gebhart/patrepeval huggingface dataset:
A Simple Approach of Estimating the Shear Strength Parameters for Unsaturated Soil-Aggregate Systems (2003)

This paper presents the results of a study that was performed to evaluate fronds of shear strength parameters in stabilization of unbound soil-aggregate systems based on the theory of unsaturated soil mechanics. Two important shear strength parameters, effective cohesion and effective angle of internal friction were estimated by the proposed approach using the results from suction measurements and unconfined compressive strength test. In addition, the effect of different addition rates of stabilizing agent was compared. Due to the stabilization process, an increase in suction potential on engineering properties of geomaterials was observed by using dielectric constant measurements. In conclusion, the results from this study show that the proposed approach can be simply used for predicting shear strength parameters of the stabilized geomaterials.
Proteins and DNA elements essential for the CRISPR adaptation process in Escherichia coli (2012)

The clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR/Cas) constitute a recently identified prokaryotic defense mechanism against invading nucleic acids. Activity of the CRISPR/Cas system comprises of three steps: (i) insertion of alien DNA sequences into the CRISPR array to prevent future attacks, in a process called 'adaptation', (ii) expression of the relevant proteins, as well as expression and processing of the array, followed by (iii) RNA-mediated interference with the alien nucleic acid. Here we describe a robust assay in Escherichia coli to explore the hitherto least-studied process, adaptation. We identify essential genes and DNA elements in the leader sequence and in the array which are essential for the adaptation step. We also provide mechanistic insights on the insertion of the repeat-spacer unit by showing that the first repeat serves as the template for the newly inserted repeat. Taken together, our results elucidate fundamental steps in the adaptation process of the CRISPR/Cas system.
Robust and accurate skeletal rigging from mesh sequences (2014)

We introduce an example-based rigging approach to automatically generate linear blend skinning models with skeletal structure. Based on a set of example poses, our approach can output its skeleton, joint positions, linear blend skinning weights, and corresponding bone transformations. The output can be directly used to set up skeleton-based animation in various 3D modeling and animation software as well as game engines. Specifically, we formulate the solving of a linear blend skinning model with a skeleton as an optimization with joint constraints and weight smoothness regularization, and solve it using an iterative rigging algorithm that (i) alternatively updates skinning weights, joint locations, and bone transformations, and (ii) automatically prunes redundant bones that can be generated by an over-estimated bone initialization. Due to the automatic redundant bone pruning, our approach is more robust than existing example-based rigging approaches. Furthermore, in terms of rigging accuracy, even with a single set of parameters, our approach can soundly outperform state of the art methods on various types of experimental datasets including humans, quadrupled animals, and highly deformable models.
Presence and Distribution of Cholinergic Nerves in Rat Mediastinal Brown Adipose Tissue (2004)

Brown adipose tissue (BAT) is richly provided with sympathetic noradrenergic nerves but is believed to lack a parasympathetic nerve supply. Acetylcholine is the predominant transmitter of postganglionic parasympathetic nerves. The vesicular acetylcholine transporter (VAChT) resides in synaptic vesicles of cholinergic nerve terminals and is used as a marker for peripheral cholinergic nerves. We sought cholinergic nerves in rat BAT using VAChT immunohistochemistry (IHC) on cryosections of interscapular, cervical, mediastinal, and perirenal depots. Mediastinal BAT was the sole depot provided with putative parasympathetic perivascular and parenchymal cholinergic nerves. The absence of vasoactive intestinal peptide-positive nerves suggested their nature as pure cholinergic fibers. By confocal microscopy, both cholinergic and noradrenergic nerves were detected in mediastinal BAT. Cold exposure and fasting led to increased density of VAChT-positive fibers and of noradrenergic sympathetic nerves at morphometry. The unexpected double innervation of mediastinal BAT may explain the inhibitory influence on thermogenesis observed after systemic injection of muscarinic antagonists in rats, and raises questions about the physiological role of its cholinergic nerve supply.
Molecular cloning and characterization of human WNT8A (2001)

