gebhart/patrepeval huggingface dataset:
Metastable Alumina from Theory: Bulk, Surface, and Growth of κ-Al2O3 (2001)

Aluminas are materials of high technological importance that show a fascinating structural flexibility, with a large amount of different phases (alpha, gamma, eta, delta, kappa, chi, ...) and phase transitions at relatively high temperatures. This variety provides the different alumina phases with a wide range of properties but at the same time makes experimental and theoretical investigations on them difficult to perform. In particular, a fundamental understanding at the atomistic level is lacking for metastable aluminas, for most of which not even the atomic structure is well known. In the present Thesis, I report on first-principles theoretical investigations at the quantum-mechanical level, based on the density-functional theory (DFT), to study the stability and bonding of the metastable .kappa.-Al2O3. The motivation for this is three-fold. First, the use of .kappa.-Al2O3 as a wear-resistant coating on cemented-carbide cutting tools, deposited with chemical-vapor deposition (CVD), provides a high technological interest for this material. Second, basic understanding of the stability of a metastable alumina yields general insights into metastable-alumina properties. Third, the study of a relatively complex ionic crystal like .kappa.-Al2O3 can be used to investigate the general problem of ion-crystal stability. The work is performed in three parts: (i) The atomic and electronic bulk structures of .kappa.-Al2O3 are determined; (ii) The structure and stability of the (001) and (00-1) surfaces are understood; (iii) The thermodynamics of the Al2O3 nucleation on TiC(111) is investigated. The results yield fundamental knowledge on the CVD growth process of .kappa.-Al2O3, on the stability of metastable aluminas, and on the cohesion of low-symmetry ionic crystals in general. The limited validity of point-charge models for ion-crystal stability is discussed. A surprising prediction of a 1D electron gas at the .kappa.-Al2O3(00-1) surface is furthermore revealed.
Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons (2001)

Human apolipoprotein (apo) E4, a major risk factor for Alzheimer's disease (AD), occurs in amyloid plaques and neurofibrillary tangles (NFTs) in AD brains; however, its role in the pathogenesis of these lesions is unclear. Here we demonstrate that carboxyl-terminal-truncated forms of apoE, which occur in AD brains and cultured neurons, induce intracellular NFT-like inclusions in neurons. These cytosolic inclusions were composed of phosphorylated tau, phosphorylated neurofilaments of high molecular weight, and truncated apoE. Truncated apoE4, especially apoE4(Delta 272--299), induced inclusions in up to 75% of transfected neuronal cells, but not in transfected nonneuronal cells. ApoE4 was more susceptible to truncation than apoE3 and resulted in much greater intracellular inclusion formation. These results suggest that apoE4 preferentially undergoes intracellular processing, creating a bioactive fragment that interacts with cytoskeletal components and induces NFT-like inclusions containing phosphorylated tau and phosphorylated neurofilaments of high molecular weight in neurons.
Securing distributed systems with information flow control (2008)

Recent operating systems [12, 21, 26] have shown that decentralized information flow control (DIFC) can secure applications built from mostly untrusted code. This paper extends DIFC to the network. We present DStar, a system that enforces the security requirements of mutually distrustful components through cryptography on the network and local OS protection mechanisms on each host. DStar does not require any fully-trusted processes or machines, and is carefully constructed to avoid covert channels inherent in its interface. We use DStar to build a three-tiered web server that mitigates the effects of untrustworthy applications and compromised machines. 1
Unimolecular combination therapeutics for the treatment of obesity and type 2 diabetes (2015)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
Glutamate-binding affinity ofDrosophilametabotropic glutamate receptor is modulated by association with lipid rafts (2003)

