gebhart/patrepeval huggingface dataset:
Oligosaccharide Modification in the Early Secretory Pathway Directs the Selection of a Misfolded Glycoprotein for Degradation by the Proteasome (1999)

The role of conformation-based quality control in the early secretory pathway is to eliminate misfolded polypeptides and unassembled multimeric protein complexes from the endoplasmic reticulum, ensuring the deployment of only functional molecules to distal sites. The intracellular fate of terminally misfolded human alpha1-antitrypsin was examined in hepatoma cells to identify the functional role of asparagine-linked oligosaccharide modification in the selection of glycoproteins for degradation by the cytosolic proteasome. Proteasomal degradation required physical interaction with the molecular chaperone calnexin. Altered sedimentation of intracellular complexes following treatment with the specific proteasome inhibitor lactacystin, and in combination with mannosidase inhibition, revealed that the removal of mannose from attached oligosaccharides abrogates the release of misfolded alpha1-antitrypsin from calnexin prior to proteasomal degradation. Intracellular turnover was arrested with kifunensine, implicating the participation of endoplasmic reticulum mannosidase I in the disposal process. Accelerated degradation occurred in a mannosidase-independent manner and was arrested by lactacystin, in response to the posttranslational inhibition of glucosidase II, demonstrating that the attenuated removal of glucose from attached oligosaccharides functions as the underlying rate-limiting step in the proteasome-mediated pathway. A model is proposed in which the removal of mannose from multiple attached oligosaccharides directs calnexin in the selection of misfolded alpha1-antitrypsin for degradation by the proteasome.
Fortnightly Review Acne vulgaris (1994)

#### Topical treatment for mild acne

#### Summary points

Severity of acne can be graded for therapeutic studies according to the Leeds grading scale,6 but in the general treatment of acne vulgaris most doctors would divide the condition into mild, moderate, and severe. Mild disease consists of open and closed comedones and some papules and pustules, while moderate acne encompasses more frequent papules and pustules with mild scarring. Severe disease contains all of the above plus nodular abscesses and leads to more extensive scarring which may be keloidal in some cases.

Topical preparations are the mainstay of treatment for mild acne vulgaris (see box). These are popular with patients, but their slow benefit needs careful explanation to encourage good compliance.

Benzoyl peroxide is a potent oxidising agent with antibacterial and keratolytic properties. It does not induce any change in the resistance pattern of aerobic bacteria to antibiotics; it also prevents such resistance when used concomitantly with topical erythromycin.7 Benzoyl peroxide is applied daily in lotions or creams …
Amino acid sequence and posttranslational modifications of human factor VIIa from plasma and transfected baby hamster kidney cells (1988)

Blood coagulation factor VII is a vitamin K dependent glycoprotein which in its activated form, factor VIIa, participates in the coagulation process by activating factor X and/or factor IX in the presence of Ca2+ and tissue factor. Three types of potential posttranslational modifications exist in the human factor VIIa molecule, namely, 10 gamma-carboxylated, N-terminally located glutamic acid residues, 1 beta-hydroxylated aspartic acid residue, and 2 N-glycosylated asparagine residues. In the present study, the amino acid sequence and posttranslational modifications of recombinant factor VIIa as purified from the culture medium of a transfected baby hamster kidney cell line have been compared to human plasma factor VIIa. By use of HPLC, amino acid analysis, peptide mapping, and automated Edman degradations, the protein backbone of recombinant factor VIIa was found to be identical with human factor VIIa. Neither recombinant factor VIIa nor human plasma factor VIIa was found to contain beta-hydroxyaspartic acid. In human plasma factor VIIa, the 10 N-terminally located glutamic acid residues were found to be fully gamma-carboxylated whereas 9 full and 1 partial gamma-carboxylated residues were found in the corresponding positions of the recombinant factor VIIa molecule. Asparagine residues 145 and 322 were found to be fully N-glycosylated in human plasma factor VIIa. In the recombinant factor VIIa, asparagine residue 322 was fully glycosylated whereas asparagine residue 145 was only partially (approximately 66%) glycosylated. Besides minor differences in the sialic acid and fucose contents, the overall carbohydrate compositions were nearly identical in recombinant factor VIIa and human plasma factor VIIa.(ABSTRACT TRUNCATED AT 250 WORDS)
The GA module, a mobile albumin‐binding bacterial domain, adopts a three‐helix‐bundle structure (1995)

