gebhart/patrepeval huggingface dataset:
Expression of constitutively active 4EBP-1 enhances p27Kip1 expression and inhibits proliferation of MCF7 breast cancer cells (2003)

BACKGROUND: Eukaryotic initiation factor 4E (eIF4E) is essential for cap-dependent initiation of translation. Cell proliferation is associated with increased activity of eIF4E and elevated expression of eIF4E leads to tumorigenic transformation. Many tumors express very high levels of eIF4E and this may be a critical factor in progression of the disease. In contrast, overexpression of 4EBP, an inhibitor of eIF4E, leads to cell cycle arrest and phenotypic reversion of some transformed cells. RESULTS: A constitutively active form of 4EBP-1 was inducibly expressed in the human breast cancer cell line MCF7. Induction of constitutively active 4EBP-1 led to cell cycle arrest. This was not associated with a general inhibition of protein synthesis but rather with changes in specific cell cycle regulatory proteins. Cyclin D1 was downregulated while levels of the CDK inhibitor p27Kip1 were increased. The levels of cyclin E and CDK2 were unaffected but the activity of CDK2 was significantly reduced due to increased association with p27Kip1. The increase in p27Kip1 did not reflect changes in p27Kip1 mRNA or degradation rates. Rather, it was associated with enhanced synthesis of the protein, even though 4EBP-1 is expected to inhibit translation. This could be explained, at least in part, by the ability of the p27Kip1 5'-UTR to mediate cap-independent translation, which was also enhanced by expression of constitutively active 4EBP-1. CONCLUSIONS: Expression of active 4EBP-1 in MCF7 leads to cell cycle arrest which is associated with downregulation of cyclin D1 and upregulation of p27Kip1. Upregulation of p27Kip1reflects increased synthesis which corresponds to enhanced cap-independent translation through the 5'-UTR of the p27Kip1 mRNA.
A viral protease-mediated cleavage of the transmembrane glycoprotein of Mason-Pfizer monkey virus can be suppressed by mutations within the matrix protein. (1992)

The envelope glycoprotein precursor of retroviruses undergoes proteolytic cleavage in the Golgi complex to yield the mature surface and transmembrane (TM) glycoproteins of the virus. We report here that the TM glycoprotein of Mason-Pfizer monkey virus undergoes a second proteolytic processing event during a late maturation step that can follow virus release and Gag polyprotein cleavage. Cleavage results in the conversion of the cell-associated TM glycoprotein (gp22) to a virus-associated gp20. Processing continues after virus release and yields virions that contain predominantly gp20. A mutation within the active site of the Mason-Pfizer monkey virus aspartyl protease was shown to block both TM glycoprotein cleavage and the processing of the Gag polyprotein precursor. The role of the viral protease in cleavage of the TM glycoprotein localizes the cleavage site to the cytoplasmic domain of this protein. Surprisingly, point mutations within the matrix (MA) coding region of the gag gene can affect the extent to which gp22 is processed to gp20 and in one case [p10(MA)-A79V] results in greater than 90% inhibition of gp22 cleavage. The data provide genetic evidence of a specific interaction between the capsid proteins and the cytoplasmic domain of the TM glycoprotein of a retrovirus. This interaction is required for cytoplasmic domain cleavage to occur and may play a critical role in virus assembly and viral infectivity.
Effect of 3,5-di-iodo-L-thyronine on the mitochondrial energy-transduction apparatus (1998)

