gebhart/patrepeval huggingface dataset:
The Uptake Mechanism of the Cell‐Penetrating pVEC Peptide (2013)

Peptide based drug design efforts have gained renewed interest with the discovery of cargo‐carrying or cell‐penetrating peptides. Understanding the translocation mechanism of these peptides and identifying the residues or elements that contribute to uptake can provide valuable clues toward the design of novel peptides. To this end, we have performed steered molecular dynamics (SMD) simulations on the pVEC peptide from murine vascular endothelial‐cadherin protein and its two variants. Translocation was found to occur in three stages, adsorption via the cationic residues, inclusion of the whole peptide inside the membrane accompanied by formation of a water defect, and exit of both peptide and water molecules from the bilayer. Our simulation results suggest that the precise order in which the hydrophobic, cationic, and the polar regions are located in the amphipathic pVEC peptide contributes to its uptake mechanism. These results present new opportunities for the design of novel cell‐penetrating and antimicrobial peptides.
Plantar pressure distribution analysis in normal weight young women and men with normal and claw feet: A cross-sectional study (2005)

We analyzed the plantar support in 72 normal-weight young voluntaries (46 women, 26 men), by a baropodometric platform. We considered subjects with claw foot (CFS) and subjects with normal foot (NFS). We found a significant reduction of total plantar support surface in the CFS (P < 0.0001 for women, P < 0.001 for men), due to the reduction of the forefoot and rear foot areas of both plantar imprints. Indeed, CFS of both sexes exhibited higher values of both plantar pressure and peak pressure, compared to the NFS. Moreover, the load per units of plantar surface increased in CFS compared to the NFS. In conclusion, the reduction of plantar support surfaces in CFS of both sexes was associated to a major load per units of plantar surface in the forefoot and rear foot areas, and this may be a risk factor to lower extremity overuse injuries.
Molecular cloning of the murine IL-1 beta converting enzyme cDNA (1992)

Abstract IL-1 beta is a potent modulator of immune and inflammatory responses. Murine IL-1 beta is initially synthesized as an inactive 33-kDa pro-molecule that is activated by proteolytic cleavage between Asp-117 and Val-118 to generate the 17-kDa mature IL-1 beta protein. This cleavage is catalyzed by a specific protease that has been designated the IL-1 beta converting enzyme (or IL-1 beta convertase). We have used a human IL-1 beta convertase cDNA to isolate murine convertase cDNA from a WEHI-3 library. These cDNA predicted that the murine convertase is a 402-residue protein. Overall, the murine convertase showed 71% nucleotide and 62% predicted amino acid sequence identity with the human convertase. Southern blot analysis of interspecific backcross mice indicated that the murine IL-1 beta convertase is encoded by a single copy gene located on murine chromosome 9. The murine convertase showed broad constitutive expression, being detected in mononuclear phagocyte and T lymphocyte cell lines as well as in spleen, heart, brain, and adrenal glands. The expression of the murine convertase in mononuclear phagocytes was up-regulated by treatment with LPS or rIFN-gamma. These studies establish that the IL-1 beta convertase is an evolutionarily conserved, widely expressed enzyme that can be regulated at a pretranslational level.
The CD20 homologue MS4A4 directs trafficking of KIT toward clathrin-independent endocytosis pathways and thus regulates receptor signaling and recycling (2015)

MS4A family members differentially regulate the cell cycle, and aberrant, or loss of, expression of MS4A family proteins has been observed in colon and lung cancer. However, the precise functions of MS4A family proteins and their mechanistic interactions remain unsolved. Here we report that MS4A4 facilitates trafficking of the receptor tyrosine kinase KIT through endocytic recycling rather than degradation pathways by a mechanism that involves recruitment of KIT to caveolin-1-enriched microdomains. Silencing of MS4A4 in human mast cells altered ligand-induced KIT endocytosis pathways and reduced receptor recycling to the cell surface, thus promoting KIT signaling in the endosomes while reducing that in the plasma membrane, as exemplified by Akt and PLCγ1 phosphorylation, respectively. The altered endocytic trafficking of KIT also resulted in an increase in SCF-induced mast cell proliferation and migration, which may reflect altered signaling in these cells. Our data reveal a novel function for MS4A family proteins in regulating trafficking and signaling, which could have implications in both proliferative and immunological diseases.
Class A Color Designation for Light Sources Used in General Illumination (2013)

