gebhart/patrepeval huggingface dataset:
Inherited susceptibility to uterine leiomyomas and renal cell cancer (2001)

Herein we report the clinical, histopathological, and molecular features of a cancer syndrome with predisposition to uterine leiomyomas and papillary renal cell carcinoma. The studied kindred included 11 family members with uterine leiomyomas and two with uterine leiomyosarcoma. Seven individuals had a history of cutaneous nodules, two of which were confirmed to be cutaneous leiomyomatosis. The four kidney cancer cases occurred in young (33- to 48-year-old) females and displayed a unique natural history. All these kidney cancers displayed a distinct papillary histology and presented as unilateral solitary lesions that had metastasized at the time of diagnosis. Genetic-marker analysis mapped the predisposition gene to chromosome 1q. Losses of the normal chromosome 1q were observed in tumors that had occurred in the kindred, including a uterine leiomyoma. Moreover, the observed histological features were used as a tool to diagnose a second kindred displaying the phenotype. We have shown that predisposition to uterine leiomyomas and papillary renal cell cancer can be inherited dominantly through the hereditary leiomyomatosis and renal cell cancer (HLRCC) gene. The HLRCC gene maps to chromosome 1q and is likely to be a tumor suppressor. Clinical, histopathological, and molecular tools are now available for accurate detection and diagnosis of this cancer syndrome.
Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype (2010)

Mucopolysaccharidosis type IIIB (MPS IIIB, Sanfilippo syndrome type B) is a lysosomal storage disorder caused by deficiency of the enzyme N-acetyl-α-D-glucosaminidase (NAGLU). Information on the natural course of MPS IIIB is scarce but much needed in view of emerging therapies. To improve knowledge on the natural course, data on all 52 MPS IIIB patients ever identified by enzymatic studies in the Netherlands were gathered. Clinical data on 44 patients could be retrieved. Only a small number (n = 9; 21%) presented with a classical MPS III phenotype; all other patients showed a much more attenuated course of the disease characterized by a significantly slower regression of intellectual and motor abilities. The majority of patients lived well into adulthood. First signs of the disease, usually mild developmental delay, were observed at a median age of 4 years. Subsequently, patients showed a slowing and eventually a stagnation of development. Patients with the attenuated phenotype had a stable intellectual disability for many years. Molecular analysis was performed in 24 index patients. The missense changes p.R643C, p.S612G, p.E634K, and p.L497V were exclusively found in patients with the attenuated phenotype. MPS IIIB comprises a remarkably wide spectrum of disease severity, and an unselected cohort including all Dutch patients showed a large proportion (79%) with an attenuated phenotype. MPS IIIB must be considered in patients with a developmental delay, even in the absence of a progressive decline in intellectual abilities. A key feature, necessitating metabolic studies, is the coexistence of behavioral problems.
Embryonic Stem Cells as a Model to Study Cardiac, Skeletal Muscle, and Vascular Smooth Muscle Cell Differentiation (2003)

Embryonic stem (ES) cells, the undifferentiated cells of early embryos are established as permanent lines (1,2) and are characterized by their self-renewal capacity and the ability to retain their developmental capacity in vivo (3) and in vitro (4–6). The pluripotent properties of ES cells are the basis of gene targeting technologies used to create mutant mouse strains with inactivated genes by homologous recombination (7).
A Mechanistic Understanding of Asphaltene Precipitation from Varying Saturate Concentration Perspective (2015)

