gebhart/patrepeval huggingface dataset:
Antibody Is Critical for the Clearance of Murine Norovirus Infection (2008)

Human noroviruses cause more than 90% of epidemic nonbacterial gastroenteritis. However, the role of B cells and antibody in the immune response to noroviruses is unclear. Previous studies have demonstrated that human norovirus specific antibody levels increase upon infection, but they may not be protective against infection. In this report, we used murine norovirus (MNV), an enteric norovirus, as a model to determine the importance of norovirus specific B cells and immune antibody in clearance of norovirus infection. We show here that mice genetically deficient in B cells failed to clear primary MNV infection as effectively as wild-type mice. In addition, adoptively transferred immune splenocytes derived from B-cell-deficient mice or antibody production-deficient mice were unable to efficiently clear persistent MNV infection in RAG1(-/-) mice. Further, adoptive transfer of either polyclonal anti-MNV serum or neutralizing anti-MNV monoclonal antibodies was sufficient to reduce the level of MNV infection both systemically and in the intestine. Together, these data demonstrate that antibody plays an important role in the clearance of MNV and that immunoglobulin G anti-norovirus antibody can play an important role in clearing mucosal infection.
Enzymatic glycocalyx treatment impairs insulin‐mediated recruitment of microvascular blood volume and decreases insulin sensitivity in rats (2011)

Agonist‐induced impairment of the blood‐exclusion properties of the glycocalyx has been shown to effectively increase microvascular blood volume (MBV) (VanTeeffelen, CVR 2010). Since the rapid insulin‐mediated increase in MBV has been suggested to contribute to insulin's metabolic actions (Vincent, Diabetes 2004), we hypothesize that loss of glycocalyx impairs the ability of insulin to increase MBV and to subsequently dispose blood glucose. In rats, loss of glycocalyx was induced by a bolus of hyaluronidase; saline served as control. During anesthesia the microcirculation of hindlimb muscle was visualized with a Side Stream Dark field camera before and during intravenous insulin infusion. The RBC column width distribution of visible microvessels was determined in time. In control, median RBC column width did not change during insulin infusion but the P75 and P90 increased rapidly (&lt;10 min) with 0.3 ± 0.1 μm and 0.8 ± 0.4 μm respectively. In the hyaluronidase treated group insulin had no effect on median, P75 and P90 of RBC column width. To measure insulin sensitivity an intravenous insulin tolerance test was performed in conscious rats. The insulin‐mediated decline in blood glucose after 15 minutes was found to be decreased after hyaluronidase treatment from 62 ± 1 to 53 ± 2% (P&lt;0.05). It is concluded that glycocalyx degradation is associated with an impaired ability for insulin to increase MBV and to dispose glucose. Supported by DFN 2006.00.027 and NHF 2005T037
Thermal characteristics of the self-healing response in poly(ethylene- co -methacrylic acid) copolymers (2006)

A class of poly(ethylene-co-methacrylic acid) (EMAA) copolymers and ionomers has shown the unique ability to instantaneously self-heal following ballistic puncture. It is noteworthy that the thermomechanical healing process active in these materials appears to be significantly different in capability and mechanism than any of the other self-repairing systems studied. To better understand this phenomenon, the thermal response during EMAA self-healing was examined. Tests of various damage types, including sawing, cutting and puncture, revealed high-energy transfer damage modes to produce heat and store energy favourable to healing. DSC probed healed specimens revealing they had reached the viscoelastic melt believed requisite to healing response. Low-temperature ballistic experiments demonstrated films continue healing even when punctured at -30 degrees C; analysis showed healing efficacy comparable to room temperature, holding significant pressures of approximately 3 MPa. At the lowest temperature, brittle fracture occurred in one material indicating insufficient heat transfer to store recoverable energy. In total, the results supported the defined healing model and provided additional information on the healing process in both its thermal dependence and general mechanism. Finally, a new DSC method was developed for probing the thermal history of healed films which may lead to a more complete mechanistic model.
Occurrence of lipid A variants with 27-hydroxyoctacosanoic acid in lipopolysaccharides from members of the family Rhizobiaceae (1991)

