gebhart/patrepeval huggingface dataset:
PD-1/PD-L1 Based Combinational Cancer Therapy: Icing on the Cake (2020)

Cancer has been a major global health problem due to its high morbidity and mortality. While many chemotherapy agents have been studied and applied in clinical trials or in clinic, their application is limited due to its toxic side effects and poor tolerability. Monoclonal antibodies specific to the PD-1 and PD-L1 immune checkpoints have been approved for the treatment of various tumors. However, the application of PD-1/PD-L1 inhibitors remains suboptimal and thus another strategy comes in to our sight involving the combination of checkpoint inhibitors with other agents, enhancing the therapeutic efficacy. Various novel promising approaches are now in clinical trials, just as icing on the cake. This review summarizes relevant investigations on combinatorial therapeutics based on PD-1/PD-L1 inhibition.
<i>Yersinia enterocolitica</i> infection in children (1985)

The role of Yersinia enterocolitica as a human pathogen has been documented in publications from over 30 countries, and Y. enterocolitica has been recognized increasingly to cause gastrointestinal disease in children. In 1979, an Australian survey yielded only three isolates of Y. enterocolitica from 3298 faecal specimens obtained from adults. We screened all stool specimens received during a 22-month period for Yersinia by means of a recently developed selective agar medium. Y. enterocolitica was isolated from 32 of 4136 (0.7%) specimens. Most isolates were of serotype O:3, biotype 4. During the study, 154 Salmonella spp. (3.7%), 196 Campylobacter spp. (47%), seven Shigella spp. (0.2%) and 27 Aeromonas spp. (0.9% of 2779) were recovered. Children infected with Y. enterocolitica presented with acute diarrhoea associated with fever and pharyngitis; chronic or recurrent diarrhoea; or pain in the right iliac fossa associated with mesenteric adenitis. Gastrointestinal symptoms usually resolved spontaneously within two weeks. However, some children were treated successfully with cotrimoxazole.
Generalizing motion edits with Gaussian processes (2009)

One way that artists create compelling character animations is by manipulating details of a character's motion. This process is expensive and repetitive. We show that we can make such motion editing more efficient by generalizing the edits an animator makes on short sequences of motion to other sequences. Our method predicts frames for the motion using Gaussian process models of kinematics and dynamics. These estimates are combined with probabilistic inference. Our method can be used to propagate edits from examples to an entire sequence for an existing character, and it can also be used to map a motion from a control character to a very different target character. The technique shows good generalization. For example, we show that an estimator, learned from a few seconds of edited example animation using our methods, generalizes well enough to edit minutes of character animation in a high-quality fashion. Learning is interactive: An animator who wants to improve the output can provide small, correcting examples and the system will produce improved estimates of motion. We make this interactive learning process efficient and natural with a fast, full-body IK system with novel features. Finally, we present data from interviews with professional character animators that indicate that generalizing and propagating animator edits can save artists significant time and work.
Self-Reporting Degradable Fluorescent Grafted Copolymer Micelles Derived from Biorenewable Resources (2015)

A series of hydrolytically degradable fluorescent poly(ferulic acid-<i>co</i>-tyrosine)-<i>g</i>-<i>m</i>PEG graft copolymers were synthesized and shown to undergo self-assembly in aqueous media to yield fluorescent micelles. The polymers and their micellar assemblies exhibited greater fluorescence emission intensity than did their small molecular building blocks, which provides a self-reporting character that has potential for monitoring the polymer integrity and also for performing in theranostics applications. The amphiphilic <i>graft</i>-copolymers were synthesized by Cu-assisted azide-alkyne "click" addition of azido-functionalized <i>m</i>PEG polymers onto fluorescent degradable hydrophobic copolymers displaying randomly distributed alkyne side-chain groups along their biorenewably derived poly(ferulic acid-<i>co</i>-tyrosine) backbones. The morphologies and photophysical properties of the supramolecular assemblies generated in aqueous solutions were evaluated by DLS, TEM, AFM, and steady-state optical spectroscopies. The 15-30 nm sized micelles behaved as broad-band emitters in the 350-600 nm range, which highlights their potential as self-reporting nanomaterials for in vitro studies.
Studies on Thermal Stability and Fluid Property of PVC Filled with Hydrotalcite (2002)

