gebhart/patrepeval huggingface dataset:
Blue light from light-emitting diodes elicits a dose-dependent suppression of melatonin in humans (2010)

Light suppresses melatonin in humans, with the strongest response occurring in the short-wavelength portion of the spectrum between 446 and 477 nm that appears blue. Blue monochromatic light has also been shown to be more effective than longer-wavelength light for enhancing alertness. Disturbed circadian rhythms and sleep loss have been described as risk factors for astronauts and NASA ground control workers, as well as civilians. Such disturbances can result in impaired alertness and diminished performance. Prior to exposing subjects to short-wavelength light from light-emitting diodes (LEDs) (peak λ = 469 nm; 1/2 peak bandwidth = 26 nm), the ocular safety exposure to the blue LED light was confirmed by an independent hazard analysis using the American Conference of Governmental Industrial Hygienists exposure limits. Subsequently, a fluence-response curve was developed for plasma melatonin suppression in healthy subjects (n = 8; mean age of 23.9 ± 0.5 years) exposed to a range of irradiances of blue LED light. Subjects with freely reactive pupils were exposed to light between 2:00 and 3:30 AM. Blood samples were collected before and after light exposures and quantified for melatonin. The results demonstrate that increasing irradiances of narrowband blue-appearing light can elicit increasing plasma melatonin suppression in healthy subjects (P < 0.0001). The data were fit to a sigmoidal fluence-response curve (R(2) = 0.99; ED(50) = 14.19 μW/cm(2)). A comparison of mean melatonin suppression with 40 μW/cm(2) from 4,000 K broadband white fluorescent light, currently used in most general lighting fixtures, suggests that narrow bandwidth blue LED light may be stronger than 4,000 K white fluorescent light for suppressing melatonin.
Severity of Gentamicin's Nephrotoxic Effect on Patients with Infective Endocarditis: A Prospective Observational Cohort Study of 373 Patients (2008)

The nephrotoxic effect of gentamicin is directly related to treatment duration, with a decrease in EECC of 0.5% per day of gentamicin treatment. In patients treated with gentamicin, the in-hospital decrease in EECC was not related to postdischarge mortality. Consequently, this study does not support abolishment of gentamicin in treatment of IE.
Generation of redesigned homing endonucleases comprising DNA-binding domains derived from two different scaffolds (2009)

Homing endonucleases have become valuable tools for genome engineering. Their sequence recognition repertoires can be expanded by modifying their specificities or by creating chimeric proteins through domain swapping between two subdomains of different homing endonucleases. Here, we show that these two approaches can be combined to create engineered meganucleases with new specificities. We demonstrate the modularity of the chimeric DmoCre meganuclease previously described, by successfully assembling mutants with locally altered specificities affecting both I-DmoI and I-CreI subdomains in order to create active meganucleases with altered specificities. Moreover these new engineered DmoCre variants appear highly specific and present a low toxicity level, similar to I-SceI, and can induce efficient homologous recombination events in mammalian cells. The DmoCre based meganucleases can therefore offer new possibilities for various genome engineering applications.
Modulation of rabbit articular chondrocyte (RAC) proliferation by TGF‐β isoforms (1995)

Abstract We have previously shown that TGF‐β1 exerts a bifunctional effect on RAC proliferation. Added to quiescent cultures, it inhibits the entry of G 0 /G 1 cells into S phase whereas in S phase synchronized populations, it stimulates the DNA replication rate with a delayed G 2 + M phase and a subsequent transient increase of cell number. As TGF‐β2 and β3 isoforms are also expressed in bone and cartilage tissues, it was of interest to study their effect on RAC proliferation, in comparison to that of TGF‐β1. Using cell counting and tritiated thymidine incorporation, we found that all the TGF‐βs used here induced an increase of RAC proliferation rate occurring between 24 and 48 h of exposure. TGF‐β2 appeared as the most efficient form as judged from the maximum of thymidine labelling. However, TGF‐β3 induced an increase of cell number slightly higher than both TGF‐β1 and TGF‐β2 (+30% versus 20% for TGF‐β1 and β2). TGF‐β2 and β3 were able to stimulate the DNA replication rate as previously demonstrated for TGF‐β1. However, the effect occurred later for TGF‐β2 and β3 (12 h) than for TGF‐β1 (6 h). This was confirmed by flow cytometric analysis of DNA content. In addition, immunodetection by flow cytometry demonstrated that all TGF‐β isoforms enhanced endogenous expression of TGF‐β‐related peptides. The effect was shown to be associated with the cell cycle S phase and was greater for TGF‐β3 than for TGF‐β1 and β2. These findings suggest that TGF‐βs could act on RAC functions via autocrine and paracrine ways. Taken together, these data indicate that TGF‐βs may modulate proliferation of articular chondrocytes and therefore could play a role in the activation of these cells in the early stages of osteoarthritis.
Little Evidence for Developmental Plasticity of Adult Hematopoietic Stem Cells (2002)

