gebhart/patrepeval huggingface dataset:
'Opening Up' Literary Cloze (2002)

This article reports on case-study research which explored English as a second language (ESL) learners' perceptions of the role played by the literary cloze activity in the development of their language and literary awareness. The subjects, four students from a variety of language, cultural and literary backgrounds, attended a semester-long university ESL subject which adopted a language-based approach to literature. Data included the subjects' evaluations of the technique, a multiple-choice literary cloze exercise and an audiotaped discussion in which the subjects retrospectively explained and analysed their responses. The findings shed light on why the subjects considered that the cloze procedure and following discussion had influenced their vocabulary acquisition and development, interpretative skills and confidence to form and express opinions. Data analysis demonstrated that cloze may be used to highlight the cohesive structure of a text and 'open up' its meaning, and equally to sensitise learners to stylistic features. Finally, the findings provide an indication of the way language proficiency may have influenced the subjects' responses to the cloze activity, but also suggest that cultural and literary background, as well as personality and age factors, may have affected their ability to interpret and express opinions about the text.
Shared ACVR1 mutations in FOP and DIPG: Opportunities and challenges in extending biological and clinical implications across rare diseases (2017)

Gain-of-function mutations in the Type I Bone Morphogenic Protein (BMP) receptor ACVR1 have been identified in two diseases: Fibrodysplasia Ossificans Progressiva (FOP), a rare autosomal dominant disorder characterized by genetically driven heterotopic ossification, and in 20-25% of Diffuse Intrinsic Pontine Gliomas (DIPGs), a pediatric brain tumor with no effective therapies and dismal median survival. While the ACVR1 mutation is causal for FOP, its role in DIPG tumor biology remains under active investigation. Here, we discuss cross-fertilization between the FOP and DIPG fields, focusing on the biological mechanisms and principles gleaned from FOP that can be applied to DIPG biology. We highlight our current knowledge of ACVR1 in both diseases, and then describe the growing opportunities and barriers to effectively investigate ACVR1 in DIPG. Importantly, learning from other seemingly unrelated diseases harboring similar mutations may uncover novel mechanisms or processes for future investigation.
Ribozyme modulation of lipopolysaccharide‐induced tumor necrosis factor‐α production by peritoneal cells in vitro and in vivo (1996)

We have utilized synthetic ribozymes to modulate the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-alpha) by peritoneal cells. Two hammerhead ribozymes (mRz1 and mRz2) were prepared by transcription in vitro and their activities in vitro and in vivo were investigated. Both ribozymes cleaved their RNA target with an apparent turnover number (kcat) of 2 min(-1), and inhibited TNF-alpha gene expression in vitro by 50% and 70%, respectively. When mRz1 and mRz2, entrapped in liposomes, were delivered into mice by intraperitoneal injection, they inhibited LPS-induced TNF-alpha gene expression in vivo with mRz2 being the most effective. This enhanced activity could result from the facilitation of catalysis by cellular endogenous proteins, since they specifically bind to mRz2 as compared to mRz1. Furthermore, a significant mRz2 activity can be recovered from peritoneal cells 2 days post-administration in vivo. The anti-TNF-alpha ribozyme treatment in vivo resulted in a more significant reduction of LPS-induced IFN-gamma protein secretion compared to IL-10. In contrast to this pleiotropic effect, the anti-TNF-alpha ribozyme treatment did not affect the heterogenous expression of Fas ligand by peritoneal cells, indicating the specificity of the treatment. Taken together, the present data indicate that the biological effects of TNF-alpha can be modulated by ribozymes. In addition, the data suggest that ribozymes can be administered in a drug-like manner, and therefore indicate their potential in clinical applications.
CpG Stimulation of Primary Mouse B Cells Is Blocked by Inhibitory Oligodeoxyribonucleotides at a Site Proximal to NF- κ B Activation (2001)