Hydrotalcite can act as a co-stabilizer with other main stabilizer for poly(vinyl chloride)(PVC). The thermal stability and fluid property of PVC filled with hydrotalcite surface-treated with titanate and silane were studied in this work. Organic Sn is a main stabilizer and hydrotalcite is a stabilizing assistant. The stability of the PVC resin mixed with organic Sn and hydrotalcite is better than that of the PVC resin mixed with organic Sn alone. It is shown that the PVC resin filled with hydrotalcite possesses a better static and dynamic heat stability. Moreover, hydrotalcite can improve the fluid property of PVC, which is advantageous to the processing of PVC, and the optimum content of hydrotalcite is about 1%-2%(mass fraction).
An Instrument for the Measurement of Heat Flux from a Surface with Uniform Temperature (1980)

Technical Briefs An Instrument for the Measurement of Heat Flux from a Surface with Uniform Temperature J. S. Kraabel, J. S. Kraabel Sandia Laboratories, Livermore, Calif. Search for other works by this author on: This Site PubMed Google Scholar J. W. Baughn, J. W. Baughn Department of Mechanical Engineering, University of California, Davis, Calif. 95616 Search for other works by this author on: This Site PubMed Google Scholar A. A. McKillop A. A. McKillop Department of Mechanical Engineering, University of California, Davis, Calif. 95616 Search for other works by this author on: This Site PubMed Google Scholar Author and Article Information J. S. Kraabel Sandia Laboratories, Livermore, Calif. J. W. Baughn Department of Mechanical Engineering, University of California, Davis, Calif. 95616 A. A. McKillop Department of Mechanical Engineering, University of California, Davis, Calif. 95616 J. Heat Transfer. Aug 1980, 102(3): 576-578 (3 pages) https://doi.org/10.1115/1.3244346 Published Online: August 1, 1980 Article history Received: May 2, 1979 Online: October 20, 2009
Molecular epidemiological studies of human herpesvirus 6 in families (1994)

The mode of transmission of human herpesvirus 6 (HHV-6) was investigated by molecular epidemiological techniques in four families. HHV-6 was isolated from the peripheral blood of seven infants with exanthem subitum, including siblings, and from the saliva of two mothers. These isolates were examined for genetic relatedness by means of restriction enzymes analysis of purified DNA. While the profiles of the digestion patterns differed among families, they were very similar in a particular family. These results may suggest that HHV-6 is transmitted primarily from mother to child.
Steady-state current-voltage relationship of the Na/K pump in guinea pig ventricular myocytes. (1989)

Whole-cell currents were recorded in guinea pig ventricular myocytes at approximately 36 degrees C before, during, and after exposure to maximally effective concentrations of strophanthidin, a cardiotonic steroid and specific inhibitor of the Na/K pump. Wide-tipped pipettes, in combination with a device for exchanging the solution inside the pipette, afforded reasonable control of the ionic composition of the intracellular solution and of the membrane potential. Internal and external solutions were designed to minimize channel currents and Na/Ca exchange current while sustaining vigorous forward Na/K transport, monitored as strophanthidin-sensitive current. 100-ms voltage pulses from the -40 mV holding potential were used to determine steady-state levels of membrane current between -140 and +60 mV. Control experiments demonstrated that if the Na/K pump cycle were first arrested, e.g., by withdrawal of external K, or of both internal and external Na, then neither strophanthidin nor its vehicle, dimethylsulfoxide, had any discernible effect on steady-state membrane current. Further controls showed that, with the Na/K pump inhibited by strophanthidin, membrane current was insensitive to changes of external [K] between 5.4 and 0 mM and was little altered by changing the pipette [Na] from 0 to 50 mM. Strophanthidin-sensitive current therefore closely approximated Na/K pump current, and was virtually free of contamination by current components altered by the changes in extracellular [K] and intracellular [Na] expected to accompany pump inhibition. The steady-state Na/K pump current-voltage (I-V) relationship, with the pump strongly activated by 5.4 mM external K and 50 mM internal Na (and 10 mM ATP), was sigmoid in shape with a steep positive slope between about 0 and -100 mV, a less steep slope at more negative potentials, and an extremely shallow slope at positive potentials; no region of negative slope was found. That shape of I-V relationship can be generated by a two-state cycle with one pair of voltage-sensitive rate constants and one pair of voltage-insensitive rate constants: such a two-state scheme is a valid steady-state representation of a multi-state cycle that includes only a single voltage-sensitive step.
Molecular magnetic resonance imaging with targeted contrast agents (2003)

