gebhart/patrepeval huggingface dataset:
Abstract 2645: BAY 1436032: A highly selective, potent and orally available inhibitor of mutant forms of IDH1 (2016)

Abstract Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme that is frequently mutated in certain cancers, with incidence rates ranging from 7-90% for glioma, chondrosarcoma, intrahepatic cholangiocarcinoma and AML. Wildtype IDH1 (wtIDH1) catalyzes the conversion of isocitrate to α-ketoglutarate (αKG), while tumor-associated mutant IDH1 (mIDH1) catalyzes a rogue reaction: the production of 2-hydroxyglutarate (2-HG) from αKG. 2-HG therefore represents an “oncometabolite” that is believed to play a role in cancer by interfering with αKG-dependent enzymes, which in turn causes hypermethylation of histones/DNA and a block of normal cellular differentiation. Mutant IDH1 is a “driver” oncogene and the inhibition of this altered enzyme will decrease the growth of mIDH1 dependent tumors. We report for the first time the preclinical profile and structure of BAY 1436032, a novel selective mIDH1 inhibitor. An optimization program based on a high throughput screening resulted in the identification of the clinical candidate BAY 1436032 for the treatment of mIDH1 dependent cancer. BAY 1436032 is a double-digit nanomolar and selective pan-inhibitor of the enzymatic activity of various IDH1-R132X mutants in vitro and displayed potent inhibition of 2-HG release (nanomolar range) in patient derived and engineered cell lines expressing different IDH1 mutants. In line with the proposed mode of action, a concentration-dependent lowering of 2-HG was observed in vitro accompanied by differentiation and maturation of mIDH1 tumor cells. Furthermore, BAY 1436032 showed a favourable selectivity profile against wtIDH1/2 and a large panel of off-targets in vitro. To the best of our knowledge we were able to show for the first time single agent in vivo efficacy in mIDH1 patient derived glioma and intrahepatic cholangiocarcinoma solid tumor models with this clinical candidate along with monitoring of intratumoral 2-HG levels as a predictive biomarker. The BBB penetration profile of BAY 1436032 is further supported by preclinical data on in vivo brain-plasma ratios. In conclusion, our data provide in vitro and in vivo proof of concept for BAY 1436032 as a potent and highly selective inhibitor of mutant forms of IDH1. The start of a Phase I study with BAY 1436032 is currently in preparation to determine the safety, tolerability, pharmacokinetics and preliminary anti-tumor and pharmacodynamic biomarker responses in patients with solid tumors. Citation Format: Olaf Panknin, Stefan Pusch, Lena Herbst, Stefan Kaulfuss, Katja Zimmermann, Hartmut Rehwinkel, Roland Neuhaus, Sven Ring, Michael Brüning, Claudia Stark, Katja Prelle, Martin Michels, Michael Jeffers, Holger Hess-Stumpp, Karl Ziegelbauer, Michael Brands, Alwin Krämer, Andreas von Deimling. BAY 1436032: A highly selective, potent and orally available inhibitor of mutant forms of IDH1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2645.
Estimating primaries by sparse inversion and application to near-offset data reconstruction (2009)

Abstract Accurate removal of surface-related multiples remains a challenge in many cases. To overcome typical inaccuracies in current multiple-removal techniques, we have developed a new primary-estimation method: estimation of primaries by sparse inversion (EPSI). EPSI is based on the same primary-multiple model as surface-related multiple elimination (SRME) and also requires no subsurface model. Unlike SRME, EPSI estimates the primaries as unknowns in a multidimensional inversion process rather than in a subtraction process. Furthermore, it does not depend on interpolated missing near-offset data because it can reconstruct missing data simultaneously. Sparseness plays a key role in the new primary-estimation procedure. The method was tested on 2D synthetic data.
Chemokines, Chemokine Receptors, and Renal Disease (2000)

Leukocyte trafficking from peripheral blood into affected tissues is an essential component of the inflammatory reaction to virtually all forms of injury and is an important factor in the development of many kidney diseases. Advances in the past few years have highlighted the central role of a family of chemotactic cytokines called chemokines in this process. Chemokines help to control the selective migration and activation of inflammatory cells into injured renal tissue. Chemokines and their receptors are expressed by intrinsic renal cells as well as by infiltrating cells during renal inflammation. This study summarizes the in vitro and in vivo data on chemokines and chemokine receptors in renal diseases with a special focus on potential therapeutic effects on inflammatory processes.
Absolut “copper catalyzation perfected”; robust living polymerization of NIPAM: Guinness is good for SET-LRP (2013)

