gebhart/patrepeval huggingface dataset:
Avelumab (MSB0010718C; anti-PD-L1) in combination with other cancer immunotherapies in patients with advanced malignancies: The phase 1b/2 JAVELIN Medley study. (2016)

TPS3106 Background: Programmed death-1 receptor ligand (PD-L1) is a key therapeutic target in the reactivation of the immune response against multiple cancers. Additionally, 4-1BB agonists have been shown to enhance T-cell proliferation and anti-tumor immunity. Avelumab*, a fully human anti-PD-L1 IgG1 antibody, and PF-05082566, a fully human anti-4-1BB (CD137) IgG2 antibody, are being investigated in separate trial programs. In preclinical models, anti-4-1BB/anti-PD-L1 combination therapy had significantly improved anti-tumor activity compared with monotherapy of either agent. This open-label, phase 1b/2 study (NCT02554812) evaluates the combination of avelumab + anti-4-1BB in patients (pts) with selected advanced solid tumors. Other avelumab + immune modulator combinations are planned. The goal of this study is to determine safety, tolerability, and clinical activity of these combination therapies. Methods: A total of approximately 147 pts with histologically confirmed advanced selected solid tumors, ECOG PS 0-1, and archival or fresh tumor tissue (not preselected for PD-L1 expression) will be enrolled in this combination study. During the phase 1b lead-in for the study arm with PF-05082566, pts with NSCLC that has progressed on standard therapy will be randomized (1:1:1) to receive avelumab (10 mg/kg; 1h intravenous [IV] infusion Q2W) + PF-05082566 (500 mg, 100 mg, or 20 mg; 1h IV infusion Q4W). Based on dose-limiting toxicity (DLT) analysis in these cohorts, phase 2 will continue enrolling pts with NSCLC with expanded enrollment criteria at selected dose levels. In addition, pts with melanoma or squamous cell carcinoma of the head and neck will be enrolled at a single dose level selected for phase 2. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are DLT (phase 1b) and confirmed objective response (RECIST 1.1). Secondary endpoints include progression-free survival, overall survival, duration of response, pharmacokinetics, immunogenicity, tumor biomarkers, and adverse events (NCI-CTCAE v4.03). Enrollment began in Nov 2015. *Proposed INN. Clinical trial information: NCT02554812.
Highly-Economized Multi-View Binary Compression for Scalable Image Clustering (2018)

How to economically cluster large-scale multi-view images is a long-standing problem in computer vision. To tackle this challenge, we introduce a novel approach named Highly-economized Scalable Image Clustering (HSIC) that radically surpasses conventional image clustering methods via binary compression. We intuitively unify the binary representation learning and efficient binary cluster structure learning into a joint framework. In particular, common binary representations are learned by exploiting both sharable and individual information across multiple views to capture their underlying correlations. Meanwhile, cluster assignment with robust binary centroids is also performed via effective discrete optimization under L21-norm constraint. By this means, heavy continuous-valued Euclidean distance computations can be successfully reduced by efficient binary XOR operations during the clustering procedure. To our best knowledge, HSIC is the first binary clustering work specifically designed for scalable multi-view image clustering. Extensive experimental results on four large-scale image datasets show that HSIC consistently outperforms the state-of-the-art approaches, whilst significantly reducing computational time and memory footprint.
Optimization of the Generation and Propagation of Gutless Adenoviral Vectors (2003)

Adenoviral vectors devoid of all viral coding regions are referred to by many names, including gutless vectors. Gutless vectors display reduced toxicity and immunogenicity, increased duration of transgene expression, and increased coding capacity compared to early generation vectors, which contain the majority of the viral backbone genes. However, the production of gutless vectors at a scale and purity suitable for clinical use has limited the utility of this technology. In this work we describe the optimization of the production of gutless vectors. We constructed an improved helper virus and generated an alternative gutless vector producer cell line, PERC6-Cre. We demonstrated increased gutless vector yields, minimal helper virus contamination, and no replication-competent adenovirus contamination using the optimized system. Furthermore, the PERC6-Cre cells were adapted to serum-free suspension culture and high-titer gutless vector preparations were produced using bioreactor technology, suggesting the feasibility of gutless vector scale-up for clinical use. Finally, we observed that helper virus lacking a packaging signal could be packaged at a low frequency, revealing an inherent limitation to the differential packaging strategy for gutless vector propagation.
P-185 Microbial-Dependent CX3CR1+ MNP Production of TL1A Co-stimulates ILC3 to Promote Mucosal Healing (2016)

