gebhart/patrepeval huggingface dataset:
Efficient inhibition of tumor angiogenesis and growth by a synthetic peptide blocking S100A4-methionine aminopeptidase 2 interaction (2015)

The prometastatic calcium-binding protein, S100A4, is expressed in endothelial cells, and its downregulation markedly suppresses tumor angiogenesis in a xenograft cancer model. Given that endothelial S100A4 can be a molecular target for inhibiting tumor angiogenesis, we addressed here whether synthetic peptide capable of blocking S100A4-effector protein interaction could be a novel antiangiogenic agent. To examine this hypothesis, we focused on the S100A4-binding domain of methionine aminopeptidase 2, an effector protein, which plays a role in endothelial cell growth. Overexpression of the domain in mouse endothelial MSS31 cells reduced DNA synthesis, and the corresponding synthetic peptide (named NBD) indeed interacted with S100A4 and inhibited capillary formation in vitro and new blood vessel formation in vivo. Intriguingly, a single intra-tumor administration of the NBD peptide in human prostate cancer xenografts significantly reduced vascularity, resulting in tumor regression. Mechanistically, the NBD peptide enhanced assembly of nonmuscle myosin IIA filaments along with Ser1943 phosphorylation, stimulated formation of focal adhesions without phosphorylation of focal adhesion kinase, and provoked G1/S arrest of the cell cycle. Altogether, the NBD peptide is a potent inhibitor for tumor angiogenesis, and is the first example of an anticancer peptide drug developed on the basis of an endothelial S100A4-targeted strategy.
Preparation of Protein Extracts from Yeast (1993)

Three protocols are presented for preparing protein extracts; they differ primarily in the way the cells are broken. In the basic protocol, cells are enzymatically converted to spheroplasts, which are then lysed by a combination of osmotic shock and Dounce homogenization. A support protocol for isolating intact nuclei by differential centrifugation is also presented. An alternate protocol describes mechanical breakage of cells by vortexing in the presence of glass beads. In a second alternate protocol, growing cells are frozen immediately in liquid nitrogen and then lysed by grinding in an industrial-strength blender in the presence of liquid nitrogen.
Advanced materials for a damage resilient divertor concept for DEMO: Powder-metallurgical tungsten-fibre reinforced tungsten (2016)

Material issues pose a significant challenge for future fusion reactors like DEMO. When using materials in a fusion environment a highly integrated approach is required. Damage resilience, power exhaust, as well as oxidation resistance during accidental air ingress are driving issues when deciding for new materials. Neutron induced effects, e.g. transmutation adding to embrittlement is crucial to material performance. Here advanced materials, e.g. Wf/W or W/Cu, Wf/Cu composites allow the step towards a fusion reactor. Recent developments in the area of multi-fibre powder-metallurgical Wf/W mark a possible path towards a component based on standard tungsten production technologies. Field assisted sintering technology is used as production route to achieve 94% dense materials. Initial mechanical tests and micro-structural analyses show potential for pseudo-ductile behavior of materials with a reasonable (30%) fibre fraction. In the as-fabricated condition samples showed step-wise cracking while the material is still able to bear rising load, the typical pseudo-ductile behavior of a composite. Yttria is used as the interface material in order to allow the energy dissipation mechanisms to become active. Wf/W as plasma facing material contributes here to advanced material strength and crack resilience even with a brittle matrix embrittlement, while W/Cu, Wf/Cu composites at the coolant level allow for higher strength at elevated cooling temperatures. In addition to the use of pure tungsten it is demonstrated that tungsten-based self-passivating alloys can also be used in the composite approach.
Reduced Material Loss in Thin-film Lithium Niobate Waveguides (2022)

Thin-film lithium niobate has shown promise for scalable applications ranging from single-photon sources to high-bandwidth data communication systems. Realization of the next generation high-performance classical and quantum devices, however, requires much lower optical losses than the current state of the art ($\sim$10 million). Unfortunately, material limitations of ion-sliced thin-film lithium niobate have not been explored, and therefore it is unclear how high-quality factor can be achieved in this platform. Here we evaluate the material limited quality factor of thin-film lithium niobate photonic platform can be as high as $Q\approx 1.8\times10^{8}$ at telecommunication wavelengths, corresponding to a propagation loss of 0.2 dB/m.
Numerical modeling and uncertainty analysis of light emitting diodes for photometric measurements (2015)