We present the first study of the secondary structure and global fold of an albumin-binding domain. Our data show that the GA module from protein PAB, an albumin-binding protein from the anaerobic bacterial species Peptostreptococcus magnus, is composed of a left-handed three-helix bundle. The helical regions were identified by sequential and medium range NOEs, values of NH-C alpha H coupling constants, chemical shift indices, and the presence of slowly exchanging amide protons, as determined by NMR spectroscopy. In addition, circular dichroism studies show that the module is remarkably stable with respect to both pH and temperature.
Neuraminidase-Inhibiting Antibody Titers Correlate with Protection from Heterologous Influenza Virus Strains of the Same Neuraminidase Subtype (2018)

Immune responses induced by currently licensed inactivated influenza vaccines are mainly directed against the hemagglutinin (HA) glycoprotein, the immunodominant antigen of influenza viruses. The resulting antigenic drift of HA requires frequent updating of the vaccine composition and annual revaccination. On the other hand, the levels of antibodies directed against the neuraminidase (NA) glycoprotein, the second major influenza virus antigen, vary greatly. To investigate the potential of the more conserved NA protein for the induction of subtype-specific protection, vesicular stomatitis virus-based replicons expressing a panel of N1 proteins from prototypic seasonal and pandemic H1N1 strains and human H5N1 and H7N9 isolates were generated. Immunization of mice and ferrets with the replicon carrying the matched N1 protein resulted in robust humoral and cellular immune responses and protected against challenge with the homologous influenza virus with an efficacy similar to that of the matched HA protein, illustrating the potential of the NA protein as a vaccine antigen. The extent of protection after immunization with mismatched N1 proteins correlated with the level of cross-reactive neuraminidase-inhibiting antibody titers. Passive serum transfer experiments in mice confirmed that these functional antibodies determine subtype-specific cross-protection. Our findings illustrate the potential of NA-specific immunity for achieving broader protection against antigenic drift variants or newly emerging viruses carrying the same NA but a different HA subtype.<b>IMPORTANCE</b> Despite the availability of vaccines, annual influenza virus epidemics cause 250,000 to 500,000 deaths worldwide. Currently licensed inactivated vaccines, which are standardized for the amount of the hemagglutinin (HA) antigen, primarily induce strain-specific antibodies, whereas the immune response to the neuraminidase (NA) antigen, which is also present on the viral surface, is usually low. Using NA-expressing single-cycle vesicular stomatitis virus replicons, we show that the NA antigen conferred protection of mice and ferrets against not only the matched influenza virus strains but also viruses carrying NA proteins from other strains of the same subtype. The extent of protection correlated with the level of cross-reactive NA-inhibiting antibodies. This highlights the potential of the NA antigen for the development of more broadly protective influenza vaccines. Such vaccines may also provide partial protection against newly emerging strains with the same NA but a different HA subtype.
Terminal Velocity Of A Bubble Rise In A Liquid Column (2007)

As it is known, buoyancy and drag forces rule bubble's rise velocity in a liquid column. These forces are strongly dependent on fluid properties, gravity as well as equivalent's diameter. This study reports a set of bubble rising velocity experiments in a liquid column using water or glycerol. Several records of terminal velocity were obtained. The results show that bubble's rise terminal velocity is strongly dependent on dynamic viscosity effect. The data set allowed to have some terminal velocities data interval of 8.0 ? 32.9 cm/s with Reynolds number interval 1.3 -7490. The bubble's movement was recorded with a video camera. The main goal is to present an original set data and results that will be discussed based on two-phase flow's theory. It will also discussed, the prediction of terminal velocity of a single bubble in liquid, as well as the range of its applicability. In conclusion, this study presents general expressions for the determination of the terminal velocity of isolated gas bubbles of a Reynolds number range, when the fluid proprieties are known.
Preventing the ubiquitin–proteasome-dependent degradation of frataxin, the protein defective in Friedreich's ataxia (2011)

