gebhart/patrepeval huggingface dataset:
Synthetic Studies of Halichondrin B, an Antitumor Polyether Macrolide Isolated from a Marine Sponge. 7. Synthesis of Two C27-C36 Units via Construction of the F Ring and Completely Stereoselective C-Glycosylation Using Mixed Lewis Acids. (1997)

Two C27-C36 units of halichondrin B were synthesized starting from a C31-C34 alcohol, which was easily available from dimethyl L-tartrate, via construction of the F ring, methylation at the C31 position and C-glycosylation. These crucial reactions proceeded completely stereoselectively, and in particular the stereoselective C-glycosylation with allyltrimethylsilane took place only in the presence of both of two Lewis acids, boron trifluoride etherate and trimethylsilyl triflate.
Social GAN: Socially Acceptable Trajectories with Generative Adversarial Networks (2018)

Understanding human motion behavior is critical for autonomous moving platforms (like self-driving cars and social robots) if they are to navigate human-centric environments. This is challenging because human motion is inherently multimodal: given a history of human motion paths, there are many socially plausible ways that people could move in the future. We tackle this problem by combining tools from sequence prediction and generative adversarial networks: a recurrent sequence-to-sequence model observes motion histories and predicts future behavior, using a novel pooling mechanism to aggregate information across people. We predict socially plausible futures by training adversarially against a recurrent discriminator, and encourage diverse predictions with a novel variety loss. Through experiments on several datasets we demonstrate that our approach outperforms prior work in terms of accuracy, variety, collision avoidance, and computational complexity.
Comparative study of annealed neon-, argon-, and krypton-ion implantation damage in silicon (1978)

Comparative annealing studies were carried out upon Si layers implanted with Ne+, Ar+, and Kr+ ions. Ion doses were in the range 6×1014/cm2–6×1015/cm2, and ion energies were chosen so that the matrix damage had approximately the same depth for each ion type. Annealing was carried out in a N2/dilute O2 ambient or in vacuum at 600, 900, or 1100 °C. Implanted layer structures were studied using electron-microscope and ion-backscattering techniques. The orientation of the Si substrate and ion-beam heating effects were found to be important in determining layer-annealing behavior. The latter depended weakly, if at all, upon the nature of the annealing ambient. Layer recrystallization was studied as a function of implanted ion type and dose, and the effects of inert gases trapped in the Si lattice were examined. The suitability of implantations for device gettering applications were considered. Crystallographic defects produced by annealing ranged from polycrystals and microtwins to simple dislocation networks. Faceted gas bubbles invariably occurred in annealed layers, and their geometry gave information regarding low-energy planes in Si. Electron diffraction and He+-ion channeling effects produced by twins in recrystallized layers have also been examined.
Rendering 3D volumes using per-pixel displacement mapping (2007)

Rendering 3D Volumes Using Per-Pixel Displacement Mapping offers a simple and practical solution to the problem of seamlessly integrating many highly detailed 3D objects into a scene without the need to render large sets of polygons or introduce the overhead of an obtrusive scene-graph. This work takes advantage of modern programmable GPU's as well as recent related research in the area of per-pixel displacement mapping to achieve view independent fully 3D rendering with per-pixel level of detail. To achieve this, a box is used to bound texture-defined volumes. The box acts as a surface to which the volume will be drawn on. By computing a viewing ray from the camera to a point on the box and using that point as a ray origin, the correct intersection with the texture volume can be found using various per-pixel displacement mapping techniques. Once the correct intersection is found, the final color value for the corresponding point on the box can be computed. The technique supports various effects taken both from established raycasting and ray-tracing methods such as reflection, refraction, selfshadowing on models, a simple animation scheme and an efficient method for finding distances through volumes. Copyright © 2007 by the Association for Computing Machinery, Inc.
Multi-process Structuring and the THOTH Operating System (1978)