With the rapid evolution of new, energy-efficient solid-state lighting (SSL) systems, a requirement has risen for new performance metrics and measurement methods to address their unique construction and operating conditions. In this paper, light propagation characteristics in light emitting diodes are analyzed for measurement uncertainty through numerical modeling and simulation. A general 2D EM simulator with PML boundary conditions is formulated to solve Maxwell's equations using finite-difference time domain (FDTD) numerical method to describe the light propagation in LEDs. A practical GaN LED used in SSL systems is simulated for light propagation. The optical properties of dispersive materials are modeled using multi-pole Lorentz-Drude model. The input dipole source for the LED structure is modeled explicitly through a Gaussian pulse line source at a central wavelength of 460 nm corresponding to GaN emission. Finally, the expression for combined standard uncertainty in the light extraction efficiency due to uncertainties in inputs such as emission in the active layer and EM fields is developed using the GUM law of propagation of uncertainties. The uncertainty in GaN LED emission wavelength obtained from Full Width Half Maximum (FWHM) of the emission spectrum is computed to be 16.98 nm. Therefore, the uncertainty analysis model is then used to compute the corresponding uncertainties in the LED output measurements i.e. light extraction efficiency, LED output power and EM fields.
SOLUBLE CTLA4Ig MODIFIES PARAMETERS OF ACUTE INFLAMMATION IN RAT LUNG ALLOGRAFT REJECTION WITHOUT ALTERING LYMPHOCYTIC INFILTRATION OR TRANSCRIPTION OF KEY CYTOKINES1 (1995)

The efficacy of CTLA4Ig in blocking immune activation and allograft rejection (AR) was tested in an aggressive and rapid model of rat lung AR (Brown Norway [BN] → Lewis [LEW]). CTLA4Ig is a recombinant soluble protein that binds with high affinity to rat B7/BB1 and other surface molecules on APCs, subsequently blocking the binding of B7/BB1 to CD28/CTLA4 on T cells. This interrupts the costimulatory pathway critical for complete T cell activation and completion of the AR process. Left single-lung transplants were performed between BN→Lew. Five allograft recipients were examined in each group. At transplantation, animals received 250 μg of CTLA4Ig or 250 μg of control Ig intraperitoneally daily until sacrifice. Animals were sacrificed on days 2, 4, and 7 after transplant. Control (BN→Lew) grafts show irreversible rejection by day 7. Syngeneic (Lew→Lew) grafts show no AR on day 7. AR episodes were graded histologically (stages 0-IV) and pathologic intensity of inflammation was graded on percentage of involvement. Cytokine transcript levels were measured in control and CTLA4Ig-treated animals (n = 5 in each group) on day 7 using reverse transcriptase polymerase chain reaction techniques. The most profound differences were found on day 7 after transplant. The degree of lymphocytic infiltration was greater in the CTLA4Ig group (perivascular: 4±0 vs. 2.6±0.6, peribronchial: 4±0 vs. 2.2±0.4, and peribronchiolar: 3.6± 0.5 vs. 2±0.3,P<0.01). However, in striking contrast, the stage of AR (3±0 vs. 4±0,P<0.01), vasculitis (1±0.7 vs. 2.6±0.6,P<0.05), hemorrhage (0.4±0.6 vs. 3.2±0.4,P<0.01), and necrosis (0±0 vs. 2.4±0.5,P<0.005) were significantly reduced in animals treated with CTLA4Ig. Since CTLA4Ig blocks Th1 cell activation in vitro, we compared the levels of Th1 inflammatory cytokines IL-2, γ-IFN, and TNF-αin the two models. The intragraft ratios (CTLA4Ig/control) were IL-2:0.77, γ-IFN: 1.29, and TNF-α:1.33. Thus, CTLA4Ig did not significantly block intragraft production of Th1 cytokines on day 7. Transcript ratios for cytokines known to suppress Th1 cell activation (IL-4, IL-10, and transforming growth factor-β1) in CTLA4Ig to control Ig were all about 1, which indicates no preferential expression of Th2 cytokines in CTLA4Ig-treated animals. Cytotoxic T cell serine protease andc-myctranscript levels were similar in both groups. Our findings suggest that: (1) CTLA4Ig exerts a profound and statistically significant inhibitory effect on inflammatory and cytodestructive events in the BN→Lew allograft model on day 7; (2) there is no effect on lymphocytic infiltration, cellular proliferation, Th1, Th2 cytokine transcript levels, serine protease transcript levels, andc-myctranscript levels; (3) the inability of CTLA4Ig to completely block cellular infiltration and cytokine transcription may be related to its known decreased efficacy in rat models, possibly related to potent costimulatory signals that are independent of the CD28/B7 pathway.
LIDAR (2013)

