gebhart/patrepeval huggingface dataset:
Adeno-Associated Virus (AAV) Mediated Dystrophin Gene Transfer Studies and Exon Skipping Strategies for Duchenne Muscular Dystrophy (DMD) (2015)

Duchenne muscular dystrophy (DMD), an X-linked inherited musclewasting disease primarily affecting young boys with prevalence of between1:3,500- 1:5,000, is a rare genetic disease caused by defects in the gene for dystrophin. Dystrophin protein is critical to the stability of myofibers in skeletal and cardiac muscle. There is currently no cure available to ameliorate DMD and/or its patho-physiology. A number of therapeutic strategies including molecular-based therapeutics that replace or correct the missing or nonfunctional dystrophin protein have been devised to correct the patho-physiological consequences induced by dystrophin absence. We will review the current in vivo experimentation status (including preclinical models and clinical trials) for two of these approaches, namely: 1) Adeno-associated virus (AAV) mediated (micro) dystrophin gene augmentation/ supplementation and 2) Antisense oligonucleotide (AON)-mediated exon skipping strategies.
Generative Adversarial Networks as Variational Training of Energy Based Models (2016)

In this paper, we study deep generative models for effective unsupervised learning. We propose VGAN, which works by minimizing a variational lower bound of the negative log likelihood (NLL) of an energy based model (EBM), where the model density $p(\mathbf{x})$ is approximated by a variational distribution $q(\mathbf{x})$ that is easy to sample from. The training of VGAN takes a two step procedure: given $p(\mathbf{x})$, $q(\mathbf{x})$ is updated to maximize the lower bound; $p(\mathbf{x})$ is then updated one step with samples drawn from $q(\mathbf{x})$ to decrease the lower bound. VGAN is inspired by the generative adversarial networks (GANs), where $p(\mathbf{x})$ corresponds to the discriminator and $q(\mathbf{x})$ corresponds to the generator, but with several notable differences. We hence name our model variational GANs (VGANs). VGAN provides a practical solution to training deep EBMs in high dimensional space, by eliminating the need of MCMC sampling. From this view, we are also able to identify causes to the difficulty of training GANs and propose viable solutions. \footnote{Experimental code is available at https://github.com/Shuangfei/vgan}
Proximity operators : So near and yet so far (1995)

Testing of the hypothesis that good precision-recall performance can be based entirely on proximity relationships is a focus of current TREC work at ANU. PADRE&amp;apos;s &amp;quot;Z-mode&amp;quot; method (based on proximity spans) of scoring relevance has been shown to produce reasonable results for hand-crafted queries in the Adhoc section. It is capable of producing equally good results in database merging and routing contexts due to its independence from collection statistics. Further work is needed to determine whether Z-mode is capable of achieving top-flight results. A new approach to automatic query generation designed to work with the shorter TREC-4 queries produced reasonable results relative to other groups but fell short of expectations based on training performance. Investigation of causes is still under way. 1 Introduction The Parallel Document Retrieval Engine (PADRE) has previously demonstrated that full text scanning methods supported by parallel hardware permit powerful query constructors and ...
Xenograft models of head and neck cancers (2009)

Head and neck cancers are among the most prevalent tumors in the world. Despite advances in the treatment of head and neck tumors, the survival of patients with these cancers has not markedly improved over the past several decades because of our inability to control and our poor understanding of the regional and distant spread of this disease. One of the factors contributing to our poor understanding may be the lack of reliable animal models of head and neck cancer metastasis. The earliest xenograft models in which human tumor cells were grown in immunosuppressed mice involved subcutaneous implantation of human head and neck cancer cell lines. Subcutaneous xenograft models have been popular because they are easy to establish, easy to manage, and lend themselves to ready quantitation of the tumor burden. More recently, orthotopic xenograft models, in which the tumor cells are implanted in the tumor site of origin, have been used with greater frequency in animal studies of head and neck cancers. Orthotopic xenograft models are advantageous for their ability to mimic local tumor growth and recapitulate the pathways of metastasis seen in human head and neck cancers. In addition, recent innovations in cell labeling techniques and small-animal imaging have enabled investigators to monitor the metastatic process and quantitate the growth and spread of orthopically implanted tumors. This review summarizes the progress in the development of murine xenograft models of head and neck cancers. We then discuss the advantages and disadvantages of each type of xenograft model. We also discuss the potential for these models to help elucidate the mechanisms of regional and distant metastasis, which could improve our ability to treat head and neck cancers.
Influence of optical probe packaging on a 3D MEMS scanning micro-mirror for optical coherence tomography (OCT) applications (2008)

