gebhart/patrepeval huggingface dataset:
Discovery of SIRT3 Inhibitors Using SAMDI Mass Spectrometry (2015)

Lysine acetylation plays a critical role in cellular regulation and is implicated in human disease. Sirtuin deacetylases remove acetyl groups from modified lysine residues, and sirtuin 3 (SIRT3) has been identified as a target for cancer therapeutics. Robust and high-throughput screening methods for these targets will be important to the development of therapeutics. This article describes the use of self-assembled monolayer desorption/ionization mass spectrometry, or SAMDI-MS-a label-free drug discovery tool--to characterize SIRT3 activity and discover inhibitors. SAMDI-MS was used to analyze a peptide array having 361 distinct acetylated peptides to identify an active SIRT3 substrate (GYK(Ac)RGC). This peptide was used in a screen of 100,000 small molecules to identify inhibitors of SIRT3. A total of 306 SIRT3 inhibitors were identified, with one compound, SDX-437, having an IC(50) of 700 nM with >100-fold selectivity for SIRT3 over SIRT1.
Intracellular signaling in M‐CSF‐induced microglia activation: Role of Iba1 (2002)

Microglia are reactively activated by various environmental stimulations caused by brain injury or disease. Activated microglia exhibit morphological transformation, proliferation, migration, phagocytosis, and the production of bioactive molecules. Various molecules are reported and suggested to activate microglia. Among them, macrophage-colony-stimulating factor (M-CSF) is considered one of the most convincing candidates responsible for maintaining activation properties of microglia. Therefore, the focus of the present study is on intracellular molecular events that arise downstream of M-CSF stimulation. M-CSF activates its receptor, Fms tyrosine kinase, and Fms sequentially activates a number of signaling molecules, including PI3K or phospholipase Cgamma (PLCgamma). Stimulation of continuing signaling cascades results in the activation of a small GTPase, Rac, the key molecule in microglia activation. Rac is known to be activated downstream of receptor tyrosine kinases and to regulate reorganization of the actin cytoskeleton, which profoundly underlies the above-mentioned properties of activated microglia. Iba1, a macrophage/microglia-specific calcium-binding protein, was identified by our group and was shown to be involved in the Rac signaling pathway. Further, we introduce a novel signaling pathway in which Rac is activated, dependent on PLCgamma and Iba1. However, to understand the molecular details of microglia activation, future work is required.
Analysis of a VMP-like sequence (vls) locus in Borrelia garinii and Vls homologues among four Borrelia burgdorferi sensu lato species (2001)

The VMP-like sequence (vls) locus that consists of one expressed vlsE gene and 15 silent vls cassettes has been described in Borrelia burgdorferi sensu stricto B31. In the present study, the vls locus from a Borrelia garinii isolate A87SA was analyzed. DNA fragments that contained three complete and five partial vls cassettes were cloned and sequenced. Pulsed-field gel electrophoresis (PFGE) analysis and Southern hybridization of the PFGE blot indicated that the vls locus of B. garinii A87SA, consisting of at least eight vls cassettes, was located on a 21-kb linear plasmid. The size of the three complete vls cassettes varied from 573 to 612 bp. They had 93.8-94.3% identity at the nucleotide level and 84.9-87.3% amino acid identity. The amino acid sequences of the three vls cassettes of B. garinii A87SA exhibited 45.9-50.8% identity to the VlsE sequence of B. burgdorferi B31, and 30.0-33.8% identity to the VMP17 sequence of B. hermsii HS1. Homologues of the vls locus of B. garinii were detected by dot blot hybridization among 24 of the 30 (80.0%) isolates representing four B. burgdorferi sensu lato species distributed widely in Europe. Our findings indicate that B. garinii might possess a similar vls structure to that described in B. burgdorferi sensu stricto. The highly conserved nature of the vls locus among various B. burgdorferi sensu lato species suggests that it may be important in the physiology and pathogenesis of Lyme disease spirochetes.
The Acid Stabilization of Plasminogen Activator Inhibitor-1 Depends on Protonation of a Single Group That Affects Loop Insertion into β-Sheet A (1995)