Abstract Asphaltene precipitation can severely hamper the petroleum extraction by plugging the pores or precipitation in production lines. Although the effect of temperature and pressure on asphaltene deposition is well known, how the variations in oil composition affect the asphaltene precipitation mechanism requires more clarity. This work investigates the effect of compositional changes on asphaltene stability. The impact of oil composition is explained by preparing pseudo-components by blending the crude oil with their own saturate fractions. A systematic characterization of 11 different bitumen and crude oil samples is carried out on the basis of their density, viscosity, asphaltene content, and asphaltene composition. n-pentane is used to determine the asphaltene content of each sample by following a standard method. The asphaltene composition is then determined with Fourier Transform InfraRed (FTIR) spectroscopy. The asphaltene stability is tested by performing the onset asphaltene precipitation (OAP) tests. The results from the characterization study indicated that there is no direct relationship between the asphaltene content and the density or the viscosity of the bulk samples. However, the FTIR profiles suggest that the polarity of the asphaltene molecules greatly influence the size of the precipitated clusters. The outcomes from the OAP tests were used to decipher the thermodynamic equilibrium state on the mechanism of asphaltene destabilization as per the change in the polar (resins and asphaltenes) to nonpolar (saturates and aromatics), saturates to aromatics, and resins to asphaltenes fraction of the bulk sample. It was observed that the increase in saturates concentration destabilized the asphaltene molecules and resulted in more precipitation. The presence of polar functional groups, as observed from the FTIR of the saturate fraction are believed to cause higher asphaltene precipitation. During oil production, the temperature and pressure changes can lead to asphaltene deposition and alteration in the crude oil chemical composition. A holistic understanding of the thermodynamic equilibrium corresponding to these changes can be achieved by analyzing asphaltene destabilization or restabilization processes, specifically by changing the saturate concentrations. These results are extremely useful to comprehend the asphaltene stabilization mechanism and can improve the accuracy of existing asphaltene models.
Evaluation of Hypromellose Acetate Succinate (HPMCAS) as a Carrier in Solid Dispersions (2004)

The utility of hypromellose acetate succinate (HPMCAS), a cellulosic enteric coating agent, as a carrier in a solid dispersion of nifedipine (NP) was evaluated in comparison with other polymers, including hypromellose (HPMC), hypromellose phthalate (HPMCP), methacrylic acid ethyl acrylate copolymer (MAEA), and povidone (PVP). An X-ray diffraction study showed that the minimum amount of HPMCAS required to make the drug completely amorphous was the same as that of other cellulosic polymers, and less than that in dispersions using non-cellulosic polymers. Hypromellose acetate succinate showed the highest drug dissolution level from its solid dispersion in a dissolution study using a buffer of pH 6.8. This characteristic was unchanged after a storage test at high temperature and high humidity. The inhibitory effect of HPMCAS on recrystallization of NP from a supersaturated solution was the greatest among all the polymers examined. Further, the drug release pattern could be modulated by altering the ratio of succinoyl and acetyl moieties in the polymer chain. Our results indicate that HPMCAS is an attractive candidate for use as a carrier in solid dispersions.
Decreased Expression of Negative Immune Checkpoint VISTA by CD4+ T Cells Facilitates T Helper 1, T Helper 17, and T Follicular Helper Lineage Differentiation in GCA (2019)

Loss of immune checkpoint (IC) Programmed Death-1 (PD-1) and PD-Ligand1 (PD-L1) expression has been implicated in the immunopathology of Giant Cell Arteritis (GCA). The contribution of the negative immune checkpoint V-domain Immunoglobulin-containing suppressor of T cell activation (VISTA) to GCA pathology has not yet been studied. The aim of our study was to investigate if expression of VISTA and other IC molecules by peripheral blood (PB) immune cells is modulated in GCA and at the site of vascular inflammation. In addition, we assessed the effect of VISTA-Ig engagement on <i>in vitro</i> CD4+ T helper (Th) lineage differentiation. To this end, frequencies of monocytes expressing CD80/86, PD-L1, PD-L2, and VISTA were determined in blood samples from 30 GCA patients and 18 matched healthy controls by flow cytometry. In parallel, frequencies of CD4+ cells expressing CD28, Cytotoxic T-Lymphocyte-associated antigen-4 (CTLA-4), PD-1, and VISTA were determined. Immunohistochemistry was employed to detect VISTA, PD-1, and PD-L1-expressing cells in temporal artery biopsies (TABs) diagnostic of GCA. Furthermore, the effect of VISTA-Ig on <i>in vitro</i> CD4+ Th lineage differentiation in patients and controls was determined. Our study shows that frequencies of CD80/CD86+ and VISTA+ monocytes were decreased in treated GCA patients only. Moreover, proportions of PD-1+ and VISTA+ Th cells were significantly decreased in GCA patients. Clear infiltration of VISTA+, PD1+, and PD-L1+ cells was seen in GCA TABs. Finally, VISTA-Ig engagement failed to suppress Th1, Th17, and Tfh lineage development in GCA. Our results indicate that decreased expression of VISTA may facilitate development of pathogenic Th1 and Th17 cells in GCA.
The Warwick Metadata Workshop: A Framework for the Deployment ofResource Description (1996)

