gebhart/patrepeval huggingface dataset:
Site-Specific Trastuzumab Maytansinoid Antibody–Drug Conjugates with Improved Therapeutic Activity through Linker and Antibody Engineering (2014)

Antibody-drug conjugates (ADCs) have a significant impact toward the treatment of cancer, as evidenced by the clinical activity of the recently approved ADCs, brentuximab vedotin for Hodgkin lymphoma and ado-trastuzumab emtansine (trastuzumab-MCC-DM1) for metastatic HER2+ breast cancer. DM1 is an analog of the natural product maytansine, a microtubule inhibitor that by itself has limited clinical activity and high systemic toxicity. However, by conjugation of DM1 to trastuzumab, the safety was improved and clinical activity was demonstrated. Here, we report that through chemical modification of the linker-drug and antibody engineering, the therapeutic activity of trastuzumab maytansinoid ADCs can be further improved. These improvements include eliminating DM1 release in the plasma and increasing the drug load by engineering four cysteine residues into the antibody. The chemical synthesis of highly stable linker-drugs and the modification of cysteine residues of engineered site-specific antibodies resulted in a homogeneous ADC with increased therapeutic activity compared to the clinically approved ADC, trastuzumab-MCC-DM1.
Substituent control of the poly(C)-directed oligomerization of guanosine 5'-phosphoroimidazolide (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSubstituent control of the poly(C)-directed oligomerization of guanosine 5'-phosphoroimidazolideTan Inoue and Leslie E. OrgelCite this: J. Am. Chem. Soc. 1981, 103, 25, 7666–7667Publication Date (Print):December 1, 1981Publication History Published online1 May 2002Published inissue 1 December 1981https://pubs.acs.org/doi/10.1021/ja00415a051https://doi.org/10.1021/ja00415a051research-articleACS PublicationsRequest reuse permissionsArticle Views574Altmetric-Citations97LEARN 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
Discourse Complements Lexical Semantics for Non-factoid Answer Reranking (2014)

We propose a robust answer reranking model for non-factoid questions that integrates lexical semantics with discourse information, driven by two representations of discourse: a shallow representation centered around discourse markers, and a deep one based on Rhetorical Structure Theory. We evaluate the proposed model on two corpora from different genres and domains: one from Yahoo! Answers and one from the biology domain, and two types of non-factoid questions: manner and reason. We experimentally demonstrate that the discourse structure of nonfactoid answers provides information that is complementary to lexical semantic similarity between question and answer, improving performance up to 24% (relative) over a state-of-the-art model that exploits lexical semantic similarity alone. We further demonstrate excellent domain transfer of discourse information, suggesting these discourse features have general utility to non-factoid question answering.
Rapid Fluorescence Detection of in Situ Hybridization with Biotinylated Bovine Herpesvirus-1 DNA Probes (1989)

The use of biotinylated DNA hybridization probes for clinical detection of bovine herpesvirus-1 was investigated. Biotinylated DNA hybridization probes were prepared from bovine herpesvirus-1 DNA purified from infected cell cultures. The viral DNA was nick translated in the presence of biotin-dUTP with DNA polymerase to incorporate biotin into the newly synthesized strand. The probe was tested for specificity in in situ hybridization assays with bovine herpesvirus-1 DNA. Hybridization was detected using avidin-fluorescein single sandwich systems and an avidin-globulin with anti-globulin-fluorescein double sandwich system. Hybridization was detected by specific fluorescence of infected cells. Fluorescence was present only in bovine herpesvirus-1-infected cell culture and not in noninfected cell culture or cell cultures infected with several other viruses. The assay was performed in 6 hr.
Optimization of the PiggyBac Transposon System for the Sustained Genetic Modification of Human T Lymphocytes (2009)