Solid state lighting has reignited interest among lighting specialists and manufacturers in the color qualities of illumination used in architectural applications. This renewed interest has highlighted the known problems with the two currently accepted metrics used by the lighting industry to communicate the color qualities of sources of illumination, correlated color temperature (CCT) and color rendering index (CRI). These two metrics are poor predictors of viewer responses to the color characteristics of illumination and both metrics are poorly understood among consumers. The proposed “Class A color” designation serves two important purposes for helping to move the consumer market toward a broader acceptance of solid state lighting. First, the “Class A color” designation reflects bundled metrics shown to be predictive of user acceptance of color attributes from sources of illumination and, second, the designation can be readily understood by consumers as denoting light sources of high color quality.
Fluorescent Polymer Nanoparticles Based on Dyes: Seeking Brighter Tools for Bioimaging (2016)

Speed, resolution and sensitivity of today's fluorescence bioimaging can be drastically improved by fluorescent nanoparticles (NPs) that are many-fold brighter than organic dyes and fluorescent proteins. While the field is currently dominated by inorganic NPs, notably quantum dots (QDs), fluorescent polymer NPs encapsulating large quantities of dyes (dye-loaded NPs) have emerged recently as an attractive alternative. These new nanomaterials, inspired from the fields of polymeric drug delivery vehicles and advanced fluorophores, can combine superior brightness with biodegradability and low toxicity. Here, we describe the strategies for synthesis of dye-loaded polymer NPs by emulsion polymerization and assembly of pre-formed polymers. Superior brightness requires strong dye loading without aggregation-caused quenching (ACQ). Only recently several strategies of dye design were proposed to overcome ACQ in polymer NPs: aggregation induced emission (AIE), dye modification with bulky side groups and use of bulky hydrophobic counterions. The resulting NPs now surpass the brightness of QDs by ≈10-fold for a comparable size, and have started reaching the level of the brightest conjugated polymer NPs. Other properties, notably photostability, color, blinking, as well as particle size and surface chemistry are also systematically analyzed. Finally, major and emerging applications of dye-loaded NPs for in vitro and in vivo imaging are reviewed.
A Targeted Library of Small-Molecule, Tyrosine, and Dual-Specificity Phosphatase Inhibitors Derived from a Rational Core Design and Random Side Chain Variation (1997)

Tyrosine phosphatases (PTPases) dephosphorylate phosphotyrosines while dual-specificity phosphatases (DSPases) dephosphorylate contiguous and semicontiguous phosphothreonine and phosphotyrosine on cyclin dependent kinases and mitogen-activated protein kinases. Consequently, PTPases and DSPases have a central role controlling signal transduction and cell cycle progression. Currently, there are few readily available potent inhibitors of PTPases or DSPases other than vanadate. Using a pharmacophore modeled on natural product inhibitors of phosphothreonine phosphatases, we generated a refined library of novel, phosphate-free, small-molecule compounds synthesized by a parallel, solid-phase combinatorial-based approach. Among the initial 18 members of this targeted diversity library, we identified several inhibitors of DSPases: Cdc25A, -B, and -C and the PTPase PTP1B. These compounds at 100 microM did not significantly inhibit the protein serine/threonine phosphatases PP1 and PP2A. Kinetic studies with two members of this library indicated competitive inhibition for Cdc25 DSPases and noncompetitive inhibition for PTP1B. Compound AC-alphaalpha69 had a Ki of approximately 10 microM for recombinant human Cdc25A, -B, and -C, and a Ki of 0.85 microM for the PTP1B. The marked differences in Cdc25 inhibition as compared to PTP1B inhibition seen with relatively modest chemical modifications in the modular side chains demonstrate the structurally demanding nature of the DSPase catalytic site distinct from the PTPase catalytic site. These results represent the first fundamental advance toward a readily modifiable pharmacophore for synthetic PTPase and DSPase inhibitors and illustrate the significant potential of a combinatorial-based strategy that supplements the rational design of a core structure by a randomized variation of peripheral substituents.
Dendritic Cells Pulsed with a Tumor-specific Peptide Induce Long-lasting Immunity and Are Effective against Murine Intracerebral Melanoma (2002)

