gebhart/patrepeval huggingface dataset:
The Identification of Neuropeptide Gene Regulatory Elements in Transgenic Mice (2003)

The typical mammalian genome contains 3 × lo9bp of DNA. This amount of DNA is believed to include 3-4 × lo4 unique protein- encoding genes. Even complex, highly specialized cells, such as neurons, express a small fraction, perhaps 20%, of all the possible genes, how- ever. A major problem in neurobiology, therefore, is to characterize the mechanisms involved in neural-specific gene expression. Significant progress has been made in our understanding of the factors that restrict the expression of genes to particular cell lineages. A particularly good example is the growth hormone (GH) gene. Growth hormone belongs to a gene family that includes prolactin and chorionic somatomammotropin. Despite a high degree of homology between these genes derived from a single common ancestral gene, GH is exclusively expressed in one cell type in the mammal, the pitu- itary somatotroph. The first step in defining the molecular basis of somatotroph-specific gene expression was the identification of the minimal nucleotide sequences within the GH gene that confer strict pituitary-specific expression. Utilizing pituitaryderived cell lines trans- fected with reporter genes that contained putative cell-specific human or rat GH gene regulatory sequences, several groups of investigators delineated two binding sites in the promoter region that are essential
New approaches to treatment of primary immunodeficiencies: fixing mutations with chemicals (2008)

Primary immunodeficiencies are monogenic disorders. The characterization and classification of disease-causing mutations facilitate the design and development of new mutation-targeted treatments. To date, using ataxia-telangiectasia (A-T) as a model primary immunodeficiency, the most promising advances have been with chemicals that read through various premature stop codons as well as with antisense oligonucleotides that mask aberrant splice sites. These principles can now be applied to other primary immunodeficiencies.
Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27. (1997)

An autosomal recessive form of juvenile Parkinsonism (AR-JP) (MIM 600116) is a levodopa-responsive Parkinsonism whose pathological finding is a highly selective degeneration of dopaminergic neurons in the zona compacta of the substantia nigra. By linkage analysis of diallelic polymorphism of the Mn-superoxide dismutase gene (SOD2), we found a family with AR-JP showing perfect segregation of the disease with the SOD2 locus. By extending the linkage analysis to 13 families with AR-JP, we discovered strong evidence for the localization of the AR-JP gene at chromosome 6q25.2-27, including the SOD2 locus, with the maximal cumulative pairwise LOD scores of 7.26 and 7.71 at D6S305 (theta = .03) and D6S253 (theta = .02), respectively. Observation of obligate recombination events, as well as multipoint linkage analysis, placed the AR-JP gene in a 17-cM interval between D6S437 and D6S264. Delineation of the AR-JP gene will be an important step toward our understanding of the molecular mechanism underlying selective degeneration of the nigral neurons.
Valence and Conduction Band Densities of States of Metal Halide Perovskites: A Combined Experimental–Theoretical Study (2016)

We report valence and conduction band densities of states measured via ultraviolet and inverse photoemission spectroscopies on three metal halide perovskites, specifically methylammonium lead iodide and bromide and cesium lead bromide (MAPbI3, MAPbBr3, CsPbBr3), grown at two different institutions on different substrates. These are compared with theoretical densities of states (DOS) calculated via density functional theory. The qualitative agreement achieved between experiment and theory leads to the identification of valence and conduction band spectral features, and allows a precise determination of the position of the band edges, ionization energy and electron affinity of the materials. The comparison reveals an unusually low DOS at the valence band maximum (VBM) of these compounds, which confirms and generalizes previous predictions of strong band dispersion and low DOS at the MAPbI3 VBM. This low DOS calls for special attention when using electron spectroscopy to determine the frontier electronic states of lead halide perovskites.
Fused Pyrimidine Based Inhibitors of Phosphodiesterase 7 (PDE7): Synthesis and Initial Structure—Activity Relationships. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Bayesian Inference in the General Linear Model (2002)

10.1002/9780470317105.ch12.abs The prelims comprise: Introduction Simple Linear Regression Multivariate Regression Model Multivariate Analysis of Variance Model Bayesian Inference in the Multivariate Mixed Model
Conformations of complexes between pyrrolo[1,4]benzodiazepines and DNA segments (1986)

