gebhart/patrepeval huggingface dataset:
Isolation, characterization, and expression of cDNAs encoding murine alpha-mannosidase II, a Golgi enzyme that controls conversion of high mannose to complex N-glycans. (1991)

Golgi alpha-mannosidase II (GlcNAc transferase I-dependent alpha 1,3[alpha 1,6] mannosidase, EC 3.2.1.114) catalyzes the final hydrolytic step in the N-glycan maturation pathway acting as the committed step in the conversion of high mannose to complex type structures. We have isolated overlapping clones from a murine cDNA library encoding the full length alpha-mannosidase II open reading frame and most of the 5' and 3' untranslated region. The coding sequence predicts a type II transmembrane protein with a short cytoplasmic tail (five amino acids), a single transmembrane domain (21 amino acids), and a large COOH-terminal catalytic domain (1,124 amino acids). This domain organization which is shared with the Golgi glycosyl-transferases suggests that the common structural motifs may have a functional role in Golgi enzyme function or localization. Three sets of polyadenylated clones were isolated extending 3' beyond the open reading frame by as much as 2,543 bp. Northern blots suggest that these polyadenylated clones totaling 6.1 kb in length correspond to minor message species smaller than the full length message. The largest and predominant message on Northern blots (7.5 kb) presumably extends another approximately 1.4-kb downstream beyond the longest of the isolated clones. Transient expression of the alpha-mannosidase II cDNA in COS cells resulted in 8-12-fold overexpression of enzyme activity, and the appearance of cross-reactive material in a perinuclear membrane array consistent with a Golgi localization. A region within the catalytic domain of the alpha-mannosidase II open reading frame bears a strong similarity to a corresponding sequence in the rat liver endoplasmic reticulum alpha-mannosidase and the vacuolar alpha-mannosidase of Saccharomyces cerevisiae. Partial human alpha-mannosidase II cDNA clones were also isolated and the gene was localized to human chromosome 5.
Lipopolysaccharide can block the potential of monocytes to differentiate into dendritic cells (1999)

We examined whether priming monocytes (MO) with lipopolysaccharide (LPS) influenced their further differentiation into either macrophages (Mphi) or dendritic cells (DC). LPS-primed MO differentiated into Mphi when cultured further with Mphi colony-stimulating factor (M-CSF) but, if cultured then with granulocyte/Mphi (GM)-CSF and IL-4 (interleukin-4), only about 30% of the cells differentiated into CD1a+ CD14- DC and half became CD1a- CD14+ Mphi. Cytokines present during LPS priming could affect subsequent MO differentiation. Relative to priming with LPS alone, adding M-CSF to LPS did not modify differentiation of MO to Mphi in further culture with M-CSF, nor did it change the way of differentiation of MO into DC was altered if culture was later switched to GM-CSF/IL-4. Using GM-CSF/IL-4 plus LPS upon priming did not modify differentiation of MO to Mphi in further culture with M-CSF, as compared to priming with GM-CSF/IL-4 alone, but it counteracted the effect of LPS on the differentiation of MO to DC in further culture with GM-CSF/IL-4: about 75% of cells then became DC. Alternatively, despite activation by LPS, mature M-CSF-induced Mphi preserved the potential to differentiate into DC on subsequent culture with GM-CSF/IL-4. Thus, LPS, a bacterial product known to sustain maturation of MO/Mphi as well as of DC, may block the differentiation of MO into DC, except if signal triggering DC differentiation is delivered concomitantly, and modulate in this manner the induction of adaptive immune responses to infection.
Synthesis and Singlet Oxygen Reactivity of 1,2‐Diaryloxyethenes and Selected Sulfur and Nitrogen Analogs (2012)

1,2-Diaryloxyethene has recently been proposed as a linker in singlet oxygen-mediated drug release. Even though 1,2-diaryloxyethenes look very simple, their synthesis was not an easy task. Previous methods are limited to symmetric molecules, lengthy step and low yield. We report on a facile synthetic method not only for 1,2-diaryloxyethenes but also their sulfur and nitrogen analogs in yields ranging from 40 to 90% with more than 90% purity at the vinylation reaction.
Procalcitonin as a diagnostic tool in lower respiratory tract infections and tuberculosis (2003)