This paper presents information regarding work done during the OCLC/UKOLN Warwick Metadata Workshop held in April 1996 at Warwick University, Warwick, U.K. The focus of this workshop was on the problem of the deployment of metadata for networked information resources. The Dublin Core metadata elements, defined at the OCLC/NCSA Metadata Workshop held in March 1995 in Dublin, Ohio, formed the basis for the discussions. The final deliverable was the Warwick Framework, a description of a container architecture for aggregating metadata objects of interchange, as well as descriptions for how to implement this architecture.
Design methodology of FinFET devices that meet IC-Level HBM ESD targets (2008)

A new design methodology for FinFET devices is presented which takes into account all complex dependencies on both layout and process parameters of the electrical ESD device parameters of FinFET gated diodes and NMOS FinFET devices in both parasitic bipolar and active MOS operation mode. This methodology allows optimization towards a given ESD target (area consumption, leakage current, parasitic capacitance,...) while fulfilling several imposed design constraints. KiloVolt HBM levels in FinFETs are demonstrated meeting the full IC-level ESD requirements.
Volumetric depth peeling for medical image display (2006)

<i>Volumetric depth peeling</i> (VDP) is an extension to volume rendering that enables display of otherwise occluded features in volume data sets. VDP decouples occlusion calculation from the volume rendering transfer function, enabling independent optimization of settings for rendering and occlusion. The algorithm is flexible enough to handle multiple regions occluding the object of interest, as well as object self-occlusion, and requires no pre-segmentation of the data set. VDP was developed as an improvement for virtual arthroscopy for the diagnosis of shoulder-joint trauma, and has been generalized for use in other simple and complex joints, and to enable non-invasive urology studies. In virtual arthroscopy, the surfaces in the joints often occlude each other, allowing limited viewpoints from which to evaluate these surfaces. In urology studies, the physician would like to position the virtual camera outside the kidney collecting system and see inside it. By rendering invisible all voxels between the observer's point of view and objects of interest, VDP enables viewing from unconstrained positions. In essence, VDP can be viewed as a technique for automatically defining an optimal data- and task-dependent clipping surface. Radiologists using VDP display have been able to perform evaluations of pathologies more easily and more rapidly than with clinical arthroscopy, standard volume rendering, or standard MRI/CT slice viewing.
Isolation and purification of collagen alpha 1(I) receptor from human platelet membrane. (1982)

EDTA, 0.01 M Tris-HC1, 0.14 M NaCl
The significance of telomerase activation and cellular immortalization in human cancer (2002)

Repression of telomerase in the somatic tissues of humans, and probably other long-lived mammals, appears to have evolved as a powerful protective barrier against cancer. Immortalization in vitro of normal human cells that lack telomerase involves the reactivation of telomerase or, rarely, an alternative (ALT) mechanism for maintaining telomeres. Inactivation of the effectors of replicative senescence, i.e. genes encoding one or more elements of the p16/pRB and/or ARF/p53/p21 anti-proliferative pathways, is required for telomerase depression leading to immortalization. Regulation of telomerase in normal human cells is mediated primarily by transcriptional repression of hTERT, the gene encoding the catalytic subunit of telomerase. Rodent cells do not possess stringent controls on telomerase activity in the soma and this explains why they are so readily immortalized and transformed in culture compared with their human counterparts. Because active telomerase has been found to exist in the proliferative compartments of self-renewing tissues, it is not yet clear whether the telomerase present in 90% of human cancers exists as a consequence of selection of pre-existing telomerase-positive cells during carcinogenesis or through induction of hTERT expression in cells in which it is normally tightly repressed. In support of the latter, chromosome transfer techniques have revealed the presence of genes on normal human chromosomes that are able to extinguish hTERT transcription in cancer cells and induce them to undergo senescence. It is clear that telomerase is obligatory for continuous tumour cell proliferation, clonal evolution and malignant progression. Telomerase therefore represents an attractive target at which to aim new anti-cancer drugs. Results with a variety of telomerase inhibitory strategies in human cancer cells have confirmed that its functional inactivation results in progressive telomere shortening, leading to growth arrest and/or cell death through apoptosis. Promising candidate small molecule inhibitors are beginning to emerge that will form the basis for anti-telomerase drug development.
Enterobacter aerogenes and Enterobacter cloacae; versatile bacterial pathogens confronting antibiotic treatment (2015)