The molecular mechanics program AMBER, assisted by CHEMLAB II, was used to model the covalent and noncovalent binding of anthramycin, tomaymycin, and neothramycin A to the hexanucleotide conformation. Structures covalently bonded at N2 of guanine gave excellent fits when placed in either direction in the minor groove. However, energy analysis showed a preference for the direction wherein the side chain points toward the 5' end of the covalently bound strand. This preference agrees with published NMR studies. Noncovalent binding of anthramycin in the minor groove near guanine gave good fits with almost no distortion in the helix, and the reactive center of the ligand was close enough to N2 for subsequent covalent bond formation. Anthramycin also gave a good noncovalent complex near adenine in the minor groove, but binding in the major groove had decreased dispersion attractions. Binding of tomaymycin was similar to that of anthramycin, although the smaller size of tomaymycin resulted in less binding energy. Neothramycin noncovalent binding was characterized by strong electrostatic interactions, partly involving the 3-OH group, and by part of the molecule lying outside the minor groove. AMBER was used for the exploratory design of an anthramycin analogue that theoretically would bind as well as anthramycin but not cause cardiotoxicity. A related study involving anthramycin, tomaymycin, and the pentanucleotide duplex d(AAGAA/TTCTT) was undertaken to evaluate further the ability of AMBER to predict sequence specificity. It indicated a preferred direction of binding toward 5' in the minor groove of the duplex, but rather weak interaction with the noncovalently bound strand. This prediction agreed with experiments on tomaymycin that showed separation of the duplex and alignment of the drug toward the 5' end of the covalently bound strand.
Finite-state control of a trans-femoral (TF) prosthesis (2002)

A nonanalytic (soft) finite-state control was developed for a controlled trans-femoral (TF) prosthesis. The control and actions are performed according to a rule-base written in a natural language. A systematic procedure of developing a knowledge base prosthesis controller and an effective way for estimating the gait speed are presented. The prosthesis prototype with sensing, microcomputer based electronics, and a servo controlled knee damper were integrated and successfully tested in the clinic. The stability to support the body weight, absorption of ground impact, and smooth forward progression reported by the amputee. An improved body support on a bent knee during mid-stance and instant response to a change in walking speed were recorded.
Human embryo research (1991)

This review evaluates recent developments in the application as well as legalization of human embryo research. A number of European countries, including the United Kingdom and Spain, have recently enacted comprehensive legislation to regulate embryo research. Research reviewed here was conducted either with the aim to alleviate certain medical conditions or to improve the low success rates of assisted reproductive technology. Research was usually conducted on embryos that were considered unfit for immediate transfer or unsuitable for cryopreservation. Research projects were aimed at 1) studying the metabolism of the embryo, 2) promoting embryonic viability, 3) assisting fertilization in patients with fertilization disorders, and 4) determining gene disorders in embryos from couples at risk for transmitting genetic disease.
In Vitro and In Vivo Gene Therapy Vector Evolution via Multispecies Interbreeding and Retargeting of Adeno-Associated Viruses (2008)

Adeno-associated virus (AAV) serotypes differ broadly in transduction efficacies and tissue tropisms and thus hold enormous potential as vectors for human gene therapy. In reality, however, their use in patients is restricted by prevalent anti-AAV immunity or by their inadequate performance in specific targets, exemplified by the AAV type 2 (AAV-2) prototype in the liver. Here, we attempted to merge desirable qualities of multiple natural AAV isolates by an adapted DNA family shuffling technology to create a complex library of hybrid capsids from eight different wild-type viruses. Selection on primary or transformed human hepatocytes yielded pools of hybrids from five of the starting serotypes: 2, 4, 5, 8, and 9. More stringent selection with pooled human antisera (intravenous immunoglobulin [IVIG]) then led to the selection of a single type 2/type 8/type 9 chimera, AAV-DJ, distinguished from its closest natural relative (AAV-2) by 60 capsid amino acids. Recombinant AAV-DJ vectors outperformed eight standard AAV serotypes in culture and greatly surpassed AAV-2 in livers of naïve and IVIG-immunized mice. A heparin binding domain in AAV-DJ was found to limit biodistribution to the liver (and a few other tissues) and to affect vector dose response and antibody neutralization. Moreover, we report the first successful in vivo biopanning of AAV capsids by using a new AAV-DJ-derived viral peptide display library. Two peptides enriched after serial passaging in mouse lungs mediated the retargeting of AAV-DJ vectors to distinct alveolar cells. Our study validates DNA family shuffling and viral peptide display as two powerful and compatible approaches to the molecular evolution of novel AAV vectors for human gene therapy applications.
Antimicrobial Peptides Keep Insect Endosymbionts Under Control (2011)

