gebhart/patrepeval huggingface dataset:
New insight into the molecular control of bacterial functional amyloids (2015)

Amyloid protein structure has been discovered in a variety of functional or pathogenic contexts. What distinguishes the former from the latter is that functional amyloid systems possess dedicated molecular control systems that determine the timing, location, and structure of the fibers. Failure to guide this process can result in cytotoxicity, as observed in several pathologies like Alzheimer's and Parkinson's Disease. Many gram-negative bacteria produce an extracellular amyloid fiber known as curli via a multi-component secretion system. During this process, aggregation-prone, semi-folded curli subunits have to cross the periplasm and outer-membrane and self-assemble into surface-attached fibers. Two recent breakthroughs have provided molecular details regarding periplasmic chaperoning and subunit secretion. This review offers a combined perspective on these first mechanistic insights into the curli system.
Correlations between abnormalities in chromium and glucose metabolism in a group of diabetics. (1988)

Journal Article Correlations between abnormalities in chromium and glucose metabolism in a group of diabetics. Get access B W Morris, B W Morris Search for other works by this author on: Oxford Academic Google Scholar H Griffiths, H Griffiths Search for other works by this author on: Oxford Academic Google Scholar G J Kemp G J Kemp Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 34, Issue 7, 1 July 1988, Pages 1525–1526, https://doi.org/10.1093/clinchem/34.7.1525a Published: 01 July 1988
PAM-type Ply Bond Strength agent “Himoloc MJ-450” (2003)

High ply bond strength is required in combination board. Some kinds of starches are used as ply bond strength agents in spraying their suspension to the combined plies. Starchsuspension, without cooking, is sprayed, and the particles of starch are gelatinized in the drying process, large ply bond is occurred. But there are some problems such as putrefaction in using starches. Recently, synthesized ply bond strength agents have been used, for example poly acrylic amide type (PAM). Our company developed cationic dispersion PAM as retention aids and drainage aids for the first time in the world. Furthermore, we have developed anionic dispersion PAM, “Himoloc MJ-450”, as ply bond strength agent.“MJ-450” has great performance in small dosage because of its large particle size. The particle size of “MJ-450” is much the same as it of starches, and larger than it of the existing PAM. In this issue, we discuss the differences in the fixing mechanism of particles onto the ply between starches, existing PAM, and “MJ-450”.
The Bacteria Fight Back (2008)

In their ongoing war against antibiotics, the bacteria seem to be winning, and the drug pipeline is verging on empty.
Structure and evolutionary origin of the gene encoding mouse NF-M, the middle-molecular-mass neurofilament protein (1987)

We describe the complete sequence of the gene encoding mouse NF-M, the middle-molecular-mass neurofilament protein. The coding sequence is interrupted by two intervening sequences which align perfectly with the first two intervening sequences in the gene encoding NF-L (the low-molecular-mass neurofilament protein); there is no intron in the gene encoding NF-M corresponding to the third intron in NF-L. Therefore, both the number of introns and their arrangement in the genes coding NF-L and NF-M contrast sharply with the number and arrangement of introns in the genes of known sequence, encoding other members of the intermediate filament multigene family (desmin, vimentin, glial fibrillary acidic protein and the acidic and basic keratins); with the exception of a single truncated keratin gene that lacks an encoded tailpiece, these genes all contain eight introns, of which at least six are placed at homologous locations. Assuming the existence of a primordial intermediate filament gene containing most (if not all) the introns found in contemporary non-neurofilament intermediate filament genes, it seems likely that an RNA-mediated transposition event was involved in the generation of an ancestral gene encoding the NF polypeptides. A combination of insertional transposition and gene-duplication events could then explain the anomalous number and placement of introns within these genes. Consistent with this notion, we show that the genes encoding NF-M and NF-L are linked.
City-scale landmark identification on mobile devices (2011)

