gebhart/patrepeval huggingface dataset:
RNAi-based Gene Therapy for Dominant Limb Girdle Muscular Dystrophies (2012)

Limb Girdle Muscular Dystrophy (LGMD) refers to a group of 25 genetic diseases linked by common clinical features, including wasting of muscles supporting the pelvic and shoulder girdles. Cardiac involvement may also occur. Like other muscular dystrophies, LGMDs are currently incurable, but prospective gene replacement therapies targeting recessive forms have shown promise in pre-clinical and clinical studies. In contrast, little attention has been paid to developing gene therapy approaches for dominant forms of LGMD, which would likely benefit from disease gene silencing. Despite the lack of focus to date on developing gene therapies for dominant LGMDs, the field is not starting at square one, since translational studies on recessive LGMDs provided a framework that can be applied to treating dominant forms of the disease. In this manuscript, we discuss the prospects of treating dominantly inherited forms of LGMD with gene silencing approaches.
The Cellulose Microfibril as an Imperfect Array of Elementary Fibrils (1975)

Cellulose microfibrils are viewed as imperfect array of elementary fibrils. We have investigated the possible defects in Valonia cellulose microfibrils, which are such that the microfibrils can be broken into elementary fibrils by deformation, but are not sufficient to allow for a small angle maximum corresponding to the elementary fibril dimension. The microfibril has been constructed by convolution of th elementary fibril with a two dimensional point lattice. Defects have been incorporated in the microfibril, first by introduction of gaps between the elementary fibrils. These regular gaps were then replaced by a statistical distribution of the elementary fibrils about the lattice points, modeled by Hosemann distortions of the first type. The cylindrically averaged transforms of such structures show that significant distortions can be incorporated within the microfibril without producing large scale changes in the equatorial intensity distribution. Larger distortions are necessary before a small angle maximum corresponding to the 35 A elementary fibril is predicted, by which stage the wide angle x-ray pattern is unacceptable.
Total Syntheses of Epothilones A and B via a Macrolactonization-Based Strategy (1997)

The total syntheses of epothilones A (1) and B (2) and several analogues thereof are described. The reported strategy relies on a macrolactonization approach and features selective epoxidation of the macrocycle double bond in precursors 3 and 4 (Scheme 1), respectively, as well as high convergency and flexibility. Building blocks 9−12 and 15 were constructed by asymmetric processes and coupled via Wittig, aldol, and macrolactonization reactions to afford the basic skeleton of epothilones and that of several of their analogues by a relatively short route. The utilization of intermediate 14, obtained via a stereoselective Wittig reaction and its Enders coupling to SAMP hydrazone 13 (Scheme 8), in combination with a stereoselective aldol reaction with the modified substrate 69 (Scheme 10) improved the stereoselectivity and efficiency of the total synthesis of these new and highly potent microtubule binding antitumor agents.
Osteogenic Potential of Human Adipose Tissue-Derived Stromal Cells as an Alternative Stem Cell Source (2004)

Adult bone marrow contains mesenchymal stem cells (bone marrow-derived mesenchymal stem cells; BMSCs) which contribute to the generation of mesenchymal tissue such as bone, cartilage, muscle and adipose. However, using bone marrow as a source of stem cells has the limitation of a low cell number. An alternate source of adult stem cells that could be obtained in large quantities, under local anesthesia, with minimal discomfort would be advantageous. Human adipose tissue obtained by liposuction was processed to obtain a fibroblast-like population of cells or adipose tissue-derived stromal cells (ATSCs). In this study, we compared the osteogenic differentiation of ATSCs with that of BMSCs. Both cell types were cultured in atelocollagen honeycomb-shaped scaffolds with a membrane seal (ACHMS scaffold) for three-dimensional culturing in a specific osteogenic induction medium. Optimal osteogenic differentiation in both cell types, as determined by alkaline phosphatase cytochemistry, secretion of osteocalcin, mineral (calcium phosphate) deposition and scanning electron microscopy, was obtained with the same three-dimensional culture. Furthermore, osteoblastic lining in vivo was examined using ATSC-seeded or BMSC-seeded scaffolds in nude mice. The present results show that ATSCs have a similar ability to differentiate into osteoblasts to that of BMSCs.
Tumor localization of adoptively transferred indium-111 labeled tumor infiltrating lymphocytes in patients with metastatic melanoma. (1989)

