Miracle-dz/UniFAR-FTUs huggingface dataset:
Blue light irradiation suppresses dendritic cells activation in vitro

Blue light is a UV‐free irradiation suitable for treating chronic skin inflammation, for example, atopic dermatitis, psoriasis, and hand‐ and foot eczema. However, a better understanding of the mode of action is still missing. For this reason, we investigated whether dendritic cells (DC) are directly affected by blue light irradiation in vitro. Here, we report that irradiation neither induced apoptosis nor maturation of monocyte‐derived and myeloid DC. However, subsequent DC maturation upon LPS/IFNγ stimulation was impaired in a dose‐dependent manner as assessed by maturation markers and cytokine release. Moreover, the potential of this DC to induce cytokine secretion from allogeneic CD4 T cells was reduced. In conclusion, unlike UV irradiation, blue light irradiation at high and low doses only resulted in impaired DC maturation upon activation and a reduced subsequent stimulatory capacity in allogeneic MLRs with strongest effects at higher doses.
Current status of fibrosis markers

Purpose of review Improved understanding of the pathophysiology of fibrosis and recent technological advances have resulted in the development of several serum biomarkers and imaging tools as noninvasive alternatives to biopsy. Most of these markers have been developed in chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) patients. This review highlights some of the recent advances and potential clinical application of these modalities. Recent findings Many noninvasive approaches initially developed for binary disease staging in CHC continue to be refined for diagnostic use in other chronic liver disease such as NAFLD. A combination of serum markers and imaging tools appears useful in reducing the need for biopsy for the diagnosis of cirrhosis, and providing functional assessment in advanced stage disease. Cytokeratin-18 fragments, controlled attenuation parameter (CAP), real-time elastography, and magnetic resonance imaging approaches appear promising for NAFLD, but require further validation. Summary Current noninvasive tests of fibrosis provide good diagnostic and prognostic utility for advanced stage liver disease, and have been adapted into clinical practice for CHC. Reliable biomarkers for steatosis, nonalcoholic steatohepatitis, and assessment of fibrosis progression in chronic liver disease are still required. Continued advances in bioimaging and functional genomics will be important for quantitative assessment of fibrosis and future biomarker development.
Background calibration of integrator leakage in discrete-time delta-sigma modulators

This paper presents an integration-leakage calibration technique for the switched-capacitor integrators in a delta-sigma modulator (DSM). Integrators realized with low-gain opamps are lossy. A DSM that uses lossy integrators exhibits a degraded signal-to-quantization-noise ratio. To calibrate an integrator, its integration leakage is detected in the digital domain, and the leakage compensation is applied to the same integrator in the analog domain. The proposed scheme can calibrate all integrators in a discrete-time DSM of any form. It can be proceed in the background without interrupting the normal DSM operation. The design considerations for the proposed calibration scheme are discussed. Design cases of a 1st-order, a 2nd-order, and a 3rd-order DSM are demonstrated and simulated.
Expression and localisation of insulin receptor substrate 2 in normal intestine and colorectal tumours. Regulation by intestine-specific transcription factor CDX2

Background and aims: Self-renewal and differentiation of intestinal epithelium is a tightly regulated process, whose perturbations are implicated in human colorectal tumourigenesis. The insulin/insulin-like growth factor (IGF) signalling pathway may play an important role in intestinal epithelium homeostasis. Insulin receptor substrate 2 (IRS2) is a poorly characterised component in this pathway. Methods: Using complementary in vitro and in vivo human and murine models, expression (mRNA and protein levels), localisation (immunohistochemistry) and regulation of IRS2 were investigated in the normal intestine and colorectal tumours. In silico analysis of the human IRS2 promoter was performed together with reporter and chromatin immunoprecipitation assays. Results: Significant IRS2 expression was detected in the intestine, with specific protein localisation in the villus region of the ileum and in the surface epithelium of the colon. In human HT29 and Caco2 cells, IRS2 mRNA levels increased with spontaneous and induced differentiation, together with CDX2 (caudal-related homeobox protein 2), P21 and KLF4 (Krüppel-like factor 4). Adenoviral infection with human CDX2 induced IRS2 expression in APC- (adenomatous polyposis coli) and β-catenin-mutated cells. On the other hand, IRS2 downregulation was observed in differentiated enterocytes after adenoviral infection with short hairpin CDX2 (shCDX2), in the intestine of CDX2 heterozygous mice and in colorectal tumours of ApcMin/+ and patients with familial adenomatous polyposis (FAP). The human IRS2 promoter region presents several CDX2-binding sites where CDX2 immunoprecipitated in vivo. IRS2 reporters were functionally activated via CDX2 and blocked via a dominant-negative CDX2 protein. Conclusions: Combining gain- and loss-of-function approaches, an intriguing scenario is presented whereby IRS2 is significantly expressed in the apical intestinal compartment and is directly controlled by CDX2 in normal intestine and tumours.
Soda-lime silicate glass under hydrostatic pressure and indentation: a micro-Raman study

