gebhart/patrepeval huggingface dataset:
R(+) pramipexole as a mitochondrially focused neuroprotectant: Initial early phase studies in ALS (2008)

R+ pramipexole (PPX) is a lipophilic cation that concentrates into brain and mitochondria and efficiently scavenges reactive oxygen and nitrogen species (RONS). Under the auspices of a Physician-Sponsor IND, R+PPX was dosed to small numbers of ALS patients for tolerability and safety while efficacy measures were also collected. The purpose of this paper is to describe the outcomes of these initial clinical studies. In a futility design study, 30 patients with early SALS were evaluated monthly for ALSFRS-R scores and FVC measurements for three months during lead-in, followed by open-label dosing at 30 mg/day of R+PPX for the next six months. In the dose escalation study, 10 subjects with early ALS received daily doses of R+PPX from 10 mg t.i.d. to 100 mg t.i.d. over seven weeks. In the open-label extension analysis, subjects from the initial studies were treated with 30 mg/day for at least six months, then switched to 60 mg/day. R+PPX was tolerated well in all studies. In the futility study, slopes of decline in ALSFRS-R scores and neurophysiological index (NI) values yielded non-significant reductions during treatment. In the dose-escalation study, all subjects increased daily R+PPX intake safely to 100 mg t.i.d. Markers of ALS did not change (ALSFRS-R) or improved (FVC). Trough and peak plasma (PPX) increased linearly with dosing, and several subjects achieved plasma (PPX) >1 microM. In the open-label extension protocol, changing from 30 to 60 mg/day caused a non-significant 17% reduction in slope of decline of ALSFRS-R. It was concluded that R+PPX was tolerated well in long-term dosing at 30 and 60 mg/day. Encouraging but non-significant effects of R+PPX on ALS decline were observed. High doses of R+PPX were tolerated well and yielded neuroprotective plasma levels. These findings support longer-term testing of higher R+PPX doses as a potential disease-altering therapy for SALS.
The expression of CD26 and CD40 ligand is mutually exclusive in human T- cell non-Hodgkin's lymphomas/leukemias (1995)

CD26 and CD40 ligand (CD40L) are surface molecules on human activated T lymphocytes that play a critical role in the regulation of lymphopoiesis. Both molecules are expressed on a restricted fraction of human T-cell non-Hodgkin's lymphomas (NHL)/leukemias; however, little is known about their functional and/or clinical significance in these disorders. In this study, the pattern of expression of CD40L was compared with that of the CD26 molecule. A series of 67 human T-cell NHL/leukemias and a panel of leukemia/lymphoma T-cell lines were evaluated by immunohistochemistry, flow cytometry, and RNA studies. The overall frequency of CD26+ and CD40L+ samples was rather similar (25/67 [37%] v 18/67 [27%]). However, the majority of CD26-expressing cases clustered in the lymphoblastic lymphomas (LBL)/T-acute lymphoblastic leukemias (ALL; 12/23) and CD30+ anaplastic large-cell (ALC) lymphomas (5/8), whereas CD40L+ lymphomas included a large fraction of mycosis fungoides (11/21 [52%]). CD26 and CD40L coexpression was found only in 2 myocosis fungoides cases and 1 small lymphocytic lymphoma. Thus, the expression of the two antigens was mutually exclusive in almost all T-cell lymphomas/leukemias. Accordingly, lymphoma cell lines expressed either one of the molecules or the relative amounts of CD26 and CD40L were inversely proportional. In contrast, reactive T lymphocytes from patients with non-neoplastic T-cell expansions and in vitro activated CD3+ or CD4+ normal T cells were found to coexpress CD40L and CD26. Results of a multivariate analysis showed that the expression of CD26 in T-cell LBL/ALL patients was associated to a worse outcome in terms of survival, as compared with patients with CD26- tumors (P < or = .0001). Based on our results, it can be concluded that, (1) as opposed to activated or reactive normal T cells, the expression of CD26 and of CD40L is mutually exclusive in human T-cell lymphomas/leukemias; (2) expression of CD26 is restricted to aggressive pathologic entities, such as T-cell LBL/ALL and T-cell CD30+ ALC lymphomas, whereas CD40L is expressed on slow progressing diseases such as mycosis fungoides; and (3) within the T-cell LBL/ALL group of tumors, CD26 may identify a subset of poor prognosis patients.
Electrospray ionisation-cleavable tandem nucleic acid mass tag–peptide nucleic acid conjugates: synthesis and applications to quantitative genomic analysis using electrospray ionisation-MS/MS (2006)