In a murine melanoma model, immunization with DCs mixed with tumor-specific peptide results in an antigen-specific immunological response that recognizes the EGFRvIII mutation, has potent antitumor efficacy against intracerebral tumors that express EGFRvIII, and results in long-lasting antitumor immunity.
Lack of Previous Exposure to Paternal Antigens Does not Predispose to Hypertensive Pregnancy Complications (1998)

Objective: To test the hypothesis that previous exposure to paternal antigens should protect against preeclampsia and pregnancy-induced hypertension, we compared the occurrence of these complications and intrauterine growth retardation in pregnancies in women who conceived using sperm from a donor (no previous exposure to fertilizing sperm) or from the husband (maximal previous exposure to fertilizing sperm).Subjects and Design: Follow-up study of 123 pregnancies in 123 primigravid women who conceived either by donor sperm (donor insemination or in vitro fertilization) (n = 73) or by husbands' sperm (spontaneous, insemination, or in vitro fertilization) (n = 50) after 2-10 years of infertility.Main Outcome Measures: Occurrence of preeclampsia (elevation in blood pressure and proteinuria), pregnancy-induced hypertension (elevation in blood pressure, no proteinuria), and intrauterine growth retardation (birth weight < mean — 2 SD).Results: The multiple pregnancy rate was 14% in both study groups. Preeclampsia developed in one woman in the donor group (1.4%) as compared with seven women in the control group (14.0%) [odds ratio = 0.09, 95% confidence interval (CI) = 0.01-0.72]. Two women in the donor group (2.7%) and three women in the control group (6.0%) had pregnancy-induced hypertension. The risk of either preeclampsia or pregnancy-induced hypertension was reduced in the donor group (odds ratio = 0.17, CI = 0.04-0.65). The rate of intrauterine growth retardation in singleton pregnancies in the donor group (3.2%) did not differ from that in die control group (4.6%).Conclusions: Lack of previous exposure to paternal antigens does not enhance the risk of preeclampsia and/or pregnancy-induced hypertension. Our data raise doubts about previous suggestions that exposure to paternal antigens should protect against hypertensive pregnancy complications.
Characterizing the portability of RecT-mediated oligonucleotide recombination (2020)

Abstract Bacterial genome editing methods are used to engineer strains for biotechnology and fundamental research. Homologous recombination (HR) is the most versatile method of genome editing, but traditional techniques using endogenous RecA-mediated pathways are inefficient and laborious. Phage encoded RecT proteins can improve HR over 1000-fold, but these proteins have limited portability between species. Using Escherichia coli , Lactococcus lactis, Mycobacterium smegmatis, Lactobacillus rhamnosus , and Caulobacter crescentus we investigated the hostlimited functionality of RecTs. We find that these proteins specifically recognize the 7 C-terminal amino acids of the bacterial single-stranded DNA-binding protein (SSB), and are portable between species only if compatibility with this host domain is maintained. Furthermore, in some species, we find that co-expressing otherwise incompatible RecTs with a paired bacterial SSB is sufficient to establish functionality. Finally, we demonstrate that high-efficiency HR surpasses the mutational capacity of more widely used error-prone methods for genome diversification, and can be used to identify exceptional phenotypes inaccessible through sequential nucleotide conversions.
A Sorangium cellulosum (myxobacterium) gene cluster for the biosynthesis of the macrolide antibiotic soraphen A: cloning, characterization, and homology to polyketide synthase genes from actinomycetes (1995)

A 40-kb region of DNA from Sorangium cellulosum So ce26, which contains polyketide synthase (PKS) genes for synthesis of the antifungal macrolide antibiotic soraphen A, was cloned. These genes were detected by homology to Streptomyces violaceoruber genes encoding components of granaticin PKS, thus extending this powerful technique for the identification of bacterial PKS genes, which has so far been applied only to actinomycetes, to the gram-negative myxobacteria. Functional analysis by gene disruption has indicated that about 32 kb of contiguous DNA of the cloned region contains genes involved in soraphen A biosynthesis. The nucleotide sequence of a 6.4-kb DNA fragment, derived from the region with homology to granaticin PKS genes, was determined. Analysis of this sequence has revealed the presence of a single large open reading frame beginning and ending outside the 6.4-kb fragment. The deduced amino acid sequence indicates the presence of a domain with a high level of similarity to beta-ketoacyl synthases that are involved in polyketide synthesis. Other domains with high levels of similarity to regions of known polyketide biosynthetic functions were identified, including those for acyl transferase, acyl carrier protein, ketoreductase, and dehydratase. We present data which indicate that soraphen A biosynthesis is catalyzed by large, multifunctional enzymes analogous to other bacterial PKSs of type I.
An atlas of human gene expression from massively parallel signature sequencing (MPSS) (2005)

