gebhart/patrepeval huggingface dataset:
Room-to-grow: responding to community cultural needs to support positive parenting. (1997)

Preventive services to assist parents to understand their children's developmental needs and to devise positive, culturally appropriate strategies for managing them are not recognized as important by most third party health service payers, especially managed care programs. Room-To-Grow is an intervention designed to meet identified community needs in a culturally appropriate and sensitive way. This article discusses the evolution of this intervention and the problems encountered in finding appropriate reimbursement streams.
The accessible chromatin landscape of the human genome (2012)

DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify ∼2.9 million DHSs that encompass virtually all known experimentally validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. We connect ∼580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is organized with dozens to hundreds of co-activated elements, and the transcellular DNase I sensitivity pattern at a given region can predict cell-type-specific functional behaviours. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation.
What Are Natural Retinoids? (1999)

Vitamin A (retinol) is the prototype of all other natural retinoids. It is composed of a nonaromatic ring structure, a polyprenoid side chain and a carbonyl end group. These features make it liable to metabolic interconversion and protein interactions but also cause detergent-like properties and a sensitivity to UV irradiation and oxidation. Natural retinoids are present in all living organisms, either as preformed vitamin A or as carotenoids, and are required for a vast number of biological processes, e.g. vision, cellular growth and differentiation and reproduction. Although retinol is the most omnipotent compound, natural retinoids like all-trans-, 9-cis- and didehydroretinoic acid (RA) are clearly more potent outside the retina and trigger gene expression via binding to nuclear retinoid receptors. Retinaldehyde takes an intermediate position in this respect, with ability to convert to both retinol and RA. Over the years, many natural retinoids have been tried therapeutically against skin disorders with the best effects achieved with retinol, retinaldehyde, 13-cis-RA and all-trans-RA. The latter compound was the prototype when new, synthetic derivatives of vitamin A were sought, hoping for a better therapeutic index and a higher functional specificity. Inevitably, treatment with such drugs will influence the effects of coexisting natural retinoids. An understanding of the basic principles of these interactions may have major impact on patient outcome.
Adalimumab: A new tumor necrosis factor antagonist and the treatment of Crohn′s disease (2007)

Antibody-neutralization studies have implicated tumor necrosis factor-alpha (TNF-alpha) and IL-12 p40 in the pathogenesis of Crohn's disease (CD). Many randomized controlled trials (RCTs) have demonstrated the efficacy of infliximab, a chimeric monoclonal antibody to TNF, in inducing and maintaining disease remission in patients with moderate to severe CD, including those with draining fistulas. However, infliximab is administered intravenously and is associated with immunological reactions and development of antibodies, and hence reduced efficacy. In this article, we describe the efficacy and safety profiles of a newly available recombinant, fully humanized, subcutaneously-administered, anti-TNF-alpha monoclonal antibody, adalimumab (Humira) in patients with moderate to severe CD. Many recent RCTs have shown that adalimumab is not only similar to infliximab in the mode of action, efficacy, and safety, but it has the advantages of causing less anaphylactic or immunological reactions, being administered by the subcutaneous route, less need for hospitalization, and a half-life of 2 weeks that allows every other week dosage. Adalimumab has also shown some efficacy in infliximab-intolerant or resistant cases. Therefore, it represents a new horizon in the treatment of CD patients, and may reduce the number of patients who require surgical intervention.
Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results. (1998)

The MTD for administration of 131I-labeled 81C6 into the SCRCs of previously irradiated patients with recurrent primary or metastatic brain tumors was 100 mCi. The dose-limiting toxicity was neurologic toxicity. We are encouraged by the minimal toxicity and survival in this phase I trial. Radiolabeled mAbs may improve the current therapy for brain tumor patients.
Retinal pigment epithelium pathologies investigated with phase resolved polarization sensitive optical coherence tomography (2006)