Bacterial DNA and CpG-oligodeoxyribonucleotides (ODN) are powerful B cell activators, inducing apoptosis protection, cell cycle entry, proliferation, costimulatory molecule expression, immunoglobulin (Ig) and interleukin-6 (IL-6) secretion. However, proximal events in B cell activation by ODN are only partially characterized, including the translocation of NF-kappaB to the nucleus. In this paper, we provide evidence that CpG-ODN-induced cell cycle entry and apoptosis protection are blocked by SN50 or gliotoxin and thus require NF-kappaB activation. NF-kappaB activation occurred within 30 minutes of stimulation of murine B cells with a phosphorothioate (S) CpG-ODN and persisted for up to 40 hours, with p50, p65, and c-Rel as the major components. Similar to other NF-kappaB inducers, CpG-ODN caused an early IkappaBalpha and IkappaBbeta degradation plus cleavage of the p50 precursor and subsequent NF-kappaB nuclear translocation. A group of closely related S-ODN, which specifically blocked CpG-induced B cell activation at submicromolar concentrations, also prevented NF-kappaB DNA binding and transcriptional activation. These inhibitory S-ODN differed from stimulatory S-ODN by having 2-3 G substitutions in the central motif. As inhibitory S-ODN did not directly interfere with the NF-kappaB DNA binding but prevented CpG-induced NF-kappaB nuclear translocation of p50, p65, and c-Rel and blocked p105, IkappaBalpha, and IkappaBbeta degradation, we concluded that their putative target must lie upstream of inhibitory kinase (IKK) activation.
The p75 Neurotrophin Receptor Activates Akt (Protein Kinase B) through a Phosphatidylinositol 3-Kinase-dependent Pathway (2001)

The Akt kinase plays a crucial role in supporting Trk-dependent cell survival, whereas the p75 neurotrophin receptor (p75NTR) facilitates cellular apoptosis. The precise mechanism that p75NTR uses to promote cell death is not certain, but one possibility is that p75NTR-dependent ceramide accumulation inhibits phosphatidylinositol 3-kinase-mediated Akt activation. To test this hypothesis, we developed a system for examining p75NTR-dependent apoptosis and determined the effect of p75NTR on Akt activation. Surprisingly, p75NTR increased, rather than decreased, Akt phosphorylation in a variety of cell types, including human Niemann-Pick fibroblasts, which lack acidic sphingomyelinase activity. The p75NTR expression level required to elicit Akt phosphorylation was much lower than that required to activate the JNK pathway or to mediate apoptosis. We show that p75NTR-dependent Akt phosphorylation was independent of TrkA signaling, required active phosphatidylinositol 3-kinase, and was associated with increased tyrosine phosphorylation of p85 and Shc and with reduced cytosolic tyrosine phosphatase activity. Finally, we show that p75NTR expression increased survival in cells exposed to staurosporine or subjected to serum withdrawal. These findings indicate that p75NTR facilitates cell survival through novel signaling cascades that result in Akt activation.
Antibiotics in Laboratory Medicine. (1980)

The Breakpoint 1 Matthew A. Wikler, Paul G. Ambrose Antimicrobial Susceptibility on Solid Media 8 John D. Turnidge, Jan M. Bell Susceptibility Testing of Antimicrobials in Liquid Media 61 Daniel Amsterdam Antimicrobial Susceptibility Testing of Anaerobic Bacteria 144 David W. Hecht Antimycobacterial Agents: In Vitro Susceptibility Testing and Mechanisms of Action and Resistance 155 Clark B. Inderlied and Kevin A. Nash Antifungal Drugs: Mechanisms of Action, Drug Resistance, Susceptibility Testing, and Assays of Activity in Biological Fluids 226 Michael A. Pfaller, Daniel J. Diekema, and Michael G. Rinaldi Antimicrobial Susceptibility Testing for Some Atypical Microorganisms (Chlamydia, Mycoplasma, Rickettsia, Ehrlichia, Coxiella, and Spirochetes) 266 Jean-Marc Rolain, Didier Raoult Applications, Significance of, and Methods for the Measurement of Antimicrobial Concentrations in Human Body Fluids 290 Roger D. Klein and Stephen C. Edberg Antimicrobial Combinations 365 Satish K. Pillai, Robert C. Moellering, Jr., and George M. Eliopoulos Genetic and Biochemical Mechanisms of Bacterial Resistance to Antimicrobial Agents 441 Louis B. Rice and Robert A. Bonomo Molecular Methods for the Detection of Antibacterial Resistance Genes 509 Margareta Ieven Molecular Mechanisms of Action for Antimicrobial Agents: General Principles and Mechanisms for Selected Classes of Antibiotics 532 Charles W. Stratton The Antivirogram and the Modes of Action of Antiviral Agents, HIV, Hepatitis, Influenza, and Cytomegalovirus 564 Pierre Dellamonica, Vincent Calvez, Anne-Genevieve Marcelin, Albert Tran, Pierre-Marie Roger, Marie-Christine Mazeron, and Bruno Lina Disinfectants and Antiseptics, Modes of Action, Mechanisms of Resistance, and Testing 615 Joseph M. Ascenzi, Martin S. Favero Evaluation of Antimicrobials in Experimental Animal Infections 654 Terry O' Reilly, D. A. Andes, Ch. Ostergaard, N. Frimodt-Moller Extravascular Antimicrobial Distribution and the Respective Blood and Urine Concentrations in Humans 719 David M. Bamberger, John W. Foxworth, Darcie L. Bridwell, Christopher S. Shain, and Dale N. Gerding Epidemiology of Antimicrobial Resistance: Species Prevalence, Susceptibility Profiles, and Resistance Trends 815 Thomas R. Fritsche, Helio S. Sader, Ronald N. Jones Index 851
Increasing frequencies of site-specific mutagenesis and gene targeting in Arabidopsis by manipulating DNA repair pathways (2013)