The serpin plasminogen activator inhibitor-1 (PAI-1) spontaneously adopts an inactive or latent conformation by inserting the N-terminal part of the reactive center loop as strand 4 into the major beta-sheet (sheet A). To examine factors that may regulate reactive loop insertion in PAI-1, we determined the inactivation rate of the inhibitor in the pH range 4.5-13. Below pH 9, inactivation led primarily to latent PAI-1, and one predominant effect of pH on the corresponding rate constant could be observed. Protonation of a group exhibiting a pKa of 7.6 (25 degrees C, ionic strength = 0.15 M) reduced the rate of formation of latent PAI-1 by a factor of 35, from 0.17 h-1 at pH 9 to about 0.005 h-1 below pH 6. The ionization with a pKa 7.6 was found to have no effect on the rate by which PAI-1 inhibits trypsin and is therefore unlikely to change the flexibility of the loop or the orientation of the reactive center. The peptides Ac-TEASSSTA and Ac-TVASSSTA (cf. P14-P7 in the reactive loop of PAI-1) formed stable complexes with PAI-1 and converted the inhibitor to a substrate for tissue type plasminogen activator. We found that peptide binding and formation of latent PAI-1 are mutually exclusive events, similarly affected by the pKa 7.6 ionization. This is direct evidence that external peptides can substitute for strand 4 in beta-sheet A of PAI-1 and that the pKa 7.6 ionization regulates insertion of complementary, internal or external, strands into this position. A model that accounts for the observed pH effects is presented, and the identity of the ionizing group is discussed based on the structure of latent PAI-1. The group is tentatively identified as His-143 in helix F, located on top of sheet A.
Periodontal Diseases in the United States Population (1998)

Recent epidemiologic surveys and studies have provided important information on the prevalence, extent, and severity of periodontal diseases in the United States. Over 50% of adults had gingivitis on an average of 3 to 4 teeth. Subgingival calculus was present in 67% of the population. Adult periodontitis, measured by the presence of periodontal pockets > or = 4 mm, was found in about 30% of the population on an average of 3 to 4 teeth. Severe pockets > or = 6 mm were found in less than 5% of the population. Attachment loss > or = 3 mm was found in 40% of the population. Gingival recession accounted for a significant amount of attachment loss. The prevalence of early-onset periodontitis ranged from less than 1% in 14- to 17-year-olds to 3.6% in young adults aged 18 to 34. Extensive and severe periodontitis was much more prevalent in minorities, people with less than a high school education, and those who had seen a dentist infrequently and had subgingival calculus. Smoking and diabetes have been identified as risk factors, especially diabetics with poor metabolic control, a long duration of the disease, and extensive subgingival calculus. Under managed care, there has been an expansion of soft tissue management programs in the offices of general dentists and referral guidelines which limit referral of patients with moderate periodontitis. Quality-assurance mechanisms will be essential for the diagnosis and treatment of persons with periodontitis.
Source and channel coding in wireless sensor networks using LDPC codes (2005)

In this paper, we study two problems of providing reliable data transmission and developing aggregation techniques for correlated data in wireless sensor networks. A system with forward error correction (FEC) can provide an objective reliability while using less transmission power than a system without FEC. Because of the additional parity bits and encoding/decoding energy consumptions, we study the effect of FEC on energy efficiency. We propose to use LDPC codes for FEC. We show that wireless sensor networks using LDPC codes are almost 45% more energy efficient than those that use BCH codes, which were shown to be 15% more energy efficient than the best performing convolutional codes. Then we study the problem of providing aggregation for two and three correlated nodes in wireless sensor networks. We propose to use LDPC codes in wireless sensor networks for source and channel coding to obtain a two-fold energy savings. For two correlated nodes, we study both distributed source coding and joint source-channel coding. While distributed source coding using LDPC codes was studied before, joint source-channel coding using LDPC codes is introduced for the first time. The difference between our work in distributed source coding using LDPC codes and the previous work lies in the LDPC code design procedure. The simulation results show that our proposed design criteria improves the performance of the source coding. The convergence of the non-uniform LDPC code of our design technique is almost 60% closer to the Slepian-Wolf limit. For three correlated nodes, we study distributed source coding using LDPC codes. We simplified the problem of design procedure to randomly punctured LDPC codes. This is a new approach for designing LDPC codes and the simulation results for code of length 1000 shows that the convergence of the LDPC code is achieved at compression rate 0.3174 which is only 0.08 away from the Slepian-Wolf limit.
Molecular probes for diagnosis of fungal infections (1995)

