gebhart/patrepeval huggingface dataset:
Dendritic Cells Require the NF-κB2 Pathway for Cross-Presentation of Soluble Antigens (2008)

NF-kappaB-inducing kinase (NIK) is responsible for activation of the non-canonical p100 processing pathway of NF-kappaB activation. This kinase has been shown to be critical for activation of this pathway after signaling through several TNF family members including CD40. The functional importance of this pathway in CD40 and TLR-induced dendritic cell (DC) differentiation was studied in vivo in the alymphoplasia (Aly) mouse. The Aly mouse expresses a mutant NIK molecule that prohibits the induction of the non-canonical pathway. We show that while MHC class II presentation and in vivo migration of Aly DCs is intact, these cells are unable to cross-prime CD8+ T cells to exogenous Ag. Gene expression array analysis of DCs matured in vivo indicates multiple defects in Ag processing pathways after maturation and provide a global view of the genes that are regulated by the NF-kappaB2 pathway in DCs. These experiments indicate a possible role for NIK in mediating cross-priming of soluble Ag. In addition, our findings explain the profound immune unresponsiveness of the Aly mouse.
Formation of dispersions using ‘‘flow focusing’’ in microchannels (2018)

A flow-focusing geometry is integrated into a microfluidic device and used to study drop formation in liquid–liquid systems. A phase diagram illustrating the drop size as a function of flow rates and flow rate ratios of the two liquids includes one regime where drop size is comparable to orifice width and a second regime where drop size is dictated by the diameter of a thin ‘‘focused’’ thread, so drops much smaller than the orifice are formed. Both monodisperse and polydisperse emulsions can be produced.
Molecular Scale Buckling Mechanics in Individual Aligned Single-Wall Carbon Nanotubes on Elastomeric Substrates (2007)

We have studied the scaling of controlled nonlinear buckling processes in materials with dimensions in the molecular range (i.e., approximately 1 nm) through experimental and theoretical studies of buckling in individual single-wall carbon nanotubes on substrates of poly(dimethylsiloxane). The results show not only the ability to create and manipulate patterns of buckling at these molecular scales, but also, that analytical continuum mechanics theory can explain, quantitatively, all measurable aspects of this system. Inverse calculation applied to measurements of diameter-dependent buckling wavelengths yields accurate values of the Young's moduli of individual SWNTs. As an example of the value of this system beyond its use in this type of molecular scale metrology, we implement parallel arrays of buckled SWNTs as a class of mechanically stretchable conductor.
[Caustic esophagitis in children]. (1992)

Treatment of caustic ingestion in children is a difficult and controversial problem which has not yet to be resolved. Here we report the evolution of fourteen children with esophageal injury after caustic ingestion that were treated with steroids at high-doses, nasogastric intubation and antibiotics. An early esophagoscopy was performed in all patients. Four patients developed esophageal strictures, three of which were mild and subsequent dilatation was successful. Only one patient was referred to surgery. We think that although it cannot be established, the use of high-dose of steroids and nasogastric intubation may be helpful for children with caustic esophagitis. We conclude that early endoscopy is useful to evaluate the severity of the lesions and to establish the necessity for treatment.
Animal Models for Periodontal Disease (2011)

Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis) in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed.
Heat shock causes the collapse of the intermediate filament cytoskeleton in Drosophila embryos (1990)

Heat shock has a dramatic effect on the organization of the cytoplasm, causing the intermediate filament cytoskeleton to aggregate at the nucleus. This has previously been shown in cultured Drosophila and mammalian cells. In this paper we analyze the heat lability of the intermediate filament cytoskeleton in early Drosophila embryos by indirect immunofluorescence. At all stages of embryogenesis tested, the intermediate filament cytoskeleton, which is maternally provided, is severely disturbed by 30 min heat shock at 37 degrees C. After the nuclei have migrated to the subcortical cytoplasm, it collapses around them. Nuclei in all heat-shocked embryos are considerably enlarged and become displaced. Embryos before cellular blastoderm stage, in which heat shock protein synthesis is not inducible, are irreversibly arrested in development by heat shock. Embryos at or after cellular blastoderm, which do synthesize heat shock proteins in response to stress, are also immediately arrested in development but continue development when returned to 25 degrees C. We discuss the possibility that cytoplasmic events such as the intermediate filament cytoskeleton rearrangement may be involved in heat shock-mediated phenocopy induction.
The Targeted Oncolytic Poxvirus JX-594 Demonstrates Antitumoral, Antivascular, and Anti-HBV Activities in Patients With Hepatocellular Carcinoma (2008)

