gebhart/patrepeval huggingface dataset:
C-C chemokines differentially alter interleukin-4 production from lymphocytes. (1997)

The expression of cytokines can dictate the intensity, chronicity, and type of immune/inflammatory response that is produced. These events may be regulated by accumulation of particular cell populations at a site of immune response that can be regulated by the expression of specific chemokines. Recent data have indicated that chemokines also have direct effects on cellular activation. In particular, T lymphocyte responses have been divided into two distinct phenotypes, designated by TH1- and TH2-type cytokine expression. Although it is recognized that divergent T-lymphocyte-derived cytokine phenotypes exist, the mechanisms that dictate the expression of these cytokines and ultimately the division of these immune responses is not entirely clear. In the present study, we present data that the C-C chemokine family members may be a factor influencing the direction of T-cell-derived lymphokine production. To elucidate the role of C-C chemokines, MIP-1 alpha and MCP-1, we have used both antigen-specific (schistosomal egg antigen (SEA)) and nonspecific (conconavalin (Con) A) stimuli. Using TH2-type lymphocyte populations from SEA-sensitized mice, a significant increase in IL-4 mRNA expression and protein production was observed when MCP-1 was added to the culture. Conversely, MIP-1 alpha treatment appeared to decrease interleukin (IL)-4 production. Interestingly, the proliferative response in the TH2-type (SEA-specific) response was up-regulated by MIP-1 alpha whereas MCP-1 down-regulated the response, inversely correlating with IL-4 production. Primary stimulation of naive lymphocytes with Con A induces a predominant interferon (IFN)-gamma response, whereas the second stimulation of the same lymphocytes with Con A induces both IFN-gamma and IL-4. When the two C-C chemokines were individually co-incubated with Con-A-stimulated lymphocytes, both up-regulated IFN-gamma production and proliferation during the primary stimulation. Similarly, in the secondary response, both chemokines further upregulated IFN-gamma production; however, only MCP-1 co-stimulation increased IL-4 production, whereas MIP-1 alpha significantly decreased IL-4 production in these same cell populations. These results were also reflected in steady-state levels of mRNA expression. These results suggest that the production of C-C chemokines (MCP-1 or MIP-1 alpha) during an immune response may aid in determining the type of cytokines produced and the level of lymphocyte activation during a particular response.
Structural aspects of activation pathways of aspartic protease zymogens and viral 3C protease precursors (1999)

The three-dimensional structures of the inactive protein precursors (zymogens) of the serine, cysteine, aspartic, and metalloprotease classes of proteolytic enzymes are known. Comparisons of these structures with those of the mature, active proteases reveal that, in general, the preformed, active conformations of the residues involved in catalysis are rendered sterically inaccessible to substrates by the residues of the zymogens' N-terminal extensions or prosegments. The prosegments interact in nonsubstrate-like fashions with the residues of the active sites in most of the cases. The gastric aspartic proteases have a well-characterized zymogen conversion pathway. Structures of human progastricsin, the inactive intermediate 2, and active human pepsin are known and have been used to define the conversion pathway. The structure of the zymogen precursor of plasmepsin II, the malarial aspartic protease, shows a new twist on the mode of inactivation used by the gastric zymogens. The prosegment of proplasmepsin disrupts the active conformation of the two catalytic aspartic acid residues by inducing a major reorientation of the two domains of the mature protease. The picornaviral 2A and 3C proteases have a chymotrypsin-like tertiary structure but with a cysteine nucleophile. These enzymes cleave themselves from the viral polyprotein in cis (intramolecular cleavage) and carry out trans cleavages of other scissile peptides important for the virus life cycle. Although the structure of the precursor viral polyprotein is unknown, it probably resembles the organization of the proenzymes of the bacterial serine proteases, subtilisin, and alpha-lytic protease. Cleavage of the prosegment is known to occur in cis for these precursor molecules.
Vasorelaxing Alkaloids and Flavonoids fromCassytha filiformis (2008)

Two new aporphine alkaloids, isofiliformine ( 1) and cassythic acid ( 3), along with 22 known compounds were isolated from whole herb of Cassytha filiformis. Cassythic acid ( 3), cassythine ( 4), neolitsine ( 7), and dicentrine ( 8) had potent vasorelaxing effects on precontracted rat aortic preparations with mean IC 50 values between 0.08 and 2.48 microM. Compounds 1, 1,2-methylenedioxy-3,10,11-trimethoxyaporphine ( 2), (-)- O-methylflavinatine ( 10), (-)-salutaridine ( 11), isohamnetin-3- O-beta-glucoside, and isohamnetin-3- O-rutinoside exerted moderate vessel-relaxing activities with IC 50 values from 16.50 to 32.81 microM at the test concentrations.
<title>High-efficiency coupling for high-aspect-ratio laser diodes</title> (1996)

