gebhart/patrepeval huggingface dataset:
Nanoparticles - A review (2007)

For the past few decades, there has been a considerable research interest in the area of drug delivery using particulate delivery systems as carriers for small and large molecules. Particulate systems like nanoparticles have been used as a physical approach to alter and improve the pharmacokinetic and pharmacodynamic properties of various types of drug molecules. They have been used in vivo to protect the drug entity in the systemic circulation, restrict access of the drug to the chosen sites and to deliver the drug at a controlled and sustained rate to the site of action. Various polymers have been used in the formulation of nanoparticles for drug delivery research to increase therapeutic benefit, while minimizing side effects. Here, we review various aspects of nanoparticle formulation, characterization, effect of their characteristics and their applications in delivery of drug molecules and therapeutic genes. Keywords: nanoparticles, drug delivery, targeting, drug release > Tropical Journal of Pharmaceutical Research Vol. 5 (1) 2006: pp. 561-573
Probing the Ring Size of Epothilones: Total Synthesis of [14]-, [15]-, [17]-, and [18]Epothilones A (1998)

Unfamiliar rings. The pharmocophore of epothilone A does not tolerate changes in ring size. The 14-, 15-, 17-, and 18-membered ring analogues 1 (n = 1, 2, 4, 5) of epothilone and their deoxy counterparts show only low levels of activity in tubulin polymerization assays, with the exception of [18]desoxyepothilone A. These findings underscore the high specificity of the tubulin receptor.
Biosynthesis of lipid A in Escherichia coli. Acyl carrier protein-dependent incorporation of laurate and myristate. (1990)

In previous studies we described enzyme(s) from Escherichia coli that transfer two 3-deoxy-D-manno-octulosonate (KDO) residues from two CMP-KDO molecules to a tetraacyldisaccharide-1,4'-bis-phosphate precursor of lipid A, termed lipid IVA (Brozek, K. A., Hosaka, K., Robertson, A. D., and Raetz, C. R. H. (1989) J. Biol. Chem. 264, 6956-6966). The product, designated (KDO)2-IVA, can be prepared in milligram quantities and/or radiolabeled with 32P at position 4' of the IVA moiety. We now demonstrate the presence of enzymes in E. coli extracts that transfer laurate and/or myristate residues from lauroyl or myristoyl-acyl carrier protein (ACP) to (KDO)2-IVA. Thioesters of coenzyme A are not substrates. The cytosolic fraction catalyzes rapid acylation with lauroyl-ACP, but not with myristoyl, R-3-hydroxymyristoyl, palmitoyl, or palmitoleoyl-ACP. The membrane fraction transfers both laurate and myristate to (KDO)2-IVA. Evidence for the enzymatic acylation of (KDO)2-IVA is provided by (a) conversion of [4'-32P](KDO)2-IVA to more rapidly migrating products in the presence of the appropriate acyl-ACP, (b) incorporation of [1-14C]laurate or [1-14C]myristate into these metabolites in the presence of (KDO)2-IVA, (c) fast atom bombardment-mass spectrometry, and (d) 1H NMR spectroscopy. At protein concentrations less than 0.5 mg/ml, the acylation of (KDO)2-IVA by the cytoplasmic fraction is absolutely dependent upon the addition of exogenous acyl-ACP. These acyltransferases cannot utilize lipid IVA as a substrate, demonstrating that they possess novel KDO recognition domains. The unusual substrate specificity of these enzymes provides compelling evidence for their involvement in lipid A biosynthesis. Depending on the conditions it is possible to acylate (KDO)2-IVA with 1 or 2 lauroyl residues, with 1 or 2 myristoyl residues, or with 1 of each.
DLK induces developmental neuronal degeneration via selective regulation of proapoptotic JNK activity (2011)

