gebhart/patrepeval huggingface dataset:
Gingipains fromPorphyromonas gingivalis— complex domain structures confer diverse functions (2011)

Gingipains, a group of arginine or lysine specific cysteine proteinases (also known as RgpA, RgpB and Kgp), have been recognized as major virulence factors in Porphyromonas gingivalis. This bacterium is one of a handful of pathogens that cause chronic periodontitis. Gingipains are involved in adherence to and colonization of epithelial cells, haemagglutination and haemolysis of erythrocytes, disruption and manipulation of the inflammatory response, and the degradation of host proteins and tissues. RgpA and Kgp are multi-domain proteins composed of catalytic domains and haemagglutinin/adhesin (HA) regions. The structure of the HA regions have previously been defined by a gingipain domain structure hypothesis which is a set of putative domain boundaries derived from the sequences of fragments of these proteins extracted from the cell surface. However, multiple sequence alignments and hidden Markov models predict an alternative domain architecture for the HA regions of gingipains. In this alternate model, two or three repeats of the so-called "cleaved adhesin" domains (and one other undefined domain in some strains) are the modules which constitute the substructure of the HA regions. Recombinant forms of these putative cleaved adhesin domains are indeed stable folded protein modules and recently determined crystal structures support the hypothesis of a modular organisation of the HA region. Based on the observed K2 and K3 structures as well as multiple sequence alignments, it is proposed that all the cleaved adhesin domains in gingipains will share the same β-sandwich jelly roll fold. The new domain model of the structure for gingipains and the haemagglutinin (HagA) proteins of P. gingivalis will guide future functional studies of these virulence factors.
Necrotizing Enterocolitis (2006)

After completing this article, readers should be able to: 

1. Define the pathophysiology of necrotizing enterocolitis (NEC).

2. Explain the relationship among minimal enteral nutrition, subsequent feedings, and NEC.

3. List the factors that render human milk enteral feedings protective against NEC.

4. Explain what measures should promote advances in mortality and morbidity associated with NEC in the near future.

5. Describe the complications of NEC.

Necrotizing enterocolitis (NEC) is one of the most serious and devastating diseases encountered in the neonatal intensive care unit (NICU). It is the most common gastrointestinal malady in neonates. It affects 1% to 8% of all infants admitted to the NICU and has a mortality rate of 10% to 50%. NEC accounts for at least 1,000 deaths annually in the United States. The increased incidence of NEC over the past few decades may be attributable to advancements in perinatal care, which have allowed very preterm infants to survive long enough to develop NEC.

The only consistently defined risk factor for NEC is prematurity; the incidence varies inversely with birthweight and gestational age. NEC strikes 4% to 13% of all very low-birthweight babies (<1,500 g). Although NEC primarily affects preterm infants, 5% to 28% of cases occur in term and near-term babies. The disease is rare in older children.

Asphyxia, congenital heart disease, polycythemia, umbilical catheterization, and the use of indomethacin and methylxanthines have been proposed as risk factors, although none has been shown to have a consistent association with NEC.

The age of onset of NEC also varies inversely with gestational age. In term infants, the median age at onset is 2 days; the preterm infant may develop the disease at several weeks of age. The risk remains high in preterm infants until they reach 35 to 36 weeks postconceptional age. The disparity in age of onset between term …
Pupil Abnormalities in Selected Autonomic Neuropathies (2006)

Examination of the pupil provides an opportunity to detect disturbances in the autonomic innervation of the eye. The pupil is frequently affected in patients with generalized autonomic neuropathies. This literature review confirms a high prevalence of sympathetic deficits and parasympathetic deficits in acute or subacute dysautonomia, diabetes, amyloidosis, pure autonomic failure, paraneoplastic syndromes, Sjögren syndrome, familial dysautonomia, and dopamine beta-hydroxylase deficiency. It confirms the relative scarcity of a pupil abnormality in patients with multiple system atrophy. There are difficulties in clinical diagnosis of pupil abnormalities and interpretation of pupil pharmacologic tests, particularly when combined sympathetic and parasympathetic deficits are present.
Synthesis of 5,5,10,10‐tetramethyl‐1‐oxacyclotridecane‐6,7,8,9‐tetrone – on the mechanism of the Rubottom reaction (1995)