The synthesis and characterization of isotopomer tandem nucleic acid mass tag-peptide nucleic acid (TNT-PNA) conjugates is described along with their use as electrospray ionisation-cleavable (ESI-Cleavable) hybridization probes for the detection and quantification of target DNA sequences by electrospray ionisation tandem mass spectrometry (ESI-MS/MS). ESI-cleavable peptide TNT isotopomers were introduced into PNA oligonucleotide sequences in a total synthesis approach. These conjugates were evaluated as hybridization probes for the detection and quantification of immobilized synthetic target DNAs using ESI-MS/MS. In these experiments, the PNA portion of the conjugate acts as a hybridization probe, whereas the peptide TNT is released in a collision-based process during the ionization of the probe conjugate in the electrospray ion source. The cleaved TNT acts as a uniquely resolvable marker to identify and quantify a unique target DNA sequence. The method should be applicable to a wide variety of assays requiring highly multiplexed, quantitative DNA/RNA analysis, including gene expression monitoring, genetic profiling and the detection of pathogens.
Assembly of functional skeletal muscle troponin complex in Escherichia coli (1994)

The production of multi-subunit proteins of eukaryotic origin in Escherichia coli usually relies on the different subunits being expressed individually and the protein being reassembled in vitro. Here we describe the construction and characterization of plasmids capable of coexpressing the three subunits of chicken skeletal muscle troponin complex in E. coli. We demonstrate that the troponin subunits assembled in the cytoplasm of E. coli cell are fully functional. The troponin complex was purified to homogeneity in high yields. When reconstituted into actin filaments, the complex assembled in vivo was capable of regulating the myosin ATPase with a calcium dependence that was identical to the complex reconstituted in vitro. These results demonstrate that the coexpression of the subunits of a protein complex can prevent the accumulation of denatured proteins in inclusion granules.
Transgenic Expression of a Soluble Complement Inhibitor Protects Against Renal Disease and Promotes Survival in MRL/ lpr Mice (2002)

To investigate the role of complement in lupus nephritis, we used MRL/lpr mice and a transgene overexpressing a soluble complement regulator, soluble CR1-related gene/protein y (sCrry), both systemically and in kidney. Production of sCrry in sera led to significant complement inhibition in Crry-transgenic mice relative to littermate transgene negative controls. This complement inhibition with sCrry conferred a survival advantage to MRL/lpr mice. In a total of 154 animals, 42.5% transgene-negative animals had impaired renal function (blood urea nitrogen > 50 mg/dl) compared with 16.4% mice with the sCrry-producing transgene (p < 0.001). In those animals that died spontaneously, MRL/lpr mice with the sCrry-producing transgene did not die of renal failure, while those without the transgene did (blood urea nitrogen values of 46.6 +/- 9 and 122 +/- 29 mg/dl in transgene-positive and transgene-negative animals, respectively; p < 0.001). Albuminuria was reduced in those transgenic animals in which sCrry expression was maximally stimulated (urinary albumin/creatinine = 12.4 +/- 4.3 and 36.9 +/- 7.7 in transgene-positive and transgene-negative animals, respectively; p < 0.001). As expected in the setting of chronic complement inhibition, there was less C3 deposition in glomeruli of sCrry-producing transgenic mice compared with transgene-negative animals. In contrast, there was no effect on glomerular IgG deposition, levels of anti-dsDNA Ab and rheumatoid factor, or spleen weights between the two groups. Thus, long-term complement inhibition reduces renal disease in MRL/lpr mice, which translates into improved survival. MRL/lpr mice in which complement is inhibited still have spontaneous mortality, yet this is not from renal disease.
Fast Membrane Osmometer as Alternative to Freezing Point and Vapor Pressure Osmometry (2008)