We have developed 21 specific nucleic acid probes which target the large subunit rRNA genes from Aspergillus flavus, Aspergillus fumigatus, Aspergillus glaucus, Aspergillus niger, Aspergillus terreus, Blastomyces dermatitidis, Candida albicans, Candida (Torulopsis) glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Coccidioides immitis, Cryptococcus neoformans var. gattii, Cryptococcus neoformans var. neoformans, Filobasidiella neoformans var. bacillispora, Filobasidiella neoformans var. neoformans, Histoplasma capsulatum, Pseudallescheria boydii, and Sporothrix schenckii. A section of the 28S rRNA gene from approximately 100 fungi, representing about 50 species of pathogens and commonly encountered saprophytes, was sequenced to develop universal PCR primers and species-specific oligonucleotide probes. Each step in the process of detection and identification was standardized to a common set of conditions applicable without modification to all fungi of interest and all types of clinical specimens. These steps consist of DNA extraction by boiling specimens in an alkaline guanidine-phenol-Tris reagent, amplification of a variable region of the 28S rRNA gene with universal primers, and amplicon identification by probe hybridization or DNA sequencing performed under conditions identical for all fungi. The results obtained by testing a panel of fungal isolates and a variety of clinical specimens indicate a high level of specificity.
The Clonality ofStaphylococcus aureusNasal Carriage (2005)

Nasal carriage of Staphylococcus aureus is often a prelude to infection with the same strain. The prevailing assumption has been that colonized individuals carry a single strain. The present study investigated the frequency of simultaneous nasal carriage of multiple strains of S. aureus. Three bacterial colonies from plated samples from colonized subjects were initially compared by pulsed-field gel electrophoresis. Fourteen of 148 S. aureus-positive samples demonstrated at least a difference of a single band; 7 of these 14 samples contained different strains, and 3 of these 7 also belonged to different accessory gene regulator (agr) types. The remaining 7 samples contained clonally related isolates; 3 of these 7 contained pairs that differed by the presence or absence of the staphylococcal chromosomal cassette mec type IV. A mathematical model that we developed predicted that approximately 6.6% of S. aureus-colonized individuals carry >1 strain. The present study demonstrates that carriage of discordant S. aureus strains in individuals with nasal colonization occurs regularly and suggests that the nares are likely sites for horizontal genetic exchange among strains.
Laser-induced fluorescence imaging of bacteria (1998)

This paper outlines a method for optically detecting bacteria on various backgrounds, such as meat, by imaging their laser induced auto-fluorescence response. This method can potentially operate in real-time, which is many times faster than current bacterial detection methods, which require culturing of bacterial samples. This paper describes the imaging technique employed whereby a laser spot is scanned across an object while capturing, filtering, and digitizing the returned light. Preliminary results of the bacterial auto-fluorescence are reported and plans for future research are discussed. The results to date are encouraging with six of the eight bacterial strains investigated exhibiting auto-fluorescence when excited at 488 nm. Discrimination of these bacterial strains against red meat is shown and techniques for reducing background fluorescence discussed.
Dielectrophoretic assembly of reversible and irreversible metal nanowire networks and vertically aligned arrays (2006)

We demonstrate the dielectrophoretic control of metallic nanowires (NWs) in liquid suspensions. By varying a range of parameters including the magnitude and frequency of the applied electric field, the liquid suspending the NWs, and the flow conditions, we demonstrate control over NW network formation and dissolution, as well as ordering of NWs into vertically aligned arrays. These results suggest a straightforward strategy for NW assembly and integration in devices.
Reduced axonal transport in Parkinson's disease cybrid neurites is restored by light therapy (2009)