Optimal implementation of adoptive T-cell therapy for cancer will likely require multiple and maintained genetic modifications of the infused T cells and their progeny so that they home to tumor sites and recognize tumor cells, overcome tumor immune evasion strategies, and remain safe. Retroviral vectors readily transduce T cells and integrate into the host cell genome, but have a limited capacity for multigene insertion and cotransduction and are prohibitively expensive to produce at clinical grade. Genetic modification of T cells using transposons as integrating plasmids is an attractive alternative because of the increased simplicity and cost of production. Of available transposons, piggyBac has the higher transposase activity and larger cargo capacity, and we now evaluate piggyBac for potential adoptive therapies with primary T cells. PiggyBac transposons mediated stable gene expression in approximately 20% of primary T cells without selection. Treatment and maintenance of T cells with interleukin-15 increased stable transgene expression up to approximately 40% and expression was sustained through multiple logs of expansion for over 9 weeks in culture. We demonstrate simultaneous integration of 2 independent transposons in 20% of T cells, a frequency that could be increased to over 85% by selection of a transgenic surface marker (truncated CD19). PiggyBac could also deliver transposons of up to 13 kb with 10,000-fold expansion of transduced T cells in culture and finally we demonstrate delivery of a functional suicide gene (iCasp9). PiggyBac transposons may thus be used to express the multiple integrated transgenes that will likely be necessary for the broader success of T-cell therapy.
New Class of HIV-1 Integrase (IN) Inhibitors with a Dual Mode of Action (2012)

tert-Butoxy-(4-phenyl-quinolin-3-yl)-acetic acids (tBPQA) are a new class of HIV-1 integrase (IN) inhibitors that are structurally distinct from IN strand transfer inhibitors but analogous to LEDGINs. LEDGINs are a class of potent antiviral compounds that interacts with the lens epithelium-derived growth factor (LEDGF) binding pocket on IN and were identified through competition binding against LEDGF. LEDGF tethers IN to the host chromatin and enables targeted integration of viral DNA. The prevailing understanding of the antiviral mechanism of LEDGINs is that they inhibit LEDGF binding to IN, which prevents targeted integration of HIV-1. We showed that in addition to the properties already known for LEDGINs, the binding of tBPQAs to the IN dimer interface inhibits IN enzymatic activity in a LEDGF-independent manner. Using the analysis of two long terminal repeat junctions in HIV-infected cells, we showed that the inhibition by tBPQAs occurs at or prior to the viral DNA 3'-processing step. Biochemical studies revealed that this inhibition operates by compound-induced conformational changes in the IN dimer that prevent proper assembly of IN onto viral DNA. For the first time, tBPQAs were demonstrated to be allosteric inhibitors of HIV-1 IN displaying a dual mode of action: inhibition of IN-viral DNA assembly and inhibition of IN-LEDGF interaction.
Laser-Driven Particle Accelerators (2006)

A new generation of particle accelerators that use laser acceleration can sit on the benchtop. These instruments are being actively developed for widespread applications.
A Review of Autism and the Immune Response (2004)

This article has no abstract.
Impaired Intracellular Trafficking of Adeno-Associated Virus Type 2 Vectors Limits Efficient Transduction of Murine Fibroblasts (2000)

Although adeno-associated virus type 2 (AAV) has gained attention as a potentially useful alternative to the more commonly used retrovirus- and adenovirus-based vectors for human gene therapy, efficient gene transfer and transgene expression by AAV vectors require that the following two obstacles be overcome. First, the target cell must express the receptor and the coreceptor for AAV infection, and second, the cell must allow for viral second-strand DNA synthesis. We now describe a third obstacle, impaired intracellular trafficking of AAV to the nucleus, which results in the lack of transgene expression in murine fibroblasts which do express the AAV receptor and the coreceptor and which are permissive for viral second-strand DNA synthesis. We document that AAV vectors bind efficiently and gain entry successfully into NIH 3T3 cells, but trafficking into the nucleus is significantly impaired in these cells. In contrast, viral trafficking to the nucleus in cells known to be efficiently transduced by AAV vectors is both rapid and efficient. The demonstration of yet another obstacle in AAV-mediated gene transfer has implications for the optimal use of these vectors in human gene therapy.
Detecting logical argumentation in text via communicative discourse tree (2018)