Magnetic resonance imaging (MRI) produces high-resolution three-dimensional maps delineating morphological features of the specimen. Differential contrast in soft tissues depends on endogenous differences in water content, relaxation times, and/or diffusion characteristics of the tissue of interest. The specificity of MRI can be further increased by exogenous contrast agents (CA) such as gadolinium chelates, which have been successfully used for imaging of hemodynamic parameters including blood perfusion and vascular permeability. Development of targeted MR CA directed to specific molecular entities could dramatically expand the range of MR applications by combining the noninvasiveness and high spatial resolution of MRI with specific localization of molecular targets. However, due to the intrinsically low sensitivity of MRI (in comparison with nuclear imaging), high local concentrations of the CA at the target site are required to generate detectable MR contrast. To meet these requirements, the MR targeted CA should recognize targeted cells with high affinity and specificity. They should also be characterized by high relaxivity, which for a wide variety of CA depends on the number of contrast-generating groups per single molecule of the agent. We will review different designs and applications of targeted MR CA and will discuss feasibility of these approaches for in vivo MRI.
Gender effects on age-related changes in brain structure. (2000)

The effect of gender on brain atrophy with aging varied in different subregions of the brain. There was more brain atrophy with aging in male subjects than in female subjects.
Human caspase-4 mediates noncanonical inflammasome activation against gram-negative bacterial pathogens (2015)

Inflammasomes are critical for host defense against bacterial pathogens. In murine macrophages infected by gram-negative bacteria, the canonical inflammasome activates caspase-1 to mediate pyroptotic cell death and release of IL-1 family cytokines. Additionally, a noncanonical inflammasome controlled by caspase-11 induces cell death and IL-1 release. However, humans do not encode caspase-11. Instead, humans encode two putative orthologs: caspase-4 and caspase-5. Whether either ortholog functions similar to caspase-11 is poorly defined. Therefore, we sought to define the inflammatory caspases in primary human macrophages that regulate inflammasome responses to gram-negative bacteria. We find that human macrophages activate inflammasomes specifically in response to diverse gram-negative bacterial pathogens that introduce bacterial products into the host cytosol using specialized secretion systems. In primary human macrophages, IL-1β secretion requires the caspase-1 inflammasome, whereas IL-1α release and cell death are caspase-1-independent. Instead, caspase-4 mediates IL-1α release and cell death. Our findings implicate human caspase-4 as a critical regulator of noncanonical inflammasome activation that initiates defense against bacterial pathogens in primary human macrophages.
Novel Drug Delivery Systems Fighting Glaucoma: Formulation Obstacles and Solutions (2020)

Glaucoma is considered to be one of the biggest health problems in the world. It is the main cause of preventable blindness due to its asymptomatic nature in the early stages on the one hand and patients' non-adherence on the other. There are several approaches in glaucoma treatment, whereby this has to be individually designed for each patient. The first-line treatment is medication therapy. However, taking into account numerous disadvantages of conventional ophthalmic dosage forms, intensive work has been carried out on the development of novel drug delivery systems for glaucoma. This review aims to provide an overview of formulation solutions and strategies in the development of in situ gel systems, nanosystems, ocular inserts, contact lenses, collagen corneal shields, ocular implants, microneedles, and iontophoretic devices. The results of studies confirming the effectiveness of the aforementioned drug delivery systems were also briefly presented.
Ischemic Cardiomyopathy and Heart Failure After Acute Myocardial Infarction (2022)

Novel therapeutic approaches, such as mechanical unloading and modulation of the inflammatory response, appear to be promising. Furthermore, the understanding of the mechanisms by which, despite optimal treatment, heart failure ensues after AMI, with or without adverse remodeling and systolic dysfunction, is a critical step in the search for novel ways to tackle heart failure risk beyond preservation of left ventricular volumes and systolic function. In this review article, we explore the principal pathophysiological mechanisms and pathways of heart failure in ischemic cardiomyopathy, therapeutic opportunities, and knowledge gaps in this area.
'Core-shell' Cathode Materials for Lithium-ion Batteries Prepared via Mechanochemical Route (2009)

