gebhart/patrepeval huggingface dataset:
L-Tryptophan Supplementation in Parkinson's Disease (1989)

Two female Parkinsonian patients with levodopa-induced "On-Off" responded dramatically to administration of L-tryptophan supplementation. This report highlights the role of serotonergic deficiency in the pathophysiology of Parkinson's disease and of levodopa-induced motor fluctuations, and suggests that L-tryptophan supplementation may be useful in ameliorating motor complications of chronic levodopa therapy in the disease. The possibility that L-tryptophan supplementation with initiation of levodopa therapy may be useful in preventing levodopa-induced motor complications is discussed.
Cerebellar Stimulation for Seizure Control: 17-Year Study (1992)

Since 1974, 32 seizure patients have undergone chronic cerebellar stimulation (CCS); 27 have been contacted with 9 (7 spastic, 2 epileptic) continuing to use CCS for an average of 14.3 years (10-17 years). 6 (67%) are seizure-free and 3 (33%) have a reduction of seizure frequency. In the last 2 years, 2 other patients with spastic seizures, who were using CCS for 13 years, died of respiratory illness; 1 had been seizure-free and the other had a reduction. Of the remaining 16 patients (12 spastic, 4 epileptic) who did use CCS for an average of 8.3 years (2-14 years) and now have nonfunctioning stimulators, 5 (31%) continue to be seizure-free, 7 (44%) have a reduction and 4 (25%) have no change or a slight increase. Overall, 23 (85%) patients have benefitted from CCS. Stimulation charge densities were 0.9-2.5 microC/cm2/phase delivered at 10-180 pulses/sec to bilateral electrode pads on the superomedial cerebellar cortex. CCS is relatively safe and nonablative, and could be offered for patients with intractable seizures originating from bilateral or extratemporal foci.
Potent Antithrombin Activity and Delayed Clearance From the Circulation Characterize Recombinant Hirudin Genetically Fused to Albumin (1997)

In this study we sought to extend the plasma half-life while maintaining the potent antithrombin activity of hirudin. We hypothesized that gene fusion of hirudin to albumin would result in the expression of a slowly cleared hirudin molecule. A hirudin variant 3 (HV3) cDNA was obtained by gene synthesis, while a 1,996-bp full-length rabbit serum albumin (RSA) cDNA was selected from a rabbit liver cDNA library. Expression of the former in COS-1 cells conferred antithrombin activity on media conditioned by the cells, while expression of the latter resulted in the secretion of a 67-kD protein that reacted with mono-specific anti-RSA antibodies. Having shown independent expression of the two proteins, we next expressed two fusion proteins: HV3 linked via its C-terminus to albumin (HLA), and HV3 linked via its N-terminus to albumin (ALH). The former, but not the latter, inhibited both the amidolytic and fibrinogenolytic activities of thrombin. HLA also retained the dye-binding characteristics of RSA, as judged by Affi-Gel Blue chromatography. Highly similar concentrations of either commercial HV1 (40 nmol/L) or HLA (30 nmol/L) were required to halve the initial rate of thrombin reaction with chromogenic substrate S2238, suggesting the retention of high-affinity inhibition of thrombin by the fusion protein. An His-tagged form of HLA was purified by Ni2+-chelate affinity and heparin-Sepharose chromatography. The purified, radioiodinated protein was injected into rabbits, and demonstrated a catabolic half-life of 4.60 +/- 0.16 days. This represents an extension of hirudin half-life in vivo of greater than two orders of magnitude; gel analysis of HLA(H)6 recovered from rabbits showed that it circulated in intact form. Our results provide a rationale for future testing of the biological effects of HLA, and support our initial hypothesis.
cDNA Cloning and Chromosomal Localization of the Human and Mouse Isoforms of Ksp-Cadherin (1998)