We solve the argument mining problem by investigating discourse and communicative text structure. A new formal graph-based structure called communicative discourse tree (CDT) is defined. It consists of a discourse tree with additional labels on edges, which stand for verbs. These verbs represent communicative actions. Discourse trees are based on rhetoric relations, extracted from a text according to Rhetoric Structure Theory. The problem is tackled as a binary classification task, where the positive class corresponds to texts with arguments and the negative class corresponds to texts with no arguments. The feature engineering for the classification task is conducted, deciding on which syntactic and discourse features are associated with logical argumentation. Text classification framework based on syntactic, discourse and communicative discourse text structures with a number of learning approaches is implemented. Evaluation on a combined data-set is provided.
Self-Assembly and Gelation of Oxidized Glutathione in Organic Solvents (2001)

The oxidized disulfide form of the ubiquitous tripeptide glutathione (gamma-glu-cys-gly) (GSSG) is shown to produce transparent, thermoreversible gels in aqueous solutions of dimethyl sulfoxide, dimethylformamide, and methanol, at GSSG concentrations as low as 1.5 mM. The gels bind Congo Red and exhibit dramatic green birefringence when observed between crossed polarizers, characteristic of amyloid structures. By transmission electron microscopy, the gels appear to consist of a network of fibrous structures about 75 nm in diameter. Several structurally related peptides, including the glutathione isomer glu-cys-gly and the aspartyl analogue of glutathione (beta-asp-cys-gly), failed to produce gels under similar conditions. These results suggest that the interactions which produce gelation are highly specific and that the unusual peptide geometry introduced by gamma-glu-cys linkage is critical to the gelation behavior. (1)H NMR indicates solvent-dependent perturbation of the gamma-glutamyl alpha- and beta-protons and circular dichroism reveals a shift in the geometry of the disulfide bond under conditions producing gelation. We propose that in appropriate organic solvents, GSSG self-assembles into an extended network of beta-sheetlike structures capable of immobilizing bulk solvent. While obviously speculative, it is interesting to consider possible physiological consequences of glutathione self-recognition in such processes as abnormal protein aggregation and the thiol-disulfide exchange which is believed to participate in protein folding.
Engineering the Monomer Composition of Polyhydroxyalkanoates Synthesized in Saccharomyces cerevisiae (2006)

Polyhydroxyalkanoates (PHAs) have received considerable interest as renewable-resource-based, biodegradable, and biocompatible plastics with a wide range of potential applications. We have engineered the synthesis of PHA polymers composed of monomers ranging from 4 to 14 carbon atoms in either the cytosol or the peroxisome of Saccharomyces cerevisiae by harnessing intermediates of fatty acid metabolism. Cytosolic PHA production was supported by establishing in the cytosol critical beta-oxidation chemistries which are found natively in peroxisomes. This platform was utilized to supply medium-chain (C6 to C14) PHA precursors from both fatty acid degradation and synthesis to a cytosolically expressed medium-chain-length (mcl) polymerase from Pseudomonas oleovorans. Synthesis of short-chain-length PHAs (scl-PHAs) was established in the peroxisome of a wild-type yeast strain by targeting the Ralstonia eutropha scl polymerase to the peroxisome. This strain, harboring a peroxisomally targeted scl-PHA synthase, accumulated PHA up to approximately 7% of its cell dry weight. These results indicate (i) that S. cerevisiae expressing a cytosolic mcl-PHA polymerase or a peroxisomal scl-PHA synthase can use the 3-hydroxyacyl coenzyme A intermediates from fatty acid metabolism to synthesize PHAs and (ii) that fatty acid degradation is also possible in the cytosol as beta-oxidation might not be confined only to the peroxisomes. Polymers of even-numbered, odd-numbered, or a combination of even- and odd-numbered monomers can be controlled by feeding the appropriate substrates. This ability should permit the rational design and synthesis of polymers with desired material properties.
On the coefficients of absorption of nitrogen and oxygen in distilled water and sea-water, and of atmospheric carbonic acid in sea-water (1909)