Vertically transmitted endosymbionts persist for millions of years in invertebrates and play an important role in animal evolution. However, the functional basis underlying the maintenance of these long-term resident bacteria is unknown. We report that the weevil coleoptericin-A (ColA) antimicrobial peptide selectively targets endosymbionts within the bacteriocytes and regulates their growth through the inhibition of cell division. Silencing the colA gene with RNA interference resulted in a decrease in size of the giant filamentous endosymbionts, which escaped from the bacteriocytes and spread into insect tissues. Although this family of peptides is commonly linked with microbe clearance, this work shows that endosymbiosis benefits from ColA, suggesting that long-term host-symbiont coevolution might have shaped immune effectors for symbiont maintenance.
Exploring Privileged Structures: The Combinatorial Synthesis of Cyclic Peptides (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Microfluidic Synthesis of Colloidal Silica (2004)

We demonstrate the design, fabrication, and operation of microfluidic chemical reactors for the synthesis of colloidal silica particles. Two reactor configurations are examined: laminar flow reactors and segmented flow reactors. We analyze particle sizes and size distributions and examine their change with varying linear flow velocity and mean residence time. Laminar flow reactors are affected by axial dispersion at high linear velocities, thus leading to wide particle size distributions under these conditions. Gas is used to create a segmented flow, consisting liquid plugs separated by inert gas bubbles. The internal recirculation created in the liquid plugs generates mixing, which eliminates the axial dispersion effects associated with laminar flow reactors and produces a narrow size distribution of silica nanoparticles.
Rat Pancreatic Duct Epithelium Cultured on a Porous Support Coated with Extracellular Matrix (1991)

A method was developed for the isolation and culture of rat pancreatic duct epithelium of predominantly interlobular duct origin. Purified duct epithelial fragments were cultured on a porous support (HATF filters, Millipore) at 37 degrees C in a 1:1 mixture of Dulbecco's Modified Eagle's and Ham's F-12 media supplemented with insulin, cholera toxin, epidermal growth factor, bovine pituitary extract (BPE), and Nu-Serum (Collaborative Research) in a humidified atmosphere of 95% air and 5% CO2. The filters were coated with an extracellular matrix of either rat tail collagen or Matrigel (Collaborative Research), both of which significantly enhanced growth of the duct epithelium in comparison with untreated filters. The cells grew from the tissue fragments as epithelial islands, which merged to form a confluent sheet of epithelium covering at least 80% of the filter within 10 days in culture. The mitotic index of the spreading epithelium increased with time, reaching a maximum of 0.6% on days 3 and 5 and then declining. The epithelial monolayer consisted of tightly packed cells, with a few large cells and a few cells undergoing abnormal mitoses. Fibroblast contamination was negligible. The cells retained carbonic anhydrase activity, consistent with their pancreatic ductal origin and with the maintenance of differentiation in culture. The epithelium could be subcultured but with a low efficiency. A defined, serum-free medium was established with the addition of ethanolamine, bovine serum albumin, and transferrin and the deletion of serum and BPE. The epithelial cells grew nearly as well in this medium as in the serum-containing medium.(ABSTRACT TRUNCATED AT 250 WORDS)
Bacterial Artificial Chromosome Mutagenesis Using Recombineering (2010)

Gene expression from bacterial artificial chromosome (BAC) clones has been demonstrated to facilitate physiologically relevant levels compared to viral and nonviral cDNA vectors. BACs are large enough to transfer intact genes in their native chromosomal setting together with flanking regulatory elements to provide all the signals for correct spatiotemporal gene expression. Until recently, the use of BACs for functional studies has been limited because their large size has inherently presented a major obstacle for introducing modifications using conventional genetic engineering strategies. The development of in vivo homologous recombination strategies based on recombineering in E. coli has helped resolve this problem by enabling facile engineering of high molecular weight BAC DNA without dependence on suitably placed restriction enzymes or cloning steps. These techniques have considerably expanded the possibilities for studying functional genetics using BACs in vitro and in vivo.
Analysis of 1-Year Clinical Outcomes in the SIRIUS Trial (2004)