Given the advanced set of capabilities offered by smartphone and tablet computing devices, they have become the platform of choice for many users for day-to-day work and leisure. There is however a fundamental difference in the attitude of a typical user when it comes to using their mobile device as compared to their personal computers. While the use of anti-virus software on PCs to protect our security and privacy is ubiquitous today, there is little by the way of security and privacy protection available on these mobile computing platforms. Our work focuses on developing a Layered Intrusion Detection and Remediation framework (LIDAR) to automatically detect, analyze, protect, and remediate security threats in this domain. We have focused on Android devices and have developed several algorithms that would help detect abnormal behavior in the operation of Android smartphone and tablets that could potentially detect presence of malware. In this paper, we present a high-level overview of our approach and briefly summarize a suite of algorithms developed to identify certain types of malicious behavior.
Modeling Nucleation and Growth in Zeolites (2003)

Modeling techniques have been used for many years in investigations of structures, properties, and reactivities of microporous materials (1). Early work focused on modeling of crystal structures (2), but applications quickly developed in the fields of sorption (see Chapter 9 in this volume) and diffusion (see Chapter 10). In recent years, extensive use has been made of high-level quantum mechanical methods in the study of reaction mechanisms in zeolites (see Chapter 15).
718 WTX-124 is a novel IL-2 pro-drug that is conditionally activated in tumors and drives antitumor immunity in murine syngeneic cancer models (2021)

<h3>Background</h3> Cancer immunotherapy has established itself as the fourth pillar of cancer treatment thanks to the clinical success of checkpoint inhibitors. However, durable anti-tumor responses following immunotherapy are still limited to certain cancer types, and only a fraction of patients respond to the treatment, demonstrating the need for additional immunotherapeutic agents. Preclinical and clinical studies have demonstrated the promise of cytokine therapy to increase antitumor immunity. One of these key cytokines, interleukin-2 (IL-2), is approved for clinical use in metastatic melanoma and renal cell carcinoma. Unfortunately, this treatment requires dosing every 8 hours due to its poor pharmacokinetic profile and is linked to serious toxicities which limits its utility. <h3>Methods</h3> To address these limitations, we designed WTX-124, an IL-2 pro-drug (IL-2 INDUKINE™ protein) that takes advantage of dysregulated protease activity in the tumor microenvironment (TME) to selectively deliver active IL-2 to the tumor after systemic administration. Peripheral inactivation is achieved by linking the cytokine to an inactivation domain using a tumor protease-sensitive linker. The INDUKINE™ molecule is also engineered with a half-life extension element to improve the pharmacokinetic profile and maintain longer exposure in the tumor. Once the IL-2 INDUKINE™ protein reaches the tumor, tumor-associated proteases cleave the linker and release the fully active cytokine. <h3>Results</h3> Treatment with WTX-124 resulted in the complete rejection of MC38 tumors in a manner dependent on proteolytic processing of the INDUKINE™ protein, as a non-cleavable version of WTX 124 lacked anti-tumor activity. Furthermore, the INDUKINE™ format greatly enhanced the PK profile of WTX 124 over free IL-2, resulting in greater exposure with less overall dosing, and demonstrating a favorable accumulation of free IL-2 in tumors compared to plasma. Mechanistically, WTX 124 treatment drove the expansion and activation of tumor infiltrating CD8+ T cells and NK cells which increased the production of effector cytokines in the tumor. This resulted in tumor rejection that translated into durable immune memory, as animals that rejected the tumors upon IL-2 INDUKINE™ protein treatment were protected against a subsequent re-challenge with the same tumor cells. WTX 124 also demonstrated favorable pharmacokinetic and tolerability characteristics in cynomolgus monkeys resulting in minimal release of IL-2 in the periphery. <h3>Conclusions</h3> The combination of tumor-selective activation of WTX-124 with reduced peripheral toxicities and its favorable pharmacokinetic profile supports moving this compound into clinical development. <h3>Ethics Approval</h3> All animal in vivo work was performed in accordance with current regulations and standards of the U.S. Department of Agriculture and the NIH.
Stereoselectivity in Intramolecular Cyclization of Non-conjugated Unsaturated Ketones by Electroreduction (2002)