Lymphoid cells infiltrating into human tumors can be expanded in vitro in medium containing interleukin-2 (IL-2). Adoptive transfer of these tumor-infiltrating lymphocytes (TIL) mediates potent antitumor effects in murine tumor models. Clinical trials to evaluate the efficacy of these cells in patients with advanced cancer are underway. We have investigated whether infused TIL labeled with indium 111 (111In) oxine can traffic and localize to metastatic deposits of tumor. Six patients with metastatic malignant melanoma who had multiple sites of subcutaneous, nodal, and/or visceral disease were the subjects of the study. The patients received cyclophosphamide 36 hours before receiving the intravenous (IV) infusion of TIL followed by IL-2 IV every eight hours. The distribution and localization of the TIL were evaluated using serial whole body gamma camera imaging, serial blood and urine samplings, and serial biopsies of tumor and normal tissue. 111In-labeled TIL localized to lung, liver, and spleen within two hours after the infusion of activity. Activity in the lung diminished within 24 hours. As early as 24 hours after injection of 111In-labeled TIL, localization of TIL to sites of metastatic deposits was demonstrated in all six patients using either imaging studies or biopsy specimens or both. 111In activity in tumor tissue biopsies ranged from three to 40 times greater than activity in normal tissue. A progressive increase in the radioactive counts at sites of tumor deposit was seen. This study shows that labeled TIL can localize preferentially to tumor, and provides information concerning the possible mechanism of the therapeutic effects of TIL.
High-dose interleukin-2 (HD IL-2) for advanced melanoma: a single center experience from the University of Pittsburgh Cancer Institute (2017)

In this large series of patients spanning more than two decades, OR/CR rates with HD IL-2 were 18.1%/8.0% respectively. Toxicity data was consistent with prior reports. Pre-treatment LDH values and site(s) of metastatic disease may be useful markers to select patients at greater likelihood of benefit to HD IL-2 therapy.
The Scanning Ion-Conductance Microscope (1989)

A scanning ion-conductance microscope (SICM) has been developed that can image the topography of nonconducting surfaces that are covered with electrolytes. The probe of the SICM is an electrolyte-filled micropipette. The flow of ions through the opening of the pipette is blocked at short distances between the probe and the surface, thus, limiting the ion conductance. A feedback mechanism can be used to maintain a given conductance and in turn determine the distance to the surface. The SICM can also sample and image the local ion currents above the surfaces. To illustrate its potential for imaging ion currents through channels in membranes, a topographic image of a membrane filter with 0.80-micrometer pores and an image of the ion currents flowing through such pores are presented.
Evolutionary conservation of apoptosis mechanisms: Lepidopteran and baculoviral inhibitor of apoptosis proteins are inhibitors of mammalian caspase-9 (2000)

We cloned a new inhibitor of apoptosis protein (IAP) homolog, SfIAP, from Spodoptera frugiperda Sf-21 cells, a host of insect baculoviruses. SfIAP contains two baculovirus IAP repeat domains followed by a RING domain. SfIAP has striking amino acid sequence similarity with baculoviral IAPs, CpIAP and OpIAP, suggesting that baculoviral IAPs may be host-derived genes. SfIAP and baculoviral CpIAP inhibit Bax but not Fas-induced apoptosis in human cells. Their apoptosis-suppressing activity in mammalian cells requires both baculovirus IAP repeat and RING domains. Further biochemical data suggest that SfIAP and CpIAP are specific inhibitors of mammalian caspase-9, the pinnacle caspase in the mitochondria/cytochrome c pathway for apoptosis, but are not inhibitors of downstream caspase-3 and caspase-7. Thus the mechanisms by which insect and baculoviral IAPs suppress apoptosis may involve inhibition of an insect caspase-9 homologue. Peptides representing the IAP-binding domain of the Drosophila cell death protein Grim abrogated human caspase suppression by SfIAP and CpIAP, implying evolutionary conservation of the functions of IAPs and their inhibitors.
Role of p53 and ras genes in radiation‐induced transformation of immortalized human epidermal keratinocytes (1994)

