gebhart/patrepeval huggingface dataset:
An Overactivated ATR/CHK1 Pathway Is Responsible for the Prolonged G2 Accumulation in Irradiated AT Cells (2003)

Induction of checkpoint responses in G1, S, and G2 phases of the cell cycle after exposure of cells to ionizing radiation (IR) is essential for maintaining genomic integrity. Ataxia telangiectasia mutated (ATM) plays a key role in initiating this response in all three phases of the cell cycle. However, cells lacking functional ATM exhibit a prolonged G2 arrest after IR, suggesting regulation by an ATM-independent checkpoint response. The mechanism for this ataxia telangiectasia (AT)-independent G2-checkpoint response remains unknown. We report here that the G2 checkpoint in irradiated human AT cells derives from an overactivation of the ATR/CHK1 pathway. Chk1 small interfering RNA abolishes the IR-induced prolonged G2 checkpoint and radiosensitizes AT cells to killing. These results link the activation of ATR/CHK1 with the prolonged G2 arrest in AT cells and show that activation of this G2 checkpoint contributes to the survival of AT cells.
The Herpes Simplex Virus Type 1 US7 Gene Product Is a 66K Glycoprotein and Is a Target for Complement-dependent Virus Neutralization (1988)

The US7 open reading frame of herpes simplex virus type 1 (HSV-1), previously identified by nucleotide sequencing, has been expressed in a recombinant vaccinia virus (US7-VAC). Antiserum raised against HSV-1 reacted with a 66K glycoprotein in US7-VAC-infected cells and this polypeptide was present on both nuclear and cell surface membranes. In the presence of tunicamycin the protein was reduced in size to 58K showing it contained N-linked sugar residues. Antisera from animals vaccinated with US7-VAC recognized 66K and 58K polypeptides in HSV-1-infected cells and neutralized HSV-1 infectivity in vitro in the presence of complement.
A Novel Antiapoptotic Role for α 1 -Antitrypsin in the Prevention of Pulmonary Emphysema (2006)

Our findings suggest that inhibition of structural alveolar cell apoptosis by alpha1-antitrypsin represents a novel protective mechanism of the serpin against emphysema. Further elucidation of this mechanism may extend the therapeutic options for emphysema caused by reduced level or loss of function of alpha1-antitrypsin.
Evaluation of Fungicidal Action in Vitro and in a Skin Model Considering the Influence of Penetration Kinetics of Various Standard Antimycotics (1988)

Ciclopiroxolamine (Loprox) was the first representative of hydroxpyridones to be developed as a topical antifungal. In the microtitration test and in a skin model using excised skin prices of slaughtered pigs, the fungistatic and fungicidal activity as well as the penetration kinetics of ciclopiroxolamine and ciclopirox were compared with those of the azole compounds bifonazole, clotrimazole, econazole, miconazole, oxiconazole, and tioconazole, and with other antimycotics such as naftifine, sulbentine, tolciclate, and tolnaftate. Clotrimazole had an in vitro inhibitory activity superior to that of the hydroxypyridone ciclopiroxolamine; the latter compound, however, exhibited faster penetration and higher inhibitory or fungicidal activity than the azoles and other antimycotics in the pig skin model. Studies of cream formulations with antimycotics at the bottom layer of the stratum corneum (close to the stratum granulosum) showed that ciclopiroxolamine cream had the most prominent inhibitory effect (93%) and the highest fungicidal activity (98%). The other antimycotics tested exhibited growth inhibition rates of 50% or less and lower fungicidal rates. Inoculated pig skin was treated with lacquer formulations to show that ciclopirox completely inhibited the growth of Trichophyton mentagrophytes, whereas the clotrimazole-treated samples allowed only 0.47% growth. The fungicidal activity of lacquer formulations was 99% for ciclopirox and around 90% for most of the azoles on the pig skin model. The necessity of models tackling the complex penetration kinetics in human skin was discussed.
2C4, a monoclonal antibody against HER2, disrupts the HER kinase signaling pathway and inhibits ovarian carcinoma cell growth (2005)

2C4 is able to disrupt the HER signaling pathway and inhibit the in vitro and in vivo growth of ovarian carcinoma cell lines. The response appears limited to lines in which HER2 heterodimers were able to transduce proliferative signals. Our findings suggest a strong rationale to conduct clinical trials of 2C4 in a subset of patients with ovarian tumors.
Comparative repellency of 38 essential oils against mosquito bites (2005)

