gebhart/patrepeval huggingface dataset:
Copper−Doxorubicin as a Nanoparticle Cargo Retains Efficacy with Minimal Toxicity (2010)

Repeated administration of chemotherapeutics is typically required for the effective treatment of highly aggressive tumors and often results in systemic toxicity. We have created a copper-doxorubicin complex within the core of liposomes and applied the resulting particle in multidose therapy. Copper and doxorubicin concentrations in the blood pool were similar at 24 h (∼40% of the injected dose), indicating stable circulation of the complex. Highly quenched doxorubicin fluorescence remained in the blood pool over tens of hours, with fluorescence increasing only with the combination of liposome disruption and copper trans-chelation. At 48 h after injection, doxorubicin fluorescence within the heart and skin was one-fifth and one-half, respectively, of fluorescence observed with ammonium sulfate-loaded doxorubicin liposomes. After 28 days of twice per week doxorubicin administration of 6 mg/kg, systemic toxicity (cardiac hypertrophy and weight and hair loss) was not detected with the copper-doxorubicin liposomes but was substantial with ammonium sulfate-loaded doxorubicin liposomes. We then incorporated two strategies designed to enhance efficacy, mTOR inhibition (rapamycin) to slow proliferation and therapeutic ultrasound to enhance accumulation and local diffusion. Tumor accumulation was ∼10% ID/g and was enhanced approximately 2-fold with the addition of therapeutic ultrasound. After the 28-day course of therapy, syngeneic tumors regressed to a premalignant phenotype of ∼(1 mm)(3) or could not be detected.
A hardware accelerator for smart information systems (2002)

The authors outline an autonomous agent architecture and one of its instantiations. The architecture models agents with conscious and unconscious behaviors. The architecture provides for grounded symbolic representations through embodied perception, and provides a mechanism for learning behaviors. The authors discuss how the Air Battle Simulation implements an autonomous agent conforming to the architecture, and how knowledge migration and various other features of the architecture apply to it.
Estimation of Modal Decay Parameters from Noisy Response Measurements (2002)

Estimation of modal decay parameters from noisy measurements of reverberant and resonating systems is a common problem in audio and acoustics, e.g., in room and concert hall measurements or musical instrument modeling. In this paper, reliable methods to estimate the initial response level, decay rate, and noise floor level from noisy measurement data are studied and compared. A new method, based on nonlinear optimization of a model for exponential decay plus stationary noise floor, is presented. Comparison with traditional decay parameter estimation techniques using simulated measurement data shows that the proposed method outperforms in accuracy and robustness, especially in extreme SNR conditions. Three cases of practical applications of the method are demonstrated. 0
Identification of multiple and distinct CD8+ T cell suppressor activities: dichotomy between infected and uninfected individuals, evolution with progression of disease, and sensitivity to γ irradiation (1996)

Using an in vitro model system that reflects the cellular interactions occurring in the microenvironment of lymphoid organs (i.e., the interaction between dendritic cells (DC) and CD4+ T lymphocytes), the ability of CD8+ T cells to inhibit HIV replication was investigated. DC, the most potent APC in the paracortical region of lymphoid organs, were cocultured with autologous, unstimulated CD4+ T cells resulting in viral replication in the absence of exogenous stimulation. Using two variations of DC cocultures, one an acute infection system and the other an endogenous infection system, two sets of activities were identified. One activity was expressed in both HIV-infected and -uninfected individuals, and a second was found only in HIV-infected individuals. These activities can be differentiated further by their evolution or lack thereof with disease progression in infected individuals and their sensitivity to gamma irradiation. Furthermore, the results indicate that CD8+ T cell modulation of HIV replication in CD4+ T cells is a multifactorial phenomenon involving both inhibitory and stimulatory effects on HIV replication.
Measurement of Slow (μs−ms) Time Scale Dynamics in Protein Side Chains by <sup>15</sup>N Relaxation Dispersion NMR Spectroscopy:  Application to Asn and Gln Residues in a Cavity Mutant of T4 Lysozyme (2001)

