gebhart/patrepeval huggingface dataset:
Sugar metabolism of hyperthermophiles (1996)

In recent years a number of hyperthermophiles with the ability to utilize sugars as source for carbon and energy have been isolated. Analysis of their central metabolism may reveal adaptations to the extreme environment, or give information about the evolution of the primary pathways involved. The best studied representative is Pyrococcus furiosus, which has become the model organism of the heterotrophic hyperthermophiles. This deeply branched archaeon utilizes a modified Embden-Meyerhof Pathway, which involves a set of unprecedented ADP-dependent kinases, and a unique glyceraldehyde-3-phosphate: ferredoxin oxidoreductase. Moreover, pyruvate is converted via acetyl-CoA to acetate, involving an ADP-forming acetyl-CoA synthetase, which is not encountered in Bacteria. Reductant generated by ferrodoxin-linked enzymes is released either by S0-reduction to H2S, by proton reduction to H2 or by the formation of alanine. Yield studies suggest that in addition to ATP synthesis by substrate level phosphorylation in the ultimate acetate-forming step, there are alternative energy conserving systems. The ADP-dependent Embden-Meyerhof pathway is probably shared by other members of the Thermococcales. In contrast, an ATP-dependent Embden-Meyerhof pathway is operating in the S0-respiring archaeon Thermoproteus tenax, although it involves a PPi-dependent phosphofructokinase. Finally, hyperthermophilic bacteria such as Thermotoga maritima utilize a classical Embden-Meyerhof pathway. Thus, the presence of the different versions of the Embden-Meyerhof pathway in these deeply rooted microbes indicates that the hypothesis that the Entner-Doudoroff pathway is more primitive is not correct.
Abstract 2555: A cell based bioluminescent reporter assay for rapid measuring function of PD-1 or PD-L1 therapeutic antibodies (2014)

Abstract Programmed death-1(PD-1) and its ligand (PD-L1) are important immunotherapy targets for cancer. PD-1 serves as a negative costimulatory receptor on various cell types, including T and B cells as well as myeloid-derived cells. Its ligand PD-L1 (B7-H1) is not expressed by normal epithelial tissues, but it is aberrantly expressed on a wide array of human cancers including melanoma, non-small cell lung carcinoma, breast cancer, pancreatic cancer, etc. Engagement of PD-1 by its ligands PD-L1 expressed on tumor cells associated with poorer prognosis by disabling the host antitumor response. The most recent investigational anti-PD-1 immunotherapy drugs such as nivolumab from BMS and lambrolizumab (MK-3475) from Merck have all demonstrated significant overall survival rate in patients with advanced melanoma. Here we developed a cell based bioluminescent reporter assay that can be used for rapid quantifying function of PD-1 or PD-L1 therapeutic antibodies as measured by activation of NFAT signaling pathway. For this, Jurkat T-cell line stably expressing NFAT-luciferase reporter and human PD-1 was generated. Raji stably expressing human PD-L1 was generated as antigen presenting cells (APC). by co-cultivating the two cell lines in the present of CD3 and IgG, Raji cells fully activate Jurkat NFAT pathway via CD28 binding to CD80 (B7-1) and CD86 (B7-2) endogenously expressed on Raji cells. PD-1 signaling in Jurkat cells following engagement of PD-L1 ectopically expressed on Raji cells inhibits T cell function, and results in NFAT pathway inhibition. Blockade of PD-L1 using anti-PD-L1 mAb reversed NFAT pathway activation. Citation Format: Mei Cong, Natasha Karassina, Jey Cheng, Frank Fan. A cell based bioluminescent reporter assay for rapid measuring function of PD-1 or PD-L1 therapeutic antibodies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2555. doi:10.1158/1538-7445.AM2014-2555
Inhibition of angiogenesis and breast cancer in mice by the microtubule inhibitors 2-methoxyestradiol and taxol. (1997)