Colonic lamina propria mononuclear phagocytes (MNPs) expressing the fractalkine receptor CX3CR1 play a critical role in maintaining barrier homeostasis. Recently, we have shown that these MNPs promote mucosal healing in response to microbial signals by supporting group 3 innate lymphoid cell (ILC3) production of IL-22 in both mouse models and human colitis. Mechanistically, we identified a role for CX3CR1+ MNP production of TNF family cytokine TL1A—whose gene, TNFSF15, encodes functional polymorphisms strongly associated with IBD—in regulating ILC3 effector cytokine production; however, the mechanism and physiologic importance of TL1A expression by MNPs and signaling via receptor DR3 in promoting mucosal healing have not been defined. CX3CR1-GFP mice were used to evaluate TL1A expression in intestinal MNPs. Gnotobiotic mice and human endoscopic biopsy specimens were used to evaluate the role for microbiota and colitis, respectively, in driving TL1A expression. To examine the physiologic role for DR3 in mucosal healing, mice deficient for DR3 and littermate controls were exposed to 2% dextran sodium sulfate (DSS) for 7 days. Lamina propria mononuclear cells were analyzed ex vivo to evaluate effector cytokine production by ILC3 and to characterize the responsible signaling pathway. Analysis of MNPs ex vivo revealed reduced TL1A expression in germ free mice compared to SPF controls, and colonization with segmented filamentous bacteria was sufficient to induce TL1A expression by qPCR. Consistent with the microbial-dependence of TL1A production, CD11c+ MHCII+ CX3CR1+ splenocytes were upregulated TL1A in response to LPS stimulation in vitro. During DSS-induced colitis, increased expression of surface TL1A was seen in MHCII+ CX3CR1+ LPMCs. An increase in TL1A expression was similarly seen in CD14+ MHCII+ LPMCs from IBD patients. In response to DSS challenge, DR3-deficient mice had significantly more weight loss, more severe pathology, and reduced survival. Analysis of lamina propria cellular immune responses revealed a statistically significant reduction in innate lymphoid cell (Lin−/CD127+) production of IL-22 and GM-CSF. No difference in Th1, Th17, Treg, Foxp3/RORgt+ CD4+ T, or ILC2 production of IL-13 was seen, suggesting a critical role for DR3 signaling in ILC3 in vivo. Our data in ILC3 show that TL1A synergy with IL-23 is independent of IL-1R and MyD88 signaling and not complemented by related TNFSF members (including OX40L, TRAIL, or TNFa). Soluble inhibitors revealed a critical role for MAPK signaling—specifically p38 MAPK—in mediating DR3 co-stimulation of ILC3. Collectively, these data highlight a key role for microbial regulation of MNP-derived TL1A in co-stimulating ILC3 effector cytokine production in vivo via p38 MAPK signaling. A mechanistic understanding of both the microbial components which induce TL1A in MNPs and the critical signaling pathways required for ILC3 co-stimulation will provide therapeutic targets to promote mucosal healing.
The nonpeptide WIN 64338 is a bradykinin B2 receptor antagonist. (1994)

