gebhart/patrepeval huggingface dataset:
Cholesterol enhances cationic liposome-mediated DNA transfection of human respiratory epithelial cells (1995)

Cationic liposome transfection reagents are useful for transferring polynucleotides into cells, and have been proposed for human pulmonary gene therapy. The effect of adding cholesterol to cationic lipid preparations has been tested by first formulating the cationic lipid N-[1-(2,3-dioleoyloxy)propyl-N-[1-(2-hydroxy)ethyl]-N,N-dimethyl ammonium iodide (DORI) with varying amounts of dioleoylphosphatidylethanolamine (DOPE) and cholesterol. Cholesterol was found to enhance lipid-mediated transfection in both the respiratory epithelial cells and mouse fibroblasts. These findings will facilitate nucleic acid transfection of many cell types including differentiated epithelial cell monolayers, and therefore may be useful for examining gene regulation in various cell types and for developing pulmonary gene therapy.
Regulation of the Activity of p38 Mitogen-Activated Protein Kinase by Akt in Cancer and Adenoviral Protein E1A-Mediated Sensitization to Apoptosis (2003)

The adenoviral early region 1A (E1A) protein mediates sensitization to different stimulus-induced apoptosis, such as tumor necrosis factor alpha, UV and gamma irradiation, and different categories of anticancer drugs. However, the molecular mechanisms underlying E1A-mediated sensitization to apoptosis are still not completely defined. Here, we show that E1A-mediated sensitization to apoptosis by the inactivation of a key survival factor Akt and the activation of a pro-apoptotic factor p38. Also, inactivation of Akt by either a specific inhibitor or a genetic knockout of Akt1 results in p38 activation, possibly through the release of the activity of p38 upstream kinases, including ASK1 and MEKK3. In addition, we showed that p38 phosphorylation is downregulated and Akt phosphorylation is upregulated in multiple human tumor tissues, and this correlates with tumor stage in human breast cancer. A deletion mutation of a conserved domain of E1A, which is required for E1A-induced downregulation of Akt activity, disrupts E1A-mediated upregulation of p38 activity and also eliminates E1A-mediated chemosensitization. Thus, activation of p38 and inactivation of Akt may have general implications for tumor suppression and sensitization to apoptosis.
Lattice gas hydrodynamics in two and three dimensions (1986)

Hydrodynamical phenomena can be simulated by discrete lattice gas models obeing cellular automata rules (U. Frisch, B. Hasslacher, and Y. Pomeau, Phys. Rev. Lett. 56, 1505, (1986); D. d'Humieres, P. Lallemand, and U. Frisch, Europhys. Lett. 2, 291, (1986)). It is here shown for a class of D-dimensional lattice gas models how the macrodynamical (large-scale) equations for the densities of microscopically conserved quantities can be systematically derived from the underlying exact ''microdynamical'' Boolean equations. With suitable restrictions on the crystallographic symmetries of the lattice and after proper limits are taken, various standard fluid dynamical equations are obtained, including the incompressible Navier-Stokes equations in two and three dimensions. The transport coefficients appearing in the macrodynamical equations are obtained using variants of fluctuation-dissipation and Boltzmann formalisms adapted to fully discrete situations.
A Novel Orally Available Proteasome Inhibitor NPI-0052 Induces Killing in Multiple Myeloma (MM) Cells Resistant to Conventional and Bortezomib Therapies. (2004)