2-Methoxyestradiol (2-ME), an endogenous estrogen metabolite which disrupts microtubule function, has been shown to inhibit proliferating cells in vitro and suppress certain murine tumors in vivo. In vitro screening has determined that breast cancer cell lines are most sensitive to inhibition by 2-ME. Additionally, 2-ME has been shown to inhibit angiogenesis in vitro. We tested whether 2-ME suppresses cytokine-induced angiogenesis in vivo and inhibits growth of a human breast carcinoma in severe combined immunodeficient mice. A model of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF)-induced corneal neovascularization in C57BL/6 mice was used to evaluate the antiangiogenic effects of 2-ME and other microtubule inhibitors such as Taxol, vincristine, and colchicine. 2-ME (150 mg/kg p.o., n = 20) inhibited bFGF and VEGF-induced neovascularization by 39% and 54%, respectively. Taxol (6 mg/kg i.p., n = 17) inhibited bFGF and VEGF-induced neovascularization by 45% and 37%, respectively. Vincristine (0.2 mg/kg i.p., n = 8) and colchicine (0.25 mg/kg i.p., n = 8) had no effect. Treatment with 2-ME (75 mg/kg p.o., n = 9) for 1 month suppressed the growth of a human breast carcinoma in mice by 60% without toxicity. Recognition of the antiangiogenic and antitumor properties of 2-ME and Taxol may be crucial in planning clinical applications to angiogenesis-dependent diseases.
Exploring the Substrate Promiscuity of Drug‐Modifying Enzymes for the Chemoenzymatic Generation of N‐Acylated Aminoglycosides (2009)

Aminoglycosides are broad-spectrum antibiotics commonly used for the treatment of serious bacterial infections. Decades of clinical use have led to the widespread emergence of bacterial resistance to this family of drugs limiting their efficacy in the clinic. Here, we report the development of a methodology that utilizes aminoglycoside acetyltransferases (AACs) and unnatural acyl coenzyme A analogues for the chemoenzymatic generation of N-acylated aminoglycoside analogues. Generation of N-acylated aminoglycosides is followed by a simple qualitative test to assess their potency as potential antibacterials. The studied AACs (AAC(6')-APH(2'') and AAC(3)-IV) show diverse substrate promiscuity towards a variety of aminoglycosides as well as acyl coenzyme A derivatives. The enzymes were also used for the sequential generation of homo- and hetero-di-N-acylated aminoglycosides. Following the clinical success of the N-acylated amikacin and arbekacin, our chemoenzymatic approach offers access to regioselectively N-acylated aminoglycosides in quantities that allow testing of the antibacterial potential of the synthetic analogues making it possible to decide which molecules will be worth synthesizing on a larger scale.
Address Resolution for Instant Messaging and Presence (2004)

Presence and instant messaging are defined in RFC 2778. The Common
Profiles for Presence and Instant Messaging define two Universal
Resource Identifier (URI) schemes: 'im' for INSTANT INBOXes and
'pres' for PRESENTITIES. This document provides guidance for
locating the resources associated with URIs that employ these schemes.
[STANDARDS-TRACK]
Optical/digital incoherent image processing for extended depth of field (1987)

For a severely defocused incoherent system, its optical transfer function (OTF) has isolated zeros; therefore, an exact inverse filtering cannot be performed. Isolated zeros in the OTF can be avoided by choosing an annular aperture with a proper radius ratio, as the aperture can extend the depth of focus of the system. However, in the process of increasing the depth of focus of the system, this method results in a loss of image contrast. A simple hybrid optical/digital image processing system in which a TV camera device is coupled with an annular aperture is considered. Annular-pass filtering to compensate for the loss of contrast is performed by a digital computer. Experimental results are presented.
Development of an in Vitro Bioassay System for Human Thrombopoietin by Constructing a Recombinant Murine Cell Line Expressing Human Thrombopoietin Receptor (1997)

