gebhart/patrepeval huggingface dataset:
New insights in Type I and II CD20 antibody mechanisms‐of‐action with a panel of novel CD20 antibodies (2018)

Based on their mechanisms-of-action, CD20 monoclonal antibodies (mAbs) are grouped into Type I [complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC)] and Type II [programmed cell death (PCD) and ADCC] mAbs. We generated 17 new hybridomas producing CD20 mAbs of different isotypes and determined unique heavy and light chain sequence pairs for 13 of them. We studied their epitope binding, binding kinetics and structural properties and investigated their predictive value for effector functions, i.e. PCD, CDC and ADCC. Peptide mapping and CD20 mutant screens revealed that 10 out of these 11 new mAbs have an overlapping epitope with the prototypic Type I mAb rituximab, albeit that distinct amino acids of the CD20 molecule contributed differently. Binding kinetics did not correlate with the striking differences in CDC activity among the mIgG2c mAbs. Interestingly, chimerization of mAb m1 resulted in a mAb displaying both Type I and II characteristics. PCD induction was lost upon introduction of a mutation in the framework of the heavy chain affecting the elbow angle, supporting that structural changes within this region can affect functional activities of CD20 mAbs. Together, these new CD20 mAbs provide further insights in the properties dictating the functional efficacy of CD20 mAbs.
Learning to Estimate the Travel Time (2018)

Vehicle travel time estimation or estimated time of arrival (ETA) is one of the most important location-based services (LBS). It is becoming increasingly important and has been widely used as a basic service in navigation systems and intelligent transportation systems. This paper presents a novel machine learning solution to predict the vehicle travel time based on floating-car data. First, we formulate ETA as a pure spatial-temporal regression problem based on a large set of effective features. Second, we adapt different existing machine learning models to solve the regression problem. Furthermore, we propose a Wide-Deep-Recurrent (WDR) learning model to accurately predict the travel time along a given route at a given departure time. We then jointly train wide linear models, deep neural networks and recurrent neural networks together to take full advantages of all three models. We evaluate our solution offline with millions of historical vehicle travel data. We also deploy the proposed solution on Didi Chuxing's platform, which services billions of ETA requests and benefits millions of customers per day. Our extensive evaluations show that our proposed deep learning algorithm significantly outperforms the state-of-the-art learning algorithms, as well as the solutions provided by leading industry LBS providers.
Ribozyme Mediated gRNA Generation for In Vitro and In Vivo CRISPR/Cas9 Mutagenesis (2016)

CRISPR/Cas9 is now regularly used for targeted mutagenesis in a wide variety of systems. Here we report the use of ribozymes for the generation of gRNAs both in vitro and in zebrafish embryos. We show that incorporation of ribozymes increases the types of promoters and number of target sites available for mutagenesis without compromising mutagenesis efficiency. We have tested this by comparing the efficiency of mutagenesis of gRNA constructs with and without ribozymes and also generated a transgenic zebrafish expressing gRNA using a heat shock promoter (RNA polymerase II-dependent promoter) that was able to induce mutagenesis of its target. Our method provides a streamlined approach to test gRNA efficiency as well as increasing the versatility of conditional gene knock out in zebrafish.
Health-related Quality of Life in Patients with Psoriasis and Atopic Dermatitis Measured with SF-36, DLQI and a Subjective Measure of Disease Activity (2000)

The impact of skin diseases on health-related quality of life is considerable. It is important to quantify the patient's perspective of the severity of their disease. Health-related quality of life was measured in 366 patients with skin diseases attending the dermatology outpatient clinic in Uppsala, Sweden, from November 1996 to December 1997, with 1 generic (SF-36) and 1 disease-specific (DLQI) health-related quality of life instrument, and a subjective measure of disease activity. The SF-36 mean scores were below those of the age- and gender-matched general population in Sweden. No difference in health-related quality of life was found between men and women or between patients with atopic dermatitis and psoriatic patients. However, patients with psoriatic arthritis had significantly poorer health-related quality of life than both patients with atopic dermatitis and psoriatic patients. The estimated correlations between the instruments were in the expected direction and mostly significant. The results confirm that skin diseases have an adverse impact on patients' health-related quality of life.
IL-21 promotes the expansion of CD27+CD28+ tumor infiltrating lymphocytes with high cytotoxic potential and low collateral expansion of regulatory T cells (2013)