Abstract This study showed some decrease in stereoselectivity in electroreductive intramolecular cyclization of nitrogen-containing non-conjugated enones in comparison with high stereoselectivity for the corresponding enones possessing an all-carbon-chain or a sulfur-containing chain. This phenomenon may provide some actual experimental supports for the remarkable stereochemical features of the electroreductive cyclization.
Dynamic Scheimpflug Ocular Biomechanical Parameters in Healthy and Medically Controlled Glaucoma Eyes (2019)

Eyes with medically controlled glaucoma were more deformable than healthy eyes, which may increase the risk of optic nerve damage through an underestimation of IOP and biomechanical vulnerability of the globe. Many parameters showed a significant correlation with baseline factors, suggesting the importance of adjustment for these confounding factors when evaluating the correlation between biomechanical parameters and ocular diseases. These results suggest the relevance of measuring biomechanical properties of glaucoma eyes for accurate IOP measurement and risk assessment.
SCAI/HRS expert consensus statement on transcatheter left atrial appendage closure (2023)

Exclusion of the left atrial appendage to reduce thromboembolic risk related to atrial fibrillation was first performed surgically in 1949. Over the past 2 decades, the field of transcatheter endovascular left atrial appendage closure (LAAC) has rapidly expanded, with a myriad of devices approved or in clinical development. The number of LAAC procedures performed in the United States and worldwide has increased exponentially since the Food and Drug Administration approval of the WATCHMAN (Boston Scientific) device in 2015. The Society for Cardiovascular Angiography & Interventions (SCAI) has previously published statements in 2015 and 2016 providing societal overview of the technology and institutional and operator requirements for LAAC. Since then, results from several important clinical trials and registries have been published, technical expertise and clinical practice have matured over time, and the device and imaging technologies have evolved. Therefore, SCAI prioritized the development of an updated consensus statement to provide recommendations on contemporary, evidence-based best practices for transcatheter LAAC focusing on endovascular devices.
Efficient Synthesis of Propargylic Ethers under the DBU Conditions and Its Application to Natural Products Synthesis (2007)

Abstract Conversion of dibromides carrying O-functional groups at adjacent positions to the corresponding propargylic ethers was successfully carried out under the DBU conditions through 2-bromo-1-alkenes as intermediates. The optically active γ-lactone-class natural products, such as (−)-muricatacin (4) and (R,R)-sapinofuranone B (5) were synthesized using the propargylic ether intermediate produced by the elimination reaction mentioned above.
Morphology and micromechanical deformation behavior of styrene/butadiene‐block copolymers. I. Toughening mechanisms in asymmetric star block copolymers (2002)

Abstract Lamellae‐forming styrene/butadiene star block copolymers are studied to investigate the influence of morphology on micromechanical deformation mechanisms and mechanical properties by using transmission electron microscopy and tensile testing. A large homogeneous plastic deformation of polystyrene (PS) lamellae is found in styrene/butadiene star block copolymers on the basis of the new mechanism called thin‐layer yielding. This mechanism depends strongly on the thickness of the PS lamellae. At a critical thickness of PS lamellae of about 20 nm, a transition from thin‐layer yielding mechanism to a crazelike deformation was observed. These new deformation zones are similar to crazes with respect to their propagation perpendicular to direction of external stress and similar to shear bands with respect to an internal shear deformation component of the lamellae in the deformation zones. As a result of our investigations, the mechanical properties of star block copolymers can be understood in correlation with morphology and micromechanical deformation mechanisms. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 683–700, 2002
Nonlinear Creep in a Polymer Glass (2008)