JX-594 is a targeted oncolytic poxvirus that is designed to eradicate cancer cells having cell-cycle defects, through replication, cell lysis, and spread within tumors; oncolysis-induced tumor vascular shutdown and immunostimulation are augmented by granulocyte monocyte-colony-stimulating factor (GM-CSF) transgene expression. We have previously shown, in animal models of hepatocellular carcinoma (HCC), that JX-594 is a promising anticancer agent. We tested JX-594 in three patients with advanced refractory hepatitis B virus (HBV)-associated HCC through intratumoral administration. JX-594 treatment was well-tolerated and resulted in antitumoral efficacy in all three patients, despite the presence of high levels of neutralizing antibodies. JX-594 replication, its release into the circulation, distant tumor targeting were demonstrated. JX-594 administration resulted in the induction of antivascular cytokines, and was associated with tumor vascular shutdown. We also showed, for the first time, that oncolytic virotherapy can suppress underlying HBV replication in HCC patients, and that tumor tissue could be the primary source of acute HBV replication and acute post-treatment HBV release. JX-594 treatment in HBV-associated HCC warrants further clinical testing; a Phase II trial is underway.
High Mobility Group Box 1 Protein Inhibits the Proliferation of Human Mesenchymal Stem Cells and Promotes Their Migration and Differentiation along Osteoblastic Pathway (2008)

Extracellular high mobility group box 1 (HMGB1) is a novel cytokine that takes part in the processes of in: ammation, tissue damage and regeneration. Mesenchymal stem cells (MSCs) are adult stem cells characterized by their inherently suppressive activities on inflammative and allo-immune reactions. In the present study, we have addressed whether HMGB1 could affect the biological properties of human bone marrow MSCs. Transwell experiments showed that HMGB1 induced MSC migration and this effect could not be hampered by a blocking antibody against the receptor for advanced glycation end products (RAGE). MSCs exposed to HMGB1 were negative for CD31, CD45, CD80, and HLA-DR, and displayed equal levels of CD73, CD166, and HLA-ABC compared with their counterparts, but HMGB1 profoundly suppressed MSC proliferation in a dose-dependent manner as evaluated by carboxyfluorescein diacetate succinmidyl ester dye dilution assay. Furthermore, HMGB1 triggered the differentiation of MSCs into osteoblasts as identified by histochemical staining, traditional RT-PCR and real-time RT-PCR analysis on mRNA expression of lineage-specific molecular markers. The differentiation-inductive activity could neither be inhibited by RAGE neutralizing antibody. Moreover, HMGB1-treated MSCs displayed unchanged suppressive activity on in vitro lymphocyte cell proliferation elicited by ConA. Collectively, the data suggest that MSCs are a target of HMGB1.
Protophane und Polyaromaten, XXII. Nucleophile Alkylierung und Arylierung des 2,2′‐Bipyridyls (1976)

Abstract 2,2′‐Bipyridyl konnte erstmals nucleophil alkyliert werden. Bei der Umsetzung mit Methyl‐ und n‐Butyllithium entstand je nach den Bedingungen sehr selektiv die 6‐Alkyl‐ oder 6,6′‐Dialkyl Verbindung (41—64%). Die Anwendung relativ tiefer Temperaturen erlaubte in mittlerer Ausbeute auch die Darstellung von 6‐Aryl‐Verbindungen (Aryl = Phenyl, 2‐Pyridyl). Im Konkurrenzversuch zeigte 2,2′‐Bipyridyl gegenüber n‐Butyllithium deutlich höhere elektrophile Aktivität als Pyridin.
A Simple and Efficient System for Regulating Gene Expression in Human Pluripotent Stem Cells and Derivatives (2014)