We have used massively parallel signature sequencing (MPSS) to sample the transcriptomes of 32 normal human tissues to an unprecedented depth, thus documenting the patterns of expression of almost 20,000 genes with high sensitivity and specificity. The data confirm the widely held belief that differences in gene expression between cell and tissue types are largely determined by transcripts derived from a limited number of tissue-specific genes, rather than by combinations of more promiscuously expressed genes. Expression of a little more than half of all known human genes seems to account for both the common requirements and the specific functions of the tissues sampled. A classification of tissues based on patterns of gene expression largely reproduces classifications based on anatomical and biochemical properties. The unbiased sampling of the human transcriptome achieved by MPSS supports the idea that most human genes have been mapped, if not functionally characterized. This data set should prove useful for the identification of tissue-specific genes, for the study of global changes induced by pathological conditions, and for the definition of a minimal set of genes necessary for basic cell maintenance. The data are available on the Web at http://mpss.licr.org and http://sgb.lynxgen.com.
Using total-variation regularization for intensity modulated radiation therapy inverse planning with field-specific numbers of segments (2008)

Currently, there are two types of treatment planning algorithms for intensity modulated radiation therapy (IMRT). The beamlet-based algorithm generates beamlet intensity maps with high complexity, resulting in large numbers of segments in the delivery after a leaf-sequencing algorithm is applied. The segment-based direct aperture optimization (DAO) algorithm includes the physical constraints of the deliverable apertures in the calculation, and achieves a conformal dose distribution using a small number of segments. However, the number of segments is pre-fixed in most of the DAO approaches, and the typical random search scheme in the optimization is computationally intensive. A regularization-based algorithm is proposed to overcome the drawbacks of the DAO method. Instead of smoothing the beamlet intensity maps as in many existing methods, we include a total-variation term in the optimization objective function to reduce the number of signal levels of the beam intensity maps. An aperture rectification algorithm is then applied to generate a significantly reduced number of deliverable apertures. As compared to the DAO algorithm, our method has an efficient form of quadratic optimization, with an additional advantage of optimizing field-specific numbers of segments based on the modulation complexity. The proposed approach is evaluated using two clinical cases. Under the condition that the clinical acceptance criteria of the treatment plan are satisfied, for the prostate patient, the total number of segments for five fields is reduced from 61 using the Eclipse planning system to 35 using the proposed algorithm; for the head and neck patient, the total number of segments for seven fields is reduced from 107 to 28. The head and neck result is also compared to that using an equal number of four segments for each field. The comparison shows that using field-specific numbers of segments achieves a much improved dose distribution.
Nerve growth factor inhibits some acute experimental inflammations. (1989)

Nerve growth factor (NGF) displays an inhibitory effect on peritoneal dye leakage in mice and on some types of acute inflammation in rats, i.e. acetic acid peritonitis and paw oedema induced by carrageenin, serotonin and dextran. Activity was only present in a restricted dose range, either after subcutaneous (1-8 micrograms/kg) or subplantar (0.5-5 micrograms) injection, and was characterized by a rapid onset of response. In the carrageenin test, NGF administered s.c. was more potent than indomethacin (INDO) and betamethasone (BTM); in addition, while the activity of INDO and BTM was observed only 2-3 hr after carrageenin challenge, the response of NGF developed within 1 hr, suggesting that NGF inhibits the early phase of the oedema. NGF exhibited a different action than BTM and INDO also in serotonin and dextran paw oedema. NGF (0.008 mg/kg s.c.) inhibited the serotonin oedema as early as 15 min and reached its maximum at 1 hr, whereas BTM (0.8 mg/kg) required at least 3 hr to attain the same effect. Serotonin oedema was not inhibited by INDO (even at 16 mg/kg) up to 0.25-6 hr, proving that this model of inflammation is insensitive to the inhibitors of prostaglandin synthesis. When given subplantary, NGF reduced dextran oedema, whereas BTM and INDO were ineffective. Pretreatment with specific anti-NGF antibodies abolished all the above effects of NGF, but did not modify the anti-inflammatory activity of BTM and INDO. NGF was less effective in reducing the exudate volume on carrageenin pleurisy and did not prevent cell migration. Tested in vitro, NGF showed no direct scavenging effect on superoxide radicals. These findings suggest that NGF may be involved in some types of acute inflammation by reducing vascular permeability.
SCALABLE SYNTHESES OFNα-BENZYLOXYCARBONYL-l-ORNITHINE AND OFNα-(9-FLUORENYLMETHOXY)CARBONYL-l-ORNITHINEE (2002)