To rigorously test the in vivo cell fate specificity of bone marrow (BM) hematopoietic stem cells (HSCs), we generated chimeric animals by transplantation of a single green fluorescent protein (GFP)-marked HSC into lethally irradiated nontransgenic recipients. Single HSCs robustly reconstituted peripheral blood leukocytes in these animals, but did not contribute appreciably to nonhematopoietic tissues, including brain, kidney, gut, liver, and muscle. Similarly, in GFP+:GFP- parabiotic mice, we found substantial chimerism of hematopoietic but not nonhematopoietic cells. These data indicate that "transdifferentiation" of circulating HSCs and/or their progeny is an extremely rare event, if it occurs at all.
Expression of nitric oxide synthase in rat glomerular mesangial cells mediated by cyclic AMP (1994)

1. Treatment of rat mesangial cells with interleukin 1 beta (IL-1 beta) or tumour necrosis factor alpha (TNF alpha) has been shown to induce a macrophage-type of nitric oxide (NO) synthase. Here we report that adenosine 3':5'-cyclic monophosphate (cyclic AMP) is another mediator that triggers induction of NO synthase in mesangial cells. 2. Incubation of mesangial cells with the beta-adrenoceptor agonist, salbutamol, forskolin or cholera toxin, which all activate adenylate cyclase and increase intracellular cyclic AMP concentration, increased nitrite formation in a dose-dependent manner. Likewise, the addition of the membrane-permeable cyclic AMP analogue, N6, 0-2'-dibutyryladenosine 3',5'-phosphate (Bt2 cyclic AMP) or the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine enhanced NO synthase activity in a dose-dependent manner. 3. There was a lag period of about 8 h before a significantly enhanced secretion of nitrite could be detected upon exposure of cells to forskolin and for maximal stimulation, forskolin had to be present during the whole incubation period. 4. Treatment of mesangial cells with actinomycin D, cycloheximide or dexamethasone completely suppressed forskolin-stimulated NO-synthase activity, thus demonstrating that transcription and protein synthesis are necessary for nitrite formation. 5. Bt2 cyclic AMP, the most potent inducer of nitrite production, increased NO synthase mRNA levels in mesangial cells in a time- and dose-dependent fashion. Dexamethasone completely inhibited the increase of NO synthase mRNA in response to Bt2 cyclic AMP. 6. Combination of Bt2 cyclic AMP and IL-1 beta or TNF alpha revealed a strong synergy in terms of nitrite formation. Time-course studies indicated that cyclic AMP needed to be increased during the whole period of IL-1 Beta stimulation for maximal nitrite production.7. These observations suggest that cyclic AMP controls NO synthase expression in mesangial cells.Furthermore, the signalling cascades triggered by IL-1 Beta and TNF alpha synergize with the cyclic AMP pathway to stimulate NO synthase activity.
연구논문 : 중독행동에서 인지행동접근과 대안에 관한 소론 (2014)

본 연구는 중독행동에서 인지행동접근을 비판하고 대안을 논의하였다. 중독행동에서 인지행동접근은 사회복지실천현장에서 많은 사회복지사들이 시도하는 접근방법이다. 그러나 인지행동접근에 대한 개념적 명료성과 효과적인가에 대한 논의가 충분히 가시화되지 못했다. 따라서 본 연구에서는 인지행동접근에서 제기하는 다양한 이슈와 딜레마를 통해 어떤 해결책들을 제시될 수 있는지 고찰하였다. 클라이언트 몸에 대한 재해석을 통해 사회복지실천 현장의 발전을 모색하여 인지행동접근과 더불어 메를로-퐁티의 관점을 사회복지실천현장에서 양자택일 할 관점이 아니라 상호보완적인 관점으로 활용되어져야 할 것이다.
A clinical exploratory study with itolizumab, an anti-CD6 monoclonal antibody, in patients with rheumatoid arthritis (2012)