Improved methods for engineering sequence-specific nucleases, including zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs), have made it possible to precisely modify plant genomes. However, the success of genome modification is largely dependent on the intrinsic activity of the engineered nucleases. In this study, we sought to enhance ZFN-mediated targeted mutagenesis and gene targeting (GT) in Arabidopsis by manipulating DNA repair pathways. Using a ZFN that creates a double-strand break (DSB) at the endogenous ADH1 locus, we analyzed repair outcomes in the absence of DNA repair proteins such as KU70 and LIG4 (both involved in classic nonhomologous end-joining, NHEJ) and SMC6B (involved in sister-chromatid-based homologous recombination, HR). We achieved a fivefold to 16-fold enhancement in HR-based GT in a ku70 mutant and a threefold to fourfold enhancement in GT in the lig4 mutant. Although the NHEJ mutagenesis frequency was not significantly changed in ku70 or lig4, DNA repair was shifted to microhomology-dependent alternative NHEJ. As a result, mutations in both ku70 and lig4 were predominantly large deletions, which facilitates easy screening for mutations by PCR. Interestingly, NHEJ mutagenesis and GT at the ADH1 locus were enhanced by sixfold to eightfold and threefold to fourfold, respectively, in a smc6b mutant. The increase in NHEJ-mediated mutagenesis by loss of SMC6B was further confirmed using ZFNs that target two other Arabidopsis genes, namely, TT4 and MPK8. Considering that components of DNA repair pathways are highly conserved across species, mutations in DNA repair genes likely provide a universal strategy for harnessing repair pathways to achieve desired targeted genome modifications.
Interactions and management issues in HSV and HIV coinfection (2007)

Significant synergistic interactions have been observed between HIV and herpes simplex virus (HSV). HIV-induced immune compromise can cause frequent and persistent HSV disease, while poorly controlled HSV replication may influence HIV pathogenicity and transmission. HSV-2 seroprevalence is high in HIV-infected cohorts worldwide, with rates of over 80% for HSV-1 and ranging from 33% to more than 80% for HSV-2. As seen in HIV-negative individuals, HSV-2 coinfection is associated with female gender, older age and black ethnicity. HSV infection is commonly under-diagnosed in HIV-infected individuals, although the use of PCR for HSV detection in mucocutaneous swabs and HSV type-specific serology can improve the diagnostic yield. In HIV-1-infected patients with frequent clinical episodes of HSV reactivation, suppressive antiviral therapy may prove beneficial in controlling HSV disease while also reducing HSV-mediated promotion of HIV replication. Antiretroviral therapy leads to a gradual recovery of HSV-specific T-cell responses and a reduction in HSV-related morbidity, indicating that successful management of coinfection should target both HIV and HSV replication. The aim of this review is to address the more speculative issues surrounding the management of HSV/HIV coinfection and to summarize the data that inform them.
Challenges in Creating Effective Home-School Partnerships in Adolescence: Promising Paths for Collaboration. (2003)

