gebhart/patrepeval huggingface dataset:
Disease-causing missense mutations in actin binding domain 1 of dystrophin induce thermodynamic instability and protein aggregation (2010)

Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD) most commonly through loss of protein expression. In a small subpopulation of patients, missense mutations can cause DMD, Becker muscular dystrophy, or X-linked cardiomyopathy. Nearly one-half of disease-causing missense mutations are located in actin-binding domain 1 (ABD1) of dystrophin. To test the hypothesis that ABD1 missense mutations cause disease by impairing actin-binding activity, we engineered the K18N, L54R, D165V, A168D, L172H, and Y231N mutations into the full-length dystrophin cDNA and characterized the biochemical properties of each mutant protein. The K18N and L54R mutations are associated with the most severe diseases in humans and each caused a small but significant 4-fold decrease in actin-binding affinity, while the affinities of the other four mutant proteins were not significantly different from WT dystrophin. More interestingly, WT dystrophin was observed to unfold in a single-step, highly cooperative manner. In contrast, all six mutant proteins were significantly more prone to thermal denaturation and aggregation. Our results suggest that missense mutations in ABD1 may all cause loss of dystrophin function via protein instability and aggregation rather than through loss of ligand binding function. However, more severe disease progressions may be due to the combinatorial effects of some mutations on both protein aggregation and impaired actin-binding activity.
La théorie marxiste du parti (2009)

This paper examines the conceptions of the revolutionary party among some of the most importantMarxist thinkers of the XXth century, through three interrelated essential issues&#160;: 1) the levels of classconsciousness&#160;; 2) the relationship of the party to the masses, in particular during a revolution&#160;; 3) theinternal structure of the party. In our view, the chosen authors &#8211; Lenin, Rosa Luxemburg, Gramsci,Lukacs, Trotsky &#8211; belong to the same &#171;&#160;current&#160;&#187; in Marxism, a current which tries to develop, considering the conditions of the XXth century, Marx&#8217;s theses on the communist revolution and theproletarian self-emancipation&#160;; a current which is contradictory and diverse, inside of which Leninand Luxemburg represent two partially opposed and partially complementary poles.
Corneal keratocytes: in situ and in vitro organization of cytoskeletal contractile proteins. (1994)

This study demonstrates that there are major structural differences in the organization of contractile cytoskeletal proteins between normal, quiescent (in situ), and activated (in vitro) keratocytes. In situ, contractile proteins appear to be associated with the cortical f-actin network, probably related to maintenance of cell shape and interconnectivity. Alternatively, activated keratocytes were characterized by the presence of a putative contractile apparatus comprised of f-actin, myosin, and alpha-actinin organized into sarcomeric, muscle-like bundles (stress fibers) associated with focal contacts containing alpha 5 beta 1 integrin. These data suggest that activation of keratocytes, i.e. myofibroblast transformation, must involve the reorganization of cytoplasmic contractile proteins as well as the expression of alpha 5 beta 1 integrin and the formation of focal contacts.
Silencing of P2Y2 receptors reduces intraocular pressure in New Zealand rabbits (2011)

P2Y(2) receptors increase IOP in New Zealand rabbits. The application of a siRNA for this receptor significantly reduced IOP, suggesting that this technology might be used for the treatment of glaucoma.
A Novel Two-Transistor Floating-Body/Gate Cell for Low-Power Nanoscale Embedded DRAM (2008)

A novel two-transistor (2T) floating-body cell (FBC) for embedded-DRAM applications is proposed and demonstrated via device/circuit simulations using a process/physics-based compact model, with numerical-simulation support. Significant advantages of the 2T cell, in which the charged/discharged body of one transistor (1T) drives the gate of the other, over the currently popular 1T-DRAM FBC are noted and explained. Furthermore, a modification of the basic 2T-FBC structure, which in essence results in a floating-body/gate cell (FBGC), is shown to yield dramatic reduction in power dissipation in addition to better signal margin, longer data retention, and higher memory density. Design and processing issues that need to be addressed for optimal performance and for sustained FBGC viability in nanoscale CMOS are discussed.
Spectral beam combining of thulium fiber laser systems (2010)