Abstract The synthesis of 5,5,10,10‐tetramethyl‐1‐oxacyclotridecan‐6,7,8,9‐tetrone ( 12 ) was achieved via a multistep procedure involving an oxidation known as the Rubottom reaction. The key intermediates were the dialdehyde ( 25 ), the diacid ( 33 ), the cyclic diketone ( 39 ) and the bis(silyl enol ether) ( 42 ). The oxidation of 42 with m CPBA yielded two diastereomers, the syn and anti bis(α‐hydroxy ketones) ( 44, 45 ) the ratio of which depends strongly on the solvent used. This result combined with the isolation of the diepoxide ( 43 ) gives an insight into the stereochemistry of the Rubottom reaction.
Binding of the bovine caseinoglycopeptide to the platelet membrane glycoprotein GPIbα (1997)

The bovine caseinoglycopeptide (residues 106-169), the C-terminal part of kappa-casein, inhibited the von Willebrand factor-dependent platelet aggregation in a dose-dependent manner. An affinity matrix made of the caseinoglycopeptide selectively bound the platelet membrane glycoprotein GPIb alpha which contains the von Willebrand factor binding site. The amino acid residues of GPIb alpha participating in the caseinoglycopeptide binding were located after residue Glu 90.
I . Interaction of Al Films with  O 2 at Low Pressures (1982)

Thin films of Al were deposited under UHV conditions and then exposed to oxygen at low pressures over a range of temperatures. The optical properties (at 5461Å) and the thicknesses of the reaction products were characterized by in situellipsometer measurements. The results were compatible with a place exchange model wherein oxygen atoms were incorporated into the top surface of the (111) oriented Al. Certain physical parameters estimated from the ellipsometric findings were in agreement with the general view of the place exchange process. Optical parameters of the surface layer show a gradual shift toward those of with prolonged oxygen exposures.
The effects of breathing 5% CO2 on human cardiovascular responses and tolerance to orthostatic stress (2004)

Breathing carbon dioxide (CO2) is known to induce hypercapnic acidosis and to affect chemoreceptor regulation of the cardiovascular system. However, there is limited information in the literature regarding the effects of breathing CO2 upon tolerance to orthostatic stress where cardiovascular regulation is challenged. The purpose of this study was to investigate the effect of breathing 5% CO2 on presyncopal tolerance to lower body negative pressure (LBNP). Nine subjects (five males and four females; average +/-s.d. age 21.9 +/- 0.9 years, height 172.4 +/- 9.7 cm, mass 70.3 +/- 7.1 kg) volunteered to participate in this study. Orthostatic tolerance was determined by exposing subjects to LBNP until the onset of presyncopal signs and symptoms on two occasions each separated by approximately 1 week. On one occasion investigations were carried out while subjects were breathing room air and on the other while subjects were breathing air containing 5% CO2, inducing hypercapnia and stimulating systemic chemoreceptors. During hypercapnic conditions, as compared with normocapnia, there were significant increases (P < 0.05) in minute ventilation, end-tidal CO2 and estimated arterial P(CO2). Furthermore, under hypercapnic conditions there was an increase in orthostatic tolerance, peak heart rate and time to peak heart rate during LBNP. The LBNP-induced increase in calf circumference was significantly attenuated at -50 mmHg of LBNP in addition to a further 22.3% reduction in stroke volume under hypercapnic conditions. In conclusion, these results suggest that the possible protective element of presyncope was delayed during hypercapnia at the expense of further reductions in stroke volume. This delayed presyncopal response may have been associated with increases in cerebral blood flow (CBF) induced by the increased arterial P(CO2).
Stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc) and ureido-DNJNAc derivatives as new hexosaminidase inhibitors (2015)

2-Acetamido-1,2-dideoxyiminosugars are selective and potent inhibitors of hexosaminidases and therefore show high therapeutic potential for the treatment of various diseases, including several lysosomal storage disorders. A stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc), the iminosugar analog of N-acetylglucosamine, with a high overall yield is here described. This novel procedure further allowed accessing ureido-DNJNAc conjugates through derivatization of the endocyclic amine on a key pivotal intermediate. Remarkably, some of the ureido-DNJNAc representatives behaved as potent and selective inhibitors of β-hexosaminidases, including the human enzyme, being the first examples of neutral sp(2)-iminosugar-type inhibitors reported for these enzymes. Moreover, the amphiphilic character of the new ureido-DNJNAc is expected to confer better drug-like properties.
Monoclonal Antibodies to the Soluble Human IL-6 Receptor: Affinity Purification, ELISA, and Inhibition of Ligand Binding (1991)