The mosquito repellent activity of 38 essential oils from plants at three concentrations was screened against the mosquito Aedes aegypti under laboratory conditions using human subjects. On a volunteer's forearm, 0.1 mL of oil was applied per 30 cm2 of exposed skin. When the tested oils were applied at a 10% or 50% concentration, none of them prevented mosquito bites for as long as 2 h, but the undiluted oils of Cymbopogon nardus (citronella), Pogostemon cablin (patchuli), Syzygium aromaticum (clove) and Zanthoxylum limonella (Thai name: makaen) were the most effective and provided 2 h of complete repellency. From these initial results, three concentrations (10%, 50% and undiluted) of citronella, patchouli, clove and makaen were selected for repellency tests against Culex quinquefasciatus and Anopheles dirus. As expected, the undiluted oil showed the highest protection in each case. Clove oil gave the longest duration of 100% repellency (2-4 h) against all three species of mosquito.
The RNA exosome complex central channel controls both exonuclease and endonuclease Dis3 activities in vivo and in vitro (2013)

The RNA exosome is an essential ribonuclease complex involved in RNA processing and decay. It consists of a 9-subunit catalytically inert ring composed of six RNase PH-like proteins forming a central channel and three cap subunits with KH/S1 domains located at the top. The yeast exosome catalytic activity is supplied by the Dis3 (also known as Rrp44) protein, which has both endo- and exoribonucleolytic activities and the nucleus-specific exonuclease Rrp6. In vitro studies suggest that substrates reach the Dis3 exonucleolytic active site following passage through the ring channel, but in vivo support is lacking. Here, we constructed an Rrp41 ring subunit mutant with a partially blocked channel that led to thermosensitivity and synthetic lethality with Rrp6 deletion. Rrp41 mutation caused accumulation of nuclear and cytoplasmic exosome substrates including the non-stop decay reporter, for which degradation is dependent on either endonucleolytic or exonucleolytic Dis3 activities. This suggests that the central channel also controls endonucleolytic activity. In vitro experiments performed using Chaetomium thermophilum exosomes reconstituted from recombinant subunits confirmed this notion. Finally, we analysed the impact of a lethal mutation of conserved basic residues in Rrp4 cap subunit and found that it inhibits digestion of single-stranded and structured RNA substrates.
Drugs for urologic disorders (2015)

At Rutgers University Ernest Mario School of Pharmacy in Piscataway, N.J., Mary B. Bridgeman is a clinical associate professor. Kavitha S. Dalal is a critical care clinical pharmacist at Virtua in Marlton, N.J. The authors have disclosed that they have no financial relationships related to this article. Unless otherwise specified, the information in the preceding summaries applies to adults, not children. Consult a pharmacist, the package insert, or a comprehensive drug reference for more details on precautions, drug interactions, and adverse reactions.
Genetic Basis for the Hierarchical Interaction Between Tobamovirus spp. and L Resistance Gene Alleles from Different Pepper Species (2010)

The pepper L gene conditions the plant's resistance to Tobamovirus spp. Alleles L(1), L(2), L(3), and L(4) confer a broadening spectra of resistance to different virus pathotypes. In this study, we report the genetic basis for the hierarchical interaction between L genes and Tobamovirus pathotypes. We cloned L(3) using map-based methods, and L(1), L(1a), L(1c), L(2), L(2b), and L(4) using a homology-based method. L gene alleles encode coiled-coil, nucleotide-binding, leucine-rich repeat (LRR)-type resistance proteins with the ability to induce resistance response to the viral coat protein (CP) avirulence effectors by themselves. Their different recognition spectra in original pepper species were reproduced in an Agrobacterium tumefaciens-mediated transient expression system in Nicotiana benthamiana. Chimera analysis with L(1), which showed the narrowest recognition spectrum, indicates that the broader recognition spectra conferred by L(2), L(2b), L(3), and L(4) require different subregions of the LRR domain. We identified a critical amino acid residue for the determination of recognition spectra but other regions also influenced the L genes' resistance spectra. The results suggest that the hierarchical interactions between L genes and Tobamovirus spp. are determined by the interaction of multiple subregions of the LRR domain of L proteins with different viral CP themselves or some protein complexes including them.
Vaccinia virions lacking the RNA helicase nucleoside triphosphate phosphohydrolase II are defective in early transcription (1996)