Beams from three frequency stabilized master oscillator power amplifier (MOPA) thulium fiber laser systems were spectrally beam combined using a metal diffraction grating. Two of the laser oscillators were stabilized with guided mode resonances filters while the third was stabilized using a gold-coated diffraction grating. Each system was capable of producing a minimum of 40 W output powers with slope efficiencies between 50-60 %. The three lasers undergoing combination were operating at wavelengths of 1984.3, 2002.1, and 2011.9 nm with spectral linewidths between 250-400 pm. Beam combining was accomplished by spatially overlapping the spectrally separated beams on a water-cooled gold-coated diffraction grating with 600 lines/mm. Beam quality measurements were completed using M<sup>2</sup> measurements at multiple power levels of the combined beam. Power levels of 49 W were achieved before thermal heating of the metal diffraction grating cause degradation in beam quality. The combining grating was ~66% efficient for the unpolarized light corresponding to a total optical-to-optical efficiency of 33% with respect to launched pump power.
Design of DNA-Binding Peptides Based on the Leucine Zipper Motif (1990)

A class of transcriptional regulator proteins bind to DNA at dyad-symmetric sites through a motif consisting of (i) a "leucine zipper" sequence that associates into noncovalent, parallel, alpha-helical dimers and (ii) a covalently connected basic region necessary for binding DNA. The basic regions are predicted to be disordered in the absence of DNA and to form alpha helices when bound to DNA. These helices bind in the major groove forming multiple hydrogen-bonded and van der Waals contacts with the nucleotide bases. To test this model, two peptides were designed that were identical to natural leucine zipper proteins only at positions hypothesized to be critical for dimerization and DNA recognition. The peptides form dimers that bind specifically to DNA with their basic regions in alpha-helical conformations.
Highly reliable 50nm contact cell technology for 256Mb PRAM (2005)

Novel small contact fabrication technologies were proposed to realize reliable high density 256Mb PRAM(phase change memory) product. Introducing the 2-step CMP (chemical mechanical polishing) process and the ring-shaped contact structure, the contact area distribution was greatly improved even at the smallest contact diameter of 50nm node. The validity of this approach was directly confirmed by the evaluation of the functionality for the fabricated 256Mbit PRAM based on 0.10/spl mu/m CMOS technology.
Vagus nerve stimulation protects against ventricular fibrillation independent of muscarinic receptor activation (2011)

We show that the vagal anti-fibrillatory action in the rabbit ventricle occurs via post-ganglionic efferent nerve fibres, independent of muscarinic receptor activation, VIP, and the endothelium. Together with our previous publications, our data support the possibility of a novel ventricular nitrergic parasympathetic innervation and highlight potential for new therapeutic targets to treat ventricular dysrhythmias.
A super-secondary structure predicted to be common to several α-1,4-d-glucan-cleaving enzymes (1989)

Predictions of protein secondary structure are used with amino acid sequence alignments to show that the N-terminal domains of cyclodextrin glucanotransferases and a yeast alpha-glucosidase may have the same super-secondary structure as alpha-amylases, i.e. an (alpha/beta)8-barrel fold. Sequence similarities provide evidence that glucanotransferases, and possibly the glucosidase, are, like alpha-amylases, Ca2+-containing enzymes. The relationship between substrate specificity and the nature of the amino acid residues proposed at the active site is discussed for the transferases and alpha-glucosidase. A set of three programs for an Apple IIe computer to carry out the calculations described by Garnier, Osguthorpe & Robson [(1978) J. Mol. Biol. 120, 97-120] and a set of four programs for an Apple IIe computer to carry out the calculations described by Levin, Robson & Garnier [(1986) FEBS Lett. 205, 303-308] have been deposited as Supplementary Publication SUP 50149 (25 pages) at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1989) 257, 5.
The strong enhancer element in the immediate early region of the human cytomegalovirus genome (1985)