A polarization sensitive optical coherence tomography (PS-OCT) instrument was used to investigate the retinal pigment epithelium (RPE). The instrument uses the polarization properties of light to record backscattered intensity, retardation and fast axis orientation simultaneously and needs only one measurement per sample location to retrieve these parameters. The polarization state of light backscattered from within the RPE was found to be random. This can be observed in PS-OCT images by random retardation and axis orientation values within the RPE layer. In diseased eyes where the normal retinal structure is corrupted (e.g. RPE atrophy, RPE detachment) the localization of the RPE within OCT images which do not provide polarization information (standard OCT) is rather difficult. Since the RPE is the only structure within the retina to cause this polarization scrambling, PS-OCT can be used for contrast enhancement and enables the exact localization of the RPE in these pathologies. Therefore it is possible to determine if the RPE is still preserved in regions of interest. Furthermore, in patients with RPE atrophy an enhanced penetration depth into the choroid and even into the sclera was observed. Because of birefringence introduced by the sclera the border between choroid and sclera could easily be determined.
B-cell depletion with rituximab as treatment for immune hemolytic anemia and chronic thrombocytopenia. (2002)

Rituximab appeared to be active and safe in some patients with refractory autoimmune hemolytic anemia and thrombocytopenia. These results, along with data from literature, suggest that this agent may have a therapeutic role in autoimmune diseases.
The challenge of antibiotic-resistant Staphylococcus: lessons from hospital nurseries in the mid-20th century. (2013)

In the late 1940s, epidemics of antibiotic-resistant strains of Staphylococcus aureus began to plague postpartum nurseries in hospitals across the United States. Exacerbated by overcrowding and nursing shortages, resistant S. aureus outbreaks posed a novel challenge to physicians and nurses heavily reliant on antibiotics as both prophylaxis and treatment. This paper explores the investigation of the reservoir, mode of transmission, and virulence of S. aureus during major hospital outbreaks and the subsequent implementation of novel infection control measures from the late 1940s through the early 1960s. The exploration of these measures reveals a shift in infection control policy as hospitals, faced with the failure of antibiotics to slow S. aureus outbreaks, implemented laboratory culture routines, modified nursery structure and layout, and altered nursing staff procedures to counter various forms of S. aureus transmission. Showcasing the need for widespread epidemiologic surveillance, ultimately manifesting itself in specialized "hospital epidemiology" training promoted in the 1970s, the challenges faced by hospital nurses in the 1950s prove highly relevant to the continued struggle with methicillin-resistant Staphylococcus aureus (MRSA) and other resistant nosocomial infections.
DNA Sequencing Based on Intrinsic Molecular Charges (2006)

In charge: Label-free DNA sequencing can be performed by using a field-effect transistor to detect the intrinsic molecular charges (see picture). Oligonucleotide probes are immobilized on the Si3N4 gate surface, and complementary target DNA is hybridized with them. The change in charge density on the Si3N4/SiO2 gate caused by each single-base extension can be measured as a shift in the threshold voltage. VG=gate voltage.
Development of a blood-based gene expression algorithm for assessment of obstructive coronary artery disease in non-diabetic patients (2011)

PREDICT, Personalized Risk Evaluation and Diagnosis in the Coronary Tree, http://www.clinicaltrials.gov, NCT00500617.
Action of Tocopherol‐Type Compounds in Directing Reactions Forming Flavor Compounds in Autoxidizing Fish Oils (1989)

Abstract Menhaden and cod liver oils without additives or containing either α‐tocopherol (670 ppm) or Trolox C (1000 ppm) with or without copper (II) cations (20 ppm) were oxidized under air at 65‡C, and their headspace volatiles were quantitatively measured by capillary gas chromatography. Samples prepared without additives contained very little l,5‐octadien‐3‐one. Fish oils with Trolox C had distinct metallic, vinyl‐ketone aromas, while those with a‐tocopherol exhibited extremely fishy, cod liver‐like aromas. High levels of 1,5‐octadien‐3‐one and 1,5‐octadien‐3‐ol and moderate levels of 2,4,7‐decatrienals were found in samples with Trolox C, while moderate levels of the 8‐carbon compounds and high levels of the 2,4,7‐decatrienals were present in the α‐tocopherol samples. Copper (II) greatly accelerated the overall rate of oxidation in samples, and in the presence of Trolox C it induced the formation of very high levels of 1,5‐octadien‐3‐ol.
Synthetic Reactions by Complex Catalysts XXXV. A Facile Synthetic Method of Cyclic Imino Ethers and Imino Thioethers (1974)