Solid state mechanical activation method was applied for surface modification of LiCoO2 by simple oxides (Al2O3, TiO2, MgO and Li2O•2B2O3) and of LiMn2O4 by LiMO2 (M=Co, Ni). Pristine materials were ground with correspondent precursors and then heat treated at different temperatures. As prepared materials were studied by XRD, 6,7Li and 27Al MAS NMR spectroscopy, XPS, SEM and electrochemical tests. It has been shown that electrochemical properties of coated cathodes strongly depend on the composition and the thickness of coating layer.
A Noncommunication Adaptive Single-Pole Autoreclosure Scheme Based on the ACUSUM Algorithm (2013)

In this paper, a new noncommunication-based adaptive single-pole autoreclosure (ASPAR) scheme is proposed, by which the extinction of secondary arc can be detected rapidly, in 4 ms. The proposed algorithm applies the adaptive cumulative sum method (ACUSUM) to a local bus voltage signal in order to reveal the occurrence of three successive events during a fault, that is, fault inception, circuit breaker (CB) opening (primary arc extinction), and secondary arc extinction; while detection of the last event can lead to CB reclosing. According to the fact that the two first events result in abrupt decreases in local voltage amplitude and the third one imposes an abrupt increase, this sequence of changes in voltage amplitude distinguishes temporary faults. To evaluate the robustness of the proposed scheme against transient faults, the results of investigations on different conditions, including fault location, amount of load, power-flow direction, and short-circuit levels of local and remote buses are presented; where, in all cases, the highest reliability has been achieved.
Simple Face-detection Algorithm Based on Minimum Facial Features (2007)

This article presents a algorithm for rapid and accurate face-detection. The algorithm detects human faces by the geometric correlations between locations of faces and hairs. Ranges of skin color are used to figure out possible face regions so as to initially localize the faces; furthermore, probable hair blocks in an image are determined by means of hair color spectrums. Grouped skin and hair blocks decide candidate face areas in light of the geometric relation. The accuracy of the single-face detection is higher than 92% with the frame-rate of 10 fps, if tested with a simple background and sufficient light source. The algorithm can be transferred from a PC to embedded devices, such as a DSP platform. This system-level implementing ability brings great potential to customized and reusable applications as well as miniature systems.
Ultrasmall Superparamagnetic Particles of Iron Oxide in Patients With Acute Myocardial Infarction (2012)

Following acute MI, uptake of ultrasmall superparamagnetic particles of iron oxide occurs with the infarcted and remote myocardium. This technique holds major promise as a potential method for assessing cellular myocardial inflammation and left ventricular remodelling, which may have a range of applications in patients with MI and other inflammatory cardiac conditions.
Optical MMSE gear-shifting algorithm for the fast synchronization of DPLL (2002)

Since most digital phase-locked loops (DPLLs) used in digital data transmission receivers require fast acquisition of input frequency and phase in the beginning and substantial jitter reduction in the steady-state, the DPLL loop bandwidth should be adjusted accordingly. An optimal gear-shifting algorithm which allows very fast acquisition time is presented. This algorithm suggests a sequence of control parameters which achieves the fastest initial acquisition time by trying to minimize the jitter variance (minimum mean squared error: MMSE) in any given time instance. The algorithm can be used for carrier recovery or clock recovery in data modems, local area networks and disk drives that require a very short initial preamble period.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Fiber-chip edge coupler with large mode size for silicon photonic wire waveguides (2016)

