gebhart/patrepeval huggingface dataset:
Mitigation of reversible self-association and viscosity in a human IgG1 monoclonal antibody by rational, structure-guided Fv engineering (2016)

Undesired solution behaviors such as reversible self-association (RSA), high viscosity, and liquid-liquid phase separation can introduce substantial challenges during development of monoclonal antibody formulations. Although a global mechanistic understanding of RSA (i.e., native and reversible protein-protein interactions) is sufficient to develop robust formulation controls, its mitigation via protein engineering requires knowledge of the sites of protein-protein interactions. In the study reported here, we coupled our previous hydrogen-deuterium exchange mass spectrometry findings with structural modeling and in vitro screening to identify the residues responsible for RSA of a model IgG1 monoclonal antibody (mAb-C), and rationally engineered variants with improved solution properties (i.e., reduced RSA and viscosity). Our data show that mutation of either solvent-exposed aromatic residues within the heavy and light chain variable regions or buried residues within the heavy chain/light chain interface can significantly mitigate RSA and viscosity by reducing the IgG's surface hydrophobicity. The engineering strategy described here highlights the utility of integrating complementary experimental and in silico methods to identify mutations that can improve developability, in particular, high concentration solution properties, of candidate therapeutic antibodies.
Selective Tropism of Seneca Valley Virus for Variant Subtype Small Cell Lung Cancer (2013)

We assessed the efficacy of Seneca Valley virus (SVV-001), a neuroendocrine cancer-selective oncolytic picornavirus, in primary heterotransplant mouse models of small cell lung cancer (SCLC), including three lines each of classic and variant SCLC. Half-maximal effective concentrations for cell lines derived from three variant heterotransplants ranged from 1.6×10(-3) (95% confidence interval [CI] = 1×10(-3) to 2.5×10(-3)) to 3.9×10(-3) (95% CI = 2.8×10(-3) to 5.5×10(-3)). Sustained tumor growth inhibition in vivo was only observed in variant lines (two-sided Student t test, P < .005 for each). Doses of 10(14) vp/kg were able to completely and durably eradicate tumors in a variant SCLC heterotransplant model in two of six mice. Gene expression profiling revealed that permissive lines are typified by lower expression of the early neurogenic transcription factor ASCL1 and, conversely, by higher expression of the late neurogenic transcription factor NEUROD1. This classifier demonstrates a sensitivity of .89, specificity of .92, and accuracy of .91. The NEUROD1 to ASCL1 ratio may serve as a predictive biomarker of SVV-001 efficacy.
Magnetic field induced resistance properties at filling factor 5/2 consistent with non-Abelian e/4 quasiparticles in multiple sized interferometers (2012)

Non-Abelian e/4 quasiparticles at 5/2 filling factor in a correlated two-dimensional electron gas have a proposed specific property in an interference measurement of their edge propagation: encircling an even number of localized e/4 quasiparticles allows expression of e/4 Aharonov-Bohm (A-B) oscillations, but suppression of these oscillations will occur with an odd number encircled. This picture is tested explicitly here in multiple interferometers of different areas. The encircled localized e/4 quasiparticle number near 5/2 filling factor is changed by sweeping B-field, and oscillations are observed in resistance near 5/2 of period specific to that device area for each interferometer. The product of the measured interferometric area of each device and the respective 5/2 resistance oscillation period is found to agree with the expected flux quanta addition needed for parity change in the localized e/4 number. This result shows a highly specific non-Abelian property of the quasiparticle excitations at 5/2 filling expressed in multiple interferometers.
Enhancing Realism of Wet Surfaces in Temporal Bone Surgical Simulation (2009)

We present techniques to improve visual realism in an interactive surgical simulation application: a mastoidectomy simulator that offers a training environment for medical residents as a complement to using a cadaver. As well as displaying the mastoid bone through volume rendering, the simulation allows users to experience haptic feedback and appropriate sound cues while controlling a virtual bone drill and suction/irrigation device. The techniques employed to improve realism consist of a fluid simulator and a shading model. The former allows for deformable boundaries based on volumetric bone data, while the latter gives a wet look to the rendered bone to emulate more closely the appearance of the bone in a surgical environment. The fluid rendering includes bleeding effects, meniscus rendering, and refraction. We incorporate a planar computational fluid dynamics simulation into our three-dimensional rendering to effect realistic blood diffusion. Maintaining real-time performance while drilling away bone in the simulation is critical for engagement with the system.
The Art of Capacity Planning: Scaling Web Resources (2008)

