gebhart/patrepeval huggingface dataset:
Palmitoyl acyltransferase assays and inhibitors (Review) (2009)

Palmitoylated proteins have been implicated in several disease states including Huntington's, cardiovascular, T-cell mediated immune diseases, and cancer. To proceed with drug discovery efforts in this area, it is necessary to: identify the target enzymes, establish efficient assays for palmitoylation, and conduct high-throughput screening to identify inhibitors. The primary objectives of this review are to examine the types of assays used to study protein palmitoylation and to discuss the known inhibitors of palmitoylation. Six main palmitoylation assays are currently in use. Four assays, radiolabeled palmitate incorporation, fatty acyl exchange chemistry, MALDI-TOF MS and azido-fatty acid labeling are useful in the identification of palmitoylated proteins and palmitoyl acyltransferase (PAT) enzymes. Two other methods, the in vitro palmitoylation (IVP) assay and a cell-based peptide palmitoylation assay, are useful in the identification of PAT enzymes and are more amenable to screening for inhibitors of palmitoylation. To date, two general types of palmitoylation inhibitors have been identified. Lipid-based palmitoylation inhibitors broadly inhibit the palmitoylation of proteins; however, the mechanism of action of these compounds is unknown, and each also has effects on fatty acid biosynthesis. Conversely, several non-lipid palmitoylation inhibitors have been shown to selectively inhibit the palmitoylation of different PAT recognition motifs. The selective nature of these compounds suggests that they may act as protein substrate competitors, and may produce fewer non-specific effects. Therefore, these molecules may serve as lead compounds for the further development of selective inhibitors of palmitoylation, which may lead to new therapeutics for cancer and other diseases.
Single crystal growth from separated educts and its application to lithium transition-metal oxides (2016)

Thorough mixing of the starting materials is the first step of a crystal growth procedure. This holds true for almost any standard technique, whereas the intentional separation of educts is considered to be restricted to a very limited number of cases. Here we show that single crystals of α-Li<sub>2</sub>IrO<sub>3</sub> can be grown from separated educts in an open crucible in air. Elemental lithium and iridium are oxidized and transported over a distance of typically one centimeter. In contrast to classical vapor transport, the process is essentially isothermal and a temperature gradient of minor importance. Single crystals grow from an exposed condensation point placed in between the educts. The method has also been applied to the growth of Li<sub>2</sub>RuO<sub>3</sub>, Li<sub>2</sub>PtO<sub>3</sub> and β-Li<sub>2</sub>IrO<sub>3</sub>. A successful use of this simple and low cost technique for various other materials is anticipated.
A Randomized Controlled Trial of the Effect of Pertussis Vaccines on Atopic Disease (1998)

We found no support for a drastic increase in allergic manifestations after pertussis vaccination. There was a positive association between whooping cough and asthma by 2 1/2 years of age. There seems to be little reason to withhold pertussis vaccination from infants, irrespective of family history of allergy.
The Preparation and Rearrangement of Phenylglycosides (1942)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Preparation and Rearrangement of PhenylglycosidesEdna M. Montgomery, Nelson K. Richtmyer, and C. S. HudsonCite this: J. Am. Chem. Soc. 1942, 64, 3, 690–694Publication Date (Print):March 1, 1942Publication History Published online1 May 2002Published inissue 1 March 1942https://pubs.acs.org/doi/10.1021/ja01255a060https://doi.org/10.1021/ja01255a060research-articleACS PublicationsRequest reuse permissionsArticle Views571Altmetric-Citations104LEARN 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-Alertsclose Get e-Alerts
Parallel global optimization with the particle swarm algorithm (2004)