Osmometry is an essential technique for solution analysis and the investigation of chemical and biological phenomena. Commercially available osmometers rely on the measurements of freezing point, vapor pressure, and osmotic pressure of solutions. Although vapor pressure osmometry (VPO) and freezing point osmometry (FPO) can perform rapid and inexpensive measurements, they are indirect techniques, which rely on thermodynamic assumptions, which limit their applicability. While membrane osmometry (MO) provides a potentially unlimited direct measurement of osmotic pressure and solution osmolality, the conventional technique is often time-consuming and difficult to operate. In the present work, a novel membrane osmometer is presented. The instrument significantly reduces the conventional MO measurement time and is not subject to the limitations of VPO and FPO. For this paper, the osmotic pressure of aqueous sucrose solutions was collected in a molality range 0-5.5, by way of demonstration of the new instrument. When compared with data found in the literature, the experimental data were generally in good agreement. However, differences among results from the three techniques were observed.
Antibody microarrays: An evaluation of production parameters (2003)

Antibody microarrays could have an enormous impact on the functional analysis of cellular activity and regulation, especially at the level of protein expression and protein-protein interaction, and might become an invaluable tool in disease diagnostics. The array surface is bound to have a tremendous influence on the findings from such studies. Apart from the basic issue of how to attach antibodies optimally without affecting their function, it is also important that the cognate antigens, applied within a complex protein mixture, all bind to the arrayed antibodies irrespective of their enormous variety in structure. In this study, various factors in the production of antibody microarrays on glass support were analysed: the modification of the glass surface; kind and length of cross-linkers; composition and pH of the spotting buffer; blocking reagents; antibody concentration and storage procedures, in order to evaluate their effect on array performance. Altogether, data from more than 700 individual array experiments were taken into account. In addition to home-made slides, commercially available systems were also included in the analysis.
Microbial and Enzyme-Induced Flavors in Dairy Foods (1990)

Microbial and enzymatic processes have become major routes for the production of flavors that comply with the definition of "natural" in the Federal Register. 1bis paper focuses on micro- organism, enzymes, substrates, and the production of significant odorants and tastants. The topics to be addressed include the following: a review of the dairy flavor symposia convened since 1969 by the author; retrospective of papers by the author on industrial dairy flavors; controlled dairy fermentations (microorganisms, enzymes, taste, and odor products); cheese (taste and odor constituents from microorganisms, proteins, and lipids); accelerated-ripened and enzyme-modified cheese (history, production, properties, and flavor constituents); dairy flavor bases (their characteristics and use in flavoring); and starter distillates (key flavor chemicals and microorganisms involved).
Degradation of Human Thyroperoxidase in the Endoplasmic Reticulum Involves Two Different Pathways Depending on the Folding State of the Protein (2000)

Human thyroperoxidase (hTPO), a type I transmembrane glycoprotein, plays a key role in thyroid hormone synthesis. In a previous paper (Fayadat, L., Niccoli, P., Lanet, J., and Franc, J. L. (1998) Endocrinology 139, 4277-4285) we established that after the synthesis, only 15-20% of the hTPO molecules were recognized by a monoclonal antibody (mAb15) directed against a conformational structure and that only 2% were able to reach the cell surface. In the present study using pulse-chase experiments in the presence or absence of protease inhibitors followed by immunoprecipitation procedures with monoclonal antibodies recognizing unfolded or partially folded hTPO forms we show that: (i) unfolded hTPO forms are degraded by the proteasome and (ii) partially folded hTPO forms are degraded by other proteases. It was also established upon incubating endoplasmic reticulum (ER) membranes in vitro that the degradation of the partially folded hTPO was carried out by serine and cysteine integral ER membrane proteases. These data provide valuable insights into the quality control mechanisms whereby the cells get rid of misfolded or unfolded proteins. Moreover, this is the first study describing a protein degradation process involving two distinct degradation pathways (proteasome and ER cysteine/serine proteases) at the ER level, depending on the folding state of the protein.
Molecular evidence for somatic recombination in the ribosomal DNA of Tetrahymena thermophila. (1988)