The results from this study support our proposal that axonal transport is reduced in sporadic PD and that a single, brief treatment with near-infrared light can restore axonal transport to control levels. These results are the first demonstration that LLLT can increase axonal transport in model human dopaminergic neuronal cells and they suggest that LLLT could be developed as a novel treatment to improve neuronal function in patients with PD.
Increased cytosine DNA-methyltransferase activity is target-cell-specific and an early event in lung cancer. (1996)

The association between increased DNA-methyltransferase (DNA-MTase) activity and tumor development suggest a fundamental role for this enzyme in the initiation and progression of cancer. A true functional role for DNA-MTase in the neoplastic process would be further substantiated if the target cells affected by the initiating carcinogen exhibit changes in enzyme activity. This hypothesis was addressed by examining DNA-MTase activity in alveolar type II (target) and Clara (nontarget) cells from A/J and C3H mice that exhibit high and low susceptibility, respectively, for lung tumor formation. Increased DNA-MTase activity was found only in the target alveolar type II cells of the susceptible A/J mouse and caused a marked increase in overall DNA methylation in these cells. Both DNA-MTase and DNA methylation changes were detected 7 days after carcinogen exposure and, thus, were early events in neoplastic evolution. Increased gene expression was also detected by RNA in situ hybridization in hypertrophic alveolar type II cells of carcinogen-treated A/J mice, indicating that elevated levels of expression may be a biomarker for premalignancy. Enzyme activity increased incrementally during lung cancer progression and coincided with increased expression of the DNA-MTase activity are strongly associated with neoplastic development and constitute a key step in carcinogenesis. The detection of premalignant lung disease through increased DNA-MTase expression and the possibility of blocking the deleterious effects of this change with specific inhibitors will offer new intervention strategies for lung cancer.
Bridges from hospitals to the laboratory: genetic portraits of methicillin-resistantStaphylococcus aureusclones (2004)

Methicillin-resistant Staphylococcus aureus (MRSA) emerged in the early 1960's after the acquisition of the methicillin resistance gene mecA, which is carried by the staphylococcal cassette chromosome mec (SCCmec). MRSA seemed to have arisen by multiple introductions of SCCmec into successful methicillin-susceptible S. aureus (MSSA) lineages. MRSA is one of the most common agents of nosocomial infections worldwide increasing the cost and mortality compared to MSSA infections. Little by little, MRSA has acquired resistance to all antibiotics available in clinical practice, which complicates treatment. This situation was further aggravated by the recent reports of vanA-mediated vancomycin-resistant S. aureus. As a reaction to the emergence and spread of multidrug-resistant MRSA worldwide, international surveillance systems such as the CEM/NET initiative have been created. The characterization of over 3000 MRSA isolates from different regions of the world evidenced the existence of only a few epidemic clones spread worldwide, namely the Iberian, Brazilian, Hungarian, New York/Japan, Pediatric and EMRSA-16 clones. It was found that in surveillance or evolutionary studies strains should be characterized by a combination of different typing methods, namely pulsed-field gel electrophoresis, multi-locus sequence typing and SCCmec typing. In recent years, community-acquired MRSA (CA-MRSA) has become a growing public health concern. However, although many authors reported the emergence of CA-MRSA isolates, a standard definition has not been created and the prevalence of MRSA among persons without risk factors seems to remain very low. CA-MRSA has distinct properties compared to epidemic nosocomial clones and its origin is still unclear. Certain authors suggest there is MRSA transmission from the hospital setting to the community, namely transfer of nosocomial MRSA minor clones or sporadic isolates showing a high degree of similarity with CA-MRSA; others believe CA-MRSA strains represent new acquisitions of SCCmec DNA in susceptible backgrounds. Many questions concerning this extraordinarily versatile and threatening pathogen remain unanswered, needing future investigation
Ultrawideband radar imaging system for biomedical applications (2006)