We examined the effect of a single injection of 3,5-di-iodo-L-thyronine (3,5-T2) (150 microg/100 g body weight) on the rat liver mitochondrial energy-transduction apparatus. We applied 'top-down' elasticity analysis, which allows identification of the site of action of an effector within a metabolic pathway. This kinetic approach considers oxidative phosphorylation as two blocks of reactions: those generating the mitochondrial inner-membrane potential (DeltaPsi; 'substrate oxidation') and those 'consuming' it ('proton leak' and 'phosphorylating system'). The results show that 1 h after the injection of 3,5-T2, state 4 (respiratory state in which there is no ATP synthesis and the exogenous ADP added has been exhausted) and state 3 (respiratory state in which ATP synthesis is at maximal rate) of mitochondrial respiration were significantly increased (by approx. 30%). 'Top-down' elasticity analysis revealed that these increases were due to the stimulation of reactions involved in substrate oxidation; neither 'proton leak' nor the 'phosphorylating system' was influenced by 3,5-T2. Using the same approach we divided the respiratory chain into two blocks of reactions: cytochrome c reducers and cytochrome c oxidizers. We found that both cytochrome c reducers and cytochrome c oxidizers are targets for 3,5-T2. The rapidity with which 3,5-T2 acts in stimulating the mitochondrial respiration rate suggests to us that di-iodo-L-thyronine may play an important role in the physiological conditions in which rapid energy utilization is required, such as cold exposure or overfeeding.
AVLC technology today: a developmental history of automatic vehicle location and control systems for the transit environment (1993)

Vehicular location systems are able to pinpoint a vehicle to within several meters of its true position. These systems share the common requirement of being highly application specific. The application of vehicular location systems to public transit is examined by presenting some of the highlights of the developmental history of automatic vehicle location and control systems for the North American public transit environment.
Multiwalled Carbon Nanotubes by Chemical Vapor Deposition Using Multilayered Metal Catalysts (2002)

Multiwalled carbon nanotubes (MWCNTs) have been grown on various substrates by thermal chemical vapor deposition using multilayered metal catalysts. Ion beam sputtering is used to deposit various metal layers sequentially. Underlayers of Al (2−20 nm) are shown to influence the growth characteristics with Fe or Ni used as active catalysts. The as-sputtered catalyst surface, characterized using atomic force and scanning tunneling microscopies, consists of nanometer scale (<10 nm) catalyst particles. High-resolution transmission electron microscopy and Raman analysis are used to characterize the MWCNTs. Optimization of the two layers allows growth of MWCNT towers on patterned and unpatterned substrates.
Facile and gentle method for quantitative lysis of Escherichia coli and Salmonella typhimurium (1984)

Garrett et al. (Mol. Gen. Genet. 182:326-331, 1981) constructed strains of Escherichia coli harboring derivatives of plasmid pBR322 that carry the lysis genes (S, R, and Rz) of phage lambda. The plasmid construction placed the genes under control of the lactose operon operator-promotor (and thus of lac repressor). Induction of E. coli strains carrying these plasmids resulted in rapid lysis of the culture unless the S gene was defective, in which case the cells grew normally. A freeze-thaw treatment of induced cells carrying an S- plasmid gave quantitative lysis of either E. coli or Salmonella typhimurium cells under exceptionally gentle conditions. The method was equally effective on exponential phase cells and stationary phase cells and was readily extended to a large number of independent cultures.
New Realization Method for Three-Dimensional Photonic Crystal in Optical Wavelength Region (1996)

A new realization method for three-dimensional photonic crystals in the optical wavelength region is proposed. Microfabrication techniques using wafer-bonding, selective etching, and laser beam deflection pattern observation techniques are successfully combined, and the feasibility of the proposed method is experimentally demonstrated.
Influence of Melatonin Treatment on Human Circadian Rhythmicity before and after a Simulated 9-Hr Time Shift (1991)

The hormone melatonin is currently proposed by some investigators to be an efficient means for decreasing the impairing effects of jet lag. Eight healthy male subjects, aged 20 to 32, underwent a 9-hr advance shift in the isolation facility of our institute during two periods each of 15 days' duration. In a double-blind, crossover design, subjects took either melatonin or placebo at 1800 hr local time for 3 days before the time shift and at 1400 hr for 4 days afterwards. The time shift was simulated on days 7 and 8 by shortening the sleep period by 6 hr and the following wake period by 3 hr. Body temperature was recorded every 90 min, and urine was collected at 3-hr intervals all day and night. Melatonin treatment enhanced the resynchronization speed of some, but not all, hormone and electrolyte excretion rates for several days after the time shift. The adaptation speed of the temperature rhythm significantly increased during one postshift day. In addition, the circadian temperature rhythm had a significantly higher amplitude under melatonin treatment than under placebo after the time displacement. For the placebo group, the rhythm of 6-hydroxymelatoninsulfate excretion exhibited an advance shift in five subjects, whereas the other three showed a delay shift, and adjustment did not achieve more than one-half of the expected value within 8 days. A significantly different adjustment could be observed in the melatonin-treated group: Seven subjects underwent an advance shift of the expected 9 hr within an average of 8 days. The results suggest that melatonin treatment can accelerate resynchronization of the melatonin excretion rhythm after eastward time zone transitions. The improvement is not, however, sufficiently great that we can recommend melatonin for the alleviation of jet lag.
New high power diode model with both forward and reverse recovery (1994)