Raman micro-spectroscopy is used to analyse the plastic behaviour of window glass (a soda-lime silicate glass) under high hydrostatic pressure and Vickers indentation. We show pressure-induced irreversible structural changes, notably an increase of Q2 species at the expense of Q3. For the first time, a very accurate calibration curve has been established. Local density variations of a Vickers indented window glass have been characterized by micro-Raman mapping using a high spatial resolution device. The effects of glass depolymerization on indentation and hydrostatic compression are discussed. Differences between window glass and pure SiO2 glass behaviour under high stresses are also highlighted and analysed at a local scale.
Multi-view video and audio transmission with MPEG-DASH and its QoE

In this paper, we assess QoE of multi-view video and audio (MVV-A) IP transmission with MPEG-DASH by a subjective experiment. An MVV-A system by means of MPEG-DASH is implemented. We then compare QoE of transmitting a selected viewpoint from four viewpoints by the user with that of transmitting a pre-determined viewpoint (i.e., single-view). We assess QoE multidimensionally with many adjective pairs. We then show that MVV-A by means of MPEG-DASH can enhance QoE under lightly loaded condition.
Long-term effects of outpatient rehabilitation of COPD: A randomized trial.

OBJECTIVE To examine the short- and long-term effects of an outpatient pulmonary rehabilitation program for COPD patients on dyspnea, exercise, health-related quality of life, and hospitalization rate. SETTING Secondary-care respiratory clinic in Barcelona. METHODS We conducted a randomized controlled trial with blinding of outcome assessment and follow-up at 3, 6, 9, 12, 18, and 24 months. Sixty patients with moderate to severe COPD (age 65 +/- 7 years; FEV(1) 35 +/- 14%) were recruited. Thirty patients randomized to rehabilitation received 3 months of outpatient breathing retraining and chest physiotherapy, 3 months of daily supervised exercise, and 6 months of weekly supervised breathing exercises. Thirty patients randomized to the control group received standard care. RESULTS We found significant differences between groups in perception of dyspnea (p < 0.0001), in 6-min walking test distance (p < 0.0001), and in day-to-day dyspnea, fatigue, and emotional function measured by the Chronic Respiratory Questionnaire (p < 0. 01). The improvements were evident at the third month and continued with somewhat diminished magnitude in the second year of follow-up. The PR group experienced a significant (p < 0.0001) reduction in exacerbations, but not the number of hospitalizations. The number of patients needed to treat to achieve significant benefit in health-related quality of life for a 2-year period was approximately three. CONCLUSION Outpatient rehabilitation programs can achieve worthwhile benefits that persist for a period of 2 years.
The footprint of spatial attention in V4 receptive fields.

Spatial attention modulates responses of visual neurons at virtually all levels of cortical processing. Studies of attentional modulation of neural selectivity for stimulus properties like orientation and contrast have found that directing attention into a V4 receptive field (RF) alters neuronal gain. Little, however, is known about how attention affects the spatial structure of V4 RFs. Nor do we know how, or even if, attentional modulation is constrained to neurons with RFs within the attentional focus (AF). To address these questions we recorded from V4 neurons in monkeys performing a spatiotopic attention task where they responded to targets appearing at a cued location in space. On alternating blocks of trials, the attended location was either in the lower or upper visual field. One of three fixation points was chosen at random on each trial to control the spatial relationship between the RF and AF. Ignored low contrast probe stimuli were displayed in and around RFs during trials. Neuronal responses to probe stimuli were used to characterize the spatiotemporal RF. Over half of V4 neurons showed significant attentional modulation (attend-in vs -out), with 70% of neurons showing facilitation and 30% suppression. We observed both multiplicative and additive modulatory effects. Interestingly, the sign of these effects were often in opposite directions. About half of the attentionally modulated neurons were modulated only when the RF fell inside the AF, consistent with behavioral performance. The remaining neurons were modulated even when the RF was located more than one diameter outside the AF, suggesting that at the neuronal level attention can spread beyond the AF, as defined by enhanced behavioral performance. Consistent with proposed ventral stream contributions to spatiotopic processing, we found activity in >70% of the V4 neurons studied was also modulated by gaze angle position, reminiscent of dorsal stream gain fields. Meeting abstract presented at VSS 2015.
Reduction of disease activity and disability with high-dose cyclophosphamide in patients with aggressive multiple sclerosis.