The ribosomal DNA (rDNA) in Tetrahymena thermophila is a 21-kilobase-pair palindromic DNA molecule that replicates autonomously in the macronucleus and is maintained at the level of about 10,000 copies per macronucleus. The rDNA of inbred strain C3 outreplicates the rDNA of inbred strain B in most B/C3 heterozygous macronuclei, generating macronuclei containing exclusively C3 rDNA sequences. In 1% or less of the B/C3 heterozygous macronuclei, however, rDNA sequences derived from both B and C3 strains persist in the macronucleus (co-maintainers). We report here that long-term culture of co-maintainers has yielded recombinant rDNA molecules combining sequences from both parental inbred strains. The genetic structure of such molecules also gives us virtual certainty that the differential replication of C3 rDNA with respect to B rDNA is due to the DNA sequence difference previously reported in domain 2 of the rDNA replication regions of the two strains.
Glycosylphosphatidylinositol-anchored proteins: structure, function, and cleavage by phosphatidylinositol-specific phospholipase C (2002)

A wide variety of proteins are tethered by a glycosylphosphatidylinositol (GPI) anchor to the extracellular face of eukaryotic plasma membranes, where they are involved in a number of functions ranging from enzymatic catalysis to adhesion. The exact function of the GPI anchor has been the subject of much speculation. It appears to act as an intracellular signal targeting proteins to the apical surface in polarized cells. GPI-anchored proteins are sorted into sphingolipid- and cholesterol-rich microdomains, known as lipid rafts, before transport to the membrane surface. Their localization in raft microdomains may explain the involvement of this class of proteins in signal transduction processes. Substantial evidence suggests that GPI-anchored proteins may interact closely with the bilayer surface, so that their functions may be modulated by the biophysical properties of the membrane. The presence of the anchor appears to impose conformational restraints, and its removal may alter the catalytic properties and structure of a GPI-anchored protein. Release of GPI-anchored proteins from the cell surface by specific phospholipases may play a key role in regulation of their surface expression and functional properties. Reconstitution of GPI-anchored proteins into bilayers of defined phospholipids provides a powerful tool with which to explore the interactions of these proteins with the membrane and investigate how bilayer properties modulate their structure, function, and cleavage by phospholipases.
Highly increased levels of tumor necrosis factor-alpha and other proinflammatory cytokines in psoriatic arthritis synovial fluid. (1997)

The pattern of expression of proinflammatory cytokines seen in PsA is similar to that in RA. Since PsA is also a destructive arthropathy, cytokines, in particular TNF-alpha and IL-1, may be principle factors in joint destruction.
An Intelligent Surveillance System for Dangerous Situation Detection in Home Environments. (2004)

In this paper we address the problem of human posture classification, in particular focusing to an indoor surveillance application. The approach was initially inspired to a previous works of Haritaoglou et al. [5] that uses histogram projections to classify people’s posture. Projection histograms are here exploited as the main feature for the posture classification, but, differently from [5], we propose a supervised statistical learning phase to create probability maps adopted as posture templates. Moreover, camera calibration and homography are included to solve perspective problems and to improve the precision of the classification. Furthermore, we make use of a finite state machine to detect dangerous situations as falls and to activate a suitable alarm generator. The system works on-line on standard workstations with network cameras.
Electrical and mechanical response of arteries to stimulation of sympathetic nerves (1966)

