gebhart/patrepeval huggingface dataset:
[O2–09–02]: EVALUATION OF SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF MEDI1814, A BETA‐AMYLOID 42 (Aβ42)‐SPECIFIC ANTIBODY, IN PATIENTS WITH MILD‐MODERATE ALZHEIMER'S DISEASE (2017)

MEDI1814 is a fully human IgG1λ monoclonal antibody, engineered for selective, high-affinity binding of Aβx-42 (Aβ42) peptides and for reduced effector function by virtue of a triple mutation (TM) introduced into the Fc region. In vitro, MEDI1814 selectively binds all forms of Aβ42 peptides. In rats and cynomolgus monkeys, MEDI1814 increases total and decreases free CSF Aβ42 peptides, but does not affect total CSF Aβ40 levels. In a two-part single (SAD) and multiple ascending dose (MAD) study we set out to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of MEDI1814 in patients with mild to moderate Alzheimer's Disease (AD). Eligibility criteria for the trial included: age 55–85, > 6-month history of probable AD according to National Institute of Aging-Alzheimer's Association (NIA-AA) criteria, and a MMSE score of 16–26 inclusive. In the SAD part, N=45 subjects received placebo or MEDI1814 at doses of 25, 100, 300, 900 and 1800 mg intravenously (IV) or 100mg subcutaneously (SC). Doses in the MAD phase (N=32) were 300, 900 and 1800 mg IV or 200 mg SC (administered every 4 weeks for 3 doses). Safety evaluations included cerebral MRI scans at baseline and follow-up. Administration of MEDI1814 or placebo to 77 AD patients was not associated with any medically important changes in safety parameters across all doses tested. No SAEs were reported. No cases of amyloid-related imaging abnormalities (ARIA) were observed. Predictable and dose-proportional changes in serum PK for MEDI1814 were observed across cohorts. CSF PK demonstrated CNS penetration of MEDI1814. PD data showed dose-dependent suppression of free Aβ42 and increases in total Aβ42 in CSF, but no change in total Aβ40 across doses, consistent with the results seen in preclinical species. Administration of MEDI1814 to N= 57 AD patients in single or repeat doses up to 1800 mg IV or 200mg SC demonstrated a safety and tolerability profile consistent with further development. There was no evidence of ARIA. The PK and PD data provide evidence of dose-dependent and selective Aβ42 target engagement by MEDI1814 in the central compartment. Results from a final analysis of the first-in-human study data will be presented.
Planetary Lander Testbed for Technology Demonstration (2013)

Masten Space Systems has developed several Vertical-Takeoff-Vertical-Lander (VTVL) vehicles for suborbital research and as vertical landing technology demonstrators. Their Xombie vehicle competed in and won the Lunar Lander Challenge X-Prize in 2009. The Xogdor and Xaero VTVL single-engine vehicles are being developed for sub-orbital missions. These vehicles will be used for Masten participation in NASA’s Flight Opportunities Program, operated out of NASA Dryden. A technology demonstration program utilizing the Masten VTVL vehicles would be able to demonstrate the precision landing and hazard avoidance (PLH propulsion (e.g. green propellants, novel engine systems, and propellant slosh models); Lidar and synthetic aperture radar imaging sensors; distributed avionics and Integrated Vehicle Health Management (IVHM); relative navigation algorithms; autonomous flight operations; adaptive GNC smart landing gear algorithms; autonomous response for engine failure; and many more. The paper provides an overview of an approach to utilizing the Masten vehicles (Xaero, Xogdor and others) to develop and demonstrate these technologies in a vehicle-in-the-loop environment. 1 Systems Engineer, Boeing BDS, 5301 Bolsa Avenue, Huntington Beach, CA 92647/Mail Stop H017-D728, AIAA Member. 2 Flight Simulation Engineer, Boeing BDS, 5301 Bolsa Avenue, Huntington Beach, CA 92647/Mail Stop H022C328, AIAA Member. 3 Senior Manager, Flight Systems, Boeing BDS, 5301 Bolsa Avenue, Huntington Beach, CA 92647/Mail Stop H013-C328, AIAA Member. 4 Senior Engineer, Flight Systems, Boeing BDS, 5301 Bolsa Avenue, Huntington Beach, CA 92647/Mail Stop H017-D728, AIAA Member. 5 Director of Business Development, Masten Space Systems, 1570 Sabovich St., Mojave, CA 93501, AIAA Member 6 Chief Executive Officer, Masten Space Systems, 1570 Sabovich St., Mojave, CA 93501, AIAA Member
Lymphoid tissue–specific homing of bone marrow–derived dendritic cells (2009)

