gebhart/patrepeval huggingface dataset:
Distinct functions for Aldh1 and Raldh2 in the control of ligand production for embryonic retinoid signaling pathways (1999)

During vertebrate embryogenesis retinoic acid (RA) synthesis must be spatiotemporally regulated in order to appropriately stimulate various retinoid signaling pathways. Various forms of mammalian aldehyde dehydrogenase (ALDH) have been shown to oxidize the vitamin A precursor retinal to RA in vitro. Here we show that injection of Xenopus embryos with mRNAs for either mouse Aldh1 or mouse Raldh2 stimulates RA synthesis at low and high levels, respectively, while injection of human ALDH3 mRNA is unable to stimulate any detectable level of RA synthesis. This provides evidence that some members of the ALDH gene family can indeed perform RA synthesis in vivo. Whole-mount immunohistochemical analyses of mouse embryos indicate that ALDH1 and RALDH2 proteins are localized in distinct tissues. RALDH2 is detected at E7.5–E10.5 primarily in trunk tissue (paraxial mesoderm, somites, pericardium, midgut, mesonephros) plus transiently from E8.5–E9.5 in the ventral optic vesicle and surrounding frontonasal region. ALDH1 is first detected at E9.0–E10.5 primarily in cranial tissues (ventral mesencephalon, dorsal retina, thymic primordia, otic vesicles) and in the mesonephros. As previous findings indicate that embryonic RA is more abundant in trunk rather than cranial tissues, our findings suggest that Raldh2 and Aldh1 control distinct retinoid signaling pathways by stimulating high and low RA biosynthetic activities, respectively, in various trunk and cranial tissues. Dev. Genet. 25:353–364, 1999. © 1999 Wiley-Liss, Inc.
SERS of Semiconducting Nanoparticles (TiO2 Hybrid Composites) (2009)

Raman scattering of molecules adsorbed on the surface of TiO(2) nanoparticles was investigated. We find strong enhancement of Raman scattering in hybrid composites that exhibit charge transfer absorption with TiO(2) nanoparticles. An enhancement factor up to approximately 10(3) was observed in the solutions containing TiO(2) nanoparticles and biomolecules, including the important class of neurotransmitters such as dopamine and dopac (3,4-dihydroxy-phenylacetic acid). Only selected vibrations are enhanced, indicating molecular specificity due to distinct binding and orientation of the biomolecules coupled to the TiO(2) surface. All enhanced modes are associated with the asymmetric vibrations of attached molecules that lower the symmetry of the charge transfer complex. The intensity and the energy of selected vibrations are dependent on the size and shape of nanoparticle support. Moreover, we show that localization of the charge in quantized nanoparticles (2 nm), demonstrated as the blue shift of particle absorption, diminishes SERS enhancement. Importantly, the smallest concentration of adsorbed molecules shows the largest Raman enhancements suggesting the possibility for high sensitivity of this system in the detection of biomolecules that form a charge transfer complex with metal oxide nanoparticles. The wavelength-dependent properties of a hybrid composite suggest a Raman resonant state. Adsorbed molecules that do not show a charge transfer complex show weak enhancements probably due to the dielectric cavity effect.
Tools for Teaching Gas Separation Using Polymers (2003)

This article describes analytical and web-based models of gas separation using polymer membranes. Emphasis is placed on using simple analytical models to develop physical insight and a more powerful, web-based simulation tool to addres realistic examples of gas separation using polymer membranes. Several examples are provided to serve as in-class exercises or homework problems.
Regulation of Immune Responses of the Intestinal Mucosa (1996)