Abstract The recent success of bortezomib/proteasome inhibitor PS-341 (VelcadeTm) provides evidence that proteasome inhibitors can be safely utilized clinically. Specifically, bortezomib is currently being used to treat MM patients (pts) who have relapsed after initial therapy and refractory to current therapy and is under evaluation for treatment of newly diagnosed pts. Although bortezomib kills MM cells, prolonged exposure is associated with attendant toxicity and development of bortezomib-resistance. Here we show that a novel non-peptide proteasome inhibitor NPI-0052 triggers apoptosis even in bortezomib-resistant patient MM cells, without affecting the viability of normal cells. NPI-0052 overcomes MM cell-resistance to conventional therapies including melphalan (LR5), doxorubicin (Dox-40), dexamethasone (MM.1R, U266, RPMI-8226) and retains its anti-tumor activity in cells harboring two major mechanisms of drug-resistance: overexpression of P-glycoprotein and altered topoisomerase-II activity. Importantly, NPI-0052, like bortezomib, blocks MM cell growth induced by both adhesion to bone marrow stromal cells (BMSCs) and related cytokine secretion, thereby depriving MM cells of the growth and survival advantage conferred by the BM microenvironment. Moreover, NPI-0052-triggers MM cells apoptosis despite the presence of interleukin-6 or insulin-like growth factor-1 (IGF-1), two major growth and anti-apoptotic factors for MM cells. NPI-0052 also overcomes the cytoprotective effects of anti-apoptotic proteins Bcl2 and Hsp27, as well as NF-kB-mediated growth/survival, and drug-resistance in MM cells. Initial in vivo studies in animal models using either oral or intravenous administration have established the maximum tolerated dose (MTD) based on the whole blood proteasome activity. NPI-0052 decreased proteasome activity in packed whole blood lysates in a dose dependent fashion, and these data also suggest that NPI-0052 is orally active. The mechanisms whereby NPI-0052-trigger MM cell death includes: loss of mitochondrial membrane potential; Superoxide generation; release of mitochondrial proteins cytochrome-c/Smac; and activation of caspase-8/9/3. Conversely, the pan caspase inhibitor Z-VAD-fmk abrogates NPI-0052-induced apoptosis. Finally, combining NPI-0052 and bortezomib triggers synergistic apoptosis. Together, these findings provide the framework for clinical evaluation of NPI-0052, either alone or in combination with bortezomib, to inhibit tumor cell growth, reduce bortezomib-related toxicity, overcome bortezomib-resistance, and improve patient outcome in MM.
Characterization of a small plasmid from Desulfovibrio desulfuricans and its use for shuttle vector construction (1993)

A 2.3-kb plasmid present in about 20 copies per genome was identified in extracts of Desulfovibrio desulfuricans G100A and designated pBG1. It appears to be unable to replicate in Escherichia coli. Although composite plasmids of pBG1 inserted into pTZ18U are stable in E. coli, few if any pBG1-specific transcripts are detectable. The plasmid sequence reveals several features typical of the origin of replication of non-ColE1 enterobacterial plasmids as well as several potential open reading frames. This small replicon has been shown to support the replication of recombinant plasmids in D. desulfuricans G100A and Desulfovibrio fructosovorans. A conjugable shuttle vector has been constructed.
Adaptive trellis coded modulation for bandlimited meteor burst channels (2003)

The author investigates the throughput performance of an adaptive information-rate technique on the bandlimited meteor burst channel. It is shown that an adaptive technique that uses trellis-coded modulation (TCM) can increase throughput over the conventional constant-rate modem by more than a factor of 3. An expression for the theoretical information capacity of the bandlimited meteor burst channel is based on Shannon's well-known capacity formula. The capacity expression provides a point of reference against which future adaptive schemes can be judged. Although the proposed technique offers large performance gains, it still only achieves 40% of the channel capacity predicted by Shannon's capacity formula.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Regulation of Interleukin 2 Gene Expression by CD28 Costimulation in Mouse T-Cell Clones: both Nuclear and Cytoplasmic RNAs Are Regulated with Complex Kinetics (1995)

T-cell receptor (TCR) signalling is required to induce expression of the interleukin 2 (IL-2) gene in mouse T cells. Additional costimulation through CD28 augments IL-2 production by 30- to 100-fold. Using IL-2 RNA accumulation and transcription reporter assays, we have addressed potential mechanisms of CD28 regulation at various time points of stimulation. The kinetic regulation of IL-2 mRNA by TCR and CD28 signals is complex: (i) at the earliest detectable time point, CD28 signalling causes a 20-fold increase compared with TCR signalling alone; (ii) both groups rapidly accumulate mRNA for the first 4 h; (iii) IL-2 mRNA then disappears from cells stimulated through the TCR alone but plateaus or increases slightly in cells costimulated through CD28; and (iv) after 8 h, the mRNA disappears in cultures with the anti-CD28 antibody. Transcription reporter assays did not show a specific effect of CD28 signalling on IL-2 enhancer driven transcription. This was true for either a 353- or a 1.9-kb enhancer, over a broad range of kinetics and TCR occupancy, and with several TCR signal mimics. The early component of CD28 costimulation is nuclear, however, since the initial enhancement of mRNA is also found in unspliced IL-2 RNA. Between 2 and 6 h, there is a marked difference in the rates of decay of IL-2 mRNA in the presence and absence of the CD28 signalling. Rapid decay of IL-2 mRNA commences after 8 h even in the presence of CD28 signals, although the decay occurs at a rate slower than that seen after 4 h of anti-TCR stimulation alone. This complexity suggests the existence of two interesting molecular mechanisms by which CD28 costimulates lymphokine gene expression.
Towards easier human-robot interaction to help inexperienced operators in SMEs (2012)