Temperature-sensitive mutations (ts10, ts18, and ts39) of the vaccinia virus RNA helicase nucleoside triphosphate phosphohydrolase II (NPH-II) result in the production of noninfectious progeny virions at the restrictive temperature. The noninfectious mutant particles contain the wild-type complement of virion core and envelope polypeptides, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results of Western blot (immunoblot) analysis indicate that these particles lack NPH-II, whereas other enzymatic components of the virus core are present. These components include the following: DNA-dependent RNA polymerase subunits rpo147, rpo132, rpo94, rpo35, rpo30, rpo22, and rpo18; early transcription initiation factor subunits A8 and D6; mRNA capping enzyme subunits D1 and D12; RNA cap 2'-O-methyltransferase; A18 DNA helicase; DNA-dependent ATPase NPH-I; and DNA topoisomerase. Although RNA polymerase is encapsidated by the mutant viruses, mRNA synthesis in vitro by permeabilized mutant virions is only 5 to 20% that of the wild-type virus, as judged by nucleoside monophosphate incorporation into acid-insoluble material. Moreover, the transcripts synthesized by the mutant particles are longer than normal and remain virion associated. Transcription initiation by mutant virions occurs accurately at an endogenous genomic promoter, albeit at reduced levels (1 to 7%) compared with that of wild-type virions. In contrast, extracts of the mutant virions catalyze the wild-type level of transcription from an exogenous template containing an early promoter. We conclude that NPH-II is required for early mRNA synthesis uniquely in the context of the virus particle. Possible roles in transcription termination and RNA transport are discussed.
One-step synthesis of porous graphene-based hydrogels containing oil droplets for drug delivery (2013)

Three-dimensional graphene hydrogels with a porous network have attractive potential in electrode materials, catalysis, and drug delivery. A series of porous graphene-based hydrogels containing oil droplets is fabricated on the basis of Pickering emulsions co-stabilized by graphene oxide and Fe3O4 nanoparticles. The volume ratio of water to oil and the concentration of stabilizers have significant effects on Pickering emulsion stability. A hierarchical pore structure is observed in the hybrid hydrogels prepared by in situ reduction of graphene oxide. Owing to the inner oil droplets distributing in the hydrogels which can be loaded with oil-soluble materials, the obtained reduced graphene oxide hydrogels show sustained release of hydrophobic drugs, which makes them a candidate for drug delivery.
6-Hydroxy-4-[2-di-n-propylaminoethyl]indole: synthesis and dopaminergic actions (1984)

The title compound was proposed to be a biologically active metabolite of a dopaminergic agent, 4-[2-(di-n-propylamino)ethyl]indole. This proposed metabolite was synthesized by a multistep sequence beginning with methyl 3,5-dinitro o-toluate, and involving the Batcho-Leimgruber modification of the Reissert indole synthesis. The target compound exhibited high potency/activity in vivo in a cat cardioaccelerator nerve assay and in vitro in an isolated cat atrium assay. It manifested maximal pharmacological effect less than 5 min after intravenous administration in cats, as compared with a 20-min lag time following intravenous administration of the nonoxygenated congener. These pharmacological data are consistent with the proposal that the target compound is a metabolite of 4-[2-(di-n-propylamino)ethyl]indole.
Immunology in the Era of Single-Cell Technologies (2020)

Immune cells are characterized by diversity, specificity, plasticity, and adaptability-properties that enable them to contribute to homeostasis and respond specifically and dynamically to the many threats encountered by the body. Single-cell technologies, including the assessment of transcriptomics, genomics, and proteomics at the level of individual cells, are ideally suited to studying these properties of immune cells. In this review we discuss the benefits of adopting single-cell approaches in studying underappreciated qualities of immune cells and highlight examples where these technologies have been critical to advancing our understanding of the immune system in health and disease.
Simulation-Based Military Regional Anesthesia Training System (2008)