The largest lymphoid organ in the body, the intestine, is also the most intriguing and complex. At its root, the gastrointestinal immune system must permit the absorption of nutrients while protecting against invasion of pathogens. In the process, it must sort through vast antigenic challenges and orchestrate an immune response appropriate to the occasion. Whereas the general outline of mucosal immunity has been defined with respect to the phenotype of the immune cells that compose the mucosal immune system, the ontogeny of these immune cells, and the regulation of IgA responses, the details that control mucosal T cell activation and suppression that coordinate this elaborate mucosal network continue to perplex. This review highlights unique aspects of T cell regulation within the intraepithelial lymphocyte (IEL) and lamina propria lymphocyte (LPL) compartments when compared with lymphocytes in the periphery. In general, IEL are largely extrathymically derived, have a limited TCR repertoire capable of recognizing common microbiologic Ags, and demonstrate predominantly cytolytic functions. LPL are thymically derived, highly activated lymphocytes with predominantly Th2 phenotype. LPL activation is distinct from classic memory T cells in their CD2/CD28 predominance that likely contributes to limiting TCR/CD3-mediated signals in the mucosa. Ag presentation in the gut may involve nonclassical, nonpolymorphic class I-like molecules expressed by epithelial cells that may positively select extrathymically derived lymphocyte populations as well as tolerize self-reactive lymphocytes. These special features of the mucosal immune system are integrated to downregulate immune responses to ubiquitous lumenal Ags.
Experimental Simulation of Contaminant Deposition on a Film Cooled Turbine Vane Pressure Side With a Trench (2011)

An important issue in the use of coal- or biomass-derived synthetic gaseous (syngas) fuels is the deposition of contaminants on film cooled turbine surfaces, which alter cooling and aerodynamic performance and increase material degradation. The current study applied a new experimental technique that simulated the key physical aspects of contaminant deposition on a film cooled turbine vane. The depositing contaminants were modeled in a wind tunnel facility with a spray of molten wax droplets of a size range that matched the Stokes number of the contaminant particles in engine conditions. Most experiments were performed using a vane model with a thermal conductivity selected such that the model had the same Biot number of an actual engine airfoil, resulting in a cooler surface temperature. Some experiments were performed using an approximately adiabatic model for comparison. The film cooling design consisted of three rows of showerhead cooling at the leading edge and one row of body film cooling holes on the pressure side. Two designs of pressure side body film cooling holes were considered: a standard design of straight, cylindrical holes and an advanced design of “trenched” cooling holes in which the hole exits were situated in a recessed, transverse trench. The results showed thin deposits formed in the trench, with the thickest deposits on its downstream wall between coolant jets. Adiabatic film effectiveness levels were essentially unchanged by the presence of deposits for either film configuration. Deposit formation was strongly influenced by the model surface temperature with cooler surfaces inhibiting deposition. There was evidence of a threshold surface temperature above which deposits became significantly thicker.
Local Drug Infiltration Analgesia During Knee Surgery to Reduce Postoperative Pain in Rats (2016)

Our animal study suggests that clinical trials with LIA combinations of local anesthetic, nonsteroidal anti-inflammatory drug, and corticosteroid might be useful for reducing postoperative pain after knee surgery, with the nonsteroidal anti-inflammatory drug having the greatest effect.Perioperative physicians should consider delivering LIA earlier during the procedure as opposed to solely at the time of wound closure.
Abstract 2864: Acetylation regulates TET2 stability and enzymatic activity (2015)

