gebhart/patrepeval huggingface dataset:
Elevated Soluble ST2 Protein Levels in Sera of Patients with Asthma with an Acute Exacerbation (2001)

Previous studies have reported that ST2 is preferentially expressed on Th2 cells and plays a critical part in controlling airway inflammation in murine models of asthma. However, the clinical role of ST2 in patients with bronchial asthma remains unclear. In our study, we examined 56 patients with atopic asthma in a nonattack phase and 200 nonatopic normal volunteers for healthy control, and analyzed the relationship of their serum ST2 levels to asthma severity, pulmonary function, and laboratory data. Of the 56 patients with atopic asthma, 30 exhibited asthmatic exacerbation, and their serum ST2 levels were also analyzed. The serum ST2 levels were low, but a statistical difference was found between patients with nonattack asthma and the healthy control group (p < 0.05). We also found a differential rise of serum ST2 level that correlates well with the severity of asthma exacerbation. Furthermore, the serum ST2 levels during asthma exacerbation statistically correlated with the percentage of predicted peak expiratory flow (r = -0.634, p = 0.004) and Pa(CO(2)) (r = 0.516, p = 0.003). These results suggest that soluble human ST2 protein in sera may be related to Th2-mediated allergic inflammation inducing acute exacerbation in patients with atopic asthma.
Current challenges in the management of epilepsy. (2011)

A series of conceptual reconsiderations and therapeutic advances in recent years has resulted in meaningful changes in the classification, diagnosis, and treatment of epilepsy. The first step in evaluation of the person with epilepsy is determining whether the seizures are partial or generalized in onset; this determination will guide further evaluation and is mandatory in choosing an antiepileptic drug (AED). With 12 new AEDs and 1 device approved for use in epilepsy by the US Food and Drug Administration since 1993, the choice of AED has become more complex and it is impossible to predict whether a patient will respond favorably to a drug based on clinical features or clinical laboratory results. AEDs have many different mechanisms of action, but there does not seem to be a strong base of evidence to demonstrate that AED choice should be based on mechanism of action. Yet, a new secondary analysis of data from clinical trials of the new AED lacosamide suggests that combining this AED with another AED that has minimal or no activity at the sodium channel may lead to better tolerability and efficacy. The new AEDs have been tested in randomized controlled trials and compared with placebo; however, there are few head-to-head trials assessing the efficacy of various AEDs, and none of them provide evidence of a clear first choice drug or first add-on drug. Adverse effect profiles of the new generation of AEDs generally show better overall tolerability, but the choice of AED must be individualized (often based on comorbidities) because the adverse effect profiles of the newer AEDs differ widely. One area where the new AEDs consistently outperform the older AEDs is pharmacokinetic profile. Three new AEDs have no hepatic metabolism or protein binding, and others have minimal drug-drug interactions. Ultimately, selection of an appropriate agent involves matching a patient to a medication, or combination of medications, with the best record of efficacy while avoiding issues of tolerability and unwanted drug interactions (specifically tied to the needs of a given patient). Despite major advances in AED development, approximately one-third of people with epilepsy will have incomplete control of seizures no matter which AED is used alone or in combination, emphasizing the need for more effective AEDs. Patients with medication-resistant epilepsy may be candidates for epilepsy surgery, a highly effective treatment that is underutilized in this population.
12-O-tetradecanoylphorbol-13-acetate-induced apoptosis in LNCaP cells is mediated through ceramide synthase. (1998)

Protein kinase C (PKC) activation is often antiapoptotic, although in a few cell types PKC initiates apoptosis by an unknown mechanism. Recent investigations showed that activation of PKC alpha by 12-O-tetradecanoylphorbol 13-acetate (TPA) induced apoptosis in LNCaP prostate cancer cells. The present studies examine the mechanism of this effect and show that de novo ceramide generation through the enzyme ceramide synthase is required. TPA induced rapid ceramide generation, which was detectable by 1 h and increased linearly for 12 h. TPA-induced apoptosis was measurable by 12 h and was progressive for 48 h. Investigations into the mechanism of TPA-induced ceramide generation revealed that acid and neutral sphingomyelinase activities were not enhanced. However, TPA induced an increase in ceramide synthase activity that persisted for at least 16 h. Treatment with fumonisin B1, a specific natural inhibitor of ceramide synthase, abrogated both ceramide production and TPA-induced apoptosis. Ceramide analogues bypassed fumonisin B1 inhibition to initiate apoptosis directly. Thus, ceramide appears to be a necessary signal for TPA-induced apoptosis in LNCaP cells. This represents the first description of a pathway by which PKC may signal apoptosis.
Competing risks analysis of patients with osteosarcoma: a comparison of four different approaches (2001)