This report explores the idea of structuring programs as many concurrent processes. It is based on work done in designing, implementing, and using the Thoth operating system. Thoth implements an ahstraction that provides facilities to make this type of structuring attractive, namely inexpensive processes, efficient interprocess communication, dynamic process creation and destruction, and groups of processes sharing a common address space. .br The Thoth abstraction is described, including measurements of its performance and comments on its portability. This abstraction is motivated by considering various design and implementation tradeoffs. Then, the design of multi-process programs is discussed, both in terms of general principles and by giving specific uses and examples to demonstrate the adequacy of the abstraction. Examples are drawn from the operating system and the Thoth text editor. Finally, the feasibility of verifying the system is considered. This is motivated by the desire to exploit the multi-process structure of the system to aid in verification. .br We conclude that structuring programs as multiple processes can have significant benefits, especially for programs that respond to asynchronous events.
Functionalized Cellular Carbon‐MgO Composites: From Interface Processing to Thermal Shock Resistant Low‐Carbon MgO‐C Refractories (2013)

Carbon‐containing refractories have received great attention over the last years, as they are widely used in steel making industry due to their superior properties, such as high thermal shock resistance, high fracture energies in the high‐temperature range, and high slag resistance. However, their main disadvantage is the carbon oxidation associated with considerable CO 2 emissions. Aiming to improve carbon oxidation resistivity whilst maintaining improved thermomechanical characteristics, reinforced, and functionalized cellular carbon MgO‐C (FCC‐MgO‐C) refractories are investigated. Experimentally determined thermomechanical data are used to model final crack density characteristics based on an extended Hasselman's thermal shock theory approach. Data calculated are compared with those of pitch‐bonded MgO‐C refractories. The dominant influence of functionalization and tailoring of microstructural phase constitution is reflected in increased fracture energies during crack propagation after thermal shock treatment.
TRAIL, Fasl and a blocking anti-DR5 antibody augment paclitaxel-induced apoptosis in human non-small-cell lung cancer (2002)

Lung carcinoma is one of the most frequent causes of malignancy-related mortality in the world. Paclitaxel (PA) is an antineoplastic agent used in the treatment of non-smallcell lung cancer (NSCLC) and possesses a single-agent response rate approaching 25%. PA kills tumor cells by inducing both cellular necrosis and apoptosis. Fas and Trail receptors (DR4 and DR5) are TNF family members and act as death signal transduction proteins in the apoptosis cascade. Despite the importance of PA in lung cancer treatment, the function of Fas, DR4 and DR5 in PA-induced apoptosis, as well as the effect of their respective ligands FasL and TRAIL alone or in combination with PA, remains poorly understood. We show here that 10 M PA induces a significant 10-to 57-fold increase in primary lung cancer cell apoptosis and is associated with 20 -215% increases in caspase-3 activity in various NSCLC cell types. All the lung cancer cells express Fas, FasL, DR4 and DR5; however PA did not significantly modify their levels. We provide here the first time evidence that TRAIL is a potent inducer of apoptosis in multiple NSCLC cell lines. Noticeably, CH11, the Fas receptor cross-linking and the antagonistic anti-DR5 antibody enhance considerably the spontaneous apoptotic rate in 3 out of 5 cell types. The combination treatments, FasLPA, TRAILPA or PAanti-DR5 antibody, greatly enhance PA-apoptotic effect in most cell lines. These data suggest that the use of new combination treatment with PA and ligands targeting Fas or TRAIL receptors would be particularly efficacious.
Interferon-αPrimed Tumor-Infiltrating Lymphocytes Combined with Interleukin-2 and Interferon-αas Therapy for Metastatic Renal Cell Carcinoma (1993)

Murine models demonstrate therapeutic synergy for the combination of interleukin-2, interferon-alpha and tumor-infiltrating lymphocytes. We treated 11 patients with metastatic renal cell carcinoma with a novel regimen consisting of in vivo primed tumor-infiltrating lymphocytes, interferon-alpha and interleukin-2. Patients received interferon-alpha before radical nephrectomy; in vivo primed tumor-infiltrating lymphocytes were isolated and expanded in vitro. Low dose continuous infusion interleukin-2 at a dose of 2 x 10(6) units per m.2 per day was administered for 96 hours during each treatment week and interferon-alpha was administered as a subcutaneous injection at a dose of 6 x 10(6) units per m.2 per day on days 1 and 4 of the interleukin-2 infusion. No therapy was given during the last 3 days of a treatment week. One course of therapy consisted of 3 weeks of therapy followed by 3 weeks of rest. Patients were treated until maximal response, disease progression or dose limiting toxicity. A maximum of 6 courses of therapy were administered. Eleven patients underwent interferon-alpha priming and subsequent radical nephrectomy. In vivo primed tumor-infiltrating lymphocytes were successfully expanded in all 11 patients with an expansion index of greater than 170. In vivo primed tumor-infiltrating lymphocytes maintained their lytic activity for greater than 5 to 8 weeks in culture as demonstrated in the 4-hour 51chromium release assay. Ten patients underwent multimodality biological therapy and 3 (30%, 95% confidence interval 6 to 65%) have achieved complete response (2 clinical and 1 surgical) with durations of 24+, 23+ and 5+ months. Patients with stable disease received no additional therapy. No deaths and no grade 4 toxicities occurred. Immunotherapy using a combination of interferon-alpha primed tumor-infiltrating lymphocytes, low dose continuous infusion interleukin-2 and interferon-alpha can induce significant and durable antitumor responses in some patients with advanced renal cell carcinoma.
Imaging of Human Tumor Xenografts With an Indium-111-Labeled Anti-Epidermal Growth Factor Receptor Monoclonal Antibody (1989)

