fibers used for illumination of a region of interest, the scope diameter is therefore limited by the individual pixel size of a camera or by the diameter of optical fibers used to acquire the image. Therefore, it is apparent to achieve scopes with less than 3 mm overall diameter using current technologies, resolution and/or FOV must be sacrificed by having fewer pixel elements. All commercially available scopes suffer from this fundamental tradeoff between high image quality and small size. More recently, our research has been working on developing a 2-D electro-optic scanner potentially be implemented for clinical endoscopic imaging application. The proposed optical device has several unique advantages. Electro-optical scanning offers a sensitive, facile, accurate, and superb quality method to capture images of physical and biological tissues. In addition, the minute physical size of the imaging system has a much needed advantage over conventional imaging systems. The proposed design is based on the fact that the propagation direction of a light beam can be changed when the index of refraction of an electro-optic medium is altered by the application of an external electric field. The basic design of the system consists of a thin film electro-optic polymer waveguide with built-in cascaded prisms structure for horizontal beam deflection and an electro-optic grating structure for vertical beam deflection. The cascaded prisms are combined with the electro-optic polymer to create a voltage-controlled horizontal beam deflection. A grating coupler, a structure that is commonly used as light coupling device for dielectric waveguide, is combined with the EO polymer to create the vertical controlled beam deflection. A collimated light beam coupled into the waveguide by a mechanical coupler via an optical fiber cascaded down these two deflection stages. When the beam exits, the emitted light beam is displaced along two orthogonal directions in a raster pattern. A photodetector array integrated in the same substrate captured the reflected intensity. The scanned imaged is then analyzed and reconstruct based on the received signal.
Conversation as Action Under Uncertainty (2013)

Conversations abound with uncetainties of various kinds. Treating conversation as inference and decision making under uncertainty, we propose a task independent, multimodal architecture for supporting robust continuous spoken dialog called Quartet. We introduce four interdependent levels of analysis, and describe representations, inference procedures, and decision strategies for managing uncertainties within and between the levels. We highlight the approach by reviewing interactions between a user and two spoken dialog systems developed using the Quartet architecture: Prsenter, a prototype system for navigating Microsoft PowerPoint presentations, and the Bayesian Receptionist, a prototype system for dealing with tasks typically handled by front desk receptionists at the Microsoft corporate campus.
Fecal Microbiota Transplant for Relapsing Clostridium difficile Infection Using a Frozen Inoculum From Unrelated Donors: A Randomized, Open-Label, Controlled Pilot Study (2014)

NCT01704937.
Prototype filter design for filter bank based multicarrier transmission (2009)

This paper concentrates on an efficient prototype filter design in the context of filter bank based multicarrier (FBMC) transmission. An advantage of the chosen method, frequency sampling technique, is that near perfect reconstruction prototype filters can be expressed using a closed-form representation with only a few adjustable parameters. The performance of various designs are analyzed using the offset-QAM based FBMC system. Numerical results are provided to characterize different optimization criteria in terms of frequency selectivity of resulting prototype filters and total interference level of the filter bank structure. Furthermore, it is shown what kind of performance trade-offs can be obtained by adjusting those free parameters. In this sense, the presented results offer useful information to a system designer. 1.
Targeting KRAS-Mutant Non–Small Cell Lung Cancer with the Hsp90 Inhibitor Ganetespib (2012)

Mutant KRAS is a feature of more than 25% of non-small cell lung cancers (NSCLC) and represents one of the most prevalent oncogenic drivers in this disease. NSCLC tumors with oncogenic KRAS respond poorly to current therapies, necessitating the pursuit of new treatment strategies. Targeted inhibition of the molecular chaperone Hsp90 results in the coordinated blockade of multiple oncogenic signaling pathways in tumor cells and has thus emerged as an attractive avenue for therapeutic intervention in human malignancies. Here, we examined the activity of ganetespib, a small-molecule inhibitor of Hsp90 currently in clinical trials for NSCLCs in a panel of lung cancer cell lines harboring a diverse spectrum of KRAS mutations. In vitro, ganetespib was potently cytotoxic in all lines, with concomitant destabilization of KRAS signaling effectors. Combinations of low-dose ganetespib with MEK or PI3K/mTOR inhibitors resulted in superior cytotoxic activity than single agents alone in a subset of mutant KRAS cells, and the antitumor efficacy of ganetespib was potentiated by cotreatment with the PI3K/mTOR inhibitor BEZ235 in A549 xenografts in vivo. At the molecular level, ganetespib suppressed activating feedback signaling loops that occurred in response to MEK and PI3K/mTOR inhibition, although this activity was not the sole determinant of combinatorial benefit. In addition, ganetespib sensitized mutant KRAS NSCLC cells to standard-of-care chemotherapeutics of the antimitotic, topoisomerase inhibitor, and alkylating agent classes. Taken together, these data underscore the promise of ganetespib as a single-agent or combination treatment in KRAS-driven lung tumors.
Activation of hypoxia-inducible factor 1 in human T-cell leukaemia virus type 1-infected cell lines and primary adult T-cell leukaemia cells (2007)