An optical probe is developed for imaging in an optical coherence tomography (OCT) system. A 3D micro mirror is used for steering the beam from the source to the sample. A GRIN lens, fiber and micro mirror are assembled in a silicon optical bench. The assembled components are housed in the bio-compatible microinjection molded housing. The images obtained using this probe is studied with respect to probe assembly. Tolerance of GRIN lens placement, micro mirror placement on the substrate, deformation of the mirror, housing transparency and housing curvature are studied with respect to the final image from the probe. In this study it is found that a higher mirror curvature affects the depth of focus on the sample and mirror placement reduces the coupling efficiency during the optical assembly.
Incremental Context-Dependent Analysis for Language-Based Editors (1983)

Knowledge of a programming language's grammar allows language-based editors to enforce syntactic correctness at all times during development by restricting editing operations to legitimate modifications ot ~ the program's context-free derivation tree; however, not all language constraints can be enforced in this way because not all features can be described by the context-free formalism. Attribute grammars permit context-dependent language features to be expressed in a modular, declarative fashion and thus are a good basis for specifying language-based editors. Such editors represent programs as attributed trees, Which are modified by operations such as subtree pruning and grafting. Incremental analysis is performed by updating attribute values after every modification. This paper discusses how updating can be carried out and presents several algorithms for the task, including one that is asymptotically optimal in time.
Effect of Carvedilol on Survival in Severe Chronic Heart Failure (2001)

The previously reported benefits of carvedilol with regard to morbidity and mortality in patients with mild-to-moderate heart failure were also apparent in the patients with severe heart failure who were evaluated in this trial.
The −169C/T polymorphism in FCRL3 is not associated with susceptibility to rheumatoid arthritis or systemic lupus erythematosus in a case–control study of Koreans (2006)

The association of the -169C/T SNP in FCRL3 with RA and SLE that was observed in Japanese patients was not replicated in a Korean population.
BLyS and APRIL in rheumatoid arthritis (2005)

The cytokines B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) enhance autoimmune disease by sustaining B cell activation. In RA, B cells contribute to the formation of 3 functionally distinct types of lymphoid microarchitectures in the inflamed synovium: ectopic GCs; T cell-B cell aggregates lacking GC reactions; and unorganized, diffuse infiltrates. We examined 72 tissues representing the 3 types of synovitis for BLyS and APRIL production and for expression of APRIL/BLyS receptors. Biologic effects of BLyS and APRIL were explored by treating human synovium-SCID mouse chimeras with the APRIL and BLyS decoy receptor transmembrane activator and CAML interactor:Fc (TACI:Fc). GC+ synovitis had the highest levels of APRIL, produced exclusively by CD83+ DCs. BLyS was present in similar levels in all tissue types and derived exclusively from CD68+ macrophages. In GC+ synovitis, treatment with TACI:Fc resulted in GC destruction and marked inhibition of IFN-gamma and Ig transcription. In contrast, inhibition of APRIL and BLyS in aggregate and diffuse synovitis left Ig levels unaffected and enhanced IFN-gamma production. These differential immunomodulatory effects correlated with the presence of TACI+ T cells in aggregate and diffuse synovitis and their absence in GC+ synovitis. We propose that BLyS and APRIL regulate B cell as well as T cell function and have pro- and antiinflammatory activities in RA.
Characterization of human monoclonal antibodies directed against hepatitis B surface antigen (1992)

Four hybridoma cell lines stably secreting human monoclonal antibodies directed against hepatitis B surface antigen have been isolated. The monoclonal antibodies have been characterized by determining several allotypes, measuring affinity for HBsAg, binding to two HBsAg subtypes, and kinetics of antibody binding to solid adsorbed antigen. In addition, the relative position of the epitopes have been determined by competition in binding to HBsAg. The results indicate that human anti-HBsAg monoclonal antibodies of quite different properties can be isolated. Pharmacokinetics of one antibody have been measured in two rhesus monkeys. This monoclonal antibody, OST 577, has been compared to hyperimmune gamma globulins in a Bureau of Biologics approved radioimmunoassay. It is expected that these antibodies will be useful in preventing and treating hepatitis B.
The polymerase chain reaction in the diagnosis of vertically transmitted HIV infection (1990)

