gebhart/patrepeval huggingface dataset:
CotA laccase: high-throughput manipulation and analysis of recombinant enzyme libraries expressed in E. coli using droplet-based microfluidics (2014)

We present a high-throughput droplet-based microfluidic analysis/screening platform for directed evolution of CotA laccase: droplet-based microfluidic modules were combined to develop an efficient system that allows cell detection and sorting based on the enzymatic activity. This platform was run on two different operating modes: the "analysis" mode allowing the analysis of the enzymatic activity in droplets at very high rates (>1000 Hz) and the "screening" mode allowing sorting of active droplets at 400 Hz. The screening mode was validated for the directed evolution of the cytoplasmic CotA laccase from B. subtilis, a potential interesting thermophilic cathodic catalyst for biofuel cells. Single E. coli cells expressing either the active CotA laccase (E. coli CotA) or an inactive frameshifted variant (E. coli ΔCotA) were compartmentalized in aqueous droplets containing expression medium. After cell growth and protein expression within the droplets, a fluorogenic substrate was "picoinjected" in each droplet. Fluorescence-activated droplet sorting was then used to sort the droplets containing the desired activity and the corresponding cells were then recultivated and identified using colorimetric assays. We demonstrated that E. coli CotA cells were enriched 191-fold from a 1 : 9 initial ratio of E. coli CotA to E. coli ΔCotA cells (or 437-fold from a 1 : 99 initial ratio) using a sorting rate of 400 droplets per s. This system allows screening of 10(6) cells in only 4 h, compared to 11 days for screening using microtitre plate-based systems. Besides this low error rate sorting mode, the system can also be used at higher throughputs in "enrichment" screening mode to make an initial purification of a library before further steps of selection. Analysis mode, without sorting, was used to rapidly quantify the activity of a CotA library constructed using error-prone PCR. This mode allows analysis of 10(6) cells in only 1.5 h.
Identification of Natural MHC Class II Presented Phosphopeptides and Tumor-Derived MHC Class I Phospholigands (2009)

MHC molecules present protein-derived peptides to T lymphocytes. By developing TiO2-based microcentrifugation columns, we identified the first phosphorylated MHC class I ligands from tumor tissue (renal cell carcinoma) and, by comparison to healthy renal tissue, found one Brf1-derived ligand as potentially tumor-associated. We further discovered the first natural phosphorylated MHC class II ligands. They revealed several novel phosphorylation sites of significant transmembrane receptors, such as Frizzled 6, CXCR4 and CD20.
Requirement of activation of complement C3 and C5 for antiphospholipid antibody–mediated thrombophilia (2005)

These data show that complement activation mediates 2 important effectors of aPL, induction of thrombosis and activation of endothelial cells.
An Omnidirectional Stereo Vision System Using a Single Camera (2006)

We describe a new omnidirectional stereo imaging system that uses a concave lens and a convex mirror to produce a stereo pair of images on the sensor of a conventional camera. The light incident from a scene point is split and directed to the camera in two parts. One part reaches camera directly after reflection from the convex mirror and forms a single-viewpoint omnidirectional image. The second part is formed by passing a subbeam of the reflected light from the mirror through a concave lens and forms a displaced single viewpoint image where the disparity depends on the depth of the scene point. A closed-form expression for depth is derived. Since the optical components used are simple and commercially available, the resulting system is compact and inexpensive. This, and the simplicity of the required image processing algorithms, make the proposed system attractive for real-time applications, such as autonomous navigation and object manipulation. The experimental prototype we have built is described.
Identification of NY‐ESO‐1, MAGE‐1, and MAGE‐3 in head and neck squamous cell carcinoma (2003)

There is high expression of MAGE-1 and MAGE-3 antigens in head and neck squamous cell carcinomas, whereas NY-ESO-1 is not significantly expressed. IH correlates but is not as sensitive as RT-PCR for detection of these antigens. There is no correlation between antigen expression and patient data. On the basis of the high levels of MAGE-1 and MAGE-3 expression, use of these antigens may serve as a potential approach to immunotherapy for squamous cell carcinoma from head and neck sources.
Synaptonemal complex morphogenesis and sister-chromatid cohesion require Mek1-dependent phosphorylation of a meiotic chromosomal protein (1998)