Lipopolysaccharides (LPSs) isolated from several strains of Rhizobium, Bradyrhizobium, Agrobacterium, and Azorhizobium were screened for the presence of 27-hydroxyoctacosanoic acid. The LPSs from all strains, with the exception of Azorhizobium caulinodans, contained various amounts of this long-chain hydroxy fatty acid in the lipid A fractions. Analysis of the lipid A sugars revealed three types of backbones: those containing glucosamine (as found in Rhizobium meliloti and Rhizobium fredii), those containing glucosamine and galacturonic acid (as found in Rhizobium leguminosarum bv. phaseoli, trifolii, and viciae), and those containing 2,3-diamino-2,3-dideoxyglucose either alone or in combination with glucosamine (as found in Bradyrhizobium japonicum and Bradyrhizobium sp. [Lupinus] strain DSM 30140). The distribution of 27-hydroxyoctacosanoic acid as well as analysis of lipid A backbone sugars revealed the taxonomic relatedness of various strains of the Rhizobiaceae.
Inhibition of growth of nonbasal planes in ice by fish antifreezes. (1989)

Peptide and glycopeptide antifreezes from a variety of cold-water fishes cause ice single crystals grown from the melt to assume unusual and strikingly similar habits. The antifreezes inhibit growth on the prism faces but allow limited growth on the basal plane. As new layers are deposited on the basal plane, pyramidal surfaces develop on the outside of the crystal, and large hexagonal pits form within the basal plane. The pits are rotated 30 degrees with respect to the normal orientation of hexagonal ice crystals. Growth inhibition on the prism, pyramidal, and pit faces indicates that these faces contain sites of adsorption of the antifreeze molecules. Several properties of the antifreeze pits are consistent with (but do not prove) an origin of the pits at dislocations. The similarity of crystal habit imposed on ice by antifreezes with wide differences in composition and structure indicates a common mechanism.
Replacement therapy for Addison's disease: recent developments (2008)

Patients with Addison's disease require mineralocorticoid replacement, i.e., fludrocortisone 0.05 - 0.20 mg once daily. Starting doses of glucocorticoids should be 15 - 20 mg for hydrocortisone or 20 - 30 mg for cortisone acetate, divided into two or three doses, and preferentially weight-adjusted. There are indications that the synthetic glucocorticoids have undesirable metabolic long-term effects, which make them less suitable as first-line treatment. Timed-release hydrocortisone tablets and continuous subcutaneous hydrocortisone infusion are promising new treatment modalities. Studies of replacement with the adrenal androgen dehydroepiandrosterone (DHEA) in adrenal failure have shown inconsistent benefit on HRQoL. DHEA, or possibly testosterone replacement is likely to be beneficial for selected groups of patients with Addison's disease but this remains to be shown. We here give our opinion of the best treatment and future direction of research in this area.
Inhibition of Ras for Cancer Treatment: The Search Continues (2011)

The RAS oncogenes (HRAS, NRAS and KRAS) comprise the most frequently mutated class of oncogenes in human cancers (33%), thus stimulating intensive effort in developing anti-Ras inhibitors for cancer treatment. Despite intensive effort, to date, no effective anti-Ras strategies have successfully made it to the clinic. We present an overview of past and ongoing strategies to inhibit oncogenic Ras in cancer. Since approaches to directly target mutant Ras have not been successful, most efforts have focused on indirect approaches to block Ras membrane association or downstream effector signaling. While inhibitors of effector signaling are currently under clinical evaluation, genome-wide unbiased genetic screens have identified novel directions for future anti-Ras drug discovery.
Fetal Brain Extracellular Matrix Boosts Neuronal Network Formation in 3D Bioengineered Model of Cortical Brain Tissue (2015)