Present day engineering optimization problems often impose large computational demands, resulting in long solution times even on a modern high-end processor. To obtain enhanced computational throughput and global search capability, we detail the coarse-grained parallelization of an increasingly popular global search method, the particle swarm optimization (PSO) algorithm. Parallel PSO performance was evaluated using two categories of optimization problems possessing multiple local minima-large-scale analytical test problems with computationally cheap function evaluations and medium-scale biomechanical system identification problems with computationally expensive function evaluations. For load-balanced analytical test problems formulated using 128 design variables, speedup was close to ideal and parallel efficiency above 95% for up to 32 nodes on a Beowulf cluster. In contrast, for load-imbalanced biomechanical system identification problems with 12 design variables, speedup plateaued and parallel efficiency decreased almost linearly with increasing number of nodes. The primary factor affecting parallel performance was the synchronization requirement of the parallel algorithm, which dictated that each iteration must wait for completion of the slowest fitness evaluation. When the analytical problems were solved using a fixed number of swarm iterations, a single population of 128 particles produced a better convergence rate than did multiple independent runs performed using sub-populations (8 runs with 16 particles, 4 runs with 32 particles, or 2 runs with 64 particles). These results suggest that (1) parallel PSO exhibits excellent parallel performance under load-balanced conditions, (2) an asynchronous implementation would be valuable for real-life problems subject to load imbalance, and (3) larger population sizes should be considered when multiple processors are available.
Development of a Creatinine ELISA and an Amperometric Antibody-Based Creatinine Sensor with a Detection Limit in the Nanomolar Range (2000)

Creatinine-specific antibodies have been generated and used for highly sensitive and specific immunochemical creatinine determinations. Creatinine was derivatized at N3 and coupled to KLH carrier protein. On the basis of this immunogen, monoclonal antibodies were developed by hybridoma technology. Antibodies from various clones have been characterized with BIAcore 2000 with respect to the dissociation constant and specificity. Antibodies of clone B90-AH5 exhibited the lowest dissociation constant (0.74 microM) and the highest specificity for creatinine and were chosen for the development of a competitive ELISA and an amperometric creatinine sensor. The creatinine sensor was constructed by fixing a creatinine-modified membrane on the top of a platinum working electrode which was then incorporated into a stirred electrochemical measuring cell. For creatinine determination the creatinine-containing sample was incubated with B90-AH5 and anti-IgG(mouse)-glucose oxidase conjugate and applied to the measuring cell. After a washing step glucose was added and the produced hydrogen peroxide was registered at Eappl = +600 mV vs Ag/AgCl. The measuring range was 0.01-10 microg/mL. The highest sensitivity for creatinine was achieved at 330 ng/mL (3 microM) and the lower detection limit at 4.5 ng/mL (40 nM). This is far below the relevant clinical range, which is 5-17 microg/mL (44-150 microM) and allows a reliable determination of very low creatinine concentrations in serum, where standard methods cannot be applied. After each measurement the sensor was regenerated with 10 mM HCl without any loss in binding activity.
Proteasomal non‐catalytic subunit PSMD2 as a potential therapeutic target in association with various clinicopathologic features in lung adenocarcinomas (2011)

We previously identified PSMD2, a subunit of the 19S regulatory complex of proteasomes, as a constituent of a signature associated with the acquisition of metastatic phenotype and poor prognosis in lung cancers. In the present study, we found that knockdown of PSMD2 decreased proteasome activity, and induced growth inhibition and apoptosis in lung cancer cell lines. These effects of siRNA-mediated PSMD2 inhibition were associated with changes in the balance between phosphorylated AKT and p38, as well as with induction of p21. In addition, patients with higher PSMD2 expression had poorer prognosis and a small fraction of lung cancer specimens carried increased copies of PSMD2. Notably, our findings clearly illustrate that lung adenocarcinomas can be divided into two groups; those with and without general upregulation of proteasome pathway genes including PSMD2. This general upregulation was significantly more prevalent in the non-terminal respiratory unit (non-TRU)-type, a recently proposed genetically and clinicopathologically relevant expression profile-defined classification of adenocarcinomas (P < 0.001 by Fisher's exact test). Patients with adenocarcinomas with general upregulation had significantly shorter survival after potentially curative resection (P = 0.0001 by log-rank test) independent of disease stage, as shown by multivariate Cox regression analysis. Our results suggest that PSMD2 may be a good molecular target candidate and that other co-regulated proteasome pathway genes and/or their common regulator(s) might also be potential targets, warranting future study including elucidation of the underlying common regulatory mechanism.
Substituted triazoles as anti-inflammatory agents. (1984)