Regulatable transgene expression in human pluripotent stem cells (hPSCs) and their progenies is often necessary to dissect gene function in a temporal and spatial manner. However, hPSC lines with inducible transgene expression, especially in differentiated progenies, have not been established due to silencing of randomly inserted genes during stem cell expansion and/or differentiation. Here, we report the use of transcription activator-like effector nucleases-mediated targeting to AAVS1 site to generate versatile conditional hPSC lines. Transgene (both green fluorescent protein and a functional gene) expression in hPSCs and their derivatives was not only sustained but also tightly regulated in response to doxycycline both in vitro and in vivo. We modified the donor construct so that any gene of interest can be readily inserted to produce hPSC lines with conditional transgene expression. This technology will substantially improve the way we study human stem cells.
Tumor necrosis factor-alpha and hematopoietic progenitors: effects of tumor necrosis factor on the growth of erythroid progenitors CFU-E and BFU-E and the hematopoietic cell lines K562, HL60, and HEL cells. (1987)

Macrophages can modulate the growth of hematopoietic progenitors. We have examined the effects of tumor necrosis factor-alpha, a product of activated macrophages, on human erythroid progenitors (CFU-E, BFU-E) and the hematopoietic cell lines K562, HL60, and HEL cells. Tumor necrosis factor (TNF) significantly inhibited CFU-E and BFU-E growth at concentrations as low as 10(-11)-10(-12) M (0.2 U/ml), although erythroid colony and burst formation were not totally ablated. Preincubation of marrow samples with TNF for 15 min was sufficient to suppress erythroid colony and burst formation. Addition of TNF after the start of culture inhibited CFU-E- and BFU-E-derived colony formation if TNF was added within the first 48 h of culture. Additionally, TNF inhibited the growth of highly purified erythroid progenitors harvested from day 5 BFU-E. The colonies which formed in cultures treated with TNF were significantly smaller than those formed in control cultures. TNF (10(-8)-10(-10) M) also suppressed the growth of the hematopoietic cell lines K562, HL60, and HEL cells, with 40%-60% of the cells being sensitive to TNF. Preincubation of HL60 cells with TNF for 15 min significantly inhibited their growth. K562, HL60, and HEL cells expressed high-affinity receptors for TNF in low numbers (6000-10,000 receptors per cell). Fluorescence-activated cell sorter analysis of TNF binding to HEL cells demonstrated that the majority of these cells expressed TNF receptors. These data suggest that: (1) TNF is a rapid irreversible and extremely potent inhibitor of CFU-E, BFU-E, and hematopoietic cell lines K562, HL60, and HEL cells; (2) TNF appears to be acting on a subpopulation of erythroid cells, predominantly CFU-E, BFU-E, and possibly proerythroblasts; (3) TNF appears not to require accessory cells such as lymphocytes or macrophages to inhibit erythroid progenitors; and (4) the presence of TNF receptors on hematopoietic cells is not sufficient to confer sensitivity to TNF since the majority (80%-95%) of HEL cells express TNF receptors while only 40%-60% are inhibited by TNF.
A Quantitative Positioning Device For Transcranial Magnetic Stimulation (2005)

A device and method are presented which allow for improved accuracy and repeatability of magnetic stimulation tests.
The ubiquitin-proteasome system and nonsense-mediated mRNA decay in hypertrophic cardiomyopathy (2009)

Cardiomyopathies represent an important cause of cardiovascular morbidity and mortality due to heart failure, arrhythmias, and sudden death. Most forms of hypertrophic cardiomyopathy (HCM) are familial with an autosomal-dominant mode of inheritance. Over the last 20 years, the genetic basis of the disease has been largely unravelled. HCM is considered as a sarcomeropathy involving mutations in sarcomeric proteins, most often beta-myosin heavy chain and cardiac myosin-binding protein C. 'Missense' mutations, more common in the former, are associated with dysfunctional proteins stably integrated into the sarcomere. 'Nonsense' and frameshift mutations, more common in the latter, are associated with low mRNA and protein levels derived from the diseased allele, leading to haploinsufficiency of the remaining healthy allele. The two quality control systems responsible for the removal of the affected mRNAs and proteins are the nonsense-mediated mRNA decay (NMD) and the ubiquitin-proteasome system (UPS), respectively. This review discusses clinical and genetic aspects of HCM and the role of NMD and UPS in the regulation of mutant proteins, evidence for impairment of UPS as a pathogenic factor, as well as potential therapies for HCM.
Learning to share (2008)