Friedreich's ataxia (FRDA) is a devastating orphan disease, with no specific treatment. The disease is caused by reduced expression of the protein frataxin, which results in mitochondrial defects and oxidative damage. Levels of residual frataxin critically affect onset and progression of the disease. Understanding the molecular mechanisms that regulate frataxin stability and degradation may, therefore, be exploited for the design of effective therapeutics. Here we show that frataxin is degraded by the ubiquitin-proteasome system and that K(147) is the critical residue responsible for frataxin ubiquitination and degradation. Accordingly, a K(147)R substitution generates a more stable frataxin. We then disclose a set of lead compounds, computationally selected to target the molecular cleft harboring K(147), that can prevent frataxin ubiquitination and degradation, and increase frataxin levels in cells derived from FRDA patients. Moreover, treatment with these compounds induces substantial recovery of aconitase activity and adenosine-5'-triphosphate levels in FRDA cells. Thus, we provide evidence for the therapeutic potential of directly interfering with the frataxin degradation pathway.
Mobile Communication Satellites (1995)

Expanding markets for cellular telephones emerging trends in communications satellites mobile communications on the high seas spaceborne land-mobile communications systems satellite messaging services for commercial jets selecting the proper constellation architecture mobile communications systems and Geosynch little constellations in low-altitude orbit big constellations in low-altitude orbit medium-altitude constellations crystal ball predictions for the 21st century.
Private Web browsing (1997)

This paper describes a communications primitive, anonymous connections, that supports bidirectional and near real-time channels that are resistant to both eavesdropping and traffic analysis. The connections are made anonymous, although communication
A Universal T Cell Vaccine Against Influenza A (2008)

A bivalent influenza virus (INFV) A vaccine composed of purified HA and NA has been available for INFV protection. However, this vaccine requires annual re‐administration. We have developed a novel T cell‐based vaccine that obviates this need. Our trivalent vaccine, is comprised of highly conserved peptides derived from H1N1 M2, HA, and NP peptides formulated with the TLR ligands (TLRLs), MPL, TDM and Poly (I:C) in a liposomal matrix. The tripeptide vaccine (50 μl) was given IN to WT mice on d‐21, ‐14, and ‐7 prior to challenge. Additional groups of WT and Rag1 −/− mice received only TLRL once ‐2d prior to challenge. All animals were challenged on d0 with LD 90 INFV A H3N2. Survival, weight loss, and symptom scores were monitored. On d0, tissues were collected and assessed for secretion of peptide specific IFN‐γ. In addition, lung cells were assessed for NP tetramer + CD8 cells and also lung histopathology. M2/TLRL and NP/TLRL immunizations provoked marked inflammation of the lung airways. Immunization with the tripeptide vaccine resulted in 100% survival and minimal weight loss and elevation of symptom scores relative to naïve controls (0% survival). M2 and NP specific IFN‐γ responses were observed predominantly in the lungs. Staining of lung cells with NP tetramer demonstrated ≈5% positive T cells. IN vaccination with TLRL ‐2d prior to challenge also protected WT and Rag1 −/− mice against lethal challenge.
Human immunodeficiency virus type 1 viral protein R localization in infected cells and virions (1993)

The subcellular localization of human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) was examined by subcellular fractionation. In HIV-1-infected peripheral blood mononuclear cells, Vpr was found in the nuclear and membrane fractions as well as the conditioned medium. Expression of Vpr without other HIV-1 proteins, in two different eukaryotic expression systems, demonstrated a predominant localization of Vpr in the nuclear matrix and chromatin extract fractions. Deletion of the carboxyl-terminal 19-amino-acid arginine-rich sequence impaired Vpr nuclear localization. Indirect immunofluorescence confirmed the nuclear localization of Vpr and also indicated a perinuclear location. Expression of Vpr alone did not result in export of the protein from the cell, but when coexpressed with the Gag protein, Vpr was exported and found in virus-like particles. A truncated Gag protein, missing the p6 sequence and a portion of the p9 sequence, was incapable of exporting Vpr from the cell. Regulation of Vpr localization may be important in the influence of this protein on virus replication.
A comparison of TCP automatic tuning techniques for distributed computing (2003)