The presence of HIV-1 DNA sequences in DNA from peripheral blood mononuclear cells (PBMCs) was investigated in a two-stage polymerase chain reaction ('double' PCR) using four sets of nested primers. The PBMCs tested were obtained from 46 children born to HIV-seropositive mothers, seven 'control' children born to HIV-seronegative mothers and seropositive fathers, and 45 healthy adult blood donors who were HIV seronegative. Nine of the children had symptomatic HIV infection and other laboratory features characteristic of HIV infection: all nine were PCR-positive with each set of primers in each of their 22 blood samples tested. The remaining 44 children had no clinical or laboratory evidence of HIV infection, and each of their 50 samples was PCR-negative with each set of primers, as were all blood donor samples. PCR-positive samples were tested in more detail using two of the sets of primers, which spanned hypervariable regions in the env gene. Polyacrylamide gel electrophoresis of DNA amplified from these regions yielded patterns of amplified DNA length variation which were characteristic for each child, and which changed little with time (in serial samples obtained over periods of 3-7 months). This excluded contamination as a cause of PCR positivity. This is the first report of the use of a double PCR for the diagnosis of HIV infection. The results demonstrate the specificity of this PCR method in diagnosis, with failure to reveal in this cohort any cases of vertically transmitted HIV-1 infection in addition to those already confirmed by conventional laboratory techniques.
Endothelial renin-angiotensin pathway: evidence for intracellular synthesis and secretion of angiotensins. (1987)

Cultured bovine aortic endothelial cells (BAEC) contain renin and angiotensinogen. To examine whether angiotensins are synthesized intracellularly and secreted by these cells, we assayed cell extracts as well as serum-free media of intact confluent BAEC. Angiotensins were identified by their retention time on reverse phase high performance liquid chromatography and direct radioimmunoassay. BAEC and their media contain angiotensin II and angiotensin III. The rate of angiotensin accumulation in the media was a nonlinear function of time; the highest rate occurred in the first 15 minutes. The amount of angiotensin II accumulated in 30 minutes exceeded 200% of the intracellular concentration and that of angiotensin III exceeded 500% of the initial intracellular content. Neither renin nor angiotensinogen could be detected in the media. The viability of these cells was supported by low lactic dehydrogenase activity in the media (less than 0.5% of cellular level). These data suggest that BAEC is capable of synthesizing and secreting angiotensins. We postulate that this endothelial-derived angiotensin system may play an important paracrine or autocrine role in influencing local vascular tone.
Percutaneous dermal drug delivery for local pain control. (2006)

Topical anesthetics have evolved from a simple solution of cocaine to creams, ointments, gels, liposomal preparations, and to the latest sophisticated patches and peels. Topical anesthetics are essential for performing diagnostic, therapeutic, and cosmetic dermatology procedures. These anesthetics noninvasively deliver anesthesia in locally required areas. In this review, we present an overview on the mechanism of precutaneous absorption of skin and address the composition, duration of onset of anesthetic effect, uses, and side effects that are applicable for the products. Also discussed are the novel advances of using heat to enhance penetration of the anesthetic as seen in Synera(trade mark) patch and delivery of anesthesia using a peel method as seen in the yet to be US Food and Drug Administration-approved S-Caine peel.
High-Capacity Thermal Desorption Modulators for Gas Chromatography (1988)

A thermal desorption modulator is a short segment of a fused-silica capillary column placed at the head of an analytical column. The concentration of the retained substances flowing continuously through the column can be effectively modulated by varying the temperature of this segment. The purpose of this investigation is to demonstrate the operation and the advantages of high capacity modulators. A continuously flowing stream or a headspace sample can be introduced directly through the modulator. This can be used for multiplex or correlation chromatography to make frequent, reproducible injections over a short period of time. Since the high-capacity modulators have high modulation efficiency, their use results in higher throughput. Volatile components can be modulated using these modulators.
Characterization of the disulfide motif in BNBD-12, an antimicrobial beta-defensin peptide from bovine neutrophils. (1993)