Abstract DNA methylation, one of the key epigenetic modifications in the mammalian genome, plays fundamental roles in development and disease. Although DNA methylation and DNA methyltransferases (DNMTs) have been studied intensively, our knowledge about DNA demethylation is just starting to emerge. The Ten-eleven translocation (TET) family of proteins are newly identified methylcytosine dioxygenases/demethylases that can oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), and promote DNA demethylation either passively through DNA replication, or actively via thymine DNA glycosylase (TDG)-mediated base excision repair. TET-mediated DNA demethylation has also been shown to play important roles in diverse biological processes and tumorigenesis. Human TET2 is frequently mutated in myeloid malignancies, while loss of 5hmC and TETs expressions have been broadly observed in many other cancer types. Recent studies suggested that TETs may be regulated by microRNAs and calpain proteases, but, overall, the regulation of TET activities is not well outlined. Here we show, in human ovarian cancer cells, that TET2 activity may be significantly modulated by post-translational modifications. TET2 is acetylated by p300/CBP at K110/111, and this acetylation can be reversed by HDAC1/2 and SIRT1/2 deacetylases. Acetylation increases TET2 stability by protecting it from ubiquitination and proteasome-mediated degradation. Interestingly, DNMT1 physically associates with and stabilizes TET2 protein, and a TET2 acetylation deficient mutant (2KR) disrupts this association, indicating that acetylation of TET2 may stimulate DNMT1 binding which prevents TET2 from degradation. In addition, we show that acetylation increases TET2 enzymatic activity. Treatment of cells with HDAC inhibitors TSA/NAM, or knocking down HDAC1/2, significantly increases global 5hmC levels. Consistent with these latter observations, the 2KR mutant almost completely abolishes TET2 catalytic activity, and this mutant protein is less efficient in forming dimer with wild type TET2. Thus acetylation events may increase the activity of TET2 through enhanced dimerization of the protein. Taken together, our study reveals a novel acetylation-dependent regulatory mechanism controlling the function of TET2. Citation Format: Yang Zhang, Yi Cai, Wenbing Xie, Hariharan Easwaran, Stephen B. Baylin. Acetylation regulates TET2 stability and enzymatic activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2864. doi:10.1158/1538-7445.AM2015-2864
2D measurements of cup orientation are less reliable than 3D measurements (2015)

Errors in version in 2D were due to the difficulty in delineating the cup rim, which was obscured by a large-diameter metal head of the same radio-opacity. This can be overcome with 3D analysis. The present study demonstrates that measurements using EBRA have poor agreement and are less reliable than those with 3D-CT when measuring cup version and inclination in MoM hips.
Techniques for operational data warehousing (2004)

Traditionally, data warehouses have been used to analyze historical data. Recently, there has been a growing trend to use data warehouses to support real-time decision-making about an enterprise's day-to-day operations. The needs for improved query and update performance are two challenges that arise from this new application of a data warehouse. To address these needs, new data warehouse functionality is needed including: (1) better access to early query results while queries are running and (2) making the information stored in a data warehouse as fresh as possible. 
For the first problem, we introduce a non-blocking parallel hash ripple join algorithm to support interactive queries in a parallel DBMS. Compared to previous work, our parallel hash ripple join algorithm (1) combines parallelism with sampling to speed convergence, and (2) maintains good performance in the presence of memory overflow. We demonstrate the performance of our approach with a prototype implementation in a parallel DBMS. 
For the second problem, we propose two techniques to improve the efficiency of immediate materialized view maintenance. We identify two challenges for immediate materialized view maintenance: (1) In parallel RDBMSs, simple single-node updates to base relations can give rise to expensive all-node operations for materialized view maintenance. (2) Immediate materialized view maintenance with transactional consistency, if enforced by generic concurrency control mechanisms, can result in low levels of concurrency and high rates of deadlock. 
To address the first challenge, we present a comparison of three materialized join view maintenance methods in a parallel RDBMS, which we refer to as the naive, auxiliary relation, and global index methods. The last two methods improve performance at the cost of using more space. 
To address the second challenge, we extend previous high concurrency locking techniques to apply to materialized view maintenance, and show how this extension can be implemented even in the presence of indices on the materialized view.
A Surfactant-Based Dressing to Treat and Prevent Acinetobacter baumannii Biofilms (2017)