A method of improving the coupling efficiency of an elliptical light beam into an optical fiber is achieved with a novel cylindrical concave microlens. Coupling efficiencies of 87% from single transverse mode diode lasers into single-mode optical fiber have been achieved with this microlens when used in conjunction with a pair of bulk optic asphere lenses. The microlens is amenable to production processes, is effective for a wide range of beam aspect ratios and represents a significant improvement over the 60 - 65% coupling efficiency which is typical of volume fiber coupling techniques to date.
Abstract 4573: STINGVAX - A novel tumor vaccine with cyclic dinucleotides - can induce potent anti-tumor responses in vivo. (2013)

Abstract Cyclic dinucleotides (CDN) are ubiquitous bacterial intracellular messengers, and they have recently been shown to also function as a pathogen associated molecular pattern (PAMP) molecules that are sensed by eukaryotic host Stimulator of Interferon Genes (STING) that can activate the TBK-1/IRF-3 signaling pathway to induce type I interferon and other co-regulated genes. CDN was found to induce STING dependent augmentation of T-cell priming in multiple vaccination models, potentially by activating dendritic cells. We formulated CDN with a GM-CSF secreting tumor cell vaccine (STINGVAX) to mobilize and as well as activate dendritic cells both in vitro and in vivo. STINGVAX was tested in a stringent B16 melanoma treatment model, and we demonstrated significant reduction of tumor growth rate in vivo. STINGVAX's anti-tumor response was correlated with increased tumor infiltrating CD8 T-cells as well as increased number of p15E tumor-specific cytotoxic T-cells. STINGVAX's in vivo anti-tumor response was T-cell dependent as well as STING dependent. When we combined STINGVAX with multiple TLR 4/7/8 agonists signaling through the MyD88/TRIF pathway that is distinct from CDN/STING/TBK-1 signaling treatment of palpable B16 tumor resulted in regression of 30-60% of these non-immunogenic tumors. When the STINGVAX treated tumor microenvironment was examined, both IFNγ+CD8+ and PD-L1 was upregulated, potentially demonstrating an adaptive immune resistance mechanism which would render STINGVAX an excellent candidate to be combined with anti-PD-1 blockade. Cumulatively, STINGVAX is a novel tumor vaccine with a high potential for translation in clinical oncology. Citation Format: Thomas W. Dubensky, Meredith L. Leong, David B. Kanne, Edward E. Lemmens, Ken Metchette, Weiqun Liu, Marcella Fasso, Juan Fu, Joshua J. Woodward, Drew Pardoll, Daniel A. Portnoy, Young J. Kim. STINGVAX - A novel tumor vaccine with cyclic dinucleotides - can induce potent anti-tumor responses in vivo. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4573. doi:10.1158/1538-7445.AM2013-4573
Phenylamino‐Pyrimidine (PAP) Derivatives: A New Class of Potent and Selective Inhibitors of Protein Kinase C (PKC) (1996)

Phenylamino-pyrimidines represent a novel class of inhibitors of the protein kinase C with a high degree of selectivity versus other serine/threonine and tyrosine kinases. Steady state kinetic analysis of N-(3-[1-imidazolyl]-phenyl-4-(3-pyridyl)-2-pyrimidinamine (5), which showed potent inhibitory activity, revealed competitive kinetics relative to ATP. The adjacent H-bond acceptor of the pyrimidine moiety next to an H-bond donor of the phenylamine was found to be crucial for inhibitory activity. N-(3-Nitro-phenyl)-4-(3-pyridyl)-2-pyrimidinamine (7) preferentially inhibited PKC-alpha (IC50 = 0.79 microM) and not the other subtypes tested. The inhibition constants of PKC-alpha and the antiproliferative effect on T24 human bladder carcinoma cells showed a qualitative correlation, although with some exceptions.
Development of Extrauterine Fetal Incubation System Using Extracorporeal Membrane Oxygenator (1987)