C. J. J. Fox, Trans. Faraday Soc., 1909, 5, 68 DOI: 10.1039/TF9090500068
Government Failures in Development (1990)

By the 1970s and early 1980s, governments in most developing countries were mired down in economic policies that were manifestly unworkable. Whether market failures had been present or not, most knowledgeable observers concluded that there had been colossal government failures. In many countries, there could be little question but that government failure significantly outweighed market failure. This essay focuses on insights relating directly to government behavior affecting economic activity and economic growth in developing countries. It briefly examines each of the following questions: 1) What is “the government”? 2) What is the comparative advantage of government? 3) What are the dynamics of government intervention? 4) Can a positive theory of political behavior be formulated that will help explain when and how alternative policies will evolve in the political arena?
Tissue factor pathway inhibitor‐2 suppresses the production of active matrix metalloproteinase‐2 and is down‐regulated in cells harboring activated ras oncogenes (2000)

A human placenta cDNA expression library was screened for genes inducing flat reversion when transfected into a v-K-ras-transformed NIH3T3 cell line, DT. One such gene was found to encode a Kunitz-type serine protease inhibitor, tissue factor pathway inhibitor-2 (TFPI-2). While the TFPI-2 mRNA can be detected in normal human fibroblasts (MRC-5), it is down-regulated in MRC-5 cells expressing an activated H-ras oncogene and in the human fibrosarcoma cell line, HT1080. Restored expression of the TFPI-2 gene in HT1080 cells resulted in the suppression of matrix invasion activity in vitro with concomitant decrease in the relative amount of active matrix metalloproteinase-2 secreted from the cells. When DT cells were cultured in the presence of conditioned medium and extracellular matrix prepared from TFPI-2-transfected HT1080 cells, increased attachment and flat reversion were observed. These results suggest that TFPI-2 may be required for the maintenance of the integrity of extracellular matrix in normal tissues and its down-regulation as a result of oncogene activation may contribute to the malignant phenotypes of tumor cells.
Transhemispheric exchange of Lyme disease spirochetes by seabirds (1995)

Lyme disease is a zoonosis transmitted by ticks and caused by the spirochete Borrelia burgdorferi sensu lato. Epidemiological and ecological investigations to date have focused on the terrestrial forms of Lyme disease. Here we show a significant role for seabirds in a global transmission cycle by demonstrating the presence of Lyme disease Borrelia spirochetes in Ixodes uriae ticks from several seabird colonies in both the Southern and Northern Hemispheres. Borrelia DNA was isolated from I. uriae ticks and from cultured spirochetes. Sequence analysis of a conserved region of the flagellin (fla) gene revealed that the DNA obtained was from B. garinii regardless of the geographical origin of the sample. Identical fla gene fragments in ticks obtained from different hemispheres indicate a transhemispheric exchange of Lyme disease spirochetes. A marine ecological niche and a marine epidemiological route for Lyme disease borreliae are proposed.
ROC Curve Analysis: An Example Showing the Relationships Among Serum Lipid and Apolipoprotein Concentrations in Identifying Patients with Coronary Artery Disease (1992)

Clinical accuracy, defined as the ability to discriminate between states of health, is the fundamental property of any diagnostic test or system. It is readily expressed as clinical sensitivity and specificity, and elegantly represented by the receiver operating characteristic (ROC) curve. To demonstrate the use of ROC curves, we reexamine a study of the ability of serum lipid and apolipoprotein measures to discriminate among degrees of coronary artery disease in patients undergoing coronary angiography. ROC curve analysis reveals that none of these indexes is highly accurate, but demonstrates a modest increase in the accuracy of apolipoprotein over lipid indexes.
Glypican 3: A Novel Marker in Testicular Germ Cell Tumors (2006)