The c-Jun N-terminal kinase (JNK) signaling pathway is essential for neuronal degeneration in multiple contexts but also regulates neuronal homeostasis. It remains unclear how neurons are able to dissociate proapoptotic JNK signaling from physiological JNK activity. In this paper, we show that the mixed lineage kinase dual leucine zipper kinase (DLK) selectively regulates the JNK-based stress response pathway to mediate axon degeneration and neuronal apoptosis without influencing other aspects of JNK signaling. This specificity is dependent on interaction of DLK with the scaffolding protein JIP3 to form a specialized JNK signaling complex. Local activation of DLK-based signaling in the axon results in phosphorylation of c-Jun and apoptosis after redistribution of JNK to the cell body. In contrast, regulation of axon degeneration by DLK is c-Jun independent and mediated by distinct JNK substrates. DLK-null mice displayed reduced apoptosis in multiple neuronal populations during development, demonstrating that prodegenerative DLK signaling is required in vivo.
Least-squares curve fitting for velocity and time zero (2015)

Indirect least-squares algorithms developed for bistatic antenna configurations are derived to simultaneously invert for propagation velocity, time zero, depth, and lateral offset for buried objects approximating point diffractors. An alternative direct algorithm is derived for antenna geometries approximating the monostatic antenna configuration. Least-squares fitting for velocity, depth, and lateral offset using multiple diffraction curves is combined with a time zero grid search algorithm to provide a robust solution when inverting for time zero.
Bax and Adenine Nucleotide Translocator Cooperate in the Mitochondrial Control of Apoptosis (1998)

The proapoptotic Bax protein induces cell death by acting on mitochondria. Bax binds to the permeability transition pore complex (PTPC), a composite proteaceous channel that is involved in the regulation of mitochondrial membrane permeability. Immunodepletion of Bax from PTPC or purification of PTPC from Bax-deficient mice yielded a PTPC that could not permeabilize membranes in response to atractyloside, a proapoptotic ligand of the adenine nucleotide translocator (ANT). Bax and ANT coimmunoprecipitated and interacted in the yeast two-hybrid system. Ectopic expression of Bax induced cell death in wild-type but not in ANT-deficient yeast. Recombinant Bax and purified ANT, but neither of them alone, efficiently formed atractyloside-responsive channels in artificial membranes. Hence, the proapoptotic molecule Bax and the constitutive mitochondrial protein ANT cooperate within the PTPC to increase mitochondrial membrane permeability and to trigger cell death.
Liquidity management policies of select Indian Pharmaceutical companies in the post-reform regime (2015)

With the advent of economic reforms in India in late 1980s, on one hand we have multiple investment opportunities before us and on the other hand our country is exposed to unprecedented challenges emanating from dynamic and volatile nature of socio-political economy. As a result, the earnings trends, cost behaviour pattern, financing strategies, working capital (WC) management policies and other allied issues in the business world have altered notably and to survive in such a competitive corporate world the business houses are forced to rethink about their existing corporate strategies. In the study an effort was made to assess the impact of working capital investment policy and financing policy on overall profitability. The results were obtained from the study were conflicting. The results of the analysis of correlation between DIP and ROCE showed positive relationship in almost all the cases which mismatches with the accepted norm. The outcome derived from the correlation analysis between DFP and ROCE reinforced the generally accepted fact that higher levels of short term funds have positive influence on overall profitability. Regression analysis proved that in ninety per cent cases the ROCE stepped up with an increase DIP whereas in eighty percent cases the ROCE increased due to one unit increase in DFP.
The impact of tourism in developing countries on the health of the local host communities: the need for more research (1999)