Development of yeast meiotic chromosome cores into full-length synaptonemal complexes requires the MEK1 gene product, a meiosis-specific protein kinase homolog. The Mek1 protein associates with meiotic chromosomes and colocalizes with the Red1 protein, which is a component of meiotic chromosome cores. Mek1 and Red1 interact physically in meiotic cells, as demonstrated by coimmunoprecipitation and the two-hybrid protein system. Hop1, another protein associated with meiotic chromosome cores, also interacts with Mek1 but only in the presence of Red1. Red1 displays Mek1-dependent phosphorylation, both in vitro and in vivo, and Mek1 kinase activity is necessary for Mek1 function in vivo. Fluorescent in situ hybridization analysis indicates that Mek1-mediated phosphorylation of Red1 is required for meiotic sister-chromatid cohesion, raising the possibility that cohesion is regulated by protein phosphorylation.
Non-small cell lung cancer cycloxygenase activity and proliferation are inhibited by non-steroidal antiinflammatory drugs. (1998)

The effects of non-steroidal antiinflammatory drugs (NSAIDs) on non-small cell lung cancer (NSCLC) were investigated. Arachidonic acid (AA) was metabolized to prostaglandin E2 (PGE2) in NSCLC cells. NSAIDs such as aspirin or indomethacin reduced PGE2 levels in NCI-H157 and H1264 cells, and the decrease caused by PGE2 was reversed by epidermal growth factor (EGF). By RT-PCR, both cyclooxygenase (COX)-1 and COX-2 mRNAs are detected in NCI-H157 and H1264 cells. By Northern analysis, COX-2 mRNA was induced by EGF and phorbol ester. By immunocytochemistry, COX-1 and COX-2 enzymes were localized to NSCLC tumors. Aspirin, indomethacin and ibuprofen decreased NSCLC growth in vitro. Aspirin and indomethacin inhibited proliferation of NSCLC xenografts in nude mice. These data suggest that COX enzymes may be important regulatory components of NSCLC.
The WT1 Wilms tumor gene product: a developmentally regulated transcription factor in the kidney that functions as a tumor suppressor (1993)

Alteration of transcription factor function is becoming a common theme in molecular mechanisms of oncogenesis. A recent example of this trend is the isolation and characterization of the chromosome 11p13 Wilms tumor suppressor gene, WT1. The WT1 protein contains a DNA binding domain consisting of four zinc fingers of the Cys2-His2 class and a proline-glutamine rich region capable of regulating transcription. Deletions of the WT1 gene or point mutations which destroy the DNA binding activity of the protein are associated with the development of the pediatric nephroblastoma Wilms tumor and Denys-Drash syndrome. This article reviews the role of WT1 in normal kidney development processes, the known biochemical functions of the protein and the status of identifying target genes regulated by this potentially oncogenic transcription factor.
Smooth-Muscle-Cell Proliferation and Differentiation in Neointima Formation and Vascular Restenosis (1994)

Other| November 01 1994 Smooth-Muscle-Cell Proliferation and Differentiation in Neointima Formation and Vascular Restenosis Paolo Pauletto; Paolo Pauletto 1Istituto di Medicina Clinica, Università di Padova, Padova, Italy Search for other works by this author on: This Site PubMed Google Scholar Saverio Sartore; Saverio Sartore *Dipartimento di Scienze Biomediche, Università di Padova, Padova, Italy Search for other works by this author on: This Site PubMed Google Scholar Achille Cesare Pessina Achille Cesare Pessina 1Istituto di Medicina Clinica, Università di Padova, Padova, Italy Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1994) 87 (5): 467–479. https://doi.org/10.1042/cs0870467 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation Paolo Pauletto, Saverio Sartore, Achille Cesare Pessina; Smooth-Muscle-Cell Proliferation and Differentiation in Neointima Formation and Vascular Restenosis. Clin Sci (Lond) 1 November 1994; 87 (5): 467–479. doi: https://doi.org/10.1042/cs0870467 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search Keywords: arterial wall, intimal proliferation, restenosis, smooth muscle cells, smooth-muscle-cell differentiation This content is only available as a PDF. © 1994 The Biochemical Society and the Medical Research Society1994 Article PDF first page preview Close Modal You do not currently have access to this content.
Tissue-targeted antisense c-fos retroviral vector inhibits established breast cancer xenografts in nude mice. (1996)