Success on the web is measured by usage and growth. Web-based companies live or die by the ability to scale their infrastructure to accommodate increasing demand. This book is a hands-on and practical guide to planning for such growth, with many techniques and considerations to help you plan, deploy, and manage web application infrastructure. The Art of Capacity Planning is written by the manager of data operations for the world-famous photo-sharing site Flickr.com, now owned by Yahoo! John Allspaw combines personal anecdotes from many phases of Flickr's growth with insights from his colleagues in many other industries to give you solid guidelines for measuring your growth, predicting trends, and making cost-effective preparations. Topics include: Evaluating tools for measurement and deployment Capacity analysis and prediction for storage, database, and application servers Designing architectures to easily add and measure capacity Handling sudden spikes Predicting exponential and explosive growth How cloud services such as EC2 can fit into a capacity strategy In this book, Allspaw draws on years of valuable experience, starting from the days when Flickr was relatively small and had to deal with the typical growth pains and cost/performance trade-offs of a typical company with a Web presence. The advice he offers in The Art of Capacity Planning will not only help you prepare for explosive growth, it will save you tons of grief.
Histone deacetylases: novel targets for prevention of colitis-associated cancer in mice (2008)

These results indicate that inhibition of histone deactylases can attenuate inflammation-mediated tumour growth, which is paralled by an inhibition of NF-kappaB. Thus histone deacetylase inhibitors provide a promising strategy that combines anti-inflammatory and proapoptotic modes of action.
Obscurin determines the architecture of the longitudinal sarcoplasmic reticulum (2009)

The giant protein obscurin is thought to link the sarcomere with the sarcoplasmic reticulum (SR). The N-terminus of obscurin interacts with the M-band proteins titin and myomesin, whereas the C-terminus mediates interactions with ankyrin proteins. Here, we investigate the importance of obscurin for SR architecture and organization. Lack of obscurin in cross-striated muscles leads to changes in longitudinal SR architecture and disruption of small ankyrin-1.5 (sAnk1.5) expression and localization. Changes in SR architecture in obscurin knockout mice are also associated with alterations in several SR or SR-associated proteins, such as ankyrin-2 and beta-spectrin. Finally, obscurin knockout mice display centralized nuclei in skeletal muscles as a sign of mild myopathy, but have normal sarcomeric structure and preserved muscle function.
Optical Absorption Properties of Semiconducting Nanostructures with Different Shapes (2013)

In this study, a detailed experimental and theoretical investigation of optical absorption properties of indium sulfide (In 2 S 3 ) nanostructure arrays in different shapes are presented. Zigzags, springs, screws, tilted rods, and vertical rods of In 2 S 3 are grown using a glancing angle deposition (GLAD) technique. Nanostructured coatings are of similar material volume and porosity, yet with different shapes. Total optical reflection, transmission, and absorption profiles of In 2 S 3 nanostructures are obtained by UV‐vis‐NIR spectroscopy using an integrating sphere. Measurements reveal that optical absorption of semiconducting nanostructures can strongly depend on their shapes. Under normal incidence of light, 3D geometries such as springs, screws, and vertical rods can provide enhanced absorption compared to zigzags, and tilted rods. Results of finite difference time domain (FDTD) simulations predict that spring, screw, and tapered‐rod shapes can introduce a uniform distribution of diffracted light intensity and stronger absorption within the nanostructured layer, indicating an enhanced diffuse light scattering and light trapping. Zigzags and tilted rods show a relatively weaker absorption, similar to the experimental results. Experimental and simulation results are also compared to the predictions of effective medium theory. Current effective medium approximations are not sufficient to explain the high optical absorption of the nanostructures.
Pituitary adenylate cyclase-activating peptide affects homeostatic sleep regulation in healthy young men (2006)

