gebhart/patrepeval huggingface dataset:
Simplified low-cost production of O-antigen from Salmonella Typhimurium Generalized Modules for Membrane Antigens (GMMA) (2015)

The Novartis Vaccines Institute for Global Health is developing vaccines using outer membrane particles, known as Generalized Modules for Membrane Antigens (GMMA). These are blebs of outer membrane and periplasm, shed from the surface of living Gram-negative bacteria following the targeted deletion of proteins involved in maintaining the integrity of the inner and outer membranes. The current study investigates the use of GMMA as starting material for extraction of membrane components, focusing on the O-antigen polysaccharide portion of lipopolysaccharide from Salmonella Typhimurium. We show that the amount of O-antigen extracted from GMMA by acid hydrolysis is comparable to the quantity extracted from whole wild type bacteria, but with less protein and DNA contaminants. Compared to conventional purification, GMMA enabled a reduction in the number of purification steps required to obtain the O-antigen polysaccharide with the same purity. Purification processes from GMMA and bacteria were characterised by similar final yields. Use of GMMA as starting material provides the possibility to simplify the purification process of O-antigen, with a consequent decrease in manufacturing costs of O-antigen-based glyconjugate vaccines against Salmonella strains and potentially other Gram-negative bacteria.
Superior antitumoral activity of dimerized targeted single-chain TRAIL fusion proteins under retention of tumor selectivity (2012)

Although targeting of the death receptors (DRs) DR4 and DR5 still appears a suitable antitumoral strategy, the limited clinical responses to recombinant soluble TNF-related apoptosis inducing ligand (TRAIL) necessitate novel reagents with improved apoptotic activity/tumor selectivity. Apoptosis induction by a single-chain TRAIL (scTRAIL) molecule could be enhanced >10-fold by generation of epidermal growth factor receptor (EGFR)-specific scFv-scTRAIL fusion proteins. By forcing dimerization of scFv-scTRAIL based on scFv linker modification, we obtained a targeted scTRAIL composed predominantly of dimers (Db-scTRAIL), exceeding the activity of nontargeted scTRAIL ∼100-fold on Huh-7 hepatocellular and Colo205 colon carcinoma cells. Increased activity of Db-scTRAIL was also demonstrated on target-negative cells, suggesting that, in addition to targeting, oligomerization equivalent to an at least dimeric assembly of standard TRAIL per se enhances apoptosis signaling. In the presence of apoptosis sensitizers, such as the proteasomal inhibitor bortezomib, Db-scTRAIL was effective at picomolar concentrations in vitro (EC(50) ∼2 × 10(-12) M). Importantly, in vivo, Db-scTRAIL was well tolerated and displayed superior antitumoral activity in mouse xenograft (Colo205) tumor models. Our results show that both targeting and controlled dimerization of scTRAIL fusion proteins provides a strategy to enforce apoptosis induction, together with retained tumor selectivity and good in vivo tolerance.
Peptide Helicity and Membrane Surface Charge Modulate the Balance of Electrostatic and Hydrophobic Interactions with Lipid Bilayers and Biological Membranes (1996)

An amphipathic model peptide, KLALKLALKALKAAKLA-NH2, and its complete double D-amino acid replacement set was used to analyze the process of peptide binding at lipid vesicles of different surface charge and to determine the structure of the lipid-bound peptides using CD spectroscopy. The relationship between peptide helicity, model membrane permeability, and biological activity has been studied by dye release from liposomes and investigation of antibacterial and hemolytic activity. The accumulation of cationic KLAL peptides at and the membrane-disturbing effect on bilayers of high negative surface charge were found to be dominated by charge interactions. Independent of any structural propensity, the cationic peptide side chains bind to the anionic phosphatidylglycerol moieties. The charge interactions hold the peptides at the bilayer surface, where they may disturb preferentially lipid headgroup organization by formation of peptide-lipid clusters. In contrast, KLAL peptide interaction with bilayers of low negative surface charge is highly dependent on peptide helicity. With decreasing amounts of anionic phosphatidylglycerol in the bilayer the membrane-disturbing effect of KLAL and other helical analogs substantially increases despite drastically reduced binding affinity. Less helical peptides exhibit reduced bilayer-disturbing activity, showing that the hydrophobic helix domain is decisive for binding at and inducing permeability in membranes of low negative surface charge. It is suggested that hydrophobic interactions drive the penetration of the amphipathic peptide structure into the inner membrane region, thus disturbing the arrangement of the lipid acyl chains and causing local disruption. On the basis of the proposed model for membrane disturbance, interactions modulating antibacterial and hemolytic activity are discussed.
Transition From Chronic Compensated to Acute Decompensated Heart Failure (2008)