1. When common carotid arteries of sheep were studied in vitro by the sucrose-gap method, application of acetylcholine or nicotine caused small irregular spikes of depolarization. The discharge was prevented by hexamethonium, Hydergine, phentolamine, or chronic denervation, indicating that it represented electrical activity of groups of smooth muscle cells induced by the stimulation of sympathetic nerve fibres.2. The size of spikes produced by acetylcholine or nicotine, together with counts of the total number of smooth muscle cells in cross-sections of the arterial strips, indicated that the larger groups of smooth muscle cells activated by one sympathetic nerve fibre contained approximately 1300 cells.3. Sections of arteries treated with hot formaldehyde vapour contained numerous fluorescent fibres which were intensified by previous injection of noradrenaline into the animal and were scanty or absent after chronic sympathetic denervation. They are therefore believed to be post-ganglionic sympathetic nerve fibres.4. Most of these fibres ran circularly in the outer (1/2)-(3/4) of the media. A few ran longitudinally in the adventitia. There were none in the inner (1/4)-(1/2) of the media.5. Electrical stimulation of the cervical sympathetic nerve of anaesthetized sheep caused large contractions of the common carotid artery of the same side, reducing its external diameter by 30-39%.
Dimerization of Resistin and Resistin-like Molecules Is Determined by a Single Cysteine (2001)

Resistin is a peptide hormone secreted by adipocytes. Cysteine residues comprise 11 of 94 (12%) amino acids in resistin. The arrangement of these cysteines is unique to resistin and its recently discovered family of tissue-specific secreted proteins, which have been independently termed resistin-like molecules (RELMs) and the FIZZ (found in inflammatory zone) family. Here we show that resistin is a disulfide-linked homodimer that can be converted to a monomer by reducing conditions. The intestine-specific RELM beta has similar characteristics. Remarkably, however, the adipose-enriched RELM alpha is a monomer under non-reducing conditions. We note that RELM alpha lacks a cysteine residue, closest to the cleaved N terminus, that is present in resistin and RELM beta in multiple species. Conversion of this cysteine to alanine abolishes dimerization of resistin. Thus, a single disulfide bond is necessary to connect two resistin subunits in a homodimer. The additional 10 cysteines most likely participate in intramolecular disulfide bonds that define the conserved structure of the family members. The monomeric nature of RELM alpha suggests structural and potentially functional divergence between resistin and this close family member.
Auditory-perceptual approaches to phonetic perception (1982)

While acknowledging the important role of “top-down” processing in perceiving and understanding the speech of others, it is argued that an auditory-perceptual system which is modifiable by early experience and which is highly sensitive to spectral-temporal relations within speech sounds may eventually account for many of the facts of phonetic perception. Evidence pointing in this direction can be found in the perception of human speech by animals and human infants; in data pointing toward invariant, relational acoustic cues for phones whether consonant or vowels, and in comparison of the identification, discrimination, and adaptation of speech and nonspeech. The major shortcoming of auditory-perceptual interpretations has been the failure to provide a sensible approach to phenomena such as talker and rate normalization, cross-language differences, effects of “spectral trajectories,” and phoneme boundary shifts based on spectral-temporal alterations of synthetic syllables. Suggestions for new approaches to these matters are offered. [Supported by NINCDS Grant NS 03856.]
Seasonal distribution of pasture production in New Zealand (1982)

Abstract Pasture growth rates over 6 years are presented for 2 sites at Kowhitirangi near Hokitika on the West Coast of the South Island, on a gley recent soil and at Ahaura near Greymouth on a yellow brown earth soil. Growth rates from grazed pastures were assessed by a standardised cutting method at 4‐weekly intervals using a moveable cage technique. At both sites, pasture growth rate peaked in late spring, declined to a steady level from January to the end of March, and then declined further to a low level from May to September. The seasonal distribution of pasture growth was similar at both sites. On average, 5% of the anual yield was produced during winter, 37% in spring, 37% in summer, and 21% in autumn. The mean annual production was 8100 kg DM/ha at Kowhitirangi and 9370 kg DM/ha at Ahaura. Climatological data are given for each site or from nearby meteorological stations.
Recent Advances in AI Planning (1999)

The past five years have seen dramatic advances in planning algorithms, with an emphasis on propositional methods such as GRAPHPLAN and compilers that convert planning problems into propositional conjunctive normal form formulas for solution using systematic or stochastic SAT methods. Related work, in the context of spacecraft control, advances our understanding of interleaved planning and execution. In this survey, I explain the latest techniques and suggest areas for future research.