A new NMR experiment is presented for the measurement of micros-ms time scale dynamics of Asn and Gln side chains in proteins. Exchange contributions to the (15)N line widths of side chain residues are determined via a relaxation dispersion experiment in which the effective nitrogen transverse relaxation rate is measured as a function of the number of refocusing pulses in constant-time, variable spacing CPMG intervals. The evolution of magnetization from scalar couplings and dipole-dipole cross-correlations, which has limited studies of exchange in multi-spin systems in the past, does not affect the extraction of accurate exchange parameters from relaxation profiles of NH(2) groups obtained in the present experiment. The utility of the method is demonstrated with an application to a Leu --> Ala cavity mutant of T4 lysozyme, L99A. It is shown that many of the side chain amide groups of Asn and Gln residues in the C-terminal domain of the protein are affected by a chemical exchange process which may be important in facilitating the rapid binding of hydrophobic ligands to the cavity.
RAGE in inflammation: a new therapeutic target? (2006)

High-molecular group box 1-protein, S100/calgranulins, advanced glycation end products (AGEs), amyloid-beta peptides and the family of beta-sheet fibrils contribute to a number of inflammatory conditions by promoting cellular dysfunction and breaking immune tolerance. The receptor of AGE (RAGE) is a multiligand receptor of the immunoglobulin superfamily of cell surface molecules that acts as a pattern recognition receptor. Besides binding ligands actively participating in inflammation and immune responses, RAGE serves as an endothelial adhesion receptor for leukocyte integrins and promotes leukocyte recruitment and extravasation of infiltrating cells. Engagement of RAGE subsequently converts transient cellular stimulation into sustained cellular dysfunction driven by long-term activation of the proinflammatory nuclear factor-kappaB. Deletion of RAGE and pharmacological interventions targeting interruption of RAGE-ligand interaction suppresses inflammation and dampens tissue damage in experimental models of inflammatory disorders, thus delineating RAGE as a potential therapeutic target in inflammation.
Inert Metal-Modified, Composite Ceramic−Carbon, Amperometric Biosensors:  Renewable, Controlled Reactive Layer (1996)

A new type of sol-gel-derived, inert metal-modified, composite, amperometric biosensor is developed. The electrodes are comprised of a dispersion of biochemically and chemically modified graphite powder in a porous, organically modified silicate (Ormosil) network. The percolating carbon dispersion provides electrical conductivity, oxidoreductase enzymes (e.g., glucose oxidase, lactate oxidase, or l-amino acid oxidase) are used for biocatalysis, metallic palladium is used for electrocatalysis of the biochemical reaction product, and the porous organically modified silica provides a rigid skeleton. The hydrophobicity of this composite material guarantees that only a limited section of the electrode is wetted by the aqueous analyte, thus providing a controlled-thickness reactive layer. The thickness of the reaction layer can be tuned by the addition of hydrophilic components. The electrode can be reproducibly renewed by removing its upper layer and exposing a new, thin, porous bioreactive section. The same technology is applicable for the production of thick-film, low-leaching, disposable sensors. In this configuration, the analysis is conducted using a single drop of the analyte applied on the hydrophobic film. The sensors are found to be stable over long periods.
Donor demographic and laboratory predictors of allogeneic peripheral blood stem cell mobilization in an ethnically diverse population (2008)

A reliable estimate of peripheral blood stem cell (PBSC) mobilization response to granulocyte colony-stimulating factor (G-CSF) may identify donors at risk for poor mobilization and help optimize transplantation approaches. We studied 639 allogeneic PBSC collections performed in 412 white, 75 black, 116 Hispanic, and 36 Asian/Pacific adult donors who were prescribed G-CSF dosed at either 10 or 16 microg/kg per day for 5 days followed by large-volume leukapheresis (LVL). Additional LVL (mean, 11 L) to collect lymphocytes for donor lymphocyte infusion (DLI) and other therapies was performed before G-CSF administration in 299 of these donors. Day 5 preapheresis blood CD34(+) cell counts after mobilization were significantly lower in whites compared with blacks, Hispanics, and Asian/Pacific donors (79 vs 104, 94, and 101 cells/microL, P < .001). In addition, donors who underwent lymphapheresis before mobilization had higher CD34(+) cell counts than donors who did not (94 vs 79 cells/microL, P < .001). In multivariate analysis, higher post-G-CSF CD34(+) cell counts were most strongly associated with the total amount of G-CSF received, followed by the pre-G-CSF platelet count, pre-G-CSF mononuclear count, and performance of prior LVL for DLI collection. Age, white ethnicity, and female gender were associated with significantly lower post-G-CSF CD34(+) cell counts.
A rational approach to the design of bracing to resist stability forces and a review of the CSA S16.1-99 proposals : technical paper (2000)