The capability to use advanced tools, devices, and software is essential for enterprises to survive in global competition. Inter-cognitive communication is an important element in the development of engineering applications where natural and artificial cognitive systems should work together efficiently. Small and medium-sized enterprises (SMEs) are becoming increasingly important in society, as our economies depend heavily on SMEs, which represent the majority of jobs created. Global competition has forced these SMEs to change and develop their production systems radically, to be more flexible. Industrial robots are seen as a key element in flexible manufacturing systems. However, currently, industrial robots are not commonly used in SMEs; one reason is the complex handling, especially the time-consuming programming. Industrial robot systems usually lack simple user interfaces, and the programming is usually carried out by the typical teach pendant teaching method. This method is a tedious and time-consuming task that requires a remarkable amount of expertise. In industry, this type of robot programming can be justified economically only for the production of large lot sizes, which are not typical for SMEs. Therefore, new approaches to human-robot interaction are required. Cognitive infocommunication can play a key role in these applications. Accordingly, our main goal in this paper is to present experiences in developing easier human-robot interaction to help even inexperienced operators use robots in SMEs. These examples show a variety of ways that inter-cognitive communication between human and artificial cognitive systems can be utilized in robotics. We also present our system and software architecture used in the development of generic industrial robot programming for easy-to-use applications, as well as some examples of our service robot development. Service robotics offers numerous possibilities to utilize cognitive infocommunication, but development of reliable and flexible solutions is challenging, due to dynamic environments, and because inexperienced users often understand very little about the robots and their internal states.
In vivo optical coherence tomography imaging of human skin: norm and pathology (2000)

BACKGROUND/AIMS: Since the majority of skin diseases are known to be accompanied by structural alterations, research efforts are focused on the development of various novel diagnostic techniques capable of providing in vivo information on the skin structure. An essential parameter here is spatial resolution. In this paper we demonstrate the capabilities of optical coherence tomography (OCT) in detecting in vivo specific features of thin and thick skin. A particular focus is made on the identification of OCT patterns typical of certain pathological processes in skin, by performing parallel histological and tomographical studies. METHODS: To obtain images of the skin, we used a compact fiber OCT system developed at the Institute of Applied Physics of the Russian Academy of Sciences. A low coherence source (superluminescent diode) operated at a wavelength of 1280 nm; the output power was 0.5-2 mW. This power is low enough to conform to the ANSI safety standards for light exposure. The in-depth resolution limited by the spectral bandwidth (40-50 nm) of the probing light was approximately 20 &mgr;m. The lateral resolution determined by the probe light focusing ranged from 15 to 30 &mgr;m. In this series of experiments the maximum depth of imaging did not extend beyond 1.5 mm. Obtaining images of skin regions 2-6 mm long took 2-4 s. OCT capabilities for imaging normal skin of different localization and some skin diseases were studied in 12 healthy volunteers and 24 patients. RESULTS: OCT imaging of the skin can detect in vivo such general pathological reactions of the human body as active inflammation and necrosis. OCT is useful for in vivo diagnosis of some specific processes in the skin, including hyperkeratosis, parakeratosis and formation of intradermal cavities. OCT imaging is noninvasive and therefore allows frequent multifocal examination of skin without any adverse effects. OCT can perform monitoring of disease progress and recovery in the course of therapy. Morphometric studies, measurements of the depth and extension of skin pathology within the human body can be easily performed by OCT. CONCLUSIONS: OCT allows imaging of subsurface soft tissues with the spatial resolution of 15-20 &mgr;m, a resolution one order of magnitude higher than that provided by other clinically available noninvasive diagnostic techniques. An imaging depth of up to 1.5-2 mm, given by current OCT technology, is sufficient to examine the skin. Real time OCT imaging can provide information not only on the structure, but also on some specific features in the functional state, of tissues. OCT imaging is a noninvasive technique, i.e., OCT does not cause trauma and has no side effects since it utilizes radiation in the near infrared wavelength range at a power as low as 1 mW.
Coniochaeta elegans sp. nov., Coniochaeta montana sp. nov. and Coniochaeta nivea sp. nov., three new species of endophytes with distinctive morphology and functional traits (2021)