Our data rationalize the clinical application of IL-21-secreting aAPC as a standardized cell-based platform in the expansion of "young" effector TIL for ACT.
In vitro antimicrobial activity of benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex, determined by the radiometric method (1993)

MICs of a newly developed benzoxazinorifamycin derivative, KRM-1648, for Mycobacterium avium complex (MAC) were determined by the BACTEC 460 TB system and compared with those of other known antimicrobial agents. The radiometric method gave a fast, accurate, and reproducible MIC for each antimicrobial agent. MICs of KRM-1648 for 30 strains of MAC (10 strains each of M. avium isolated from AIDS and non-AIDS patients and of Mycobacterium intracellulare isolated from non-AIDS patients) were measured. The MICs, ranging from 0.004 to 0.0625 microgram/ml, were the lowest of all tested drugs, including rifampin, rifabutin, streptomycin, kanamycin, isoniazid, ethambutol, ofloxacin, ciprofloxacin, sparfloxacin, and clarithromycin. The MICs were 2 to 512 and 1 to 32 times lower than those of rifampin and rifabutin, respectively. With rifampin and ethambutol, there were some differences between the MICs for M. avium isolated from AIDS patients (American) and those for M. avium from non-AIDS patients (Japanese). Moreover, appreciable differences between the MICs of some drugs against M. avium and M. intracellulare isolated from non-AIDS patients were found. Many strains of M. avium were more susceptible to ofloxacin than M. intracellulare, but, conversely, M. avium was more resistant to rifampin, streptomycin, ethambutol, and clarithromycin than M. intracellulare.
Effect of Experimental Dry Eye on Tear Sodium Concentration in the Mouse (2005)

These experiments show the ability of these new techniques for determining tear volume and estimating tear osmolarity in mice. By mimicking the findings of human dry eye disease, these findings validate the relevance of the mouse model for studying the pathogenesis of human keratoconjunctivitis sicca.
INTERLANGUAGE VARIATION: THE INFLUENCE OF CONTEXTUALIZED LANGUAGE ON L2 PHONOLOGICAL PRODUCTION (2003)

This study analyzes the production of the English /I/ in obligatory contexts by a Spanish-speaking L2 learner of English, whose phonological system does not include /I/. This study investigates how context—defined by Duranti and Goodwin (1992) as “a frame that surrounds the event being examined and provides resources for its appropriate interpretation” (p. 3)—affects a speaker’s ability to accurately produce native-like phonemes in their L2. The main research question that focuses this study is the following: How do differing levels of textual formality and degrees of contextualization affect the phonological production of the English high/front, lax vowel /I/ by a Spanish-speaking learner of English? Contrary to Labov’s hypotheses (1966) for L1 speech, the results of the study showed that the participant was most accurate in her production of /I/ in the more vernacular register, i.e. narration, than in the more formal register, i.e. minimal pair naming. Apparently, contextual clues influenced the speakers’ pronunciation of semantically-familiar words. Future studies need to consider what psycholinguistic and reading processes are occurring that cause familiar words, out of context, to be pronounced differently than those embedded in contextualized language. The presence of contextualized language appears to prime the speaker and activate not just lexical features but also phonological components. In spite of being familiar with the semantics of the target words, the subject of the current study achieved greater phonological success when the words were contextualized.
A Home Terminal System Using the Home Area Information Network (1984)