In failure time studies involving a chronic disease such as cancer, several competing causes of mortality may be operating. Commonly, the conventional statistical technique of Kaplan-Meier, which is only meaningfully interpreted by assuming independence of failure types and the censoring mechanism, is employed in clinical research involving competing risks data. Some authors have advocated the use of a cause-specific cumulative incidence function which takes into account the existence of other events within a competing risks framework, without making any assumption about independence. Lunn and McNeil have proposed an approach based on an extension of the Cox proportional hazards regression, which enables direct comparisons between failure types. We have extended this approach to estimate cause-specific cumulative incidence. As it is often not easy to follow competing risks methodology in the literature, this paper sets out systematically the assumptions made and the steps taken to implement four different methods of analysing competing risks data using cumulative incidence rates or the Kaplan-Meier estimates of cause-specific failure probabilities. The data obtained from a randomized trial of patients with osteosarcoma were used to compare these four approaches. As illustrated using the osteosarcoma data, the estimates of the classical Kaplan-Meier methods have larger numerical values than the cause-specific cumulative incidence. On the other hand, estimates of the cause-specific cumulative incidence rates from the conventional method and the modified Cox method are highly comparable.
BRAF in Melanoma: Current Strategies and Future Directions (2013)

Selective BRAF inhibitors have now been established as a standard of care option for patients diagnosed with metastatic melanoma whose tumors carry a BRAF mutation. Their successful development represents a milestone in the treatment of this disease, and has the potential to impact therapy for other malignancies as well. The use of these agents, however, has introduced a number of critical questions about the optimal use and selection of patients for BRAF inhibitor therapy. This review discusses the current status of BRAF inhibitor clinical development, the clinicopathologic features of BRAF-mutated melanoma, as well as strategies for overcoming resistance.
Sequential transcription of the genes of vesicular stomatitis virus. (1976)

Increasing exposure of vesicular stomatitis virus particles to ultraviolet radiation caused differential inhibition of the synthesis in vitro of individual mRNA species which code for the viral structural proteins L, G, M, NS, and N.
MiR423-5p As a Circulating Biomarker for Heart Failure (2010)

Rationale : Aberrant expression profiles of circulating microRNAs (miRNAs) have been described in various diseases and provide high sensitivity and specificity. We explored circulating miRNAs as potential biomarkers in patients with heart failure (HF). Objective : The goal of this study was to determine whether miRNAs allow to distinguish clinical HF not only from healthy controls but also from non-HF forms of dyspnea. Methods and Results : A miRNA array was performed on plasma of 12 healthy controls and 12 HF patients. From this array, we selected 16 miRNAs for a second clinical study in 39 healthy controls and in 50 cases with reports of dyspnea, of whom 30 were diagnosed with HF and 20 were diagnosed with dyspnea attributable to non–HF-related causes. This revealed that miR423-5p was specifically enriched in blood of HF cases and receiver-operator-characteristics (ROC) curve analysis showed miR423-5p to be a diagnostic predictor of HF, with an area under the curve of 0.91 ( P &lt;0.001). Five other miRNAs were elevated in HF cases but also slightly increased in non-HF dyspnea cases. Conclusion : We identify 6 miRNAs that are elevated in patients with HF, among which miR423-5p is most strongly related to the clinical diagnosis of HF. These 6 circulating miRNAs provide attractive candidates as putative biomarkers for HF.
Bodies in motion: Monitoring daily activity and exercise with motion sensors in people with chronic pulmonary disease (2003)