We have developed a simple and rapid in vitro bioassay system for human thrombopoietin (hTPO) by constructing a recombinant murine BaF3 cell line expressing the hTPO receptor. The cDNA encoding hTPO receptor (c-Mpl) was cloned from human erythroleukemia (HEL) cells by reverse transcription-polymerase chain reaction (RT-PCR) and linked to the human cytomegalovirus promoter in pcDNA3 to yield expression plasmid phTR. The expression plasmid was stably transfected into BaF3 cells. The resulting transformants were initially selected in RPMI medium containing G418 and murine IL-3 (MuIL-3) and subjected to positive selection in the medium containing hTPO. Finally, cell proliferation of the selected clones in response to hTPO was measured using a colorimetric MTT assay. Most transformants showed a dose-dependent proliferation in response to 0.1 to 100 ng/ml hTPO, among them a cell clone (BaF-mpl), that showed a saturation density of 1.0 x 10(6) cells/ml and a doubling time of 16 h in the log growth phase. This clone was chosen for further characterization of hTPO-dependent proliferation. The BaF-mpl cells showed specificity for TPO, and they died within 24 h in the absence of TPO, which enabled us to complete the assay within 2 days. In addition, optimal MTT assay conditions were established for MTT treatment time and the number of cells to be added in the assay.
Rapid generation of incremental truncation libraries for protein engineering using alpha-phosphothioate nucleotides (2001)

Incremental truncation for the creation of hybrid enzymes (ITCHY) is a novel tool for the generation of combinatorial libraries of hybrid proteins independent of DNA sequence homology. We herein report a fundamentally different methodology for creating incremental truncation libraries using nucleotide triphosphate analogs. Central to the method is the polymerase catalyzed, low frequency, random incorporation of alpha-phosphothioate dNTPs into the region of DNA targeted for truncation. The resulting phosphothioate internucleotide linkages are resistant to 3'-->5' exonuclease hydrolysis, rendering the target DNA resistant to degradation in a subsequent exonuclease III treatment. From an experimental perspective the protocol reported here to create incremental truncation libraries is simpler and less time consuming than previous approaches by combining the two gene fragments in a single vector and eliminating additional purification steps. As proof of principle, an incremental truncation library of fusions between the N-terminal fragment of Escherichia coli glycinamide ribonucleotide formyltransferase (PurN) and the C-terminal fragment of human glycinamide ribonucleotide formyltransferase (hGART) was prepared and successfully tested for functional hybrids in an auxotrophic E.coli host strain. Multiple active hybrid enzymes were identified, including ones fused in regions of low sequence homology.
Phase-change materials for Group-IV electro-optical switching and modulation (2015)

This paper reviews the invention, design and theoretical simulation of 2 x 2 and 1 x 4 optical routing switches. Insertion loss and crosstalk performance in the 1.55 to 3.0 μm wavelength range are predicted. The electrically actuated optical layer is a thin film of Ge <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> Sb <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> Te <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sub> or GeTe or GeSe whose thickness is in the 10 to 100-nm range. This film was embedded at the centerline of an SOI, SON, or GeOI channel waveguide structure for MZI and directional-coupler switching Alternatively, to switch free-space light beams, Ge prisms sandwiching the film were employed. Devices are self-sustaining in each of their two states. Experiments are needed to confirm assumptions made in the theory about voltage requirements, speed, PCM index, and manufacturing techniques.
Atomic interferometry using stimulated Raman transitions (1991)

The mechanical effects of stimulated Raman transitions on atoms have been used to demonstrate a matter-wave interferometer with laser-cooled sodium atoms. Interference has been observed for wave packets that have been separated by as much as 2.4 mm. Using the interferometer as an inertial sensor, the acceleration of a sodium atom due to gravity has been measured with a resolution of 3\ifmmode\times\else\texttimes\fi{}${10}^{\mathrm{\ensuremath{-}}6}$ after 1000 sec of integration time.
The effective synthesis of propylene carbonate catalyzed by silica-supported hexaalkylguanidinium chloride (2005)

We have described that both homogeneous and a silica-supported hexaalkylguanidinium chloride were effective catalysts for CO2 fixation to carbonate without any solvent under mild reaction conditions (4.5 MPa, 120 °C, 4 h), the silica-supported hexaalkylguanidinium chloride showing the great advantage that it could be recycled easily at least 5 further times without any obvious decrease in its catalytic activity, after simple filtration.
Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine (2018)

clinicaltrials.gov Identifier: NCT02629861.
Growth requirements in vitro of oligodendrocyte cell lines and neonatal rat brain oligodendrocytes. (1986)