Because of their potent immunoregulatory capacity, dendritic cells (DCs) have been exploited as therapeutic tools to boost immune responses against tumors or pathogens, or dampen autoimmune or allergic responses. Murine bone marrow-derived DCs (BM-DCs) are the closest known equivalent of the blood monocyte-derived DCs that have been used for human therapy. Current imaging methods have proven unable to properly address the migration of injected DCs to small and deep tissues in mice and humans. This study presents the first extensive analysis of BM-DC homing to lymph nodes (and other selected tissues) after intravenous and intraperitoneal inoculation. After intravenous delivery, DCs accumulated in the spleen, and preferentially in the pancreatic and lung-draining lymph nodes. In contrast, DCs injected intraperitoneally were found predominantly in peritoneal lymph nodes (pancreatic in particular), and in omentum-associated lymphoid tissue. This uneven distribution of BM-DCs, independent of the mouse strain and also observed within pancreatic lymph nodes, resulted in the uneven induction of immune response in different lymphoid tissues. These data have important implications for the design of systemic cellular therapy with DCs, and in particular underlie a previously unsuspected potential for specific treatment of diseases such as autoimmune diabetes and pancreatic cancer.
COLLECTING DUCT RENAL CELL CARCINOMA: CLINICAL STUDY OF A RARE TUMOR (2002)

Collecting duct carcinoma is a rare type of renal cell carcinoma that affects younger patients, and is associated with aggressive regional and distant spread. The clinical and pathological features of 6 patients with collecting duct carcinoma treated at a single institution are described.There were 6 patients with collecting duct carcinoma included in the University of California School of Medicine, Los Angeles, Kidney Cancer Database. Demographic, clinical, pathological and survival data were gathered.Average patient age plus or minus standard deviation was 56 +/- 11 years, and 5 of 6 had TNM stage IV disease. The average survival of these patients was 11.5 months (range 7 to 17). There was 1 patient who had TNM stage I disease and survived without evidence of disease at 5 years. Transient response to chemotherapy was seen in 1 patient.Collecting duct carcinoma is associated with poor prognosis. For the majority of patients surgical treatment will not result in a cure. Previously recommended chemotherapy and/or immunotherapy appears to have a limited role in treatment of this disease, and early detection may be the best method for prolonging patient survival.
A novel role for the mitochondrial HTRA2/OMI protease in aging (2012)

HTRA2/OMI is an ATP-independent serine protease located in the intermembrane space of the mitochondria and is thought to function as a protein quality control protease. Our previous studies showed that loss of the enzymatic activity of HTRA2 due to a Ser276Cys missense mutation in its catalytic domain is associated with early onset neurodegeneration, multiple tissue atrophy and premature lethality in homozygous htra2 (mnd2) mice, suggesting that HTRA2 is neuroprotective. To further investigate the role of HTRA2 in neuronal cell survival and the impact of its loss of function in non-neuronal tissues of adult mice, we generated transgenic htra2 (mnd2) mice expressing a neuron-targeted human HTRA2 transgene. Notably, this HTRA2 transgene rescues htra2 (mnd2) mice from early onset neurodegeneration, and other phenotypic abnormalities and prevents their early death, indicating that HTRA2 activity in neuronal mitochondria is important for neuronal cell survival. However, as the rescued htra2 (mnd2) mice grow older they exhibit specific phenotypic abnormalities indicative of premature aging. These include premature weight loss, osteoporosis, lordokyphosis, muscle atrophy, heart enlargement, increased autophagy and reduced life span. There is also a significant increase in the levels of clonally expanded mitochondrial DNA (mtDNA) deletions in their tissues. Our findings suggest that HTRA2-regulated protein quality control in the intermembrane space of mitochondria is important for the maintenance of mitochondrial homeostasis, and loss of HTRA2 activity can lead to both neurodegeneration and aging.
Varactor Diode Selection Based on Spice Simulation for Application in Discrete Nonlinear Transmission Lines (2021)

