gebhart/patrepeval huggingface dataset:
Performance evaluation of a silk protein‐based matrix for the enzymatic conversion of tyrosine to L‐DOPA (2007)

L-DOPA (3,4-dihydroxyphenyl-L-alanine), one of the most important intermediates in the melanin biosynthesis pathway, is used for the treatment of Parkinson's disease. With a view of developing a cheaper and more effective method for the bioconversion of tyrosine to L-DOPA, the potential and performance of a novel fibrous matrix prepared from Bombyx mori silk protein fibroin were evaluated for the immobilization of tyrosinase. Cross-linkage between fibroin and tyrosinase using glutaraldehyde was evident from Fourier transform infra red spectroscopy. Maximum product formation occurred when 1000 U enzyme was immobilized on 20 mg fibroin. The optimum conditions for maximal L-DOPA production using immobilized tyrosinase were 40 degrees C and pH 5.5, conditions that caused a 50% loss of free enzyme activity. Immobilized tyrosinase also showed to have a higher degree of stability during storage and it retained 80% of its original activity after repeated reuses. The efficiency of this immobilized tyrosinase system to produce L-DOPA was high, as evident from a high effectiveness factor, between 0.7 and 0.8, thereby making this method feasible for the large-scale production of L-DOPA.
Risk and Safety of Probiotics (2015)

Probiotics have been used safely for years. Safety outcomes are inconsistently reported in published clinical trials. In 2011, a report released by the Agency for Healthcare Research and Quality concluded that, although the existing probiotic clinical trials reveal no evidence of increased risk, "the current literature is not well equipped to answer questions on the safety of probiotics in intervention studies with confidence." Critics point out that the preponderance of evidence, including the long history of safe probiotic use as well as data from clinical trials, and animal and in vitro studies all support the assumption that probiotics are generally safe for most populations. Theoretical risks have been described in case reports, clinical trial results and experimental models, include systemic infections, deleterious metabolic activities, excessive immune stimulation in susceptible individuals, gene transfer and gastrointestinal side effects. More research is needed to properly describe the incidence and severity of adverse events related to probiotics.
Polymer–Metal–Organic Frameworks (polyMOFs) as Water Tolerant Materials for Selective Carbon Dioxide Separations (2015)

Recently, polymer-metal-organic frameworks (polyMOFs) were reported as a new class of hybrid porous materials that combine advantages of both organic polymers and crystalline MOFs. Herein, we report a bridging coligand strategy to prepare new types of polyMOFs, demonstrating that polyMOFs are compatible with additional MOF architectures besides that of the earlier reported IRMOF-1 type polyMOF. Gas sorption studies revealed that these polyMOF materials exhibited relatively high CO2 sorption but very low N2 sorption, making them promising materials for CO2/N2 separations. Moreover, these polyMOFs demonstrated exceptional water stability attributed to the hydrophobicity of polymer ligands as well as the cross-linking of the polymer chains within the MOF.
Regulation of tumor necrosis factor receptor-1 and the IKK-NF-κB pathway by LDL receptor–related protein explains the antiinflammatory activity of this receptor (2008)

Low-density lipoprotein receptor-related protein (LRP-1) functions in endocytosis and in cell signaling directly (by binding signaling adaptor proteins) or indirectly (by regulating levels of other cell-surface receptors). Because recent studies in rodents suggest that LRP-1 inhibits inflammation, we conducted activity-based protein profiling experiments to discover novel proteases, involved in inflammation, that are regulated by LRP-1. We found that activated complement proteases accumulate at increased levels when LRP-1 is absent. Although LRP-1 functions as an endocytic receptor for C1r and C1s, complement protease mRNA expression was increased in LRP-1-deficient cells, as was expression of inducible nitric oxide synthase (iNOS) and interleukin-6. Regulation of expression of inflammatory mediators was explained by the ability of LRP-1 to suppress basal cell signaling through the I kappaB kinase-nuclear factor-kappaB (NF-kappaB) pathway. LRP-1-deficient macrophages, isolated from mice, demonstrated increased expression of iNOS, C1r, and monocyte chemoattractant protein-1 (MCP-1); MCP-1 expression was inhibited by NF-kappaB antagonism. The mechanism by which LRP-1 inhibits NF-kappaB activity involves down-regulating cell-surface tumor necrosis factor receptor-1 (TNFR1) and thus, inhibition of autocrine TNFR1-initiated cell signaling. TNF-alpha-neutralizing antibody inhibited NF-kappaB activity selectively in LRP-1-deficient cells. We propose that LRP-1 suppresses expression of inflammatory mediators indirectly, by regulating TNFR1-dependent cell signaling through the I kappaB kinase-NF-kappaB pathway.
Convexity-preserving B-spline modification (1997)