T cells are involved in the pathogenesis of rheumatoid arthritis (RA). CD6 is a co-stimulatory molecule, predominantly expressed on lymphocytes, that has been linked to autoreactive responses. The purpose of this study was to evaluate the safety, immunogenicity and preliminary efficacy of itolizumab, a humanized anti-CD6 monoclonal antibody, in patients with active rheumatoid arthritis. Fifteen patients were enrolled in a phase I, open-label, dose-finding study. Five cohorts of patients received a weekly antibody monotherapy with a dose-range from 0.1 to 0.8 mg/kg. Itolizumab showed a good safety profile, with no severe or serious adverse events reported so far. No signs or symptoms associated with immunosuppression were observed in the study. Objective clinical responses were achieved in more than 80% of patients after treatment completion, and these responses tend to be sustained afterwards. This clinical study constitutes the first evidence of the safety and positive clinical effect of a monotherapy using an anti-CD6 antibody in patients with rheumatoid arthritis.
Suppression of Immune Response and Protective Immunity to a Japanese Encephalitis Virus DNA Vaccine by Coadministration of an IL-12-Expressing Plasmid (2001)

IL-12 plays a central role in both innate and acquired immunity and has been demonstrated to potentiate the protective immunity in several experimental vaccines. However, in this study, we show that IL-12 can be detrimental to the immune responses elicited by a plasmid DNA vaccine. Coadministration of the IL-12-expressing plasmid (pIL-12) significantly suppressed the protective immunity elicited by a plasmid DNA vaccine (pE) encoding the envelope protein of Japanese encephalitis virus. This suppressive effect was associated with marked reduction of specific T cell proliferation and Ab responses. A single dose of pIL-12 treatment with plasmid pE in initial priming resulted in significant immune suppression to subsequent pE booster immunization. The pIL-12-mediated immune suppression was dose dependent and evident only when the IL-12 gene was injected either before or coincident with the pE DNA vaccine. Finally, using IFN-gamma gene-disrupted mice, we showed that the suppressive activity of the IL-12 plasmid was dependent upon endogenous production of IFN-gamma. These results demonstrate that coexpression of the IL-12 gene can sometimes produce untoward effects to immune responses, and thus its application as a vaccine adjuvant should be carefully evaluated.
Statistical analysis of watermarking schemes for copyright protection of images (1999)

In this paper, we address the problem of the performance analysis of image watermarking systems that do not require the availability of the original image during ownership verification. We focus on a statistical approach to obtain models that can serve as a basis for the application of decision theory to the design of efficient detector structures. Special attention is paid to the possible nonexistence of a statistical description of the original image. Different modeling approaches are proposed for the cases when such a statistical characterization is known and when it is not. Watermarks may encode a message, and the performance of the watermarking system is evaluated using as a measure the probability of false alarm, the probability of detection when the presence of the watermark is tested, and the probability of error when the information that it carries is extracted. Finally, the modeling techniques studied are applied to the analysis of two watermarking schemes, one of them defined in the spatial domain, and the other in the direct cosine transform (DCT) domain. The theoretical results are contrasted with empirical data obtained through experimentation covering several cases of interest. We show how choosing an appropriate statistical model for the original image can lead to considerable improvements in performance.
Microparticle Concentration and Separation by Traveling-Wave Dielectrophoresis (twDEP) for Digital Microfluidics (2007)