Today, microcomputers are included in many kinds of home electrical devices. Also, there has been a rapid proliferation in the number of home information devices such as home computers, video discs, VTR's, and other home information processing or storage means. On the other hand, communications network services have reached new stages of advancement with the development of new communications media such as videotex, broadcast satelites, teletex, and two-way CATV. These have given portability and allowed multiple installation for the home terminal situation.
Characterization of an Adenovirus Vector Containing a Heterologous Peptide Epitope in the HI Loop of the Fiber Knob (1998)

The utility of the present generation of recombinant adenovirus vectors for gene therapy applications could potentially be improved by designing targeted vectors capable of gene delivery to selected cell types in vivo. In order to achieve such targeting, we are investigating the possibilities of incorporation of ligands in the adenovirus fiber protein, which mediates primary binding of adenovirus to its cell surface receptor. Based on the proposed structure of the cell-binding domain of the fiber, we hypothesized that the HI loop of the fiber knob can be utilized as a convenient locale for incorporation of heterologous ligands. In this study, we utilized recombinant fiber proteins expressed in baculovirus-infected insect cells to demonstrate that the incorporation of the FLAG octapeptide into the HI loop does not ablate fiber trimerization and does not disturb formation of the cell-binding site localized in the knob. We then generated a recombinant adenovirus containing this modified fiber and showed that the short peptide sequence engineered in the knob is compatible with the biological functions of the fiber. In addition, by using a ligand-specific antibody, we have shown that the peptide incorporated into the knob remains available for binding in the context of mature virions containing modified fibers. These findings suggest that heterologous ligands can be incorporated into the HI loop of the fiber knob and that this locale possesses properties consistent with its employment in adenovirus retargeting strategies.
Probing minimal independent folding units in dihydrofolate reductase by molecular dissection (1997)

Molecular dissection was employed to identify minimal independent folding units in dihydrofolate reductase (DHFR) from Escherichia coli. Eight overlapping fragments of DHFR, spanning the entire sequence and ranging in size from 36 to 123 amino acids, were constructed by chemical cleavage. These fragments were designed to examine the effect of tethering multiple elements of secondary structure on folding and to test if the secondary structural domains represent autonomous folding units. CD and fluorescence spectroscopy demonstrated that six fragments containing up to a total of seven alpha-helices or beta-strands and, in three cases, the adenine binding domain (residues 37-86), are largely disordered. A stoichiometric mixture of the two fragments comprising the large discontinuous domain, 1-36 and 87-159, also showed no evidence for folding beyond that observed for the isolated fragments. A fragment containing residues 1-107 appears to have secondary and tertiary structure; however, spontaneous self-association made it impossible to determine if this structure solely reflects the behavior of the monomeric form. In contrast, a monomeric fragment spanning residues 37-159 possesses significant secondary and tertiary structure. The urea-induced unfolding of fragment 37-159 in the presence of 0.5 M ammonium sulfate was found to be a well-defined, two-state process. The observation that fragment 37-159 can adopt a stable native fold with unique, aromatic side-chain packing is quite striking because residues 1-36 form an integral part of the structural core of the full-length protein.
Hypermethylation and Transcriptional Downregulation of the TIMP3 Gene is Associated with Allelic Loss on 22q12.3 and Malignancy in Meningiomas (2009)