This report discusses the problem of modifying the shape of a cubic B-spline curve while retaining its convexity. This is achieved by moving control points in such a way as to maintain the appropriate shape of the corresponding control polygon. The problem is formulated as a linear programming problem, which may be solved using the simplex method. Two examples, taken from cross-sections of a ship hull, are discussed.
RNA-mediated pathogenic mechanisms in polyglutamine diseases and amyotrophic lateral sclerosis (2014)

Gene transcription produces a wide variety of ribonucleic acid (RNA) species in eukaryotes. Individual types of RNA, such as messenger, structural and regulatory RNA, are known to play distinct roles in the cell. Recently, researchers have identified a large number of RNA-mediated toxicity pathways that play significant pathogenic roles in numerous human disorders. In this article, we describe various common RNA toxicity pathways, namely epigenetic gene silencing, nucleolar stress, nucleocytoplasmic transport, bi-directional gene transcription, repeat-associated non-ATG translation, RNA foci formation and cellular protein sequestration. We emphasize RNA toxicity mechanisms that involve nucleotide repeat expansion, such as those related to polyglutamine (polyQ) disorders and frontotemporal lobar degeneration-amyotrophic lateral sclerosis.
Stress‐mediated signaling in PC12 cells – the role of the small heat shock protein, Hsp27, and Akt in protecting cells from heat stress and nerve growth factor withdrawal (2002)

We have investigated the role of stress-activated signaling pathways and the small heat shock protein, Hsp27, in protecting PC12 cells from heat shock and nerve growth factor (NGF) withdrawal-induced apoptosis. PC12 cells and a stable cell line overexpressing Hsp27 (HSPC cells) were subjected to heat shock. This resulted in the rapid activation of Akt followed by p38 mitogen-activated protein kinase (MAPK) signaling, with phosphorylation and intracellular translocation of Hsp27 also detectable. Hsp27 was found to form an immunoprecipitable complex with Akt and p38 MAPK in both non-stimulated and heat shocked cells, although after heat shock there was a gradual dissociation of Akt and p38 from the Hsp27. Cells were differentiated with NGF and then subjected to NGF withdrawal, a treatment which results in substantial cell death over 24-72 h. Hsp27 was shown to be protective against this treatment, since HSPC cells which overexpress Hsp27 showed significantly less cell death than the parental PC12 cells. In addition, we observed that phosphorylation of Akt was maintained in HSPC cells subjected to heat shock and NGF withdrawal compared with the parental cells. Taken together, our results suggest that Hsp27 may protect Akt from dephosphorylation and may also act in stabilizing Akt.
IL2RA/CD25 Gene Polymorphisms: Uneven Association with Multiple Sclerosis (MS) and Type 1 Diabetes (T1D) (2009)

These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases.
Energy efficient indexing on air (1994)

We consider wireless broadcasting of data as a way of disseminating information to a massive number of users. Organizing and accessing information on wireless communication channels is different from the problem of organizing and accessing data on the disk. We describe two methods, (1,m) Indexing and Distributed Indexing, for organizing and accessing broadcast data. We demonstrate that the proposed algorithms lead to significant improvement of battery life, while retaining a low access time.
Optical properties of PbTe and PbSe (2012)

We report optical properties of PbTe and PbSe as obtained from first-principles calculations with the Tran-Blaha modified Becke-Johnson potential. The results are discussed in relation to existing experimental data, particularly in relation to the temperature dependence of the band gap.
Transfer of phagocytosed particles to the parasitophorous vacuole of Leishmania mexicana is a transient phenomenon preceding the acquisition of annexin I by the phagosome (1997)