This paper describes highly efficient in-droplet particle concentration and separation where particles are concentrated and separated into droplets by traveling-wave dielectrophoresis (DEP) and subsequent electrowetting-on-dielectric droplet splitting. A successful concentration for 5-mum aldehyde sulfate (AS) latex particles was experimentally achieved using microfabricated devices, showing that 98% of the total particles were concentrated into a split daughter droplet. In addition, in-droplet particle separation was successfully achieved using the following two different cases of particle mixtures: case 1) a mixture of 5-mum AS latex beads and 8-mum glass beads; and case 2) a mixture of ground pine (GP) spores and 8-mum glass beads. In case 1), 97% of the total AS beads were separated into one split droplet and 77% of the total glass beads into the other split droplet. In case 2), over 92% of the GP spores were separated into a split daughter droplet, whereas 86% of the glass beads were separated into the other split daughter droplet. In all these concentration and separation experiments, the applied frequency and the conductivity medium are key parameters influencing the concentration and separation performance, which have been optimally determined by measuring the DEP and electrorotation spectra of the used particles prior to the concentration and separation experiments. This integrated in-droplet separation and concentration method may provide an additional functionality to digital microfluidics.
Variance of Marker Estimates of Parental Contribution to F2 and BC1‐Derived Inbreds (2000)

An Essentially Derived Variety is a cultivar or inbred that largely retains the characteristics of an ancestral cultivar or inbred. The parental contribution to F 2 ‐derived inbreds ( p F 2 ) and BC 1 ‐derived inbreds ( p BC 1 ) can be estimated with molecular markers. A recombinant inbred (RI) with p F 2 or p BC 1 greater than a specified threshold is then considered essentially derived. Our objectives were (i) to derive the variance of p F 2 and p BC 1 , and (ii) to determine the probability of obtaining an essentially derived RI for different numbers of marker loci in different species. The variances of p F 2 and p BC 1 are a function of the number of chromosomes, length of each chromosome, and number of marker loci on each chromosome. The standard errors (SE) of p F 2 and p BC 1 were smallest when the two marker loci closest to the ends of each chromosome were included. The minimum values of SE ( p F 2 ) and SE ( p BC 1 ) are useful for setting minimum values of thresholds for declaring essential derivation. Suppose selfing from the BC 1 is permissible and the maximum error rate for falsely declaring an RI is essentially derived is set at 2.5%. The minimum value of the threshold for these conditions is 0.881 in maize ( Zea mays L.). For a threshold of 0.90, the probabilities of an essentially derived RI from the BC 1 generation were &gt;6% in rye ( Secale cereale L.), &gt;3% in barley ( Hordeum vulgare L.), &lt;3% in tomato ( Lycopersicon spp.), rice ( Oryza spp.), and maize, and &lt;1% wheat ( Triticum aestivum L.). These results suggest that the thresholds used to declare essential derivation should differ among species.
Characterization of a dCTP Transport Activity Reconstituted from Human Mitochondria (1999)

A protein fraction of mitochondria from human acute lymphocytic leukemia cells, which could be reconstituted into proteoliposomes to have dCTP transport activity, has been partially purified by hydroxyapatite and blue Sepharose chromatography. The dCTP transport activity in proteoliposomes was time-dependent and could be activated by Ca2+ and to a lesser extent by Mg2+. None of the other divalent cations tested could activate the transport activity. The Km value of dCTP in the presence of Ca2+ was shown to be 3 microM. dCDP but not dCMP or dCyd could inhibit the transport activity. Other deoxynucleoside triphosphates could also inhibit the uptake of dCTP with the potency dGTP = dATP > TTP. Although ATP could competitively inhibit dCTP uptake with a Ki value of 8 microM, the reconstituted dCTP uptake activity was not sensitive to the ATP/ADP carrier inhibitor atractyloside or the sulfhydryl reagent N-ethylmaleimide. This suggests that the dCTP transport system studied is not the same as the ATP/ADP carrier. In conclusion, these studies describe the first functionally reconstituted mitochondrial carrier that displays an efficient transport activity for dCTP.
Population BRCA1 and BRCA2 Mutation Frequencies and Cancer Penetrances: A Kin–Cohort Study in Ontario, Canada (2006)

BRCA1 and BRCA2 mutations may be more frequent in general populations than previously thought and may be associated with various types of cancers.
Tyrosine Kinase Inhibitors (2010)