I have defined the basic requirements for the proliferation of cell lines expressing oligodendrocyte properties and for the survival of galactocerebroside-positive oligodendrocytes derived from neonatal rat brains. Conventional serum-containing medium can be replaced by 01 medium, a chemically defined medium supplemented with insulin, transferrin, sodium selenite, and biotin. Thyroid hormone is not required. When cells are plated directly into O1 medium, the substratum has to be modified by precoating with polylysine and adding fibronectin to the medium prior to the cells. Both cell lines and brain cells can be subcultured numerous times in O1 medium without initial culture in serum-containing medium. Brain cultures can be maintained in O1 medium for several months and contain a significantly higher percentage of mature oligodendrocytes, a lower number of astrocytes, and no fibroblasts as compared to cells maintained in serum-containing medium.
Temporal and spatial profiles of cell loss after spinal cord injury: Reduction by a metalloporphyrin (2007)

This study presents quantitative temporal and spatial profiles of neuronal loss and apoptosis following a contusion spinal cord injury (50 g . cm). The profiles were evaluated by counting the cresol violet-stained surviving cells and the total number of TUNEL-positive cells and of TUNEL-positive neurons in sections 0- 4 mm from the epicenter and 1, 6, 12, 24, 48, and 72 hr and 1 week postinjury. We demonstrated that neurons continue to disappear over 1 week postinjury and that neuronal loss shifts to areas longer distances from the epicenter over time. TUNEL-positive cells in both gray and white matter appeared after 6 hr, gradually increased to a peak level after 48 hr, and declined by 72 hr postinjury. TUNEL-positive neurons peaked earlier and were present for 1 week, although the total number of neurons was reduced significantly by the end of the week. The neuronal loss and apoptosis were partially prevented by a metalloporphyrin [Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP)]. We demonstrated that MnTBAP (10 and 50 mg/kg, given intraperitoneally) significantly reduced neuronal death in the sections 1-2.5 mm rostral and 1 mm caudal from the epicenter compared with that in the vehicle-treated group, suggesting MnTBAP is more effective in the sections rostral than in those caudal to the epicenter. MnTBAP (10 mg/kg) significantly reduced the number of TUNEL-positive neurons in the sections 1 mm caudal from the epicenter. Our profiles provide a database for pharmacological intervention, and our results on MnTBAP treatment support an important role for antioxidant therapy in spinal cord injury.
Beam steering microwave reflector based on electrically tunable impedance surface (2002)

A periodic resonant texture can transform a conductive sheet into a high-impedance surface. By adjusting the resonance frequency using varactor diodes, the surface impedance and the reflection phase are tuned. The reflection phase can be varied across the surface, to create an electronically tunable phase gradient, which can steer a reflected beam in two dimensions.
Retroviral and Transposon-Based Tet-Regulated All-In-One Vectors with Reduced Background Expression and Improved Dynamic Range (2010)

The regulated expression of therapeutic genes may become crucial in gene therapy when their constitutive expression interferes with cell fate in vivo. The efficient regulation of transgene expression requires tightly controlled inducible promoters, as shown for the tetracycline regulatory system (tet-system). However, its application requires the introduction of two components into the target cell genome: the tet-responsive transactivator and the regulated expression cassette. In order to facilitate the usage of the tet-system for approaches in gene therapy, both components have to be transferred by a single vector, thus eliminating the preselection of transactivator positive cells. Published "all-in-one" vectors for regulated transgene expression display a relatively low signal-to-noise ratio, resulting in regulatory windows of around 500-fold even in selected clones. In this study, we show that a modified vector architecture combined with the introduction of new tet-responsive promoters, Ptet, improved the dynamic range of such all-in-one vectors to levels up to 14,000-fold for viral and 25,000-fold for nonviral transfer vectors in nonclonal human cell lines, and up to 2,800-fold in murine hematopoietic cell lines. This improved regulation was the result of a strong reduction of background expression in the off-state, even if cells were transduced at high multiplicity of infection, while induction remained at high levels. In addition, the results indicated that successful regulation of gene expression in different target cells depended on vector architecture as well as the choice of the Ptet-promoter.
Development cell by cell (2018)

