gebhart/patrepeval huggingface dataset:
Precision and error of three‐dimensional phenotypic measures acquired from 3dMD photogrammetric images (2005)

The genetic basis for complex phenotypes is currently of great interest for both clinical investigators and basic scientists. In order to acquire a thorough understanding of the translation from genotype to phenotype, highly precise measures of phenotypic variation are required. New technologies, such as 3D photogrammetry are being implemented in phenotypic studies due to their ability to collect data rapidly and non-invasively. Before these systems can be broadly implemented, the error associated with data collected from images acquired using these technologies must be assessed. This study investigates the precision, error, and repeatability associated with anthropometric landmark coordinate data collected from 3D digital photogrammetric images acquired with the 3dMDface System. Precision, error due to the imaging system, error due to digitization of the images, and repeatability are assessed in a sample of children and adults (n = 15). Results show that data collected from images with the 3dMDface System are highly repeatable and precise. The average error associated with the placement of landmarks is sub-millimeter; both the error due to digitization and due to the imaging system are very low. The few measures showing a higher degree of error include those crossing the labial fissure, which are influenced by even subtle movement of the mandible. These results suggest that 3D anthropometric data collected using the 3dMDface System are highly reliable and, therefore, useful for evaluation of clinical dysmorphology and surgery, analyses of genotype-phenotype correlations, and inheritance of complex phenotypes.
Transcriptome transfer provides a model for understanding the phenotype of cardiomyocytes (2011)

We show that the transfer of the adult ventricular myocyte (AVM) transcriptome into either a fibroblast or an astrocyte converts the host cell into a cardiomyocyte. Transcriptome-effected cardiomyocytes (tCardiomyocytes) display morphologies, immunocytochemical properties, and expression profiles of postnatal cardiomyocytes. Cell morphology analysis shows that tCardiomyoctes are elongated and have a similar length-to-width ratio as AVMs. These global phenotypic changes occur in a time-dependent manner and confer electroexcitability to the tCardiomyocytes. tCardiomyocyte generation does not require continuous overexpression of specific transcription factors; for example, the expression level of transcription factor Mef2c is higher in tCardiomyocytes than in fibroblasts, but similar in tCardiomyocytes and AVMs. These data highlight the dominant role of the gene expression profile in developing and maintaining cellular phenotype. The transcriptome-induced phenotype remodeling-generated tCardiomyocyte has significant implications for understanding and modulating cardiac disease development.
Hybridization effects and metallicity in small radius carbon nanotubes (1994)

Hybridization of the ${\mathrm{\ensuremath{\sigma}}}^{\mathrm{*}}$ and ${\mathrm{\ensuremath{\pi}}}^{\mathrm{*}}$ states of the graphene network is shown to be as important as band-folding effects in determining the metallicity of small radius carbon nanotubes. Using detailed plane-wave ab initio pseudopotential local density functional (LDA) calculations, we find that the electronic properties of small tubes are significantly altered from those obtained in previous tight-binding calculations. Strongly modified low-lying conduction band states are introduced into the band gap of insulating tubes because of strong ${\mathrm{\ensuremath{\sigma}}}^{\mathrm{*}\mathrm{\ensuremath{-}}}$${\mathrm{\ensuremath{\pi}}}^{\mathrm{*}}$ hybridization. As a result, the LDA gaps of some tubes are lowered by more than 50%, and a tube previously predicted to be semiconducting is shown to be metallic.
Effect of Silica Nanoparticle Content on the Structure and Electrostatic Bonding of PEDOT:PSS (2012)

Conducting poly(3,4-ethylenedioxythiophene):poly(styrene-4-sulfonate) (PEDOT:PSS) containing hydroxyl surface rich SiO2 nanoparticles were investigated. Rearrangement and bonding of PEDOT:PSS were affected by the content of SiO2 nanoparticles, which resulted in the modification of an electronic band structure and electrical characteristics. A slight decrease in work function and a shift of the highly occupied molecular orbital edge to the Fermi level were induced by SiO2 nanoparticle addition. The current path was also tuned by SiO2 nanoparticles and resistance of the composite film was diminished. SiO2 nanoparticles affect electrostatic bonding between PEDOT:PSS and doping of PEDOT as well as increase the packing density of PEDOT:PSS.
A Band of Surgeons, a Long Healing Line (2010)