Results of molecular dynamics simulations are presented for the nonlinear creep response of a model polymer glass under both tension and compression. The structure of the material was examined as a function of time; it is found that the overall structure, as measured by the structure factor, changes appreciably during the deformation. The intensity of the first peak is decreased under stress and the polymer chains are deformed. The dynamics are studied using both the bond autocorrelation function and the incoherent dynamic structure factor. It is found that the dynamics are strongly correlated with the strain rate in the material. Additionally, each measure of the dynamics is uniformly enhanced by the same amount. Previous simulations have shown that the enhanced dynamics do not correlate with changes in the volume in any clear manner; here, evidence from simulations indicates that the enhanced dynamics correlate with the energy of the inherent structures of the material, suggesting that changes in the materials’ position on the potential energy landscape lead to the observed enhanced dynamics. Finally, the results of simulations are discussed in terms of two theories of stress-induced dynamics.
Smart materials and structures (1999)

A smart structure is a system containing multifunctional parts that can perform sensing, control, and actuation; it is a primitive analogue of a biological body. Smart materials are used to construct these smart structures, which can perform both sensing and actuation functions.

The “I.Q.” of smart materials is measured in terms of their “responsiveness” to environmental stimuli and their “agility.” The first criterion requires a large amplitude change, whereas the second assigns faster response materials with higher “I.Q.” Commonly encountered smart materials and structures can be categorized into three different levels: ( i ) single-phase materials, ( ii ) composite materials, and ( iii ) smart structures. Many ferroic materials and those with one or more large anomalies associated with phase-transition phenomena belong to the first category. Functional composites are generally designed to use nonfunctional materials to enhance functional materials or to combine several functional materials to make a multifunctional composite. The third category is an integration of sensors, actuators, and a control system that mimics the biological body in performing many desirable functions, such as synchronization with environmental changes, self-repair of damages, etc. These three levels cover the general definition of smart materials and structures. In this short summary, we will use a few examples to illustrate such systems and to provide some general guidelines for designing “smart” systems.

The difference between an ordinary and a “smart” material can be demonstrated through the following positive temperature coefficient (PTC)-resistance materials. A large group of temperature sensors is based on the temperature dependence of the electrical resistivity of conductors. Platinum, for example, is a widely used metal for PTC sensors. The resistance rises constantly with increasing temperature over a wide range from about 20 to 1,500 K. …
ChemInform Abstract: NUCLEOSIDES. XXXV. SYNTHESIS, PROPERTIES, AND REACTIVITY OF LUMAZINE 5‐OXIDE RIBOSIDES (1981)

Abstract Aus den Lumazinribosiden (I) erhält man durch Oxidation mit H 2 O 2 in TFA die 5‐Oxide (II); (IIa) und (IIb) werden nach A) (IIc) nach B) desacyliert unter Bildung der freien Nucleosid‐N‐oxide (III).
Systemic Administration of a Calpain Inhibitor Reduces Behavioral Deficits and Blood–Brain Barrier Permeability Changes after Experimental Subarachnoid Hemorrhage in the Rat (2002)

Increases in intracellular calcium and subsequent activation of calcium-activated proteases (e.g., calpains) may play a critical role in central nervous system injury. Several studies have implicated calpain activation following subarachnoid hemorrhage (SAH). This study evaluated the effect of a calpain inhibitor administration following SAH in the rat on behavioral deficits (postinjury days 1-5, employing a battery of well-characterized assessment tasks), and blood-brain barrier permeability changes (48 h post-SAH, quantifying the microvascular alterations according to the extravasation of protein-bound Evans Blue using a spectrophotofluorimetric technique). Rats were injected with 400 microl of autologous blood into the cisterna magna to induce SAH. Within 5 min after the surgical procedure, Calpain Inhibitor II or vehicle was continuously administered intravenously for 2 days. Results indicated that Calpain Inhibitor II treatment after SAH significantly improved (a) beam balance time (day 1, p < 0.05), but not beam balance score, (b) latency to traverse the beam on days 1-4 (day 1-3, p < 0.001; day 4, p < 0.01), and (c) loss in body weight on days 4-5 (p < 0.05). Evans Blue dye extravasation was significantly less in SAH Calpain Inhibitor II-treated rats compared to SAH vehicle-treated rats in seven out of the eight brain regions studied (p < 0.001, 0.01, and 0.05). These results suggest that pharmacological inhibition of a relatively selective, membrane-permeant calpain inhibitor can significantly reduce some pathophysiological SAH consequences, and indicate that the inhibition of calpain may be a beneficial therapeutic approach to reduce post-SAH global brain dysfunction.