The c-fos proto-oncogene has been implicated as a regulator of estrogen-mediated cell proliferation. We have tested the tissue specificity and antitumor efficacy of a mouse mammary tumor virus-regulated antisense c-fos retroviral vector. Systemically administered vector could be detected in several tissues but was only expressed in breast epithelium, thus supporting targeting to mouse mammary tumor virus-regulated tissues. Ex vivo transduction of 30-70% of MCF-7 human breast cancer cells produced expression of antifos RNA, decreased expression of the c-fos target mRNA, induction of differentiation, and inhibition of s.c. tumor growth and invasiveness. In vivo transduction of established i.p. MCF-7 tumors with a single injection of XM6:antifos inhibited tumor growth in athymic mice with a corresponding inhibition of c-fos, transforming growth factor beta1 and transforming growth factor alpha expression. Four daily injections with the antifos RNA induced a much larger MCF-7 i.p. tumor inhibition, with a marked prolongation of survival in the absence of any host tissue toxicity. These results indicate that inhibition of key nuclear genes such as c-fos may lead to disruption of paracrine factors and an antitumor effect, providing a strategy for cancer gene therapy.
A write-time based memristive PUF for hardware security applications (2013)

Hardware security has emerged as an important field of study aimed at mitigating issues such as piracy, counterfeiting, and side channel attacks. One popular solution for such hardware security attacks are physical unclonable functions (PUF) which provide a hardware specific unique signature or identification. The uniqueness of a PUF depends on intrinsic process variations within individual integrated circuits. As process variations become more prevalent due to technology scaling into the nanometer regime, novel nanoelectronic technologies such as memristors become viable options for improved security in emerging integrated circuits. In this paper, we describe a novel memristive PUF (M-PUF) architecture that utilizes variations in the write-time of a memristor as an entropy source. The results presented show strong statistical performance for the M-PUF in terms of uniqueness, uniformity, and bit-aliasing. Additionally, nanoscale M-PUFs are shown to exhibit reduced area utilization as compared to CMOS counterparts.
Current concepts in periodontal bioengineering (2005)

Repair of tooth supporting alveolar bone defects caused by periodontal and peri-implant tissue destruction is a major goal of reconstructive therapy. Oral and craniofacial tissue engineering has been achieved with limited success by the utilization of a variety of approaches such as cell-occlusive barrier membranes, bone substitutes and autogenous block grafting techniques. Signaling molecules such as growth factors have been used to restore lost tooth support because of damage by periodontal disease or trauma. This paper will review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Several different polymer delivery systems that aid in the targeting of proteins, genes and cells to periodontal and peri-implant defects will be highlighted. Results from preclinical and clinical trials will be reviewed using the topical application of bone morphogenetic proteins (BMP-2 and BMP-7) and platelet-derived growth factor-BB (PDGF) for periodontal and peri-implant regeneration. The paper concludes with recent research on the use of ex vivo and in vivo gene delivery strategies via gene therapy vectors encoding growth promoting and inhibiting molecules (PDGF, BMP, noggin and others) to regenerate periodontal structures including bone, periodontal ligament and cementum.
Morphology of the normal human lens (2021)