Abstract This communication describes a simple and versatile method for the synthesis of cyclic imino ethers and imino thioethers, in which amino-alcohol and aminothiol, respectively, were reacted with isonitrile in the presence of PdCl2 catalyst (eq 1). Thus, heterocycles such as 2-oxazolines, 2-thiazolines and 5,6-dihydro-4H-1, 3-oxazine were readily prepared in high yields by a single-step reaction. Some typical results are shown in Table I.
Human De-Etiolated-1 Regulates c-Jun by Assembling a CUL4A Ubiquitin Ligase (2004)

Arabidopsis thaliana De-etiolated-1 (AtDET1) is a highly conserved protein, with orthologs in vertebrate and invertebrate organisms. AtDET1 negatively regulates photomorphogenesis, but its biochemical mechanism and function in other species are unknown. We report that human DET1 (hDET1) promotes ubiquitination and degradation of the proto-oncogenic transcription factor c-Jun by assembling a multisubunit ubiquitin ligase containing DNA Damage Binding Protein-1 (DDB1), cullin 4A (CUL4A), Regulator of Cullins-1 (ROC1), and constitutively photomorphogenic-1. Ablation of any subunit by RNA interference stabilized c-Jun and increased c-Jun-activated transcription. These findings characterize a c-Jun ubiquitin ligase and define a specific function for hDET1 in mammalian cells.
Response to PD-1 Blockade in Microsatellite Stable Metastatic Colorectal Cancer Harboring aPOLEMutation (2017)

Recent clinical evidence has demonstrated that microsatellite instability (MSI) or defective mismatch repair (MMR) and high tumor mutational load can predict response to the programmed cell death 1 (PD-1) receptor inhibitor pembrolizumab in metastatic colorectal cancer (mCRC). Mutations in polymerase ε (<i>POLE</i>), a DNA polymerase involved in DNA replication and repair, contribute to an ultramutated but microsatellite stable (MSS) phenotype in colorectal tumors that is uniquely distinct from MSI tumors. This report presents the first case in the literature describing a clinical response to pembrolizumab in an 81-year-old man with treatment-refractory mCRC characterized by an MSS phenotype and <i>POLE</i> mutation identified on genomic profiling by next-generation sequencing. On tumor immunostaining, a large amount of CD8-positive tumor infiltrating lymphocytes (TILs) were present, with >90% of these expressing PD-1. More than 99% of PD-L1 expression was identified on nontumor cells in the tumor microenvironment that were close to the PD-1-positive CD8 TILs. mCRC tumors harboring <i>POLE</i> mutations represent a hypermutated phenotype that may predict response to anti-PD-1 therapy.
Bitblox: Printable digital materials for electromechanical machines (2014)

As additive manufacturing of mechanical parts gains broad acceptance, efforts to embed electronic or electromechanical components in these parts are intensifying. We discuss recent work in printable electronics and introduce an alternative, which we call Bitblox. Bitblox are small, modular, interconnecting blocks that embed simple electromechanical connectivity and functionality. Not all blocks are identical; instead the unique combinations and positions of Bitblox within an assembly determine the mechanical and electrical properties of the assembly. We describe the design details of Bitblox, compare them to similar materials, and demonstrate their use in a working three-dimensional printer through several examples.
High Speed Surface Illuminated Si Photodiode Using Microstructured Holes for Absorption Enhancements at 900–1000 nm Wavelength (2017)