The mouse monoclonal antibody (mAb) 225 IgG1 against the epidermal growth factor (EGF) receptor has been investigated for its capacity to localize in human tumor xenografts. The EGF receptor is the product of the c-erb-B proto-oncogene (also known as EGFR). Elevated expression of EGF receptors has been demonstrated in many human tumors and tumor cell lines. We studied A431 human vulvar squamous cell carcinoma cells, with 2 X 10(6) receptors per cell; MDA-MB-468 (MDA 468) human breast adenocarcinoma cells, with 3 X 10(5) receptors per cell; and MCF-7 human breast adenocarcinoma cells, with 5 X 10(3) receptors per cell. The 111In-labeled pentetic acid (DTPA), derivative of mAb 225 (111In-DTPA-225) was injected intraperitoneally into nude mice bearing subcutaneous tumor xenografts. We measured uptake by quantifying radioactivity in tumor and normal tissues and by obtaining gamma camera images. Uptake in A431 xenografts was 28% +/- 2.4% of the injected dose per gram of tumor on day 3 and 12.4% +/- 3.0% on day 7. Distribution ratios comparing uptake in the tumor with that in normal tissues were consistently greater than 4. In contrast, there was far less uptake of the control mAb KS1/4S-1 labeled with 111In. This conjugate, 111In-DTPA-KS1/4S-1, has an IgG1 isotype but does not bind to human or murine cells. Imaging of the tumor with mAb 225 was excellent, especially on days 3-7. MDA 468 xenografts exhibited reduced localization of mAb 225 in the tumor. For MCF-7 xenografts, the tumor uptake of mAb 225 after 7 days was only 0.70% +/- 0.10% of the injected dose per gram of tumor, which was comparable to the uptake of the KS1/4S-1 control mAb. The ratio of the concentration of radioactivity in the tumor to that in normal tissue (distribution ratio) showed poor selectivity of uptake, and imaging was not obtained. These observations suggest that labeled mAb can target the product of a proto-oncogene, the EGF receptor, when it is expressed at high levels in human tumor xenografts.
State-of-the-art human gene therapy: part I. Gene delivery technologies. (2015)

Safe and effective gene delivery is a prerequisite for successful gene therapy. In the early age of human gene therapy, setbacks due to problematic gene delivery vehicles plagued the exciting therapeutic outcome. However, gene delivery technologies rapidly evolved ever since. With the advancement of gene delivery techniques, gene therapy clinical trials surged during the past decade. As the first gene therapy product (Glybera) has obtained regulatory approval and reached clinic, human gene therapy finally realized the promise that genes can be medicines. The diverse gene delivery techniques available today have laid the foundation for gene therapy applications in treating a wide range of human diseases. Some of the most urgent unmet medical needs, such as cancer and pandemic infectious diseases, have been tackled by gene therapy strategies with promising results. Furthermore, combining gene transfer with other breakthroughs in biomedical research and novel biotechnologies opened new avenues for gene therapy. Such innovative therapeutic strategies are unthinkable until now, and are expected to be revolutionary. In part I of this review, we introduced recent development of non-viral and viral gene delivery technology platforms. As cell-based gene therapy blossomed, we also summarized the diverse types of cells and vectors employed in ex vivo gene transfer. Finally, challenges in current gene delivery technologies for human use were discussed.
Revisiting biomarker discovery by plasma proteomics (2017)