WNT - beta-catenin - TCF pathway is involved in carcinogenesis and fetal development. Xenopus wnt-8 is one of the most potent Wnts with the capacity to activate beta-catenin - TCF pathway in the Xenopus axis duplication assay. Here, we have cloned and characterized WNT8A, a novel human homologue of Xenopus wnt-8. The WNT8A gene, consisting of at least 6 exons, was found to encode a 351-amino-acid polypeptide with the N-terminal signal peptide, three N-linked glycosylation sites, and conserved amino-acid residues of the WNT family. WNT8A showed 63.2% total-amino-acid identity to WNT8B. C-terminal region of WNT8A, WNT8B, WNT2, WNT2B1 and WNT2B2 were longer than that of other WNTs. Among various normal human tissues and 34 human cancer cells lines, the 3.5-kb WNT8A mRNA was detected only in a human teratocarcinoma cell line NT2. These results strongly suggest that WNT8A might be implicated in development of early embryos as well as germ cell tumors through activation of the WNT - beta-catenin - TCF pathway.
Hyperbranched polyphenylene and hyperbranched polyesters: new soluble, three-dimensional, reactive polymers (1995)

Hyperbranched polymers prepared by step-growth polymerization of ABx monomers carry a very large number of reactive groups at their numerous chain-ends as well as throughout the macromolecule. These hyperbranched polymers are characterized by very high solubilities and unusually low solution viscosities when compared to linear analogs. This is a result of their globular shape and lack of crystallinity. The preparation and selected properties of two types of hyperbranched polymers, polyphenylene and polyesters, is discussed.
Salivary biomarker development using genomic, proteomic and metabolomic approaches (2012)

The use of saliva as a diagnostic sample provides a non-invasive, cost-efficient method of sample collection for disease screening without the need for highly trained professionals. Saliva collection is far more practical and safe compared with invasive methods of sample collection, because of the infection risk from contaminated needles during, for example, blood sampling. Furthermore, the use of saliva could increase the availability of accurate diagnostics for remote and impoverished regions. However, the development of salivary diagnostics has required technical innovation to allow stabilization and detection of analytes in the complex molecular mixture that is saliva. The recent development of cost-effective room temperature analyte stabilization methods, nucleic acid pre-amplification techniques and direct saliva transcriptomic analysis have allowed accurate detection and quantification of transcripts found in saliva. Novel protein stabilization methods have also facilitated improved proteomic analyses. Although candidate biomarkers have been discovered using epigenetic, transcriptomic, proteomic and metabolomic approaches, transcriptomic analyses have so far achieved the most progress in terms of sensitivity and specificity, and progress towards clinical implementation. Here, we review recent developments in salivary diagnostics that have been accomplished using genomic, transcriptomic, proteomic and metabolomic approaches.
Production of recombinant proteins in Mycobacterium smegmatis for structural and functional studies (2014)

Protein production using recombinant DNA technology has a fundamental impact on our understanding of biology through providing proteins for structural and functional studies. Escherichia coli (E. coli) has been traditionally used as the default expression host to over-express and purify proteins from many different organisms. E. coli does, however, have known shortcomings for obtaining soluble, properly folded proteins suitable for downstream studies. These shortcomings are even more pronounced for the mycobacterial pathogen Mycobacterium tuberculosis, the bacterium that causes tuberculosis, with typically only one third of proteins expressed in E. coli produced as soluble proteins. Mycobacterium smegmatis (M. smegmatis) is a closely related and non-pathogenic species that has been successfully used as an expression host for production of proteins from various mycobacterial species. In this review, we describe the early attempts to produce mycobacterial proteins in alternative expression hosts and then focus on available expression systems in M. smegmatis. The advantages of using M. smegmatis as an expression host, its application in structural biology and some practical aspects of protein production are also discussed. M. smegmatis provides an effective expression platform for enhanced understanding of mycobacterial biology and pathogenesis and for developing novel and better therapeutics and diagnostics.
Analysis of genomic sequences of 95 papillomavirus types: uniting typing, phylogeny, and taxonomy (1995)