The human cytomegalovirus (HCMV), a member of the herpesvirus group, was found to possess a strong transcription enhancer in the immediate early gene region. Co-transfection of enhancerless SV40 DNA with randomly fragmented HCMV DNA yielded two SV40-like recombinant viruses , each containing HCMV DNA fragments that were substituting for the missing SV40 enhancer. The two inserts , 341 and 262 bp in length , are overlapping segments of genuine viral DNA representing part of the 5'flanking region of the major immedistte early gene i n HCMV. Studies with deletion mutants showed that different nonoverlapping subsets of the HCMV enhancer region can substitute for the 72 bp repeats of SV40. Transient expression assays indicated that the HCMV enhancer is significantly stronger than the SV40 element, activating cis-linked heterologous promoters in a wide spectrum of cultured cells. It appears that the HCMV enhancer is positively regulated by viral immediate early genes.
ChemInform Abstract: Local Structure of Defects on Hydrogen‐ and Vacuum‐Reduced TiO2 Surfaces (1993)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Inhibition of mitochondrial metabolism by methyl-2-cyano-3,12-dioxooleana-1,9-diene-28-oate induces apoptotic or autophagic cell death in chronic myeloid leukemia cells (2008)

The initial success of the first synthetic bcr-abl kinase inhibitor imatinib has been dampened by the emergence of imatinib-resistant disease in blast crisis chronic myeloid leukemia. Here, we report that the novel triterpenoid methyl-2-cyano-3,12-dioxooleana-1,9-diene-28-oate (CDDO-Me) potently induced cytotoxicity in imatinib-resistant KBM5 cells expressing the T315I mutation of bcr-abl (24-h EC50, 540 nmol/L). In long-term culture, CDDO-Me abrogated the growth of human parental KBM5 and KBM5-STI cells with 96-h IC50 of 205 and 221 nmol/L, respectively. In addition, CDDO-Me rapidly decreased the viability of murine lymphoid Ba/F3 cells expressing wild-type p210 as well as the imatinib-resistant E255K and T315I mutations of bcr-abl. The low-dose effects of CDDO-Me are associated with inhibition of mitochondrial oxygen consumption, whereas the cytotoxic effects appear to be mediated by a rapid and selective depletion of mitochondrial glutathione that accompanies the increased generation of reactive oxygen species and mitochondrial dysfunction. Interestingly, the mitochondriotoxic effects of CDDO-Me are followed by the rapid autophagocytosis of intracellular organelles or the externalization of phosphatidylserine in different cell types. We conclude that alterations in mitochondrial function by CDDO-Me can result in autophagy or apoptosis of chronic myeloid leukemia cells regardless of the mutational status of bcr-abl. CDDO-Me is in clinical trials and shows signs of clinical activity, with minimal side effects and complete lack of cardiotoxicity. Studies in leukemias are in preparation.
Instructional Course Lectures, The American Academy of Orthopaedic Surgeons - Articular Cartilage. Part II (1997)

BUCKWALTER, J. A. M.D.‡, IOWA CITY, IOWA; MANKIN, H. J. M.D.§, BOSTON, MASSACHUSETTS Author Information
Killer cells in chronic obstructive pulmonary disease (2008)

COPD (chronic obstructive pulmonary disease) is a treatable and preventable disease state, characterized by progressive airflow limitation that is not fully reversible. It is a current and growing cause of mortality and morbidity worldwide, with the WHO (World Health Organization) projecting that total deaths attributed to COPD will increase by more than 30% in the next 10 years. The pathological hallmarks of COPD are destruction of the lung parenchyma (pulmonary emphysema), inflammation of the central airways (chronic bronchitis) and inflammation of the peripheral airways (respiratory bronchiolitis). The destructive changes and tissue remodelling observed in COPD are a result of complex interactions between cells of the innate and adaptive immune systems. The focus of the present review is directed towards the role of CD8(+) T-lymphocytes, NK (natural killer) cells and NKT cells (NK T-cells). These three classes of killer cell could all play an important part in the pathogenesis of COPD. The observed damage to the pulmonary tissue could be caused in three ways: (i) direct cytotoxic effect against the lung epithelium mediated by the activities of perforin and granzymes, (ii) FasL (Fas ligand)-induced apoptosis and/or (iii) cytokine and chemokine release. The present review considers the role of these killer cells in COPD.
Induction of cytotoxicity in human T cells coated with anti-glioma × anti-CD3 bispecific antibody against human glioma cells (1990)