Enterobacter aerogenes and E. cloacae have been reported as important opportunistic and multiresistant bacterial pathogens for humans during the last three decades in hospital wards. These Gram-negative bacteria have been largely described during several outbreaks of hospital-acquired infections in Europe and particularly in France. The dissemination of Enterobacter sp. is associated with the presence of redundant regulatory cascades that efficiently control the membrane permeability ensuring the bacterial protection and the expression of detoxifying enzymes involved in antibiotic degradation/inactivation. In addition, these bacterial species are able to acquire numerous genetic mobile elements that strongly contribute to antibiotic resistance. Moreover, this particular fitness help them to colonize several environments and hosts and rapidly and efficiently adapt their metabolism and physiology to external conditions and environmental stresses. Enterobacter is a versatile bacterium able to promptly respond to the antibiotic treatment in the colonized patient. The balance of the prevalence, E. aerogenes versus E. cloacae, in the reported hospital infections during the last period, questions about the horizontal transmission of mobile elements containing antibiotic resistance genes, e.g., the efficacy of the exchange of resistance genes Klebsiella pneumoniae to Enterobacter sp. It is also important to mention the possible role of antibiotic use in the treatment of bacterial infectious diseases in this E. aerogenes/E. cloacae evolution.
Understanding Internal Consistency Reliability Estimates: A Conceptual Primer on Coefficient Alpha (2001)

Although often ignored, reliability is critical when interpreting study effects and test results. Accordingly, this article focuses on the most commonly used estimate of reliability, internal consistency coefficients, with emphasis on coefficient alpha. An interpretive framework is provided for applied researchers and others seeking a conceptual understanding of these estimates.
Wireless integrated network sensors (WINS): distributed in situ sensing for mission and flight systems (2002)

Wireless Integrated Network Sensors (WINS) form a new distributed information technology of combined sensor, actuator, and processing systems. WINS distributed nodes form autonomous, self-organized, wireless sensing and control networks. WINS nodes include microsensors, signal processing, computation and low power wireless networking. WINS enable distributed measurements for applications ranging from aerospace system condition monitoring to distributed environmental science monitoring. This paper will discuss the enabling technology advances of WINS for mission and flight system in situ sensing. This will include the complete set of technologies, from new MEMS devices through information technology. Finally, a new WINS generation, GlobalWINS, will be described. GlobalWINS has been developed for planetary-wide distribution of science instruments.
The murine Ia alpha chains, E alpha and A alpha, show a surprising degree of sequence homology. (1983)

The I region of the murine major histocompatibility complex codes for a group of glycoproteins, the Ia antigens, thought to be involved in the control of immune responsiveness. Each Ia antigen complex contains a "heavy chain," a "light chain," and the "invariant chain." We describe here the isolation and characterization of genomic and cDNA clones for one of the heavy chains, Ak alpha. The complete nucleotide sequence of the cDNA clone is presented, and the predicted amino acid sequence is compared with that of another alpha chain, Ek alpha. About 50% of the amino acids are identical, a finding somewhat unexpected on the basis of preliminary protein sequence data.
Drug Delivery to the Central Nervous System: General Principles and Relevance to Therapy for Infections of the Central Nervous System (1989)