Newly synthesized triazoles were evaluated for their anti-inflammatory and antiproteolytic activities. These derivatives possessed potent anti-inflammatory and antiproteolytic activities. In addition, these compounds were relatively less toxic.
Preeclamptic sera induce nephrin shedding from podocytes through endothelin-1 release by endothelial glomerular cells (2008)

In preeclampsia (PE), proteinuria has been associated with a reduced expression of nephrin by podocytes. In the present study, we investigated in vitro on human cultured podocytes the mechanism responsible for nephrin loss in PE. Sera from patients with PE did not directly downregulate the expression of nephrin. In contrast, conditioned medium obtained from glomerular endothelial cells incubated with PE sera induced loss of nephrin and synaptopodin, but not of podocin, from podocytes. Nephrin loss was related to a rapid shedding of the protein from the cell surface due to cleavage of its extracellular domain by proteases and to cytoskeleton redistribution. The absence of nephrin mRNA downregulation together with nephrin reexpression within 24 h confirm that the loss of nephrin was not related to a reduced synthesis. Studies with an endothelin-1 (ET-1) receptor antagonist that abrogated the loss of nephrin triggered by glomerular endothelial conditioned medium of PE sera indicated that ET-1 was the main effector of nephrin loss. Indeed, ET-1 was synthesized and released from glomerular endothelial cells when incubated with PE sera, and recombinant ET-1 triggered nephrin shedding from podocytes. Moreover, VEGF blockade induced ET-1 release from endothelial cells, and in turn the conditioned medium obtained triggered nephrin loss. In conclusion, the present study identifies a potential mechanism of nephrin loss in PE that may link endothelial injury with enhanced glomerular permeability.
Identification of the Genes Involved in Enhanced Fenretinide-Induced Apoptosis by Parthenolide in Human Hepatoma Cells (2005)

Fenretinide (N-4-hydroxyphenyl retinamide, 4HPR) is a synthetic anticancer retinoid that is a well-known apoptosis-inducing agent. Recently, we observed that the apoptosis induced by fenretinide could be effectively enhanced in hepatoma cells by a concomitant treatment with parthenolide, which is a known inhibitor of nuclear factor-kappaB (NF-kappaB). Furthermore, treatment with fenretinide triggered the activation of NF-kappaB during apoptosis, which could be substantially inhibited by parthenolide, suggesting that NF-kappaB activation during fenretinide-induced apoptosis has an antiapoptotic effect. This study investigated the molecular mechanism of this apoptotic potentiation by NF-kappaB inhibition. The genes involved in the enhanced fenretinide-induced apoptosis by parthenolide were identified using the differential display-PCR method and subsequent Northern blot or semiquantitative reverse transcriptase PCR analysis. This study identified 35 apoptosis-related genes including 12 unknown genes that were either up- or down-regulated by parthenolide. Interestingly, one up-regulated gene (HA1A2) was isolated and cloned from the liver cDNA, and was found to be identical to ANKRD1, which is also referred to as the CARP gene. Compared with controls treated with an empty vector or with antisense cDNA, the ectopic expression of ANKRD1 led to reduced colony formation and to enhanced apoptotic cell death in hepatoma cells. These results suggest that ANKRD1 and the other genes, whose expressions were substantially modulated by the parthenolide-mediated inhibition of NF-kappaB activation, play roles in the enhanced drug-induced apoptosis. In addition, this study suggests that those identified genes may be useful in anticancer strategies against hepatoma.
Lysophosphatidic acid stimulates phospholipase D activity and cell proliferation in PC-3 human prostate cancer cells (1998)