Soluble IL-6 receptor (IL-6-R) purified to homogeneity from normal human urine was used for immunization of mice and rabbits. Spleen cells derived from a mouse showing a high binding titer to IL-6-R in an inverted solid phase radioimmunoassay (IsRIA) and in a Western blotting analysis were fused to mouse myeloma cells. The hybridomas were screened by the IsRIA, and 30 positive clones were isolated and characterized. They were suitable for affinity purification of the IL-6-R and for its detection by Western blot analysis, by ELISA and by sandwich type sRIA. Most of them inhibited the binding of labeled IL-6-R to IL-6 in a solid phase RIA.
Ultra-Fast Acting Insulin Analogues (2014)

Insulin analogues are a major improvement in diabetes pharmacotherapy. Rapid acting insulins have certain advantages over regular insulin, but there is a need to develop even faster acting insulin preparations, which mimic physiological insulin release in a better manner. This review discusses recent developments and patents in the field of Ultra- fast acting insulins. It classifies various approaches towards creation of an Ultra-fast acting insulin profile based upon the method used to achieve a faster onset of action. These include change in formulation of insulin, addition of excipients to insulin, and utilization of novel insulin sites or delivery methods. It examines the current state of evidence, and the developments in the field of newer insulin analogues & delivery methods.
Selectivity and invariance for visual object perception (2008)

The sight of an object triggers a complex set of processes in the brain. Although it is already well established that object perception is performed by a hierarchical network, the so-called ventral visual pathway, we are only starting to understand how neurons along this pathway encode visual information at each processing stage. In this review, we discuss basic principles of neural coding for object perception and describe evidence showing that it mainly relies on two principles: selectivity and invariance.
High Toughness, High Conductivity Ion Gels by Sequential Triblock Copolymer Self-Assembly and Chemical Cross-Linking (2013)

Self-assembly of ABA triblocks in ionic liquids provides a versatile route to highly functional physical ion gels, with promise in applications ranging from plastic electronics to gas separation. However, the reversibility of network formation, so favorable for processing, restricts the ultimate mechanical strength of the material. Here, we describe a novel ABA system that can be chemically cross-linked in a second annealing step, thereby providing greatly enhanced toughness. The ABA triblock is a poly(styrene-b-ethylene oxide-b-styrene) polymer in which about 25 mol % of the styrene units have a pendant azide functionality. After self-assembly of 10 wt % triblock in the ionic liquid [EMI][TFSA], the styrene domains are cross-linked by annealing at elevated temperature for ca. 20 min. The high ionic conductivity (ca. 10 mS/cm) of the physical ion gels is preserved in the final product, while the tensile strength is increased by a factor of 5.
A Matter of Life and Cell Death (1998)

In multicellular organisms, mutations in somatic cells affecting critical genes that regulate cell proliferation and survival cause fatal cancers. Repair of the damage is one obvious option, although the relative inconsequence of individual cells in metazoans means that it is often a "safer" strategy to ablate the offending cell. Not surprisingly, corruption of the machinery that senses or implements DNA damage greatly predisposes to cancer. Nonetheless, even when oncogenic mutations do occur, there exist potent mechanisms that limit the expansion of affected cells by suppressing their proliferation or triggering their suicide. Growing understanding of these innate mechanisms is suggesting novel therapeutic strategies for cancer.
Could Human Papillomaviruses Be Spread through Blood? (2005)