Metabotropic glutamate receptors (mGluRs) are responsible for the effects of glutamate in slow synaptic transmission, and are implicated in the regulation of many processes in the CNS. Recently, we have reported the expression and purification of a mGluR from Drosophila melanogaster (DmGluRA), a homologue of mammalian group II mGluRs. We have shown that ligand binding to reconstituted DmGluRA requires the presence of ergosterol in the liposomes [Eroglu, C., Cronet, P., Panneels, V., Beaufils, P. &amp; Sinning, I. (2002) EMBO Rep. 3, 491-496]. Here we demonstrate that the receptor exists in different affinity states for glutamate, depending on the membrane composition. The receptor is in a high-affinity state when associated with sterol-rich lipid microdomains (rafts), and in a low-affinity state out of rafts. Enrichment of the membranes with cholesterol shifts the receptor into the high-affinity state, and induces its association with rafts. The receptor was crosslinked to photocholesterol. Our data suggest that sterol-rich lipid rafts act as positive allosteric regulators of DmGluRA.
Dynamics of T‐cell infiltration during the course of ovarian cancer: The gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T‐cells (2012)

The type of immune cells that are present within the tumor microenvironment can play a crucial role in the survival of patients. However, little is known about the dynamics of the tumor-infiltrating immune cells during disease progression. We studied the immune cells that infiltrated the tumor tissues of ovarian cancer patients at different stages of disease. The early stages of development of ovarian carcinomas were characterized by a strong Th17 immune response, whereas in stage II patients, recruitment of high numbers of Th1 cells was observed. In disseminated tumors (Stages III-IV), we detected a dominant population of Helios(+) activated regulatory T cells (Tregs) along with high numbers of monocytes/macrophages and myeloid dendritic cells (mDCs). Tumor-infiltrating Tregs had markedly lower expression of CCR4 than circulating Tregs, and the numbers of tumor-infiltrating Tregs significantly correlated with the levels of CCL22 in ovarian tumor cell culture supernatants, suggesting their recruitment via a CCR4/CCL22 interaction. CCL22 was mainly produced by tumor cells, monocytes/macrophages and mDCs in the primary ovarian tumors, and its expression markedly increased in response to IFNγ. Taken together, the specific recruitment of Tregs, probably triggered by inflammatory stimuli, leads to a significant immune suppression in the advanced stages of ovarian cancer.
Long-term asynchronous decoding of arm motion using electrocorticographic signals in monkey (2010)

Brain-machine interfaces (BMIs) employ the electrical activity generated by cortical neurons directly for controlling external devices and have been conceived as a means for restoring human cognitive or sensory-motor functions. The dominant approach in BMI research has been to decode motor variables based on single-unit activity (SUA). Unfortunately, this approach suffers from poor long-term stability and daily recalibration is normally required to maintain reliable performance. A possible alternative is BMIs based on electrocorticograms (ECoGs), which measure population activity and may provide more durable and stable recording. However, the level of long-term stability that ECoG-based decoding can offer remains unclear. Here we propose a novel ECoG-based decoding paradigm and show that we have successfully decoded hand positions and arm joint angles during an asynchronous food-reaching task in monkeys when explicit cues prompting the onset of movement were not required. Performance using our ECoG-based decoder was comparable to existing SUA-based systems while evincing far superior stability and durability. In addition, the same decoder could be used for months without any drift in accuracy or recalibration. These results were achieved by incorporating the spatio-spectro-temporal integration of activity across multiple cortical areas to compensate for the lower fidelity of ECoG signals. These results show the feasibility of high-performance, chronic and versatile ECoG-based neuroprosthetic devices for real-life applications. This new method provides a stable platform for investigating cortical correlates for understanding motor control, sensory perception, and high-level cognitive processes.
CAR-T Cell Therapy for Lymphoma (2015)

Lymphomas arise from clonal expansions of B, T, or NK cells at different stages of differentiation. Because they occur in the immunocyte-rich lymphoid tissues, they are easily accessible to antibodies and cell-based immunotherapy. Expressing chimeric antigen receptors (CARs) on T cells is a means of combining the antigen-binding site of a monoclonal antibody with the activating machinery of a T cell, enabling antigen recognition independent of major histocompatibility complex restriction, while retaining the desirable antitumor properties of a T cell. Here, we discuss the basic design of CARs and their potential advantages and disadvantages over other immune therapies for lymphomas. We review current clinical trials in the field and consider strategies to improve the in vivo function and safety of immune cells expressing CARs. The ultimate driver of CAR development and implementation for lymphoma will be the demonstration of their ability to safely and cost-effectively cure these malignancies.
Pathogenesis, Natural History, Treatment, and Prevention of Hepatitis C (2000)