The diagnostic significance of procalcitonin concentrations in lower respiratory tract infections and tuberculosis is not known. A prospective analysis was, therefore, performed in patients with acute exacerbation of chronic bronchitis (AECB), community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and tuberculosis and their procalcitonin levels compared with those of patients with noninfectious lung diseases (controls). In addition, standard inflammatory parameter data were collected. A prospective clinical study was performed with four different groups of patients and a control group that consisted of patients with noninfectious lung diseases. A total of 129 patients were included: 25 with HAP, 26 CAP, 26 AECB, 27 tuberculosis, and 25 controls. C-reactive protein level, blood cell counts and procalcitonin concentration were evaluated on the first day after onset of clinical and inflammatory symptoms prior to treatment. The median procalcitonin concentrations in HAP, CAP, AECB and tuberculosis were not elevated in relation to the cut-off level of 0.5 ng x mL(-1). In the HAP group, in four of five patients who subsequently died, procalcitonin concentrations of >0.5 ng x mL(-1) were found. In acute lower respiratory infections, such as HAP, CAP and AECB, significantly elevated levels were found in comparison to the control group, but below the usual cut-off level. No differences were observed between tuberculosis and the control group. Relative to the current cut-off level of 0.5 ng x mL(-1), procalcitonin concentration is not a useful parameter for diagnosis of lower respiratory tract infections. However, compared to the control group, there were significantly elevated levels in patients with hospital-acquired pneumonia, community-acquired pneumonia and acute exacerbation of chronic bronchitis below the current cut-off level, which should be further investigated.
Pseudomonas aeruginosa Pyocyanin Is Critical for Lung Infection in Mice (2004)

Pseudomonas aeruginosa secretes copious amounts of the redox-active phenazine, pyocyanin (PCN), during cystic fibrosis lung infection. PCN has been shown to interfere with a variety of cellular processes in cultured lung epithelial cells. Here, by using two respiratory tract models of infection, we demonstrate that PCN mediates tissue damage and necrosis during lung infection.
Addressing Safety Liabilities of TfR Bispecific Antibodies That Cross the Blood-Brain Barrier (2013)

Bispecific antibodies using the transferrin receptor (TfR) have shown promise for boosting antibody uptake in brain. Nevertheless, there are limited data on the therapeutic properties including safety liabilities that will enable successful development of TfR-based therapeutics. We evaluate TfR/BACE1 bispecific antibody variants in mouse and show that reducing TfR binding affinity improves not only brain uptake but also peripheral exposure and the safety profile of these antibodies. We identify and seek to address liabilities of targeting TfR with antibodies, namely, acute clinical signs and decreased circulating reticulocytes observed after dosing. By eliminating Fc effector function, we ameliorated the acute clinical signs and partially rescued a reduction in reticulocytes. Furthermore, we show that complement mediates a residual decrease in reticulocytes observed after Fc effector function is eliminated. These data raise important safety concerns and potential mitigation strategies for the development of TfR-based therapies that are designed to cross the blood-brain barrier.
Cloning and characterization of a human DEAH-box RNA helicase, a functional homolog of fission yeast Cdc28/Prp8 (1998)

During the splicing process, spliceosomal snRNAs undergo numerous conformational rearrangements that appear to be catalyzed by proteins belonging to the DEAD/H-box superfamily of RNA helicases. We have cloned a new RNA helicase gene, designated DBP2 (DEAH-boxprotein), homologous to the Schizosaccaromyces pombe cdc28(+)/prp8(+) gene involved in pre-mRNA splicing and cell cycle progression. The full-length DBP2 contains 3400 nucleotides and codes for a protein of 1041 amino acids with a calculated mol. wt of 119 037 Da. Transfection experiments demonstrated that the GFP-DBP2 gene product, transiently expressed in HeLa cells, was localized in the nucleus. The DBP2 gene was mapped by FISH to the MHC region on human chromosome 6p21.3, a region where many malignant, genetic and autoimmune disease genes are linked. Because the expression of DBP2 gene in S.pombe prp8 mutant cells partially rescued the temperature-sensitive phenotype, we conclude that DBP2 is a functional human homolog of the fission yeast Cdc28/Prp8 protein.
Trough concentrations of cyclosporine in blood following administration with grapefruit juice (1993)