With recent advances in mobile computing, the demand for visual localization or landmark identification on mobile devices is gaining interest. We advance the state of the art in this area by fusing two popular representations of street-level image data - facade-aligned and viewpoint-aligned - and show that they contain complementary information that can be exploited to significantly improve the recall rates on the city scale. We also improve feature detection in low contrast parts of the street-level data, and discuss how to incorporate priors on a user's position (e.g. given by noisy GPS readings or network cells), which previous approaches often ignore. Finally, and maybe most importantly, we present our results according to a carefully designed, repeatable evaluation scheme and make publicly available a set of 1.7 million images with ground truth labels, geotags, and calibration data, as well as a difficult set of cell phone query images. We provide these resources as a benchmark to facilitate further research in the area.
Low pressure organic vapor phase deposition of small molecular weight organic light emitting device structures (1997)

A new technique for the deposition of amorphous organic thin films, low pressure organic vapor phase deposition (LP-OVPD), was used to fabricate organic light emitting devices (OLEDs) consisting of a film of aluminum tris-(8 hydroxyquinoline) (Alq3) grown on the surface of a film of N′-diphenyl-N,N′-bis(3-methylphenyl)1-1′biphenyl-4-4′diamine. The resulting heterojunction OLED was found to have a performance similar to conventional, small molecular weight OLEDs grown using thermal evaporation in vacuum. The LP-OVPD grown device has an external quantum efficiency of 0.40±0.05% and a turn-on voltage of approximately 6 V. The rapid throughput demonstrated with LP-OVPD has the potential to facilitate low cost mass production of conventional small molecule based OLEDs, and its use of low vacuum in a horizontal reactor lends itself to roll-to-roll deposition of organic films for many photonic device applications.
Molecular cloning, characterization, and complete nucleotide sequence of the gene for pneumolysin, the sulfhydryl-activated toxin of Streptococcus pneumoniae (1987)

A recombinant lambda bacteriophage has been isolated that carries DNA from Streptococcus pneumoniae and expresses a potent hemolysin that has been shown to be pneumolysin, the sulfhydryl-activated toxin of the pneumococcus. Hemolytic activity is inhibited by cholesterol and neutralized by serum against streptolysin O. The cloned gene expresses two polypeptides (Mrs, 56,000 and 53,000) in an Escherichia coli in vitro transcription-translation system, and both are precipitated by the addition of anti-alveolysin serum and anti-streptolysin O serum in the presence of Staphylococcus aureus cells. Expression of pneumolysin occurs when the gene is cloned in both possible orientations in pUC8. The DNA sequence of a 5-kilobase ClaI fragment that carries the pneumolysin gene has been determined. An open reading frame was identified that encodes a polypeptide of 471 amino acids that is hydrophobic in character and has an N-terminal amino acid sequence which is identical to that deduced from amino acid sequencing of the purified protein. The predicted amino acid sequence of the polypeptide reveals a single cysteine residue located 44 residues from the C terminus. Putative promoter and ribosome binding sites have been identified 5' to the pneumolysin coding sequence.
TIGIT and PD-1 impair tumor antigen–specific CD8+ T cells in melanoma patients (2015)

T cell Ig and ITIM domain (TIGIT) is an inhibitory receptor expressed by activated T cells, Tregs, and NK cells. Here, we determined that TIGIT is upregulated on tumor antigen-specific (TA-specific) CD8⁺ T cells and CD8⁺ tumor-infiltrating lymphocytes (TILs) from patients with melanoma, and these TIGIT-expressing CD8⁺ T cells often coexpress the inhibitory receptor PD-1. Moreover, CD8⁺ TILs from patients exhibited downregulation of the costimulatory molecule CD226, which competes with TIGIT for the same ligand, supporting a TIGIT/CD226 imbalance in metastatic melanoma. TIGIT marked early T cell activation and was further upregulated by T cells upon PD-1 blockade and in dysfunctional PD-1⁺TIM-3⁺ TA-specific CD8⁺ T cells. PD-1⁺TIGIT⁺, PD-1⁻TIGIT⁺, and PD-1⁺TIGIT⁻ CD8⁺ TILs had similar functional capacities ex vivo, suggesting that TIGIT alone, or together with PD-1, is not indicative of T cell dysfunction. However, in the presence of TIGIT ligand-expressing cells, TIGIT and PD-1 blockade additively increased proliferation, cytokine production, and degranulation of both TA-specific CD8⁺ T cells and CD8⁺ TILs. Collectively, our results show that TIGIT and PD-1 regulate the expansion and function of TA-specific CD8⁺ T cells and CD8⁺ TILs in melanoma patients and suggest that dual TIGIT and PD-1 blockade should be further explored to elicit potent antitumor CD8⁺ T cell responses in patients with advanced melanoma.
Probucol prevents oxidative injury to endothelial cells. (1991)