Varactor diode is a semiconductor component widely used in a telecommunication system, such as amplitude modulation, due to the capacitance variation with the voltage. When reversely polarized, the PN junction capacitance decreases with voltage, which is a nonlinear characteristic used for pulse sharpening 1 . This nonlinear capacitance behavior is also employed in nonlinear transmission lines (NLTL) to produce radiofrequency waves in the same way used with ceramic capacitors for high power applications 2 . Low power discrete nonlinear transmission lines use a net of inductors and varactors, where the latter is a nonlinear element 1 . In this work using SPICE simulation, we investigated five different commercial varactor diodes for applications in NLTLs. The first parameters observed were the nominal capacitance and the breakdown voltage. The highest capacitance variation observed was with the 1SV149 model of about 96.67% near the breakdown voltage of 9 V and the nominal capacitance of the order of 500 pF. But the better result, looking for the highest frequency oscillation generated by the NLTL, was obtained for the BB405 model, with a frequency generated along of the line of the order 100 MHz with 30 line sections and a load of 50 Ω. For BB405, the nominal capacitance was 19 pF with a variation of 90.00% near the breakdown voltage of 28 V. However, the oscillation obtained in the NLTL using the 1SV149 diode was only 12.5 MHz, using the same number of sections and load. In conclusion, simulation results show that the highest nonlinear behavior of the varactor does not mean the highest frequency oscillation generated in an NLTL. Also, it is necessary to take both the nonlinearity and initial or nominal capacitance for the project.
Publisher’s Note: Model-independent measurement ofS-waveK−π+systems usingD+→Kππdecays from Fermilab E791 [Phys. Rev. D 73, 032004 (2006)] (2006)

A model-independent partial-wave analysis of the S-wave component of the K system from decays of D + mesons to the three-body K - + + final state is described.Data come from the Fermilab E791 experiment.Amplitude measurements are made independently for ranges of K - + invariant mass, and results are obtained below 825 MeV/c 2 , where previous measurements exist only in two mass bins.This method of parametrizing a three-body decay amplitude represents a new approach to analysing such decays.Though no model is required for the S-wave, a parametrization of the relatively well-known reference P -and D-waves, optimized to describe the data used, is required.In this paper, a Breit-Wigner model is adopted to describe the resonances in these waves.The observed phase variation for the S-, P -and D-waves do not match existing measurements of I = 1 2 K - + scattering in the invariant mass range in which scattering is predominantly elastic.If the data are mostly I = 1 2 , this observation indicates that the Watson theorem, which requires these phases to have the same dependence on invariant mass, may not apply to these decays without allowing for some interaction with the other pion.The production rate of K - + from these decays, if assumed to be predominantly I = 1 2 , is also found to have a significant dependence on invariant mass in the region above 1.25 GeV/c 2 .These measurements can provide a relatively model-free basis for future attempts to determine which strange scalar amplitudes contribute to the decays.
2,4-Di-C-methyl-α-L-arabinose monohydrate (2007)

In aqueous solution, the title compound, C7H14O5·H2O, consists of a mixture of the open-chain furan­ose and pyran­ose forms; it crystallizes solely as the α-pyran­ose form. The crystal structure exists as an extensively hydrogen-bonded network, with each mol­ecule acting as a donor and acceptor for seven hydrogen bonds. The absolute configuration of this sugar is determined by the use of 2-C-methyl-d-ribono-1,4-lactone as the starting material.
Perceptually Optimised Video Compression (2015)

The Marie Skłodowska-Curie Initial Training Network on Perceptually Optimised Video Compression, called PROVISION, is a collaborative network between academic and industrial partners within the 7th Framework Programme of the European Commission. Its key aim is to deliver technical advances well beyond the capabilities of current video compression standards, focusing on human visual perception for the future of video compression. This paper gives an overview of the PROVISION project, including the challenges that motivated its creation, the related scientific work supporting the project and its main objectives. Examples of some specific research topics addressed in the context of the project are also presented.
Functionalized Nanocarriers for Enhanced Bioactive Delivery to Squamous Cell Carcinomas: Targeting Approaches and Related Biopharmaceutical Aspects (2015)