The human papillomaviruses (HPVs) are epitheliotropic viruses that require the environment of a differentiating squamous epithelium for their life cycle. HPV infection through abrasion of the skin or sexual intercourse causes benign warts and sometimes cancer. HPV DNA detected in the blood has been interpreted as having originated from metastasized cancer cells. The present study examined HPV DNA in banked, frozen peripheral blood mononuclear cells (PBMCs) from 57 U.S. human immunodeficiency virus (HIV)-infected pediatric patients collected between 1987 and 1996 and in fresh PBMCs from 19 healthy blood donors collected in 2002 to 2003. Eight patients and three blood donors were positive mostly for two subgroups of the HPV type 16 genome. The HPV genome detected in all 11 PBMC samples existed as an episomal form, albeit at a low DNA copy number. Among the eight patients, seven acquired HIV from transfusion (three associated with hemophilia) and one acquired HIV through vertical transmission; this patient also had received a transfusion before sampling. Our data suggest that PBMCs may be HPV carriers and might spread the virus through blood.
Chemokines and serpentines: the molecular biology of chemokine receptors (1993)

Chemokines are pro-inflammatory molecules with a diverse array of biological and biochemical functions. These molecules induce the migration of a number of leukocyte subsets including monocytes, neutrophils, and T-cells. The recent cloning of the IL-8, GRO, and MIP-1 alpha chemokine receptors revealed that these glycoproteins belong to the serpentine family of seven transmembrane G-protein-coupled receptors. Other members of this family include the chemotactic receptors for fMLP and C5a, indicating that a common pathway for eliciting the directional migration of leukocytes is probably transduced via G proteins. Ligand binding to chemokine receptors is complex, featured by multiple chemokines binding to a single receptor and multiple receptors binding a specific ligand. Future directions in this field appear to be focused on the cloning of novel receptors and the identification of ligands for orphaned receptors.
Recombinant Expression of Human Follistatin with 315 and 288 Amino Acids: Chemical and Biological Comparison with Native Porcine Follistatin* (1991)

Follistatin is a glycosylated monomeric protein originally isolated from ovarian follicular fluid based on its ability to specifically inhibit pituitary FSH release. To further explore the physiological role of follistatin, we have expressed recombinant human follistatins with 315 (rhFS-315) and 288 (rhFS-288) amino acids in Chinese hamster ovary cells under the control of the simian virus-40 promoter. The two types of FS originated from alternatively spliced mRNAs and rhFS-315 differed from rhFS-288 by having an extra 27-amino acid sequence at the carboxyl-terminal. The yield of the purified rhFS-315 and rhFS-288 after a single step of affinity chromatography on an activin-coupled Affi-Gel column was 3-5 mg/liter conditioned medium. Using the rhFS-315 and rhFS-288 as molecular mass markers, Western blotting with FS carboxyl-terminal-specific antibodies demonstrated that the majority of native FS isolated from porcine ovarian follicular fluid was neither FS-315 nor FS-288, but was composed of 300 amino acids in various forms of glycosylation. This finding is consistent with our earlier results obtained from tryptic peptide fragment analysis of native FS. Only a very small percentage (less than 1%) of native porcine FS was FS-288. In cultures of rat anterior pituitary cells, rhFS-315 (ED50, 115.2 +/- 16.2 pM) is equipotent to native porcine FS (ED50, 86.7 +/- 14.1 pM) on the suppression of FSH release, but, surprisingly, rhFS-288 (ED50, 9.6 +/- 2.2 pM) is 8-10 times more potent than the native protein, similar to the potency of inhibin-A (ED50, 8.6 +/- 0.9 pM). Interestingly, when the in vivo FSH-suppressing activity of rhFS-288 was compared to that of inhibin-A in 1-week ovariectomized adult rats, it was found that rhFS-288 was more potent and longer acting than inhibin-A. Hence, these results indicate that FS-288 is probably one of the most potent natural FSH suppressors.
Neurodegenerative lysosomal disorders: A continuum from development to late age (2008)

Neuronal survival requires continuous lysosomal turnover of cellular constituents delivered by autophagy and endocytosis. Primary lysosomal dysfunction in inherited congenital "lysosomal storage" disorders is well known to cause severe neurodegenerative phenotypes associated with accumulations of lysosomes and autophagic vacuoles (AVs). Recently, the number of inherited adult-onset neurodegenerative diseases caused by proteins that regulate protein sorting and degradation within the endocytic and autophagic pathways has grown considerably. In this Perspective, we classify a group of neurodegenerative diseases across the lifespan as disorders of lysosomal function, which feature extensive autophagic-endocytic-lysosomal neuropathology and may share mechanisms of neurodegeneration related to degradative failure and lysosomal destabilization. We highlight Alzheimer's disease as a disease within this group and discuss how each of the genes and other risk factors promoting this disease contribute to progressive lysosomal dysfunction and neuronal cell death.
Bioenergetics of the Staphylococcal Multidrug Export Protein QacA (1999)