Wideband technologies in the unlicensed spectrum can satisfy the ever-increasing demands for wireless bandwidth created by emerging rich media applications. The key challenge for such systems, however, is to allow narrowband technologies that share these bands (say, 802.11 a/b/g/n, Zigbee) to achieve their normal performance, without compromising the throughput or range of the wideband network. This paper presents SWIFT, the first system where high-throughput wideband nodes are shown in a working deployment to coexist with unknown narrowband devices, while forming a network of their own. Prior work avoids narrowband devices by operating below the noise level and limiting itself to a single contiguous unused band. While this achieves coexistence, it sacrifices the throughput and operating distance of the wideband device. In contrast, SWIFT creates high throughput wireless links by weaving together non-contiguous unused frequency bands that change as narrowband devices enter or leave the environment. This design principle of cognitive aggregation allows SWIFT to achieve coexistence, while operating at normal power, and thereby obtaining higher throughput and greater operating range. We implement SWIFT on a wideband hardware platform, and evaluate it in the presence of 802.11 devices. In comparison to a baseline that coexists with narrowband devices by operating below their noise level, SWIFT is equally narrowband-friendly but achieves 3.6-10.5x higher throughput and 6x greater range.
Pathogen inactivation ofLeishmania donovani infantumin plasma and platelet concentrates using riboflavin and ultraviolet light (2005)

There is no donor screen for Leishmania and other pathogens constantly emerging in our blood supply. The Mirasol PRT System for Platelets and Plasma is an effective means of killing Leishmania and other emerging pathogens in these blood products.
The pharmacodynamics of lansoprazole administered via gastrostomy as intact, non‐encapsulated granules (1998)

Lansoprazole can effectively suppress intragastric acidity when given through a gastrostomy as intact, non-encapsulated granules in orange juice.
Adenovirus-mediated Transfer of a Truncated Transforming Growth Factor-β (TGF-β) Type II Receptor Completely and Specifically Abolishes Diverse Signaling by TGF-β in Vascular Wall Cells in Primary Culture (1996)

We constructed an adenoviral vector expressing a mutated human type II transforming growth factor-beta (TGF-beta) receptor that was truncated of its kinase domain (AdexCATbetaTR) and examined whether this truncated receptor could abolish signaling by TGF-beta using arterial endothelial cells and smooth muscle cells, as well as a lung epithelial cell line (Mv1Lu). Infection of cells with AdexCATbetaTR induced expression of the truncated receptor, the amount of which would be excessive compared with those of both full-length type I and type II receptors, as assessed by levels of their mRNAs. The antiproliferative effect of TGF-beta was completely eliminated in both endothelial cells and Mv1Lu that were infected with AdexCATbetaTR. The transcriptional activation by TGF-beta of plasminogen activator inhibitor-1 and fibronectin was entirely suppressed. Abrogation of the TGF-beta-enhanced production of type I collagen in infected smooth muscle cells was confirmed by immunocytostaining and by [14C]proline incorporation in a quantitative manner. Mitogenic response to other growth factors remained unaffected in infected cells. Our data demonstrated that the adenovirus-mediated transfer of a truncated type II TGF-beta receptor completely and specifically abolishes the diverse effects of TGF-beta as a dominant-negative mutation, supporting the hypothesis that both the type I and type II receptors are required for all signaling by TGF-beta. This method may facilitate the clarification of the role of TGF-beta both in vitro and in vivo.
Combined targeting of adenoviruses to integrins and epidermal growth factor receptors increases gene transfer into primary glioma cells and spheroids. (2001)