Clinical analysis of blood is the most widespread diagnostic procedure in medicine, and blood biomarkers are used to categorize patients and to support treatment decisions. However, existing biomarkers are far from comprehensive and often lack specificity and new ones are being developed at a very slow rate. As described in this review, mass spectrometry (MS)-based proteomics has become a powerful technology in biological research and it is now poised to allow the characterization of the plasma proteome in great depth. Previous "triangular strategies" aimed at discovering single biomarker candidates in small cohorts, followed by classical immunoassays in much larger validation cohorts. We propose a "rectangular" plasma proteome profiling strategy, in which the proteome patterns of large cohorts are correlated with their phenotypes in health and disease. Translating such concepts into clinical practice will require restructuring several aspects of diagnostic decision-making, and we discuss some first steps in this direction.
High-performance liquid chromatography/mass spectrometry of vitamin D compounds employing derivatization with Cookson-type reagents. (2002)

生体内のビタミンD (D) 化合物の分析は, 臨床, 栄養診断あるいは新薬の開発上重要であり, その体液中レベルや熱安定性などを考慮すると, 方法論として高速液体クロマトグラフィー/質量分析法が有望視される. しかし, 本法はイオン化法がソフトであるため期待したほどの構造情報が得られないことや, D化合物のイオン化効率が低く実用的な感度が得られないなどの問題を抱えている. そこで著者らは, D化合物のs-シス-ジエンと選択的に反応するCookson型試薬に着目し, これを用いる誘導体化によりこれらの問題の解決を試みた. すなわち, 構造解析及び高感度検出の両面からその有用性を検討し, 本誘導体化が代謝部位の決定に有益なプロダクトイオンを与えること及びD化合物のイオン化効率を数十倍増加させることを見いだした. これらの知見を基にDの新規代謝経路の解明及び超微量活性型D製剤の血中濃度測定に成功した.
16S rRNA Mutation Associated with Tetracycline Resistance in a Gram-Positive Bacterium (1998)

A genetic basis for tetracycline resistance in cutaneous propionibacteria was suggested by comparing the nucleotide sequences of the 16S rRNA genes from 16 susceptible and 21 resistant clinical isolates and 6 laboratory-selected tetracycline-resistant mutants of a susceptible strain. Fifteen clinical isolates resistant to tetracycline were found to have cytosine instead of guanine at a position cognate with Escherichia coli 16S rRNA base 1058 in a region important for peptide chain termination and translational accuracy known as helix 34. Cytosine at base 1058 was not detected in the laboratory mutants or the tetracycline-susceptible strains. The apparent mutation was recreated by site-directed mutagenesis in the cloned E. coli ribosomal operon, rrnB, encoded by pKK3535.E. coli strains carrying the mutant plasmid were more resistant to tetracycline than those carrying the wild-type plasmid both in MIC determinations and when grown in tetracycline-containing liquid medium. These data are consistent with a role for the single 16S rRNA base mutation in clinical tetracycline resistance in cutaneous propionibacteria.
Classification of Clear-Cell Sarcoma as a Subtype of Melanoma by Genomic Profiling (2003)

Gene expression profiles support the classification of CCS/MSP as a distinct genomic subtype of melanoma. Analysis of these gene profiles using the SVM may be an important diagnostic tool. Genomic analysis identified potential targets for the development of therapeutic strategies in the treatment of this disease.
Selectively 13C-enriched 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine (trimethoprim) and 2,4-diaminopyrimidine (1986)

Samples of 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine (Trimethoprim) were synthesized, enriched with 13C at the following positions: 2 and 5; 4 and 6; α and 4-methoxy. For the first two series (having 13C-enrichment at the pyrimidine), appropriately labelled cyanoacetic acid was converted into labelled methyl 2-(3,4,5-trimethoxybenzyl)cyanoacetate and thence to the labelled 6-hydroxy derivative of Trimethoprim. For the last series (having 13C-enrichment at the trimethoxybenzyl moiety), the key reaction was the nucleophilic attack of C–5 of 2,4-diamino-6-hydroxypyrimidine on labelled 3,4,5-trimethoxybenzyl bromide, again yielding the labelled 6-hydroxy derivative of Trimethoprim. The conversion of the 6-hydroxy derivatives into 13C-enriched Trimethoprim was via the 6-chloride. Also synthesized was [6-13C]-2,4-diaminopyrimidine by cyclization of guanidine and [3-13C]-3-anilinoacrylonitrile. The identity, and the site(s) of the 13C label(s) of each final product and intermediate, were established on the basis of 1H and 13C n.m.r. spectral evidence.
Oral agents in the management of type 2 diabetes mellitus. (2001)