The design of bracing to resist stability forces involves a complex interaction between the bracing system and the member. Most studies have involved sophisticated computer analysis and as such the behavioural aspects have been clouded, especially when the results of such studies evolve into design methods. This paper deals with simplified mathematical models, which clearly illustrate the interaction between the stiffness and strength of the brace itself and the buckling capacity of the strut. The proposed design rules are consistent with the behaviour, have a sound theoretical basis and are simple enough to be applied directly in a design context.
Versican and the control of inflammation (2014)

Versican is an extracellular matrix (ECM) proteoglycan that interacts with cells by binding to non-integrin and integrin receptors and to other ECM components that associate with the cell surface. Recent studies have shown also that versican interacts with myeloid and lymphoid cells promoting their adhesion and production of inflammatory cytokines. Versican is produced by stromal cells, as well as leukocytes, and is markedly increased in inflammation. Inflammatory agonists, such as double-stranded RNA mimetics (e.g., poly I:C), stimulate stromal cells, smooth muscle cells and fibroblasts, to produce fibrillar ECMs enriched in versican and hyaluronan (HA) that interact with leukocytes promoting their adhesion. Interference with the incorporation of versican into this ECM blocks monocyte adhesion and dampens the inflammatory response. Tumor cells also express elevated levels of versican which interact with myeloid cells to promote an inflammatory response, through stimulating cytokine release, and metastasis. In addition, myeloid cells, such as macrophages in tumors, synthesize versican which affects tumor cell phenotypes, inflammation, and subsequent metastasis. Versican, by binding to hyaluronan, influences T lymphocyte phenotypes and in part controls the ability of these cells to synthesize and secrete cytokines that influence the immune response. Collectively, these studies indicate that versican as an ECM molecule plays a central role in inflammation and as a result it is emerging as a potential target promising wide therapeutic benefits.
Structure of bacteriophage SPP1 head-to-tail connection reveals mechanism for viral DNA gating (2009)

In many bacterial viruses and in certain animal viruses, the double-stranded DNA genome enters and exits the capsid through a portal gatekeeper. We report a pseudoatomic structure of a complete portal system. The bacteriophage SPP1 gatekeeper is composed of dodecamers of the portal protein gp6, the adaptor gp15, and the stopper gp16. The solution structures of gp15 and gp16 were determined by NMR. They were then docked together with the X-ray structure of gp6 into the electron density of the approximately 1-MDa SPP1 portal complex purified from DNA-filled capsids. The resulting structure reveals that gatekeeper assembly is accompanied by a large rearrangement of the gp15 structure and by folding of a flexible loop of gp16 to form an intersubunit parallel beta-sheet that closes the portal channel. This stopper system prevents release of packaged DNA. Disulfide cross-linking between beta-strands of the stopper blocks the key conformational changes that control genome ejection from the virus at the beginning of host infection.
Compliant Mechanisms: Design of Flexure Hinges (2002)

With a rigorous and comprehensive coverage, the second edition of Compliant Mechanisms: Design of Flexure Hinges provides practical answers to the design and analysis of devices that incorporate flexible hinges. Complex-shaped flexible-hinge mechanisms are generated from basic elastic segments by means of a bottom-up compliance (flexibility) approach. The same compliance method and the classical finite element analysis are utilized to study the quasi-static and dynamic performances of these compliant mechanisms. This book offers easy-to-use mathematical tools to investigate a wealth of flexible-hinge configurations and two- or three-dimensional compliant mechanism applications.

FEATURES


Introduces a bottom-up compliance-based approach to characterize the flexibility of new and existing flexible hinges of straight- and curvilinear-axis configurations


Develops a consistent linear lumped-parameter compliance model to thoroughly describe the quasi-static and dynamic behavior of planar/spatial, serial/parallel flexible-hinge mechanisms


Utilizes the finite element method to analyze the quasi-statics and dynamics of compliant mechanisms by means of straight- and curvilinear-axis flexible-hinge elements


Covers miscellaneous topics such as stress concentration, yielding and related maximum load, precision of rotation of straight- and circular-axis flexible hinges, temperature effects on compliances, layered flexible hinges and piezoelectric actuation/sensing


Offers multiple solved examples of flexible hinges and flexible-hinge mechanisms.


