gebhart/patrepeval huggingface dataset:
Bcl-2 antisense oligonucleotide (G3139, Genasense) chemosensitizes human nasopharyngeal carcinoma to cisplatin in vivo in a SCID xenotransplantation model (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

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Nasopharyngeal carcinoma (NPC) is causally linked to Epstein-Barr virus (EBV), and EBV latent membrane protein 1 (LMP-1) is expressed in the majority of NPCs. LMP-1 upregulates anti-apoptotic genes, including bcl-2, and Bcl-2 protein is co-expressed with LMP-1 in NPC. Given the anti-apoptotic and chemoprotective effects of Bcl-2, it represents a rational therapeutic target in NPC. We have investigated the anti-tumor and chemosensitizing effects in NPC of G3139 (Genasense; Genta, Inc), a phosphorothioated antisense oligodeoxynucleotide targeted to the first six codons of Bcl-2 mRNA. In previous in vitro studies in C666-1, a stably infected NPC-derived line which co-expresses LMP-1 and bcl-2, we have shown that G3139 treatment caused sequence-dependent inhibition of growth and depletion of Bcl-2 protein. Although G3139 had anti-tumor effects in vivo, delaying establishment and inhibiting growth of C666-1 engrafted s.c. in SCID mice, G3139 did not prevent establishment or extend survival compared to untreated and control oligonucleotide-treated animals. Since Bcl-2 mediates chemoresistance, and G3139 enhances sensitivity to chemotherapy, we sought to determine whether G3139 sensitizes NPC to cisplatin (CDDP) in our NPC xenotransplantation model. Animals were injected with 5 million C666-1 cells on day 1 and randomized to treatment arms (n = 5-6). Tumor volumes were measured at 3 day intervals and mean tumor volumes were compared using Student’s t test. EBV DNA load in serum was measured serially by real-time quantitative PCR. Results: In the first experiment, G3139 (25 mg/kg i.p. q 3 days x 5 starting on day 7) + CDDP (8 mg i.p. on day 14) prevented tumor establishment in 80% of animals compared to CDDP alone (0%) or CDDP + a reverse control oligonucleotide (RV) (0%). CDDP + RV had no effect on tumor establishment or growth compared to CDDP alone. Tumor burden correlated directly with EBV DNA load in serum. In a second experiment, treatment was delayed until tumor was established. On day 21, animals with measurable tumor were randomized and treated as above with CDDP, G3139 + CDDP, or CDDP + MM (two base mismatch control oligonucleotide). In contrast to CDDP or CDDP + MM, G3139 + CDDP resulted in partial tumor regressions in 4 of 6 animals, and significantly inhibited tumor growth. Survival analysis and correlative studies on tumor tissue to assess in vivo mechanisms are in progress. Conclusions: These studies demonstrate that the pro-apoptotic bcl-2 antisense oligonucleotide G3139 sensitizes EBV-positive NPC to CDDP in vivo. The sequence-dependency of this effect is consistent with an antisense mechanism. Moreover, these studies support the use of this animal model of EBV-positive NPC to test novel targeted therapies for NPC, including anti-viral agents.
Combination of EP 4 antagonist MF-766 and anti-PD-1 promotes anti-tumor efficacy by modulating both lymphocytes and myeloid cells (2021)

Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), an arachidonic acid pathway metabolite produced by cyclooxygenase (COX)-1/2, has been shown to impair anti-tumor immunity through engagement with one or more E-type prostanoid receptors (EP<sub>1-4</sub>). Specific targeting of EP receptors, as opposed to COX-1/2 inhibition, has been proposed to achieve preferential antagonism of PGE<sub>2</sub>-mediated immune suppression. Here we describe the anti-tumor activity of MF-766, a potent and highly selective small-molecule inhibitor of the EP<sub>4</sub> receptor. EP<sub>4</sub> inhibition by MF-766 synergistically improved the efficacy of anti-programmed cell death protein 1 (PD-1) therapy in CT26 and EMT6 syngeneic tumor mouse models. Multiparameter flow cytometry analysis revealed that treatment with MF-766 promoted the infiltration of CD8<sup>+</sup> T cells, natural killer (NK) cells and conventional dendritic cells (cDCs), induced M1-like macrophage reprogramming, and reduced granulocytic myeloid-derived suppressor cells (MDSC) in the tumor microenvironment (TME). <i>In vitro</i> experiments demonstrated that MF-766 restored PGE<sub>2</sub>-mediated inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production in THP-1 cells and human blood, and PGE<sub>2</sub>-mediated inhibition of interleukin (IL)-2-induced interferon (IFN)-γ production in human NK cells. MF-766 reversed the inhibition of IFN-γ in CD8<sup>+</sup> T-cells by PGE<sub>2</sub> and impaired suppression of CD8<sup>+</sup> T-cells induced by myeloid-derived suppressor cells (MDSC)/PGE<sub>2.</sub> In translational studies using primary human tumors, MF-766 enhanced anti-CD3-stimulated IFN-γ, IL-2, and TNF-α production in primary histoculture and synergized with pembrolizumab in a PGE<sub>2</sub> high TME. Our studies demonstrate that the combination of EP<sub>4</sub> blockade with anti-PD-1 therapy enhances antitumor activity by differentially modulating myeloid cell, NK cell, cDC and T-cell infiltration profiles.
Light Intensity Stabilization Using Highly-Efficient Faraday Rotator (1982)