Pituitary adenylate cyclase-activating peptide (PACAP) is involved in autonomous regulation, including timekeeping, by its action on the suprachiasmatic nucleus and on neuroendocrine secretion, energy metabolism, and transmitter release. In particular, the interactions between PACAP and the glutamatergic system are well recognized. We compared the effect of intravenously administered PACAP to that of placebo in eight healthy male subjects. PACAP in a concentration of 4x12.5 microg was administered in a pulsatile fashion hourly between 2200 and 0100. Sleep EEG was recorded from 2300 to 1000, which was also the time when subjects were allowed to sleep. Blood samples were taken every 20 min between 2200 and 0700 for the determination of cortisol, GH, and prolactin. PACAP administration led to no changes in the macro-sleep structure as assessed according to standard criteria. Spectral analysis revealed a significant reduction in the theta-frequency range in the first 4-h interval and of the spindle frequency range in the second 4-h interval of the registration period. This was accompanied by an increase in the time constant tau of the physiological delta-power decline in the course of the night, i.e., a less pronounced dynamic of the reduction of delta-power with time. This was accompanied by a trend (P<0.1) toward decreased prolactin secretion in the first 4-h period of the night. No other changes in endocrine secretion were observed. We concluded that PACAP leads to a reduction of the dynamics of homeostatic sleep regulation and prolactin secretion. Both effects are the opposite of those seen after sleep deprivation but similar to the changes after napping, i.e., a reduced sleep propensity. This implies that PACAP might be involved in homeostatic sleep regulation.
Analogies Emerge from Learning Dyamics in Neural Networks. (2017)

When a neural network is trained on multiple analogous tasks,previous research has shown that it will often generate rep-resentations that reflect the analogy. This may explain thevalue of multi-task training, and also may underlie the powerof human analogical reasoning – awareness of analogies mayemerge naturally from gradient-based learning in neural net-works. We explore this issue by generalizing linear analysistechniques to explore two sets of analogous tasks, show thatanalogical structure is commonly extracted, and address somepotential implications.
HLA class II antigens and the HIV envelope glycoprotein gp120 bind to the same face of CD4. (1994)

Abstract Although the HIV gp120 binding site of CD4 is well characterized, its interaction site with HLA class II molecules is still controversial. Sixty-seven mutations within the four extracellular domains of CD4 were examined for their effects on cell surface expression and conformational changes and for adhesion of HLA class II-expressing B lymphocytes and HIV gp120 binding to CD4-transfected COS cells. Mutations within the gp120 binding site affected both assays similarly, indicating that the two sites fully overlap. A few additional substitutions of residues mapping on the same face of domains 1 and 2 induced decreased rosette formation. Molecular modeling studies indicated that this is likely to be the consequence of conformational changes induced by the mutations. Thus, CD4 appears to interact with HLA class II molecules mainly through the HIV gp120 binding site and possibly through a second minor interaction site mapping on the same face of the molecule.
Pressure Ulcer Healing with a Concentrated, Fortified, Collagen Protein Hydrolysate Supplement (2006)

By week 8, PUSH tool scores-a measurement of pressure ulcer healing-showed approximately twice the rate of pressure ulcer healing in the treatment group compared with the control group. A concentrated, fortified, collagen protein hydrolysate supplement may be of benefit to residents of long-term-care facilities who have pressure ulcers.
A novel method for hydrogen production from liquid ethanol/water at room temperature (2004)

We demonstrated that non-catalytic ethanol steam reforming proceeds efficiently and selectively without coking at the conditions of room temperature and atmospheric pressure using low-energy pulsed (LEP) discharge in combination with carbon fiber electrodes.
A Molecular Mechanism for Ibuprofen-Mediated RhoA Inhibition in Neurons (2010)

