Miracle-dz/UniFAR-FTUs huggingface dataset:
Human cerebral venous outflow pathway depends on posture and central venous pressure

Internal jugular veins are the major cerebral venous outflow pathway in supine humans. In upright humans the positioning of these veins above heart level causes them to collapse. An alternative cerebral outflow pathway is the vertebral venous plexus. We set out to determine the effect of posture and central venous pressure (CVP) on the distribution of cerebral outflow over the internal jugular veins and the vertebral plexus, using a mathematical model. Input to the model was a data set of beat‐to‐beat cerebral blood flow velocity and CVP measurements in 10 healthy subjects, during baseline rest and a Valsalva manoeuvre in the supine and standing position. The model, consisting of 2 jugular veins, each a chain of 10 units containing nonlinear resistances and capacitors, and a vertebral plexus containing a resistance, showed blood flow mainly through the internal jugular veins in the supine position, but mainly through the vertebral plexus in the upright position. A Valsalva manoeuvre while standing completely re‐opened the jugular veins. Results of ultrasound imaging of the right internal jugular vein cross‐sectional area at the level of the laryngeal prominence in six healthy subjects, before and during a Valsalva manoeuvre in both body positions, correlate highly with model simulation of the jugular cross‐sectional area (R2= 0.97). The results suggest that the cerebral venous flow distribution depends on posture and CVP: in supine humans the internal jugular veins are the primary pathway. The internal jugular veins are collapsed in the standing position and blood is shunted to an alternative venous pathway, but a marked increase in CVP while standing completely re‐opens the jugular veins.
Identification of Non-diphtheriae Corynebacterium by Use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

ABSTRACT We evaluated the Bruker Biotyper matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry for identification of 92 clinical isolates of Corynebacterium species in comparison to identification using rpoB or 16S rRNA gene sequencing. Eighty isolates (87%) yielded a score of ≥1.700, and all of these were correctly identified to the species level with the exception of Corynebacterium aurimucosum being misidentified as the closely related Corynebacterium minutissimum.
Plant regeneration directs changes in grassland composition after extreme drought: a 13‐year study in southern Switzerland

1 The cover of plant species was recorded annually from 1988 to 2000 in nine spatially replicated plots in a species‐rich, semi‐natural meadow at Negrentino (southern Alps). This period showed large climatic variation and included the centennial maximum and minimum frequency of days with ≥ 10 mm of rain. 2 Changes in species composition were compared between three 4‐year intervals characterized by increasingly dry weather (1988–91), a preceding extreme drought (1992–95), and increasingly wet weather (1997–2000). Redundancy analysis and anova with repeated spatial replicates were used to find trends in vegetation data across time. 3 Recruitment capacity, the potential for fast clonal growth and seasonal expansion rate were determined for abundant taxa and tested in general linear models (GLM) as predictors for rates of change in relative cover of species across the climatically defined 4‐year intervals. 4 Relative cover of the major growth forms present, graminoids and forbs, changed more in the period following extreme drought than at other times. Recruitment capacity was the only predictor of species’ rates of change. 5 Following perturbation, re‐colonization was the primary driver of vegetation dynamics. The dominant grasses, which lacked high recruitment from seed, therefore decreased in relative abundance. This effect persisted until the end of the study and may represent a lasting response to an extreme climatic event.
Challenges in the Management of Severe Asthma: Role of Current and Future Therapies

Severe asthma is a complex and heterogeneous phenotype characterized by persistent symptoms and poor control. While some patients respond to high doses of inhaled corticosteroids in combination with long-acting beta-agonists, a significant subset require oral corticosteroids to achieve symptom control. This issue has led to the development of alternative therapeutic strategies for severe asthma. This article provides an overview of current therapeutic strategies and suggests how they can be best applied to the treatment of severe asthma. The article then reviews alternative therapeutic strategies including macrolide antibiotics, biologic agents, modulators of signal transduction pathways and bronchial thermoplasty. The challenge remains to determine the appropriate phenotype for each therapeutic strategy in view of the heterogeneity of severe asthma.
Autonomous Expression of the slo Gene of the Bicistronic nga-slo Operon of Streptococcus pyogenes