Ksp-cadherin is a novel kidney-specific member of the cadherin superfamily of cell adhesion molecules. We have determined the complete cDNA coding sequences of both the human and the mouse isoforms of Ksp-cadherin. The inferred amino acid sequences of the human and mouse isoforms are 79 and 75% identical to the originally described rabbit isoform of Ksp-cadherin (Thomson et al., 1995; J. Biol. Chem. 270, 17594-17601), respectively. The relative locations of cadherin-specific sequence motifs, putative N-glycosylation sites, and characteristic protein domains are entirely conserved in all three isoforms. Multiple organ Northern analyses indicate that, as in the rabbit, both the human and the mouse Ksp-cadherin transcripts appear to have distinct kidney-specific distributions. The human Ksp-cadherin gene (CDH16) maps to chromosome 16q21-proximal 16q22. The mouse Ksp-cadherin gene (Cdh16) was localized to a highly syntenic region of distal Chromosome 8. Both the human and the mouse Ksp-cadherin genes were localized to previously identified clusters of cadherin gene sequences, consistent with the hypothesis that most cadherin family members arose by gene duplication from a single ancestral gene at a relatively early stage in the evolution of the mammalian genome.
Establishment and Characterization of Hepatic Stem-like Cell lines from Normal Adult Rat Liver (2008)

The liver is a unique organ with the potential to regenerate from injury. Hepatic stem cells contribute to liver regeneration when surviving hepatocytes in injured liver are unable to proliferate. To investigate the mechanism of liver regeneration in vitro, we established hepatic stem cell lines named HY1, HY2 and HY3, derived from a healthy liver of adult rat. HY cells showed an expression pattern similar to oval cells, and efficiently induced hepatic differentiation following sequential treatment with type I collagen, transforming growth factor-beta1 (TGF-beta1), and hepatocyte growth factor (HGF) or oncostatin M (OSM). These results suggested that HY cells are liver stem cells representing an excellent tool for in vitro studies on liver regeneration.
The effect of arachidonic- and eicosapentaenoic acid on the synthesis of prostacyclin-like material in human umbilical vasculature. (1980)

All cis-5,8,11,14,17 eicosapentaenoic acid (EPA) inhibits platelet aggregation. The mechanisms for this inhibition are not known in detail. One of them might be a competitive inhibition of TXA2 production. Even if rat and human vasculature in pure systems covert EPA to PGI3 with the same properties as PGI2, it is essential to known if EPA influences the conversion of arachidonic acid (AA) to PGI2 in human vasculature. This problem was investigated in human umbilical vascular tissue deprived of substrate for PGI synthesis. After incubation with AA or EPA alone and in combinations, prostacyclin synthesis was measured as PGI2. Prostacyclin production in assays with AA and EPA in combinations in the incubation mixture, was found additive as calculated from assays with pure substrates. Thus, EPA did not influence the conversion of AA to PGI2 but gave obviously rise to additional synthesis of PGI-like material.
Human CD4 + CD25 + regulatory cells have marked and sustained effects on CD8 + T cell activation (2003)

Amongst the many types of regulatory cells that have been described during the past few years, the spontaneously occurring population that is characterized by co-expression of CD4 and CD25 appears to play a key role in the prevention of autoimmunity and the maintenance of transplantation tolerance. In this study we have examined the ability of CD4(+)CD25(+) T cells to regulate human CD8(+) T cells, and the behavior of CD8(+) T cells following activation in the presence of regulatory CD4(+)CD25(+) T cells. The experiments described here demonstrate that human CD4(+)CD25(+) T cells cause pronounced and sustained inhibition of CD8(+) T cell proliferation in response to polyclonal and allogeneic stimulation. The regulation of CD8(+) T cell activation was cell contact-dependent and included inhibition of perforin, granzyme B and IFN-gamma cytokine production at the transcriptional level and impaired cytotoxicity. The regulated CD8(+) T cell population showed sustained hyporesponsiveness and refractoriness to exogenous IL-2. These data provide insights into the short- and long-term effects of CD4(+)CD25(+) T cells on CD8(+) T cells that could be of considerable value in optimizing vaccination against tumor and viral antigens.
Rheumatoid Factor and Immune Networks (1987)