A method of stabilizing light intensity using a magneto-optic modulator with a highly-efficient Faraday rotator is proposed. The method utilizes the limiting action of the optical bistability. The maximum stabilization factor reached is 3.7×10 -3 , and to obtain the highest stability requires a current of only 0.1 A in the coils of the electromagnet, which is a favorable feature for the practical use of the stabilizer. The effects of the bias coil current and the relative angle of orientation of the polarizers on the stabilization factor are clarified. This stabilization method is suitable for depressing dc or low frequency noise.
Managing Hierarchical Supramolecular Organization with Holographic Tweezers (2010)

The use of light for controlling objects led to the development of optical tweezers. Now, the applications have expanded into the creation of three-dimensional structures and the control of surface structures.
Highly efficient light emission from III-nitride photonic crystal (2004)

Photonic crystal LEDs based on InGaN/GaN QWs was fabricated and exhibited eight-fold enhancement of light emission in far field. Polarization and pumping condition dependence of photonic crystal light emission were further studied
Kontrastverstärkte MRT zum Nachweis morphologischer Veränderungen des Herzens bei Patienten mit dilatativer Kardiomyopathie (2004)

Ziele: Nachweis morphologischer myokardialer Veränderungen bei Patienten mit dilatativer Kardiomyopathie (DCM). Methode: An einem 1,5 T Magnetom Sonata (Siemens) wurden 12 Patienten (8 Männer, 4 Frauen, MW 56,3 Jahre) mit Verdacht auf DCM untersucht. Eine relevante KHK konnte zuvor angiographisch ausgeschlossen werden. Neben der LV-Funktionsanalyse in kurzachsenparalleler Schnittführung (Cine TrueFisp-Sequenz: TR 3.2ms, TE 1.6ms) erfolgte die Applikation von Gd-DTPA (0,2 mmol/kg KG) zum Nachweis morphologischer Veränderungen (late Enhancement). LV-Funktionsparameter wurden unter Verwendung der Argus-Software (manuelle Segmentierung) bestimmt. Das Kontrastierungsverhalten wurde qualitativ und quantitativ (S/N und CNR-Messungen, Referenz Skelettmuskulatur) an definierten Regionen (17 Segmente) ermittelt und mit Referenzdaten eines Probandenkollektives (n=10) verglichen. Ergebnis: Neben einer signifikanten Erhöhung enddiastolischer Volumina (p<0,01) und einer reduzierten EF als Folge einer globalen LV-Funktionseinschränkung zeigten alle Patienten ein pathologisches late Enhancement. Es konnten qualitativ-visuell charakteristische Verteilungsmuster differenziert werden: endokardiale, fokal-fleckige sowie intramyokardial-lineare Manifestationen. Quantitative Messungen bei Patienten zeigten ein signifikant (p<0,05) erhöhtes S/N (2,59±1,44 gegenüber 2,1±1,6) sowie eine Erhöhung des CNR (1,42±0,79 gegenüber 1,01±0,37). Keiner der Probanden zeigte ein late enhancement. Schlussfolgerung: Eine Linksherzinsuffizienz als Folge einer DCM kann anhand von morphologischen und funktionellen Veränderungen mit der MRT evaluiert und gegenüber der KHK abgegrenzt werden.
Applications of Size-SelectiveMacrolactonizations to the Synthesis of Benzolactone-EnamideCore Structures (2003)