Phospholipase D (PLD) is activated in mammalian cells in response to a variety of growth factors and may play a role in cell proliferation. Lysophosphatidic acid (LPA) is a bioactive metabolite potentially generated as a result of PLD activation. Two human prostate cancer cell lines, PC-3 and LNCaP, express membrane PLD activity. The effects of LPA on PLD activity and proliferation were examined in PC-3 cells, which express hPLD1a/1b. Phorbol 12-myristate 13-acetate (PMA) induced a prolonged activation of PLD, as detected in both intact cells and membranes. LPA induced a transient activation of PLD that was maximal by 10 minutes. The EC50 for LPA-induced PLD activation was approximately 1 microM. Pertussis toxin did not inhibit activation of PLD by LPA or PMA. Ro-31-8220 and bisindolylmaleimide I, inhibitors of protein kinase C, blocked activation by PLD by both PMA and LPA. PMA-induced activation of PLD did not appear to require translocation of PLDs from cytosol to membrane. LPA stimulated proliferation of PC-3 cells with an EC50 of approximately 0.2 microM; this response was not inhibited by pertussis toxin. Perillyl alcohol, an anti-cancer drug, reversibly inhibited proliferation in response to either serum or LPA but did not inhibit activation of PLD by PMA or LPA. These data establish that LPA activates PLD and stimulates proliferation via Gi-independent pathways in a human prostate cancer cell line.
A survey of image registration techniques (1992)

Registration is a fundamental task in image processing used to match two or more pictures taken, for example, at different times, from different sensors, or from different viewpoints. Virtually all large systems which evaluate images require the registration of images, or a closely related operation, as an intermediate step. Specific examples of systems where image registration is a significant component include matching a target with a real-time image of a scene for target recognition, monitoring global land usage using satellite images, matching stereo images to recover shape for autonomous navigation, and aligning images from different medical modalities for diagnosis. Over the years, a broad range of techniques has been developed for various types of data and problems. These techniques have been independently studied for several different applications, resulting in a large body of research. This paper organizes this material by establishing the relationship between the variations in the images and the type of registration techniques which can most appropriately be applied. Three major types of variations are distinguished. The first type are the variations due to the differences in acquisition which cause the images to be misaligned. To register images, a spatial transformation is found which will remove these variations. The class of transformations which must be searched to find the optimal transformation is determined by knowledge about the variations of this type. The transformation class in turn influences the general technique that should be taken. The second type of variations are those which are also due to differences in acquisition, but cannot be modeled easily such as lighting and atmospheric conditions. This type usually effects intensity values, but they may also be spatial, such as perspective distortions. The third type of variations are differences in the images that are of interest such as object movements, growths, or other scene changes. Variations of the second and third type are not directly removed by registration, but they make registration more difficult since an exact match is no longer possible. In particular, it is critical that variations of the third type are not removed. Knowledge about the characteristics of each type of variation effect the choice of feature space, similarity measure, search space, and search strategy which will make up the final technique. All registration techniques can be viewed as different combinations of these choices. This framework is useful for understanding the merits and relationships between the wide variety of existing techniques and for assisting in the selection of the most suitable technique for a specific problem.
A bone-like nano-hydroxyapatite/collagen loaded injectable scaffold (2009)

From a clinical perspective, the use of injectable scaffolds is very attractive as it minimizes patient discomfort, risk of infection, scar formation and the cost of treatment. Bone refers to a family of materials that are constructed by mineralized collagen fibrils. The main objective of this research was to develop a bone-like nano-hydroxyapatite/collagen (nHAC) loaded chitosan (C)/beta-glycerophosphate (GP) injectable scaffold. The feasibility of developing a thermo-sensitive and injectable chitosan solution in the presence of nHAC was demonstrated. Bone-marrow-derived messenchymal stem cells (MSCs) were used to measure the cell proliferation of C/GP/nHAC scaffolds based on the cell count kit-8 (CCK-8) assay. It was found that MSCs proliferated normally with the C/GP/nHAC composite scaffolds. The C/GP/nHAC composite scaffolds developed in this study exhibited good injectability, thermo-irreversible properties and solidified under mild conditions. No more than 0.02 g ml(-1) of nHAC filler was required to form a non-decaying hydrogel.
The Rat Glomerular Filtration Barrier Does Not Show Negative Charge Selectivity (2002)