Over the last few years, many papers have been published in the area of diode modelling. However, satisfactory representation of both forward and reverse recovery phenomena for high power diodes has yet to be published. This paper presents the development of a new high power diode model, based on the combination of two different strategies that produce forward recovery voltage and reverse recovery current separately. The model is verified by comparing the SABER simulation results against those produced by an experimental rig for a high power diode at turn-on and turn-off.
Low-Temperature Nonoxidative Activation of Methane over H -Galloaluminosilicate (MFI) Zeolite (1997)

Conversion of methane to higher hydrocarbons by its low-temperature activation without forming undesirable carbon oxides is of great scientific and practical importance. Methane can be highly activated, yielding high rates of conversion to higher hydrocarbons and aromatics (10 to 45 percent) at low temperatures (400&deg; to 600&deg;C), by its reaction over H-galloaluminosilicate ZSM-5 type (MFI) zeolite in the presence of alkenes or higher alkanes. The methane activation results from its hydrogen-transfer reaction with alkenes.
Complement-targeted therapy: development of C5- and C5a-targeted inhibition (2016)

The complement system is a major effector of humoral immunity and natural immunity. The complement system has three independent pathways of complement activation: a classical pathway, an alternative pathway, and a lectin pathway. These pathways converge to a common pathway that activates C3. This pathway also leads to the formation of various bioactive molecules such as C5a and the formation of membrane attack complex on the surface of target cells. In the past, the only preparations with anti-complementary action were C1 inhibitors (C1-INH), but an anti-C5 monoclonal antibody (eculizumab) appeared a few years ago, and this antibody has yielded encouraging results. In addition, a C5a receptor (C5aR) antagonist is in the clinical trial phase, and this antagonist should also prove efficacious. Anti-complement agents have garnered attention as a new treatment strategy for refractory inflammatory diseases.
Inhibiting Caspase Cleavage of Huntingtin Reduces Toxicity and Aggregate Formation in Neuronal and Nonneuronal Cells (2000)

Huntington's disease is a neurodegenerative disorder caused by CAG expansion that results in expansion of a polyglutamine tract at the extreme N terminus of huntingtin (htt). htt with polyglutamine expansion is proapoptotic in different cell types. Here, we show that caspase inhibitors diminish the toxicity of htt. Additionally, we define htt itself as an important caspase substrate by generating a site-directed htt mutant that is resistant to caspase-3 cleavage at positions 513 and 530 and to caspase-6 cleavage at position 586. In contrast to cleavable htt, caspase-resistant htt with an expanded polyglutamine tract has reduced toxicity in apoptotically stressed neuronal and nonneuronal cells and forms aggregates at a much reduced frequency. These results suggest that inhibiting caspase cleavage of htt may therefore be of potential therapeutic benefit in Huntington's disease.
The Structure and Biosynthesis of Glycosyl Phosphatidylinositol Protein Anchors (1993)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Amyloid β‐protein monomer structure: A computational and experimental study (2006)

The structural properties of the Abeta42 peptide, a main constituent of the amyloid plaques formed in Alzheimer's disease, were investigated through a combination of ion-mobility mass spectrometry and theoretical modeling. Replica exchange molecular dynamics simulations using a fully atomic description of the peptide and implicit water solvent were performed on the -3 charge state of the peptide, its preferred state under experimental conditions. Equilibrated structures at 300 K were clustered into three distinct families with similar structural features within a family and with significant root mean square deviations between families. An analysis of secondary structure indicates the Abeta42 peptide conformations are dominated by loops and turns but show some helical structure in the C-terminal hydrophobic tail. A second calculation on Abeta42 in a solvent-free environment yields compact structures turned "inside out" from the solution structures (hydrophobic parts on the outside, polar parts on the inside). Ion mobility experiments on the Abeta42 -3 charge state electrosprayed from solution yield a bimodal arrival time distribution. This distribution can be quantitatively fit using cross-sections from dehydrated forms of the three families of calculated solution structures and the calculated solvent-free family of structures. Implications of the calculations on the early stages of aggregation of Abeta42 are discussed.
Generation of tumor-initiating cells by exogenous delivery of OCT4transcription factor (2011)