Our aim was to study the phylogenetic relationships of all known papillomaviruses (PVs) and the possibility of establishing a supratype taxonomic classification based on this information. Of the many detectably homologous segments present in PV genomes, a 291-bp segment of the L1 gene is notable because it is flanked by the MY09 and MY11 consensus primers and contains highly conserved amino acid residues which simplify sequence alignment. We determined the MY09-MY11 sequences of human PV type 20 (HPV-20), HPV-21, HPV-22, HPV-23, HPV-24, HPV-36, HPV-37, HPV-38, HPV-48, HPV-50, HPV-60, HPV-70, HPV-72, HPV-73, ovine (sheep) PV, bovine PV type 3 (BPV-3), BPV-5, and BPV-6 and created a database which now encompasses HPV-1 to HPV-70, HPV-72, HPV-73, seven yet untyped HPV genomes, and 15 animal PV types. Three additional animal PVs were analyzed on the basis of other sequence data. We constructed phylogenies based on partial L1 and E6 gene sequences and distinguished five major clades that we call supergroups. One of them unites 54 genital PV types, which can be further divided into eleven groups. The second supergroup has 24 types and unites most PVs that are typically found in epidermodysplasia verruciformis patients but also includes several types typical of other cutaneous lesions, like HPV-4. The third supergroup unites the six known ungulate fibropapillomaviruses, the fourth includes the cutaneous ungulate PVs BPV-3, BPV-4, and BPV-6, and the fifth includes HPV-1, HPV-41, HPV-63, the canine oral PV, and the cottontail rabbit PV. The chaffinch PV and two rodent PVs, Micromys minutus PV and Mastomys natalensis PV, are left ungrouped because of the relative isolation of each of their lineages. Within most supergroups, groups formed on the basis of cladistic principles unite phenotypically similar PV types. We discuss the basis of our classification, the concept of the PV type, speciation, PV-host evolution, and estimates of their rates of evolution.
Organizing DNA Origami Tiles into Larger Structures Using Preformed Scaffold Frames (2011)

Structural DNA nanotechnology utilizes DNA molecules as programmable information-coding polymers to create higher order structures at the nanometer scale. An important milestone in structural DNA nanotechnology was the development of scaffolded DNA origami in which a long single-stranded viral genome (scaffold strand) is folded into arbitrary shapes by hundreds of short synthetic oligonucleotides (staple strands). The achievable dimensions of the DNA origami tile units are currently limited by the length of the scaffold strand. Here we demonstrate a strategy referred to as "superorigami" or "origami of origami" to scale up DNA origami technology. First, this method uses a collection of bridge strands to prefold a single-stranded DNA scaffold into a loose framework. Subsequently, preformed individual DNA origami tiles are directed onto the loose framework so that each origami tile serves as a large staple. Using this strategy, we demonstrate the ability to organize DNA origami nanostructures into larger spatially addressable architectures.
Human Papillomavirus Infection Requires Cell Surface Heparan Sulfate (2001)

Using pseudoinfection of cell lines, we demonstrate that cell surface heparan sulfate is required for infection by human papillomavirus type 16 (HPV-16) and HPV-33 pseudovirions. Pseudoinfection was inhibited by heparin but not dermatan or chondroitin sulfate, reduced by reducing the level of surface sulfation, and abolished by heparinase treatment. Carboxy-terminally deleted HPV-33 virus-like particles still bound efficiently to heparin. The kinetics of postattachment neutralization by antiserum or heparin indicated that pseudovirions were shifted on the cell surface from a heparin-sensitive into a heparin-resistant mode of binding, possibly involving a secondary receptor. Alpha-6 integrin is not a receptor for HPV-33 pseudoinfection.
Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection (2000)