Abstract The biological effects of exposure to ionizing radiation have particular relevance to radiation protection and risk assessment. Since most cancers are of epithelial origin, it is important to obtain a better understanding of radiation‐induced oncogenic transformation in this cell type. Our previous studies have demonstrated the potential of ionizing radiations to transform human epidermal keratinocytes (RHEK‐1) [Thraves et al.: Proc Natl Acad Sci USA 87:1174–1177, 1990; Thraves et al.: Carcinogenesis (in press)] and have described the cellular characteristics, saturation density, anchorage‐independent growth, and tumorigenicity of these transformed cells, together with a preliminary determination of the role of cellular ras genes. The present study has expanded these molecular studies to conclude a molecular analysis of all the ras genes and the tumor suppressor gene p53. Single‐strand conformational polymorphism (SSCP) analysis and DNA sequencing demonstrated the absence of point mutations, deletions, and rearrangements in codons 12/13 and 61 in the Ha‐ras or N‐ras genes and exons 4–9 of the p53 tumor suppressor gene. These studies demonstrate that mutations in either the cellular p53 or ras genes do not occur in these immortalized human epithelial cells (RHEK‐1) transformed to a malignant phenotype with ionizing radiation. © Wiley‐Liss, Inc.
Pelvic Positioning Creates Error in CT Acetabular Measurements (2011)

Small changes in pelvic obliquity and tilt were associated with variances in acetabular measurements. The measured changes were directly proportional to the changes in obliquity and tilt, and were additive. Pelvic rotation created no changes in measurement.
Reductive alkylation of lysine residues to alter crystallization properties of proteins. (1997)

Publisher Summary This chapter discusses the reductive alkylation of lysine residues to alter the crystallization properties of proteins. Chemical modification has played an essential role in the development of protein function. The reductive alkylation of lysine residues involves the initial formation of a Schiff base between the ɛ-amino group of a lysine residue and a ketone or aldehyde that is then reduced to a secondary or tertiary amine. In principle, a wide variety of alkyl moieties can be added to an amino group by reductive alkylation. In practice, the majority of cases employing this chemical modification have focused on adding methyl groups using formaldehyde because of the greater reactivity of formaldehyde than other ketones or aldehydes and because this modification has the mildest effect on the biochemical properties of a protein. The protocols described in the chapter are designed for complete modification of all available lysine residues. Amino acid analysis is the best way of determining the degree of modification of the lysine residues after reductive alkylation. It has the advantage of quantitatively defining the number of non-, mono-, di-, and tri-methylated lysine residues. It reveals the presence of any side reactions with other reactive amino acid side chains in a protein.
Phase I Trial of the Oral Antiangiogenesis Agent AG-013736 in Patients With Advanced Solid Tumors: Pharmacokinetic and Clinical Results (2005)

In this study, we have demonstrated clinical activity and safety of AG-013736 in patients with advanced solid tumors and identified the dose for phase II testing. The unique phase I study design allowed early identification of important absorption and metabolic issues critical to phase II testing of this agent.
Tobacco-specific N-Nitrosamines [TSNA] in Green Mature and Processed Tobacco Leaves from India (1987)

Abstract Tobacco-specific N -nitrosamines [TSNA] and tobacco alkaloids were determined in green mature tobacco leaves, sun-dried leaves and processed tobacco from the species N. rustica and N. tabacum cultivated in two different locations. Analyses showed the presence of TSNA in green mature tobacco leaves and the levels of TSNA increased further upon sun-drying and processing. N. rustica showed relatively higher amounts of nornicotine as well as of N’ -nitrosonornicotine [NNN]. A clear correlation between the amount of nicotine and nornicotine and the use of fertilizers was not found.
Time synchronization for wireless sensor networks (2005)

If one assumes I have not gone insane, credit for this may go to my family, who have provided endless emotional support.In particular, I'd like to thank my parents Norton and Sandy, and siblings Franny and David, for tirelessly being there through success and failure
Functional Consequences of Complementarity-determining Region Deactivation in a Multifunctional Anti-nucleic Acid Antibody (2013)