The controlled polymerization of <italic>N</italic>-isopropyl acrylamide (NIPAM) is reported in a range of international beers, wine, ciders and spirits utilizing Cu(0)-mediated living radical polymerization (SET-LRP).
Oxidation of Steroids. III. Selective Oxidations and Acylations in the Bile Acid Series1 (1950)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxidation of Steroids. III. Selective Oxidations and Acylations in the Bile Acid Series1Louis F. Fieser and Srinivasa RajagopalanCite this: J. Am. Chem. Soc. 1950, 72, 12, 5530–5536Publication Date (Print):December 1, 1950Publication History Published online1 May 2002Published inissue 1 December 1950https://pubs.acs.org/doi/10.1021/ja01168a046https://doi.org/10.1021/ja01168a046research-articleACS PublicationsRequest reuse permissionsArticle Views1261Altmetric-Citations184LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
DianNao (2014)

Machine-Learning tasks are becoming pervasive in a broad range of domains, and in a broad range of systems (from embedded systems to data centers). At the same time, a small set of machine-learning algorithms (especially Convolutional and Deep Neural Networks, i.e., CNNs and DNNs) are proving to be state-of-the-art across many applications. As architectures evolve towards heterogeneous multi-cores composed of a mix of cores and accelerators, a machine-learning accelerator can achieve the rare combination of efficiency (due to the small number of target algorithms) and broad application scope. Until now, most machine-learning accelerator designs have focused on efficiently implementing the computational part of the algorithms. However, recent state-of-the-art CNNs and DNNs are characterized by their large size. In this study, we design an accelerator for large-scale CNNs and DNNs, with a special emphasis on the impact of memory on accelerator design, performance and energy. We show that it is possible to design an accelerator with a high throughput, capable of performing 452 GOP/s (key NN operations such as synaptic weight multiplications and neurons outputs additions) in a small footprint of 3.02 mm2 and 485 mW; compared to a 128-bit 2GHz SIMD processor, the accelerator is 117.87x faster, and it can reduce the total energy by 21.08x. The accelerator characteristics are obtained after layout at 65 nm. Such a high throughput in a small footprint can open up the usage of state-of-the-art machine-learning algorithms in a broad set of systems and for a broad set of applications.
Real-time vehicle location with desired accuracy (2002)

Magnetic markers are provided on automated highway system for lateral control of vehicles within a lane. We propose a pseudo-noise (PN) code to be carried by the magnetic markers. The PN code will be used by vehicles for range measurement. Every vehicle is provided with the code layout on the road with respect to the physical location of every binary magnetic signal. A vehicle has a replica of the signal and measures the phase of the received signal with respect to the replica and infers its position on the road. The positioning accuracy is subject to design and depends on the magnetic markers layout on the road. The probability of error with short range magnetic signals is negligible compared with radio navigation systems. Unlike radio signals, magnetic codes do not interfere, and multipath is not an issue. However, errors do exist and an attractive feature of the method is its error detection capability. Errors can be detected and corrected shortly after they occur and the error detection and correction delays are subject to design. Error bounds can also be specified with respect to the signal code design.
Sustained release of antibiotics from injectable and thermally responsive polypeptide depots (2008)

Biodegradable polymeric scaffolds are of interest for delivering antibiotics to local sites of infection in orthopaedic applications, such as bone and diarthrodial joints. The objective of this study was to develop a biodegradable scaffold with ease of drug loading in aqueous solution, while providing for drug depot delivery via syringe injection. Elastin-like polypeptides (ELPs) were used for this application, biopolymers of repeating pentapeptide sequences that were thermally triggered to undergo in situ depot formation at body temperature. ELPs were modified to enable loading with the antibiotics, cefazolin, and vancomycin, followed by induction of the phase transition in vitro. Cefazolin and vancomycin concentrations were monitored, as well as bioactivity of the released antibiotics, to test an ability of the ELP depot to provide for prolonged release of bioactive drugs. Further tests of formulation viscosity were conducted to test suitability as an injectable drug carrier. Results demonstrate sustained release of therapeutic concentrations of bioactive antibiotics by the ELP, with first-order time constants for drug release of approximately 25 h for cefazolin and approximately 500 h for vancomycin. These findings illustrate that an injectable, in situ forming ELP depot can provide for sustained release of antibiotics with an effect that varies across antibiotic formulation. ELPs have important advantages for drug delivery, as they are known to be biocompatible, biodegradable, and elicit no known immune response. These benefits suggest distinct advantages over currently used carriers for antibiotic drug delivery in orthopedic applications.
The Continuing Failure of Bexarotene in Alzheimer’s Disease Mice (2015)