OBJECTIVE To explore the safety and effectiveness of high-dose cyclophosphamide (HiCy) without bone marrow transplantation in patients with aggressive multiple sclerosis (MS). DESIGN A 2-year open-label trial of patients with aggressive relapsing-remitting multiple sclerosis (RRMS) given an immunoablative regimen of HiCy (50 mg/kg/d for 4 consecutive days) with no subsequent immunomodulatory therapy unless disease activity reappeared that required rescue therapy. SETTING The Johns Hopkins University Multiple Sclerosis Center, Baltimore, Maryland. Patients A total of 21 patients with RRMS were screened for eligibility and 9 patients were enrolled in the trial. Patients were required to have 2 or more gadolinium-enhancing lesions on each of 2 pretreatment magnetic resonance imaging scans, at least 1 clinical exacerbation in the 12 months prior to HiCy treatment, or a sustained increase of 1.0 point or higher on the Expanded Disability Status Scale (EDSS) in the preceding year. Intervention Patients received 50 mg/kg/d of cyclophosphamide intravenously for 4 consecutive days, followed by 5 mug/kg/d of granulocyte colony-stimulating factor 6 days after completion of HiCy treatment, until the absolute neutrophil count exceeded 1.0 x 10(9) cells/L for 2 consecutive days. MAIN OUTCOME MEASURES The primary outcome of the study was the safety and tolerability of HiCy in patients with RRMS. Secondary outcome measures included a change in gadolinium-enhancing lesions on magnetic resonance images and a change in disability measures (EDSS and Multiple Sclerosis Functional Composite). RESULTS Nine patients were treated and followed up for a mean period of 23 months. Eight patients had failed conventional therapy and 1 was treatment naive. The median age at time of entry was 29 years (range, 20-47 years). All patients developed transient total or near-total pancytopenia as expected, followed by hematopoietic recovery in 10 to 17 days, stimulated by granulocyte colony-stimulating factor. There were no deaths or unexpected serious adverse events. There was a statistically significant reduction in disability (EDSS) at follow-up (mean [SD] decrease, 2.11 [1.97]; 39.4%; P = .02). The mean (SD) number of gadolinium-enhancing lesions on the 2 pretreatment scans were 6.5 (2.1) and 1.2 (2.3) at follow-up (81.4% reduction; P = .01). Two patients required rescue treatment with other immunomodulatory therapies during the study owing to MS exacerbations. CONCLUSION Treatment with HiCy was safe and well tolerated in our patients with MS. Patients experienced a pronounced reduction in disease activity and disability after HiCy treatment. This immunoablative regimen of cyclophosphamide for patients with aggressive MS is worthy of further study and may be an alternative to bone marrow transplantation. Published online June 9, 2008 (doi:10.1001/archneurol.65.8.noc80042).
UNTERSUCHUNG DES ZUSAMMENWIRKENS ZWISCHEN DEM FAHRER UND EINEM ACC-SYSTEM IN GRENZSITUATIONEN