Far removed from modern perceptions of cosmetic surgery, plastic and craniofacial surgery largely began centuries ago with efforts to redeem the destruction and loss from battlefield violence. Successive generations of surgeons responding with compassion to the functional and aesthetic loss of those wounded in war have achieved the progress that benefits 21st century patients. Although the historic role of war has to a degree been supplanted by jet travel, electronic communications, and academic medical centers, leadership continues to be the primary force responsible for advances. This article outlines the evolution of modern craniofacial surgery in 4 phases described by the Latin terms pluresartes, plurestelae, pluraloca, and pluresfontes.
SHORTFINDER: a graphical CAD tool for locating net-to-net shorts in VLSI chip layouts (1990)

Locating the geometrical features causing shorts is often the most vexing problem faced during the layout verification process. A description is given of an interactive CAD tool called Shortfinder that enables the user to find VLSI layout errors resulting in electrical shorts between complex nets quickly and with minimal effort. This is accomplished by displaying a cycle-free shortest electrical path between two points indicated by the user on a graphical display of the layout. Shortfinder was implemented as a modular enhancement to an existing layout viewing program; its data structures and algorithms are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Gene disruption of a G4-DNA-dependent nuclease in yeast leads to cellular senescence and telomere shortening. (1995)

The yeast gene KEM1 (also named SEP1/DST2/XRN1/RAR5) produces a G4-DNA-dependent nuclease that binds to G4 tetraplex DNA structure and cuts in a single-stranded region 5' to the G4 structure. G4-DNA generated from yeast telomeric oligonucleotides competitively inhibits the cleavage reaction, suggesting that this enzyme may interact with yeast telomeres in vivo. Homozygous deletions of the KEM1 gene in yeast block meiosis at the pachytene stage, which is consistent with the hypothesis that G4 tetraplex DNA may be involved in homologous chromosome pairing during meiosis. We conjectured that the mitotic defects of kem1/sep1 mutant cells, such as a higher chromosome loss rate, are also due to failure in processing G4-DNA, especially at telomeres. Here we report two phenotypes associated with a kem1-null allele, cellular senescence and telomere shortening, that provide genetic evidence that G4 tetraplex DNA may play a role in telomere functioning. In addition, our results reveal that chromosome ends in the same cells behave differently in a fashion dependent on the KEM1 gene product.
Adverse reactions after large-scale treatment of onchocerciasis with ivermectin: combined results from eight community trials. (1989)

Eight community trials were carried out by the Onchocerciasis Control Programme in West Africa to determine the safety of the new microfilaricide ivermectin during large-scale treatment of onchocerciasis. The trial areas were located in eight different countries and varied greatly in endemicity level; a total of 50,929 persons were treated and monitored for 72 hours. Overall treatment coverage was 60% of the census population, the main reasons for non-treatment being the exclusion criteria. Of those treated, 9% reported with adverse reactions, 2.4% with moderate reactions, and 0.24% with severe reactions. Most reactions were reported during the first day of follow-up, the most frequent severe reaction being severe symptomatic postural hypotension (in 49 cases). Three cases of severe dyspnoea were life-threatening but their relationship with ivermectin treatment is uncertain. The incidence of adverse reactions was directly related to skin microfilarial load and was highest in the foci with the highest endemicity levels. Treatment resulted in 98% reductions in mean microfilarial loads at all endemicity levels. The benefit of treatment largely compensated for the discomfort due to adverse reactions, which were all transient and managed successfully. Ivermectin thus appears to be sufficiently safe for large-scale treatment but monitoring by resident nurses for at least 36 hours is recommended.
Effect of Overexpressing the Transcription Factor E2F2 on Cell Cycle Progression in Rabbit Corneal Endothelial Cells (2004)