Glypican 3 (GPC3), a membrane-bound heparin sulfate proteoglycan, may play a role in promoting embryonic cell growth and differentiation. GPC3 is mutated in Simpson-Golabi-Behmel syndrome, characterized by tissue overgrowth and an increased risk of embryonal malignancies. Recently, GPC3 was reported to be one of the over-expressed genes in testicular yolk sac tumors by gene expression microarray analysis. However, the presence of the GPC3 protein in germ cell tumors has never been investigated. The purpose of the study was to investigate the GPC3 expression in various histologic components of testicular germ cell tumors using immunohistochemistry and to assess its possible utility as a diagnostic marker. Tumors from 71 patients were examined, including components of 42 seminomas, 37 embryonal carcinomas, 24 yolk sac tumors, 20 teratomas with mature elements, 16 teratomas with immature elements, and 7 choriocarcinomas. Cytoplasmic and membranous immunoreactivity was semiquantitatively evaluated. All yolk sac tumor (24/24) and choriocarcinoma (7/7) components were immunoreactive for GPC3, whereas only 38% of teratomas with immature elements and 8% of embryonal carcinomas expressed GPC3. There was no immunoreactivity in benign testicular tissue, intratubular germ cell neoplasia, seminomas (0/42), or teratomas with mature elements (0/20). We conclude that the oncofetal protein GPC3 is a novel immunohistochemical marker in testicular germ cell tumors with differential expression in defined histologic subtypes. Our findings suggest a possible role of GPC3 in tumor cell differentiation. Furthermore, GPC immunostaining may be useful in the pathologic diagnosis of nonseminomatous germ cell tumors, particularly yolk sac tumor, and choriocarcinoma.
On Anisotropic Mesh Generation and Quality Control in Complex Flow Problems. (2001)

As automatic mesh generation procedures for general geometric domains mature, attention has begun to focus on consideration of issues aimed at ensuring the meshes are the “best meshes ” for the task at hand. There are multiple
Forging a Link Between Biofilms and Disease (1999)

The sticky conglomerations of bacteria known as biofilms are being linked to common human diseases ranging from tooth decay to prostatitis and kidney infections. Aided by support from a new program at the National Institutes of Health, researchers are now working to understand how and why biofilms form. The goal is to identify their Achilles9 heel and devise better treatments, which are badly needed, because bacteria sequestered in biofilms are shielded from attack by the host9s immune system and are often much harder to kill with antibiotics than their free-floating counterparts.
A novel method to predict die shift during compression molding in embedded wafer level package (2009)

The increased functionality of cellular phones and handheld devices requires system level integration. Thus there is a strong demand in cell phone maker to move to embedded micro wafer level packaging (EMWLP). But the major problem encountered is die shift during compression molding. This paper presents a novel method to predict the die shift during wafer level molding process. A series of parametric studies are performed by changing the die thickness, die pitch distance and top mold chaste compression velocity. The effect of thinning down the chip thickness affects the pressure difference and local shear rate on the chip surfaces. The rate of change of epoxy mold compound fluid pressure across the die top surfaces is not constant. The local shear rate is increasing linearly from the centre of the wafer to the outermost die. From the parametric studies, the die shift is inversely proportional to the die thickness for wafer level molding. Such a phenomenon will reduce the lithography alignment error in the next process. This paper also shows that by reducing die pitch distance of a 5 × 5 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , 500 µm thick chip, the die shift decreases by a factor of 12%. In addition, the top mold chaste compression velocity contributes to the die shift by as much as 28% when the velocity is reduced by 50% from 100 µm/sec to 50 µm/sec Finally it is observed from experiment result that the die shift is not constant in all directions.
An Outlook on Microalgal Biofuels (2010)

Microalgae are considered one of the most promising feedstocks for biofuels. The productivity of these photosynthetic microorganisms in converting carbon dioxide into carbon-rich lipids, only a step or two away from biodiesel, greatly exceeds that of agricultural oleaginous crops, without competing for arable land. Worldwide, research and demonstration programs are being carried out to develop the technology needed to expand algal lipid production from a craft to a major industrial process. Although microalgae are not yet produced at large scale for bulk applications, recent advances-particularly in the methods of systems biology, genetic engineering, and biorefining-present opportunities to develop this process in a sustainable and economical way within the next 10 to 15 years.