A bifunctional hetero-F(ab')2 antibody fragment was developed that contained the Fab portions from anti-CD3 and anti-glioma monoclonal antibodies. The antibody simultaneously recognized two different molecules, the CD3 complex on effector T cells and a human glioma-associated antigen; thus, it could cross-link effector and target cells. This bispecific F(ab')2 fragment induced peripheral blood mononuclear cells (PBMC's) from healthy donors to lyse cells of the human glioma cell line, U251MG, which are resistant to natural killer cell-mediated cytolysis. The effect of the bispecific antibody on lymphokine-activated killer (LAK) cell activity was tested in patients suffering from malignant glioma. For this study, PBMC's from these patients were preactivated with recombinant interleukin-2 and their killer activity against U251MG cells was investigated in vitro with and without the bispecific antibody. The LAK cell activity of the PBMC's from patients with malignant gliomas was found to be suppressed compared with those of healthy donors. However, after preincubation with bispecific antibody, the patients' LAK cells exhibited marked cytolytic activity against U251MG cells. These findings suggest that this bispecific antibody may be a useful addition to anti-glioma immunotherapy.
Association of the Quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) Score With Excess Hospital Mortality in Adults With Suspected Infection in Low- and Middle-Income Countries (2018)

When assessed among hospitalized adults with suspected infection in 9 LMIC cohorts, the qSOFA score identified infected patients at risk of death beyond that explained by baseline factors. However, the predictive validity varied among cohorts and settings, and further research is needed to better understand potential generalizability.
A microRNA-Hippo pathway that promotes cardiomyocyte proliferation and cardiac regeneration in mice (2015)

In contrast to lower vertebrates, the mammalian heart has limited capacity to regenerate after injury in part due to ineffective reactivation of cardiomyocyte proliferation. We show that the microRNA cluster miR302-367 is important for cardiomyocyte proliferation during development and is sufficient to induce cardiomyocyte proliferation in the adult and promote cardiac regeneration. In mice, loss of miR302-367 led to decreased cardiomyocyte proliferation during development. In contrast, increased miR302-367 expression led to a profound increase in cardiomyocyte proliferation, in part through repression of the Hippo signal transduction pathway. Postnatal reexpression of miR302-367 reactivated the cell cycle in cardiomyocytes, resulting in reduced scar formation after experimental myocardial infarction. However, long-term expression of miR302-367 induced cardiomyocyte dedifferentiation and dysfunction, suggesting that persistent reactivation of the cell cycle in postnatal cardiomyocytes is not desirable. This limitation can be overcome by transient systemic application of miR302-367 mimics, leading to increased cardiomyocyte proliferation and mass, decreased fibrosis, and improved function after injury. Our data demonstrate the ability of microRNA-based therapeutic approaches to promote mammalian cardiac repair and regeneration through the transient activation of cardiomyocyte proliferation.
A telecommunications buildings/power infrastructure in a new era of public networking (2002)

The growth of data communications and the Internet and the onset of convergence following worldwide divestitures and deregulation spawned a new era in networking and increased the number of competitive carriers and service providers. The new era network will be a convergent circuit switch and packet public network (PN) that will be able to transport and process voice, video, data and Internet traffic at higher speeds and lower cost than today's PSTN. Co-location mandated by the government to enhance competition is deemed to be expensive and restrictive by competitive carriers and service providers. This together with the exploding growth of the Internet, second lines and data communications spawned a new outsourcing industry comprising carrier hotels or telehousing and Internet Data Centers. These businesses render space for telecommunications equipment in buildings that they refurbish or construct to replicate a CO environment. It is impacting power in two ways. It has increased the demand for higher capacity CO power plants and energized the debate over the preferred powering for telecommunications; nonstop DC systems used in telephone offices or UPS protected AC systems used in data communications. Nonstop operation is key to Quality of Service which is a major concern as the PSTN evolves to the PN. The trend to outsourcing presents ILECs a timely opportunity to convert a cost center into a profit center by consolidating their huge investment in COs and POPs into business units that would lease equipment space to both incumbents and competitors.
Cyclophosphamide Induces the Development of Early Myeloid Cells Suppressing Tumor Cell Growth by a Nitric Oxide-Dependent Mechanism (2001)