ABSTRACT A recent model for cytolysin-mediated translocation in Streptococcus pyogenes proposes that NAD-glycohydrolase is translocated through streptolysin O-generated pores into a host cell (J. Madden, N. Ruiz, and M. Caparon, Cell 104:143-152, 2001). This model also assumes that the NAD-glycohydrolase (nga) and streptolysin O (slo) genes that code for these products are organized in an operon-like structure expressed from a single promoter only (nga). We expand this model by showing that slo possesses its own autonomous promoter, which is located 155 bp upstream of the slo gene. Under experimental conditions in which S. pyogenes is grown in THY medium, the strength of the slo promoter, as measured by the activity of a lacZ reporter gene, resulted in low but highly reproducible values. Finally, we demonstrated that sloR, a S. pyogenes gene that closely resembles the Clostridium perfringens pfoR gene, exerts a negative effect on the expression of the slo gene.
The use and acceptance of new media entertainment technology by elderly users: development of an expanded technology acceptance model

Research on elderly people's ICT acceptance and use often relies on the technology acceptance model (TAM) framework, but has been mostly limited to task-oriented uses. This article expands approaches in technology acceptance and use by developing a model to explain entertainment-related uses of new media technology by elderly people. On a theoretical level, we expand the TAM perspective by adding concepts that act as barriers and/or facilitators of technology acceptance, namely technophobia, self-efficacy and previous experience and expertise with technology. We develop an expanded TAM by testing the role of these concepts in two studies on entertainment media technology. In Study 1, we investigate behavioural intention to use 3D cinema among N = 125 German elderly media users (Age 50+). In Study 2, we focus the actual use of a computer game simulation by N = 115 German and US elderly media users (Age 50+). Findings in both studies point towards the central role of perceived usefulness, here modelled as enjoyment, as the reason for elderly people's use and acceptance of entertainment media technology. Perceived ease of use is seen as a precondition for enjoyment, particularly for interactive media.
Splitting the scotoperiod: effects on feeding behaviour, intestinal fill and digestive transit time in broiler chickens

1. The aim of this study was to evaluate how splitting the dark period (scotoperiod) affects feeding behaviour and associated intestinal measures in broilers. 2. Ross 308 broilers were reared to 37 d in groups given either a daily 8-h continuous scotoperiod (DARK 8) or an intermittent light schedule with two equally spaced 4-h scotoperiods (DARK 4 + 4), which yielded the same total duration of darkness per 24 h. 3. Feeding behaviour was recorded weekly from 24-h video recordings of 24 groups each of 64 birds. Empty intestinal weights as well as their contents were measured weekly at 4 time points (n = 192). Digestive transit time was estimated on d 29 using a chromic oxide marker; production variables and the extent of foot pad dermatitis were also recorded. 4. In the 3 h prior to a scotoperiod, feeding activity increased in chickens from DARK 8 but not DARK 4 + 4. This increase was reflected in a higher relative content of the crop in DARK 8 at this time. 5. Immediately following the scotoperiod, feeding activity peaked and, although the chickens in DARK 4 + 4 expressed more feeding behaviour in the first 20 min after the scotoperiod, the chickens in DARK 8 had overall higher feeding activity across the day. However, DARK 4 + 4 had a higher feed intake and weight gain. The occurrence and severity of foot pad dermatitis was similar between treatments. 6. In conclusion, broilers modify their feeding behaviour according to the prevailing light schedule. Eight consecutive hours of darkness reduced growth, but did not affect overall feed conversion efficiency, and did not appear to exacerbate hunger or foot pad dermatitis to any great extent.
4 W highly linear and reliable GaN power amplifier for C-band applications

A C-band GaN amplifier is reported. The design method is focused on high linearity load optimization and use of non-linear transistor models to predict harmonic generation and intermodulation products. The amplifier is characterized in terms of S-parameters, single tone and two tone output power. The measured small signal gain is 24.6 dB. The 1 dB compression point is measured at 36 dBm and the output third order intercept point (OIP3) is above 45 dBm. The power consumption is 10.7 W, the channel temperature 205 °C at drain bias 15 V avoiding stress on the device for reliable operation.
Promoting Community Awareness of the Need for Colorectal Cancer Screening: A Pilot Study

The purpose of this pilot study was to determine if a community education program based on the Health Belief Model effectively promotes awareness of the need for colorectal cancer (CRC) prevention and screening. An education program was given to 20 employees of an accounting firm in a midwestern city. A survey evaluated the participants' beliefs about CRC, before and after the presentation. The results support a significant increase in the belief that CRC is preventable, and in 5 of 6 screening factors from the Health Belief Model. Participants were encouraged to share what they learned and reported that they anticipate sharing with at least 31 others. A screening questionnaire was distributed as a "cue to action" to discuss CRC screening with their physicians. Participants' intention to discuss CRC with their physicians also increased. The actual effectiveness will be evaluated with 11 participants who volunteered for a 1-year follow-up study. This community education concept had several advantages, including simultaneous access to many participants who share personal testimonials and who invite peers to become screened. The program was effective in increasing awareness of the need for CRC prevention and screening, even beyond those in attendance. The results of the 1-year follow-up study may provide more insight to what education factors promote screening most effectively.
Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch repair (MMR) gene mutation status: a literature review assessing utility of tumour features for MMR variant classification