Abstract : Deployed American troops suffering injuries to the extremities are best treated with regional anesthesia, which renders only a portion of the body, such as a limb, insensate. However, it is possible for long-lasting damage to occur when regional anesthesia is improperly applied. Though nerve block procedures present fairly low risk in a hospital setting, the same may not be true on the battlefield-where severe trauma cases are prevalent and fellowship trained pain management specialists are not always available. There is a need for all military anesthesiologists to undergo training for the administration of peripheral nerve blocks, yet currently no suitable mass training curriculum or training system exists. The training system must be accurate, intuitive, and convenient. Under contract with the Telemedicine & Advanced Technology Research Center (TATRC), Energid Technologies is developing such a training system. It includes instructional content in a standard, configurable framework, and immersive simulation of procedures to reinforce the instructional content.
Lack of expression of aminoacylase-1 in small cell lung cancer. Evidence for inactivation of genes encoded by chromosome 3p. (1989)

A deletion involving chromosome 3p (14-23) characteristically occurs in small cell lung cancer (SCLC). Reduction to homozygosity, rather than complete loss, is typically observed for genes in the deleted region. Lack of expression for genes encoded by this region, implying inactivation of all alleles, has not been previously described. We have examined the expression of aminoacylase-1 (ACY-1), encoded by chromosome 3p21, using both an electrophoretic activity assay and a monoclonal antibody-based ELISA. A variety of human tissues, including lung, brain, liver, kidney, heart, adrenal medulla, and erythrocytes have previously been tested for ACY-1 activity and antigen; all but erythrocytes are positive. Thus, ACY-1 is expressed in all nucleated human cells examined to date. ACY-1 was undetectable in a significant number of SCLC cell lines (4/29) and tumors (1/8), but not in non-small cell lung cancer (NSCLC) cell lines (0/19) or tumors (0/9), nor in a variety of other human cell lines (0/15) or colon tumors (0/8). In addition, reduced (approximately 10% of normal) ACY-1 expression was common in SCLC cell lines (14/29) and tumors (3/8), but not in NSCLC cell lines (1/19) or tumors (0/9), nor in other human cell lines (0/15) or colon tumors (0/8). Thus, low or undetectable ACY-1 expression is highly specific for SCLC and occurs in both cell lines and tumor tissue. The finding of undetectable ACY-1 expression in SCLC supports the hypothesis that inactivation of all alleles of specific chromosome 3p genes occurs in a SCLC in a fashion analogous to Rb gene inactivation in retinoblastoma, and suggests that the structural gene for ACY-1 may be closely linked to a putative SCLC tumor suppressor gene.
Surface-micromachined components for articulated microrobots (1996)

A class of articulated micromanipulator robots with multiple degrees of freedom, workspaces on the order of a cubic millimeter, and payloads on the order of a milligram are proposed. Rigid links, mechanical couplings, and large-force, large-displacement micromotors have been created. Hollow triangular beams made from rotated microhinged polysilicon plates with polysilicon locks can withstand axial loads of up to 2.6 gm. Mechanical couplings with sliding mechanisms are used to rotate hinged structures off the substrate. The typical frictional force observed is approximately 2 /spl mu/N. Linear electrostatic stepper motors with an estimated force of 6.5 /spl mu/N at 35 V and a travel of 40 /spl mu/m have also been demonstrated.
B-myc inhibits neoplastic transformation and transcriptional activation by c-myc. (1993)

B-myc is a recently described myc gene whose product has not been functionally characterized. The predicted product of B-myc is a 168-amino-acid protein with extensive homology to the c-Myc amino-terminal region, previously shown to contain a transcriptional activation domain. We hypothesized that B-Myc might also function in transcriptional regulation, although its role in regulating gene expression is predicted to be unique, because B-Myc lacks the specific DNA-binding motif found in other Myc proteins. To determine whether B-Myc could interact with the transcriptional machinery, we studied the transcriptional activation properties of a chimeric protein containing B-Myc sequences fused to the DNA-binding domain of the yeast transcriptional activator GAL4 (GAL4-B-Myc). We found that GAL4-B-Myc strongly activated expression of a GAL4-regulated reporter gene in mammalian cells. In addition, full-length B-Myc was able to inhibit or squelch reporter gene activation by a GAL4 chimeric protein containing the c-Myc transcriptional activation domain. We also observed that B-Myc dramatically inhibited the neoplastic cotransforming activity of c-Myc and activated Ras in rat embryo cells. Because B-Myc inhibits both neoplastic transformation and transcriptional activation by c-Myc, we suggest that the transforming activity of c-Myc is related to its ability to regulate transcription. Whether B-Myc functions biologically to squelch transcription and/or to regulate transcription through a specific DNA-binding protein remains unestablished.
Structures of a Series of 6-kDa Trypsin Inhibitors Isolated from the Stigma of Nicotiana alata (1995)