We report the synthesis and in vitro biological activity of the nonpeptide bradykinin receptor antagonist WIN 64338, [[4-[[2-[[bis(cyclohexylamino)methylene]amino]-3-(2- naphthyl)-1-oxopropyl]amino]phenyl]methyl]tributylphosphonium chloride monohydrochloride. WIN 64338 inhibits [3H]-bradykinin binding to the bradykinin B2 receptor on human IMR-90 cells with a binding inhibition constant (Ki) of 64 +/- 8 nM and demonstrates competitive inhibition of bradykinin-stimulated 45Ca2+ efflux from IMR-90 cells (pA2 = 7.1). The antagonist inhibits bradykinin-mediated guinea pig ileum contractility (pA2 = 8.2) and has significantly weaker activity against acetylcholine-induced contractility in the same preparation. WIN 64338 is not active in a rabbit aorta bradykinin B1 receptor assay, demonstrating that it is a selective bradykinin B2 receptor antagonist. The compound inhibits [3H]quinuclidinyl benzilate binding to the rat brain muscarinic receptor (Ki = 350 nM) but is 25- to 100-fold more selective for the bradykinin receptor compared with other receptors against which it has been tested. Synthesis of WIN 64338 has provided a nonpeptide competitive bradykinin B2 antagonist active in both bradykinin radioligand binding and functional assays.
Shallow drain extension by angled ion implantation (1996)

In a technology driven enterprise, such as the semiconductor industry, pure research and development often overshadows manufacturing concerns. Typically, “discovery” is the result of miniaturization efforts with integration into existing process flows a secondary concern. However, it is often the case that fabrication of devices is complicated by next generations of technologies. Since revenue and profits are ultimately determined by the speed and ease with which a wafer may be processed, the streamlining of process flows assumes a certain level of importance. In this work, we describe the construction and microstructural characterization of a simple spacerless metal-oxide semiconductor (MOS) transistor with a self-aligned shallow drain extension. Transistor structures were fabricated at Stanford University's Center for Integrated Systems usinga single masking step to pattern the gate mask for the self-aligned structures. A 200Å gate oxide wasgrown and a 3000Å polysilicon blanket film was subsequently deposited on the wafer. Thepolysilicon was patterned into an array of 2.0μm lines and 3.0μm spaces.
Antigenicity and Immunogenicity of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against <i>Haemophilus influenzae</i> Type b (2004)

Polysaccharide-protein conjugates as vaccines have proven to be very effective in preventing Haemophilus influenzae type b infections in industrialized countries. However, cost-effective technologies need to be developed for increasing the availability of anti-H. influenzae type b vaccines in countries from the developing world. Consequently, vaccine production with partially synthetic antigens is a desirable goal for many reasons. They may be rigidly controlled for purity and effectiveness while at the same time being cheap enough that they may be made universally available. We describe here the antigenicity and immunogenicity of several H. influenzae type b synthetic oligosaccharide-protein conjugates in laboratory animals. The serum of H. influenzae type b-immunized animals recognized our synthetic H. influenzae type b antigens to the same extent as the native bacterial capsular polysaccharide. Compared to the anti-H. influenzae type b vaccine employed, these synthetic versions induced similar antibody response patterns in terms of titer, specificity, and functional capacity. The further development of synthetic vaccines will meet urgent needs in the less prosperous parts of the world and remains our major goal.
Respiration mode detection using a wireless instrumented mouthguard (2015)

Many ongoing research and commercial efforts seek to develop head-mounted sensor systems primarily intended to measure the severity of impacts to the head and body. The majority of these systems incorporate computational and data acquisition electronics close to the mouth or ears. The prospect of utilizing such devices for health and safety assessment during athletic, occupational, and recreational activities presents a unique opportunity to use these systems for additional physiological monitoring and detection. In particular, instrumented mouthguards provide access to bone, mucosa, arteries, saliva, and inspirated and expirated air. We have developed an instrumented mouthguard with a primary function of inertial measurement of the skull, but present a secondary functionality of measuring respiration using a simple palate impedance measurement capable of identifying respiration rate and respiration mode.
An algorithm and implementation system for measuring impedance in the D-Q domain (2011)

As power electronics infiltrates the electric power distribution and conversion systems, stability issues become increasingly significant. The risk of instability due to the use of constant power loads stems from the implementation of controlled output power conversion systems. In three phase converters, these issues are difficult to measure. Although there have been developments in the determination of system stability at interfaces due to stability, a framework to perform measurements necessary for such a determination has not been fully developed. This paper presents a method to measure three phase impedances in the D-Q rotating reference frame for three phase AC systems and demonstrates the successful implementation and operation of such a system. Results are shown measuring a three phase passive load with a 2 kW source.
The DM mutation; diagnostic applications in the Finnish population (1993)