Home-school partnerships for adolescents should extend beyond a focus on school performance issues to a broader set of common concerns for parents and teachers, including helping students forge a positive, constructive identity. After providing an overview of key elements in adolescent identity development, we highlight five critical development needs that comprise essential aspects of posi-tive identities: appreciation, belonging, confidence, competencies, and contribu-tion. Then we describe four co-occurring processes—love and caring, laughter, limits, and linkages—that must be kept in balance in order for these outcomes to be achieved. Families and school personnel can keep these processes in balance when both sets of partners work together, each from their own vantage points and strengths. Specific examples of contexts that lend themselves to home-school partnerships include: academics, routine parent-school interactions, everyday parent-child interactions at home, and lifestyle habits. We offer recommendations about ways educators and parents can collaborate with each other in these contexts to benefit young people. As each group reaches out effectively to the other, new the school community journal 134 home-school partnerships in adolescence 135 contexts for partnership are likely to be forged, and the challenge to find new and lasting pathways for home-school partnership is likely to be met. Key Words: school family partnerships, home school relations, parent involve-ment, adolescents, adolescence, identity formation
Genetic polymorphism of human serum ribonuclease I (RNase I). (1988)

One of the human urinary ribonucleases (RNases) was isolated and purified to homogeneity (SDS-PAGE) by means of a series of column chromatographies. The enzyme, designated RNase 1, is a glycoprotein with a molecular weight of approximately 16,000. Rabbit antibody to the purified RNase 1 reacted with human urine and sera, as well as with the purified RNase 1. The genetic polymorphism of serum RNase 1 was studied by polyacrylamide gel isoelectric focusing (IEF-PAGE) in a pH range of 5-8, followed by immunoblotting with antisera specific for RNase 1. Two common phenotypes, RNASE1 1 and RNASE1 1-2, were easily recognized. The homogeneous phenotype, RNASE1 1, consisted of four major bands with different pI values, and the heterogeneous phenotype, RNASE1 1-2, was presumed to represent a mixture of each of the homogeneous phenotypes 1 and 2; however, the other homogeneous phenotype, RNASE1 2, was not detected in our samples. Family studies are in agreement with an autosomal codominant transmission of the two alleles. Population studies indicate that the frequencies of the RNASE 1 and RNASE1 2 alleles are .988 and .012, respectively.
Drug-loaded biodegradable microspheres for image-guided combinatory epigenetic therapy in cells (2011)

We synthesize drug-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres for image-guided combinatory epigenetic therapy in MCF-10A human mammary epithelial cells. LY294002 and Nile Red are encapsulated in microspheres for sustained drug release and fluorescence microscopic imaging. Drug-loaded microspheres target MCF-10A cells through a three-step binding process involving biotinylated antibody, streptavidin, and biotinylated microspheres. LY294002 loaded microspheres and 5-Aza-2-deoxycytidine are applied to MCF-10A cells for combinatory PI3K∕AKT inhibition and deoxyribonucleic acid (DNA) demethylation. Our study implies the technical potential of disease targeting and image-guided combinatory epigenetic therapy using drug-loaded multifunctional biodegradable PLGA microspheres.
Physical Resource Matching Under Power Asymmetry (2006)

Manufacturing related variations are predicted to have a significant impact on power consumption for near future technology generations. Due to both die-to-die and within-die parameter variations, the power consumption of identically designed hardware resources can vary randomly on a per instance basis. This introduces fabrication induced asymmetry, which can undermine basic assumptions about power/performance balances in a design. Specifically, architects expect that superscalar pipeline resources and cores in a homogenous CMP design are truly homogenous when fabricated on a chip. In this paper, we describe implications that fabrication power asymmetry have on a CMP design with respect to the allocation and utilization of hardware resources and the mapping between applications and physical cores. We introduce hardware/software management techniques that can overcome power asymmetry by considering the dissimilar power profiles of physical resources under parameter variation. 1
Automated Versus Manual In Vivo Segmentation of Carotid Plaque MRI (2012)

In 40 patients with carotid stenosis, our results indicated that it was possible to automatically detect carotid plaque components with substantial or good agreement with visual identification, and that the volumes obtained manually and automatically were reasonably consistent for hemorrhage and lipids but not for calcium.
Obtaining 2-Octanol, 2-Octanone, and Sebacic Acid from Castor Oil by Microwave-Induced Alkali Fusion (2008)