The eukaryotic intracellular pathogen Leishmania mexicana resides inside macrophages contained within a membrane bound parasitophorous vacuole which, as it matures, acquires the characteristics of a late endosomal compartment. This study reports the selectivity of fusion of this compartment with other particle containing vacuoles. Phagosomes containing zymosan or live Listeria monocytogenes rapidly fused with L. mexicana parasitophorous vacuoles, while those containing latex beads or heat killed L. monocytogenes failed to do so. Fusigenicity of phagosomes was not primarily dependent on the receptor utilized for ingestion, as opsonization with defined ligands could not overcome the exclusion of either latex beads or heat killed organisms. However modulation of intracellular pH by pharmacological agents such as chloroquine and ammonium chloride increased delivery of live Listeria and also induced transfer of previously excluded particles. The absence of fusion correlated with the acquisition of annexin I, a putative lysosomal targeting, molecule, on the phagosome membrane. We propose that the acquisition of cellular membrane constituents such as annexin I during phagosome maturation can ultimately direct the fusion pathway of the vesicles formed and have described a model system to further document changes in vesicle fusigenicity within cells.
Loss of Angiopoietin-like 7 diminishes the regeneration capacity of hematopoietic stem and progenitor cells (2015)

Successful expansion of hematopoietic stem cells (HSCs) would benefit the use of HSC transplants in the clinic. Angiopoietin-like 7 promotes the expansion of hematopoietic stem and progenitor cells (HSPC) in vitro and ex vivo. However, the impact of loss of Angptl7 on HSPCs in vivo has not been characterized. Here, we generated Angptl7-deficient mice by TALEN-mediated gene targeting and found that HSC compartments in Angptl7-null mice were compromised. In addition, wild type (WT) HSPCs failed to repopulate in the BM of Angptl7-null mice after serial transplantations while the engraftment of Angptl7-deficient HSPCs in WT mice was not impaired. These results suggest that Angptl7 is required for HSPCs repopulation in a non-cell autonomous manner.
Palmitate Inhibits Insulin Gene Expression by Altering PDX-1 Nuclear Localization and Reducing MafA Expression in Isolated Rat Islets of Langerhans (2005)

Abnormalities in lipid metabolism have been proposed as contributing factors to both defective insulin secretion from the pancreatic beta cell and peripheral insulin resistance in type 2 diabetes. Previously, we have shown that prolonged exposure of isolated rat islets of Langerhans to excessive fatty acid levels impairs insulin gene transcription. This study was designed to assess whether palmitate alters the expression and binding activity of the key regulatory factors pancreas-duodenum homeobox-1 (PDX-1), MafA, and Beta2, which respectively bind to the A3, C1, and E1 elements in the proximal region of the insulin promoter. Nuclear extracts of isolated rat islets cultured with 0.5 mm palmitate exhibited reduced binding activity to the A3 and C1 elements but not the E1 element. Palmitate did not affect the overall expression of PDX-1 but reduced its nuclear localization. In contrast, palmitate blocked the stimulation of MafA mRNA and protein expression by glucose. Combined adenovirus-mediated overexpression of PDX-1 and MafA in islets completely prevented the inhibition of insulin gene expression by palmitate. These results demonstrate that prolonged exposure of islets to palmitate inhibits insulin gene transcription by impairing nuclear localization of PDX-1 and cellular expression of MafA.
Effects of a Circulating-water Garment and Forced-air Warming on Body Heat Content and Core Temperature (2004)

The circulating-water system transferred more heat than forced air, with the difference resulting largely from posterior heating. Circulating water rewarmed patients 0.4 degrees C/h faster than forced air. A substantial peripheral-to-core tissue temperature gradient with each device indicated that peripheral tissues insulated the core, thus slowing heat transfer.
3'-Azido-3'-deoxythymidine triphosphate as an inhibitor and substrate of purified human immunodeficiency virus reverse transcriptase (1987)