Overexpression of the transcription factor E2F2 in nonproliferating rabbit corneal endothelial cells induces cell cycle progression without inducing significant apoptosis.
Vaccination with the Recombinant Major Outer Membrane Protein Elicits Antibodies to the Constant Domains and Induces Cross-Serovar Protection against Intranasal Challenge with Chlamydia trachomatis (2013)

To determine the ability of the major outer membrane protein (MOMP) to elicit cross-serovar protection, groups of mice were immunized by the intramuscular (i.m.) and subcutaneous (s.c.) routes with recombinant MOMP (rMOMP) from Chlamydia trachomatis serovars D (UW-3/Cx), E (Bour), or F (IC-Cal-3) or Chlamydia muridarum strain Nigg II using CpG-1826 and Montanide ISA 720 VG as adjuvants. Negative-control groups were immunized i.m. and s.c. with Neisseria gonorrhoeae recombinant porin B (Ng-rPorB) or i.n. with Eagle's minimal essential medium (MEM-0). Following vaccination, the mice developed antibodies not only against the homologous serovar but also against heterologous serovars. The rMOMP-vaccinated animals also mounted cell-mediated immune responses as assessed by a lymphoproliferative assay. Four weeks after the last immunization, mice were challenged i.n. with 10(4) inclusion-forming units (IFU) of C. muridarum. The mice were weighed for 10 days and euthanized, and the number of IFU in their lungs was determined. At 10 days postinfection (p.i.), mice immunized with the rMOMP of C. muridarum or C. trachomatis D, E, or F had lost 4%, 6%, 8%, and 8% of their initial body weight, respectively, significantly different from the negative-control groups (Ng-rPorB, 13%; MEM-0, 19%; P < 0.05). The median number of IFU recovered from the lungs of mice immunized with C. muridarum rMOMP was 0.13 × 10(6). The median number of IFU recovered from mice immunized with rMOMP from serovars D, E, and F were 0.38 × 10(6), 7.56 × 10(6), and 11.94 × 10(6) IFU, respectively. All the rMOMP-immunized animals had significantly less IFU than the Ng-rPorB (40 × 10(6))- or MEM-0 (70 × 10(6))-immunized mice (P < 0.05). In conclusion, vaccination with rMOMP can elicit protection against homologous and heterologous Chlamydia serovars.
Stromal and vascular invasion in an human in vitro bladder cancer model. (1997)

In transitional cell carcinoma (TCC) of the urinary bladder, disease spread may occur through local invasion of the bladder wall and/or via hematogenous dissemination. Although the metastatic phenotype is well studied, little is known about the mechanisms that determine and regulate secondary dispersion via stromal and vascular routes. The aim of this study was to develop an in vitro system to study TCC invasion using normal human urinary tract stroma in organ culture. Human de-epithelialized urinary tract stromas were seeded with established human TCC cell lines (RT4, RT112, and EJ) and maintained in organ culture at an air-liquid interface for up to 8 weeks. The composite tissues were analyzed immunohistochemically using antibodies to a proliferation-associated antigen, cell adhesion molecules, extracellular matrix components, and cytokeratin isotypes. The phenotype of TCC cell lines maintained as monolayer cultures were compared with the composite tissues to assess the regulatory effects of the stroma. On a normal urothelial stroma, the TCC cell lines proliferated and underwent a degree of differentiation related to the grade of the original tumor. RT4 cells formed a stratified epithelium with low proliferation, some characteristics of urothelial differentiation, and no evidence of stromal invasion over the 8-week culture period. RT12 cells formed a stratified epithelium with limited differentiation and by 2 weeks showed intravasation of the subepithelial capillary bed. Anaplastic EJ cells did not stratify but diffusely invaded the stromal matrix and the superficial vasculature. In conclusion, the urothelial stroma can support cytodifferentiation in vitro and influence the behavior of malignant TCC cells. The model has application for determining genetic and epigenetic factors that influence whether a tumor progresses by local and/or hematogenous spread. Furthermore, it may offer a useful approach in evaluating prognostic and diagnostic markers and strategies for preventing invasion.
Molecular-Level Control over Surface Order in Self-Assembled Monolayer Films of Thiols on Gold (1988)