In this study, the effect of microwave irradiation on alkali fusion of castor oil was investigated using different NaOH/oil ratios (8:15, 12:15, and 14:15), reaction temperatures (473, 493, 503, 513, and 523 K), and reaction times (15, 20, 25, and 30 min) in order to obtain oleochemicals (2-octanol, 2-octanone, and sebacic acid) in the presence of 1% catalyst (Pb3O4) by weight (w/w). The yields of 2-octanol (4.4−62.6%), 2-octanone (1.6−37.4%), and sebacic acid (9.1−76.2%) were obtained according to reaction conditions. Maximum yields of oleochemicals were obtained using methylated then presaponified castor oil (sodium ricinoleate), 14/15 NaOH/oil ratio at temperature 513 K and 20 min reaction time. 2-Octanol, 2-octanone, and sebacic acid were determined by GC and GC/MS analysis, and purity of sebacic acid (98.7%) was further assessed by its acid value (444) and melting point (406.5 K). Reaction time compared to conventional heating was dramatically decreased by microwave heating system from 5 h reaction time to 20 min.
A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19 ARF –p53 signaling (2002)

Senescence limits the proliferative capacity of primary cells in culture. We describe here a genetic screen to identify genes that allow bypass of this checkpoint. Using retroviral cDNA expression libraries, we identify BCL6 as a potent inhibitor of senescence. BCL6 is frequently activated in non-Hodgkin's lymphoma, but its mechanism of action has remained unclear. BCL6 efficiently immortalizes primary mouse embryonic fibroblasts and cooperates with RAS in oncogenic transformation. BCL6 overrides the senescence response downstream of p53 through a process that requires induction of cyclin D1 expression, as cyclin D1 knockout fibroblasts are specifically resistant to BCL6 immortalization. We show that BCL6 expression also dramatically extends the replicative lifespan of primary human B cells in culture and induces cyclin D1 expression, indicating that BCL6 has a similar activity in lymphoid cells. Our results suggest that BCL6 contributes to oncogenesis by rendering cells unresponsive to antiproliferative signals from the p19(ARF)-p53 pathway.
Extension of TOPAS for the simulation of proton radiation effects considering molecular and cellular endpoints (2015)

The aim of this work is to extend a widely used proton Monte Carlo tool, TOPAS, towards the modeling of relative biological effect (RBE) distributions in experimental arrangements as well as patients. TOPAS provides a software core which users configure by writing parameter files to, for instance, define application specific geometries and scoring conditions. Expert users may further extend TOPAS scoring capabilities by plugging in their own additional C++ code. This structure was utilized for the implementation of eight biophysical models suited to calculate proton RBE. As far as physics parameters are concerned, four of these models are based on the proton linear energy transfer, while the others are based on DNA double strand break induction and the frequency-mean specific energy, lineal energy, or delta electron generated track structure. The biological input parameters for all models are typically inferred from fits of the models to radiobiological experiments. The model structures have been implemented in a coherent way within the TOPAS architecture. Their performance was validated against measured experimental data on proton RBE in a spread-out Bragg peak using V79 Chinese Hamster cells. This work is an important step in bringing biologically optimized treatment planning for proton therapy closer to the clinical practice as it will allow researchers to refine and compare pre-defined as well as user-defined models.
Parity logging with reserved space: towards efficient updates and recovery in erasure-coded clustered storage (2014)

Many modern storage systems adopt erasure coding to provide data availability guarantees with low redundancy. Log-based storage is often used to append new data rather than overwrite existing data so as to achieve high update efficiency, but introduces significant I/O overhead during recovery due to reassembling updates from data and parity chunks. We propose parity logging with reserved space, which comprises two key design features: (1) it takes a hybrid of in-place data updates and log-based parity updates to balance the costs of updates and recovery, and (2) it keeps parity updates in a reserved space next to the parity chunk to mitigate disk seeks. We further propose a workload-aware scheme to dynamically predict and adjust the reserved space size. We prototype an erasure-coded clustered storage system called CodFS, and conduct testbed experiments on different update schemes under synthetic and real-world workloads. We show that our proposed update scheme achieves high update and recovery performance, which cannot be simultaneously achieved by pure in-place or log-based update schemes.