Cancer has been described as one of the major and leading causes of death worldwide. By the year 2030, it has been postulated that over 21.4 million new cases of cancer could be expected, 17 million cancer deaths yearly and a total of 75 million people will be living with cancer within five years of diagnosis. Chemotherapy is the main therapeutic intervention for treating people living with SCC. However, drug resistance has rendered it inefficient and ineffective in combating the disease even after combination chemotherapy. Many peptides and proteins have been investigated to possess biological activities that mark them as potential anti-cancer agents. Targeting peptides are conjugated with other functional peptides or nanoparticles to augment drug delivery both <i>in vitro</i> and <i>in vivo</i> assays. The current identification of tumor-homing peptides through phage display technology has opened a new strategy for targeted therapy in SCC diseases. Despite the advances in cancer nanomedicine, targeted approaches in the delivery of therapeutics for the treatment of squamous cell carcinoma related tumours have not been well established. In this review, current drugs employed in cancer nanomedicine are highlighted, possible rate limiting factors for the application of polymeric materials in cancer nanomedicine are elucidated and functionalized nano-constructs using receptor ligands and homing peptides as targeted moieties are discussed. The combinatorial strategy of attaching both homing peptides and receptor ligands as dual moieties on nano-cargos should further strengthen the advantages of each technology in cancer targeted therapy.
Using bioluminescence resonance energy transfer (BRET) and super-resolution microscopy to investigate complex formation between VEGFR2, its co-receptor Neuropilin-1 and G protein coupled receptors (2018)

Background:
A Case Study on Condenser Water Supply Temperature Optimization with a District Cooling Plant (2021)

District cooling (DC) continues to proliferate due to increasing global cooling demands and economies of scale benefits; however, most district-scale modeling has focused on heating, and to the best of our knowledge, researchers have yet to model cooling plants featuring waterside economizers in DC settings. With the popular Modelica Buildings library expanding its capabilities to district scale, this study is one of the first to demonstrate how the open-source models can be used for detailed energy and control analysis of a DC plant. For a real-world case study, we developed and calibrated high-fidelity models for a DC system central plant at a college campus in Colorado, USA, and we optimized the condenser water supply temperature (CWST) setpoint for a DC plant across multiple time horizons using the Optimization library in Dymola. Results indicate that annual CWST optimization saves 4.7% annual plant energy, with less than 1% of additional energy savings gained through daily optimization. This confirms previous studies' findings that high frequency CWST optimizations are not necessary for the studied system.
Optimization of the synthesis of N-alkyl and N,N-dialkyl thioureas from waste water containing ammonium thiocyanate (2015)

The optimized methods for N-alkyl and N,N-dialkyl substituted thioureas synthesis starting from ammonium thiocyanates, waste water constituent from the production of tetramethylthiuram monosulfide (TMTS), and alkyl amine, are presented in this work. Therefore, thioureas synthesis was developed in two ways: Method I - reaction of the thiocyanate and alkylamine in the presence of hydrochloric acid; Method II - reaction of the thiocyanate with benzoyl chloride following by amine addition in the first step, and base hydrolysis in the second step. The structure of the synthesized compounds was confirmed by IR, 1H and 13C NMR and MS instrumental methods, and purity was determined by high-performance liquid chromatography method. It is shown that the proposed methods offer a high degree of conversion and purity of product, absence of by-products and technological applicability at industrial scale. Considering importance of the tetramethylthiuram disulfide (TMTD) and TMTS as vulcanization accelerators as well as thiourea as the pharmacologically active compounds, it can be said that application of the optimized methods of thiourea synthesis will provide significant improvement in sustainable development and implementation of eco-friendly production technology. The described, environmentally benign process of thioureas synthesis, represent a suitable option to existing methods.
Facile Strategy Enabling Both High Loading and High Release Amounts of the Water-Insoluble Drug Clofazimine Using Mesoporous Silica Nanoparticles (2018)