Components of grapefruit juice have been shown to inhibit CYP3A4 activity, the enzyme involved in cyclosporine metabolism. Eleven medically stable patients (seven males, four females) receiving cyclosporine following kidney transplantation were instructed to take their usual dose of cyclosporine with water for 1 week (Phase 1), with grapefruit juice (8 ounces) for 1 week (Phase 2) and again with water for 1 week (Phase 3). Trough blood samples were obtained at the end of each phase for measurement of cyclosporine concentration using a specific monoclonal whole blood radioimmunoassay. Cyclosporine trough concentrations averaged 116.9 +/- 51.6 ng ml(-1) in the first phase, 145.3 +/- 44.7 ng ml(-1) with grapefruit juice (P < 0.05 compared with the first and third phases) and 111.2 +/- 56.1 ng ml(-1) in the third phase. Cyclosporine concentrations increased in 8 of 11 patients when given with grapefruit juice (mean increase 32%; range -4 to 97%) and declined in 10 of 11 when subjects resumed taking cyclosporine with water (mean decrease 27%). These results suggest that grapefruit juice increases trough concentrations of cyclosporine in blood, possibly by inhibiting pre-hepatic gut wall metabolism, and could be useful in optimizing therapy with this drug.
ListeriaPathogenesis and Molecular Virulence Determinants (2001)

The gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a highly fatal opportunistic foodborne infection. Pregnant women, neonates, the elderly, and debilitated or immunocompromised patients in general are predominantly affected, although the disease can also develop in normal individuals. Clinical manifestations of invasive listeriosis are usually severe and include abortion, sepsis, and meningoencephalitis. Listeriosis can also manifest as a febrile gastroenteritis syndrome. In addition to humans, L. monocytogenes affects many vertebrate species, including birds. Listeria ivanovii, a second pathogenic species of the genus, is specific for ruminants. Our current view of the pathophysiology of listeriosis derives largely from studies with the mouse infection model. Pathogenic listeriae enter the host primarily through the intestine. The liver is thought to be their first target organ after intestinal translocation. In the liver, listeriae actively multiply until the infection is controlled by a cell-mediated immune response. This initial, subclinical step of listeriosis is thought to be common due to the frequent presence of pathogenic L. monocytogenes in food. In normal individuals, the continual exposure to listerial antigens probably contributes to the maintenance of anti-Listeria memory T cells. However, in debilitated and immunocompromised patients, the unrestricted proliferation of listeriae in the liver may result in prolonged low-level bacteremia, leading to invasion of the preferred secondary target organs (the brain and the gravid uterus) and to overt clinical disease. L. monocytogenes and L. ivanovii are facultative intracellular parasites able to survive in macrophages and to invade a variety of normally nonphagocytic cells, such as epithelial cells, hepatocytes, and endothelial cells. In all these cell types, pathogenic listeriae go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. In this way, listeriae disseminate in host tissues sheltered from the humoral arm of the immune system. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review describes in detail the molecular determinants of Listeria virulence and their mechanism of action and summarizes the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listeria infection. This article provides an updated perspective of the development of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start of the genomic era of Listeria research.
Management of concomitant hepatic artery injury in patients with iatrogenic major bile duct injury after laparoscopic cholecystectomy (2007)

Combined bile duct and hepatic artery injury during LC led to a complicated clinical course, with a high mortality rate. Reconstruction of the right hepatic artery might be helpful in reducing hepatic ischaemia, but is usually feasible only if the injury is identified early.
Current progress in enteropathogenic and enterohemorrhagic Escherichia coli vaccines (2002)