The extracellular matrix (ECM) constituting up to 20% of the organ volume is a significant component of the brain due to its instructive role in the compartmentalization of functional microdomains in every brain structure. The composition, quantity and structure of ECM changes dramatically during the development of an organism greatly contributing to the remarkably sophisticated architecture and function of the brain. Since fetal brain is highly plastic, we hypothesize that the fetal brain ECM may contain cues promoting neural growth and differentiation, highly desired in regenerative medicine. Thus, we studied the effect of brain-derived fetal and adult ECM complemented with matricellular proteins on cortical neurons using <i>in vitro</i> 3D bioengineered model of cortical brain tissue. The tested parameters included neuronal network density, cell viability, calcium signaling and electrophysiology. Both, adult and fetal brain ECM as well as matricellular proteins significantly improved neural network formation as compared to single component, collagen I matrix. Additionally, the brain ECM improved cell viability and lowered glutamate release. The fetal brain ECM induced superior neural network formation, calcium signaling and spontaneous spiking activity over adult brain ECM. This study highlights the difference in the neuroinductive properties of fetal and adult brain ECM and suggests that delineating the basis for this divergence may have implications for regenerative medicine.
Cancer-Induced Immunosuppression: IL-18–Elicited Immunoablative NK Cells (2012)

During cancer development, a number of regulatory cell subsets and immunosuppressive cytokines subvert adaptive immune responses. Although it has been shown that tumor-derived interleukin (IL)-18 participates in the PD-1-dependent tumor progression in NK cell-controlled cancers, the mechanistic cues underlying this immunosuppression remain unknown. Here, we show that IL-18 converts a subset of Kit(-) (CD11b(-)) into Kit(+) natural killer (NK) cells, which accumulate in all lymphoid organs of tumor bearers and mediate immunoablative functions. Kit(+) NK cells overexpressed B7-H1/PD-L1, a ligand for PD-1. The adoptive transfer of Kit(+) NK cells promoted tumor growth in two pulmonary metastases tumor models and significantly reduced the dendritic and NK cell pools residing in lymphoid organs in a B7-H1-dependent manner. Neutralization of IL-18 by RNA interference in tumors or systemically by IL-18-binding protein dramatically reduced the accumulation of Kit(+)CD11b(-) NK cells in tumor bearers. Together, our findings show that IL-18 produced by tumor cells elicits Kit(+)CD11b(-) NK cells endowed with B7-H1-dependent immunoablative functions in mice.
The coupling of MDSCs with a computational analytic method to detect solid tumors. (2018)

24 Background: Myeloid-derived suppressor cells (MDSCs) are key contributors in supporting tumor progression and tumor escape through their ability to suppress anti-tumor responses mediated through T cell and natural killer (NK) cell activity. Several studies have demonstrated their utility as indicators of tumor progression and possible predictors of clinical outcomes, but there is significant overlap with healthy individuals preventing discrete and accurate calls. The objective of our study was to create a non-invasive cancer detection assay that analyzes flow cytometry data in an objective method using an artificial neural network (NN) to distinguish between cancer patients (CPs) and healthy donors (HDs) based upon the flow cytometry profiles of MDSCs and other leukocytes. Methods: We used standard multiparametric flow cytometry techniques to immunophenotype MDSCs and other leukocytes found in the peripheral blood of 52 biopsy-confirmed CPs with solid tumors and 70 HDs. A series of NNs utilizing pattern recognition computational algorithms are then created using three data sets: 1) the training set - this ‘teaches’ the two output categories of cancer and not cancer, 2) the validation set – this uses backpropagation to improve the accuracy of the trained networks, and 3) the testing set – this is used to rank the trained networks against each other. Finally, a naïve testing set is then used to determine the overall sensitivity and specificity for the top-ranking networks. Results: Using traditional flow cytometry gating methods to analyze MDSCs as a biomarker for cancer detection, it is difficult to achieve both high sensitivity and specificity due to the substantial overlap with healthy individuals. Here, we incorporated a standard 12 marker flow cytometry assay with NN technology to achieve a sensitivity of 92.3% and a specificity of 90.0% with an area under the ROC curve (AUC) of 0.9477. Conclusions: Pairing the advanced analytical capabilities of our NN with surface biomarker based analysis of MDSCs and certain leukocytes measured in peripheral blood has enabled us the ability to objectively identify patterns indicative for the existence of a solid tumor.
Broad Money Demand and Financial Liberalization in Greece (1996)