Placement of the sirolimus-eluting stent results in continued clinical improvement at 1 year after initial implantation, with significant reduction in clinical restenosis as defined by target-lesion revascularization. Between 9 and 12 months, the absolute reduction of clinical restenosis continues to increase. Even in high-risk subsets of patients, there is a 70% to 80% relative reduction in clinical restenosis at 12 months with this drug-eluting stent.
Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. (1985)

Using ferritin-labeled protein A and colloidal gold-labeled anti-rabbit IgG, the fate of the sheep transferrin receptor has been followed microscopically during reticulocyte maturation in vitro. After a few minutes of incubation at 37 degrees C, the receptor is found on the cell surface or in simple vesicles of 100-200 nm, in which the receptor appears to line the limiting membrane of the vesicles. With time (60 min or longer), large multivesicular elements (MVEs) appear whose diameter may reach 1-1.5 micron. Inside these large MVEs are round bodies of approximately 50-nm diam that bear the receptor at their external surfaces. The limiting membrane of the large MVEs is relatively free from receptor. When the large MVEs fuse with the plasma membrane, their contents, the 50-nm bodies, are released into the medium. The 50-nm bodies appear to arise by budding from the limiting membrane of the intracellular vesicles. Removal of surface receptor with pronase does not prevent exocytosis of internalized receptor. It is proposed that the exocytosis of the approximately 50-nm bodies represents the mechanism by which the transferrin receptor is shed during reticulocyte maturation.
Regulation of Retinal Progenitor Cell Differentiation by Bone Morphogenetic Protein 4 Is Mediated by the Smad/Id Cascade (2010)

PURPOSE. Bone morphogenetic proteins (BMPs) are secreted signaling molecules that are implicated in the control of multiple events during mouse eye development. However, little is known about the mechanisms by which BMP signaling regulates these retinal developmental processes. METHODS. Real-time PCR, Western blot, and immunohistochemistry were used to investigate the expression of components of BMP signaling in the mouse retina. Retinal progenitor cells (RPCs) were used to study the effects of BMP4 on retinal cell differentiation and regulation of Id protein expression. RESULTS. Results showed that BMP2, -4, and -7; BMP receptor (BMPRIb) mRNAs; and proteins and downstream signaling molecule Smad1/5/8 proteins were all highly expressed in the mouse retina during the embryonic (E13.5-E18.5) and early postnatal (P)1 stage and that the expression was downregulated in the adult. On stimulation with BMP4, cultured mouse RPCs differentiated into neuronal lineage whereas astrocyte cell differentiation was inhibited. BMP4 mainly stimulated production of retinal ganglion cells (RGCs). Results also revealed that BMPs and BMPRIb were co-localized with inhibitors of differentiation (Id) (mainly Id1 and -3) in RGCs in the adult mouse retina. Exposure of RPCs to BMP4 upregulated Id1-3 expression levels, mediated through the phosphorylation of Smad1/5/8 proteins. CONCLUSIONS. These results suggest that Id genes are one of the potential targets of BMP signaling in the differentiation of RPCs.
Overexpression of the Oxygen Sensors PHD-1, PHD-2, PHD-3, and FIH Is Associated with Tumor Aggressiveness in Pancreatic Endocrine Tumors (2008)

HIF regulatory proteins are highly expressed in PET and their expression is correlated with tumor metastases, tumor recurrence, and prognosis. These molecules that play an important role in the control of hypoxia-induced genes may have a function in the regulation of cellular proliferation and differentiation during endocrine tumorigenesis.
Antiretroviral Activity of the Anti‐CD4 Monoclonal Antibody TNX‐355 in Patients Infected with HIV Type 1 (2004)

Single doses of TNX-355 reduced plasma HIV-1 RNA loads and increased CD4+ T cell counts in HIV-infected subjects. The further assessment of therapeutic potential awaits data from longer-duration trials.
Investigation of a mumps outbreak among university students with two measles–mumps–rubella (MMR) vaccinations, Virginia, September–December 2006 (2009)