Tourism is the fastest growing industry internationally. Popular areas of study are the economic, environmental and socio-cultural impacts of tourism in developing countries. Very few studies have been conducted on the impact of tourism on the hosts' health status. Nowadays, the emergence of new infectious diseases or the re-emergence of diseases thought eradicated are causing concern and travel is a major contributor to their spread. The objectives of this study were: to review literature related to the topic as a background for future research; to explore if findings obtained during a field-trip to Easter Island/Chile and Peru support the hypotheses derived from the analysis of published material; to recommend a range of research topics based on the outcome of this study; and to propose elements of a framework for the assessment of health impacts of tourism. The findings suggest that there are considerable gaps in the current knowledge on tourism's health impacts. Potential indirect and direct impacts have been identified. Workplace health and safety concerns in relation to local tourism employees have been raised. A wide range of research topics has been suggested based on these findings. Finally, elements of a possible framework for understanding tourism's health impacts and their interrelationships have been identified.
Supramolecular Control of Reactivity in the Solid State Using Linear Molecular Templates (2000)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSupramolecular Control of Reactivity in the Solid State Using Linear Molecular Templates†Leonard R. MacGillivray, Jennifer L. Reid, and John A. RipmeesterView Author Information Steacie Institute for Molecular Sciences National Research Council of Canada Ottawa, Ontario, Canada, K1A 0R6 Cite this: J. Am. Chem. Soc. 2000, 122, 32, 7817–7818Publication Date (Web):July 29, 2000Publication History Received10 April 2000Published online29 July 2000Published inissue 1 August 2000https://pubs.acs.org/doi/10.1021/ja001239ihttps://doi.org/10.1021/ja001239irapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views5131Altmetric-Citations374LEARN 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 InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (3)»Supporting Information Supporting Information SUBJECTS:Genetics,Hydrocarbons,Noncovalent interactions,Reactivity,Supramolecular chemistry Get e-Alerts
Human Aminopeptidases: A Review of the Literature (1988)

The aminopeptidases constitute a group of enzymes with closely related activities. In clinical chemistry the analysis of the aminopeptidases and of their multiple forms in serum has for a long time been hindered by considerable confusion concerning their identification, and by a lack of characterization. This is in part due to the often large, and sometimes overlapping substrate specificities of the aminopeptidases. This paper reviews the biochemical properties of the different aminopeptidases, the specificities of the assays used for their analysis in serum, some aspects of their multiple forms--which are especially known to occur for alanine aminopeptidase (EC 3.4.11.2)--and the importance of the determination of aminopeptidases and their multiple forms in clinical chemistry.
Complications of Iliac Crest Bone Graft Harvesting (1996)

Autologous bone grafts harvested from the iliac crest are commonly used in reconstructive orthopaedic surgery. Autologous bone is used to help promote bone healing in fractures and to provide structural support for reconstructive surgery. The results of autologous bone grafting are more predictable than the use of xenografts, cadaveric allografts, or synthetic bone substitutes because autologous bone grafts provide osteoinductive and osteoconductive properties, are not immunogenic, and are usually well incorporated into the graft site. In a retrospective review of 414 consecutive cases of iliac crest bone graft procedures performed at Brooke Army Medical Center from 1983 to 1993, 41 (10%) minor and 24 (5.8%) major complications were identified. Minor complications included superficial infections, superficial seromas, and minor hematomas. Major complications included herniation of abdominal contents through massive bone graft donor sites, vascular injuries, deep infections at the donor site, neurologic injuries, deep hematoma formation requiring surgical intervention, and iliac wing fractures. Harvesting of iliac crest bone graft can be associated with significant morbidity. However, with adequate preoperative planning and proper surgical technique, the incidence of these complications can be reduced.
Testase 1 (ADAM 24) a plasma membrane-anchored sperm protease implicated in sperm function during epididymal maturation or fertilization (2001)