Rheumatoid factors represent a normal component of the immune network. The autoantibodies promote complement fixation and clearance of immune complexes. They amplify the avidity of polyclonally induced IgG. Genes related to the primary structure of rheumatoid-factor light chains are widely distributed in the human population and have been conserved during the evolution and dispersion of the species. Products of these genes may be detected with anti-idiotypic antibodies against synthetic peptides corresponding to individual hypervariable regions on rheumatoid-factor light chains. Such anti-peptide antibodies provide unique reagents for analyzing the genetics of immunoglobulins in outbred populations. Precursors of rheumatoid factor are abundant among immature B lymphocytes. Some of these cells may tend to localize to mucosal surfaces, where they are stimulated directly by pathogenic microorganisms with polyclonal B cell-activating properties. Synthesis of rheumatoid factor regularly accompanies all secondary immune responses but is usually transient. Production of the autoantibody is T-cell dependent. The T cells may recognize antigen in an IgG-antigen immune complex that is processed and presented by B-cell precursors of rheumatoid factor. Rheumatoid factor-associated light-chain idiotypes are rare in serum IgG and on IgG myeloma proteins. They are common among monoclonal IgM proteins and on the surface of the malignant B cells from patients with chronic lymphatic leukemia. The rheumatoid factors that are produced by patients with mixed cryoglobulinemia, or primary Sjogren's syndrome can share idiotypic antigens with monoclonal rheumatoid factors. Rheumatoid factor synthesis in the diseases may reflect an abnormal proliferation of B-cells that is not antigen-driven and that can degenerate into malignancy. The rheumatoid factors in patients with rheumatoid arthritis are diverse and almost certainly represent the outcome of antigen-induced, T cell-dependent mechanisms. The antigens that drive the T cells have not been identified but could represent exogenous microorganisms, self components, or idiotypic antigens that fortuitously interact with rheumatoid factors.
Pareto-Based Multiobjective Machine Learning: An Overview and Case Studies (2008)

Machine learning is inherently a multiobjective task. Traditionally, however, either only one of the objectives is adopted as the cost function or multiple objectives are aggregated to a scalar cost function. This can be mainly attributed to the fact that most conventional learning algorithms can only deal with a scalar cost function. Over the last decade, efforts on solving machine learning problems using the Pareto-based multiobjective optimization methodology have gained increasing impetus, particularly due to the great success of multiobjective optimization using evolutionary algorithms and other population-based stochastic search methods. It has been shown that Pareto-based multiobjective learning approaches are more powerful compared to learning algorithms with a scalar cost function in addressing various topics of machine learning, such as clustering, feature selection, improvement of generalization ability, knowledge extraction, and ensemble generation. One common benefit of the different multiobjective learning approaches is that a deeper insight into the learning problem can be gained by analyzing the Pareto front composed of multiple Pareto-optimal solutions. This paper provides an overview of the existing research on multiobjective machine learning, focusing on supervised learning. In addition, a number of case studies are provided to illustrate the major benefits of the Pareto-based approach to machine learning, e.g., how to identify interpretable models and models that can generalize on unseen data from the obtained Pareto-optimal solutions. Three approaches to Pareto-based multiobjective ensemble generation are compared and discussed in detail. Finally, potentially interesting topics in multiobjective machine learning are suggested.
Order of action of components in the yeast pheromone response pathway revealed with a dominant allele of the STE11 kinase and the multiple phosphorylation of the STE7 kinase. (1992)

The signal transduction pathway that mediates the response of haploid yeast cells to peptide mating pheromones involves several components including the protein kinases STE7 and STE11. We have isolated and characterized a dominant allele of the STE11 gene and have demonstrated that expression of an amino-terminally truncated form of STE11 protein causes constitutive activation of the mating pathway. Expression of this dominant STE11 allele also restored mating ability to certain sterile strains. In conjunction with the results of others, our epistasis results establish the following order of action of pathway components: STE2, GPA1(SCG1), STE4, STE5, STE11, STE7, STE12. Transduction of the signal from STE11 to STE7 may involve phosphorylation because STE7 displays several phosphorylation forms, and STE7 is multiply phosphorylated in response to either pheromone or coexpression of dominant STE11 protein. Further signal propagation appears to require STE7 protein kinase activity, because a catalytically impaired STE7 mutant is defective in the mating response.
Enzyme therapy in mannose receptor-null mucopolysaccharidosis VII mice defines roles for the mannose 6-phosphate and mannose receptors (2006)