The gene for the tissue inhibitor of metalloproteinase 3 (TIMP3) on 22q12.3 had been reported to be inactivated by promoter methylation in various types of cancers, with controversial findings in meningiomas. We performed direct sodium bisulfite sequencing in a series of 50 meningiomas, including 27 benign meningiomas [World Health Organization (WHO) grade I], 11 atypical meningiomas (WHO grade II) and 12 anaplastic meningiomas (WHO grade III), and found hypermethylation of TIMP3 in 67% of anaplastic meningiomas, but only 22% of atypical and 17% of benign meningiomas. Moreover, TIMP3 methylation scores were significantly inversely correlated with TIMP3 mRNA expression levels (P = 0.0123), and treatment of the meningioma cell line Ben-Men-1 with demethylating agents induced an increased TIMP3 mRNA expression. TIMP3 is located in the chromosomal band 22q12, the allelic loss of which occurs early in meningioma tumorigenesis and preferentially targets the NF2 tumor suppressor gene. In our tumor panel, all meningiomas with TIMP3 hypermethylation--except for a single case--exhibited allelic losses on 22q12.3. Thus, TIMP3 inactivation by methylation seems fairly exclusive to meningiomas with allelic losses on 22q12 but--in contrast to NF2 mutation--appears to be involved in meningioma progression as it is associated with a more aggressive, high-grade meningioma phenotype.
II. Cationic Lipid-Formulated Plasmid DNA-Based Bacillus anthracis Vaccine: Evaluation of Plasmid DNA Persistence and Integration Potential (2005)

Several formulated plasmid DNA (pDNA)-based vaccines are being evaluated for safety and efficacy in healthy human subjects. A safety concern for any vaccine that contains genetic material, be it whole organism, live-attenuated, or gene-based, is the potential for integration into genomic DNA (gDNA). To address this concern, a preclinical pDNA persistence/integration study was conducted in rabbits to determine the level of pDNA in muscle 2, 28, and 64 days after intramuscular injection of DMRIE:DOPE-formulated pDNAs encoding Bacillus anthracis detoxified LF and PA proteins (VCL-AB01 vaccine). Total DNA was extracted from day 64 muscle tissue and fractionated by column agarose gel electrophoresis (CAGE). Plasmid copy number (PCN) in muscle 64 days after injection (geometric mean, 2808 PCN/microg of total DNA or 150,000 diploid genomes) was determined by quantitative polymerase chain reaction. Analysis of total DNA from five VCLAB01- injected rabbits revealed that two of five samples had no detectable PCN in the high molecular weight fraction after one round of CAGE, two samples had PCN under the lower limit of quantitation, and the remaining sample had 123 PCN/microg. All PCN in the latter sample cleared after an additional round of CAGE. It appears, therefore, that persisting PCN fractionate as low molecular weight material and are most likely not integrated into gDNA. Even if the worst-case assumption is made that the highest PCN found associated with gDNA represented covalently integrated pDNA inserts, the frequency of mutation would still be 500-fold lower than the autosomal spontaneous mutation rate.
Differentiation of Follicular Thyroid Adenoma from Carcinoma by Means of Gene Expression Profiling with Adapter-Tagged Competitive Polymerase Chain Reaction (2005)

This diagnostic system using the ATAC-PCR assay is expected to be clinically useful for preoperative differentiation between FTA and FTC since ATAC-PCR can be used for the small amount of RNA obtained from fine needle aspiration biopsy.
Bioreducible Cationic Polymer-Based Nanoparticles for Efficient and Environmentally Triggered Cytoplasmic siRNA Delivery to Primary Human Brain Cancer Cells (2014)

siRNA nanomedicines can potentially treat many human diseases, but safe and effective delivery remains a challenge. DNA delivery polymers such as poly(β-amino ester)s (PBAEs) generally cannot effectively deliver siRNA and require chemical modification to enable siRNA encapsulation and delivery. An optimal siRNA delivery nanomaterial needs to be able to bind and self-assemble with siRNA molecules that are shorter and stiffer than plasmid DNA in order to form stable nanoparticles, and needs to promote efficient siRNA release upon entry to the cytoplasm. To address these concerns, we designed, synthesized, and characterized an array of bioreducible PBAEs that self-assemble with siRNA in aqueous conditions to form nanoparticles of approximately 100 nm and that exhibit environmentally triggered siRNA release upon entering the reducing environment of the cytosol. By tuning polymer properties, including bioreducibility and hydrophobicity, we were able to fabricate polymeric nanoparticles capable of efficient gene knockdown (91 ± 1%) in primary human glioblastoma cells without significant cytotoxicity (6 ± 12%). We were also able to achieve significantly higher knockdown using these polymers with a low dose of 5 nM siRNA (76 ± 14%) compared to commercially available reagent Lipofectamine 2000 with a 4-fold higher dose of 20 nM siRNA (40 ± 7%). These bioreducible PBAEs also enabled 63 ± 16% gene knockdown using an extremely low 1 nM siRNA dose and showed preferential transfection of glioblastoma cells versus noncancer neural progenitor cells, highlighting their potential as efficient and tumor-specific carriers for siRNA-based nanomedicine.
Rapid Synthesis of High-Quality InP Nanocrystals (2006)