The use of nanocarriers to deliver poorly soluble drugs to the sites of diseases is an attractive and general method, and mesoporous silica nanoparticles (MSNs) are increasingly being used as carriers. However, both loading a large amount of drugs into the pores and still being able to release the drug is a challenge. In this paper, we demonstrate a general strategy based on a companion molecule that chaperones the drug into the pores and also aids it in escaping. A common related strategy is to use a miscible co-solvent dimethyl sulfoxide (DMSO), but although loading may be efficient in DMSO, this co-solvent frequently diffuses into an aqueous environment, leaving the drug behind. We demonstrate the method by using acetophenone (AP), an FDA-approved food additive as the chaperone for clofazimine (CFZ), a water-insoluble antibiotic used to treat leprosy and multidrug-resistant tuberculosis. AP enables a high amount of CFZ cargo into the MSNs and also carries CFZ cargo out from the MSNs effectively when they are in an aqueous biorelevant environment. The amount of loading and the CFZ release efficiency from MSNs were optimized; 4.5 times more CFZ was loaded in MSNs with AP than that with DMSO and 2300 times more CFZ was released than that without the assistance of the AP. In vitro treatment of macrophages infected by Mycobacterium tuberculosis with the optimized CFZ-loaded MSNs killed the bacteria in the cells in a dose-dependent manner. These studies demonstrate a highly efficient method for loading nanoparticles with water-insoluble drug molecules and the efficacy of the nanoparticles in delivering drugs into eukaryotic cells in aqueous media.
A new method for protection against electrical overheating using a sacrificial coating and a CHEMFET gas sensor (1986)

Sacrificial coatings have been examined as a means of detecting overheating in an electronics cabinet. This method makes use of a special paint which, when it is heated, will liberate ammonia as a warning gas, and a Pt gate metal oxide semiconductor field effect transistor (MOSFET) device to detect the gas. Three ammonia emitting paints, based on urea, ammonium phosphate and glycine, have been examined at 140, 160 and 265 degrees C respectively. The urea-containing paint did not show any noticeable loss of ammonia activity after 18 months storage under ambient conditions. The urea-containing paint/Pt gate MOSFET combination has been evaluated in an electronics cabinet; it was possible to detect the overheating of a resistor, having a 0.025 mm thick spray coat of the paint, at temperatures as low as 100 degrees C.
ChemInform Abstract: Properties, Preparation and Synthetic Uses of Amine N‐Oxides. An Update (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Regulation of T cell dependent immune responses by TIM family members (2005)

The T cell immunoglobulin mucin (TIM) proteins are type I membrane glycoproteins expressed on T cells and containing common structural motifs. While our understanding on the distribution and functions of TIM family members is still incomplete, data from several recent reports indicate that these proteins, together with T cell receptor and costimulatory signals, regulate the expansion and effector functions of T helper cells. In the current review, we provide evidences indicating that TIM-3 is capable of modulating the function of CD4(+)CD25(+) regulatory T cells and inhibiting aggressive Th1 mediated auto- and allo-immune responses. Similarly, additional data suggest that TIM-2 molecules function by negatively regulating Th2 immune responses. In contrast, TIM-1 appears to be an activation molecule for all T cells, although the mechanisms through which TIM-1 activates T cells remain to be elicited.
Efficient green-light generation from waveguide crystal (2008)

Data are presented of efficient single-pass green-light second-harmonic generation from a periodically-poled LiNbO3 waveguide crystal. Over 220 mW maximum green light output power with an optical-to-optical conversion efficiency of over 70% is measured. Green-induced infrared absorption is indicated to be the major absorption loss in this waveguide. A simple analytic expression is derived and used to estimate the crystal waveguide absorption coefficient, which was found to be 7×10−3 cm−1.
From the bench to clinical practice: understanding the challenges and uncertainties in immunogenicity testing for biopharmaceuticals (2015)

Unlike conventional chemical drugs where immunogenicity typically does not occur, the development of anti-drug antibodies following treatment with biologics has led to concerns about their impact on clinical safety and efficacy. Hence the elucidation of the immunogenicity of biologics is required for drug approval by health regulatory authorities worldwide. Published ADA 'incidence' rates can vary greatly between same-class products and different patient populations. Such differences are due to disparate bioanalytical methods and interpretation approaches, as well as a plethora of product-specific and patient-specific factors that are not fully understood. Therefore, the incidence of ADA and their association with clinical consequences cannot be generalized across products. In this context, the intent of this review article is to discuss the complex nature of ADA and key nuances of the methodologies used for immunogenicity assessments, and to dispel some fallacies and myths.