Previous work has demonstrated that a surfactant-based dressing was capable of eliminating any evidence of pre-existing biofilms from an ex vivo porcine skin wound model. Herein, the authors test both the surfactant's ability to prevent biofilm formation and its ability to eliminate Acinetobacter baumannii biofilms. To test biofilm formation inhibition, porcine skin explants were inoculated and incubated for 4 hours before treatment. The explants were then dressed with test or control materials. To test biofilm elimination, mature 3-day biofilms were established and then treated and wiped daily. Explants from each group were harvested daily, and total and biofilm-associated bacterial counts were generated up through day 3 posttreatment. The control explants developed a biofilm with ~106 CFU over the course of 3 days for each of the bacteria tested. The surfactant-treated samples had viable bacteria, but with the exception of a single time point for Staphylococcus aureus without silver sulfadiazine, there was no biofilm formation. Unlike previous results, the surfactants could not eliminate the A. baumannii biofilm, unless it was formulated with relevant antibiotics. The surfactant was effective in preventing the formation of biofilms over a 3-day period. Unlike the authors' previous results, the daily surfactant-based approach alone did not eliminate the A. baumannii biofilms unless relevant antibiotics were included. The data suggest that the surfactants can prevent biofilm formation, but that in the case of a confirmed A. baumannii biofilm, the surfactant must include antibiotics.
The characterization of abasic sites in DNA heteroduplexes by site specific labeling with carbon-13 (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe characterization of abasic sites in DNA heteroduplexes by site specific labeling with carbon-13Muthiah. Manoharan, Stephen C. Ransom, Abhijit. Mazumder, John A. Gerlt, Joyce A. Wilde, Jane A. Withka, and Philip H. BoltonCite this: J. Am. Chem. Soc. 1988, 110, 5, 1620–1622Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March 1988https://doi.org/10.1021/ja00213a044RIGHTS & PERMISSIONSArticle Views258Altmetric-Citations61LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (406 KB) Get e-Alerts Get e-Alerts
Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness (2016)

Trypanosoma brucei are protozoan parasites that cause African sleeping sickness in humans (also known as Human African Trypanosomiasis-HAT). Without treatment, T. brucei infections are fatal. There is an urgent need for new therapeutic strategies as current drugs are toxic, have complex treatment regimens, and are becoming less effective owing to rising antibiotic resistance in parasites. We hypothesize that targeting the HSP60/10 chaperonin systems in T. brucei is a viable anti-trypanosomal strategy as parasites rely on these stress response elements for their development and survival. We recently discovered several hundred inhibitors of the prototypical HSP60/10 chaperonin system from Escherichia coli, termed GroEL/ES. One of the most potent GroEL/ES inhibitors we discovered was compound 1. While examining the PubChem database, we found that a related analog, 2e-p, exhibited cytotoxicity to Leishmania major promastigotes, which are trypanosomatids highly related to Trypanosoma brucei. Through initial counter-screening, we found that compounds 1 and 2e-p were also cytotoxic to Trypanosoma brucei parasites (EC50=7.9 and 3.1μM, respectively). These encouraging initial results prompted us to develop a library of inhibitor analogs and examine their anti-parasitic potential in vitro. Of the 49 new chaperonin inhibitors developed, 39% exhibit greater cytotoxicity to T. brucei parasites than parent compound 1. While many analogs exhibit moderate cytotoxicity to human liver and kidney cells, we identified molecular substructures to pursue for further medicinal chemistry optimization to increase the therapeutic windows of this novel class of chaperonin-targeting anti-parasitic candidates. An intriguing finding from this study is that suramin, the first-line drug for treating early stage T. brucei infections, is also a potent inhibitor of GroEL/ES and HSP60/10 chaperonin systems.
Constrained Pseudorandom Functions and Their Applications. (2013)

We put forward a new notion of pseudorandom functions (PRFs) we call constrained PRFs. In a standard PRF there is a master key k that enables one to evaluate the function at all points in the domain of the function. In a constrained PRF it is possible to derive constrained keys ks from the master key k. A constrained key ks enables the evaluation of the PRF at a certain subset S of the domain and nowhere else. We present a formal framework for this concept and show that constrained PRFs can be used to construct powerful primitives such as identity-based key exchange and an optimal private broadcast encryption system. We then construct constrained PRFs for several natural set systems needed for these applications. We conclude with several open problems relating to this new concept.
AXONAL TRANSPORT IN NIGRO‐STRIATAL AND NIGRO‐THALAMIC NEURONS: EFFECTS OF MEDIAL FOREBRAIN BUNDLE LESIONS AND 6‐HYDROXYDOPAMINE1 (1972)