Despite the recent progress in perinatal medicine, it is still difficult to manage the extremely immature newborn. A new extrauterine incubation system has been developed using 14 goat fetuses. The goat fetus is surrounded by artificial amniotic fluid and is connected to an extracorporeal membrane oxygenator. The blood is drained from the umbilical arteries and returned to the umbilical vein. The perfused blood is recirculated and ventilated with a mixture of O2, N2, and CO2 gases to obtain a PO2 of 30-35 mm Hg and a PCO2 of 30-35 mm Hg in the umbilical venous blood. Fetal heart rate, blood pressure, electroencephalogram, and several movement parameters are continuously recorded by the polygraph. With this system, the fetuses can be kept under fairly stable physiological conditions for periods up to 165 h. This improved system might therefore become a useful method to manage the ill fetuses and newborns.
Neural network design considerations for EEG spike detection (2003)

Neural networks are being used to analyze electroencephalogram (EEG) signals for the detection of epileptiform spikes. A review is presented of the design considerations involved in implementing a real-time spike detection system. Issues addressed are generally in two areas. The first is the characterization of the source data. For example, decisions must be made relative to data rates, the number of data channels and whether to use raw data, or preprocessed data in the form of spike parameters. The second is the selection of the neural network architecture and the specific implementation of that architecture. For example, choices must be made between supervised and unsupervised learning schemes, and among the many available network learning algorithms. A discussion is presented of interim results in an EEG spike detection project, the goal of which is to provide real-time spike detection capability for a multibed epilepsy monitoring unit.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
New Feedback Control System for Overhead Cranes (1987)

An overview of several commercially available methods of crane control is given. A new feedback control system is then presented which offers some advantages over these systems, including the protection of the load and workers during a collision. The control system is suitable for cranes with DC or variable speed AC drives.
Toughness enhancements in poly(methyl methacrylate) by addition of oriented multiwall carbon nanotubes (2004)

Abstract The mechanical properties of multiwall carbon nanotube (MWNT)/poly(methyl methacrylate) (PMMA) nanocomposites were studied as a function of nanotube orientation, length, concentration, and type. Orientation and dispersion were assessed by electron microscopy. A processing parameter study revealed the robust nature of fabricating nanotube/PMMA nanocomposites. An optimal set of extrusion conditions was found for minimizing the aggregate size in single‐wall carbon nanotube (SWNT)/PMMA nanocomposites; this set was also used for the fabrication of the MWNT/PMMA composites. Good dispersion was achieved for MWNTs in PMMA at 0.1–10 wt % loading levels (with the best dispersions at the lower loading levels). The orientation of MWNTs in PMMA proved to be the only way to substantially toughen the nanocomposite. A level of 1 wt % MWNTs in PMMA (oriented nanocomposite) exhibited the largest increase in tensile toughness with a 170% improvement over oriented PMMA. Increases in the modulus and yield strength were not nearly as pronounced (and occurred only at the highest loading of MWNTs, which was 10 wt %) with increases of 38 and 25%, respectively. A failure mechanism was proposed in which orientation of the MWNTs (normal to the direction of craze propagation and crack development) enabled them to toughen the brittle PMMA by bridging cracks that developed (via craze precursors) during the tensile test. None of the nanotube/PMMA composites showed mechanical properties close to the values expected from simple rule of mixture and orientation considerations. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2690–2702, 2004
Toward Larger DNA Origami (2014)

Structural DNA nanotechnology, and specifically scaffolded DNA origami, is rapidly developing as a versatile method for bottom-up fabrication of novel nanometer-scale materials and devices. However, lengths of conventional single-stranded scaffolds, for example, 7,249-nucleotide circular genomic DNA from the M13mp18 phage, limit the scales of these uniquely addressable structures. Additionally, increasing DNA origami size generates the cost burden of increased staple-strand synthesis. We addressed this 2-fold problem by developing the following methods: (1) production of the largest to-date biologically derived single-stranded scaffold using a λ/M13 hybrid virus to produce a 51 466-nucleotide DNA in a circular, single-stranded form and (2) inexpensive DNA synthesis via an inkjet-printing process on a chip embossed with functionalized micropillars made from cyclic olefin copolymer. We have experimentally demonstrated very efficient assembly of a 51-kilobasepair origami from the λ/M13 hybrid scaffold folded by chip-derived staple strands. In addition, we have demonstrated two-dimensional, asymmetric origami sheets with controlled global curvature such that they land on a substrate in predictable orientations that have been verified by atomic force microscopy.
Acoustic Phonon Emission from a Weakly Coupled Superlattice under Vertical Electron Transport: Observation of Phonon Resonance (2006)