Despite exhaustive efforts to better manage patients with type 2 diabetes mellitus (formerly known as non-insulin-dependent diabetes mellitus), attempts at maintaining near normal blood glucose levels in these patients remains unsatisfactory. This continues to pose a real challenge to physicians as the prevalence of this disease in the United States continues to rise. Type 2 diabetes is defined as a syndrome characterized by insulin deficiency, insulin resistance and increased hepatic glucose output. Medications used to treat type 2 diabetes are designed to correct one or more of these metabolic abnormalities. Currently, there are five distinct classes of hypoglycemic agents available, each class displaying unique pharmacologic properties. These classes are the sulfonylureas, meglitinides, biguanides, thiazolidinediones and alpha-glucosidase inhibitors. In patients for whom diet and exercise do not provide adequate glucose control, therapy with a single oral agent can be tried. When choosing an agent, it is prudent to consider both patient- and drug-specific characteristics. If adequate blood glucose control is not attained using a single oral agent, a combination of agents with different mechanisms of action may have additive therapeutic effects and result in better glycemic control.
X-linked Alport Syndrome (2000)

Alport syndrome (AS) is a type IV collagen hereditary disease characterized by the association of progressive hematuric nephritis, hearing loss, and, frequently, ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease. Considerable allelic heterogeneity has been observed. A "European Community Alport Syndrome Concerted Action" has been established to delineate accurately the AS phenotype and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X-linked transmission, were collected. Characteristics of the 401 male patients belonging to the 195 families with COL4A5 mutation are presented. All male patients were hematuric, and the rate of progression to end-stage renal failure and deafness was mutation-dependent. Large deletions, non-sense mutations, or small mutations changing the reading frame conferred to affected male patients a 90% probability of developing end-stage renal failure before 30 yr of age, whereas the same risk was of 50 and 70%, respectively, in patients with missense or splice site mutation. The risk of developing hearing loss before 30 yr of age was approximately 60% in patients with missense mutations, contrary to 90% for the other types of mutations. The natural history of X-linked AS and correlations with COL4A5 mutations have been established in a large cohort of male patients. These data could be used for further evaluation of therapeutic approaches.
A total synthesis of (.+-.)-cephalotaxinamide. (1988)

(±)-Cephalotaxinamide (6) was synthesized from pyroglutamic acid via the pyrrolobenzazepine (4) through the Claisen rearrangement, the Wacker oxidation, aldol condensation, and hydroxylation with iodosobenzene.
Association between polymorphisms in PDCD1 gene and aplastic anemia in Chinese Han population (2013)

Single nucleotide polymorphism (SNP) of programmed cell death 1 (PD-1, encoded by PDCD1) has been reported to be associated with several autoimmune diseases including rheumatoid arthritis (RA), Graves' disease and multiple sclerosis (MS). In order to study the correlation between PD-1 gene polymorphism and aplastic anemia in a Chinese Han population, two SNPs, PD-1.1 G/A (rs36084323) and PD-1.6 G/A (rs10204525), were genotyped in 166 patients with aplastic anemia and 144 healthy controls by direct sequencing. All genotype distributions in both patients and controls were in Hardy-Weinberg equilibrium. Associations of genotypes and alleles with aplastic anemia were analyzed. The results suggested that the G allele of PD-1.1 was associated with an increased risk for aplastic anemia, while SNP of PD-1.6 was not associated with aplastic anemia in a Chinese Han population.
Ambiguity-Free Edge-Bundling for Interactive Graph Visualization (2011)

Graph visualization has been widely used to understand and present both global structural and local adjacency information in relational data sets (e.g., transportation networks, citation networks, or social networks). Graphs with dense edges, however, are difficult to visualize because fast layout and good clarity are not always easily achieved. When the number of edges is large, edge bundling can be used to improve the clarity, but in many cases, the edges could be still too cluttered to permit correct interpretation of the relations between nodes. In this paper, we present an ambiguity-free edge-bundling method especially for improving local detailed view of a complex graph. Our method makes more efficient use of display space and supports detail-on-demand viewing through an interactive interface. We demonstrate the effectiveness of our method with public coauthorship network data.