A primary goal of pulmonary rehabilitation is to improve health and life quality by encouraging participants to engage in exercise and to increase daily physical activity. The recent advent of motion sensors, including digital pedometers and accelerometers that measure motion as a continuous variable, have added precision to the measurement of free-living daily activity. Daily activity and exercise are variables of keen interest to proponents of the national health agenda, epidemiologists, clinical researchers, and rehabilitation interventionists. This paper summarizes issues related to conceptualizing and monitoring activity in the rehabilitation setting; reviews motion sensor methodology; compares motion-sensing devices; presents analysis issues and current and potential applications to the pulmonary rehabilitation setting; and gives practical applications and limitations.
The Pseudomonas aeruginosa quinolone signal molecule overcomes the cell density‐dependency of the quorum sensing hierarchy, regulates rhl‐dependent genes at the onset of stationary phase and can be produced in the absence of LasR (2003)

In Pseudomonas aeruginosa, diverse exoproduct virulence determinants are regulated via N-acylhomoserine lactone-dependent quorum sensing. Here we show that 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS) is also an integral component of the quorum sensing circuitry and is required for the production of rhl-dependent exoproducts at the onset of stationary phase. Analysis of spent P. aeruginosa culture supernatants revealed that PQS is produced at the end of exponential phase in the parent strain and in the late stationary phase of a lasR mutant. Mutants defective in both PQS production (pqsR-) and response (pqsE-) produced substantially reduced levels of exoproducts but retained wild-type N-butanoyl homoserine lactone (C4-HSL) levels. In the wild type, provision of exogenous PQS at the time of inoculation significantly increased PA-IL lectin, pyocyanin and elastase production during early stationary phase and promoted biofilm formation. Exogenous PQS but not PQS derivatives lacking the 3-hydroxy group overcame the cell density but not growth phase-dependent production of exoproducts. PQS also overcame the transcriptional and post-transcriptional repression of lecA (which codes for the PA-IL lectin) mediated via the negative regulators MvaT and RsmA respectively. Increased expression of lecA in the presence of exogenous PQS can be explained partially by increases in RhlR, RpoS and C4-HSL levels. A refined model for quorum sensing in P. aeruginosa is presented.
What would happen if all developing countries expanded manufactured exports (1993)

Despite the achievements of the export-oriented economies of East Asia, many policymakers doubt that a development path led by manufactured exports is feasible for all developing countries. The author examines what happens if all developing countries, rather than merely a few, expand manufactured exports. He considers two driving forces for export expansion: the liberalization of trade barriers, and productivity growth in the production of manufactured exports. With only trade liberalization, the static welfare gains are small (with the standard Armington specification used in the analysis). Even the export growth rates are far too small to replicate the essential East Asian experience. And when all developing countries participate in static trade liberalization, the small welfare gains diminish slightly. Under the more realistic assumption of dynamic export growth driven by productivity gains for manufactured exports, the welfare effects are much greater and the efforts of developing countries are mutually reinforcing. Because of strong South-South trade links, and developing countries' dependence on manufactured imports, developing countries buy more manufactured goods from each other. The author accepts the view of export pessimists that a country expanding its manufactured exports will receive depressed prices for those exports. But his results differ because he uses a general equilibrium framework with intra-industry trade rather than a partial equilibrium model of the export market. The general equilibrium model captures the fact that developing countries still import most manufactured goods, often from each other. They will suffer, but they will also benefit, from declining prices. So they are better off if they all expand those exports.
Nucleotide sequence of the phoS gene, the structural gene for the phosphate-binding protein of Escherichia coli (1984)

phoS is the structural gene for the phosphate-binding protein, which is localized in periplasm and involved in active transport of phosphate in Escherichia coli. It is also a negative regulatory gene for the pho regulon, and the gene expression is inducible by phosphate starvation. The complete nucleotide sequence of the phoS gene was determined by the method of Maxam and Gilbert (A. M. Maxam and W. Gilbert, Methods Enzymol. 65:499-560, 1980). The amino acid sequences at the amino termini of the pre-PhoS and PhoS proteins and at the carboxy terminus of the PhoS protein were determined by using the purified proteins. Furthermore, the amino acid sequence of enzymatically digested peptide fragments of the PhoS protein was determined. The combined data established the nucleotide sequence of the coding region and the amino acid sequence of the pre-PhoS and the PhoS proteins. The pre-PhoS protein contains an extension of peptide composed of 25 amino acid residues at the amino terminus of the PhoS protein, which has the general characteristics of a signal peptide. The mature PhoS protein is composed of 321 amino acid residues, with a calculated molecular weight of 34,422, and lacks the disulfide bond and methionine. The regulatory region of phoS contains a characteristic Shine-Dalgarno sequence at an appropriate position preceding the translational initiation site, as well as three possible Pribnow boxes and one -35 sequence. the nucleotide sequence of the regulatory region of phoS was compared with those of phoA and phoE, the genes constituting the pho regulon.
Improved reflectance retrieval from hyper- and multispectral imagery without prior scene or sensor information (2006)