Enteropathogenic and enterohemorrhagic Escherichia coli are important causal agents of infectious diarrhea, particularly amongst pediatric populations. While enteropathogenic E. coli is a significant health threat in developing countries, enterohemorrhagic E. coli causes sporadic, sometimes deadly outbreaks of hemorrhagic colitis, with a serious complication, hemolytic uremic syndrome, ocurring in a proportion of cases. This review discusses the pathogenesis of enterohemorrhagic and enteropathogenic E. coli, the host immune response and the current application of this knowledge towards efficacious vaccine strategies. Several lines of investigation indicate the feasibility of such strategies and justify further development of a vaccine targeting these significant intestinal pathogens.
Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by cDNA-expressed human cytochrome P-450 isozymes. (1997)

The metabolism of nortriptyline was studied in vitro using cDNA-expressed human cytochrome P450 isozymes 1A2, 3A4, 2C19, and 2D6, CYP2D6 was the sole isozyme mediating hydroxylation of nortriptyline, the quantitatively most important metabolic pathway, and only (E)-10-OH-nortriptyline was formed. CYP2D6, 2C19, and 1A2, mentioned in decreasing order of significance, mediated the demethylation reaction of nortriptyline, whereas 3A4 did not participate in the metabolism of nortriptyline. Concerning the quantitative relations, CYP2D6 exhibited a high affinity with respect to hydroxylation and demethylation (K(m) 0.48-0.74 mumol/l), a high hydroxylation capacity (Vmax 130 mol/hr/mol CYP) and a somewhat lower demethylation capacity (Vmax 19 mol/ hr/mol CYP). The affinities of 1A2 and 2C19 were 100-fold lower (K(m) 54-118 mumol/l). The capacity of 1A2 was low (Vmax 6.8 mol/hr/ mol CYP), whereas 2C19 had the highest demethylation capacity (Vmax 93 mol/hr/mol CYP). Taking into account the relative amounts of CYP isozymes present in the liver, about 90% of the metabolism was estimated to depend on CYP2D6, with CYP2C19 and 1A2 mediating the remaining 10%. In subjects lacking the 2D6 isozyme, CYP2C19 and 1A2 are expected to be of major importance for elimination of nortriptyline.
Techniques for estimating vocal-tract shapes from the speech signal (1994)

This paper reviews methods for mapping from the acoustical properties of a speech signal to the geometry of the vocal tract that generated the signal. Such mapping techniques are studied for their potential application in speech synthesis, coding, and recognition. Mathematically, the estimation of the vocal tract shape from its output speech is a so-called inverse problem, where the direct problem is the synthesis of speech from a given time-varying geometry of the vocal tract and glottis. Different mappings are discussed: mapping via articulatory codebooks, mapping by nonlinear regression, mapping by basis functions, and mapping by neural networks. Besides being nonlinear, the acoustic-to-geometry mapping is also nonunique, i.e., more than one tract geometry might produce the same speech spectrum. The authors show how this nonuniqueness can be alleviated by imposing continuity constraints.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Meta‐analysis of Hemodynamic Studies on First and Second Language Processing: Which Suggested Differences Can We Trust and What Do They Mean? (2006)

This article presents the results of a meta‐analysis of 30 hemodynamic experiments comparing first language (L1) and second language (L2) processing in a range of tasks. The results suggest that reliably stronger activation during L2 processing is found (a) only for task‐specific subgroups of L2 speakers and (b) within some, but not all regions that are also typically activated in native language processing. A tentative interpretation based on the functional roles of frontal and temporal regions is suggested.
Identification of the proteins of the yeast U1 small nuclear ribonucleoprotein complex by mass spectrometry (1997)