Approximately 4 million persons in the United States and probably more than 100 million persons worldwide are infected with hepatitis C virus. The virus has the unique ability to cause persistent infection in susceptible hosts after parenteral or percutaneous transmission, and its underlying mechanisms are not well understood. The immunologic correlates of protection and viral clearance and the pathogenesis of liver injury are yet to be defined, but recent studies suggest the importance of cell-mediated immune responses. Although 70% to 80% of infected persons become chronic carriers, most have relatively mild disease with slow progression. However, chronic and progressive hepatitis C carries significant morbidity and mortality and is a major cause of cirrhosis, end-stage liver disease, and liver cancer. Development of an effective hepatitis C virus vaccine is not imminent, but recent advances in technology and basic knowledge of molecular virology and immunology have engendered novel approaches to the fundamental problems encountered in vaccine development. Current therapy for hepatitis C, although effective in some patients, is problematic and still evolving. Advances in modern biology and immunology promise new therapies for this important disease.
State of the art and future perspectives of articular cartilage regeneration: a focus on adipose-derived stem cells and platelet-derived products (2011)

Trauma, malposition and age-related degeneration of articular cartilage often result in severe lesions that do not heal spontaneously. Many efforts over the last centuries have been undertaken to support cartilage healing, with approaches ranging from symptomatic treatment to structural cartilage regeneration. Microfracture and matrix-associated autologous chondrocyte transplantation (MACT) can be regarded as one of the most effective techniques available today to treat traumatic cartilage defects. Research is focused on the development of new biomaterials, which are intended to provide optimized physical and biochemical conditions for cell proliferation and cartilage synthesis. New attempts have also been undertaken to replace chondrocytes with cells that are more easily available and cause less donor site morbidity, e.g. adipose derived stem cells (ASC). The number of in vitro studies on adult stem cells has rapidly increased during the last decade, indicating that many variables have yet to be optimized to direct stem cells towards the desired lineage. The present review gives an overview of the difficulties of cartilage repair and current cartilage repair techniques. Moreover, it reviews new fields of cartilage tissue engineering, including stem cells, co-cultures and platelet-rich plasma (PRP).
Ethylene homopolymerization with P, O‐chelated nickel catalysts (1987)

Abstract Abstraction of phosphine from the nickel(II) P, O‐chelated complexes, Ni[Ph 2 PCHC(Ph)O] (Ph)(PPh 3 ), and related species converts them from olefin oligomerization to olefin polymerization catalysts. Phosphine acceptors such as Rh(acetylacetonate)(C 2 H 4 ) 2 or Ni(1,5‐cyclooctadiene) 2 are most effective. Alternatively, nickel complexes in which the phosphine ligand is replaced with weakly coordinated pyridine can be prepared. These active, homogeneous catalysts can be tuned to give either low or high molecular weight, linear low or high density polyethylene. Depending on the diluent, the same catalytic complex can be used as heterogeneous or homogeneous catalyst. They are tolerant of oxygenated, hydroxylic, or polar molecules that would poison normal early transition metal‐based Ziegler‐Natta catalysts. In fact, the polymerizations can be run in solvents such as ethanol or acetone, but hydrocarbon solvents are preferred.
Application of spectral decomposition to detection of dispersion anomalies associated with gas saturation (2006)

For many years geophysicists have attempted to exploit attenuation measurements in exploration seismology, because attenuation is perhaps the seismic property most closely related to the saturating fluid. The routine application of such ideas has proven elusive, however, largely because of the difficulty experienced when we attempt to measure attenuation in reflection data. Recent developments in the application of spectral decomposition methods to seismic data have opened the possibility of making further progress in this direction.
THE PROTEASOME (1999)