Rather than painful, manual, static, per-connection optimization of TCP buffer sizes simply to achieve acceptable performance for distributed applications, many researchers have proposed techniques to perform this tuning automatically. This paper first discusses the relative merits of the various approaches in theory, and then provides substantial experimental data concerning two competing implementations-the buffer autotuning already present in Linux 2.4.x and "dynamic right-sizing." The paper reveals heretofore unknown aspects of the problem and current solutions, provides insight into the proper approach for different circumstances, and points toward ways to further improve performance.
The Human Cytomegalovirus US10 Gene Product Delays Trafficking of Major Histocompatibility Complex Class I Molecules (2002)

Human cytomegalovirus (HCMV) US10 encodes a glycoprotein that binds to major histocompatibility complex (MHC) class I heavy chains. While expression of US10 delays the normal trafficking of MHC class I molecules out of the endoplasmic reticulum, US10 does not obviously facilitate or inhibit the action of two other HCMV-encoded MHC class I binding proteins, US2 and US11.
Sulfur metabolism in Escherichia coli and related bacteria: facts and fiction. (2000)

Living organisms are composed of macromolecules made of hydrogen, carbon, nitrogen, oxygen, phosphorus and sulfur. Much work has been devoted to the metabolism of the first five elements, but much remains to be understood about sulfur metabolism. We review here the situation in Escherichia coli and related bacteria, where more than one hundred genes involved in sulfur metabolism have already been discovered in this organism. Examination of the genome suggests that many more will be found, especially genes involved in regulation, scavenging of sulfur containing molecules and synthesis of coenzymes or prosthetic groups. Furthermore, the involvement of methionine as the universal start of proteins as well as that of its derivative S-adenosylmethionine in a vast variety of cell processes argue in favour of a major importance of sulfur metabolism in all organisms.
Membrane-bound peptidases of lymphocytes: functional implications. (1991)

The paper is aimed towards the role of the membrane ecto-enzymes aminopeptidase N (CD13, AP-N) and dipeptidyl peptidase IV (CD26, DP IV) in the immune system. Both peptidases have been identified on T lymphocytes, AP-N also on monocytes and non-T cells. Using enzyme inhibitors and antibodies it has been shown by different groups that DP IV plays a key role in T cell activation and growth. Inhibition studies of our laboratory, using bestatin, actinonin and probestin, also demonstrated an essential role of AP-N in regulation of T cell growth. Moreover, the action of cytokines/lymphokines having DP IV susceptible bonds, as IL-1, IL-2 and IL-6, on lymphocyte proliferation, was found to be suppressed by specific inhibitors of DP IV as well as AP-N. These results are in favour of our hypothesis that DP IV and AP-N, possibly both in a concerted action, are involved in cytokine/lymphokine mediated signalling between immune cells.
Evidence for Involvement of Photosynthetic Processes in the Stomatal Response to CO2 (2006)

Stomatal conductance (gs) typically declines in response to increasing intercellular CO2 concentration (ci). However, the mechanisms underlying this response are not fully understood. Recent work suggests that stomatal responses to ci and red light (RL) are linked to photosynthetic electron transport. We investigated the role of photosynthetic electron transport in the stomatal response to ci in intact leaves of cocklebur (Xanthium strumarium) plants by examining the responses of gs and net CO2 assimilation rate to ci in light and darkness, in the presence and absence of the photosystem II inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), and at 2% and 21% ambient oxygen. Our results indicate that (1) gs and assimilation rate decline concurrently and with similar spatial patterns in response to DCMU; (2) the response of gs to ci changes slope in concert with the transition from Rubisco- to electron transport-limited photosynthesis at various irradiances and oxygen concentrations; (3) the response of gs to ci is similar in darkness and in DCMU-treated leaves, whereas the response in light in non-DCMU-treated leaves is much larger and has a different shape; (4) the response of gs to ci is insensitive to oxygen in DCMU-treated leaves or in darkness; and (5) stomata respond normally to RL when ci is held constant, indicating the RL response does not require a reduction in ci by mesophyll photosynthesis. Together, these results suggest that part of the stomatal response to ci involves the balance between photosynthetic electron transport and carbon reduction either in the mesophyll or in guard cell chloroplasts.
Microbes and Microbial Toxins: Paradigms for Microbial- Mucosal Interactions II. The integrated response of the intestine toClostridium difficiletoxins (2001)