By utilizing Stille cross-coupling reactions four benzoic acid derivatives (18, 32, 46, 66) were prepared that carry a side chain with two secondary hydroxy groups. It could be shown that the hydroxy functions can be distinguished by size-selective macrolactonization reactions. Thus, 12-membered lactones 19 and 33 are favored over their 11- membered lactone counterparts 20 and 34, respectively, albeit with a low (60:40-70:30) ratio. The selectivity is much more pronounced if there is a competition between a 12- and 10-membered lactone. This could be shown with the two lactones 47 and 67. The 12-membered lactones 33, 47, and 67 represent core structures for analogs of the benzolactone enamides. The macrolactonization reactions were performed under Yamaguchi conditions.
Probing the Flexibility of Large Conformational Changes in Protein Structures through Local Perturbations (2009)

Protein conformational changes and dynamic behavior are fundamental for such processes as catalysis, regulation, and substrate recognition. Although protein dynamics have been successfully explored in computer simulation, there is an intermediate-scale of motions that has proven difficult to simulate - the motion of individual segments or domains that move independently of the body the protein. Here, we introduce a molecular-dynamics perturbation method, the Rotamerically Induced Perturbation (RIP), which can generate large, coherent motions of structural elements in picoseconds by applying large torsional perturbations to individual sidechains. Despite the large-scale motions, secondary structure elements remain intact without the need for applying backbone positional restraints. Owing to its computational efficiency, RIP can be applied to every residue in a protein, producing a global map of deformability. This map is remarkably sparse, with the dominant sites of deformation generally found on the protein surface. The global map can be used to identify loops and helices that are less tightly bound to the protein and thus are likely sites of dynamic modulation that may have important functional consequences. Additionally, they identify individual residues that have the potential to drive large-scale coherent conformational change. Applying RIP to two well-studied proteins, Dihdydrofolate Reductase and Triosephosphate Isomerase, which possess functionally-relevant mobile loops that fluctuate on the microsecond/millisecond timescale, the RIP deformation map identifies and recapitulates the flexibility of these elements. In contrast, the RIP deformation map of alpha-lytic protease, a kinetically stable protein, results in a map with no significant deformations. In the N-terminal domain of HSP90, the RIP deformation map clearly identifies the ligand-binding lid as a highly flexible region capable of large conformational changes. In the Estrogen Receptor ligand-binding domain, the RIP deformation map is quite sparse except for one large conformational change involving Helix-12, which is the structural element that allosterically links ligand binding to receptor activation. RIP analysis has the potential to discover sites of functional conformational changes and the linchpin residues critical in determining these conformational states.
Multiple Roles for B-Lymphocytes in Sjogren’s Syndrome (2016)

Sjogren's syndrome (SS) is a complex heterogeneous autoimmune disease resulting in loss of salivary gland and lacrimal gland function that may include multiple systemic manifestations including lymphoma. Multiple cell types participate in disease pathogenesis. This review discusses evidence for abnormal B cell subpopulations in patients with SS, critical roles of B cells in SS and the status of B cell-directed therapies in the management of patients with SS.
Regional selectivity of calcium blockers at intestinal level. (1985)

Exposure of isolated segments of rat duodenum and proximal colon to either high K+ (55.9 mM) or carbachol (0.1 mM) produced a typical biphasic contraction whose tonic component appears to be almost entirely dependent upon the presence of extracellular Ca++. Verapamil and nifedipine suppressed high K+-and carbachol-induced tonic contractions of both duodenum and proximal colon but a large component of carbachol-induced contraction of proximal colon was insensitive to these substances. Verapamil and nifedipine were: a. 5 and 3 times more effective in antagonizing high K+-induced tonic contractions in the rat duodenum than in the proximal colon, respectively, and b. 10 and 4 times more effective in antagonizing high K+ than carbachol induced tonic contractions of rat duodenum, respectively. The verapamil- or nifedipine- resistant component of carbachol induced tonic contraction of proximal colon was suppressed by drugs which, like octylonium bromide and urethane, have been shown to interfere with mobilization of Ca++ from intracellular storage sites. Experiments in Ca++-free medium indicate the existence in the proximal colon of a significant intracellular Ca++ store which could be mobilized during carbachol but not high K+-induced tonic contractions. These findings indicate that, in the rat intestine, significant regional differences exists in Ca++ pools mobilized by different activating stimuli and in sensitivity to the blocking action of drugs which interfere with Ca++ mobilization from either intra- or extracellular Ca++ pools.
Adenocarcinoma in situ or early-stage cervical cancer is a risk factor for preterm delivery after cervical conization: a multicenter observational study (2022)

Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGESPrior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization.The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.
Highly efficient gene tagging in the bryophyte Physcomitrella patens using the tobacco (Nicotiana tabacum) Tnt1 retrotransposon (2016)