A pair of marker loci, D19S63 and D19S51, which are tightly linked to the myotonic dystrophy (DM) locus, were used to evaluate diagnostic applicability in the Finnish population. Results were then compared to direct detection of the mutation. The D19S63 locus revealed a linkage disequilibrium, since in 16 DM families as many as 75% of DM chromosomes carried the same allele 3 for D19S63, and 25% carried allele 1. However, when the data for D19S51 and D19S63 were considered together as a haplotype, the statistical significance of this linkage disequilibrium was considerably reduced. As expected, the best method for reliable evaluation of the carrier risk was direct analysis of the mutation. Thirteen particularly difficult cases were resolved and in 46% of them the decision could be made only by direct visualization of the mutation. However, in a few cases where the size of the CTG-repeat expansion was close to the normal size range, linked markers proved to be useful to determine the affected chromosomes. Present findings indicate that analysis of the D19S63 locus coupled to direct demonstration of the mutation provides the basis for DNA diagnostics of DM in the Finnish population.
Iron Supplementation Inhibits Cough Associated With ACE Inhibitors (2001)

Dry cough is the most common limiting factor of ACE inhibitor (ACEI) use. Generation of NO, a proinflammatory substance on bronchial epithelial cells, is increased by ACEI. Using a randomized, double-blind, placebo-controlled trial, we tested the hypothesis that supplementing iron, an inhibitor of NO synthase, may reduce the cough associated with ACEI use. The subjects were 19 patients who had developed ACEI-induced cough. After a 2-week observation period, they were randomized to a daily morning dose of either 256-mg ferrous sulfate as a tablet or placebo for a treatment period of 4 weeks. The subjects were requested to fill out a cough diary by scoring the daily severity of the cough on a scale of 0 to 4. Mean daily cough scores for the last week of the observation and treatment period were compared. Changes in blood cell count and serum iron and ferritin concentration between the 2 periods were evaluated. Mean daily cough scores during the observation and treatment periods were 3.07+/-0.70 and 1.69+/-1.10, respectively, for the iron group and 2.57+/-0.80 and 2.35+/-1.22, respectively, for the placebo group, showing a significant reduction in cough scores with iron supplementation (P<0.01) but not with placebo. Three subjects in the iron group showed almost complete cough abolition. No significant changes in laboratory data were observed in either group. In conclusion, iron supplementation successfully decreases ACEI-induced cough. This effect may be related to the decrease of NO generation associated with the inhibition of NO synthase activity in bronchial epithelial cells.
Acyloxybutadiene Iron Tricarbonyl Complexes as Enzyme‐Triggered CO‐Releasing Molecules (ET‐CORMs) (2011)

Molecular hazardous materials transport: Enzyme-triggered CO-releasing molecules (ET-CORMs) offer new options for the delivery of CO. The cleavage of dienylester iron tricarbonyl complexes by an esterase under mild oxidative conditions generates CO, which causes a strong inhibiting activity of the compounds to inducible nitric oxide synthase as shown in a cellular assay. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Encapsulated cells producing retroviral vectors for <i>in vivo</i> gene transfer (2002)

Abstract Background Because gene therapy of the future will primarily take an in vivo approach, a number of problems associated with its current implementation exist. Currently, repeated delivery of a vector in vivo is necessary to ensure adequate transfer of the therapeutic gene. This may lead to the development of an immune response against the vector, thus interfering with gene delivery. To circumvent this problem, retroviral vector packaging cells that permanently produce recombinant retroviral vector particles have been encapsulated. Methods Vector (pBAG)‐producing amphotropic cells were encapsulated in beads composed of polymerized cellulose sulphate. These capsules were analysed in vitro for expression of the vector construct using X‐gal staining, as well as for the release of particles by performing RT‐PCR from culture supernatant. Infectivity studies were performed in vitro and in vivo . The latter was assayed using histological sections of the microcapsule and the surrounding area stained for β‐galactosidase activity and by RT‐PCR. Results In culture, the virus‐producing cells inside the capsules remained viable and released virus into the culture medium for at least 6 weeks. To test whether these capsules, upon implantation into mice, also release vector virions that infect the surrounding cells, two different models were used. In the first, capsules were implanted in the fat pad of the mammary gland of Balb/c mice. The capsules were well tolerated for at least 6 weeks and a self‐limiting inflammatory reaction without any other gross immune response was observed during this period. Furthermore, the virus‐producing cells remained viable. In the second model, SCID mice were immunologically reconstituted by subcutaneous implantation of thymus lobes from MHC‐identical Balb/c newborn mice and gene transfer into lymphoid cells was achieved by retroviral vectors released by co‐implanted capsules. Conclusion The implantation of such capsules containing cells that continually produce retroviral vector particles may be of use for in vivo gene therapy strategies. The data presented demonstrate the feasibility of the concept. Copyright © 2002 John Wiley & Sons, Ltd.
52.2: Hybrid Tandem White OLEDs with High Efficiency and Long Life‐time for AMOLED Displays and Solid‐State Lighting (2010)