We evaluated the effect of the antioxidant, probucol, on the cytotoxic effects of oxidized low density lipoprotein (OX-LDL) or of cumene hydroperoxide (CumOOH) on cultured bovine endothelial cells (EC). The addition of CumOOH to EC caused the release of lactate dehydrogenase and the accumulation of thiobarbituric acid-reacting substances (TBARS), effects that were protected against by preincubation with either probucol or tocopherol. Similarly, preincubation of EC with those antioxidants protected against OX-LDL toxicity and the accumulation of TBARS. The content of probucol in EC measured by high performance liquid chromatography was directly correlated with the extent of protection against OX-LDL toxicity. We also found that treatment of EC with serum from patients receiving treatment with probucol resulted in the detection of probucol in the cells. We conclude that probucol is transported and incorporated into EC membranes to act as a radical-trapping antioxidant, protecting the EC against oxidative stress. Our results also indicate that lipid peroxidation in cellular membranes involves cell injury inflicted by OX-LDL.
Expression of reelin in adult mammalian blood, liver, pituitary pars intermedia, and adrenal chromaffin cells (2000)

Reelin regulates telencephalic and cerebellar lamination during mammalian development and is expressed in several structures of the adult brain; however, only traces of reelin were believed to be in peripheral tissues. Because reelin structurally resembles extracellular matrix proteins, and because many of these proteins are expressed in blood, we hypothesized that reelin also might be detectable in the circulation. Reelin (420 kDa) and two reelin-like immunoreactive bands (310 and 160 kDa) are expressed in serum and platelet-poor plasma of rats, mice, and humans, but these three bands were not detectable in serum of homozygous reeler (rl/rl) mice. Reelin plasma levels in heterozygous (rl/+) mice were half of those in wild-type littermates. Western blotting and immunocytochemistry using antireelin mAbs indicated that reelin-like immunoreactivity was expressed in a subset of chromaffin cells within the rat adrenal medulla and in a subset of cells coexpressing alpha-melanocyte-stimulating hormone within the pituitary pars intermedia. However, surgical removal of adrenal or pituitary failed to decrease the amount of reelin (420-kDa band) expressed in serum. Adult liver expressed one-third of the reelin mRNA concentration expressed in adult mouse cerebral cortex. Full-length reelin protein was detectable in liver extracts in situ; acutely isolated liver cells also secreted full-length reelin in vitro. Liver appears to be a prime candidate to produce and maintain the circulating reelin pool. It now becomes relevant to ask whether circulating reelin has a physiologic role on one or more peripheral target tissues.
Structural Insight into the Pharmacophore Pocket of Human Glutamate Carboxypeptidase II (2007)

Inhibition of glutamate carboxypeptidase II (GCPII) has been shown to be neuroprotective in multiple preclinical models in which dysregulated glutamatergic transmission is implicated. Herein, we report crystal structures of the human GCPII complexed with three glutamate mimetics/derivatives, 2-(phosphonomethyl)pentanedioic acid (2-PMPA), quisqualic acid (QA), and L-serine O-sulfate (L-SOS), at 1.72, 1.62, and 2.10 A resolution, respectively. Despite the structural differences between the distal parts of the inhibitors, all three compounds share similar binding modes in the pharmacophore (i.e., S1') pocket of GCPII, where they are stabilized by a combination of polar and van der Waals interactions. The structural diversity of the distal parts of the inhibitors leads to rearrangements of the S1' site that are necessary for efficient interactions between the enzyme and an inhibitor. The set of structures presented here, in conjunction with the available biochemical data, illustrates a flexibility of the GCPII pharmacophore pocket and highlights the structural features required for potent GCPII inhibition. These findings could facilitate the rational structure-based drug design of new GCPII inhibitors in the future.
Phenotypic modulation of human articular chondrocytes by bistratene A (2002)