Long-chain omegahydroxyalkanethiols [HS(CH(2))nOH] coordinate to gold surfaces through the sulfur atom and produce ordered, hydrophilic monolayers in which the hydroxyl groups are exposed at the outer surface. Coadsorption of two omega-hydroxyalkanethiols of different chain lengths n resulted in the formation of a monolayer having a disordered surface region that was markedly less hydrophilic than the homogeneous, hydroxylic surface formed from either pure compound. By controlling the composition of the monolayer, it was also possible to control simultaneously the degree of order in the surface and its hydrophilicity. In the monolayers containing a mixture of alkanethiol components, these components apparently did not phase-segregate into macroscopic islands, but were dispersed on a molecular scale. assistance and many useful discussions.
Liposomal Delivery Systems: Design Optimization and Current Applications (2016)

The liposome, a closed phospholipid bilayered vesicular system, has received considerable attention as a pharmaceutical carrier of great potential over the past 30 years. The ability of liposomes to encapsulate both hydrophilic and hydrophobic drugs, coupled with their biocompatibility and biodegradability, make liposomes attractive vehicles in the field of drug delivery. In addition, great technical advances such as remote drug loading, triggered release liposomes, ligand-targeted liposomes, liposomes containing combinations of drugs, and so on, have led to the widespread use of liposomes in diverse areas as delivery vehicles for anti-cancer, bio-active molecules, diagnostics, and therapeutic agents. In this review, we summarize design optimization of liposomal systems and invaluable applications of liposomes as effective delivery systems.
Downregulation of amyloid precursor protein inhibits neurite outgrowth in vitro. (1995)

The amyloid precursor protein (APP) is a transmembrane protein expressed in several cell types. In the nervous system, APP is expressed by glial and neuronal cells, and several lines of evidence suggest that it plays a role in normal and pathological phenomena. To address the question of the actual function of APP in normal developing neurons, we undertook a study aimed at blocking APP expression using antisense oligonucleotides. Oligonucleotide internalization was achieved by linking them to a vector peptide that translocates through biological membranes. This original technique, which is very efficient and gives direct access to the cell cytosol and nucleus, allowed us to work with extracellular oligonucleotide concentrations between 40 and 200 nM. Internalization of antisense oligonucleotides overlapping the origin of translation resulted in a marked but transient decrease in APP neosynthesis that was not observed with the vector peptide alone, or with sense oligonucleotides. Although transient, the decrease in APP neosynthesis was sufficient to provoke a distinct decrease in axon and dendrite outgrowth by embryonic cortical neurons developing in vitro. The latter decrease was not accompanied by changes in the spreading of the cell bodies. A single exposure to coupled antisense oligonucleotides at the onset of the culture was sufficient to produce significant morphological effects 6, 18, and 24 h later, but by 42 h, there were no remaining significant morphologic changes. This report thus demonstrates that amyloid precursor protein plays an important function in the morphological differentiation of cortical neurons in primary culture.
A single C. elegans PUF protein binds RNA in multiple modes (2009)

PUF proteins specifically bind mRNAs to regulate their stability and translation. Here we focus on the RNA-binding specificity of a C. elegans PUF protein, PUF-11. Our findings reveal that PUF-11 binds RNA in multiple modes, in which the protein can accommodate variable spacings between two distinct recognition elements. We propose a structural model in which flexibility in the central region of the protein enables the protein to adopt at least two distinct structures, one of which results in base flipping.
Computational Design of Antiviral RNA Interference Strategies That Resist Human Immunodeficiency Virus Escape (2005)