We report measurements of acoustic phonon emission from a weakly coupled AlAs/GaAs superlattice (SL) under vertical electron transport. The phonons were detected using superconducting bolometers. A peak (resonance) was observed in emission parallel to the SL growth axis when the electrical energy drop per SL period matched the energy of the first SL mini-Brillouin zone-center phonon mode. This peak was mirrored by an increase of the differential conductance of the SL. These results are evidence for stimulated emission of terahertz phonons as previously predicted theoretically and suggest that such a SL may form the basis of a SASER (sound amplification by stimulated emission of radiation) device.
Clinical hyperthermia of prostate cancer using magnetic nanoparticles: Presentation of a new interstitial technique (2005)

The aim of this pilot study was to evaluate whether the technique of magnetic fluid hyperthermia can be used for minimally invasive treatment of prostate cancer. This paper presents the first clinical application of interstitial hyperthermia using magnetic nanoparticles in locally recurrent prostate cancer. Treatment planning was carried out using computerized tomography (CT) of the prostate. Based on the individual anatomy of the prostate and the estimated specific absorption rate (SAR) of magnetic fluids in prostatic tissue, the number and position of magnetic fluid depots required for sufficient heat deposition was calculated while rectum and urethra were spared. Nanoparticle suspensions were injected transperineally into the prostate under transrectal ultrasound and flouroscopy guidance. Treatments were delivered in the first magnetic field applicator for use in humans, using an alternating current magnetic field with a frequency of 100 kHz and variable field strength (0–18 kA m−1). Invasive thermometry of the prostate was carried out in the first and last of six weekly hyperthermia sessions of 60 min duration. CT-scans of the prostate were repeated following the first and last hyperthermia treatment to document magnetic nanoparticle distribution and the position of the thermometry probes in the prostate. Nanoparticles were retained in the prostate during the treatment interval of 6 weeks. Using appropriate software (AMIRA), a non-invasive estimation of temperature values in the prostate, based on intra-tumoural distribution of magnetic nanoparticles, can be performed and correlated with invasively measured intra-prostatic temperatures. Using a specially designed cooling device, treatment was well tolerated without anaesthesia. In the first patient treated, maximum and minimum intra-prostatic temperatures measured at a field strength of 4.0–5.0 kA m−1 were 48.5°C and 40.0°C during the 1st treatment and 42.5°C and 39.4°C during the 6th treatment, respectively. These first clinical experiences prompted us to initiate a phase I study to evaluate feasibility, toxicity and quality of life during hyperthermia using magnetic nanoparticles in patients with biopsy-proven local recurrence of prostate cancer following radiotherapy with curative intent. To the authors’ knowledge, this is the first report on clinical application of interstitial hyperthermia using magnetic nanoparticles in the treatment of human cancer.
Vaccine Efficacy against Malaria by the Combination of Porcine Parvovirus-Like Particles and Vaccinia Virus Vectors Expressing CS of Plasmodium (2012)

With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs) carrying the CD8(+) T cell epitope (SYVPSAEQI) of the circumsporozoite (CS) protein from Plasmodium yoelii fused to the PPV VP2 capsid protein (PPV-PYCS), and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8(+) T cell response elicited by these hybrid PPV-VLPs in BALB/c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus (VACV) vectors from the Western Reserve (WR) and modified virus Ankara (MVA) strains expressing the entire P. yoelii CS protein. The results of different immunization protocols showed that the combination of PPV-PYCS prime/poxvirus boost was highly immunogenic, inducing specific CD8+ T cell responses to CS resulting in 95% reduction in liver stage parasites two days following sporozoite challenge. In contrast, neither the administration of PPV-PYCS alone nor the immunization with the vectors given in the order poxvirus/VLPs was as effective. The immune profile induced by VLPs/MVA boost was associated with polyfunctional and effector memory CD8+ T cell responses. These findings highlight the use of recombinant parvovirus PPV-PYCS particles as priming agents and poxvirus vectors, like MVA, as booster to enhance specific CD8+ T cell responses to Plasmodium antigens and to control infection. These observations are relevant in the design of T cell-inducing vaccines against malaria.
대만에서의 일본어교육의 변화 (2010)