Reverse transcriptase was purified from human immunodeficiency virus (HIV). It utilized the artificial primer-template poly(rA)-oligo(dT)12-18 more efficiently than activated calf thymus DNA, poly(rI)-oligo(dC)12-18, poly(rC)-oligo(dG)12-18, or poly(rCm)-oligo(dG)12-18. Maximum activity was observed at pH 7.0 to 7.6 in the presence of 5 mM MgCl2 and 100 mM KCl. 3'-Azido-3'-deoxythymidine triphosphate competed with dTTP for binding to HIV reverse transcriptase. Different kinetic constants were obtained with different primer-templates. Km and Ki values of 2.8 and 0.04 microM, respectively, were obtained with poly(rA)-oligo(dT)12-18. The corresponding values were 1.2 and 0.3 microM, respectively, with activated calf thymus DNA and 0.3 and 0.01 microM, respectively, with extracted virus and native template. Inhibition of the host cell DNA polymerases alpha and beta was considerably weaker. The Km and Ki values obtained with activated calf thymus DNA as the primer-template were 2.4 and 230 microM, respectively, for DNA polymerase alpha and 6.0 and 73 microM, respectively, for DNA polymerase beta. 3'-Azido-3'-deoxythymidine triphosphate could also serve as an alternate substrate for HIV reverse transcriptase. The resulting incorporation of 3'-azido-3'-deoxythymidine triphosphate into poly(rA)-oligo(dT)12-18 caused chain termination and premature deceleration of the reaction. The terminated primer could not be elongated when incubated with dTTP and HIV reverse transcriptase.
Membrane properties of single muscle cells of the rhabdosphincter of the male urethra (2004)

Porcine RS and LLSKM myoblasts and human RS and human skeletal muscle cells show a high degree of similarity. Injection of autologous skeletal muscle myoboblasts in the lower urinary tract might, therefore, represent a promising approach to treat stress incontinence after radical prostatectomy.
Contrasting roles for integrin beta 1 and beta 5 cytoplasmic domains in subcellular localization, cell proliferation, and cell migration. (1994)

To carry out a detailed comparison of the roles of integrin beta 1 and beta 5 cytoplasmic domains, we expressed both wild type beta 1 and chimeric beta 1/5 constructs in CHO cells. In the latter, the cytoplasmic domain of beta 1 was replaced with that of beta 5. The human beta 1 and beta 1/5 constructs appeared at similar levels at the cell surface (mostly as alpha 5 beta 1 heterodimers) and contributed equally to CHO cell adhesion to fibronectin. However, beta 1 but not beta 1/5 localized to focal adhesion-like structures when CHO cells were spread on fibronectin. Furthermore, only the beta 1-CHO cells showed increased proliferation in response to fibronectin plus an integrin-activating anti-beta 1 antibody, and showed increased appearance of 32P-labeled protein (p90) that correlated with proliferation. In sharp contrast, the beta 1/5-CHO cells were notably more migratory than beta 1-CHO cells in a transwell haptotactic migration assay. These results indicate that the beta 1 and beta 5 integrin subunit cytoplasmic domains can translate similar adhesive information into highly contrasting subsequent events. Thus, we have established that "inside-out" and "outside-in" integrin signaling pathways are regulated by fundamentally distinct mechanisms. In addition, we suggest that the same properties of the beta 1 cytoplasmic domain that promote recruitment to visible focal adhesion-like structures may also be conductive to cell proliferation. Conversely, the properties of the beta 5 tail that make it less likely to localize into focal adhesion-like structures may contribute to enhanced cell migration.
Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study (2007)

We found uNGAL to be a useful early AKI marker that predicted development of severe AKI in a heterogeneous group of patients with unknown timing of kidney injury.
A Phase 1 Study of Combotox in Pediatric Patients With Refractory B-lineage Acute Lymphoblastic Leukemia (2009)

Combotox can be safely administered to children with refractory leukemia. It has clinically important anticancer activity as a single agent. The recommended dose for future studies is 5 mg/m2/dose.
Interactions of Triglyceride-Rich Lipoproteins with Receptors: Modulation by Thrombin (1986)

Large VLDL from subjects with HTG but not normal humans bind with high affinity to both the classic LDL receptor present on all cells and the beta-VLDL receptor of macrophages. Binding of HTG-VLDL to the LDL receptor is mediated by a thrombin-accessible conformation of Apo E that is absent in normal VLDL. Binding of HTG VLDL to the beta-VLDL receptor appears to be mediated by one or more apo B species. We find that thrombin-accessible apo E is required for uptake of HTG-VLDL via the LDL receptor but not by the beta-VLDL receptor. Domains within apo B that are present in native chylomicrons and HTG-VLDL or created in vitro with thrombin appear to be required for binding to the beta-VLDL receptor but not the LDL receptor. Triglyceride-rich lipoproteins could be processed in vivo by thrombin or other proteases for preferential uptake and disposal by the beta-VLDL receptor pathway. This process may be involved in the foam cell accumulation and atherosclerosis associated with some types of hypertriglyceridemia.
Sequencing Bacillus anthracis Typing Phages Gamma and Cherry Reveals a Common Ancestry (2006)