The three-dimensional structures of a series of 6-kDa trypsin inhibitors isolated from the stigma of the ornamental tobacco Nicotiana alata have been determined by 1H NMR spectroscopy combined with simulated annealing calculations. The proteins, T1-T4, are proteolytically cleaved from a 40.3-kDa precursor protein, NA-proPI, together with a chymotrypsin inhibitor, C1, the structure of which was reported recently [Nielsen, K.J., Heath, R.L., Anderson, M.A., & Craik, D.J. (1994) J. Mol. Biol. 242, 231-243]. Each of the proteinase inhibitors comprises 53 amino acids, including 8 cysteine residues which are linked to form 4 disulfide bridges. The proteins have a high degree of sequence identity and differ mainly in residues around the putative reactive sites. The structure of T1 was determined using a set of 533 interproton distance restraints derived from NOESY spectra, combined with 33 dihedral restraints derived from 3JNH-H alpha coupling constants and 16 hydrogen bonds. The structures of the remaining inhibitors (T2-T4) were deduced to be almost identical to T1, on the basis of their similar chemical shifts and 2D spectra. The current study demonstrates that the structures of the trypsin inhibitors (T1-T4) are similar to that previously found for the chymotrypsin inhibitor, C1. Despite differences in sequence, there is conservation in backbone geometry between the reactive site loops of the two classes of inhibitors. From this, it is clear that the nature of the side chain on the primary binding residue, rather than the backbone fold, is the main determinant of the enzyme specificities of these proteinase inhibitors.
Clozapine Alone versus Clozapine and Risperidone with Refractory Schizophrenia (2006)

In this short-term study, the addition of risperidone to clozapine did not improve symptoms in patients with severe schizophrenia. (ClinicalTrials.gov number, NCT00272584).
Lithographic effects of mask critical dimension error (1998)

Magnification of mask dimensional error is examined and quantified in terms of the mask error factor (MEF) for line and hole patterns on three types of masks: chrome-on-glass (COG), attenuated phase-shifting mask (PSM) and alternating PSM. The MEF is unity for large features, but increases rapidly when the critical dimension (CD) is less than 0.5 (lambda) /NA for line-space patterns and 0.75 (lambda) /NA for contacts. In general dark-field spaces exhibit higher sensitivity to mask dimensional error than light-field lines. Sensitivity of attenuated PSMs is similar to COG masks, even for applications in which attenuated PSMs provide benefits in process latitude. Alternating PSMs have the lowest MEF values. Although the MEF has only a slight dependence on feature nesting for contacts, dense lines and spaces exhibit markedly higher MEF values than isolated features. The MEF of a 0.35 (lambda) /NA isolated line is 1.6 whereas that of a dense line of the same dimension is 4.3 illumination is effective in reducing the mask error sensitivity of dense lines. Dose variation causes changes in the MEF of contacts but has little effect on line-space features; focus error degrades (increases the value of) the MEF of both pattern types. A high diffusion and low contrast photoresist process also worsens the MEF. Consequences of mask CD error amplification include tightening of mask specification, design grid reduction, shift in optimal mask bias and enhanced defect printability.
Antiinfective Applications of Toll-like Receptor 9 Agonists (2007)

The innate immune system detects pathogens by the presence of highly conserved pathogen-expressed molecules, which trigger host immune defenses. Toll-like receptor (TLR) 9 detects unmethylated CpG dinucleotides in bacterial or viral DNA, and can be stimulated for therapeutic applications with synthetic oligodeoxynucleotides containing immune stimulatory "CpG motifs." TLR9 activation induces both innate and adaptive immunity. The TLR9-induced innate immune activation can be applied in the prevention or treatment of infectious diseases, and the adaptive immune-enhancing effects can be harnessed for improving vaccines. This article highlights the current understanding of the mechanism of action of CpG oligodeoxynucleotides, and provides an overview of the preclinical data and early human clinical trial results, applying these TLR9 agonists in the field of infectious diseases.