With a trio of techniques, scientists are tracking embryo development in stunning detail.
Plenary lecture 2 (2009)

The problem of filtering unobservable or latent variables from noisy data arises naturally in many financial applications. This talk will provide a broad overview of time series filtering, with an emphasis on the theory of affine Gaussian filtering (or Kalman filtering) of discrete time series data. Empirical work is presented on two specific filtering applications in finance: modelling the short rate using observed bond yields and modelling the daily volatility of stock price based on the observed intra-day data. The talk concludes with an outline of recently proposed approximate filtering methods for nonlinear time. series.
RenderGAN: Generating Realistic Labeled Data (2018)

Deep Convolutional Neuronal Networks (DCNNs) are showing remarkable performance on many computer vision tasks. Due to their large parameter space, they require many labeled samples when trained in a supervised setting. The costs of annotating data manually can render the use of DCNNs infeasible. We present a novel framework called RenderGAN that can generate large amounts of realistic, labeled images by combining a 3D model and the Generative Adversarial Network framework. In our approach, image augmentations (e.g., lighting, background, and detail) are learned from unlabeled data such that the generated images are strikingly realistic while preserving the labels known from the 3D model. We apply the RenderGAN framework to generate images of barcode-like markers that are attached to honeybees. Training a DCNN on data generated by the RenderGAN yields considerably better performance than training it on various baselines.
A simple crab‐like cyclization procedure to prepare polyaza‐crowns and cyclams with one or two unsubstituted macroring nitrogen atoms or with a hydroxy group (1989)

Abstract A simple and convenient method to prepare polyaza‐crowns and cyclams containing one or two unsubstituted macroring nitrogen atoms or a hydroxy group is described. The process involves the reaction of a bis‐ chloroamide with a bis ‐secondary amine followed by reduction of the cyclic diamide. The bis ‐chloroamide resembles a crab with two reactive organochloride groups poised and ready to react, hence the term “crab‐like” cyclization. Nine new polyaza‐crowns and cyclams were prepared.
Mucosal immune responses associated with polynucleotide vaccination. (1997)

A variety of gene delivery technologies can be used to express antigens within somatic tissues, resulting in systemic humoral and cellular immune responses. This observation has led to the development of polynucleotide vaccine preparations for stimulation of systemic immunity. Mucosal immune responses are functionally distinct from systemic immune responses, and are stimulated by antigen presentation within specialised mucosal-associated inductor tissues. We hypothesize that mucosal genetic vaccine will require gene transfer methods which target mucosal-associated inductor tissues such as the oropharyngeal Waldeyer's ring or intestinal Peyer's patches. We have tested this hypothesis by expressing a test antigen using a replication-defective recombinant Semliki Forest Virus (SFV) preparation. Mice treated with recombinant SFV via an intravascular or intratracheal route generated systemic immune responses against the test antigen. In contrast, intranasal inoculation resulted in the production of IgA within pulmonary fluids, one hallmark of a mucosal immune response. These results indicate that transfection of mucosal effector tissues may not be sufficient for the generation of a universal mucosal immune response. Furthermore, the results predict that techniques which target transfection or transduction to mucosal inductor tissues will enable the development of a new class of polynucleotide vaccines which exploit current concepts in mucosal immunology.
Comparison of a layered slab and an atlas head model for Monte Carlo fitting of time-domain near-infrared spectroscopy data of the adult head (2014)

Near-infrared spectroscopy (NIRS) estimations of the adult brain baseline optical properties based on a homogeneous model of the head are known to introduce significant contamination from extracerebral layers. More complex models have been proposed and occasionally applied to in vivo data, but their performances have never been characterized on realistic head structures. Here we implement a flexible fitting routine of time-domain NIRS data using graphics processing unit based Monte Carlo simulations. We compare the results for two different geometries: a two-layer slab with variable thickness of the first layer and a template atlas head registered to the subject's head surface. We characterize the performance of the Monte Carlo approaches for fitting the optical properties from simulated time-resolved data of the adult head. We show that both geometries provide better results than the commonly used homogeneous model, and we quantify the improvement in terms of accuracy, linearity, and cross-talk from extracerebral layers.