Abstract Excellent performance (61 cd/A efficiency, 27% EQE, 6.2 V, 6500 K white point, 35,000 h half‐life) was obtained using 2‐stack hybrid tandem white OLED. This is >70% EQE improvement over the all‐fluorescent tandem white resulting in >30% reduction in power consumption for a 32″ AMOLED HDTV. Hybrid Tandems for lighting show EQE between 28.4 and − 30.6%, and lifetime between 70,000 and 125,000 h without outcoupling.
Functional Role of a Conformationally Flexible Homopurine/Homopyrimidine Domain of the Androgen Receptor Gene Promoter Interacting with SP1 and a Pyrimidine Single Strand DNA-Binding Protein (1997)

The androgen receptor (AR) gene promoter does not contain the TATA or CAAT box, but it contains a long (approximately 90-bp) homopurine/homopyrimidine (pur/ pyr) stretch immediately upstream of the Sp1-binding GC box site. This pur-pyr stretch is conserved at the same proximal position in the rat, mouse, and human AR gene promoters. Mutation of this region results in a 3-fold decline in promoter activity, indicating an important regulatory function. Examination of the conformational state of the AR pur/pyr region with the single-strand-specific S1 nuclease showed that it is capable of forming a non-B DNA structure involving unpaired single strands. Fine mapping of the S1-sensitive site revealed an unsymmetric cleavage pattern indicative of an intramolecular triple helical H-form DNA conformation. Electrophoretic mobility shift analyses showed that the pur/pyr region of the AR promoter can bind a novel pyrimidine single-strand-specific protein (ssPyrBF) and also a double-strand DNA-binding protein. Both oligonucleotide cross-competition and antibody supershift experiments established that the double-strand binding protein is equivalent to Sp1. Deoxyribonuclease I (DNase I) footprinting analysis showed multiple Sp1-binding to the pur/pyr site and a weaker Sp1 interaction to this region compared with the adjacently located GC box, where Sp1 functions to recruit the TFIID complex. These results suggest that the pur/pyr domain of the AR gene can serve to attract additional Sp1 molecules when it exists in the double-stranded B-DNA conformation. However, binding of ssPyrBF and the resultant stabilization of the non-B DNA structure is expected to prevent its interaction with Sp1. We speculate that in the TATA-less AR gene promoter, multiple weak Sp1 sites at the pur/pyr region adjacent to the GC box can provide a readily available source of this transcription factor to the functional GC box, thereby facilitating the assembly of the initiation complex.
Printed nanoparticulate composites for silicon thick-film electronics (2006)

Abstract The production of active semiconductor thick-film components typically involves the deposition of precursor materials and subsequent thermal processing to produce a massive semiconductor layer. In this paper, we present electronic materials, based on nanoparticulate silicon, to produce the active semiconducting layer, which can simply be printed onto low-temperature substrates such as paper. Particular emphasis will be given to the structure, morphology, and composition of the nanoparticles, which are produced by either gas-phase decomposition of silane or mechanical attrition of bulk silicon. Of further importance are the electrical characteristics of the composite materials, in which the active semiconductor is formed from an interconnecting backbone of silicon particles. These will be discussed for example structures, including junction field effect transistors (FETs), insulated-gate FETs, and photodiodes.