(2002). SCALABLE SYNTHESES OF N α-BENZYLOXYCARBONYL-l-ORNITHINE AND OF N α-(9-FLUORENYLMETHOXY)CARBONYL-l-ORNITHINEE. Organic Preparations and Procedures International: Vol. 34, No. 5, pp. 531-537.
Long-Term Ventilatory Support by Diaphragm Pacing in Quadriplegia (1976)

Thirty-seven quadriplegic patients with respiratory paralysis were treated by electrical stimulation of the phrenic nerves to pace the diaphragm. Full-time ventilatory support by diaphragm pacing was accomplished in 13 patients. At least half-time support was achieved in 10 others. There were two deaths unrelated to pacing in these two groups. Fourteen patients could not be paced satisfactorily, and 8 of these patients died, most of them from respiratory infections. The average time the 13 patients on total ventilatory support have had bilateral diaphragm pacemakers is 26 months. The longest is 60 months. Many of these patients are out of the hospital and several are in school or working. Injury to the phrenic nerves either by the initial trauma to the cervical cord or during operation for implantation of the nerve cuff was the most significant complication. Nerve damage from prolonged electrical stimulation has not been a problem thus far. A description of the pacemaker, the technique of its implantation, and the pacing schedule are reported.
Nonenzymatic Glycosylation Products on Collagen Covalently Trap Low-Density Lipoprotein (1985)

Advanced nonenzymatic glycosylation products capable of cross-linking proteins accumulate on collagen in vivo in proportion to time-averaged blood glucose concentration. In this report, we have evaluated the ability of advanced nonenzymatic glycosylation products formed on collagen in vitro to covalently bind low-density lipoprotein (LDL) in a manner similar to that which occurs in human atherosclerotic lesions. At constant LDL concentration, covalent trapping increased linearly with the extent of advanced glycosylation product formation, from 1.42 +/- 0.15 to 4.46 +/- 0.36 micrograms LDL protein/mg collagen. At a constant level of collagen advanced glycosylation product, LDL binding increased as a function of increasing LDL concentration. At an LDL-cholesterol level of 103 mg/dl, covalent trapping of LDL by nonenzymatic glycosylation products on collagen averaged 3.2 times as much as control (P less than 0.01). These data indicate that LDL is bound specifically by reactive products generated by nonenzymatic glycosylation of collagen, and suggest that excessive LDL trapping by hyperglycemia-induced advanced glycosylation endproducts may contribute to the accelerated development of atherosclerosis in patients with diabetes mellitus.
Identification and Characterization of Novel Nrf2 Inducers Designed to Target the Intervening Region of Keap1 (2010)

Transcription factor Nrf2 regulates a battery of genes encoding detoxifying enzymes. Under basal conditions, Nrf2 is sequestered in the cytoplasm by a protein known as Keap1. In response to oxidative stress, Keap1-mediated ubiquitination of Nrf2 is decreased significantly and the Nrf2 pathway is turned on. Residues C273 and C288 at the intervening region (IVR) domain of Keap1 are necessary for Keap1 to repress Nrf2, indicating a critical role of the IVR domain in the functional interaction of Keap1 with Nrf2. To identify chemical modulator targeting the IVR domain of Keap1, we built a 3D structural model of the Keap1 IVR domain and demonstrated this structural model is effective in retrieving novel Nrf2 inducers from chemical databases, BM10, 31, and 40 increase concentration of nuclear Nrf2, with a potency comparable to that of sulforaphane. We showed C297S mutation partially abolished the Nrf2-inducing effect of BM31, suggesting BM31 may target C297 in the IVR domain of Keap1. Further, BM31 and BM40 potently induce expression of ARE-regulated enzyme gamma-glutamylcysteine synthetase. We demonstrated that BM31 provides protections for the MCF-7 cells from cytotoxic damage of carcinogen benzo[a]pyrene.