Following the clinical diagnosis of the first case of mumps on September 22, 2006 at the University of Virginia (UVA), 52 suspected cases were identified through active surveillance for mumps by the end of December 2006. Samples were collected from 47 students who presented with parotitis despite a documented history of two doses of measles, mumps, and rubella (MMR) vaccine. Six of 47 serum samples (13%) were positive for mumps IgM, and 46/47 specimens were positive for mumps IgG. Endpoint titration of acute phase serum samples from laboratory-confirmed cases did not provide evidence that elevated serum IgG is a consistent marker for infection among cases due to secondary vaccine failure. Buccal swab samples from 39 of the 47 students were tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) and/or viral culture. Mumps virus or mumps RNA was detected in 12 of 39 buccal samples (31%). Genetic analysis of the virus from the outbreak at UVA indicated that the outbreak was not linked to the large mumps outbreak in the Midwestern US that occurred earlier in 2006. Our findings support the use of viral detection to improve laboratory diagnosis of mumps among persons who have received two doses of MMR.
Differences in Paclitaxel and Docetaxel Interactions with Tubulin Detected by Mutagenesis of Yeast Tubulin (2008)

A molecular model showing the yeast tubulin–paclitaxel and tubulin–docetaxel complexes in a mutated form of the protein that contains Asn at position 227 instead of His. The side chain of Asn 227 is able to form an H-bond with the carbonyl oxygen of the paclitaxel benzamide and the docetaxel carbamate groups.
Zn2+ Promotes the Self-Association of Human Immunodeficiency Virus Type-1 Integrase in Vitro (1997)

It has been recently demonstrated that the Mg(2+)-dependent 3'-processing activity of purified human immunodeficiency virus type-1 (HIV-1) integrase is stimulated by the addition of exogenous Zn2+ [Lee, S. P., & Han, M. K. (1996) Biochemistry 35, 3837-3844]. This activation was hypothesized to result from integrase self-association. In this report, we examine the Zn2+ content of purified HIV-1 integrase by atomic absorption spectroscopy and by application of a thiol modification reagent, p-(hydroxymercuri)benzenesulfonate, with a metallochromic indicator, 4-(2-pyridylazo)resorcinol. We find that the Zn2+ content of HIV-1 integrase varies from 0.1 to 0.92 equiv of Zn2+ per monomer depending on the conditions of protein purification. In vitro activity assays, time-resolved fluorescence emission anisotropy, and gel filtration chromatographic analyses all indicate that EDTA yields an apoprotein which is predominantly monomeric and less active with Mg2+. Further, sedimentation equilibrium studies reveal that reconstitution of the apoprotein with Zn2+ results in a monomer-tetramer-octamer transition. These results suggest that Zn2+ promotes a conformation with enhanced oligomerization and thereby stimulates Mg(2+)-dependent 3'-processing. This may also imply that multimers larger than dimers (tetramers and possibly octamers) are required for in vitro activity of integrase in the presence of Zn2+ and Mg2+. It should be noted, however, that the content of Zn2+ did not significantly affect the 3'-processing and strand transfer reactions with Mn2+ in vitro.
Effect of DTPA conjugation on the antigen binding activity and biodistribution of monoclonal antibodies against alpha-fetoprotein. (1985)

Indium-111-(111In) labeled monoclonal antibodies (Ab) prepared with a bifunctional chelating agent, diethylenetriaminepentaacetic acid (DTPA), have been used for the radioimmunoimaging of cancer. In the present experiment, using monoclonal Ab against human alpha-fetoprotein (AFP) as a model, we have studied the effect of DTPA conjugation on the antigen binding activity and the biodistribution in nude mice transplanted with AFP-producing human testicular tumor. In Ab heavily conjugated with DTPA, the Scatchard plot analysis demonstrated that the maximum binding capacity rather than the affinity constant was affected. Under selected conditions, 111In-labeled Ab were made available with almost full retention of the antigen binding activity and scintigrams of nude mice clearly delineated the site of the tumor. However, the number of DTPA molecules incorporated per Ab molecule markedly influenced the in vivo biodistribution as well as the in vitro antigen binding activity.