Adoptive immunotherapy with cyclophosphamide (Cy) increases the host resistance against tumor growth. The precise mechanism(s) by which this therapy enhances tumor suppression is unclear. Cy induces the development of early myeloid cells that may be strongly antiproliferative through NO production. These cells are similar to the natural suppressor cells found in normal bone marrow with a potential antitumor effect. Here we have addressed whether the development of NO-producing cells may be involved in this tumor resistance in Cy-treated mice. The results show a synergism between Cy treatment and tumor-specific lymphocytes transferred systemically (i.v.) or locally (Winn's assay) that results in a strong tumor suppression. Inhibition of NO production by N(G)-monomethyl-L-arginine at the site of tumor inoculation results in a loss of the protection achieved by the combined therapy. Cy-treated mice develop splenic early myeloid (CD11b, Gr-1, CD31 (ER-MP12), ER-MP20, ER-MP54) cells producing large amounts of NO upon T cell-derived signals (IFN-gamma plus CD40 ligation) able to inhibit tumor cell growth in vitro. Early myeloid cells (ER-MP54(+)) and cells expressing inducible NO synthase are increased at the site of tumor challenge in mice treated with the combined therapy, but not in those treated with Cy or immune cell transfer alone. Thus, Cy induces the expansion of early myeloid cells, inhibiting tumor cell growth by a mechanism involving NO. Both the recruitment and the activation of these myeloid cells at the site of tumor challenge appear to be dependent on the presence of tumor-specific lymphocytes.
Azithromycin for the treatment of acne (2000)

The results show that azithromycin is a safe and effective alternative in the treatment of inflammatory acne with few side-effects and good compliance, and suggest the need for further investigation with a clinical trial that will compare the long-term efficacy and tolerability.
Quality of life in chronic anemia of cancer during treatment with recombinant human erythropoietin (1994)

The results of rHuEPO therapy in chronic anemia of cancer are far more than cosmetics of laboratory values. They enable the patients with response to lead a physically and socially more active life with less anxiety, brighter moods, and an increased general feeling of well-being.
Sustained In Vivo Activity of Recombinant Bovine Granulocyte Colony Stimulating Factor (rbG-CSF) Using HEPES Buffer (2001)

The purpose of this study was to develop a long-acting injectable formulation of bG-CSF for veterinary use. However, in order to achieve sustained in vivo activity it was first necessary to stabilize the protein at the injection site. Preformulation studies, as well as literature, suggest that bG-CSF aggregates at neutral pH ranges (i.e., pH 6-8) and at temperatures of approximately 40 degrees C. Therefore, bG-CSF will not retain its activity for an extended period of time at the injection site. During this study we determined that HEPES buffer has a very significant impact on protein stability as well as on biological performance. Recombinant bovine granulocyte colony stimulating factor (rbG-CSF) was formulated in 1 M HEPES buffer for subcutaneous injection into cows. bG-CSF formulated in 1 M HEPES buffer resulted in sustained in vivo activity of bG-CSF compared to the "control" formulation (control formulation: 5% mannitol, 10 mM acetate buffer, 0.004% tween-80, pH 4). White blood cell (WBC) count was used as a marker to evaluate in vivo activity of the formulation. WBC numbers remained above a threshold value for only 24-30 h for the control formula. However, when bG-CSF was formulated in 1 M HEPES, the WBC remained above threshold for 3 days or 72 h. Formulating bG-CSF in 1 M HEPES at pH 7.5 also resulted in greater solution stability. This was surprising since bG-CSF is intrinsically not stable at neutral pH. The effect of 1 M HEPES on the T(M) (temperature at maximum heat flow on calorimetry scan) of bG-CSF was determined by microcalorimetry. In the absence of 1 M HEPES buffer the T(M) was 48 degrees C (onset approximately 40 degrees C), while bG-CSF formulated in 1 M HEPES buffer has a T(M) of 59 degrees C (onset approximately 50 degrees C). Similar organic buffers, such as MOPS, HEPPS, TES, and tricine, also resulted in improved solution stability as well as in sustained in vivo activity. The dramatic effect of these buffers on stability and biological performance of bG-CSF is not well understood. One hypothesis is that the electrostatic interaction between the zwitterionic form of these buffers and bG-CSF provides stabilization against denaturation.