Proteasomes are large multisubunit proteases that are found in the cytosol, both free and attached to the endoplasmic reticulum, and in the nucleus of eukaryotic cells. Their ubiquitous presence and high abundance in these compartments reflects their central role in cellular protein turnover. Proteasomes recognize, unfold, and digest protein substrates that have been marked for degradation by the attachment of a ubiquitin moiety. Individual subcomplexes of the complete 26S proteasome are involved in these different tasks: The ATP-dependent 19S caps are believed to unfold substrates and feed them to the actual protease, the 20S proteasome. This core particle appears to be more ancient than the ubiquitin system. Both prokaryotic and archaebacterial ancestors have been identified. Crystal structures are now available for the E. coli proteasome homologue and the T. acidophilum and S. cerevisiae 20S proteasomes. All three enzymes are cylindrical particles that have their active sites on the inner walls of a large central cavity. They share the fold and a novel catalytic mechanism with an N-terminal nucleophilic threonine, which places them in the family of Ntn (N terminal nucleophile) hydrolases. Evolution has added complexity to the comparatively simple prokaryotic prototype. This minimal proteasome is a homododecamer made from two hexameric rings stacked head to head. Its heptameric version is the catalytic core of archaebacterial proteasomes, where it is sandwiched between two inactive antichambers that are made up from a different subunit. In eukaryotes, both subunits have diverged into seven different subunits each, which are present in the particle in unique locations such that a complex dimer is formed that has six active sites with three major specificities that can be attributed to individual subunits. Genetic, biochemical, and high-resolution electron microscopy data, but no crystal structures, are available for the 19S caps. A first step toward a mechanistic understanding of proteasome activation and regulation has been made with the elucidation of the X-ray structure of the alternative, mammalian proteasome activator PA28.
The Influence of Instrument Configuration on Tissue Handling Force in Laparoscopy (2012)

In single-access surgery, instruments enter the abdominal cavity through only 1 incision, the position of the instruments relative to each other is different compared with that in conventional laparoscopy. Changes in instrument configuration may increase task complexity and therefore affect tissue handling skills. The aim of this study is to determine if a relation exists between instrument configuration and tissue interaction force. A study was performed to investigate the differences in manipulation force between a single-port (SP) and 2-port (TP) instrument configuration in a standard box trainer. A force platform was placed under a tissue manipulation task in a box trainer and used to measure the pulling forces and trial time. A total of 28 medical students with no previous experience in laparoscopic surgery were divided into 2 equal groups. Group 1 trained the task 6 times with the TP configuration and subsequently performed 6 trials with the SP configuration. Group 2 used the configurations in the opposite order. For both groups, the learning curves of the maximum force and task time were compared. Time and maximum pulling forces were significantly different between the 2 instrument configurations. In both groups, the participants used significantly more force in the SP configuration than in the TP configuration. The force data indicate that the increased complexity in instrument handling with straight instruments in a SP configuration increases the tissue manipulation force. Furthermore, the tissue handling skills of novices who mastered the task with the TP configuration decreased after switching to the SP configuration.
Stylized keyframe animation of fluid simulations (2014)

We present a method that combines hand-drawn artwork with fluid simulations to produce animated fluids in the visual style of the artwork. Given a fluid simulation and a set of keyframes rendered by the artist in any medium, our system produces a set of in-betweens that visually matches the style of the keyframes and roughly follows the motion from the underlying simulation. Our method leverages recent advances in patch-based regenerative morphing and image melding to produce temporally coherent sequences with visual fidelity to the target medium. Because direct application of these methods results in motion that is generally not fluid-like, we adapt them to produce motion closely matching that of the underlying simulation. The resulting animation is visually and temporally coherent, stylistically consistent with the given keyframes, and approximately matches the motion from the simulation. We demonstrate the method with animations in a variety of visual styles.
Advanced Corneal Cross-Linking System with Fluorescence Dosimetry (2012)