Chondrocytes undergo phenotypic alterations following extended periods in monolayer culture, i.e., they become bipolar and flattened, proliferate, and synthesise type I as opposed to type II collagen. This process has been termed chondrocyte dedifferentiation. Bistratene A is a macrolide polyether that specifically activates the delta isoform of protein kinase C (PKCdelta) in some cell types. Here, we show that dedifferentiated human articular chondrocytes became rounded and underwent cell growth arrest after treatment with bistratene A. In addition, bistratene A-treated chondrocytes became more immunopositive for type II collagen, but less immunopositive for type I collagen. These phenotypic changes were associated with a prior and extensive disruption of actin microfilaments and translocation of PKCdelta to the nuclear membrane. Concurrent treatments of chondrocytes with a specific inhibitor of PKCdelta, rottlerin, partially blocked the morphological effects of bistratene A.
On the impulsive nature of interchannel interference in digital communication systems (2011)

Impulsiveness, or a high degree of peakedness, of interchannel interference in digital communication systems typically results from the non-smooth nature of any physically realizable modulation scheme designed to transmit a discrete (discontinuous) message. Even modulation schemes painstakingly designed to be `smooth' are not. The non-smoothness of the modulation can be caused by a variety of hardware non-idealities and, more fundamentally, by the very nature of any modulation scheme for digital communications. In order to transmit a discrete message, such a scheme must be causal and piecewise, and cannot be smooth, or infinitely differentiable. Recursive differentiation of a non-smooth transmitted signal eventually leads to discontinuities. When observed by an out-of-band receiver, the transmissions from these discontinuities may appear as strong transients with the peak power noticeably exceeding the average power, and the received signal will have a high degree of peakedness. This impulsive nature of the interference provides an opportunity to reduce its power.
Selection of Recombinant Antibodies Specific for Pathogenic Streptococcus suis by Subtractive Phage Display (2000)

A semisynthetic antibody phage display library was used to select recombinant antibodies directed against surface components of a pathogenic strain of Streptococcus suis serotype 2 and against extracellular factor (EF), a protein known to be exclusively associated with pathogenic S. suis serotype 2 strains. Three distinct monoclonal phage antibodies directed against conformational epitopes of surface protein components of S. suis were selected. In addition, three different monoclonal phage antibodies were isolated that recognized EF. To isolate antibody fragments that recognize epitopes specific for a pathogenic S. suis serotype 2 strain, compared to a nonpathogenic serotype 2 strain, we applied a subtractive selection procedure. With this procedure, only one distinct phage antibody was found, and it was shown to be directed against EF. This demonstrates the selectivity of the applied procedure and confirms that EF is indeed differentially expressed by pathogenic and nonpathogenic strains. It also shows that EF is a very dominant antigen in phage antibody selections.
Engineered herpes simplex virus DNA polymerase point mutants: the most highly conserved region shared among alpha-like DNA polymerases is involved in substrate recognition (1990)

Eucaryotic, viral, and bacteriophage DNA polymerases of the alpha-like family share blocks of sequence similarity, the most conserved of which has been designated region I. Region I includes a YGDTDS motif that is almost invariant within the alpha-like family and that is similar to a motif conserved among RNA-directed polymerases and also includes adjacent amino acids that are more moderately conserved. To study the function of these conserved amino acids in vivo, site-specific mutagenesis was used to generate herpes simplex virus region I mutants. A recombinant virus constructed to contain a mutation within the nearly invariant YGDTDS motif was severely impaired for growth on Vero cells which do not contain a viral polymerase gene. However, three recombinants constructed to contain mutations altering more moderately conserved residues grew on Vero cells and exhibited altered sensitivities to nucleoside and PPi analogs and to aphidicolin. Marker rescue and DNA sequencing of one such recombinant demonstrated that the region I alteration confers the altered drug sensitivity phenotype. These results indicate that this region has an essential role in polymerase function in vivo and is involved directly or indirectly in drug and substrate recognition.
Intraocular pharmacokinetics and safety of a humanized monoclonal antibody in rabbits after intravitreal administration of a solution or a PLGA microsphere formulation (1999)