Enzyme replacement therapy (ERT) is available for several lysosomal storage diseases. Except for Gaucher disease, for which an enzyme with exposed mannosyl residues targets mannose receptors (MR) on macrophages, ERT targets primarily the mannose 6-phosphate receptor (MPR). Most recombinant lysosomal enzymes contain oligosaccharides with both terminal mannosyl and mannose 6-phosphate residues. Effective MPR-mediated delivery may be compromised by rapid clearance of infused enzyme by the MR on fixed tissue macrophages, especially Kupffer cells. To evaluate the impact of this obstacle to ERT, we introduced the MR-null mutation onto the mucopolysaccharidosis type VII (MPS VII) background and produced doubly deficient MR-/- MPS VII mice. The availability of both MR+/+ and MR-/- mice allowed us to study the effects of eliminating the MR on MR- and MPR-mediated plasma clearance and tissue distribution of infused phosphorylated (P) and nonphosphorylated (NP) forms of human beta-glucuronidase (GUS). In MR+/+ MPS VII mice, the MR clearance system predominated at doses up to 6.4 mg/kg P-GUS. Genetically eliminating the MR slowed plasma clearance of both P- and NP-GUS and enhanced the effectiveness of P-GUS in clearing storage in kidney, bone, and retina. Saturating the MR clearance system by high doses of enzyme also improved targeting to MPR-containing tissues such as muscle, kidney, heart, and hepatocytes. Although ablating the MR clearance system genetically is not practical clinically, blocking the MR-mediated clearance system with high doses of enzyme is feasible. This approach delivers a larger fraction of enzyme to MPR-expressing tissues, thus enhancing the effectiveness of MPR-targeted ERT.
Increase in and clearance of cell-free plasma DNA in hemodialysis quantified by real-time PCR (2006)

Plasma DNA levels significantly increase after a conventional 2.5-5-h HD session. Therefore, HD patients require special consideration for correct interpretation of plasma DNA concentrations. This parameter can be considered a reliable diagnostic tool for certain pathologies when measured at least 30 min after a HD session without further complications. The different dialysis membranes used in this study had no influence on cell-free plasma DNA concentrations, so the level of circulating DNA is not an appropriate marker of dialysis membrane biocompatibility.
Field Assays for Hygienic Behavior in Honey Bees (Hymenoptera: Apidae) (1998)

Honey bee, Apis mellifera L., hygienic behavior is a mechanism of disease resistance and a mode of defense against the parasitic mite Varroa jacobsoni Oudemans. Hygienic bees uncap and remove diseased and parasitized brood from the nest. The propagation of colonies that demonstrate resistance to chalkbrood and American foulbrood and that remove pupae infested by Varroa mites is becoming increasingly important in apiculture. This study evaluates 2 commonly used field assays used to screen colonies for hygienic behavior: the freeze-killed brood and the pierced brood assays. Both involve determining the time required for worker bees to remove dead capped brood from a section of comb. Colonies in the experiment displayed a wide range of removal rates and were grouped as hygienic, nonhygienic, or intermediate. The results of experiments 1 and 2 indicated that neither the age nor the source of the frozen brood had a significant effect on the removal rate by hygienic colonies (i.e., those colonies that consistently uncapped and removed freeze-killed brood within 48 h). In experiment 3, only a weak correlation was found between the removal of young freeze-killed and pierced pupae, but a significant correlation existed between the removal of pre-eclosion freeze-killed and pierced pupae. Experiment 4 examined cues that elicit removal behavior by hygienic and non hygienic colonies. When pupae were pierced with an insect pin through the base of the cell (without piercing the wax cell capping), there was no difference in the number of pupae removed by the hygienic and nonhygienic colonies. On average, 30% of all pierced pupae survived the treatment, which considerably diminished the accuracy and reproducibility of the test. When pupae were treated with hemolymph extracted from either a live or freeze-killed pupa, there was also no difference in the rate of removal by hygienic and nonhygienic colonies. These results indicate that bees from nonhygienic lines can be induced to express hygienic behavior only if a sufficiently strong stimulus is present. Both hygienic and nonhygienic colonies removed significantly more pupae treated with hemolymph from a dead pupa than hemolymph from a live pupa, indicating that the cue that stimulates removal behavior is stronger in dead pupae. It is concluded that the freeze-killed brood assay is the most conservative and reliable screening procedure for hygienic behavior. The following procedures are recommended: Randomly selected comb sections (5 by 6 cm each) of capped brood should be cut from 1 healthy colony, frozen, and introduced into the test colonies. The assay should be repeated at least twice. Only colonies that remove >95% of freeze-killed brood within 48 h in both tests should be considered hygienic. When developing hygienic breeder stock, the hygienic colonies should be challenged with the American foulbrood or chalkbrood pathogen to ensure resistance.
The ‘cleavage’ activities of foot-and-mouth disease virus 2A site-directed mutants and naturally occurring ‘2A-like’ sequences (2001)