Recent advances in cDNA and oligonucleotide DNA arrays have made it possible to measure the abundance of mRNA transcripts for many genes simultaneously. The analysis of such experiments is nontrivial because of large data size and many levels of variation introduced at different stages of the experiments. The analysis is further complicated by the large differences that may exist among different probes used to interrogate the same gene. However, an attractive feature of high-density oligonucleotide arrays such as those produced by photolithography and inkjet technology is the standardization of chip manufacturing and hybridization process. As a result, probe-specific biases, although significant, are highly reproducible and predictable, and their adverse effect can be reduced by proper modeling and analysis methods. Here, we propose a statistical model for the probe-level data, and develop model-based estimates for gene expression indexes. We also present model-based methods for identifying and handling cross-hybridizing probes and contaminating array regions. Applications of these results will be presented elsewhere.
JAK/STAT Pathways in Cytokine Signaling and Myeloproliferative Disorders: Approaches for Targeted Therapies (2010)

Hematopoiesis is the cumulative result of intricately regulated signaling pathways that are mediated by cytokines and their receptors. Studies conducted over the past 10 to 15 years have revealed that hematopoietic cytokine receptor signaling is largely mediated by a family of tyrosine kinases termed Janus kinases (JAKs) and their downstream transcription factors, termed STATs (signal transducers and activators of transcription). Aberrations in these pathways, such as those caused by the recently identified JAK2(V617F) mutation and translocations of the JAK2 gene, are underlying causes of leukemias and other myeloproliferative disorders. This review discusses the role of JAK/STAT signaling in normal hematopoiesis as well as genetic abnormalities associated with myeloproliferative and myelodisplastic syndromes. This review also summarizes the status of several small molecule JAK2 inhibitors that are currently at various stages of clinical development. Several of these compounds appear to improve the quality of life of patients with myeloproliferative disorders by palliation of disease-related symptoms. However, to date, these agents do not seem to significantly affect bone marrow fibrosis, alter marrow histopathology, reverse cytopenias, reduce red cell transfusion requirements, or significantly reduce allele burden. These results suggest the possibility that additional mutational events might be associated with the development of these neoplasms, and indicate the need for combination therapies as the nature and significance of these additional molecular events is better understood.
How does cachexia influence survival in cancer, heart failure and other chronic diseases? (2007)

Future trials to improve prognosis in patients with cachexia will require a global definition of cachexia and identification of key underlying mechanisms. Results with neurohormonal antagonists are intriguing, and clinical use of these agents would be feasible. While searching for treatments for full-blown cachexia, we should also aim to identify treatments directed at the causes in order to prevent its development.
Schedule dependency of antitumor activity in combination therapy with capecitabine/5'-deoxy-5-fluorouridine and docetaxel in breast cancer models. (2001)

Docetaxel and capecitabine are being prescribed for the treatment of breast cancer. In this study, we tried to identify the optimal administration schedule in combination therapy with these anticancer drugs in human cancer xenograft models. Capecitabine was given p.o. daily for 2 weeks (days 1-14), whereas docetaxel was given i.v. on day 1, day 8, or day 15 in a 3-week regimen to the mice bearing MX-1 human breast cancer xenograft. The combination showed better antitumor efficacy than the monotherapy of either agent in either dosing regimen. However, the most potent and synergistic activity was observed when docetaxel was given on day 8. This potent effect appears to be characteristic of the combination of docetaxel with capecitabine or its intermediate metabolite 5'-deoxy-5-fluorouridine (doxifluridine; 5'-dFUrd). Docetaxel given on day 8 showed a potent effect in combination with 5'-dFUrd, but a much weaker effect was observed in combination with 5-fluorouracil or UFT, a fixed combination of tegafur and uracil. Better efficacy was also observed in the MAXF401 human breast cancer xenograft and in the mouse A755 mammary tumor when docetaxel was given at the middle of the capecitabine or 5'-dFUrd treatment rather than other dosing regimens. In contrast, the efficacy in WiDr human colon cancer xenograft was somewhat better when docetaxel was given on day 1. One possible explanation for the synergy is that docetaxel up-regulates tumor levels of thymidine phosphorylase, the enzyme essential for the activation of capecitabine and 5'-dFUrd to 5-fluorouracil. In fact, docetaxel up-regulated the thymidine phosphorylase levels 4.8- and 1.9-fold in the WiDr and MX-1 models, respectively. However, it did not significantly up-regulate in the MAXF401 and A755 models in which a potent combination effect was observed as well. Other mechanisms, particularly those for the synergy with docetaxel given at the middle during capecitabine/5'-dFUrd administration, would also exist. Based on these observations, clinical studies on the day 8 combination regimen with docetaxel and capecitabine/5'-dFUrd are warranted.
Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood (2013)