Because of its highly efficient homologous recombination, the moss Physcomitrella patens is a model organism particularly suited for reverse genetics, but this inherent characteristic limits forward genetic approaches. Here, we show that the tobacco (Nicotiana tabacum) retrotransposon Tnt1 efficiently transposes in P. patens, being the first retrotransposon from a vascular plant reported to transpose in a bryophyte. Tnt1 has a remarkable preference for insertion into genic regions, which makes it particularly suited for gene mutation. In order to stabilize Tnt1 insertions and make it easier to select for insertional mutants, we have developed a two-component system where a mini-Tnt1 with a retrotransposition selectable marker can only transpose when Tnt1 proteins are co-expressed from a separate expression unit. We present a new tool with which to produce insertional mutants in P. patens in a rapid and straightforward manner that complements the existing molecular and genetic toolkit for this model species.
In Situ Polymerized Carboxylated Diacetylene as a Hole Conductor in Solid-State Dye-Sensitized Solar Cells (2006)

A solid-state dye-sensitized solar cell was fabricated using in situ polymerized carboxylated diacetylene for hole transporting. Our preliminary experiments showed a short-circuit current density of 4.25 mA/cm2 and an efficiency of 0.89%. These proof-of-concept results are believed to be some of the highest reported for polymeric hole transporting material based devices.
Fluorenyl based syndiotactic specific metallocene catalysts structural features, origin of syndiospecificity (2004)

Abstract The stereochemistry of propylene insertion/propagation reactions with a variety of C s symmetric fluorenyl‐ containing single site catalysts is discussed. Our recent results indicate that independent of the chemical composition of the ancillary ligand fragments, or nature of the transition metal, active sites with local C s symmetry and enantiotopic coordination positions behave syndioselectively in the general context of chain migratory insertion mechanism. Perfect bilateral symmetry neither exists nor is required in these processes. In this context the mechanism of syndiospecific polymerization is revisited by taking into account the structural characteristics and catalytic behavior of the original metallocene based (η 5 ‐C 5 H 4 ‐CMe 2 ‐η 5 ‐C 13 H 8 ) MCl 2 / MAO; M = Zr ( 1 ), Hf ( 2 ) catalyst systems and new syndiotactic specific systems including (η 5 ‐C 5 H 4 ‐CPh2‐η5‐3,6‐di‐tBut‐C 13 H 6 )ZrCl 2 ( 3 ), η 1 ,η 5 ‐(μMe 2 Si)(3,6‐di‐tBut‐Flu)(t‐ButN)MCl 2 / MAO; M =Ti ( 4 ), Zr ( 5 ) and η 1 ,η 5 ‐(μMe 2 Si)(2,7‐di‐tBut‐Flu)(t‐ButN)MCl 2 / MAO; M = Ti ( 6 ), Zr ( 7 ).
Tracker Modalities for Virtual Environments: A Comparison of Some Performance Characteristics (2002)

In this paper the authors present a comparison of some performance characteristics of two motion tracking modalities for use in a virtual environment. Ascension Technology’s Flock of Birds is an electromagnetic tracking system. Intersense’s IS-600 uses a combination of ultrasonic, infrared, and inertial principles. Case studies were performed for both tracking systems to study static distortion, temporal stability, and the effect of metal. The requirements of the virtual reality application would ultimately guide the choice of the tracker modality.
Study of Vertical and Lateral Charge Transport Properties of DPP-Based Polymer/PC61BM Films Using Space Charge Limited Current (SCLC) and Field Effect Transistor Methods and their Effects on Photovoltaic Characteristics (2015)

We studied the vertical and lateral charge transport characteristics of a diketopyrrolopyrrole polymer donor (D)–PC61BM acceptor (A) system by measuring the space charge limited current (SCLC) mobility and field-effect mobility respectively. It was found that with an increase in annealing temperature, the SCLC hole mobility decreased for the pure polymer (PDBFBT) but increased for the PDBFBT:PC61BM blends, which could be explained by changes in the crystallinity and crystal orientation (edge-on versus face-on). The pure PDBFBT and most blend films showed the maximum field-effect hole mobility (µh) when annealed at 100°C, which then declined as the annealing temperature was further increased. Surprisingly, the D/A = 1/1 blend films annealed at high temperatures exhibited an abrupt increase in the field-effect µh. This unusual phenomenon was interpreted by the antiplasticization effect of PC61BM, which promoted the molecular organization of the polymer. The effect of annealing on the carrier mobility was further correlated with the performance of inverted organic solar cell devices with the PDBFBT:PC61BM blend (D/A = 1/3). Thermal annealing at high temperatures (&amp;gt;100°C) was found to obstruct electron transport and cause the device performance to significantly deteriorate.
Torsional mechanical responses in azobenzene functionalized liquid crystalline polymer networks (2013)