Significant structural and functional differences were found between patients with SHF and those with DHF; however, elevated diastolic pressures play a pivotal role in the underlying pathophysiology of chronic compensated and acute decompensated HF in both SHF and DHF.
Phosphatidylinositol 3′-Kinase and p70s6k Are Required for Insulin but Not Bisperoxovanadium 1,10-Phenanthroline (bpV(phen)) Inhibition of Insulin-like Growth Factor Binding Protein Gene Expression (1997)

The hormonal regulation of insulin-like growth factor binding protein (IGFBP)-1 and -4 mRNA was compared in serum-free primary rat hepatocyte cultures. The combination of dexamethasone and glucagon (Dex/Gluc) strongly increased IGFBP-1 and IGFBP-4 mRNA levels. Insulin suppressed Dex/Gluc-stimulated IGFBP-1 but not IGFBP-4 mRNA levels. In contrast, the peroxovanadium compound, bisperoxovanadium 1,10-phenanthroline (bpV(phen)), completely abrogated Dex/Gluc induction of both IGFBP mRNA species. Wortmannin and rapamycin blocked the inhibitory effect of insulin but not that of bpV(phen) on Dex/Gluc-stimulated IGFBP mRNA. Thus, although phosphatidylinositol 3'-kinase and p70s6k are necessary for insulin-mediated transcriptional inhibition of the IGFBP-1 gene, a signaling pathway, independent of phosphatidyloinositol 3'-kinase and p70s6k, is activated by bpV(phen) and mediates IGFBP-1 as well as IGFBP-4 mRNA inhibition. Mitogen-activated protein (MAP) kinase activity induced by insulin was suppressed to below basal levels in the presence of Dex/Gluc, whereas in response to bpV(phen), MAP kinase activity was high and unaffected by Dex/Gluc, consistent with a role of MAP kinases in bpV(phen)-mediated inhibition of IGFBP mRNA. The specific MAP kinase kinase (MEK) inhibitor, PD98059, inhibited insulin but not bpV(phen)-stimulated MAP kinase activity, suggesting that MAP kinases can be activated in a MEK-independent fashion. Peroxovanadium compounds are strong inhibitors of tyrosine phosphatases, which may inhibit specific tyrosine/threonine phosphatases involved in the negative regulation of MAP kinases.
Two-component control of guest binding in a self-assembled cage molecule (2010)

A self-assembled M(2)L(4) palladium-pyridyl cluster with a "paddle-wheel" structure shows binding affinity in competitive organic solvents for neutral organic guests that possess both the correct size and electrostatic complementarity.
Outdoor See-Through Vision Utilizing Surveillance Cameras (2005)

This paper presents a new outdoor mixed-reality system designed for people who carry a camera-attached small handy device in an outdoor scene where a number of surveillance cameras are embedded. We propose a new functionality in outdoor mixed reality that the handy device can display live status of invisible areas hidden by some structures such as buildings, walls, etc. The function is implemented on a camera-attached, small handy subnotebook PC (HPC). The videos of the invisible areas are taken by surveillance cameras and they are precisely overlapped on the video of HPC camera, hence a user can notice objects in the invisible areas and see directly what the objects do. We utilize surveillance cameras for two purposes. (1) They obtain videos of invisible areas. The videos are trimmed and warped so as to impose them into the video of the HPC camera. (2) They are also used for updating textures of calibration markers in order to handle possible texture changes in real outdoor world. We have implemented a preliminary system with four surveillance cameras and proved that our system can visualize invisible areas in real time.
The GIS book : understanding the value and implementation of geographic information systems (1997)