Kaposi sarcoma (KS), a human herpes virus 8 (HHV-8; also called KSHV)-induced endothelial tumor, develops only in a small fraction of individuals infected with HHV-8. We hypothesized that inborn errors of immunity to HHV-8 might underlie the exceedingly rare development of classic KS in childhood. We report here autosomal recessive OX40 deficiency in an otherwise healthy adult with childhood-onset classic KS. OX40 is a co-stimulatory receptor expressed on activated T cells. Its ligand, OX40L, is expressed on various cell types, including endothelial cells. We found OX40L was abundantly expressed in KS lesions. The mutant OX40 protein was poorly expressed on the cell surface and failed to bind OX40L, resulting in complete functional OX40 deficiency. The patient had a low proportion of effector memory CD4(+) T cells in the peripheral blood, consistent with impaired CD4(+) T cell responses to recall antigens in vitro. The proportion of effector memory CD8(+) T cells was less diminished. The proportion of circulating memory B cells was low, but the antibody response in vivo was intact, including the response to a vaccine boost. Together, these findings suggest that human OX40 is necessary for robust CD4(+) T cell memory and confers apparently selective protective immunity against HHV-8 infection in endothelial cells.
Chimeric (α/β + α)-Peptide Ligands for the BH3-Recognition Cleft of Bcl-x L :  Critical Role of the Molecular Scaffold in Protein Surface Recognition (2005)

Molecules that bind to specific surface sites on proteins are of great interest from both fundamental and practical perspectives. We are exploring a ligand development strategy that is based on oligomers with discrete folding propensities ("foldamers"); we target a specific cleft on the cancer-associated protein Bcl-xL because this system is well characterized structurally. In vivo, this cleft binds to alpha-helical segments (BH3 domains) of other proteins. We evaluated several types of helical foldamer, built entirely from beta-amino acid residues or from mixtures of alpha- and beta-amino acid residues, and ultimately identified foldamers in the latter class that bind very tightly to Bcl-xL. Our results suggest that combining different types of foldamer backbones will be an effective and general strategy for creating high-affinity and specific ligands for protein surface sites.
An Introduction to Quadrupole Ion Trap Mass Spectrometry (1997)

A concise introduction is presented to the theory and application of quadrupole ion trap mass spectrometry. The presentation of the theoretical treatment is based on a demonstration of the equivalence of the force acting on an ion in a quadrupole field and the force derived from the Mathieu equation; this equivalence permits the application of the solutions of Mathieu’s equation to the confinement of gaseous ions. Resonant excitation, collision-induced dissociation, mass spectrometry, tandem mass spectrometry and chemical ionization are discussed in the context of analytical applications. Sample calculations of the trapping parameters qz and βz, the axial secular frequency, mass range, mass range extension and the magnitude of the potential well depth are given. © 1997 by John Wiley & Sons, Ltd.
Cyclic polyesters: synthetic approaches and potential applications (2010)

The synthetic strategies that have been developed for the preparation of cyclic polyesters are reviewed. While linear and branched polyesters are used extensively for biomedical and materials applications, the synthetic difficulty of preparing cyclic polyesters has limited their exploration. Recently synthetic methodologies have been developed which compliment previous techniques, and promise to increase the availability of cyclic polyesters for future studies. The relative advantages and disadvantages of each approach are discussed, as well as some of the unique physical properties demonstrated by cyclic polymers.