Im Beitrag wird das Zusammenwirken zwischen dem Fahrer eines Kraftfahrzeugs und einem ACC-System (Adaptive Cruise Control) zur automatischen Geschwindigkeits- und Abstandsregelung in Grenzsituationen im realen Verkehr untersucht. Grenzsituationen entstehen aus normalen Verkehrssituationen durch Fehler beim technischen System oder beim Fahrer oder auch durch unvorhergesehene Aenderungen der aeusseren Situation. Aufbauend auf einer begrifflichen Einordnung von Grenzsituationen mit Hilfe eines Interaktionsmodells werden experimentelle Untersuchungen mit Versuchsfahrzeugen vorgestellt. Ziel der Fahrten war es, die Auswirkungen unterschiedlicher Beschraenkungen der bei Systemeingriffen aufgewandten Bremsverzoegerung auf das Fahrverhalten, auf die subjektive Beurteilung des Risikos, der Beherrschbarkeit, das Systemverstaendnis sowie auf die Komfort- und Sicherheitseinschaetzung zu untersuchen, wobei insbesondere der zeitliche Verlauf solcher Parameter ueber mehrere Versuchsfahrten hinweg von Interesse war. Ausserdem wurde untersucht, ob und welche Praeferenzen sich eventuell bei verschiedenen Fahrertypen bezueglich unterschiedlicher ACC-Systemvarianten herausbilden. Titel in Englisch: Study of drivers' co-operation with an ACC system in borderline situations. Beitrag zur Tagung "Der Mensch im Verkehr" der VDI-Gesellschaft Fahrzeug- und Verkehrstechnik in Muenchen, 30. und 31. Januar 1997. Siehe auch Gesamtaufnahme der Tagung, IDS-Nummer 337523.
Recent microbiological studies with gentamicin.

The clinically available form of gentamicin is a mixture of 3 components, namely, gentamicins d, da, and C2 [1, 2]. The chemical structure of the components was studied recently at Schering Corporation [3]. At least 2 assay procedures have been published for determining the ratio of the components present in the complex [4, 5], and the Food and Drug Administration has approved limits established by Schering Corporation for the relative amounts of each of the components allowable in the complex [6, 7]. Weinstein and co-workers [1] presented initial studies which demonstrated that the 3 components have nearly identical in vitro activity. They also showed that the acute toxicity as well as the protective activity of the 3 components against Staphylococcus aureus were not significantly different in mice.
Therapeutic Drug Monitoring for Caffeine in Preterm Neonates: An Unnecessary Exercise?

OBJECTIVE. Our goal was to determine the value of measuring plasma caffeine levels in preterm neonates treated with caffeine for apnea. We evaluated plasma concentrations of caffeine attained in preterm neonates at standard doses, at varying postconceptual ages, with renal or hepatic dysfunction and when there was clinical lack of efficacy. We hypothesized that measurement of plasma caffeine concentrations during apnea therapy is not clinically helpful. PATIENTS/METHODS. An observational study was conducted at Hutzel Women's Hospital between January 2000 and September 2005. Preterm neonates who were being treated with caffeine and who had a plasma caffeine level measured on at least 1 occasion were included. RESULTS. A total of 231 caffeine blood levels were obtained from 101 preterm neonates with a median gestation of 28 weeks (range: 23–32 weeks) and birth weight of 1030 g (range: 540–2150 g). The caffeine citrate dose used ranged form 2.5 to 10.9 mg/kg (median: 5 mg/kg), and the levels ranged from 3.0 to 23.8 mg/L. Levels were between 5.1 and 20 mg/L in 94.8%, <5 mg/L in 2.1%, and >20 mg/L in 3.1%. Levels in the 5.1 to 20 mg/L range were attained on 91.3% of occasions when there was concomitant renal dysfunction (n = 23) and in all cases of hepatic dysfunction (n = 13). The median (25th, 75th quartiles) levels drawn for lack of efficacy (14.1 [10.2, 8.3] mg/L; n = 94) were comparable to those obtained for routine monitoring (13.7 [11, 9] mg/L; n = 107). CONCLUSIONS. A majority of preterm neonates attain plasma caffeine levels between 5 and 20 mg/L, independent of gestation. This observation held even for the small number of subjects with elevated blood urea nitrogen, serum creatinine, or liver enzyme levels. Therapeutic drug monitoring is not necessary when caffeine is used for the treatment of apnea of prematurity in neonates.
Population synthesis of ultracompact X-ray binaries in the Galactic Bulge