Ibuprofen is a nonsteroidal anti-inflammatory drug widely used to relieve pain and inflammation in many disorders via inhibition of cyclooxygenases. Recently, we have demonstrated that ibuprofen inhibits intracellular signaling of RhoA and promotes significant axonal growth and functional recovery following spinal cord lesions in rodents. In addition, another study suggests that ibuprofen reduces generation of amyloid-beta42 peptide via inactivation of RhoA signaling, although it may also regulate amyloid-beta42 formation by direct inhibition of the gamma-secretase complex. The molecular mechanisms by which ibuprofen inhibits the RhoA signal in neurons, however, remain unclear. Here, we report that the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) is essential for coupling ibuprofen to RhoA inhibition and subsequent neurite growth promotion in neurons. Ibuprofen activates PPARgamma in neuron-like PC12 and B104 cells. Activation of PPARgamma with traditional agonists mimics the RhoA-inhibiting properties of ibuprofen in PC12 cells and, like ibuprofen, promotes neurite elongation in primary cultured neurons exposed to axonal growth inhibitors. Protein knockdown with small interfering RNA specific for PPARgamma blocks RhoA suppression of PPARgamma agonists in PC12 cells. Moreover, the effect of ibuprofen on RhoA activity and neurite growth in neuronal cultures is prevented by selective PPARgamma inhibition. These findings support that PPARgamma plays an essential role in mediating the RhoA-inhibiting effect of ibuprofen. Elucidation of the novel molecular mechanisms linking ibuprofen to RhoA inhibition may provide additional therapeutic targets to the disorders characterized by RhoA activation, including spinal cord injuries and Alzheimer's disease.
Drop-Size Distributions of Newtonian Liquid Sprays Produced by Fan-Jet Pressure Nozzles (1979)

The drop size distribution was measured by Newtonian liquid sprays produced by fan-jet pressure nozzles, operating in the pressure range 500 to nearly 3000 psig (3 450 to 20 680 kPa). The fluids used were water and a water-glycerin mixture. A collection device was constructed and droplets were captured on soot coated microscope slides. Subsequent sizing of the impacted particles with a microscope yielded drop size distribution data of accumulated volume per cent versus diameter. An experimental analysis was performed to relate the nozzle wall shear to the volume median diameter of the spray distribution. A linear correlation was found to exist on a semilog graph; for the Newtonian liquid sprays, it was determined that the volume median diameter could be predicted with: Dd=+8.5183−1.1113logτρQμσ
High barrier height Schottky diodes on n-InP by low temperature deposition (2002)

The formation of ultra-high barrier height ( phi /sub B/=0.96 eV) Schottky contacts to n-InP, without an intentionally grown interfacial oxide, using metal deposition on a substrate cooled to as low as 77 K is discussed. Values of phi /sub B/=0.46-0.52 eV for diodes deposited at room temperature (RT=300 K) agree and give an ideality factor near unity. For diodes deposited at a low temperature (LT) of 77 K, the leakage current density (J/sub 0/) is reduced by more than 6-7 orders of magnitude with respect to the RT diodes. The phi /sub B/ for the LT diodes is increased from 0.48 to 0.96 eV for Pd metal and from 0.51 to 0.85 eV for Au metal, respectively. The conduction mechanisms for the LT and RT diodes are found to be controlled by thermionic-field emission (TFE) and thermionic emission (TE), respectively. It is shown that an alteration of the metal-induced interface states, inhibition of surface segregation of the released In and P atoms, and very uniform metal coverage may be responsible for the distinct differences between the RT and LT diodes.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Estimation of hyaluronidase activity of human semen and its relationship with sperm density by means of a simplified method. (1982)

Hyaluronidase activity was examined in 109 specimens of human semen of various sperm densities, seminal plasma, and spermatozoa sedimented by centrifugation. We used a modification of a method originally devised for estimation of hyaluronidase activity in Clostridia and which was bases on measurements of the area of hyaluronate digestion in agar plates. Enzyme activities in both semen and seminal plasma increased with increase in sperm density. The activity in seminal plasma, which appeared promptly after liquefaction and represented enzyme released from spermatozoa, ranged from 31% to 61% of the activity in semen. Activities of spermatozoa in sediments exhibited lower values than those calculated for sperm of whole semen, possibly due to leakage. Both activities, calculated per million sperm cells, gradually increased with decrease in sperm density. The possibility that with severe oligozoospermia the acrosome may become less prone to enzyme release or that the initial activity per cell may increase is discussed. These phenomena would represent additional characteristics of oligozoospermia.
CD19-dependent Activation of Akt Kinase in B-lymphocytes (2001)