Part 1 Defining GIS: an overview of the GIS industry and GIS software defining a GIS using a GIS why implement a GIS? GIS technology trends four leading GIS products in review. Part 2 Selecting and implementing a GIS: implementing a GIS the need for planning a GIS selecting a GIS keys to successful implementation the pitfalls of a GIS using a GIS consultant staffing a GIS financial justification of GIS base map accuracy getting CADD data into a GIS a case study in GIS implementation - Prince William County, Virginia. Appendices: resources for GIS information and training glossary of commonly-used GIS terms.
Impact of <i>MDR1 </i>Haplotypes Derived from C1236T, G2677T/A and C3435T on the Pharmacokinetics of Single-Dose Oral Digoxin in Healthy Chinese Volunteers (2008)

Our findings indicated that the MDR1 haplotype derived from C1236T, G2677T/A and C3435T is superior to predict the pharmacokinetics of digoxin. Digoxin pharmacokinetics are significantly different between individuals with the TTT-TTT haplotype and those with TGC-CGC.
Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases (2016)

The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs) niches might counteract the neuronal loss in Alzheimer’s disease (AD) and other pathologies, opening an exciting new therapeutic avenue. In the last years, druggable molecular targets and signalling pathways involved in neurogenic processes have been identified, and as a consequence, different drug types have been developed and tested in neuronal plasticity. This review focuses on recent advances in neurogenic agents acting at serotonin and/or melatonin systems, Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase (NAMPT) and nuclear erythroid 2-related factor (Nrf2).
The Institutional and Doctrinal Roles of 'Conscience' in the Law of Contract (2005)

The author asserts that conscience-based standards do not undermine contract law as long as their institutional and doctrinal roles are properly interpreted and limited. The historical and jurisprudential roots for intervention of the courts through conscience-based doctrines in private-party transactions are discussed. It is suggested that existing doctrinal limitations are not merely policy decisions, but principled outcomes of wider issues arising from the institution of contract in pluralistic market democracies. The concept of unconscionability is also discussed in some of the contexts to which it may be applied.
Modeling for Lesch‐Nyhan Disease by Gene Targeting in Human Embryonic Stem Cells (2004)

Human embryonic stem (ES) cells are pluripotent cells derived from blastocyst-stage embryos. It has been suggested that these cells should play a major role in transplantation medicine and be able to advance our knowledge in human embryology. We propose that these cells should also play a vital role in the creation of models of human disorders. This aspect would be most valuable where animal models failed to faithfully recapitulate the human phenotype. Lesch-Nyhan disease is caused by a mutation in the HPRT1 gene that triggers an overproduction of uric acid, causing gout-like symptoms and urinary stones, in addition to neurological disorders. Due to biochemical differences between humans and rodents, a mouse lacking the HPRT expression will fail to accumulate uric acid. In this research we demonstrate a model for Lesch-Nyhan disease by mutating the HPRT1 gene in human ES cells using homologous recombination. We have verified the mutation in the HPRT1 allele at the DNA and RNA levels. By using selection media, we show that HPRT1 activity is abolished in the mutant cells, and the HPRT1-cells show a higher rate of uric acid accumulation than the wild-type cells. Therefore, these cells recapitulate to some extent the characteristics of Lesch-Nyhan syndrome and can help researchers further investigate this genetic disease and analyze drugs that will prevent the onset of its symptoms. We therefore suggest that human diseases may be modeled using human ES cells.
Mixed-signal noise-decoupling via simultaneous power distribution design and cell customization in RAIL (2002)