The 2A/2B cleavage of aphtho- and cardiovirus 2A polyproteins is mediated by their 2A proteins 'cleaving' at their own C termini. We have analysed this activity using artificial reporter polyprotein systems comprising green fluorescent protein (GFP) linked via foot-and-mouth disease virus (FMDV) 2A to beta-glucuronidase (GUS) -- forming a single, long, open reading frame. Analysis of the distribution of radiolabel showed a high proportion of the in vitro translation products (approximately 90%) were in the form of the 'cleavage' products GUS and [GFP2A]. Alternative models have been proposed to account for the 'cleavage' activity: proteolysis by a host-cell proteinase, autoproteolysis or a translational effect. To investigate the mechanism of this cleavage event constructs encoding site-directed mutant and naturally occurring '2A-like' sequences were used to program in vitro translation systems and the gel profiles analysed. Analysis of site-directed mutant 2A sequences showed that 'cleavage' occurred in constructs in which all the candidate nucleophilic residues were substituted -- with the exception of aspartate-12. This residue is not, however, conserved amongst all functional '2A-like' sequences. '2A-like' sequences were identified within insect virus polyproteins, the NS34 protein of type C rotaviruses, repeated sequences in Trypanosoma spp. and a eubacterial alpha-glucosiduronasesequence(Thermatoga maritima aguA). All of the 2A-like sequences analysed were active (to various extents), other than the eubacterial alpha-glucosiduronase 2A-like sequence. This method of control of protein biogenesis may well not, therefore, be confined to members of the PICORNAVIRIDAE: Taken together, these data provide additional evidence that neither FMDV 2A nor '2A-like' sequences are autoproteolytic elements.
Novel Antisense and Peptide Nucleic Acid Strategies for Controlling Gene Expression (2002)

Antisense oligonucleotides have the potential to make revolutionary contributions to basic science and medicine. Oligonucleotides can bind mRNA and inhibit translation. Because they can be rapidly synthesized to be complementary to any sequence, they offer ideal tools for exploiting the massive amount of genome information now available. However, until recently, this potential was largely theoretical, and antisense experiments often produced inconclusive or misleading outcomes. This review will discuss the chemical and biological properties of some of the different types of oligomers now available and describe the challenges confronting in vitro and in vivo use of oligonucleotides. Oligomers with improved chemical properties, combined with advances in cell biology and success in clinical trials, are affording powerful new options for basic research, biotechnology, and medicine.
On the design of script languages for neural simulation (2012)

In neural network simulators, models are specified according to a language, either specific or based on a general programming language (e.g. Python). There are also ongoing efforts to develop standardized languages, for example NeuroML. When designing these languages, efforts are often focused on expressivity, that is, on maximizing the number of model types than can be described and simulated. I argue that a complementary goal should be to minimize the cognitive effort required on the part of the user to use the language. I try to formalize this notion with the concept of "language entropy", and I propose a few practical guidelines to minimize the entropy of languages for neural simulation.
Improved Single-Strand DNA Sizing Accuracy in Capillary Electrophoresis (1997)

Interpolation algorithms can be developed to size unknown single-stranded (ss) DNA fragments based on their electrophoretic mobilities, when they are compared with the mobilities of standard fragments of known sizes; however, sequence-specific anomalous electrophoretic migration can affect the accuracy and precision of the called sizes of the fragments. We used the anomalous migration of ssDNA fragments to optimize denaturation conditions for capillary electrophoresis. The capillary electrophoretic system uses a refillable polymer that both coats the capillary wall to suppress electro-osmotic flow and acts as the sieving matrix. The addition of 8 M urea to the polymer solution, as in slab gel electrophoresis, is insufficient to fully denature some anomalously migrating ssDNA fragments in this capillary electrophoresis system. The sizing accuracy of these fragments is significantly improved by the addition of 2-pyrrolidinone, or increased capillary temperature (60 degrees C). the effect of these two denaturing strategies is additive, and the best accuracy and precision in sizing results are obtained with a combination of chemical and thermal denaturation.