본 연구는 1990년대 전후반을 경계로 해서 학습 등에 관한 동기, 주체, 내용, 방법, 수단, 매체를 관찰하고, 대만에서의 일본어교육이 어떻게 변화해왔는가를 고찰하려는 것이다. 이 고찰에 있어서 실리지향에서 지식지향으로, 언어중시에서 학습자중시로, 분과에서 종합으로, 대면교육에서 원격교육으로 라는 4개의 항목으로 나누어, 동기의 변화, 커리큘럼의 변화, 교수법의 변화를 예로, 필자의 분석, 비판과 경험을 섞어서 논한다. 먼저 대만의 일본어학습자의 학습동기부여는 실리지향에서 지식지향, 도락지향으로 변하고 있다. 이 변화는 구민대학의 일본어교육 커리큘럼이나 시판되는 일본어학습지에는 반영되어있지만 대학의 일본어교육 커리큘럼과 교과서에는 아직 그것이 반영되어있지 않다. 대학에도 그러한 변화가 반영되어야 할 것이다. 또한 정보시대에 있어서 학습자중시의 인식을 중요시하고 인터넷 이용도 고려해서 효과적인 교육방법을 실시할 필요가 있으며, 읽는 법, 문법, 발음, 회화 등 분과시키지 않고 종합적으로 가르치는 일도 중요하다. 그 외에 학습자중시라는 관점에서 볼 때 공간과 시간의 제약을 뚫고 학습자가 자율적으로 학습할 수 있도록 네트워크를 이용한 원격교육을 보다 활발하고 충실하게 실행해 나갈 필요가 있을 것이다.
The digit vigilance test: reliability, validity, and sensitivity to diazepam (1996)

The Digit Vigilance Test (DVT), a measure of sustained attention and psychomotor speed, was evaluated in terms of test-retest and alternate-form reliability as well as sensitivity to a single dose of diazepam (10 mg). A one-page version was compared to the standard two-page format. Forty undergraduates, randomly assigned in a double-blind manner to either drug or placebo condition, were tested three times in two sessions (1 week apart). Both Page 1 and Total Time scores were found to be highly reliable across time and forms. Repeated measures ANOVAs revealed the Total Time score, but not the Page 1 score, to be significant in discriminating diazepam from placebo across time, supporting the use of the complete DVT for measuring drug effects. Findings based on convergent measures also help to validate the DVT as a measure of sustained attention.
Control of the Reversibility of Cellular Quiescence by the Transcriptional Repressor HES1 (2008)

The mechanisms by which quiescent cells, including adult stem cells, preserve their ability to resume proliferation after weeks or even years of cell cycle arrest are not known. We report that reversibility is not a passive property of nondividing cells, because enforced cell cycle arrest for a period as brief as 4 days initiates spontaneous, premature, and irreversible senescence. Increased expression of the gene encoding the basic helix-loop-helix protein HES1 was required for quiescence to be reversible, because HES1 prevented both premature senescence and inappropriate differentiation in quiescent fibroblasts. In some human tumors, the HES1 pathway was activated, which allowed these cells to evade differentiation and irreversible cell cycle arrest. We conclude that HES1 safeguards against irreversible cell cycle exit both during normal cellular quiescence and pathologically in the setting of tumorigenesis.
New antiarrhythmic agents. 2,2,5,5-Tetramethyl-3-pyrroline-3-carboxamides and 2,2,5,5-tetramethylpyrrolidine-3-carboxamides. (1986)

N-(omega-Aminoalkyl)-2,2,5,5-tetramethyl-3-pyrroline- or -pyrrolidine-3-carboxamides were acylated on the primary amino group of the side chain by means of reactive acid derivatives (acid chlorides, activated esters, phthalic anhydrides, phthalimide, 2-alkyl-4H-3,1-benzoxazin-4-ones) or they were alkylated by forming the Schiff bases and subsequent sodium borohydride reduction. Other tetramethyl-3-pyrrolinecarboxamide compounds were synthesized by acylating the aminoalkyl compounds with 2,2,6,6-tetramethyl-3,5-dibromo-4-piperidinone in a reaction involving Favorskii rearrangement. Saturation of the double bond of some pyrroline derivatives furnished the pyrrolidinecarboxamides. The new compounds of each type were active against aconitine-induced arrhythmia and several of them had higher activity and better chemotherapeutic index than quinidine. A few selected examples from each type of the active new compounds showed strong activity against ouabain-induced arrhythmia; for comparison known drugs such as lidocaine, mexiletine, and tocainide were selected. The most potent compounds were oxidized to the paramagnetic nitroxides and the latter were reduced to the N-hydroxy derivatives; these products had no or only decreased antiarrhythmic effect.