An important and largely unexplored aspect of power distribution synthesis is cell customization. Through cell customization, power I/O cell assignments and local substrate and power supply decoupling may be tailored to reduce deleterious noise effects on analog circuits in mixed-signal environments. In this paper, we describe techniques for simultaneous power grid design (topology and sizing) and cell configuration/customization which allow designers to handle more difficult chip-level noise problems. We have incorporated this new approach in the power distribution synthesis tool RAIL and demonstrate its effectiveness on an industrial mixed-signal example.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Specificity and overlap in gene segment-defined antibody repertoires (2005)

Thus, as large-scale sequencing becomes cost-effective for clinical testing, we suggest that sequencing an individual's expressed antibody repertoire has the potential to become a useful diagnostic modality.
Contactless Electrofunctionalization of a Single Pore (2009)

Customized pores are smart components that find challenging applications in a variety of fields including purification membranes and biosensing systems. The incorporation of recognition probes within pores is therefore a challenge, due to the technical difficulty of delimiting the area functionalized and obtaining the localized, specific chemical modification of pore walls. An innovative approach, named contactless electrofunctionalization (CLEF), is presented to overcome this problem. CLEF allows easy, one-step modification of the inner surface of a pore etched in a dielectric membrane. The pore wall is coated under the influence of an electric field created by the application of a voltage between two electrodes, located near but not in contact with the pore openings. This specific localization of the deposited material within the pore is extremely rapid. Coatings were reliably and reproducibly obtained using polypyrrole co-polymers bearing oligonucleotides, demonstrating that this technology has a promising future in the design of biosensors. Moreover, the versatility of this process allows the deposition of various electroactive entities such as iridium oxide and therefore indicates a strong potential for diverse applications involving porous materials.
Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma (2009)

MicroRNAs (miRs) are non-coding RNA molecules involved in cancer initiation and progression. Deregulated miR expression has been implicated in cancer; however, there are no studies implicating an miR signature associated with progression in oral squamous cell carcinoma (OSCC). Although OSCC may develop from oral leukoplakia, clinical and histological assessments have limited prognostic value in predicting which leukoplakic lesions will progress. Our aim was to quantify miR expression changes in leukoplakia and same-site OSCC and to identify an miR signature associated with progression. We examined miR expression changes in 43 sequential progressive samples from 12 patients and four non-progressive leukoplakias from four different patients, using TaqMan Low Density Arrays. The findings were validated using quantitative RT-PCR in an independent cohort of 52 progressive dysplasias and OSCCs, and five non-progressive dysplasias. Global miR expression profiles distinguished progressive leukoplakia/OSCC from non-progressive leukoplakias/normal tissues. One hundred and nine miRs were highly expressed exclusively in progressive leukoplakia and invasive OSCC. miR-21, miR-181b and miR-345 expressions were consistently increased and associated with increases in lesion severity during progression. Over-expression of miR-21, miR-181b and miR-345 may play an important role in malignant transformation. Our study provides the first evidence of an miR signature potentially useful for identifying leukoplakias at risk of malignant transformation.
Btk inhibition treats TLR7/IFN driven murine lupus (2016)

Bruton's tyrosine kinase (Btk) is expressed in a variety of immune cells and previous work has demonstrated that blocking Btk is a promising strategy for treating autoimmune diseases. Herein, we utilized a tool Btk inhibitor, M7583, to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. In BXSB-Yaa lupus mice, Btk inhibition reduced autoantibodies, nephritis, and mortality. In the pristane-induced DBA/1 lupus model, Btk inhibition suppressed arthritis, but autoantibodies and the IFN gene signature were not significantly affected; suggesting efficacy was mediated through inhibition of Fc receptors. In vitro studies using primary human macrophages revealed that Btk inhibition can block activation by immune complexes and TLR7 which contributes to tissue damage in SLE. Overall, our results provide translational insight into how Btk inhibition may provide benefit to a variety of SLE patients by affecting both BCR and FcR signaling.
Kinetics of a Model Nucleoside (Guanosine) Release from Biodegradable Poly(dl-lactide-co-glycolide) Microspheres: A Delivery System for Long-Term Intraocular Delivery (2000)