The multidrug efflux pump QacA from Staphylococcus aureus confers resistance to an extensive range of structurally dissimilar compounds. Fluorimetric analyses demonstrated that QacA confers resistance to the divalent cation 4',6-diamidino-2-phenylindole, utilizing a proton motive force-dependent efflux mechanism previously demonstrated for QacA-mediated resistance to the monovalent cation ethidium. Both the ionophores nigericin and valinomycin inhibited QacA-mediated export of ethidium, indicating an electrogenic drug/nH+ (n >/= 2) antiport mechanism. The kinetic parameters, Km and Vmax, were determined for QacA-mediated export of four fluorescent substrates, 4',6-diamidino-2-phenylindole, 3', 3'-dipropyloxacarbocyanine, ethidium, and pyronin Y. Competition studies showed that QacA-mediated ethidium export is competitively inhibited by monovalent cations, e.g. benzalkonium, and non-competitively inhibited by divalent cations, e.g. propamidine, which suggests that monovalent and divalent cations bind at distinct sites on the QacA protein. The quaternary ammonium salt, 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene, was used as a membrane-specific fluorescence probe and demonstrated that the amount of substrate entering the inner leaflet was significantly reduced in QacA-containing strains, supporting the notion that the substrate is extruded directly from the membrane.
Molecular Properties and Enhancement of Thermostability by Random Mutagenesis of Glutamate Dehydrogenase fromBacillus subtilis (2005)

The rocG gene encoding glutamate dehydrogenase from Bacillus subtilis (Bs-GluDH) was cloned, and expressed at considerable magnitude in Escherichia coli. The recombinant Bs-GluDH was purified to homogeneity and has been determined to have a hexameric structure (M(r) 270 kDa) with strict specificity for 2-oxoglutarate and L-glutamate, requiring NADH and NAD+ as cofactors respectively. The enzyme showed low thermostability with T(m) = 41 degrees C due to dissociation of the hexamer. To improve the thermostability of this enzyme, we performed error-prone PCR, introducing random mutagenesis on cloned GluDH. Two single mutant enzymes, Q144R and E27F, were isolated from the final mutant library. Their T(m) values were 61 degrees C and 49 degrees C respectively. Furthermore, Q144R had a remarkably high k(cat) value (435 s(-1)) for amination reaction at 37 degrees C, 1.3 times higher than that of the wild-type. Thus, Q144R can be used as a template gene to modify the substrate specificity of Bs-GluDH for industrial use.
IDMaps: a global Internet host distance estimation service (2001)

There is an increasing need to quickly and efficiently learn network distances, in terms of metrics such as latency or bandwidth, between Internet hosts. For example, Internet content providers often place data and server mirrors throughout the Internet to improve access latency for clients, and it is necessary to direct clients to the nearest mirrors based on some distance metric in order to realize the benefit of the mirrors. We suggest a scalable Internet-wide architecture, called IDMaps, which measures and disseminates distance information on the global Internet. Higher level services can collect such distance information to build a virtual distance map of the Internet and estimate the distance between any pair of IP addresses. We present our solutions to the measurement server placement and distance map construction problems in IDMaps. We show that IDMaps can indeed provide useful distance estimations to applications such as nearest mirror selection.
Severe Combined Immunodeficiency Due to a Specific Defect in the Production of Interleukin-2 (1990)

SEVERE combined immunodeficiency (SCID) syndrome is caused by a group of genetic diseases characterized by abnormal function of T and B lymphocytes.1 SCID was first described in children with lymphopenia, agammaglobulinemia, and absent proliferative responses to T-lymphocyte mitogens, such as phytohemagglutinin. Since the original description of X-linked lymphopenic SCID (the so-called Swiss type of agammaglobulinemia), other children have been found to have SCID due to the absence of the enzyme adenosine deaminase, which is required for the development of T lymphocytes. Together, the X-linked and adenosine deaminase—deficient forms of SCID account for approximately 40 to 50 percent of all cases. . . .