Alzheimer's disease (AD) is the most common form of dementia characterized by synaptic dysfunction, memory loss, neuroinflammation, and neuronal cell death. Amyloid-β (Aβ), recognized as the main culprit of AD, aggregates and accumulates in the extracellular compartment as neuritic plaques, after deregulation of its production or clearance. Apolipoprotein E (ApoE) plays a major role in Aβ clearance and its expression is transcriptionally regulated by the liver X receptor and retinoid X receptors (RXRs) system. Bexarotene (BEXA), an RXR agonist that increases ApoE expression and microglia phagocytosis has been proposed as a promising therapy for AD, resolving both the amyloid pathology and memory loss. Despite the first compelling report, however, multiple failures have been documented, raising concern about whether BEXA could in fact become a novel disease-modifying strategy for AD. To help clarify this, we investigated the effect of BEXA in vivo at multiple levels in TASTPM transgenic mice. Seven-day oral administration of BEXA to these mice did not achieve any significant memory improvement, plaque reduction, or enhancement of microglial cell activation. No differences were found when specifically investigating the microglial phagocytic state in vivo. In addition, a brain structural analysis with magnetic resonance did not detect any BEXA-mediated change in the volume reduction of the main affected brain areas in our mice. These results suggest that BEXA has no beneficial effects on the multi-factorial pathologic phenotype of AD mice.
Autologous serum eye drops for ocular surface disorders (2004)

Tears have antimicrobial, nourishing, mechanical, and optical properties. They contain components such as growth factors, fibronectin, and vitamins to support proliferation, migration, and differentiation of the corneal and conjunctival epithelium. A lack of these epitheliotrophic factors--for example, in dry eye, can result in severe ocular surface disorders such as persistent epithelial defects. Recently, the use of autologous serum in the form of eye drops has been reported as a new treatment for severe ocular surface disorders. Serum eye drops may be produced as an unpreserved blood preparation. They are by nature non-allergenic and their biomechanical and biochemical properties are similar to normal tears. In vitro cell culture experiments showed that corneal epithelial cell morphology and function are better maintained by serum than by pharmaceutical tear substitutes. Clinical cohort studies have reported its successful use for severe dry eyes and persistent epithelial defects. However, the protocols to prepare and use autologous serum eye drops varied considerably between the studies. As this can result in different biochemical properties protocol variations may also influence the epitheliotrophic effect of the product. Before the definitive role of serum eye drops in the management of severe ocular surface disease can be established in a large randomised controlled trial this has to be evaluated in more detail. In view of legislative restrictions and based upon the literature reviewed here a preliminary standard operating procedure for the manufacture of serum eye drops is proposed.
14-Hydroxycodeinone. Improved synthesis (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT14-Hydroxycodeinone. Improved synthesisFrank M. Hauser, Tek-Kuei Chen, and Frank I. CarrollCite this: J. Med. Chem. 1974, 17, 10, 1117Publication Date (Print):October 1, 1974Publication History Published online1 May 2002Published inissue 1 October 1974https://pubs.acs.org/doi/10.1021/jm00256a019https://doi.org/10.1021/jm00256a019research-articleACS PublicationsRequest reuse permissionsArticle Views372Altmetric-Citations23LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Gas–liquid transfer of aroma compounds during winemaking fermentations (2012)

We precisely monitored the production kinetics of 16 volatile carbon compounds corresponding to the predominant higher alcohols and esters produced during the alcoholic fermentation of wine using an on-line GC system. We studied the gas–liquid partitioning of isobutanol, isoamyl acetate and ethyl hexanoate and showed that CO2 stripping had no impact on the partition coefficient (ki). We formulated a predictive model for ki changes during the fermentation and calculated the gas–liquid balances of these volatile compounds throughout the entire fermentation process. Losses in the off-gas were highly compound-dependent. They were negligible for higher alcohols but very high for esters, with losses of up to 70% for ethyl hexanoate at 30 °C. The rates of volatile compound production, accumulation and loss could also be calculated with high precision. Loss rates were maximal at the end of fermentation, indicating that high final temperatures, although helpful in avoiding sluggish fermentations, can be very detrimental to aroma losses.
High-Level Production of Amorpha-4,11-Diene, a Precursor of the Antimalarial Agent Artemisinin, in Escherichia coli (2009)