This book should serve as a reference to students, researchers, academics and anyone interested to investigate precision flexible-hinge mechanisms by linear model-based methods in various areas of mechanical, aerospace or biomedical engineering, as well as in robotics and micro-/nanosystems.
Multiple Sclerosis: Diagnosis, Medical Management, and Rehabilitation (2000)

Contents: History; Pathology and Pathophysiology; Risk Factors and Theories of Causation; Diagnosis, Signs and Symptoms, and Classification; Treatment; Symptom Management and Rehabilitation; Societal Issues; Multiple Sclerosis in the Community.
Extensively Drug-Resistant Tuberculosis in the United States, 1993-2007 (2008)

Although the number of US XDR-TB cases has declined since 1993, coinciding with improved TB and HIV/AIDS control, cases continue to be reported each year.
<i>N</i>‐Acetyl‐5‐arylalkoxytryptamine Analogs: Probing the Melatonin Receptors for MT<sub>1</sub>‐Selectivity (2011)

A series of melatonin analogs obtained by the replacement of the ether methyl group with larger arylalkyl and aryloxyalkyl substituents was prepared in order to probe the melatonin receptors for MT(1) -selectivity. The most MT(1) -selective agents 11 and 15 were substituted with a Ph(CH(2) )(3) or a PhO(CH(2) )(3) group. Compounds 11 and 15 displayed 11.5-fold and 11-fold higher affinity for the MT(1) receptors than for the MT(2) subtype. Interestingly, in our binding assay 11 and 15 have shown considerably higher MT(1) -affinity and selectivity than the reference ligand, the dimeric agomelatine 1a.
Sensors and Artificial Intelligence Methods and Algorithms for Human–Computer Intelligent Interaction: A Systematic Mapping Study (2021)

To equip computers with human communication skills and to enable natural interaction between the computer and a human, intelligent solutions are required based on artificial intelligence (AI) methods, algorithms, and sensor technology. This study aimed at identifying and analyzing the state-of-the-art AI methods and algorithms and sensors technology in existing human-computer intelligent interaction (HCII) research to explore trends in HCII research, categorize existing evidence, and identify potential directions for future research. We conduct a systematic mapping study of the HCII body of research. Four hundred fifty-four studies published in various journals and conferences between 2010 and 2021 were identified and analyzed. Studies in the HCII and IUI fields have primarily been focused on intelligent recognition of emotion, gestures, and facial expressions using sensors technology, such as the camera, EEG, Kinect, wearable sensors, eye tracker, gyroscope, and others. Researchers most often apply deep-learning and instance-based AI methods and algorithms. The support sector machine (SVM) is the most widely used algorithm for various kinds of recognition, primarily an emotion, facial expression, and gesture. The convolutional neural network (CNN) is the often-used deep-learning algorithm for emotion recognition, facial recognition, and gesture recognition solutions.
Lessons in neural network training: overfitting may be harder than expected (1997)

For many reasons, neural networks have become very popular AI machine learning models. Two of the most important aspects of machine learning models are how well the model generalizes to unseen data, and how well the model scales with problem complexity. Using a controlled task with known optimal training error, we investigate the convergence of the backpropagation (BP) algorithm. We find that the optimal solution is typically not found. Furthermore, we observe that networks larger than might be expected can result in lower training and generalization error. This result is supported by another real world example. We further investigate the training behavior by analyzing the weights in trained networks (excess degrees of freedom are seen to do little harm and to aid convergence), and contrasting the interpolation characteristics of multi-layer perceptron neural networks (MLPs) and polynomial models (overfitting behavior is very different – the MLP is often biased towards smoother solutions). Finally, we analyze relevant theory outlining the reasons for significant practical differences. These results bring into question common beliefs about neural network training regarding convergence and optimal network size, suggest alternate guidelines for practical use (lower fear of excess degrees of freedom), and help to direct future work (e.g. methods for creation of more parsimonious solutions, importance of the MLP/BP bias and possibly worse performance of “improved ” training algorithms).
Exploring the Substrate Specificities of α‐2,6–and α‐2,3–Sialyltransferases using Synthetic Acceptor Analogues (1996)