Adenoviral-mediated gene transfer is suboptimal in human glioma and limits in vivo gene therapy approaches. There is a need for targeted vectors able to enhance gene transfer into the tumor as well as to lower the viral load in the surrounding normal tissues. We evaluated primary human tumor samples by immunohistochemistry and fluorescence-activated cell sorter for expression of the Coxsackie-adenovirus receptor and other antigens with potential utility to redirect adenoviruses (Ads) to gliomas. In the majority of the samples, Coxsackie-adenovirus receptor expression was low. This correlated with inefficient gene transfer in vitro. Epidermal growth factor receptor (EGFR) and alpha(v)beta5 integrins were often highly, but heterogeneously, expressed. We hypothesized that these receptors, overexpressed in tumor but not in normal brain, could serve as independent binding sites for alternative pathways of infection with targeted Ads. We examined this, using Ads that expressed the luciferase reporter gene under the cytomegalovirus promoter. Targeting to the EGFR was performed with a single-chain bispecific antibody directed against the human EGFR and against the fiber knob of the Ad. Targeting to the alpha(v) integrins was performed by insertion of an integrin-binding sequence, RGD-4C, in the HI-loop of the Ad. Increased luciferase gene transfer in primary glioma cells was observed in 8 of 13 samples with EGFR-targeting (2-11 times enhancement; median, 6) and in all of the samples with RGD-targeting (2-42 times enhancement; median, 12). Combining the two targeting motifs further enhanced the gene transfer in primary glioma cells in an additive manner (3-56 times; median, 20). The double-targeted Ads also strongly augmented gene transfer into organotypic glioma spheroids. Conversely, gene transfer into normal brain explants was reduced dramatically using Ads targeted to the tumor. Our findings demonstrate the feasibility and benefit of binding multiple ligands to the adenoviral fiber knob. These vectors have a great potential for clinical use in the context of tumors that are usually heterogeneous for target antigen expression at the single-cell level.
Development of Novel Photosensitive Polymer Systems Using Photoacid and Photobase Generators. (2002)

Novel photosensitive polymers using photoacid and photobase generators are described. As photosensitive polymers using photoacid generators, two topics on i) copolymers of methacrylonitrile that are transparent at 157nm and promising as F2 resists and ii) photocrosslinkable polymers with thermally degradable units from the eviwpoint of recycling of photosensitive polymers are picked up. Subjects of photosensitive polymers using photobase genrators are i) photochemistry of oxime derivatives and onium salts and their use for design of novel photosensitive polymers and ii) polymeric photobase generators and their applications. The contents in this review include topics from basic concepts to up-to-date technology.
Active DNA unwinding dynamics during processive DNA replication (2012)

Duplication of double-stranded DNA (dsDNA) requires a fine-tuned coordination between the DNA replication and unwinding reactions. Using optical tweezers, we probed the coupling dynamics between these two activities when they are simultaneously carried out by individual Phi29 DNA polymerase molecules replicating a dsDNA hairpin. We used the wild-type and an unwinding deficient polymerase variant and found that mechanical tension applied on the DNA and the DNA sequence modulate in different ways the replication, unwinding rates, and pause kinetics of each polymerase. However, incorporation of pause kinetics in a model to quantify the unwinding reaction reveals that both polymerases destabilize the fork with the same active mechanism and offers insights into the topological strategies that could be used by the Phi29 DNA polymerase and other DNA replication systems to couple unwinding and replication reactions.
Promiscuous behavior of HPV16E6 specific T cell receptor beta chains hampers functional expression in TCR transgenic T cells, which can be restored in part by genetic modification. (2010)

Promiscuous behavior of the HPV16E6 specific TCRbeta chain can in part be forced back into specific action in TCR transgenic T cells by codon modification in combination with the inclusion of an extra cysteine in the TCR chains.
Genes Affecting Early Development in Caenorhabditis elegans (1985)

We have identified several genes that appear to control the early events in the development of Caenorhabditis elegans (Hirsh and Vanderslice 1976; Wood et al. 1980). We continue to study them genetically and characterize them morphologically. We describe here three of these genes that appear to be involved in establishing the organization of the embryonic cytoplasm and in positioning the early cleavage furrows (K.J. Kemphues et al., in prep.). In addition, we review our continuing studies on the characterization of the C. elegans genome, the goal of which has been to facilitate the study of the molecular basis of the role of these genes in early development. Our earlier physical studies on the nematode genome provided an understanding of the sequence organization of the DNA and revealed considerable DNA sequence polymorphism between different strains of C. elegans (Emmons et al. 1979, 1980; Hirsh et al. 1982). Most of the DNA...