Purpose. To provide a quantitative, morphologic description of differentiated lens fiber cells in all regions of aged normal human lenses. Methods. Transparent normal human lenses (age range, 44 to 71 years) were examined with correlative transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Vibratome sections allowed examination of internal structures, whereas dissected whole lenses revealed surface characteristics. Additionally, image analysis was used to measure cross-sectional areas of fiber cells. Results. Approximate regional dimensions (percentage of diameter and thickness, respectively) were determined for whole lenses : cortex 16%, 17% ; adult nucleus 24%, 21% ; juvenile nucleus 12%, 9% ; fetal nucleus 45%, 49% ; and embryonic nucleus 3%, 4%. Cortical cells were irregularly hexagonal, and the average cross-sectional area measured 24 ± 9 μm2. Adult nuclear cells were flattened with intricate membranous interdigitations and an area of 7 ± 2 μm2. Juvenile nuclear cells had an area of 14 ± 5 μm2. Fetal nuclear cells were rounded with an area of 35 ± 22 μm2. Embryonic nuclear cells also were rounded and had a variable area of 80 ± 68 μm2. Fiber cell cytoplasm in all lens regions appeared smooth in texture and homogeneous in staining density. Conclusions. Both TEM and SEM are necessary to obtain a complete description of fiber cells. Cross-sections of fibers give new insights into the lamellar organization of the lens, indicating that each region has characteristic cell shapes and sizes. Furthermore, average dimensions were used to demonstrate that the number of cells and approximate growth rates vary significantly between adjacent regions.
MODULATION OF THE L-TYPE CALCIUM CHANNEL CAV1.2 BY NOCICEPTIN AND ITS RECEPTOR NOP1 (2014)

The endogenous neuropeptide nociceptin (N/OFQ) and its receptor, the nociceptin receptor (NOP1), are highly expressed in the hippocampus, where they regulate learning and memory by inhibiting synaptic transmission and plasticity. The L-type calcium channel (LTCC) Cav1.2 is also expressed in the hippocampus and is one of the major sources of Ca 2+ in the postsynaptic compartment of neurons. Activation of Cav1.2 regulates memory and learning-associated biochemical changes through activation of cAMP response element-binding protein (CREB) and NMDA receptor-independent long-term potentiation (LTP). It has previously been shown that activation of NOP1 receptor by nociceptin downregulates LTCCs as well as other voltage gated calcium channels in hippocampal neurons [2], but little is known regarding the molecular mechanisms of this modulation. We show that Cav1.2 and NOP1 receptor form a complex and co-immunoprecipitate from transfected tsA201 cells and from hippocampal brain tissue. Calcium imaging of cultured rat hippocampal neurons treated with nociceptin (1uM) and depolarized with 40mM KCl revealed a significant decrease in calcium influx. Treatment with the LTCC blocker, Nifedipine showed that calcium influx is partially mediated by Cav1.2. Subsequent imaging of cultured rat hippocampal neurons treated with nociceptin (100nM) and depolarized with 40mM KCl revealed a significant decrease in CREB phosphorylation in the nucleus, an important step for neuronal plasticity. Treatments with Nifedipine and NMDA receptor antagonists (MK-801 and APV) indicate that the activation of nuclear p-CREB results in part from the activation of Cav1.2, and is NMDA receptor-independent. Our data provide novel insights into the mechanisms by which the endogenous neuropeptide nociceptin affects hippocampal neuron function. Ultimately, this could identify new strategies for the alleviation of memory disorders.
Carbon Nanotube and Polypyrrole Composites: Coating and Doping (2000)

Carbon nanotube (CNT) dopants can improve both the strength and conductivityof polypyrrole (PPy), as reported here. A novel electrochemical method is described for the synthesis of these CNT–PPy composites. Evidence is presented that PPy forms remarkably uniform coatings on individual CNTs, and can also join one coated nanotube to another (see Figure).
Rapid micromeasurement of lactate in whole blood (1984)

A new lactate sensor makes it possible to measure the lactate content of whole blood directly in less than 1 min, using only a 10-microL blood sample. The procedure works equally well with plasma, serum, spinal fluid, other body fluids, or tissue homogenates. The instrument is calibrated with lactate standards between 0 and 15 mMol/L. The sensor, a polarographic enzyme electrode, gives a current which is a linear function of the lactate concentration. There is no interference from glucose, pyruvate, alcohol, ascorbate, anticoagulants, lidocaine, acetaminophen, or other drugs and metabolites commonly encountered in critically ill patients. The lactate sensor is composed of a peroxide sensor and an enzyme transducer membrane. The lactate is stoichiometrically converted to pyruvate and hydrogen peroxide by lactate oxygen oxidoreductase derived from Pediococcus species. The oxygen required for the enzymatic oxidation is supplied via an air-permeable silicone elastomeric membrane used for stirring. Comparison of our new electroenzymatic method with the Boehringer-Mannheim photoenzymatic method gives correlations of 0.997 for both whole blood and plasma.
Brain and tissue distribution of polyethylene glycol-conjugated superoxide dismutase in rats. (1992)