We describe improvements to a recently developed VNIR-SWIR atmospheric correction method for hyper- and multispectral imagery, dubbed QUAC (QUick Atmospheric Correction). It determines the atmospheric compensation parameters directly from the information contained within the scene using the observed pixel spectra. The newest implementation of QUAC is based on the assumption that the average reflectance of a collection of diverse material spectra, such as the endmember spectra in a scene, is effectively scene independent. This enables the retrieval of reasonably accurate reflectance spectra even when the sensor does not have a proper radiometric or wavelength calibration, or when the solar illumination intensity is unknown. The computational speed of the atmospheric correction method is significantly faster than for the first-principles methods, making it potentially suitable for real-time applications on aircraft and spacecraft. QUAC is applied to a diverse collection of hyper- and multispectral data sets and the results are compared to those obtained with the physics-based atmospheric correction code FLAASH (Fast Line of sight Atmospheric Analysis of Spectral Hypercubes).
Liposome Methods and Protocols (2002)

Part I. Physical Properties Preparation, Isolation, and Characterization of Liposomes Containing Natural and Synthetic Lipids Subroto Chatterjee and Dipak K. Banerjee Preparation and Use of Liposomes for the Study of Sphingolipid Segregation in Membrane Model Systems Massimo Masserini, Paola Palestini, Marina Pitto, Vanna Chigorno, and Sandro Sonnino Part II. Liposome Fusion/Modulation Peptide-Induced Fusion of Liposomes Eve-Isabelle Pecheur and Dick Hoekstra Liposomes: Applications in Protein-Lipid Interaction Studies, Sujoy Ghosh and Robert Bell Lipids in Viral Fusion Anu Puri, Maite Paternostre, and Robert Blumenthal Part III. Application of Liposomes Liposome-Mediated, Fluorescence-Based Studies of Sphingolipid Metabolism in Intact Cells Shimon Gatt, Tama Dinur, and Arie Dagan Micelles and Liposomes in Metabolic Enzyme and Glycolipid Glycosyltransferase Assays Manju Basu and Subhash Basu Liposomes and Phospholipid Binding Proteins in Glycoprotein Biosynthesis Roger K. Bretthauer and Dennis W. Welsh Therapeutic Uses of Antioxidant Liposomes William L. Stone, Shyamali Mukherjee, Milton Smith, and Salil K. Das Targeted Gene Delivery by Virosomes Debi P. Sarkar, Komal Ramani, and Sandeep K. Tyagi Liposomes Containing Ligands: Binding Specificity to Selectins Sriram Neelamegham and Khushi L. Matta Preparation and Characterization of Glycolipid-Bearing Multilamellar and Unilamellar Liposomes P. R. Satish and A. Surolia Use of Liposomes Containing Carbohydrates for Production of Monoclonal Antibodies Reiji Kannagi Inhibition of Tumor Metastasis by Liposomes Containing Glyco-Replica Peptides Takao Taki and Naoto Oku Use of Phospholipid Bilayers and Monolayers in Binding Studies of Vitamin K-Dependent BloodCoagulation Proteins Francis J. Castellino and Eric H. Ellison Index
Biodegradable microfluidic scaffolds for tissue engineering from amino alcohol-based poly(ester amide) elastomers (2010)

Biodegradable polymers with high mechanical strength, flexibility and optical transparency, optimal degradation properties and biocompatibility are critical to the success of tissue engineered devices and drug delivery systems. Most biodegradable polymers suffer from a short half life due to rapid degradation upon implantation, exceedingly high stiffness, and limited ability to functionalize the surface with chemical moieties. This work describes the fabrication of microfluidic networks from poly(ester amide), poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate) (APS), a recently developed biodegradable elastomeric poly(ester amide). Microfluidic scaffolds constructed from APS exhibit a much lower Young's Modulus and a significantly longer degradation half-life than those of previously reported systems. The device is fabricated using a modified replica-molding technique, which is rapid, inexpensive, reproducible, and scalable, making the approach ideal for both rapid prototyping and manufacturing of tissue engineering scaffolds.
Thalidomide in the treatment of multiple myeloma (2001)