The objective of this study was to prepare poly(DL-lactide-co-glycolide) (PLGA) microspheres containing guanosine as a model drug for intraocular administration. Microspheres were prepared by solvent evaporation technique using o/w emulsion system. The influence of composition and molecular weight of PLGA, drug loading efficiency, microsphere size, and in vitro and in vivo release rates were determined. Differential scanning calorimetry (DSC) and FTIR studies were conducted to examine the guanosine-polymer interaction. In vitro release studies indicated that the permeant release from microspheres exhibits an initial burst followed by slow first-order kinetics. Ascending molecular weights of the polymers generated progressively slower release rates. Three different sizes of microspheres were prepared. The release continued for 7 days with a maximum of 70% of the content released within that time period. DSC and FTIR studies showed no polymer-guanosine interaction. A novel microdialysis technique was used to examine the initial release kinetics from microspheres in isolated vitreous humor. This technique was also employed to observe in vivo intravitreal release in albino rabbits. A good correlation exists between in vitro and in vivo release rates from both 75 and 140 kDa PLGA microspheres. Guanosine-loaded microspheres could be prepared for once-a-week intravitreal injection with minimum required concentration maintained throughout the dosing interval. Because the structural and solubility characteristics of guanosine are similar to those of acyclovir and ganciclovir (two acycloguanosine analogues effective against herpes simplex virus [HSV-1] and cytomegalovirus [CMV], respectively), similar biodegradable polymer-based microsphere technology can be employed for the long-term intraocular delivery of these two drugs.
Baseline Compartment Pressure Measurements in Isolated Lower Extremity Fractures without Clinical Compartment Syndrome (2006)

Based on our data, use of direct compartment measurements with existing thresholds and formulations to determine the diagnosis of compartment syndrome may not accurately reflect a true existence of the syndrome. A search for other quantitative measures to more accurately reflect the presence of compartment syndrome is warranted.
Incidence and Predictors of Development of Acute Renal Failure Related to Treatment of Congestive Heart Failure with ACE Inhibitors (2006)

ARF and hyperkalemia are common complications in CHF patients after treatment with ACEI. Diabetic, hypertensive and class IV CHF patients who experienced a decrease in average blood pressure 25 mm Hg were more susceptible to ARF.
Probabilistic user behavior models (2004)

We present a mixture model based approach for learning individualized behavior models for the Web users. We investigate the use of maximum entropy and Markov mixture models for generating probabilistic behavior models. We first build a global behavior model for the entire population and then personalize this global model for the existing users by assigning each user individual component weights for the mixture model. We then use these individual weights to group the users into behavior model clusters. We show that the clusters generated in this manner are interpretable and able to represent dominant behavior patterns. We conduct offline experiments on around two months worth of data from CiteSeer, an online digital library for computer science research papers currently storing more than 470,000 documents. We show that both maximum entropy and Markov based personal user behavior models are strong predictive models. We also show that maximum entropy based mixture model outperforms Markov mixture models in recognizing complex user behavior patterns.
Induction of adenocarcinomas of the colon in mice by weekly injections of 1,2-dimethylhydrazine. (1973)

Summary Thirty-four CF1 mice were given weekly s.c. injections of 20 mg of 1,2-dimethylhydrazine hydrochloride per kg; this treatment induced colonic carcinomas in more than 90% of the animals after 186 days. The earliest change was found to be a widening of the proliferative compartment within the colonic crypts; at a later stage, there was an increase of the tritiated thymidine-labeling index from 9.3% at Day 45 to 16.2% at Day 87. The first histological changes were focal hyperplastic changes and focal atypias on the tip of the folds of the distal colonic mucosa (Day 38) confined to single crypts. The colonic tumors were located in the distal colon and rectum, with a high incidence of squamous cell cancers originating from the anal canal. Saline extracts of colonic tumor material precipitated specific antimouse embryonic rabbit serum. Assays of hypoxanthine phosphoribosyltransferase in the villus fraction of the small bowel of the 1,2-dimethylhydrazine hydrochloride-treated tumor-carrier mice indicated lower activity, compared to that of controls.