Soft materials capable of both planar and flexural–torsional responses could enable the development of soft robotic elements that emulate the dexterity and functionality of a multitude of creatures in the animal kingdom. Here, we examine the response of azobenzene-functionalized liquid crystal polymer networks (azo-LCNs) specifically focusing on realizing large magnitude flexural–torsional responses observed as out-of-plane twisting or coiling. Towards this end, azo-LCNs were prepared in either the twisted nematic (TN) or hybrid orientations. The characterization of the flexural–torsional photomechanical responses is complimented with examination of thermomechanical properties. The diverse range of tailorable photomechanical responses is shown to be strongly dependent on the alignment of the nematic director to the film geometry and the actinic light intensity.
Network Slicing for NOMA-Enabled Edge Computing (2021)

The 5G network presents a new horizon with tremendous opportunities for future generation wireless networks. Mobile edge computing (MEC), non-orthogonal multiple access (NOMA), and network slicing (NS) are some of the key enablers for 5G. MEC reduces the latency to a great extent for a wireless network, while NOMA gives access to more users with resource constraints. NS provides users with a better quality of service and network operators with more flexibility. In this work, we propose an NS technique enabled with NOMA for a MEC network. The proposed NS technique improves service latency for MEC users and reduces unnecessary allocation of radio resources in NOMA. The saved resources can be leveraged to accommodate more users, thus increasing the spectral efficiency of the network. We consider different types of services based on the task completion time of users in this work. The primary focus is to optimize the total energy consumption for wireless uplink transmission for the NOMA-enabled sliced MEC network. We also propose a heuristic algorithm as an alternative to reduce the time and computational complexities of the optimization algorithm and simulate the results extensively to show the effectiveness of our proposed algorithm.
Aspects of remote asymmetric induction using allylstannanes (1996)

Abstract
<title>Characteristics of blue organic electroluminescent devices with distyryl arylene derivatives</title> (1993)

We have studied organic electroluminescence (EL) characteristics for a multilayer thin film cell with distyryl arylene derivatives (DSA) as emitting materials. We found that it is very important for an emitting layer not to form exciplex or charge transfer complex (ECT) with the hole transporting layer (diamine derivatives) in addition to an ability to form a good thin film. In this paper, we report a new series of DSA not to form the ECT with the hole transporting layer owing to the molecular conformation. We substituted two hydrogen atoms for two phenyl rings and designed some new DSA which are not planar. These DSA are intense blue fluorescent materials and have good film-forming ability. A cell with ITO/hole transporting layer/emitting layer/Mg:Ag was fabricated by vacuum evaporation technique. We obtained bright emission more than 1000 cd/m<SUP>2</SUP> with dc voltage of less than 12 V and high luminous efficiency about 0.6 lm/W at 1000 cd/m<SUP>2</SUP> for several kinds of DSA as emitting materials. In these cells we successfully avoid ECT formation at the interface between the hole transporting layer and the emitting layer.
Arrays of Truncated Cone AlGaN Deep-Ultraviolet Light-Emitting Diodes Facilitating Efficient Outcoupling of in-Plane Emission (2016)

Despite a rapidly growing demand for efficient man-made deep-ultraviolet (DUV) light sources, widespread adoption of AIGaN-based DUV light-emitting diodes (LEDs) is currently obstructed by extremely poor extraction of DUV photons due to the intrinsic material properties of the AIGaN active region. Here, we present 280 nm AlGaN DUV LEDs having arrays of truncated cone (TC)-shaped active mesas coated with MgF2/Al reflectors on the inclined sidewalls of the cone to effectively extract the intrinsically strong transverse magnetic-polarized emission. Ray tracing simulations reveal that the TC DUV LEDs show an isotropic emission pattern and much enhanced light-output power in comparison with stripe-type DUV LEDs with the same MgF2/AI reflectors. Consistent with the ray tracing simulation results, the TC DUV LEDs show an isotropic emission pattern with much higher light-output power as well as lower operating voltage than the stripe-type DUV LEDs. On the basis of our results, strategies for designing high-performance DUV LEDs to further enhance the optical and electrical performances simultaneously are suggested.