Transduction of OCT4 in normal breast preparations led to the generation of cell lines possessing tumor-initiating and colonization capabilities. These cells developed high-grade, poorly differentiated breast carcinomas in nude mice. Genome-wide analysis of OTBCs outlined an embryonic TF circuitry that could be operative in TICs, resulting in up-regulation of oncogenes and loss of tumor suppressive functions. These OTBCs represent a patient-specific model system for the discovery of novel oncogenic targets in claudin-low tumors.
Polyelectrolyte Micropatterning Using Agarose Plane Stamp and a Substrate Having Microscale Features on Its Surface (2005)

We have introduced polyelectrolyte micro-patterning technique employing agarose plane stamp and a hard substrate having microscale features on its surface. With this method, chemically micropatterned surfaces with both positive and negative functionalities were successfully embedded in well-defined microstructures, and selective impartment of charge functionalities was confirmed by patterning bead bearing surface charge. Furthermore, this technique allows highly sensitive immobilization of protein onto targeted surface simply by endowing functionalities, which extends the potential of its use as a tool for high-throughput protein microarray and proteomics. Because plane agarose stamp is free of structures on its surface, there is no concern for pattern collapse, and the combination of agarose plane stamp with patterned substrate is more suited for selective protein patterning compared with adopting surface-patterned agarose stamp with flat substrate. Our technique using agarose plane stamp and a substrate having microscale features on its surface suggests a range of possible applications, including the micropatterning of biofunctionalized copolymer having polyelectrolyte block, immobilization of micro- and nanoparticle with biofunctionalities such as biotin and streptavidine, and establishing optoelectronic microstructures with micro-beads on various surfaces.
α1ESubunits Form the Pore of Three Cerebellar R-Type Calcium Channels with Different Pharmacological and Permeation Properties (2000)

R-type Ca(2+) channels cooperate with P/Q- and N-type channels to control neurotransmitter release at central synapses. The leading candidate as pore-forming subunit of R-type channels is the alpha(1E) subunit. However, R-type Ca(2+) currents with permeation and/or pharmacological properties different from those of recombinant Ca(2+) channels containing alpha(1E) subunits have been described, and therefore the molecular nature of R-type Ca(2+) channels remains not completely settled. Here, we show that the R-type Ca(2+) current of rat cerebellar granule cells consists of two components inhibited with different affinity by the alpha(1E) selective antagonist SNX482 (IC(50) values of 6 and 81 nM) and a third component resistant to SNX482. The SNX482-sensitive R-type current shows the unique permeation properties of recombinant alpha(1E) channels; it is larger with Ca(2+) than with Ba(2+) as charge carrier, and it is highly sensitive to Ni(2+) block and has a voltage-dependence of activation consistent with that of G2 channels with unitary conductance of 15 pS. On the other hand, the SNX482-resistant R-type current shows permeation properties similar to those of recombinant alpha(1A) and alpha(1B) channels; it is larger with Ba(2+) than with Ca(2+) as charge carrier(,) and it has a low sensitivity to Ni(2+) block and a voltage-dependence of activation consistent with that of G3 channels with unitary conductance of 20 pS. Gene-specific knock-down by antisense oligonucleotides demonstrates that the different cerebellar R-type channels are all encoded by the alpha(1E) gene, suggesting the existence of alpha(1E) isoforms with different pore properties.
Colloidal Zn_1−xCdxS: optical saturation of the exciton band and primary photochemistry studied by subpicosecond laser flash photolysis (1990)