Over the last ten years, several new and therapeutically relevant cancer drugs targeting tyrosine kinases signaling pathways have been developed. Tyrosine kinase inhibitors (TKIs) are a pharmaceutical class of small molecules, orally available, well-tolerated, worldwide approved drugs for the treatment of several neoplasms, including lung, breast, kidney and pancreatic cancer as well as gastro-intestinal stromal tumors and chronic myeloid leukemia. This comprehensive review focuses on the most relevant members of the first and the second generation TKIs designed to interact with receptor and nonreceptor TKs. Attention is mainly focused on molecular mechanisms in in vitro and in vivo models related to the clinical activity of the drugs and to the development of resistance to treatment, still the major challenge in cancer research and care.
Combination Therapy in Experimental Invasive Aspergillosis (1993)

Combination antifungal therapy was assessed in an immunosuppressed rabbit model of invasive aspergillosis. Treatment with fluconazole, amphotericin B, or a combination of both significantly prolonged survival of animals lethally challenged with Aspergillus fumigatus. High-dose amphotericin B was the most effective therapy for invasive aspergillosis. Although no antagonism was seen when fluconazole was given prophylactically or therapeutically in combination with amphotericin B, combination therapy did not augment the antifungal activity of amphotericin B. Animals given a sublethal challenge of A. fumigatus had lower mortality rates when given amphotericin B, fluconazole as treatment or prophylaxis, or various combination therapies. Only animals treated with flucytosine had mortality rates comparable to those of controls. No antagonism was observed with combinations of fluconazole and amphotericin B, flucytosine and amphotericin B, or fluconazole and flucytosine. These observations provide evidence that fluconazole, flucytosine, and amphotericin B used in various combinations are not antagonistic and may provide some insight into the treatment of invasive aspergillosis in humans.
Single-Molecule Lysozyme Dynamics Monitored by an Electronic Circuit (2012)

Tethering a single lysozyme molecule to a carbon nanotube field-effect transistor produced a stable, high-bandwidth transducer for protein motion. Electronic monitoring during 10-minute periods extended well beyond the limitations of fluorescence techniques to uncover dynamic disorder within a single molecule and establish lysozyme as a processive enzyme. On average, 100 chemical bonds are processively hydrolyzed, at 15-hertz rates, before lysozyme returns to its nonproductive, 330-hertz hinge motion. Statistical analysis differentiated single-step hinge closure from enzyme opening, which requires two steps. Seven independent time scales governing lysozyme's activity were observed. The pH dependence of lysozyme activity arises not from changes to its processive kinetics but rather from increasing time spent in either nonproductive rapid motions or an inactive, closed conformation.
Color and shade management in esthetic dentistry (2013)

The color and appearance of teeth is a complex phenomenon, with many factors such as lighting conditions, translucency, opacity, light scattering, gloss and the human eye and brain influencing the overall perception of tooth color. To achieve esthetics, four basic determinants are required in sequence; viz., position, contour, texture and color. The knowledge of the concept of color is essential for achieving good esthetics. This review compiles the various aspects of color, physics behind perception of color, measurements and shade matching in dentistry for various esthetic treatments.
All-optical AND and NAND gates based on cascaded second-order nonlinear processes in a Ti-diffused periodically poled LiNbO3 waveguide (2006)

All-optical AND and NAND gates have been demonstrated in a Ti-diffused periodically poled LiNbO(3) channel waveguide which has two second-harmonic phase-matching peaks by cascaded sum-frequency-generation/difference-frequency-generation (cSFG/DFG) and sum-frequency-generation (SFG) processes. The conversion efficiency of signal to idler (AND gate signal) was approximately 0 dB in cSFG/DFG process. In the second SFG process, more than 15 dB extinction ratio between signal and dropped signal (NAND gate signal) has been observed.
Neuronal nicotinic receptors: from structure to function (2001)

Molecular identification of the genes and resulting protein sequences for a large number of nicotinic acetylcholine receptor (nAChR) subunits has stimulated numerous studies highlighting their role in several human behaviors including neurological disorders and nicotine addiction. This receptor gene family is likely to be involved in release of multiple neurotransmitters in both brain and periphery that mediate sensitivity and tolerance to nicotine. Recent findings also suggest that alterations in these receptors may lead to neurological diseases, some associated with increased incidence of smoking. This review addresses current knowledge of nicotinic receptor structure, regulation of expression, and function, in both normal and psychiatric subjects.