Poly(lactic-co-glycolic) acid (PLGA) bioresorbable microspheres are used for controlled-release drug delivery and are particularly promising for ocular indications. The objective of the current study was to evaluate the pharmacokinetics and safety of a recombinant human monoclonal antibody (rhuMAb HER2) in rabbits after bolus intravitreal administration of a solution or a PLGA-microsphere formulation. On Day 0, forty-eight male New Zealand white rabbits (2.3-2.6 kg) were immobilized with intramuscular ketamine/xylazine, and the test materials were injected directly into the vitreous compartment. Group 1 animals received rhuMAb HER2 in 50:50 lactide: glycolide PLGA microspheres; Group 2 animals received rhuMAb HER2 in solution (n = 24/group). The dose for each eye was 25 microg (50 microl). After dosing, animals were sacrificed at 2 min, and on 1, 2, 4, 7, 14, 23, 29, 37, 44, 50, and 56 days (n = 2/timepoint/group). Safety assessment included direct ophthalmoscopy, clinical observations, body weight, and hematology and clinical chemistry panels. At necropsy, vitreous and plasma were collected for pharmacokinetics and analysis for antibodies to rhuMAb HER2, and the vitreal pellet (Group 1) was prepared for histologic evaluation. All animals completed the study per protocol-both treatments were well tolerated, and no suppurative or mixed inflammatory cell reaction was observed in the vitreal samples (Group 1) at any of the time points examined. Antibodies to rhuMAb HER2 were detected in plasma samples by Day 7 in both treatment groups, but infrequently in vitreous samples. There were no safety implications associated with this immune response. The in vitro characterization of the PLGA microspheres provided reasonable projections of the in vivo rhuMAb HER2 release kinetics (Group 1). The total amount of antibody that was released was similar in vitro (25.9%) and in vivo (32.4%). RhuMAb HER2 (Group 2) was cleared slowly from the vitreous compartment, with initial and terminal half-lives of 0.9 and 5.6 days, respectively. The volume of distribution approximated the vitreous volume in a rabbit eye.
Specific binding of the DNA repair enzyme AlkA to a pyrrolidine-based inhibitor (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpecific binding of the DNA repair enzyme AlkA to a pyrrolidine-based inhibitorOrlando D. Schaerer, Jean-Yves Ortholand, A. Ganesan, Khosro Ezaz-Nikpay, and Gregory L. VerdineCite this: J. Am. Chem. Soc. 1995, 117, 24, 6623–6624Publication Date (Print):June 1, 1995Publication History Published online1 May 2002Published inissue 1 June 1995https://pubs.acs.org/doi/10.1021/ja00129a039https://doi.org/10.1021/ja00129a039research-articleACS PublicationsRequest reuse permissionsArticle Views304Altmetric-Citations44LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
New towed-array shape-estimation scheme for real-time sonar systems (2003)

In real-time towed-array systems, performance degradation of array gain occurs when a line array that is not straight is assumed straight in the beamforming process. In this paper, a new method is proposed for array shape estimation. The novelty of this method is that it accounts for the variations in the tow ship's speed, which are typical during course alterations. The procedure consists of two steps. First, we solve for the tow-point induced motion in the time domain based on the constraints from the tow-point compass-sensor readings and from a discretized Paidoussis equation. At each time instance, the shape estimate is solved from a linear system of equations. We also show that this solution is equivalent to a previous frequency-domain solution while the new approach is much simpler. In the second step, we use the tail compass-sensor data to adjust the overall array shape. By noting that variations in the ship speed lead to a distortion in the normalized time axis, we first register the predicted tail displacement with the tail sensor readings along the time axis. Then, distortions in the estimated array shape over its length can be compensated accordingly. We also model a slow-changing bias between sensor zeros and remove systematic sensor errors. The effectiveness of the new algorithm is demonstrated with simulations and real sea-trial data.