These findings indicate that the rat glomerular filtration barrier restricts the transport of polysaccharide macromolecules as a function of their size and configuration but not negative charge.
Molecular cloning and nucleotide sequence of deer papillomavirus (1985)

The genome of deer papillomavirus (DPV) isolated from American white-tailed deer was cloned into pBR322, and the entire nucleotide sequence of 8,374 base pairs was determined. The overall genetic organization of the DPV genome was similar to that of other papillomaviruses. All significant open reading frames were located on one strand, and the locations of putative promoters and polyadenylation signals were similar to those identified in the closely related bovine papillomavirus type 1 (BPV-1) genome. The DPV genome was approximately colinear with BPV-1 except for a noncoding region separating the early and late regions. The regions of highest nucleotide sequence homology between DPV and BPV-1 were found in the E1 open reading frame coding for BPV-1 DNA replication function and in the L1 open reading frame, which encodes the major capsid protein of BPV-1.
An Interleukin‐1 Genotype Is Associated with Fatal Outcome of Meningococcal Disease (2000)

To determine whether known variants of the interleukin-1 (IL-1) and tumor necrosis factor (TNF) gene families are associated with severe manifestations of meningococcal disease, 276 white patients 4-70 years of age (median, 17 years) were genotyped. All patients had microbiologically proven Neisseria meningitidis infection; 39 died and 237 survived. A significant association (P<.001) was found between fatal outcome and genotype at IL1B (nucleotide position -511). Homozygous individuals, both for the common (1/1) and the rare (2/2) alleles, had increased odds ratios (ORs) for death, compared with heterozygous individuals (1/2): ORs (95% confidence intervals [CIs]) were 3.39 (1.39-8.29) and 7.35 (2.51-21.45), respectively. The mortality rates according to genotype at IL1B (-511) were 18.0% (1/1), 6.1% (1/2), and 32.3% (2/2), compared with 14.2% overall. The composite genotype, consisting of heterozygosity of IL1B (-511) together with homozygosity of the common allele of the IL-1 receptor antagonist gene (IL1RN) at +2018, was significantly associated with survival (P=.018; OR, 7.78 [95% CI, 1. 05-59.05]). There was no association between TNF genotype and fatal outcome. These data suggest that IL-1 genotype influences the severity of meningococcal disease.
Phase I study of the combination of alpha-2 interferon and cisplatinum. (1989)

Based on preclinical evidence of synergy, we performed a Phase I study of the combination of alpha-2 interferon and cisplatinum in patients with advanced malignancy. A fixed dose of 5 x 10(6) U/m2 alpha interferon was given three times weekly. Cisplatinum was given once weekly at dose levels of 5, 10, 20, 25, and 30 mg/m2. Dose-limiting toxicity consisted of flu-like symptoms and malaise leading to decreased performance status. Response was seen in a patient with metastatic melanoma. Recommended doses for Phase II study are 5 x 10(6) U/m2 of alpha-2 interferon three times weekly and 25 mg/m2 of cisplatinum once weekly.
CpG oligodeoxynucleotides induce human monocytes to mature into functional dendritic cells (2002)

Dendritic cells (DC) excel at presenting antigen to T cells and thus make a key contribution to the induction of primary and secondary immune responses. DC matured in vitro and pulsed with antigen show promise for the immunotherapy of cancer and infectious diseases. Synthetic oligonucleotides (ODN) expressing immunomodulatory "CpG motifs" were found to boost APC function in mice. Current results demonstrate that the recently identified "D" type of CpG ODN stimulate human peripheral blood monocytes to mature into functionally active DC over 2-4 days. The transition from monocyte to DC is characterized by the up-regulation of CD83, CD86, CD80, CD40 and the down-regulation of CD14. These DC support antigen-specific humoral and cellular responses in vitro and in vivo. The differentiation of these monocytes is mediated by plasmacytoid DC, which respond to D type ODN by secreting IFN-alpha. Since D type CpG motifs are present in bacterial and viral DNA, the maturation of monocytes into functional DC may reflect a physiologic response that can be harnessed therapeutically through the use of CpG ODN.