A surface-illuminated silicon photodiode with both high speed and usable external quantum efficiency from 900 to 1000 nm wavelength is highly desirable for intra/inter data center Ethernet communications, high performance computing, and laser radar application. Such Si photodiodes have the potential for monolithic integration to CMOS integrated circuits which can significantly reduce the cost of data transmission per gigabit below one US dollar. To overcome silicon’s intrinsic weakness of absorption in these wavelengths, photon-trapping microstructured hole arrays are etched into the silicon surface, and the operational wavelengths of a high-speed silicon PIN photodiode are extended to 1000 nm. In this paper, the design and fabrication of such photon-trapping structures integrated into all-silicon photodiodes with significantly reduced absorption layer thicknesses to achieve high external quantum efficiency and fast response are presented. Different designs and geometries of the submicron holes on the silicon surface can affect the light trapping and ultimately contribute to different external quantum efficiencies at these wavelengths. Some designs are capable of enhancing the absorption by more than an order of magnitude compared to a photodiode without the submicron hole arrays. With the silicon i-layer thickness less than or equal to 2 μm, the all-silicon photodiode with integrated submicron holes exhibited an external quantum efficiency of more than 40% at 900 nm and greater than 15% at 1000 nm. This thin absorption layer also allows the fast speed of the photodiode with temporal responses of ∼30 ps at these wavelengths.
The chemistry of gold extraction (1992)

Historical developments process mineralogy process selection metallurgical development principles of gold hydrometallurgy oxidative pretreatment leaching solution purification and concentration recovery surface chemical methods refining effluent treatment industrial applications.
A dynamic ontology for a dynamic reference work (2007)

The successful deployment of digital technologies by humanities scholars presents computer scientists with a number of unique scientific and technological challenges. The task seems particularly daunting because issues in the humanities are presented in abstract language demanding the kind of subtle interpretation often thought to be beyond the scope of artificial intelligence, and humanities scholars themselves often disagree about the structure of their disciplines. The future of humanities computing depends on having tools for automatically discovering complex semantic relationships among different parts of a corpus. Digital library tools for the humanities will need to be capable of dynamically tracking the introduction of new ideas and interpretations and applying them to older texts in ways that support the needs of scholars and students.
A hierarchical asynchronous replication protocol for large scale systems (2002)

The authors present a new asynchronous replication protocol that is especially suitable for wide area and mobile systems, and allows reads and writes to occur at any replica. Updates reach other replicas using a propagation scheme based on nodes organized into a logical hierarchy. The hierarchical structure enables the scheme to scale well for thousands of replicas, while ensuring reliable delivery. A new service interface is proposed that provides different levels of asynchrony, allowing strong consistency and weak consistency to be integrated into the same framework. Further, the scheme provides the ability to offer different levels of staleness, depending upon the needs of various applications, by querying from different levels of the hierarchy. Also, it allows a selection from a number of reconciliation techniques based on delivery order mechanisms. Restructuring operations are provided to build and reconfigure the hierarchy dynamically without disturbing normal operation. The scheme tolerates transmission failures, node failures and network partitions.
Adjuvant can improve protection induced by OMV vaccine againstNeisseria meningitidisserogroups B/C in neonatal mice (2004)

Meningococcal outer membrane vesicle (OMV) vaccines are weak antigens in infants. This study aimed at investigating alternative adjuvants for induction of functional antibodies in newborn mice. Serogroup B/C anti-meningococcal vaccines, consisting of capsular polysaccharide from serogroup C (PSC) conjugated to OMV from one serogroup B serosubtype prevalent in Brazil, combined with OMV from another prevalent serosubtype, were tested in newborn and adult mice with the following adjuvants: aluminum hydroxide, MPL (monophosphoryl lipid A), Titermax and MF59. Total IgG, IgG avidity index determination and bactericidal assay were performed with sera from immunized mice. Antibodies induced against PSC in newborn mice showed avidity and bactericidal titers, similar to those obtained in adult mice, independently of the adjuvant. Evidence is presented that the inclusion of MF59 enhanced the immune response against OMV in newborn mice.
Amplification of RNAi—Targeting HLA mRNAs (2005)