Production of >25 g/L amorpha-4,11-diene by fermentation followed by chemical conversion to artemisinin may allow for development of a process to provide an alternative source of artemisinin to be incorporated into ACTs.
Structure of rat skin collagen α1-CB8. Amino acid sequence of the hydroxylamine-produced fragment HA1 (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure of rat skin collagen α1-CB8. Amino acid sequence of the hydroxylamine-produced fragment HA1Gary Balian, Eva M. Click, and Paul BornsteinCite this: Biochemistry 1971, 10, 24, 4470–4478Publication Date (Print):November 1, 1971Publication History Published online1 May 2002Published inissue 1 November 1971https://doi.org/10.1021/bi00800a019Request reuse permissionsArticle Views58Altmetric-Citations67LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (2 MB) Get e-Alertsclose Get e-Alerts
The Tumor Suppressor p53 and the Oncoprotein Simian Virus 40 T Antigen Bind to Overlapping Domains on the MDM2 Protein (1993)

The oncogene mdm2 has been found to be amplified in human sarcomas, and the gene product binds to the tumor suppressor p53. In this report, we describe the dissection of the MDM2-binding domain on p53 as well as the p53-binding domain on MDM2. We also demonstrate that the oncoprotein simian virus 40 T antigen binds to the product of cellular oncogene mdm2. We have constructed several N- and C-terminal deletion mutants of p53 and MDM2, expressed them in vitro, and assayed their in vitro association capability. The N-terminal boundary of the p53-binding domain on MDM2 is between amino acids 1 and 58, while the C-terminal boundary is between amino acids 221 and 155. T antigen binds to an overlapping domain on the MDM2 protein. On the other hand, the MDM2-binding domain of p53 is defined by amino acids 1 and 159 at the N terminus. At the C terminus, binding is progressively reduced as amino acids 327 to 145 are deleted. We determined the effect of human MDM2 on the transactivation ability of wild-type human p53 in the Saos-2 osteosarcoma cell line, which does not have any endogenous p53. Human MDM2 inhibited the ability of human p53 to transactivate the promoter with p53-binding sites. Thus, human MDM2 protein, like the murine protein, can inactivate the transactivation ability of human p53. Interestingly, both the transactivation domain and the MDM2-binding domain of p53 are situated near the N terminus. We further show that deletion of the N-terminal 58 amino acids of MDM2, which eliminates p53 binding, also abolishes the capability of inactivating p53-mediated transactivation. This finding suggests a correlation of in vitro p53-MDM2 binding with MDM2's ability in vivo to interfere with p53-mediated transactivation.
Decay-accelerating factor protects human tumor cells from complement-mediated cytotoxicity in vitro. (1988)

The disialoganglioside GD2 is expressed on a wide spectrum of human tumor types, including neuroblastomas and melanomas. Upon binding of 3F8, a murine monoclonal antibody (MAb) specific for GD2, neuroblastomas and some melanomas are sensitive to killing by human complement, whereas some melanomas are not. To investigate the mechanism underlying these differences in complement mediated cytotoxicity, complement-insensitive melanoma cell lines were compared with respect to expression of the decay-accelerating factor (DAF), a membrane regulatory protein that protects blood cells from autologous complement attack. While DAF was undetectable among neuroblastomas, it was present in complement-insensitive melanomas. When the function of DAF was blocked by anti-DAF MAb, C3 uptake and complement-mediated lysis of the insensitive melanoma lines were markedly enhanced. F(ab')2 fragments were as effective in enhancing lysis as intact anti-DAF MAb. The DAF-negative and DAF-positive melanoma cell lines were comparably resistant to passive lysis by cobra venom factor-treated serum. The data suggest that in some tumors, DAF activity accounts for their resistance to complement-mediated killing. The ability to render these cells complement-sensitive by blocking DAF function may have implications for immunotherapy.
Single-cycle terahertz electromagnetic pulses: A new test bed for physical seismic modeling (2003)

Abstract We describe a new technique for physical modeling, based on the use of short pulses of electromagnetic radiation. We employ radiation at a frequency near 1 THz (1012 Hz), corresponding to a wavelength of ∼0.3 mm. Very recent advances in optoelectronic techniques have enabled the generation and detection of broadband terahertz pulses using compact room- temperature transducers. These pulses can be used to form images in a variety of modes, including a multistatic reflection configuration which mimics that of many seismic surveys. We illustrate the capabilities of the modeling technique with a simple experiment which demonstrates accurate surface reconstruction using migration techniques. With respect to conventional modeling techniques using piezoelectric transducers and microphones, the use of terahertz pulses has both benefits and limitations. To our knowledge, this work represents the first use of electromagnetic radiation for modeling acoustic imaging problems.
Therapeutic drug monitoring of vancomycin in severe sepsis and septic shock (2008)

There was consistency between the model based prediction and the experimental data so dose adjustment was performed in order to reach target concentrations above 20 mg/l and an initial dose of 3 grams of vancomycin per day was recommended to reach these levels.