Fiber-chip edge couplers are extensively used in integrated optics for coupling of light between planar waveguide circuits and optical fibers. In this work, we report on a new fiber-chip edge coupler concept with large mode size for silicon photonic wire waveguides. The coupler allows direct coupling with conventional cleaved optical fibers with large mode size while circumventing the need for lensed fibers. The coupler is designed for 220 nm silicon-on-insulator (SOI) platform. It exhibits an overall coupling efficiency exceeding 90%, as independently confirmed by 3D Finite-Difference Time-Domain (FDTD) and fully vectorial 3D Eigenmode Expansion (EME) calculations. We present two specific coupler designs, namely for a high numerical aperture single mode optical fiber with 6 µm mode field diameter (MFD) and a standard SMF-28 fiber with 10.4 µm MFD. An important advantage of our coupler concept is the ability to expand the mode at the chip edge without leading to high substrate leakage losses through buried oxide (BOX), which in our design is set to 3 µm. This remarkable feature is achieved by implementing in the SiO<sub>2</sub> upper cladding thin high-index Si<sub>3</sub>N<sub>4</sub> layers. The Si<sub>3</sub>N<sub>4</sub> layers increase the effective refractive index of the upper cladding near the facet. The index is controlled along the taper by subwavelength refractive index engineering to facilitate adiabatic mode transformation to the silicon wire waveguide while the Si-wire waveguide is inversely tapered along the coupler. The mode overlap optimization at the chip facet is carried out with a full vectorial mode solver. The mode transformation along the coupler is studied using 3D-FDTD simulations and with fully-vectorial 3D-EME calculations. The couplers are optimized for operating with transverse electric (TE) polarization and the operating wavelength is centered at 1.55 µm.
Definitive human and mouse hematopoiesis originates from the embryonic endothelium: a new class of HSCs based on VE-cadherin expression (2010)

Hematopoietic stem cells (HSCs) arise first in the third week of human ontogeny inside yolk sac developing blood vessels, and independently, from the wall of the embryonic aorta and vitelline arteries one week later. HSCs produced in the yolk sac and in the embryonic truncal arteries migrate to and transiently colonize the embryonic liver (EL), and thereafter the bone marrow (BM), their permanent site of residence. At the moment, the origin of human HSCs is still controversial; one of the main hypotheses being that they are generated by hemogenic endothelial cells (ECs). To prove definitively the endothelial origin of HSCs that arise within the human embryo, we previously purified ECs from either the yolk sac or the truncal arteries and reported that they were able to produce blood cells in vitro. We then found that some of the HSCs present in the human EL were co-expressing vascular endothelial (VE)-cadherin, an endothelial marker, CD45, a pan-hematopoietic marker, and CD34, a common endothelial and hematopoietic marker, and demonstrated that these HSCs bearing a dual hemato-endothelial phenotype were endowed with remarkably high self renewal and proliferative potentials. Furthermore, a transgenic mouse model based on the VE-cadherin cis-regulating elements that we engineered to trace the fate of the first VE-cadherin expressing cells allowed us to clearly demonstrate that a majority of adult BM HSCs derived from a VE-cadherin ancestor. Altogether our studies strongly suggest that at least a part of both the human and the murine hematopoietic systems arise from an endothelium-like ancestor.
Distinct gene-specific mechanisms of arrhythmia revealed by cardiac gene transfer of two long QT disease genes, <i>HERG</i> and <i>KCNE1</i> (2001)

The long QT syndrome (LQTS) is a heritable disorder that predisposes to sudden cardiac death. LQTS is caused by mutations in ion channel genes including HERG and KCNE1, but the precise mechanisms remain unclear. To clarify this situation we injected adenoviral vectors expressing wild-type or LQT mutants of HERG and KCNE1 into guinea pig myocardium. End points at 48-72 h included electrophysiology in isolated myocytes and electrocardiography in vivo. HERG increased the rapid component, I(Kr), of the delayed rectifier current, thereby accelerating repolarization, increasing refractoriness, and diminishing beat-to-beat action potential variability. Conversely, HERG-G628S suppressed I(Kr) without significantly delaying repolarization. Nevertheless, HERG-G628S abbreviated refractoriness and increased beat-to-beat variability, leading to early afterdepolarizations (EADs). KCNE1 increased the slow component of the delayed rectifier, I(Ks), without clear phenotypic sequelae. In contrast, KCNE1-D76N suppressed I(Ks) and markedly slowed repolarization, leading to frequent EADs and electrocardiographic QT prolongation. Thus, the two genes predispose to sudden death by distinct mechanisms: the KCNE1 mutant flagrantly undermines cardiac repolarization, and HERG-G628S subtly facilitates the genesis and propagation of premature beats. Our ability to produce electrocardiographic long QT in vivo with a clinical KCNE1 mutation demonstrates the utility of somatic gene transfer in creating genotype-specific disease models.