Here we report the rapid identification of the proteins of the spliceosomal U1 small nuclear ribonucleoprotein (snRNP) from the yeast Saccharomyces cerevisiae by searching mass spectrometric data in genomic sequence databases. The U1 snRNP, containing a histidine-tagged 70K protein, was isolated from cell extracts by anti m3G-cap immunoaffinity and subsequent nickel nitrilotriacetic acid chromatography. A U1 snRNP fraction containing 20 proteins was obtained. Further purification by glycerol gradient centrifugation identified nine U1 snRNP specific and six common proteins. The U1 snRNP proteins were partially sequenced by nanoelectrospray mass spectrometry, and their genes were identified in the data base via multiple peptide sequence tags. Apart from the already known common proteins D1, D3, F, and G, the D2 and E homologs were also identified. The same six common proteins were detected in core U2 snRNP, which was purified and analyzed separately. The biochemical association of these six proteins with yeast snRNPs is shown here for the first time. Intriguingly, the Sm B/B' homolog was not detected. In addition to the well characterized yeast U1 specific proteins [U1-70K (Snp1p), U1-A (Mud1p), Prp39p, and Prp40p] the homolog of the U1-C protein was identified together with four additional novel U1 specific proteins, which are not found in mammalian U1. This is the first time that the components of a multiprotein complex from an organism with a sequenced genome have been characterized by mass spectrometry. The technique should be applicable to any protein complex that can be biochemically purified from an organism whose genome is known.
Glucans as Biological Response Modifiers (2009)

Beta-D-glucans belong to a group of natural, physiologically active compounds, generally called biological response modifiers. Glucans represent highly conserved structural components of cell walls in yeast, fungi, or seaweed. Despite long history of research, the exact mechanisms of glucan action remain unsolved. The present review starts with the history of glucans. Next, the detailed information about the possible glucan sources is followed by a description of the mechanisms of action. Physiological functions of glucan suggest the possible use of glucans not only as non-specific immunomodulator, but also as its possible future use as a drug.
Quantum tagging: Authenticating location via quantum information and relativistic signaling constraints (2011)

We define the task of quantum tagging, that is, authenticating the classical location of a classical tagging device by sending and receiving quantum signals from suitably located distant sites, in an environment controlled by an adversary whose quantum information processing and transmitting power is unbounded. We define simple security models for this task and briefly discuss alternatives. We illustrate the pitfalls of naive quantum cryptographic reasoning in this context by describing several protocols which at first sight appear unconditionally secure but which, as we show, can in fact be broken by teleportation-based attacks. We also describe some protocols which cannot be broken by these specific attacks, but do not prove they are unconditionally secure. We review the history of quantum tagging protocols, and show that protocols previously proposed by Malaney and Chandran et al. are provably insecure.
A Human-Mouse Hybridoma which Secretes Monoclonal Thyroglobulin Autoantibody with Properties Similar to those of the Donor Patient's Serum Autoantibody (1989)

Human monoclonal antibodies produced by Epstein Barr (EB) virus transformation and/or cell fusion are frequently IgM antibodies which tend to cross react with a range of antigens and often bear little relationship to the highly specific IgG antibodies associated with human autoimmune disease. By fusing EB virus transformed B lymphocytes from a Hashimoto patient with a mouse myeloma line and selecting for synthesis of IgG class thyroglobulin (Tg) antibody, we have developed a hybridoma (VB/5) secreting Tg antibody of IgG2 subclass and lambda light chain type which has the characteristics of a monoclonal antibody on isoelectric focussing. The antibody has a high affinity for human Tg and recognises Tg from other primates but not non-primate Tg. However, it does not react with human thyroid peroxidase or a panel of other autoantigens. In terms of affinity constant, functional affinity and affinity heterogeneity, the antibody closely resembles the IgG2 lambda Tg antibody present in the serum of the Hashimoto patient whose B lymphocytes were used to develop the hybridoma. In addition to providing a useful reference standard for Tg antibody IgG subclass assays, VB/5 antibody and the hybridoma line provide a valuable starting point for detailed studies of Tg autoantibodies and the genes coding for the variable regions of their heavy and light chains.