Thalidomide--banned from clinical use in the 1960s because of severe teratogenicity--is now back in clinical practice as an effective agent in the treatment of relapsed and refractory multiple myeloma. Several clinical trials have determined that thalidomide is active in 25-35% of patients with relapsed myeloma. The role of thalidomide in early-stage myeloma is being actively investigated. Thalidomide has antiangiogenic and immunomodulatory properties and is an effective inhibitor of TNF-alpha. However, the mechanism of its action in myeloma remains unclear. Major toxicities of thalidomide include constipation, sedation, skin rash, fatigue and peripheral neuropathy. This paper summarizes the current status of thalidomide in multiple myeloma.
Synthesis and Characterization of Accessible Metal Surfaces in Calixarene-Bound Gold Nanoparticles (2009)

Use of organic ligands to partially passivate nanoparticles against sintering yet retain a degree of small molecule accessibility to the metal surface has been a lofty goal in functional materials synthesis, which in principle also enables the design of preferred electronic and steric environments on a nanoparticle surface. Catalysis using gold in particular requires donor ligands that facilitate an electron-rich metal surface and generalizable strategies for dealing with deactivation due to sintering. Here, synthesis and characterization of gold nanoparticles postsynthetically modified with the chelating ligand cone-5,11,17,23,29,35-hexa(tert-butyl)-37,39,41-tris(diphenylphosphinomethoxy)-38,40,42-trimethoxycalix[6]arene (1) is reported. In solution as well as when supported on the surface of TiO2, nanoparticles modified with tripodal calix[6]arene phosphine ligand 1 demonstrate enhanced protection against sintering relative to unmodified, tetraoctylammonium bromide-surfactant-stabilized gold nanoparticles. In between adsorbed calixarene ligands, there is accessible gold surface area in these nanoparticles, and this is measured quantitatively for the first time for a calixarene-modified nanoparticle, using a newly developed fluorescence methodology involving 2-naphthalenethiol as a relevant chemisorption probe molecule. Ligand steric bulk critically influences amount of accessible surface on the metal nanoparticle since the use of a smaller calix[4]arene ligand (MBC) results in a 7-fold lower accessible surface area relative to using 1 under otherwise similar conditions. In addition, surface coverage of 1 controls accessible surface area in an unintuitive fashion: a 4-fold increase in accessible metal surface area is observed upon increasing the surface coverage of 1 to be 1.5-fold higher than the minimum required for surface saturation. This is presumably the result of a more open ligand packing of 1 at higher surface coverages, which allows greater accessibility to 2-napthalenethiol.
An Arabidopsis histone H2A mutant is deficient in Agrobacterium T-DNA integration (2000)

Agrobacterium tumefaciens genetically transforms plant cells by transferring a portion of the bacterial Ti-plasmid, the T-DNA, to the plant and integrating the T-DNA into the plant genome. Little is known about the T-DNA integration process, and no plant genes involved in integration have yet been identified. We characterized an Arabidopsis mutant generated by T-DNA insertional mutagenesis, rat5, that is resistant to Agrobacterium root transformation. rat5 contains two copies of T-DNA integrated as a tandem direct repeat into the 3' untranslated region of a histone H2A gene, upstream of the polyadenylation signal sequence. Transient and stable beta-glucuronidase expression data and assessment of the amount of T-DNA integrated into the genomes of wild-type and rat5 Arabidopsis plants indicated that the rat5 mutant is deficient in T-DNA integration. We complemented the rat5 mutation by expressing the RAT5 histone H2A gene in the mutant plant. Overexpression of RAT5 in wild-type plants increased Agrobacterium transformation efficiency. Furthermore, transient expression of a RAT5 gene from the incoming T-DNA was sufficient to complement the rat5 mutant and to increase the transformation efficiency of wild-type Arabidopsis plants.