Drug delivery to the central nervous system (CNS) is of vital concern to the therapy for primary CNS disorders and the development of drug neurotoxicity. The factors influencing drug entry into the CSF include the status of the blood-brain barrier (BBB) and lipid solubility, molecular weight, pKa, protein binding, and removal of the drug from the CSF by an exit pump in the choroid plexus. The most important of these factors is the status of the complex BBB systems. The morphologic equivalent of the BBB and its specialized functions (e.g., transport of D-glucose, amino acids, and ions) are discussed in depth. Methods developed for increasing drug delivery to the CNS by circumvention and/or manipulation of the BBB have included direct injection into the CSF, administration of prodrugs or chemical delivery systems, or reversible "opening" of the BBB by hyperosmotic agents, pentylenetetrazole, etoposide, DMSO, or other agents. The relevance of these general principles to selected examples of CNS infections (i.e., gram-negative aerobic bacillary meningitis and subacute encephalopathy associated with AIDS) is emphasized.
The pharmacokinetics, tissue localization, and metabolic processing of recombinant human hepatocyte growth factor after intravenous administration in rats. (1994)

Hepatocyte growth factor (HGF) is a pluripotent mitogen thought to be involved in liver regeneration. It is synthesized as a single chain promitogen and requires proteolytic processing to a two-chain heterodimeric form for biological activity. The pharmacokinetics and tissue distribution of radioiodinated single chain recombinant human HGF ([125I]rhuHGF) were studied in male Sprague-Dawley rats after an iv bolus dose. Pharmacokinetic parameters were determined from trichloroacetic acid-precipitable radioactivity in serum samples. There was a rapid distribution phase (t1/2 alpha = 3.1 min) and a slower elimination phase (t1/2 beta = 114 min). Tissue distribution was assessed by whole body autoradiography 5, 60, and 1440 min after an iv bolus dose. rhuHGF rapidly distributed to the liver, kidney, adrenal gland, and spleen. The importance of the liver in the rapid clearance and subsequent conversion of single chain pro-rhuHGF to the mitogenically active two-chain form was demonstrated using an isolated rat liver perfusion system. TCA-precipitable radioactivity excreted into the bile (1.0 +/- 0.1%) and released into the venous effluent (38.9 +/- 6.1%) was monitored for 60 min after a portal vein injection. The appearance of radioactivity in both the bile and venous effluent was maximal between 20-35 min. Further characterization of the reduced samples by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed that the two-chain form of [125I]rhuHGF was the predominant form after hepatic perfusion. These studies suggest that the liver plays a major role in the rapid clearance and subsequent activation of pro-rhuHGF in vivo.
Optimization of Recombinant Adeno-Associated Viral Vectors for Human β -Globin Gene Transfer and Transgene Expression (2008)

Therapeutic levels of expression of the beta-globin gene have been difficult to achieve with conventional retroviral vectors without the inclusion of DNase I-hypersensitive site (HS2, HS3, and HS4) enhancer elements. We generated recombinant adeno-associated viral (AAV) vectors carrying an antisickling human beta-globin gene under the control of either the beta-globin gene promoter/enhancer or the erythroid cell-specific human parvovirus B19 promoter at map unit 6 (B19p6) without any enhancer, and tested their efficacy in a human erythroid cell line (K-562) and in primary murine hematopoietic progenitor cells (c-kit(+)lin()). We report here that (1) self-complementary AAV serotype 2 (scAAV2)-beta-globin vectors containing only the HS2 enhancer are more efficient than single-stranded AAV (ssAAV2)-beta-globin vectors containing the HS2+HS3+HS4 enhancers; (2) scAAV2-beta-globin vectors recombine with scAAV2-HS2+HS3+HS4 vectors after dual-vector transduction, leading to transgene expression; (3) scAAV2-beta-globin as well as scAAV1-beta-globin vectors containing the B19p6 promoter without the HS2 enhancer element are more efficient than their counterparts containing the HS2 enhancer/beta-globin promoter; and (4) scAAV2-B19p6-beta-globin vectors in K-562 cells, and scAAV1-B19p6-beta-globin vectors in murine c-kit(+)lin() cells, yield efficient expression of the beta-globin protein. Thus, the combined use of scAAV vectors and the parvovirus B19 promoter may lead to expression of therapeutic levels the beta-globin gene in human erythroid cells, which has implications in the use of these vectors in gene therapy of beta-thalassemia and sickle cell disease.