Many murine monoclonal anti-DNA antibodies (Abs) derived from mice models for systemic lupus erythematosus have additional cell-penetration and/or nucleic acid-hydrolysis properties. Here, we examined the influence of deactivating each complementarity-determining region (CDR) within a multifunctional anti-nucleic acid antibody (Ab) that possesses these activities, the catalytic 3D8 single chain variable fragment (scFv). CDR-deactivated 3D8 scFv variants were generated by replacing all of the amino acids within each CDR with Gly/Ser residues. The structure of 3D8 scFv accommodated single complete CDR deactivations. Different functional activities of 3D8 scFv were affected differently depending on which CDR was deactivated. The only exception was CDR1, located within the light chain (LCDR1); deactivation of LCDR1 abolished all of the functional activities of 3D8 scFv. A hybrid Ab, HW6/3D8L1, in which the LCDR1 from an unrelated Ab (HW6) was replaced with the LCDR1 from 3D8, acquired all activities associated with the 3D8 scFv. These results suggest that the activity of a multifunctional 3D8 scFv Ab can be modulated by single complete CDR deactivation and that the LCDR1 plays a crucial role in maintaining Ab properties. This study presents a new approach for determining the role of individual CDRs in multifunctional Abs with important implications for the future of Ab engineering.
The kinetic basis for the stabilization of staphylococcal nuclease by xylose (1997)

The effect of xylose on the rates of folding and unfolding of staphylococcal nuclease (nuclease) have been investigated using fluorescence-detected pressure-jump relaxation kinetics in order to establish the kinetic basis for the observed stabilization of nuclease by this sugar (Frye KJ, Perman CS, Royer CA, 1996, Biochemistry 35:10234-10239). The activation volumes for both folding and unfolding and the equilibrium volume change for folding were all positive. Their values were within experimental error of those reported previously (Vidugiris GJA, Markley JL, Royer CA, 1995, Biochemistry 34:4909-4912) and were independent of xylose concentration. The major effect of xylose concentration was to increase significantly the rate of folding. The large positive activation volume for folding was interpreted previously as indicating that the rate-limiting step in nuclease folding involves dehydration of a significant amount of surface area. A large effect of xylose on the rate constant for folding provides strong support for this interpretation, because xylose, an osmolyte, stabilizes the folded state of proteins through surface tension effects. These studies further characterize the transition state in nuclease folding as lying closer to the folded, rather than the unfolded state along the folding coordinate in terms of the degree of burial of surface area. The image of the transition state that emerges is consistent with a dry molten globule.
Scalable Interconnection and Integration of Nanowire Devices without Registration (2004)

A general strategy for the parallel and scalable integration of nanowire devices over large areas without the need to register individual nanowire−electrode interconnects has been developed. The approach was implemented using a Langmuir−Blodgett method to organize nanowires with controlled alignment and spacing over large areas and photolithography to define interconnects. Centimeter-scale arrays containing thousands of single silicon nanowire field-effect transistors were fabricated in this way and were shown to exhibit both high performance with unprecedented reproducibility and scalability to at least the 100-nm level. Moreover, scalable device characteristics were demonstrated by interconnecting a controlled number of nanowires per transistor in “pixel-like” device arrays. The general applicability of this approach to other nanowire and nanotube building blocks could enable the assembly, interconnection, and integration of a broad range of functional nanosystems.
Efficient gene targeting by homology-directed repair in rat zygotes using TALE nucleases (2014)

The generation of genetically modified animals is important for both research and commercial purposes. The rat is an important model organism that until recently lacked efficient genetic engineering tools. Sequence-specific nucleases, such as ZFNs, TALE nucleases, and CRISPR/Cas9 have allowed the creation of rat knockout models. Genetic engineering by homology-directed repair (HDR) is utilized to create animals expressing transgenes in a controlled way and to introduce precise genetic modifications. We applied TALE nucleases and donor DNA microinjection into zygotes to generate HDR-modified rats with large new sequences introduced into three different loci with high efficiency (0.62%-5.13% of microinjected zygotes). Two of these loci (Rosa26 and Hprt1) are known to allow robust and reproducible transgene expression and were targeted for integration of a GFP expression cassette driven by the CAG promoter. GFP-expressing embryos and four Rosa26 GFP rat lines analyzed showed strong and widespread GFP expression in most cells of all analyzed tissues. The third targeted locus was Ighm, where we performed successful exon exchange of rat exon 2 for the human one. At all three loci we observed HDR only when using linear and not circular donor DNA. Mild hypothermic (30°C) culture of zygotes after microinjection increased HDR efficiency for some loci. Our study demonstrates that TALE nuclease and donor DNA microinjection into rat zygotes results in efficient and reproducible targeted donor integration by HDR. This allowed creation of genetically modified rats in a work-, cost-, and time-effective manner.
Tissue Vibration Induces Carotid Artery Endothelial Dysfunction: A Mechanism Linking Snoring and Carotid Atherosclerosis? (2011)