This paper develops a constant, data-coherent, error correction model for broad money demand (M3) in Greece. This model contributes to a better understanding of the effects of monetary policy in Greece and of the portfolio consequences of financial innovation in general. The broad monetary aggregate M3 was targeted until recently, and current monetary policy still uses such aggregates as guidelines, yet analysis of this aggregate has been dormant for over a decade.In spite of large fluctuations in the inflation rate, introduction of new financial instruments, and liberalization of the financial system, the estimated model is remarkably stable. The dynamics of money demand are important, with price and income elasticities being much smaller in the short run than in the long run.
Ecs, an ABC transporter of Bacillus subtilis: dual signal transduction functions affecting expression of secreted proteins as well as their secretion (1999)

ecs is a three-cistron operon of Bacillus subtilis, encoding proteins with similarity to the ATPase (EcsA) and hydrophobic components (EcsB) of ABC transporters. The ecsA26 point mutation was shown to cause a strong processing defect of a secreted alpha-amylase precursor (preAmyQ) and of three other exoproteins. Northern analysis of the level of amyQ mRNA showed that ecsA26 also decreases amyQ transcription. This effect too was pleiotropic, as judged by a drastic decrease in the expression from an exoprotease promoter of a reporter protein. A knockout mutation of the ecsB cistron caused a processing defect similar to ecsA26 but, unlike ecsA26, did not affect amyQ transcription. These was also no defect in transcription in the ecsA ecsB double mutant. Thus, an intact ecsB product was required for the downregulation of amyQ by the mutant ecsA. These results suggest a dual regulatory function for Ecs, in which Ecs, possibly as part of a signal transduction mechanism, regulates some component(s) of the protein secretion apparatus as well as secretory protein transcription in a co-ordinated fashion.
Do Antibodies Stimulate Myelin Repair in Multiple Sclerosis? (1999)

One of the major goals in the study of multiple sclerosis (MS) is to identify a beneficial therapeutic intervention that mimics the intrinsic reparative process and results in long-term clinical improvement. As yet, the therapeutic strategies tested in MS have failed to accomplish this task. However, one potential therapy that has shown some promise in rodent models of demyelination involves the administration of antibodies. Studies in various models of demyelination (virus-induced, autoimmune, and toxic) indicate that a subset of autoantibodies with reactivity to CNS antigens promote remyelination. We have identified a prototypic germline IgMk monoclonal antibody, designated SCH 94.03, with reactivity to a surface antigen on oligodendrocytes that promotes CNS remyelination. This antibody has the phenotypic features of polyreactive physiological natural autoantibodies. Additionally, treatment of MS patients with intravenous immunoglobulin, which contains these natural autoantibodies, may be efficacious in a subset of patients. We propose three mechanisms (direct stimulation of oligodendrocytes, immunomodulation, and opsonization of debris) by which polyreactive natural autoantibodies directed against CNS antigen may promote remyelination. Remyelination has the potential to not only improve conduction velocity but also may protect axons from injury and improve neurological function.
Variation in sequence and organization of splicing regulatory elements in vertebrate genes (2004)

Although core mechanisms and machinery of premRNA splicing are conserved from yeast to human, the details of intron recognition often differ, even between closely related organisms. For example, genes from the pufferfish Fugu rubripes generally contain one or more introns that are not properly spliced in mouse cells. Exploiting available genome sequence data, a battery of sequence analysis techniques was used to reach several conclusions about the organization and evolution of splicing regulatory elements in vertebrate genes. The classical splice site and putative branch site signals are completely conserved across the vertebrates studied (human, mouse, pufferfish, and zebrafish), and exonic splicing enhancers also appear broadly conserved in vertebrates. However, another class of splicing regulatory elements, the intronic splicing enhancers, appears to differ substantially between mammals and fish, with G triples (GGG) very abundant in mammalian introns but comparatively rare in fish. Conversely, short repeats of AC and GT are predicted to function as intronic splicing enhancers in fish but are not enriched in mammalian introns. Consistent with this pattern, exonic splicing enhancer-binding SR proteins are highly conserved across all vertebrates, whereas heterogeneous nuclear ribonucleoproteins, which bind many intronic sequences, vary in domain structure and even presence/absence between mammals and fish. Exploiting differences in intronic sequence composition, a statistical model was developed to predict the splicing phenotype of Fugu introns in mammalian systems and was used to engineer the spliceability of a Fugu intron in human cells by insertion of specific sequences, thereby rescuing splicing in human cells.
Passivity-Based Stabilization of Underwater Gliders With a Control Surface (2014)