Colorectal cancer (CRC) that demonstrates microsatellite instability (MSI) is caused by either germline mismatch repair (MMR) gene mutations, or ‘sporadic’ somatic tumour MLH1 promoter methylation. MLH1 promoter methylation is reportedly correlated with tumour BRAF V600E mutation status. No systematic review has been undertaken to assess the value of BRAF V600E mutation and MLH1 promoter methylation tumour markers as negative predictors of germline MMR mutation status. A literature review of CRC cohorts tested for MMR mutations, and tumour BRAF V600E mutation and/or MLH1 promoter methylation was conducted using PubMed. Studies were assessed for tumour features, stratified by tumour MMR status based on immunohistochemistry or MSI where possible. Pooled frequencies and 95% CIs were calculated using a random effects model. BRAF V600E results for 4562 tumours from 35 studies, and MLH1 promoter methylation results for 2975 tumours from 43 studies, were assessed. In 550 MMR mutation carriers, the BRAF V600E mutation frequency was 1.40% (95% CI 0.06% to 3%). In MMR mutation-negative cases, the BRAF V600E mutation frequency was 5.00% (95% CI 4% to 7%) in 1623 microsatellite stable (MSS) cases and 63.50% (95% CI 47% to 79%) in 332 cases demonstrating MLH1 methylation or MLH1 expression loss. MLH1 promoter methylation of the ‘A region’ was reported more frequently than the ‘C region’ in MSS CRCs (17% vs 0.06%, p<0.0001) and in MLH1 mutation carriers (42% vs 6%, p<0.0001), but not in MMR mutation-negative MSI-H CRCs (40% vs 47%, p=0.12). Methylation of the ‘C region’ was a predictor of MMR mutation-negative status in MSI-H CRC cases (47% vs 6% in MLH1 mutation carriers, p<0.0001). This review demonstrates that tumour BRAF V600E mutation, and MLH1 promoter ‘C region’ methylation specifically, are strong predictors of negative MMR mutation status. It is important to incorporate these features in multifactorial models aimed at predicting MMR mutation status.
Magnetic resonance imaging of bone marrow in lymphoproliferative disorders: correlation with bone marrow biopsy

Summary. In a prospective clinical study 10 normal volunteers and 30 patients with lymphoma—11 patients with Hodgkin's lymphoma and 19 patients with non‐Hodgkin's lymphoma (11 low grade, 8 high grade)–were examined. Proximal femora, pelvis and lumbar spine were imaged with a 1.5 tesla superconducting MR imaging system (Siemens Magnetom). Areas of malignant infiltration in the bone marrow were clearly detected by visual and/or quantitative assessment. In most cases bone marrow involvement was demonstrated by both magnetic resonance imaging and bone marrow biopsies. However, in three of 30 patients magnetic resonance imaging showed evidence of lymphomatous involvement despite normal bone marrow histology. In one patient bone marrow cytology revealed malignant infiltration in the absence of MRI abnormalities. Thus, MRI is a sensitive method for detecting bone marrow infiltration by lymphoma.
Dioxyde de titane nanométrique : de la nécessité de proposer une valeur limite d’exposition professionnelle.