A growing interest in fungi that occur within symptom-less plants and lichens (endophytes) has uncovered previously uncharacterized species in diverse biomes worldwide. In many temperate and boreal forests, endophytic <i>Coniochaeta</i> (Sacc.) Cooke (<i>Coniochaetaceae</i>, <i>Coniochaetales, Sordariomycetes</i>, <i>Ascomycota</i>) are commonly isolated on standard media, but rarely are characterized. We examined 26 isolates of <i>Coniochaeta</i> housed at the Gilbertson Mycological Herbarium. The isolates were collected from healthy photosynthetic tissues of conifers, angiosperms, mosses and lichens in Canada, Sweden and the United States. Their barcode sequences (nuclear ribosomal internal transcribed spacer and 5.8S; ITS rDNA) were ≤97% similar to any documented species available through GenBank. Phylogenetic analyses based on two loci (ITS rDNA and translation elongation factor 1-alpha) indicated that two isolates represented <i>Coniochaeta cymbiformispora</i>, broadening the ecological niche and geographic range of a species known previously from burned soil in Japan. The remaining 24 endophytes represented three previously undescribed species that we characterize here: <i>Coniochaeta elegans</i> sp. nov., <i>Coniochaeta montana</i> sp. nov. and <i>Coniochaeta nivea</i> sp. nov. Each has a wide host range, including lichens, bryophytes and vascular plants. <i>C. elegans</i> sp. nov. and <i>C. nivea</i> sp. nov. have wide geographic ranges. <i>C. montana</i> sp. nov. occurs in the Madrean biome of Arizona (USA), where it is sympatric with the other species described here. All three species display protease, chitinase and cellulase activity <i>in vitro</i>. Overall, this study provides insight into the ecological and evolutionary diversity of <i>Coniochaeta</i> and suggests that these strains may be amenable for studies of traits relevant to a horizontally transmitted, symbiotic lifestyle.
Oligomerization of the Polycystin-2 C-terminal Tail and Effects on Its Ca2+-binding Properties (2015)

Polycystin-2 (PC2) belongs to the transient receptor potential (TRP) family and forms a Ca(2+)-regulated channel. The C-terminal cytoplasmic tail of human PC2 (HPC2 Cterm) is important for PC2 channel assembly and regulation. In this study, we characterized the oligomeric states and Ca(2+)-binding profiles in the C-terminal tail using biophysical approaches. Specifically, we determined that HPC2 Cterm forms a trimer in solution with and without Ca(2+) bound, although TRP channels are believed to be tetramers. We found that there is only one Ca(2+)-binding site in the HPC2 Cterm, located within its EF-hand domain. However, the Ca(2+) binding affinity of the HPC2 Cterm trimer is greatly enhanced relative to the intrinsic binding affinity of the isolated EF-hand domain. We also employed the sea urchin PC2 (SUPC2) as a model for biophysical and structural characterization. The sea urchin C-terminal construct (SUPC2 Ccore) also forms trimers in solution, independent of Ca(2+) binding. In contrast to the human PC2, the SUPC2 Ccore contains two cooperative Ca(2+)-binding sites within its EF-hand domain. Consequently, trimerization does not further improve the affinity of Ca(2+) binding in the SUPC2 Ccore relative to the isolated EF-hand domain. Using NMR, we localized the Ca(2+)-binding sites in the SUPC2 Ccore and characterized the conformational changes in its EF-hand domain due to trimer formation. Our study provides a structural basis for understanding the Ca(2+)-dependent regulation of the PC2 channel by its cytosolic C-terminal domain. The improved methodology also serves as a good strategy to characterize other Ca(2+)-binding proteins.
[Drug-induced diabetes mellitus: the exemple of atypical antipsychotics]. (2005)

As an example of iatrogenic diabetes, we discuss the problem of diabetes mellitus in patients receiving atypical antipsychotics. The risk of diabetes mellitus appears to be different according to various molecules with, by decreasing order, clozapine, olanzapine, risperidone and quetiapine, and finally amisulpride, aripiprazole and ziprasidone. A careful analysis of published case reports and series indicates the existence of two different problems: 1) the rather common development of impaired glucose tolerance or diabetes mellitus (often associated with metabolic syndrome) related to weight gain in individuals at risk for type 2 diabetes; and 2) the occurrence of rare cases of acute metabolic episodes with severe ketoacidosis and/or pancreatitis whose pathophysiological mechanisms remain largely unknown. Generally speaking, the pathophysiology involves both increased insulin resistance and deficient insulin secretion. Cautious metabolic monitoring of patients receiving atypical antipsychotics is recommended, and the selection of the appropriate drug should be influenced by the metabolic profile of the various molecules and the metabolic risk of the patients who should be treated with atypical antipsychotics.
Regulatory role of IgE-binding factors from rat T lymphocytes. V. The carbohydrate moieties in IgE-potentiating factors and IgE-suppressive factors. (1982)