Plasma membrane-anchored proteases have key roles in cell signaling, migration and refashioning the cell surface and its surroundings. We report the first example of a plasma membrane-anchored protease on mature sperm, testase 1 (ADAM 24). Unlike other studied sperm ADAMs (fertilin alpha and beta, cyritestin) whose metalloprotease domains are removed during sperm development, we found testase 1 retains an active metalloprotease domain, suggesting it acts as a protease on mature sperm. Testase 1 is a glycoprotein (molecular mass 88 kDa), localized to the equatorial region of the plasma membrane of cauda epididymal sperm. Typically, proteolytic removal of the pro-domain is an initial activation step for ADAM proteases. The pro-domain of the testase 1 precursor (108 kDa) is proteolytically removed as sperm transit the caput epididymis to produce processed (mature) testase 1 (88 kDa). Testase 1 is unique among all studied ADAMs in that its proteolytic processing occurs on the sperm plasma membrane instead of at an intracellular site (the Golgi). Using GST-fusion proteins and a synthetic testase 1 C-terminal peptide, we found that the cytoplasmic tail of testase 1 could be phosphorylated in vitro by protein kinase C (PKC). Thus testase 1 apparently has a cytoplasmic PKC phosphorylation site(s). Protein kinase C is known to stimulate other ADAMs' protease activity. Because events of the acrosome reaction include PKC activation, we speculate that testase 1 protease function could be important in sperm penetration of the zona pellucida after sperm PKC is activated during the acrosome reaction.
Molecular Dynamics Simulations of PNA·DNA and PNA·RNA Duplexes in Aqueous Solution (2000)

Molecular dynamics simulations have been used to study the structure and flexibility of a DNA·PNA duplex and a RNA·PNA duplex in aqueous solution. In this study, trajectories have been generated starting from three different conformations of the PNA·DNA and PNA·RNA duplexes: A-like, B-like, and PA/B-like. For the DNA·PNA duplex, the three trajectories converge within the nanosecond time scale to give structures resembling closely the PB model. The RNA·PNA duplex trajectories started from A- and PA-forms converge to give structures resembling the PA model, but the trajectory begun from the B-like conformation leads to an unfolded duplex. Despite the similarity between PA and PB structures calculations show the existence of important differences in terms of molecular recognition between both conformations. Analysis of the trajectories shows that the PNA backbone is very flexible provided that the backbone movements do not alter the positioning of the bases. It is found that PNA is able to distort the structure of RNA and especially DNA strands during the formation of the PNA·DNA and PNA·RNA hybrids. The impact of these findings in antigene and antisense therapies is discussed.
Generation and Characterization of a Mammalian Cell Line Continuously Expressing Japanese Encephalitis Virus Subviral Particles (2001)

We have generated a cell line (F cells) producing a secreted form of Japanese encephalitis virus (JEV) subviral particle (extracellular particles [EPs]) that contains the JEV envelope glycoprotein (E) and a precursor (prM) of the virion membrane protein (M). The F cells were engineered to synthesize these JEV products from a cDNA encoding a mutated (furin proteinase resistant) form of prM, since stable cell lines expressing E and the authentic form of prM could not be obtained, due (in part) to the cell-fusing ability of EPs containing E and M. Our biochemical alteration of the prM protein was critical for the successful production of EP-producing cell lines. EPs produced by F cells share the biochemical properties of empty viral particles produced by JEV-infected cells, except that the F-cell EPs lack hemagglutinating activity and M. F-cell EPs were recognized by a panel of monoclonal antibodies to E, and EPs were shown to be useful as vaccine candidates in mice and as diagnostic reagents in evaluating human immune responses to JE vaccination. The amounts of E antigen released into the culture fluid of F cells were similar to those found in virion fractions of JEV-infected cell culture fluids or JEV-infected weanling mouse brains (the current source of antigen used to produce human vaccines for JE). Thus, the F-cell line would appear to be a useful source of antigen for JE vaccines and diagnostics.
Comparison of bisacodyl and sodium picosulphate in the treatment of chronic constipation (2007)

Bisacodyl and sodium picosulphate are equally well tolerated and effective in the treatment of chronic constipation over a 4-week period.
An error resilience technique based on FMO and error propagation for H.264 video coding in error-prone channels (2009)

Flexible macroblock ordering (FMO) is one of the new error resilience techniques in H.264 that can be used to mitigate the effects of error in error prone environments. Using FMO, each macroblock can be assigned independently to a certain slice group by using a macroblock allocation map(MBAmap). FMO tool depends on how the macroblocks are ordered, and various methods of reducing the error during MBAmap creation have been proposed. However, these methods usually focused on how to reduce the effects of error macroblocks within a frame while the issue of error propagation between frames has not been considered. This study concentrates on estimating the effects caused by the damaged macroblocks of the current frame to the next frame and the other macroblocks in the same slice group. These effects can be used in the evaluation of the macroblocks' importance in the current frame, and a suitable map with a reduced effect of error propagation can be generated. Results show that this method has improvements in PSNR and the number of undecodable macroblocks when compared to the other methods that did not take the effects of inter-frame error propagation into consideration.
Ligand-Based Peptide Design and Combinatorial Peptide Libraries to Target G Protein-Coupled Receptors (2010)