Aims. We model the present-day number and properties of ultracompact X-ray binaries (UCXBs) in the Galactic bulge. The main objective is to compare the results to the known UCXB population as well as to data from the Galactic Bulge Survey, in order to learn about the formation of UCXBs and their evolution, such as the onset of mass transfer and late-time behavior. Methods. The binary population synthesis code SeBa and detailed stellar evolutionary tracks have been used to model the UCXB population in the Bulge. The luminosity behavior of UCXBs has been predicted using long-term X-ray observations of the known UCXBs as well as the thermal-viscous disk instability model. Results. In our model, the majority of UCXBs initially have a helium burning star donor. Of the white dwarf donors, most have helium composition. In the absence of a mechanism that destroys old UCXBs, we predict (0.2−1.9) × 10 5 UCXBs in the Galactic bulge, depending on assumptions, mostly at orbital periods longer than 60 min (a large number of long-period systems also follows from the observed short-period UCXB population). About 5−50 UCXBs should be brighter than 10 35 erg s −1 , mostly persistent sources with orbital periods shorter than about 30 min and with degenerate helium and carbon-oxygen donors. This is about one order of magnitude more than the observed number of (probably) three. Conclusions. This overprediction of short-period UCXBs by roughly one order of magnitude implies that fewer systems are formed, or that a super-Eddington mass transfer rate is more difficult to survive than we assumed. The very small number of observed longperiod UCXBs with respect to short-period UCXBs, the surprisingly high luminosity of the observed UCXBs with orbital periods around 50 min, and the properties of the PSR J1719−1438 system all point to much faster UCXB evolution than expected from angular momentum loss via gravitational wave radiation alone. Old UCXBs, if they still exist, probably have orbital periods longer than 2 h and have become very faint due to either reduced accretion or quiescence, or have become detached. UCXBs are promising candidate progenitors of isolated millisecond radio pulsars.
TSV optimization for BEOL interconnection in logic process

Control of Cu extrusion and delamination due to CTE mismatch between Si and Cu is a big issue for high reliable TSV formation. In this paper we tried to find some methods to reduce Cu extrusion and to prevent TSV sidewall delamination. It is demonstrated that residual Cu extrusion height can be reduced by additional high temperature heat treatment before TSV CMP. And also Cu extrusion and delamination strongly depends on TSV dimension, which leads to the conclusion that smaller vias are preferred for better reliability.
The future of anti-CD 20 monoclonal antibodies : are we making progress ?

The anti-CD20 monoclonal antibody (mAb) rituximab has revolutionized the treatment of B-cell malignancies. This unprecedented success has not only substantially changed the mindset of the clinical community about the ability of mAb to improve outcomes but has catalyzed the interest in the pharmaceutical industry to develop the next generation of anti-CD20 mAbs. Since the introduction of rituximab 15 years ago, we have learned much about the potential mechanisms underlying the therapeutic efficacy of antiCD20 mAbs. In parallel, many novel antiCD20 mAbs have entered the clinic, each designed with modifications to structure aimed at further improving efficacy. On review of the newer generation of antiCD20 mAbs entering clinical trials, it appears that the link between the novel mechanistic insights and the development of these next-generation anti-CD20 mAbs is unclear. As we move into an era of personalized medicine, it will become increasingly important for us to develop closer links between the emerging mechanistic insights and the clinical development, to further enhance the potency of anti-CD20 mAbs beyond that achieved with rituximab. (Blood. 2011;117(11): 2993-3001)
Opinión y análisis / Opinion and analysis

” y latendencia internacional de reforma del Estado quepuso sobre la mesa de discusion temas como el papeldel Estado y del mercado en el sector sanitario, ladescentralizacion, la privatizacion y la concesion demayor capacidad de eleccion a los “consumidores” delos servicios de salud.Si bien cabe reconocer que existe una amplia va-riedad de estrategias en las agendas de cambio en losdiferentes paises, determinadas por aspectos histori-cos, socioeconomicos, culturales, de contexto, de pro-yectos politicos, etc., que derivan en innumerables es-pecificidades en cada pais, es posible distinguir unconjunto de tendencias paralelas tales como:1. La racionalizacion de los recursos sanitarios a tra-ves del establecimiento de prioridades, el aumentode la coparticipacion financiera de los usuarios, labusqueda de una produccion sanitaria mas efi-ciente y la distribucion de los recursos de maneraefectiva.2. La incorporacion del concepto de “competencia ad-ministrada” como forma de establecer mercados“regulados” en el ambito sanitario y de generar me-didas de control que operen sobre la oferta y la de-manda de servicios de salud.3. La separacion entre el financiamiento y la provi-sion de servicios cuyo objetivo apunta a disminuirla produccion directa de servicios por parte delEstado, a cambio de fortalecer sus funciones deregulacion. 4. La descentralizacion de las responsabilidades en elfinanciamiento y la prestacion de los servicios tantoen los planos subnacionales de gobierno como parael sector privado (2). Los efectos de estas propuestas de cambio de-penden del pais en el que se esten aplicando; asi porejemplo, en los paises de Europa Occidental que po-seen sistemas de salud publicos, si bien se han llevadoa cabo reformas encaminadas a la separacion de las