Abstract IgE-binding factors were formed by incubation of Con A-activated cells with IgE, and the nature of the carbohydrate moieties in these factors was assessed by measuring their affinity for Con A, peanut agglutinin (PNA), and Limulus polyphenols agglutinin (LPA). It was found that IgE-suppressive factors formed by 1 µg/ml Con A-activated cells had affinity for PNA but did not bind to either Con A or LPA. The presence of tunicamycin during their biosynthesis affected neither the affinity of the factors for PNA nor their biologic activity. These results suggest that IgE-suppressive factors have an O-glycosidicalty linked oligosaccharide containing β-glycosidically linked galactose as a terminal residue. By contrast, IgE-potentiating factors formed by 10 µg/ml Con A-activated cells bound to Con A, lentil lectin, and LPA. The removal by neuraminidase of sialic acid in the potentiating factors resulted in loss of their biologic activity. When the 10 µg/ml Con A-activated cells were cultured with IgE in the presence of tunicamycin, the IgE-binding factors formed in the culture no longer bound to Con A or the lentil lectin, and selectively suppressed the IgE response. The results indicate that IgE-potentiating factors contain a N-glycosidically linked mannose-rich oligosaccharide. However, the IgE-binding factors formed in the presence of tunicamycin retained their affinity for LPA. Furthermore, neuraminidase treatment of the factors generated in the presence of tunicamycin resulted in loss of their affinity for LPA and the appearance of affinity for PNA, with persistence of IgE-suppressive activity. The biologic activity of the latter factors after neuraminidase treatment and their affinity for lectins are identical to those of IgE-suppressive factors. The results indicate that IgE-potentiating factors have not only N-glycosidically linked oligosaccharide but also O-glycosidically linked oligosaccharide, and that the former sugar side chain is essential for their biologic function. Intracellular IgE-binding factors were detected in both 10/ig/ml Con A-activated cells and 1 µg/ml Con A-activated cells after incubation with IgE for 4 hr, when no IgE-binding factors were detectable in the culture fluid. Intracellular IgE-binding factors lacked affinity for all of the lectins studied and neither enhanced nor suppressed the IgE response.
Stiction in surface micromachining (1996)

Due to the smoothness of the surfaces in surface micromachining, large adhesion forces between fabricated structures and the substrate are encountered. Four major adhesion mechanisms have been analysed: capillary forces, hydrogen bridging, electrostatic forces and van der Waals forces. Once contact is made adhesion forces can be stronger than the restoring elastic forces and even short, thick beams will continue to stick to the substrate. Contact, resulting from drying liquid after release etching, has been successfully reduced. In order to make a fail-safe device stiction during its operational life-time should be anticipated. Electrostatic forces and acceleration forces caused by shocks encountered by the device can be large enough to bring structures into contact with the substrate. In order to avoid in-use stiction adhesion forces should therefore be minimized. This is possible by coating the device with weakly adhesive materials, by using bumps and side-wall spacers and by increasing the surface roughness at the interface. Capillary condensation should also be taken into account as this can lead to large increases in the contact area of roughened surfaces.
소비자 특성별 밤 구매행태 분석(2016) (2016)

본 연구의 목적은 소비자의 특성별 밤 구매행태를 분석하고 그 결과를 바탕으로 향후 밤 산업 발전을 위한 소비 촉진 및 마케팅 등 정책적인 시사점을 제시하는 데 있다. 응답자 특성별 밤의 구매행태의 분석결과, 연령별 밤 구매 시기는 명절과 햇밤 출하시기에 주로 구매하였으며 소득별 구매 시기 역시 연령과 마찬가지로 명절, 햇밤 출하시기에 구매하는 비중이 높은 것으로 나타났다. 응답자 특성 구분 없이 밤 구매 형태는 생밤의 구매비중이 상당히 높은 것으로 나타났으며 연령이 낮을수록, 소독이 높을수록 가공밤을 구매하는 비중이 높은 것으로 나타났다. 밤 구매 시 우선고려사항은 응답자 특성 구분 없이 신선도가 1순위로 선호되었으며 그 다음으로는 외형과 원산지가 서로 번갈아가며 2,3순위로 나타났다. 현재 우리나라 밤 산업은 대 내외적인 문제를 가지고 있어 위축될 가능성이 높아지고 있다. 밤 산업을 앞으로 발전시키기 위해서 고품질의 밤을 생산하고 다양한 가공제품 개발과 동시에 소비촉진을 위한 마케팅을 시행하여 소비자의 지속적인 관심을 유도할 필요가 있다.