G protein-coupled receptors (GPCRs) are considered to represent the most promising drug targets; it has been repeatedly said that a large fraction of the currently marketed drugs elicit their actions by binding to GPCRs (with cited numbers varying from 30-50%). Closer scrutiny, however, shows that only a modest fraction of (≈60) GPCRs are, in fact, exploited as drug targets, only ≈20 of which are peptide-binding receptors. The vast majority of receptors in the humane genome have not yet been explored as sites of action for drugs. Given the drugability of this receptor class, it appears that opportunities for drug discovery abound. In addition, GPCRs provide for binding sites other than the ligand binding sites (referred to as the "orthosteric site"). These additional sites include (i) binding sites for ligands (referred to as "allosteric ligands") that modulate the affinity and efficacy of orthosteric ligands, (ii) the interaction surface that recruits G proteins and arrestins, (iii) the interaction sites of additional proteins (GIPs, GPCR interacting proteins that regulate G protein signaling or give rise to G protein-independent signals). These sites can also be targeted by peptides. Combinatorial and natural peptide libraries are therefore likely to play a major role in identifying new GPCR ligands at each of these sites. In particular the diverse natural peptide libraries such as the venom peptides from marine cone-snails and plant cyclotides have been established as a rich source of drug leads. High-throughput screening and combinatorial chemistry approaches allow for progressing from these starting points to potential drug candidates. This will be illustrated by focusing on the ligand-based drug design of oxytocin (OT) and vasopressin (AVP) receptor ligands using natural peptide leads as starting points.
Combined regression and ranking (2010)

Many real-world data mining tasks require the achievement of two distinct goals when applied to unseen data: first, to induce an accurate preference ranking, and second to give good regression performance. In this paper, we give an efficient and effective Combined Regression and Ranking method (CRR) that optimizes regression and ranking objectives simultaneously. We demonstrate the effectiveness of CRR for both families of metrics on a range of large-scale tasks, including click prediction for online advertisements. Results show that CRR often achieves performance equivalent to the best of both ranking-only and regression-only approaches. In the case of rare events or skewed distributions, we also find that this combination can actually improve regression performance due to the addition of informative ranking constraints.
Injection molding of chondrocyte/alginate constructs in the shape of facial implants (2001)

Over one million patients per year undergo some type of procedure involving cartilage reconstruction. Polymer hydrogels, such as alginate, have been shown to be effective carriers for chondrocytes in subcutaneous cartilage formation. The goal of our current study was to develop a method to create complex structures (nose bridge, chin, etc.) with good dimensional tolerance to form cartilage in specific shapes. Molds of facial implants were prepared using Silastic ERTV. Suspensions of chondrocytes in 2% alginate were gelled by mixing with CaSO(4) (0.2 g/mL) and injected into the molds. Constructs of various cell concentrations (10, 25, and 50 million/mL) were implanted in the dorsal aspect of nude mice and harvested at times up to 30 weeks. Analysis of implanted constructs indicated progressive cartilage formation with time. Proteoglycan and collagen constructs increased with time to approximately 60% that of native tissue. Equilibrium modulus likewise increased with time to 15% that of normal tissue, whereas hydraulic permeability decreased to 20 times that of native tissue. Implants seeded with greater concentrations of cells increased proteoglycan content and collagen content and equilibrium and decreased permeability. Production of shaped cartilage implants by this technique presents several advantages, including good dimensional tolerance, high sample-to-sample reproducibility, and high cell viability. This system may be useful in the large-scale production of precisely shaped cartilage implants.