Clostridium difficile, the major etiologic factor of antibiotic-associated diarrhea and colitis, mediates its effects by releasing two large protein exotoxins, toxins A and B. A major toxin effect is related to the disassembly of actin microfilaments, leading to impairment of tight junctions in human colonocytes. The mechanism of actin disaggregation involves monoglucosylation of the signaling proteins Rho A, Rac, and Cdc 42, which control stress fiber formation directly by toxins A and B. An important aspect of C. difficile infection is the acute necroinflammatory changes seen in patients with pseudomembranous colitis. The early mechanism of toxin-mediated inflammation involves toxin effects on cellular mitochondria, release of reactive oxygen species, and activation of mitogen-activated protein kinases and the transcription factor nuclear factor-kappaB. Injection of toxin A into animal intestine triggers secretion of fluid and intestinal inflammation characterized by epithelial cell destruction and neutrophil activation. A critical feature of C. difficile enterotoxicity is communication between enterocytes and lamina propria nerves, macrophages, and mast cells mediated via release of neuropeptides and proinflammatory cytokines.
Prediction of water and metal binding sites and their affinities by using the Fold-X force field (2005)

The empirical force field Fold-X was developed previously to allow rapid free energy calculations in proteins. Here, we present an enhanced version of the force field allowing prediction of the position of structural water molecules and metal ions, together called single atom ligands. Fold-X picks up 76% of water molecules found to interact with two or more polar atoms of proteins in high-resolution crystal structures and predicts their position to within 0.8 A on average. The prediction of metal ion-binding sites have success rates between 90% and 97% depending on the metal, with an overall standard deviation on the position of binding of 0.3-0.6 A. The following metals were included in the force field: Mg2+, Ca2+, Zn2+, Mn2+, and Cu2+. As a result, the current version of Fold-X can accurately decorate a protein structure with biologically important ions and water molecules. Additionally, the free energy of binding of Ca2+ and Zn2+ (i.e., the natural logarithm of the dissociation constant) and its dependence on ionic strength correlate reasonably well with the experimental data available in the literature, allowing one to discriminate between high- and low-affinity binding sites. Importantly, the accuracy of the energy prediction presented here is sufficient to efficiently discriminate between Mg2+, Ca2+, and Zn2+ binding.
[Neuroendocrine tumors of the gastrointestinal tract. Part 2: Current therapeutic concepts]. (1992)

When diagnosed, the greater proportion of functioning endocrine tumors have already metastasized. As a result, the primary aim of treatment--complete surgical removal of the growth--is possible in only a small number of patients. This gives considerable importance to palliative treatment. Interferons and somatostatin are the substances in the forefront of therapeutic interest today, cytostatic chemotherapy having proved largely ineffective and associated with considerable side effects. A feature common to interferons and somatostatin is the fact that they are much more likely to achieve a subjective improvement in clinical symptoms rather than objective remission. However, this is not disadvantage, since, in view of the slow growth of these tumors, quality of life is determined by controlling endocrine activity and not by debulking tumor mass.
THE HIV-1 REV PROTEIN (1998)

The nuclear export of intron-containing HIV-1 RNA is critically dependent on the activity of Rev, a virally encoded sequence-specific RNA-binding protein. Rev shuttles between the nucleus and the cytoplasm and harbors both a nuclear localization signal and a nuclear export signal. These essential peptide motifs have now been shown to function by accessing cellular signal-mediated pathways for nuclear import and nuclear export. HIV-1 Rev therefore represents an excellent system with which to study aspects of transport across the nuclear envelope.