Abstract —Axonal transport was studied in two efferent projections of the substantia nigra : (1) the nigro‐striatal system; and (2) the nigro‐thalamic system. [ 14 C]leucine was injected stereotaxically into the left substantia nigra of rats. At various intervals thereafter significant amounts of [ 14 C]protein were found in the midbrain (which surrounded the injection site), hypothalamus, thalamus and corpus striatum on the injected side of the brain. By determining the temporal characteristics of the distribution of [ 14 C]protein, axonal transport from the substantia nigra to the thalamus and corpus striatum could be inferred. Fast (approximately 50 mm/day) and slow (approximately 1 mm/day) rates of flow were evident in both systems. Either electrolytic lesions of the medial forebrain bundle or intraventricular pretreatment with 6‐hydroxydopamine (200 μg) produced a substantial decrease in the amount of labelled protein reaching the corpus striatum but not in that reaching the thalamus. The decrease following electrolytic lesions correlated significantly with the decrease in the activity of striatal tyrosine hydroxylase, but after 6‐hydroxydopamine the decrease in axonal transport was consistently less than the loss of striatal tyrosine hydroxylase. This difference indicated that a portion (perhaps as much as 20 per cent) of the nigro‐striatal neurons are non‐catecholaminergic. Finally, we present data which suggest that in contrast to effects on peripheral neurons, 6‐hydroxydopamine destroys the cell bodies as well as nerve terminals of adrenergic neurons in the central nervous system.
1062. Intracerebellar Injection of AAV-IGF-1 Improves Motor Function and Extends Survival in a Mouse Model of Amyotrophic Lateral Sclerosis (2006)

Amytrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by a selective loss of motor neurons in the motor cortex, brain stem and spinal cord. The etiology of motor neuron degeneration remains largely unknown. Although chronic delivery of therapeutic agents to the central nervous system has proven to be difficult, recent studies have demonstrated that intramuscular delivery of adeno-associated viral vectors encoding insulin growth factor 1 (AAV-IGF-1) slowed disease progression and extended survival in SOD1G93A mice. The efficacy of viral mediated expression of IGF-1 was mediated in part by the ability of the viral vector to undergo retrograde transport from muscle to motor neurons. Previously we demonstrated that targeting the deep cerebellar nuclei (DCN) of the cerebellum with viral vectors capable of axonal transport resulted in detection of transgene protein in both the brain stem and spinal cord (Dodge et al. 2005, PNAS 102:17822-17827). In this experiment we evaluated the efficacy of bilateral delivery of AAV1–IGF-1 and AAV2-IGF-1 to the DCN in 90 day old SOD1G93A mice. Starting at 80 days of age (and every 10 days thereafter), SOD1G93A mice underwent behavioral testing (rotarod, hindlimb and forelimb grip strength) to assess motor function. At 90 days of age (i.e., time point at which SOD1 mice exhibit overt disease symptoms of ALS) mice received stereotaxic bilateral injections of AAV1-IGF-I (n=26), AAV2-IGF-I (n=27), AAV1-GFP (n=26) or AAV2-GFP (n=25) aimed at the deep cerebellar nuclei (DCN) of the cerebellum. We found that bilateral delivery of AAV- IGF-1 treatment (regardless of serotype) to the DCN significantly promoted motor neuron survival, improved motor performance in both rotarod and grip strength behavioral tests and significantly extended lifespan (i.e., 12 day extension for AAV1-IGF-1 and 14 day extension for AAV2-IGF-1). Treatment with AAV-GFP had no effect on any of the parameters mentioned above. Our results indicate that direct administration of AAV-IGF-1 into the DCN modifies disease progression in a mouse model of ALS and that targeting the DCN with AAV vectors is an effective approach for delivering therapeutic transgenes to both the brain and spinal cord for the treatment of ALS.