CD19 is rapidly phosphorylated upon B-cell antigen receptor (BCR) cross-linking, leading to the recruitment of downstream signaling intermediates. A prominent feature of CD19 signaling is the binding and activation of phosphoinositide 3-kinase (P13K), which accounts for the majority of PI3K activity induced by BCR ligation. Recent findings have implicated activation of the serine/threonine kinase Akt as imparting survival signals in a PI3K-dependent fashion. Using CD19-deficient B-lymphoma cells and mouse splenic B-cells, we show that CD19 is necessary for efficient activation of Akt following cross-linking of surface immunoglobulin or Igbeta. In the absence of CD19, Akt kinase activity is reduced and transient. In addition, coligation of CD19 with surface immunoglobulin leads to augmented Akt activity in a dose-dependent manner. Thus, CD19 is a key regulator of Akt activity in B-cells; as such it may contribute to pre-BCR or BCR-mediated cell survival in vivo.
Simulation of a heat treatment furnace introduces industrial reality into an EET undergraduate control course (2002)

Control system simulation software for use in the classroom and for student assignments is described. The simulation, written in Microsoft QuickBASIC, permits the open- and closed-loop behavior of a heat treatment furnace to be displayed as an aid to teaching response testing and controller selection and tuning. Typical response plots are given along with details of the model of the furnace and the structure of the software.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
On-line load balancing with applications to machine scheduling and virtual circuit routing (1993)

In this paper we study an idealized problem of on-line allocation of routes to virtual circuits where the goal is to minimize the required bandwidth.
Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase (2001)

The budding yeast transcriptional activator Gcn4 is rapidly degraded in an SCF(Cdc4)-dependent manner in vivo. Upon fractionation of yeast extracts to identify factors that mediate Gcn4 ubiquitination, we found that Srb10 phosphorylates Gcn4 and thereby marks it for recognition by SCF(Cdc4) ubiquitin ligase. Srb10 is a physiological regulator of Gcn4 stability because both phosphorylation and turnover of Gcn4 are diminished in srb10 mutants. Gcn4 is almost completely stabilized in srb10Delta pho85Delta cells, or upon mutation of all Srb10 phosphorylation sites within Gcn4, suggesting that the Pho85 and Srb10 cyclin-dependent kinases (CDKs) conspire to limit the accumulation of Gcn4. The multistress response transcriptional regulator Msn2 is also a substrate for Srb10 and is hyperphosphorylated in an Srb10-dependent manner upon heat-stress-induced translocation into the nucleus. Whereas Msn2 is cytoplasmic in resting wild-type cells, its nuclear exclusion is partially compromised in srb10 mutant cells. Srb10 has been shown to repress a subset of genes in vivo, and has been proposed to inhibit transcription via phosphorylation of the C-terminal domain of RNA polymerase II. We propose that Srb10 also inhibits gene expression by promoting the rapid degradation or nuclear export of specific transcription factors. Simultaneous down-regulation of both transcriptional regulatory proteins and RNA polymerase may enhance the potency and specificity of transcriptional inhibition by Srb10.
Local trajectory planning and control for autonomous vehicles using the adaptive potential field (2017)

In this paper, a new potential field approach is proposed for trajectory planning and control in autonomous vehicles. The potential field of the surrounding environment is generated including vehicles, road boundaries and lane centers. Based on the predicted positions of the vehicles, the location of the ego vehicle and the surrounding potentials are synchronized. In addition, the potential fields of the surrounding vehicles are adaptively modified in shape depending on the relative velocity of the surrounding vehicles. The longitudinal distance required for the lateral avoidance is mathematically calculated and reflected in the potential field. Based on the proposed potential field, the trajectory of the autonomous vehicle is selected as the suboptimal path and the MPC (Model Predictive Control) method is applied for tracking control and the lateral stability of the vehicle. The performance of the proposed algorithm is verified in simulations under various conditions.