Purpose. This paper describes an advanced system that combines corneal cross-linking with riboflavin with fluorescence dosimetry, the ability to measure riboflavin diffusion within the cornea both before and during UVA treatment. Methods and Results. A corneal cross-linking system utilizing a digital micromirror device (DMD) was assembled and used to measure diffusion coefficients of 0.1% riboflavin in 20% dextran in porcine eyes. A value of (3.3 ± 0.2) × 10(-7) cm(2)/s was obtained for the stroma. Diffusion coefficients for the transepithelial formulation of 0.1% riboflavin in 0.44% saline and 0.02% BAK were also measured to be 4.7 ± 0.3 × 10(-8) cm(2)/s for epithelium only and (4.6 ± 0.4) × 10(-7) cm(2)/s for stroma only. Riboflavin consumption during a UVA treatment was also demonstrated. Conclusion. A new advanced corneal cross-linking system with fluorescence dosimetry of riboflavin has been demonstrated. It is hoped that this method may play a significant role in determining the underlying mechanisms of corneal cross-linking and assist with the development of additional riboflavin formulations. Moreover, dosimetry may prove valuable in providing a method to account for the biological differences between individuals, potentially informing cornea-specific UVA treatment doses in real time.
New antiarrhythmic treatment of atrial fibrillation (2007)

Antiarrhythmic pharmaceutical development for the treatment of atrial fibrillation (AF) is moving in several directions. The efficacy of existing drugs, such as carvedilol, for rate control and, possibly, suppression of AF, is more appreciated. Efforts are being made to modify existing agents, such as amiodarone, in an attempt to ameliorate safety and adverse effect concerns. This has resulted in promising data from the deiodinated amiodarone analog, dronedarone, and further work with celivarone and ATI-2042. In an attempt to minimize ventricular proarrhythmia, atrial selective drugs, such as intravenous vernakalant, have demonstrated efficacy in terminating AF in addition to promising data in suppression recurrences when used orally. Several other atrial selective drugs are being developed by multiple manufacturers. Other novel therapeutic mechanisms, such as drugs that enhance GAP junction conduction, are being developed to achieve more effective drug therapy than is offered by existing compounds. Finally, nonantiarrhythmic drugs, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, high-mobility group coenzyme A enzyme inhibitors and omega-3 fatty acids/fish oil, appear to have a role in suppressing AF in certain patient subtypes. Future studies will clarify the role of these drugs in treating AF.
Mice primed with swainsonine are protected against doxorubicin-induced lethality. (2003)

The anthracycline, doxorubicin is a potent cancer chemotherapeutic agent whose therapeutic usefulness is limited by both a dose- and time-dependent cardiomyopathy. We tested the ability of an immunomodulatory alkaloid swainsonine (8alphabeta-indolizidine-1alpha,2alpha,8beta-triol) to protect C57BL/6 mice against lethality within 70 days following a single bolus intraperitoneal injection of LD50/14 doxorubicin. Also, we sought the potential mechanisms responsible for this protection. This extended 70-day study in mice, which may be considered equivalent to a period of 4 to 5 years in humans, has clinical implication for delayed cardiotoxic sequela of therapy with high dose doxorubicin. Mice were pretreated with swainsonine or its diluent buffer, phosphate buffered saline for ten consecutive days prior to a single bolus intraperitoneal injection of a LD50/14 doxorubicin. We have previously defined this swainsonine pretreatment regimen as one of the two optimal conditions for swainsonine rescue of mice from death induced by LD50/14 doxorubicin. The survival and well being of groups of mice pretreated with swainsonine and phosphate buffered saline prior to LD50/14 doxorubicin, sham-treated and untreated were monitored daily for up to 70 days. The bone marrow cellularity of the mice were quantified, and in vitro progenitor cell assays were used to determine the effects of these treatment regimens on bone marrow competence following doxorubicin treatment. The effects of these treatment regimens on heart morphology and hematologic toxicities were also determined. This swainsonine pretreatment regimen significantly abrogated doxorubicin-induced lethality and prolonged survival of mice by facilitating restoration of bone marrow cellularity, accelerating restoration of blood hematocrit and total leukocyte levels, enhancing the proliferation and differentiation of bone marrow pluripotent stem cells along the different paths to progenitor lineages, and preserving the heart morphology. This study strongly suggests a potential role for swainsonine with doxorubicin in cancer chemotherapy.