Our results suggest that the blood-brain barrier becomes more permeable to polyethylene glycol-conjugated superoxide dismutase only during the hypertensive period but that the blood-cerebrospinal fluid barrier sustains more permanent injury. We suggest that the therapeutic effectiveness of polyethylene glycol-conjugated superoxide dismutase in hypertensive brain injury is due to its action in the vascular wall or to its extracellular activity in the cerebrospinal fluid.
Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in taxane-refractory prostate cancer. (2011)

158 Background: The unique expression of PSMA type II transmembrane glycoprotein on prostate cancer cells provides a potentially attractive target for antibody therapy. PSMA ADC, a fully humanized antibody to PSMA linked to the potent antitubulin agent monomethyl auristatin E (MMAE), binds PSMA and is internalized within the prostate cancer cell where cleavage and release of free MMAE occur, causing cell cycle arrest and apoptosis. We report results from an ongoing phase I dose escalation study of PSMA ADC in patients (pts) with taxane refractory metastatic prostate cancer (metCRPC). Methods: Eligibility requirements included pts ≥18 years with metCRPC after failure of a taxane- containing regimen and ECOG status of 0 or 1. PSMA ADC is administered by IV infusion Q3W for up to 4 cycles. Adverse events, PK, PSA, circulating tumor cells, clinical disease progression and immunogenic response to PSMA ADC continue to be assessed. Serum concentrations of PSMA ADC and total antibody are measured by an enzyme-linked immunosorbent assay (ELISA) method, and free MMAE is measured by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) method. Dosing cohorts ranged from 0.4 mg/kg to 1.8 mg/kg. Results: The demographics of 15 subjects enrolled in the four dosing cohorts (0.4, 0.7, 1.1 and 1.8 mg/kg) were similar. Treatment has to date been generally well tolerated and the most common laboratory abnormalities were reversible changes in liver and hematological parameters. Exposure to PSMA ADC and serum half life (t 1/2 ) increased in a dose-proportional manner. Similar PK metrics were observed after the first and third doses. Exposure to free MMAE was also dose proportional and approximately &lt;0.1% of PSMA ADC. Conclusions: In this first-in-human evaluation, PSMA ADC appears to exhibit dose-proportional PK and limited release of free MMAE. Ongoing enrollment allows for assessment of potential clinical utility of this unique potential treatment of metCRPC. [Table: see text]
Compartment Syndrome (1989)

The purpose of this study was to quantitate the intracellular high-energy phosphate compounds during 6 hours of tissue ischemia in the anterior tibial compartment of beagles subjected to an induced traumatized compartment syndrome. The goal of this work was to provide clinicians with objective criteria to augment clinical judgment regarding surgical intervention in the impending compartment syndrome. A beagle model was utilized in which the Delta pressure (difference between the mean arterial pressure and compartment pressure) could be controlled. The model, in conjunction with “P-magnetic resonance spectroscopy (MRS), allowed a measure of high-energy phosphate compounds and pH in the compartment at various Delta pressures. The extent of ischemic metabolic insult in the compartment was then quantitated. Our data suggest the following: 1) lower Delta pressures result in a proportionally greater drop in the 2) at lower Delta pressures, there is proportionally greater decline in the 3) blood pressure is extremely important and periods of hypotension may intracellular phosphocreatine ratio and pH; percentage recovery post-fasciotomy; result in increased muscle damage at lower compartment pressures.
Correlating Lightning to Severe Local Storms in the Northeastern United States (1991)

Two tornado events and an intense downburst episode were investigated in an attempt to relate cloud-to-ground lightning rates with the occurrence of severe local storms. The State University of New York at Albany lightning detection system was used to yield characteristic lightning rate tendencies and particular lightning signatures that were associated with severe storms in the northeastern United States. Tornadoes and large hail occurred about 10–15 min after a pronounced peak in the 5-min cloud-to-ground lightning rate. In the downburst event, very destructive winds occurred just after the 5-min rate peaked. Because these severe local storm activities followed well-defined peaks in the 5-min cloud-to-ground lightning rate, it may be possible that the 5-min rates could be used operationally to forecast severe weather.