Recently developed antiviral strategies based upon RNA interference (RNAi), which harnesses an innate cellular system for the targeted down-regulation of gene expression, appear highly promising and offer alternative approaches to conventional highly active antiretroviral therapy or efforts to develop an AIDS vaccine. However, RNAi is faced with several challenges that must be overcome to fully realize its promise. Specifically, it degrades target RNA in a highly sequence-specific manner and is thus susceptible to viral mutational escape, and there are also challenges in delivery systems to induce RNAi. To aid in the development of anti-human immunodeficiency virus (anti-HIV) RNAi therapies, we have developed a novel stochastic computational model that simulates in molecular-level detail the propagation of an HIV infection in cells expressing RNAi. The model provides quantitative predictions on how targeting multiple locations in the HIV genome, while keeping the overall RNAi strength constant, significantly improves efficacy. Furthermore, it demonstrates that delivery systems must be highly efficient to preclude leaving reservoirs of unprotected cells where the virus can propagate, mutate, and eventually overwhelm the entire system. It also predicts how therapeutic success depends upon a relationship between RNAi strength and delivery efficiency and uniformity. Finally, targeting an essential viral element, in this case the HIV TAR region, can be highly successful if the RNAi target sequence is correctly selected. In addition to providing specific predictions for how to optimize a clinical therapy, this system may also serve as a future tool for investigating more fundamental questions of viral evolution.
A strategy for risk mitigation of antibodies with fast clearance (2012)

A majority of human therapeutic antibody candidates show pharmacokinetic properties suitable for clinical use, but an unexpectedly fast antibody clearance is sometimes observed that may limit the clinical utility. Pharmacokinetic data in cynomolgus monkeys collected for a panel of 52 antibodies showed broad distribution of target-independent clearance values (2.4-61.3 mL/day/kg), with 15 (29%) having clearance > 10 mL/day/kg. Alteration in the interaction with the recycling FcRn receptor did not account for the faster than expected clearance observed for the antibodies; off-target binding was presumed to account for the fast clearance. We developed an assay based on ELISA detection of non-specific binding to baculovirus particles that can identify antibodies having increased risk for fast clearance. This assay can be used during lead generation or optimization to identify antibodies with increased risk of having fast clearance in both humans and cynomolgus monkeys, and thus increase the likelihood of obtaining a suitable drug candidate.
Ursodeoxycholic Acid for Patients With Primary Biliary Cirrhosis: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials Using Bayesian Approach as Sensitivity Analyses (2007)

This updated systematic review did not demonstrate any benefit of UDCA on mortality and mortality or liver transplantation in patients with PBC.
Decreased plasma concentrations of apolipoprotein M in sepsis and systemic inflammatory response syndromes (2012)

During sepsis and SIRS, the plasma concentrations of apoM decrease dramatically, the degree of decrease reflecting the severity of the disease. As a carrier for barrier-protective S1P in HDL, the decrease in apoM could contribute to the increased vascular leakage observed in sepsis and SIRS.
Protein Tyrosine Kinase Structure and Function (2000)

Tyrosine phosphorylation is one of the key covalent modifications that occurs in multicellular organisms as a result of intercellular communication during embryogenesis and maintenance of adult tissues. The enzymes that carry out this modification are the protein tyrosine kinases (PTKs), which catalyze the transfer of the phosphate of ATP to tyrosine residues on protein substrates. Phosphorylation of tyrosine residues modulates enzymatic activity and creates binding sites for the recruitment of downstream signaling proteins. Two classes of PTKs are present in cells: the transmembrane receptor PTKs and the nonreceptor PTKs. Because PTKs are critical components of cellular signaling pathways, their catalytic activity is strictly regulated. Over the past several years, high-resolution structural studies of PTKs have provided a molecular basis for understanding the mechanisms by which receptor and nonreceptor PTKs are regulated. This review will highlight the important results that have emerged from these structural studies.
Nucleotide sequence of the mitochondrial 5S rRNA gene from lupine (Lupinus luteus) (1992)

A lupine mitochondrial clone containing 5S rRNA gene is characterized. The gene is located on the same strand as 18S rRNA and separated from it by 190 nucleotides. The intergenic region in different plants shows high degree of homology. In the case of lupine and soybean 43 nucleotides upstream of 5S rRNA gene exhibits 100% of homology. Comparisons of lupine 5S rRNA gene sequence with other plant mitochondrial 5S rRNA genes displays high degree of homology (from 89.8% to 95.8%).