Quantum-size crystallites of Zn0.95Cd0.05S in an aqueous colloidal solution were optically excited using intense subpicosecond laser pump pulses tuned to the exciton band. Optical probing in the UV registered saturation and the kinetics of ground-state recovery due to carrier recombination, with lifetimes in the 0.8–30-psec range. Optical probing at 616 nm monitored the yield of Auger electron emission. The saturation and yield curves, as a function of pump fluence, are described by a simple kinetic model that involves the exciton lifetime before trapping (~30 fsec) and the maximum number of electrons (~16) that can be emitted per particle.
Investigations into Tandem Acoustic Modeling for the Aurora Task (2001)

In tandem acoustic modeling, signal features are first processed by a discriminantly-trained neural network, then the outputs of this network are treated as the feature inputs to a conventional distribution-modeling Gaussian-mixture model (GMM) speech recognizer. This arrangement achieves relative error rate reductions of 30% or more on the Aurora task, as well as supporting feature stream combination at the posterior level, which can eliminate more than 50% of the errors compared to the HTK baseline. In this paper, we explore a number of variations on the tandem structure to improve our understanding of its effectiveness. We experiment with changing the subword units used in each model (neural net and GMM), varying the data subsets used to train each model, substituting the posterior calculations in the neural net with a second GMM, and a variety of feature condition such as deltas, normalization and PCA rank reduction in the 'tandem domain' i.e. between the two models. All results are reported on the Aurora-2000 noisy digits task.
Enhanced thermal stability of Clostridium beijerinckii alcohol dehydrogenase after strategic substitution of amino acid residues with prolines from the homologous thermophilic Thermoanaerobacter brockii alcohol dehydrogenase (1998)

A comparison of the three-dimensional structures of the closely related mesophilic Clostridium beijerinckii alcohol dehydrogenase (CBADH) and the hyperthermophilic Thermoanaerobacter brockii alcohol dehydrogenase (TBADH) suggested that extra proline residues in TBADH located in strategically important positions might contribute to the extreme thermal stability of TBADH. We used site-directed mutagenesis to replace eight complementary residue positions in CBADH, one residue at a time, with proline. All eight single-proline mutants and a double-proline mutant of CBADH were enzymatically active. The critical sites for increasing thermostability parameters in CBADH were Leu-316 and Ser-24, and to a lesser degree, Ala-347. Substituting proline for His-222, Leu-275, and Thr-149, however, reduced thermal stability parameters. Our results show that the thermal stability of the mesophilic CBADH can be moderately enhanced by substituting proline at strategic positions analogous to nonconserved prolines in the homologous thermophilic TBADH. The proline residues that appear to be crucial for the increased thermal stability of CBADH are located at a beta-turn and a terminating external loop in the polypeptide chain. Positioning proline at the N-caps of alpha-helices in CBADH led to adverse effects on thermostability, whereas single-proline mutations in other positions in the polypeptide had varying effects on thermal parameters. The finding presented here support the idea that at least two of the eight extra prolines in TBADH contribute to its thermal stability.
Analysis of Firewall Policy Rules Using Data Mining Techniques (2006)

Firewall is the de facto core technology of today's network security and defense. However, the management of firewall rules has been proven to be complex, error-prone, costly and inefficient for many large-networked organizations. These firewall rules are mostly custom-designed and hand-written thus in constant need for tuning and validation, due to the dynamic nature of the traffic characteristics, ever-changing network environment and its market demands. One of the main problems that we address in this paper is that how much the firewall rules are useful, up-to-dated, well-organized or efficient to reflect the current characteristics of network traffics. In this paper, we present a set of techniques and algorithms to analysis and manage firewall policy rules: (1) Data Mining technique to deduce efficient firewall policy rules by mining its network traffic log based on its frequency, (2) Filtering-Rule Generalization (FRG) to reduce the number of policy rules by generalization, and (3) a technique to identify any decaying rule and a set of few dominant rules, to generate a new set of efficient firewall policy rules. The anomaly detection based on the mining exposes many hidden but not detectable by analyzing only the firewall policy rules, resulting in two new types of the anomalies. As a result of these mechanisms, network security administrators can automatically review and update the rules. We have developed a prototype system and demonstrated usefulness of our approaches.