The acceptor specificities of rat liver Gal(beta 1-4)GlcNAc alpha-2,6-sialyltransferase, recombinant full-length human liver Gal(beta 1-4)GlcNAc alpha-2,6-sialyltransferase, and a soluble form of recombinant rat liver Gal(beta 1-3/4)GlcNAc alpha-2,3-sialyltransferase were studied with a panel of analogues of the trisaccharide Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-O)(CH2)7CH3. These analogues contain structural variants of D-galactose, modified at either C3, C4 or C5 by deoxygenation, fluorination, O-methylation, epimerization, or by the introduction of an amino group. In addition, the enantiomer of D-galactose is included. The alpha-2,6-sialyltransferases tolerated most of the modifications at the galactose residue to some extent, whereas the alpha-2,3-sialyltransferase displayed a narrower specificity. Molecular dynamics simulations were performed in order to correlate enzymatic activity to three-dimensional structure. Ineffective acceptors for rat liver alpha-2,6-sialyltransferase were shown to be inhibitory towards the enzyme; likewise, the alpha-2,3-sialyltransferase was found to be inhibited by all non-substrates. Modified sialyloligosaccharides were obtained on a milligram scale by incubation of effective acceptors with one of each of the three enzymes, and characterized by 500-MHz 1H-NMR spectroscopy.
Ordered Mesoporous Platinum@Graphitic Carbon Embedded Nanophase as a Highly Active, Stable, and Methanol-Tolerant Oxygen Reduction Electrocatalyst (2011)

Highly ordered mesoporous platinum@graphitic carbon (Pt@GC) composites with well-graphitized carbon frameworks and uniformly dispersed Pt nanoparticles embedded within the carbon pore walls have been rationally designed and synthesized. In this facile method, ordered mesoporous silica impregnated with a variable amount of Pt precursor is adopted as the hard template, followed by carbon deposition through a chemical vapor deposition (CVD) process with methane as a carbon precursor. During the CVD process, in situ reduction of Pt precursor, deposition of carbon, and graphitization can be integrated into a single step. The mesostructure, porosity and Pt content in the final mesoporous Pt@GC composites can be conveniently adjusted over a wide range by controlling the initial loading amount of Pt precursor and the CVD temperature and duration. The integration of high surface area, regular mesopores, graphitic nature of the carbon walls as well as highly dispersed and spatially embedded Pt nanoparticles in the mesoporous Pt@GC composites make them excellent as highly active, extremely stable, and methanol-tolerant electrocatalysts toward the oxygen reduction reaction (ORR). A systematic study by comparing the ORR performance among several carbon supported Pt electrocatalysts suggests the overwhelmingly better performance of the mesoporous Pt@GC composites. The structural, textural, and framework properties of the mesoporous Pt@GC composites are extensively studied and strongly related to their excellent ORR performance. These materials are highly promising for fuel cell applications and the synthesis method is quite applicable for constructing mesoporous graphitized carbon materials with various embedded nanophases.
A multi-modal composition of the late Na+ current in human ventricular cardiomyocytes (2005)

The early phase of Na+ current decay (<40 ms) involves all three NaCh gating modes, the intermediate phase (from 40 to 300 ms) is produced by BM+LSM, although the contribution of BM decreases with depolarization, and ultra-late decay (>300 ms) is determined solely by LSM. The concept of multi-mode composition for INaL provides a new rationale for INaL modulation by factors such as voltage, temperature, pharmacological agents, and pathological conditions.
AutoSteve: electrical design analysis (1997)

When designing electrical circuits for automotive applications, engineers carry out several painstaking but repetitive design analysis tasks. The paper describes work in automating such tasks, performing the tasks while minimising the amount of work that engineers need to do. The AutoSteve system can take circuit descriptions from electrical CAD tools and simulate the behaviour of the circuit as the state of the circuit changes (for example, because switches are closed or opened). Model-based simulation can be used by engineers to understand the proper working of their circuit design, but its main use is as a basis for automated design analysis. The paper describes how model-based qualitative simulation can be used as a basis for automated generation of a human-readable FMEA report.