BNBD-12, a prototype beta-defensin peptide from bovine neutrophils, was chosen for determination of the disulfide motif in this family of tridisulfide antimicrobial peptides. Disulfide-containing fragments of BNBD-12 were generated by incubation with trypsin, and the amino acid composition of one tryptic fragment allowed for the assignment of one of the three disulfides. The remaining two disulfides, contained in a 16-residue tryptic oligopeptide, were characterized by amino acid analysis of fragments generated by a single round of Edman degradation which cleaved the Cys-Cys peptide bond present near the carboxyl terminus of BNBD-12. Cleavage of this bond produced two disulfide-containing oligopeptides, the compositions of which provided unambiguous assignments of the disulfides involved. The cystine motif in BNBD-12 differs from that of classical defensins, and indicates that the beta-defensins and defensins must have differently folded chains, though they share several functional properties.
Phentolamine Eye Drops Reverse Pharmacologically Induced Mydriasis in a Randomized Phase 2b Trial (2021)

Phentolamine mesylate ophthalmic solution at 1% reversed medically induced pupil dilation more rapidly than placebo treatment regardless of which mydriatic was used (adrenergic agonists and cholinergic blockers) with a tolerable safety profile.
Contribution of the PD‐1 ligands/PD‐1 signaling pathway to dendritic cell‐mediated CD4+ T cell activation (2006)

Dendritic cells (DC) are extremely proficient inducers of naïve CD4+ T cell activation due to their high expression level of peptide-MHC and an array of accessory molecules involved in cell migration, adhesion and co-signaling, including PD-1 ligand 1 (PD-L1) and PD-1 ligand 2 (PD-L2). Whether PD-L1 and PD-L2 have a stimulatory or inhibitory function is a matter of debate, and could be partially dependent on the model system used. In this study we examined the role of PD-L1 and PD-L2 expressed by DC in naïve CD4+ T cell activation in a more physiologically relevant model system, using OVA-specific T cells in combination with various levels of TCR stimulation. Overexpression of PD-L1 or PD-L2 by DC did not inhibit T cell proliferation, even when B7-1 and B7-2 mediated costimulation was absent, although IL-2 production was consistently decreased. Surprisingly, blocking PD-L1 and PD-L2 with soluble programmed death-1 (sPD-1) also inhibited T cell activation, probably via reverse signaling via PD-L1 and/or PD-L2 into DC, leading to reduced DC maturation. This study suggests a relatively minor contribution of PD-1 ligands in DC-driven CD4+ T cell activation and provides evidence for reverse signaling by PD-L1 and PD-L2 into DC, resulting in a suppressive DC phenotype.
Macromedia Flash MX for Windows and Macintosh (2002)

Introduction. 1. The Flash Authoring Tool. 2. Creating Simple Graphics. 3. Modifying Simple Graphics. 4. Complex Graphics on a Single Layer. 5. Graphics on Multiple Layers. 6. Saving and Reusing Graphic Elements. 7. Using Non-Flash Graphics. 8. Frame-by-Frame Animations. 9. Animation with Motion Tweening. 10. Animation with Shape Tweening. 11. More-Complex Animation Tasks. 12. Interactivity with Simple Frame Actions. 13. Interactivity with Objects. 14. Adding Sound and Video. 15. Introducing Complex Interactivity. 16. Delivering Movies to Your Audience. Appendix A. Keyboard Shortcuts. Index.
Direct (non-vector) transmission of West Nile virus in geese (2003)

During a recent epizootic, losses due to West Nile virus (WNV) infection in young goose flocks were estimated to be far greater than expected if mosquito-borne transmission was the principal route of infection. Contact transmission was investigated experimentally as an alternative explanation. A group of 10, 3-week-old geese were inoculated subcutaneously and placed in one insect-proof room with 20 geese of the same age. A group of 10 geese were housed in an adjacent insect-proof room to serve as an environmental control. All geese in the inoculated group produced antibodies, eight became viraemic and five died between 7 and 10 days after infection. Virus was shed from the cloaca and oral cavity by three geese. Two of the in-contact birds died on days 10 and 17 after infection, and WNV was recovered from another three birds. None of the environmental control group became infected. This result strongly suggests that horizontal transmission of WNV can occur in commercial flocks and may be aggravated if cannibalism and feather-picking of sick geese occur.
Dynamics of bone remodelling: biochemical and pathophysiological basis. (1996)