HTLV-1 (human T-cell leukaemia virus type 1) is the causative agent for ATL (adult T-cell leukaemia). HTLV-1 Tax can activate the PI3K (phosphoinositide 3-kinase)/Akt signalling pathway, which is responsible for survival of HTLV-1-infected T-cells. HIFs (hypoxia-inducible factors) are transcriptional regulators that play a central role in the response to hypoxia. Overexpression of HIF-1alpha in many cancers is associated with a poor response to treatment and increased patient mortality. Our objectives in the present study were to investigate whether HIF-1 was activated in HTLV-1-infected T-cells and to elucidate the molecular mechanisms of HIF-1 activation by focusing on the PI3K/Akt signalling pathway. We detected a potent pathway that activated HIF-1 in the HTLV-1-infected T-cells under a normal oxygen concentration. Enhanced HIF-1alpha protein expression and HIF-1 DNA-binding activity were exhibited in HTLV-1-infected T-cell lines. Knockdown of HIF-1alpha by siRNA (small interfering RNA) suppressed the growth and VEGF (vascular endothelial growth factor) expression of the HTLV-1-infected T-cell line. HIF-1 protein accumulation and transcriptional activity were enhanced by Tax, which was inhibited by dominant-negative Akt. Importantly, mutant forms of Tax that are defective in activation of the PI3K/Akt pathway failed to induce HIF-1 transcriptional activity. The PI3K inhibitor LY294002 suppressed HIF-1alpha protein expression, HIF-1 DNA-binding and HIF-1 transcriptional activity in HTLV-1-infected T-cell lines. In primary ATL cells, HIF-1alpha protein levels were strongly correlated with levels of phosphorylated Akt. The results of the present study suggest that PI3K/Akt activation induced by Tax leads to activation of HIF-1. As HIF-1 plays a major role in tumour progression, it may represent a molecular target for the development of novel ATL therapeutics.
Improved ecdysone receptor‐based inducible gene regulation system (2003)

To develop an ecdysone receptor (EcR)-based inducible gene regulation system, several constructs were prepared by fusing DEF domains of Choristoneura fumiferana EcR (CfEcR), C. fumiferana ultraspiracle (CfUSP), Mus musculus retinoid X receptor (MmRXR) to either GAL4 DNA binding domain (DBD) or VP16 activation domain. These constructs were tested in mammalian cells to evaluate their ability to transactivate luciferase gene placed under the control of GAL4 response elements and synthetic TATAA promoter. A two-hybrid format switch, where GAL4 DBD was fused to CfEcR (DEF) and VP16 AD was fused to MmRXR (EF) was found to be the best combination. It had the lowest background levels of reporter gene activity in the absence of a ligand and the highest level of reporter gene activity in the presence of a ligand. Both induction and turn-off responses were fast. A 16-fold induction was observed within 3 h of ligand addition and increased to 8942-fold by 48 h after the addition of ligand. Withdrawal of the ligand resulted in 50% and 80% reduction in reporter gene activity by 12 h and 24 h, respectively.
Purification of human erythropoietin. (1977)

Human erythropoietin, derived from urine of patients with aplastic anemia, has been purified to apparent homogeneity. The seven-step procedure, which included ion exchange chromatography, ethanol precipitation, gel filtration, and adsorption chromatography, yielded a preparation with a potency of 70,400 units/mg of protein in 21% yield. This represents a purification factor of 930. The purified hormone has a single electrophoretic component in polyacrylamide gels at pH 9, in the presence of sodium dodecylsulfate at pH 7, and in the presence of Triton X-100 at pH 6. Two fractions of the same potency and molecular size, by sodium dodecyl sulfate gel electrophoresis, but differing slightly in mobility at pH 9, were obtained at the last step of fractionation. The nature of the difference between these two components is not yet understood.
Natal teeth and steatocystoma multiplex: a newly recognized syndrome. (1987)

A Chinese family is reported in which five generations have exhibited natal teeth and generalized multiple steatocystomas. This autosomal dominant condition is not similar to the two reported types of pachyonychia congenita, because nail lesions, palmoplantar keratosis and hyperhidrosis, follicular keratosis, and oral leukokeratosis were not observed. Therefore, it is suggested that this family exhibits a newly recognized syndrome.
A new digital processor for phased-array ultrasound system (1988)

A microprocessor-based digital scan conversion and signal processing system has been developed. This system performs coordinate conversion and processes simultaneously multiple physiological signals and heart function calculation as well as many pre- and postprocessing functions such as image sampling, vector smoothing, frame correlation, linear interpolation, bright window, and smoothing processing along horizontal lines.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
High resolution proteome analysis of cryoglobulins using Fourier transform‐ion cyclotron resonance mass spectrometry (2003)

Cryoglobulins are cold-precipitable serum immunoglobulins associated with a number of infectious, autoimmune and neoplastic disorders such as hepatitis C, Waldenström's macroglobulinemia, multiple myeloma, chronic lymphocytic leukemia, and rheumatoid arthritis. The mechanism(s) of cryoprecipitation has remained obscure hitherto, which has prompted recent intensive efforts on the identification of cryoglobulin components. In the present study, two-dimensional gel electrophoresis (2-DE) combined with high resolution Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometry has been applied as a powerful approach for the analysis of cryoglobulins. While FT-ICR mass spectrometry has been shown to enable the high resolution identification and structure analysis of biopolymers using both electrospray (ESI) and matrix-assisted laser desorption ionization (MALDI), the recently developed MALDI-FT-ICR source is shown here to provide high (sub-ppm) mass determination accuracy and isotopic fine structure as particular advantages in the identification of proteins. The main protein components in a serum cryoprecipitate from a patient with hepatitis C virus (HCV) infection and presenting type II cryogobulinemia are immunoglobulin (Ig)M and IgG which were identified by MALDI-FT-ICR MS analysis after separation by 2-DE as mu- and gamma-heavy chains, kappa- and lambda-light chains, and J-chains. Furthermore, complementarity determining regions CDR1 and CDR2 from monoclonal IgM-RF variable region (V)L were directly identified using accurate mass determinations by FT-ICR-MS. The presence of Spalpha was ascertained as an IgM-associated protein in the serum cryoprecipitate from a patient with HCV infection.