Posttranscriptional suppression of gene expression can be achieved by introduction of sequence-specific small interfering (si) RNA duplexes and by de novo intracellular synthesis of short sequence-specific double-stranded RNAs. However, achieving desired levels of knockdown is a barrier to successful analytic and therapeutic application. We demonstrate that increasing expression of introduced short hairpin RNA (shRNA) can markedly enhance RNA interference (RNAi) and that this approach can be used to achieve maximal target down-regulation, when the choice of optimal siRNA-binding sites is restricted or when multiple genes are simultaneously targeted and the amount of siRNA is limiting. A dose-dependent RNAi effect was accomplished by placing copies of shRNA under control of the Pol III U6 small nuclear RNA promoter in tandem in a DNA vector. Using this system, we achieved simultaneous down-regulation of expression of classical human leukocyte antigen (HLA) class I genes in cultured and primary human T cells, which might be applied to help circumvent T-cell-mediated rejection of immunogenic and/or HLA-disparate allografts.
Genetic Diversity of the Pneumococcal Capsule: Implications for Molecular-Based Serotyping (2009)

Streptococcus pneumoniae remains an important pathogen despite licensure of a seven-valent pneumococcal protein conjugate vaccine. As a result, serotyping strains remains of paramount importance to both assess the effectiveness of current vaccines and closely monitor for the emergence of nonvaccine strains. Given the limitations of the quellung reaction, both molecular and immunology-based serotyping methods have been pursued. Currently, the most promising assay combines an immunologic assay with multiplex PCR of serotype-specific genes. The key limitation with a molecular-based assay is the plasticity of the pneumococcus, as capsular transformation or point mutations could easily result in serotype misclassification. Based on the currently available techniques, a comprehensive immunology-based assay appears to be the most promising alternative to the quellung reaction. In the future, assays that utilize high-throughput sequencing technology and/or matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) could lead to a novel pneumococcal serotyping method.
Rapid Emergence of Protease Inhibitor Resistance in Hepatitis C Virus (2010)

About 170 million people worldwide are infected with hepatitis C virus (HCV). The current standard therapy leads to sustained viral elimination in only approximately 50% of the treated patients. Telaprevir, an HCV protease inhibitor, has substantial antiviral activity in patients with chronic HCV infection. However, in clinical trials, drug-resistant variants emerge at frequencies of 5 to 20% of the total virus population as early as the second day after the beginning of treatment. Here, using probabilistic and viral dynamic models, we show that such rapid emergence of drug resistance is expected. We calculate that all possible single- and double-mutant viruses preexist before treatment and that one additional mutation is expected to arise during therapy. Examining data from a clinical trial of telaprevir therapy for HCV infection in detail, we show that our model fits the observed dynamics of both drug-sensitive and drug-resistant viruses and argue that therapy with only direct antivirals will require drug combinations that have a genetic barrier of four or more mutations.
Simultaneous frequency and dissipation factor QCM measurements of biomolecular adsorption and cell adhesion (1997)

We have measured the energy dissipation of the quartz crystal microbalance (QCM), operating in the liquid phase, when mono- or multi-layers of biomolecules and biofilms form on the QCM electrode (with a time resolution of ca. 1 s). Examples are taken from protein adsorption, lipid vesicle adsorption and cell adhesion studies. Our results show that even very thin (a few nm) biofilms dissipate a significant amount of energy owing to the QCM oscillation. Various mechanisms for this energy dissipation are discussed. Three main contributions to the measured increase in energy dissipation are considered. (i) A viscoelastic porous structure (the biofilm) that is strained during oscillation, (ii) trapped liquid that moves between or in and out of the pores due to the deformation of the film and (iii) the load from the bulk liquid which increases the strain of the film. These mechanisms are, in reality, not entirely separable, rather, they constitute an effective viscoelastic load. The biofilms can therefore not be considered rigidly coupled to the QCM oscillation. It is further shown theoretically that viscoelastic layers with thicknesses comparable to the biofilms studied in this work can induce energy dissipation of the same magnitude as the measured ones.