Carotid arteries subjected to 6 h of continuous peri-carotid tissue vibration displayed endothelial dysfunction, suggesting a direct plausible mechanism linking heavy snoring to the development of carotid atherosclerosis.
Construction of DNA sequences complementary to rat .alpha.1 and .alpha.2 collagen mRNA and their use in studying the regulation of type I collagen synthesis by 1,25-dihydroxyvitamin D (1984)

Type I collagen mRNA from fetal rat calvaria was used as a template for the synthesis of a cDNA that was subsequently inserted in the PstI site of the plasmic vector pBR322 and cloned. Three recombinant plasmids containing type I collagen specific sequences were characterized: p alpha 1R1 is 1600 bp and spans approximately 500 amino acid residues within the triple helical region of alpha 1(I) and p alpha 1R2 is 900 bp in size and covers the entire 3' noncoding and about half of the C-terminal propeptide region of alpha 1(I) collagen mRNA. The third recombinant p alpha 2R2 is 1500 bp and contains alpha 2(I) sequences specific for the entire 3' noncoding and C-terminal propeptide region. Partial nucleic acid sequence data revealed that the decreasing order of amino acid and nucleotide homology to similar regions of the rat cDNA was mouse greater than human greater than chick. Northern hybridization of mRNA after electrophoresis in 0.8% agarose revealed two distinctly different molecular weight patterns characteristic of alpha 1(I) (4.7 and 5.7 kb) and alpha 2(I) (4.2 and 4.5 kb) collagen mRNA when hybridized with the corresponding cDNA probe. Despite the high degree of sequence homology, DNA probes from rat or human produced a significantly reduced hybridization signal when used as an interspecies hybridization probe than to its corresponding mRNA. The rat cDNA probes were used in a dot hybridization assay to measure the type I collagen mRNA content in the fetal rat calvaria.(ABSTRACT TRUNCATED AT 250 WORDS)
Epitopic Analysis of Antigenic Determinants on the Surface of Dengue-2 Virions Using Monoclonal Antibodies * (1985)

The relative binding sites of dengue serotype-specific, dengue subcomplex-specific, dengue complex-specific, flavivirus subgroup-reactive, and flavivirus group-reactive monoclonal antibody preparations were identified by using competitive antibody binding assays. A dengue complex-specific epitope, capable of mediating infection enhancement, was identified on a 20,000 dalton protein found on intracellular virions. The other epitopes were assigned relative positions on the E glycoprotein by competitive antibody binding. These could be grouped into 3 linkage groups based on the ability of some monoclonal antibodies to block contiguous binding sites. Some antibodies were able to increase or "promote" the binding of antibodies from other linkage groups. These results suggest that a continuum of antigenic reactivities exist on the E glycoprotein of the dengue viruses, and that the conformation of this glycoprotein may be altered after antibody binding.
Style transfer for headshot portraits (2014)

Headshot portraits are a popular subject in photography but to achieve a compelling visual style requires advanced skills that a casual photographer will not have. Further, algorithms that automate or assist the stylization of generic photographs do not perform well on headshots due to the feature-specific, local retouching that a professional photographer typically applies to generate such portraits. We introduce a technique to transfer the style of an example headshot photo onto a new one. This can allow one to easily reproduce the look of renowned artists. At the core of our approach is a new multiscale technique to robustly transfer the local statistics of an example portrait onto a new one. This technique matches properties such as the local contrast and the overall lighting direction while being tolerant to the unavoidable differences between the faces of two different people. Additionally, because artists sometimes produce entire headshot collections in a common style, we show how to automatically find a good example to use as a reference for a given portrait, enabling style transfer without the user having to search for a suitable example for each input. We demonstrate our approach on data taken in a controlled environment as well as on a large set of photos downloaded from the Internet. We show that we can successfully handle styles by a variety of different artists.