Ultrawideband (UWB) (3–10GHz) radar imaging systems offer much promise for biomedical applications such as cancer detection because of their good penetration and resolution characteristics. The underlying principle of UWB cancer detection is a significant contrast in dielectric properties, which is estimated to be greater than 2:1 between normal and cancerous tissue, compared to a few-percent contrast in radiographic density exploited by x rays. This article presents a feasibility study of the UWB imaging of liver cancer tumors, based on the frequency-dependent finite difference time domain method. The reflection, radiation, and scattering properties of UWB pulses as they propagate through the human body are studied. The reflected and back-scattered electromagnetic energies from cancer tumors inside the liver are also investigated. An optimized, ultrawideband antenna was designed for near field operation, allowing for the reduction of the air-skin interface. It will be placed on the fat-liver tissue phantom with a malignant tumor stimulant. By performing an incremental scan over the phantom and removing early time artifacts, including reflection from the antenna ends, images based on the back-scattered signal from the tumor can be constructed. This research is part of our effort to develop a UWB cancer detection system with good detection and localization properties.
Tumor Associated Glycoprotein-72 is Highly Expressed in Prostatic Adenocarcinomas (1994)

We examined the expression of two well-characterized oncofetal antigens, the tumor associated glycoprotein-72 (TAG-72) and carcinoembryonic antigen (CEA), in malignant prostatic tissues. Three specific monoclonal antibodies, B72.3, CC49 and CC83, were used to examine the expression of TAG-72. Immunoreactivity was detected in 63% of the malignant specimens using B72.3. CC49 and CC83 were more sensitive than B72.3 in detecting TAG-72 expression. Immunoreactivity was detected in approximately 80% of prostatic adenocarcinomas with CC49 or CC83. The pattern and localization of TAG-72 immunoreactivity were similar for the three antibodies with most immunoreactivity observed within the cytoplasm of malignant cells and within the lumens of malignant glands. TAG-72 immunoreactivity was not detected within benign epithelium or stroma, with the exception of focal epithelial expression in areas of acute prostatitis. The COL-1 antibody to CEA did not detect CEA in benign glands, stroma, or malignant cells of prostate specimens resected for prostatic adenocarcinoma. These results demonstrate that TAG-72, but not CEA, is frequently expressed in prostatic adenocarcinomas.
Apoptosis in Human Adenocarcinoma HT29 Cells Induced by Exposure to Hypoxia (1995)

These results suggest a possible relationship between Ref-1 induction and the occurrence of apoptosis following a hypoxic exposure.
Future Immunotherapy: What Lies Ahead? (1995)

There is currently great interest in developing improved methods of immunotherapy and new techniques of immune system manipulation to ameliorate allergic diseases. This article reviews current research trends in the immunologic treatment of allergy, including the use of chemically modified allergens, nonparenteral allergen exposure, sustained-release allergen delivery, anti-immunoglobulin E antibodies, gamma-globulin, immune complexes, cytokines, and T-cell-tolerogenic peptides.
Hydride formation on the Si(100):H2O surface (1984)

${\mathrm{H}}_{2}$O chemisorption on Si(100) is studied with high-resolution infrared spectroscopy. Water molecules are found to dissociate upon room-temperature exposure forming Si-H and Si-OH. Mild annealing breaks up the O-H molecule resulting in oxide, monohydride, and dihydride species. The angle made by the effective dynamic dipole moment associated with the Si-H bond, with respect to the surface normal, is measured for the different hydrides formed.
Rapid mass spectrometric identification of human genomic polymorphisms using multiplexed photocleavable mass-tagged probes and solid phase capture (2007)

A mass spectrometric approach for rapid and simultaneous detection of several single nucleotide polymorphisms (SNPs) is reported. Oligonucleotide single base extension (SBE) primers, labelled at the 5'-end with photocleavable, quaternised and brominated peptidic mass tags, are extended by a mixture of the four dideoxynucleotides of which one is biotinylated. The 3'-biotinylated extension products are captured by streptavidin-coated solid phase magnetic beads, whilst non-biotinylated extension products and unreacted primers are washed away. Quaternised and brominated mass tags, cleaved from captured extension products during analysis by matrix-assisted laser desorption/ionisation-time-of-flight (MALDI-TOF) MS, are detected at pmol levels. This method is applied to the analysis of mitochondrial DNA polymorphisms for the purpose of human identification.