Renewal of the bone matrix is induced by bone cells called osteoblasts and osteoclasts, which act sequentially on the bone surface. This "remodelling" depends on local factors, such as cytokines and growth factors which play an important role in the bone tissue as mediators of cell-to-cell and matrix-to-cell communication. Growth factors released from the bone matrix during the resorption are responsible for the refilling of the resorption cavity by osteoblasts. Cytokines also mediate locally the effect of several hormones on bone cells. Recent work is concerned with the modulation by oestradiol of osteoblastic cytokines acting on osteoclast differentiation. In mice, an increased production of interleukin-6 production by osteoblasts is responsible for the increased bone resorption occurring after ovariectomy. Other growth factors, such as transforming growth factor-beta, whose secretion is modified by oestradiol, may also be implicated. In women, an increase in cytokine production by blood mononuclear cells is associated with the occurence of menopause and reversed by oestrogen treatment. During osteoporosis and age-related bone changes, changes in the production of insulin-like growth factor I or of one of its binding proteins could be responsible for low bone formation. In addition to their role in bone remodelling, cytokines and growth factors are now implicated in osteoporosis.
Wnt-3a and Dickkopf-1 Stimulate Neurite Outgrowth in Ewing Tumor Cells via a Frizzled3- and c-Jun N-Terminal Kinase-Dependent Mechanism (2008)

Recombinant Wnt-3a stimulated the rapid formation of elongated processes in Ewing sarcoma family tumor (ESFT) cells that were identified as neurites. The processes stained positively for polymerized actin and microtubules as well as synapsin I and growth-associated protein 43. Inhibition of the Wnt receptor, Frizzled3 (Fzd3), with antiserum or by short interfering RNA (siRNA) markedly reduced neurite extension. Knockdown of Dishevelled-2 (Dvl-2) and Dvl-3 also suppressed neurite outgrowth. Surprisingly, disruption of the Wnt/Fzd/lipoprotein receptor-related protein (LRP) complex and the associated beta-catenin signaling by treating cells either with the Wnt antagonist Dickkopf-1 (Dkk1) or LRP5/LRP6 siRNA enhanced neuritogenesis. Neurite outgrowth induced by Dkk1 or with LRP5/LRP6 siRNA was inhibited by secreted Fzd-related protein 1, a Wnt antagonist that binds directly to Wnt. Moreover, Dkk1 stimulation of neurite outgrowth was blocked by Fzd3 siRNA. These results suggested that Dkk1 shifted endogenous Wnt activity from the beta-catenin pathway to Fzd3-mediated, noncanonical signaling that is responsible for neurite formation. In particular, c-Jun amino-terminal kinase (JNK) was important for neurite outgrowth stimulated by both Wnt-3a and Dkk1. Our data demonstrate that Fzd3, Dvl, and JNK activity mediate Wnt-dependent neurite outgrowth and that ESFT cell lines will be useful experimental models for the study of Wnt-dependent neurite extension.
Supersized contorted aromatics (2013)

We describe here the synthesis and electronic device properties of a new type of polycyclic aromatic molecule, the contorted octabenzocircumbiphenyl (c-OBCB). Contorted polycyclic aromatic hydrocarbons (PAHs) are promising small active molecules for organic devices. We present two different methods to synthesize c-OBCB derivatives that allow the smooth incorporation of functional groups. The material has a highly contorted exterior with six 4-helicenes and two 5-helicenes around the exterior of the expanded core of the aromatic. With appropriate sidechains, the material is soluble in common organic solvents and forms thin films. In thin films, the tetradodecyloxy-substituted c-OBCB self-assembles to form the active layer in organic field effect transistors. It is a hole transporting organic semiconductor. In the transistors, the c-OBCB forms good contact with source and drain contacts made from graphene. The c-OBCB self-assembles into a heterojunction from solution with phenyl-C70-butyric acid methyl ester (PC70BM). We observed power conversion efficiencies of ∼2.9 % under 100 mW cm−2 illumination at a 1 : 4 weight ratio of the c-OBCB relative to PC70BM. The c-OBCB is shape complementary to the ball shaped PC70BM.