The genetic relatedness of the Bacillus anthracis typing phages Gamma and Cherry was determined by nucleotide sequencing and comparative analysis. The genomes of these two phages were identical except at three variable loci, which showed heterogeneity within individual lysates and among Cherry, Wbeta, Fah, and four Gamma bacteriophage sequences.
Visualization of the Retinal Image in an Eye Model With Spherical and Aspheric, Diffractive, and Refractive Multifocal Intraocular Lenses (2008)

This visualization technique furthers the understanding of the working principles and quality of the retinal images produced by different mono- and multifocal IOLs.
Revised Limit Cycle Oscillator Model of Human Circadian Pacemaker (1999)

In 1990, Kronauer proposed a mathematical model of the effects of light on the human circadian pacemaker. This study presents several refinements to Kronauer's original model of the pacemaker that enable it to predict more accurately the experimental results from a number of different studies of the effects of the intensity, timing, and duration of light stimuli on the human circadian pacemaker. These refinements include the following: The van der Pol oscillator from Kronauer's model has been replaced with a higher order limit cycle oscillator so that the system's amplitude recovery is slower near the singularity and faster near the limit cycle; the phase and amplitude of the circadian rhythm in sensitivity to light from Kronauer's model has been refined so that the peak sensitivity to light on the limit cycle now occurs approximately 4 h before the core body temperature minimum (CBTmin) and is three times as great as the minimum sensitivity on the limit cycle; the critical phase (at which type 1 phase response curves [PRCs] can be distinguished from type 0 PRCs) that occurs at CBT,n now corresponds to 0.8 h after the minimum of x (x(min) in this refined model rather than to the exact timing of x(min) as in Kronauer's model; a direct effect of light on circadian period was incorporated into the model such that as light intensity increases, the period decreases, which is in accordance with Aschoff's rule.
Functional Characterization of Sodium-Dependent Multivitamin Transporter in MDCK-MDR1 Cells and Its Utilization as a Target for Drug Delivery (2006)

The objective of this research is to characterize a sodium-dependent multivitamin transporter (SMVT) in MDCK-MDR1 cells (Madin-Darby canine kidney cells transfected with the human MDR1 gene) and to investigate the feasibility of utilizing the MDCK-MDR1 cell line as an in vitro model to study the permeability of biotin-conjugated prodrugs of anti-HIV protease inhibitors. Mechanism of [3H]biotin uptake and transport was delineated. Transepithelial permeability of the biotin-conjugated prodrug, i.e., biotin-saquinavir, was also studied. Reverse transcription polymerase chain reaction (RT-PCR) was carried out to confirm the existence of SMVT in MDCK-MDR1 cells. Biotin uptake was Na+, pH, and temperature dependent, but energy independent. Uptake of biotin was found to be saturable with a Km of 13.0 microM, Vmax 21.5 of pmol min-1 (mg of protein)-1, and Kd of 0.12 microL min-1 (mg of protein)-1. Both apical and basal uptake and transepithelial transport of [3H]biotin showed that SMVT localized predominantly on the apical membrane of MDCK-MDR1 cells. [3H]Biotin uptake was inhibited by excess unlabeled biotin and its structural analogues, i.e., desthiolbiotin and valeric acid, and other vitamins such as lipoic acid and pantothenic acid, but not by acetic acid, benzoic acid, biotin methyl ester, and biocytin. Biotin-saquinavir caused lowering of [3H]biotin uptake, which indicates that it is recognized by SMVT. Apical to basal transport of [3H]biotin was also significantly inhibited in the presence of excess biotin or biotin-saquinavir. Transepithelial transport studies of biotin-saquinavir in MDCK-MDR1, wild type MDCK, and Caco-2 cells revealed that permeability of biotin-saquinavir was similar in all three cell lines. A band of SMVT mRNA at 862 bp was identified by RT-PCR. A sodium-dependent multivitamin transporter, SMVT, responsible for biotin uptake and transport, was identified and functionally characterized in MDCK-MDR1 cells. Therefore, the MDCK-MDR1 cell line may be utilized as an in vitro model to study the permeability of biotin-conjugated prodrugs such as HIV protease inhibitors.