The problem of stabilizing steady gliding is critical for an underwater glider, which is subject to many non-negligible disturbances from the aquatic environment. In this paper, we propose a new systematic controller design and implementation approach for the stabilization problem, including a nonlinear, passivity-based controller and a nonlinear model-based observer, where the actuation is realized through a whale tail-like control surface. The controller is designed based on an approximation of a reduced model that is obtained through singular perturbation analysis, and consequently, it does not require full state feedback. The local stability of the full closed-loop system is established through linearization analysis. The nonlinear observer is designed to estimate the velocity-related system states, which are difficult to measure for such low-speed underwater vehicles. Simulation results are first provided to demonstrate that the proposed controller achieves rapid convergence in stabilization and the proposed observer has good performance especially in robustness against measurement noise. Experimental results using a gliding robotic fish are presented to support the effectiveness of both the controller and the observer.
A review of methods for spike sorting: the detection and classification of neural action potentials (1998)

The detection of neural spike activity is a technical challenge that is a prerequisite for studying many types of brain function. Measuring the activity of individual neurons accurately can be difficult due to large amounts of background noise and the difficulty in distinguishing the action potentials of one neuron from those of others in the local area. This article reviews algorithms and methods for detecting and classifying action potentials, a problem commonly referred to as spike sorting. The article first discusses the challenges of measuring neural activity and the basic issues of signal detection and classification. It reviews and illustrates algorithms and techniques that have been applied to many of the problems in spike sorting and discusses the advantages and limitations of each and the applicability of these methods for different types of experimental demands. The article is written both for the physiologist wanting to use simple methods that will improve experimental yield and minimize the selection biases of traditional techniques and for those who want to apply or extend more sophisticated algorithms to meet new experimental challenges.
Efficient index lookup for De-duplication backup system (2008)

We minimizes fingerprint management overhead(index lookup and index insert) via introducing main memory index lookup structure and workload-aware index partitioning of the index file in the storage. Backup server maintains three data structures for redundancy elimination: Header files, chunk files and fingerprint tables. These data structures altogether enables PRUNE to effectively eliminate redundancy and to perform efficient backup. We perform various experiment to measure the overhead of each tasks in backup operation and to examine the efficiency of redundancy elimination. Incremental modulo-K reduces the file chunking latency by approximately 60%. With filter based in-memory index data structure and index partitioning, PRUNE eliminates 99.4% of disk accesses involved in fingerprint management.
Purification and biochemical characterization of some of the properties of recombinant human kynureninase (2002)

Recombinant human kynureninase (L-kynurenine hydrolase, EC 3.7.1.3) was purified to homogeneity (60-fold) from Spodoptera frugiperda (Sf9) cells infected with baculovirus containing the kynureninase gene. The purification protocol comprised ammonium sulfate precipitation and several chromatographic steps, including DEAE-Sepharose CL-6B, hydroxyapatite, strong anionic and cationic separations. The purity of the enzyme was determined by SDS/PAGE, and the molecular mass verified by MALDI-TOF MS. The monomeric molecular mass of 52.4 kDa determined was > 99.99% of the predicted molecular mass. A UV absorption spectrum of the holoenzyme resulted in a peak at 432 nm. The optimum pH was 8.25 and the enzyme displayed a strong dependence on the ionic strength of the buffer for optimum activity. This cloned enzyme was highly specific for 3-hydroxykynurenine (Km = 3.0 microm +/- 0.10) and was inhibited by L-kynurenine (Ki = 20 microm), d-kynurenine (Ki = 12 microm) and a synthetic substrate analogue D,L-3,7-dihydroxydesaminokynurenine (Ki = 100 nm). The activity/concentration profile for kynureninase from this source was sigmoidal in all instances. There appeared to be partial inhibition by substrate, and excess pyridoxal 5'-phosphate was found to be inhibitory.