A rapid new method for preparation of monodisperse InP-nanocrystals was developed. A highly reactive indium precursor and tris(trimethylsilyl)phosphine (TMS)3P was reacted within a weakly coordinating solvent in the presence of a supporting protic agent. The yielded InP-nanocrystals had a very narrow size distribution without any size selection process. The precursor and ligand effects were considered as critical factors in control of nucleation and crystal growth process. Different ligands were introduced to study the reaction mechanism. The new method not only yielded the "best" InP-nanocrystals so far, but also includes the potential for preparation within a continuous flow reactor, because the utilized ester is liquid at room temperature.
A Potential Role for Interferon-α in the Pathogenesis of HIV-Associated Dementia (1995)

Previous studies in patients receiving interferon-alpha (IFN-alpha) therapy and patients with systemic lupus erythematosus have demonstrated that elevated cerebrospinal fluid (CSF) levels of IFN-alpha are associated with cognitive dysfunction. We measured IFN-alpha levels in CSF and blood by ELISA in human immunodeficiency virus (HIV)-positive patients with (n = 21) and without (n = 23) dementia and HIV-negative controls (n = 48). IFN-alpha was significantly elevated in the CSF of HIV-positive patients with dementia compared to those without dementia and controls. An increasing amount of IFN-alpha in the CSF was correlated with the clinical parameter of increasing Memorial Sloan Kettering scores; although these correlations were not statistically significant, they further suggest an association of increased CSF IFN-alpha with neurocognitive dysfunction in AIDS. Immunocytochemical staining of brains demonstrated IFN-alpha-positive macrophages and astrocytes in frontal cortex and white matter and IFN-alpha mRNA was detected by reverse transcriptase-polymerase chain reaction, further indicating that IFN-alpha is made by cells within the brain and suggesting that the significant increases of IFN-alpha protein found in the CSF of patients with HIV-associated dementia complex are derived from intrinsic brain cells such as macrophages and astrocytes. Increased local production of IFN-alpha during HIV infection may contribute directly or indirectly to the pathogenesis of HIV-associated dementia.
Main report - sector environmental policy and management assessment of FRSP (1999)

While the Road Sector Institutional Support Technical Assistance Project will examine rehabilitation options to minimize the need for ongoing road maintenance, the environmental assessment considers the potential environmental effects of the project on social, cultural, and economic resources, in a two-volume report covering the Katunguru - Kasese - Fort Portal Road, and Kasese - Kilembe Road - Equator Road segments. Measures to mitigate adversity are: To reduce the effects of road widening, those works within road reserves, should be conducted after harvest period, and, for those outside road reserve, compensation should be granted to affected landowners. As a result of earthworks, borrow pits will be available for waste, and spoil disposal, in an effort to reduce hydrological damage. Noise, dust, and safety risks will be minimized by limiting working hours to daytime schedules, enforcing control measures to reduce traffic speed, and, securing access to pedestrians, and cyclists through adequate traffic signals, and temporary diversions. During construction, health facilities will be available on-site, to ensure the well-being of local workforce, and communities. Maintenance of drainage infrastructure will be pursued, to avoid potential flooding of adjacent properties.