En 2004, plusieurs experts reunis par la Commission Europeenne estimaient par consensus que les risques potentiels des nanomateriaux manufactures ne pouvaient etre predits ou derives des proprietes connues de la meme matiere sous une forme plus grossiere. Selon leur estimation, fabriquer un nanomateriau revenait a creer un nouvel agent chimique different de l’agent chimique originel et un numero d’identification specifique (CAS) etait necessaire. La mise en œuvre d’une telle decision aurait permis d’initier des mesures incluant la determination de valeurs limites d’exposition professionnelle (VLEP). En 2005, l’INRS avait egalement rapporte la necessite de reevaluer les VLEP des poussieres totales et alveolaires, estimant qu’une reflexion relative aux particules ultrafines devrait par ailleurs etre entreprise, en raison de leurs proprietes toxicologiques particulieres. Depuis, en France du moins, aucune valeur limite d’exposition professionnelle relative aux nanomateriaux manufactures n’a ete determinee. Tel n’est pas le cas des Etats-Unis ou le National institute for occupational safety and health (NIOSH) a produit des 2011 une monographie dans laquelle est recommandee une VLEP pour le dioxyde de titane (TiO2) nanometrique. A partir de l’analyse fine des travaux existants, cette note a pour objectif d’engager des reflexions sur la necessite de definir des VLEP pour les nanomateriaux et plus precisement pour le dioxyde de titane nanometrique en proposant une demarche pour l’evaluation de l’exposition aux aerosols contenant du TiO2 ainsi que les principales mesures de prevention a recommander. Enfin, la necessite de reevaluer les valeurs limites d’exposition professionnelle des poussieres reputees « sans effet specifique » sera egalement abordee.
Enhanced Expression of CD20 in Human Tumor B Cells Is Controlled through ERK-Dependent Mechanisms

Rituximab, a chimeric Ab directed against CD20, induces apoptosis in targeted cells. Although the majority of B cell malignancies express the CD20 Ag, only ∼50% of patients will respond to single-agent rituximab. The available data suggest that a decreased CD20 expression could account for the lack of response observed in some patients treated with rituximab. Despite the potential critical role of CD20 in the biology of B cell malignancies, the mechanisms controlling its expression are poorly understood. We evaluated the effect of the immune modulator agent bryostatin-1 on the expression of CD20 in non-Hodgkin’s lymphoma cells. Using the B cell lines, DB and RAMOS, as well as tumor cells derived from a chronic lymphocytic leukemia patient, we demonstrated that bryostatin-1 enhanced the expression of both CD20 mRNA and protein. The enhanced expression of CD20 was associated with increased transcriptional activity of the CD20 gene, whereas the stability of CD20 mRNA was not affected. The effect of bryostatin-1 on CD20 expression in non-Hodgkin’s lymphoma cells was mediated through the MAPK kinase/ERK signal transduction pathway and involved protein kinase C, but was independent of p38 MAPK and was insensitive to dexamethasone. Cells pretreated with bryostatin-1 were more susceptible to the proapoptotic effect of anti-CD20 Ab. Overall, these data demonstrate for the first time that ERK phosphorylation is required for the up-regulated expression of CD20 on B cell malignancies. The findings also suggest that bryostatin-1 and rituximab could be a valuable combined therapy for B cell malignancies.
Stratification Directionnelle adaptative

L'estimation d'une probabilite de defaillance, ou autrement dit l'estimation d'une integrale multidimensionnelle, est une problematique classique en fiabilite des structures et de nombreuses methodes de calculs existent deja dans la litterature. Cependant, tres peu de methodes repondent simultanement aux contraintes suivantes couramment rencontrees dans un cadre industriel : une probabilite a estimer tres faible, des ressources computationnelles limitees et une estimation controlee. Dans cette optique, nous avons developpe une nouvelle methode de Monte-Carlo acceleree, nommee SDA : Stratification Directionnelle Adaptative. Celle-ci couple la methode de stratification, permettant la mise en place d'une methode adaptative a tirages preferentiels, et la simulation directionnelle, adaptee a l'estimation de faibles probabilites et possedant un bon rapport "precision/temps de calculs". Nous proposons tout d'abord un estimateur avec deux etapes, apprentissage puis estimation, SDA-2, generalise ensuite avec un nombre quelconque d'etapes, SDA-L. Dans les deux cas, nous etudions les comportements asymptotique et non asymptotique des estimateurs. Nous proposons egalement une amelioration de SDA-2, pour solutionner le probleme d'espace d'exploration trop vaste engendre par une dimension trop elevee. Pour cela, nous introduisons une statistique, evaluee a la fin de l'etape d'apprentissage, permettant une reduction pertinente du nombre de strates et une classification des variables aleatoires selon leurs influences sur la defaillance.
Itérer avec confiance

Un curseur est une structure de donnees qui permet d'obtenir successivement les elements d'une collection, tout en laissant a l'utilisateur le controle de cette iteration. Cet article propose une specification formelle de ce qu'est un curseur, dans le contexte de la verification deductive, avec le double objectif de prouver que des curseurs sont correctement realises et correctement utilises. En particulier, nous proposons une approche modulaire, ou le code utilisant un curseur peut etre prouve sans connaitre le detail d'implementation de ce curseur. Ce travail est valide experimentalement en utilisant l'outil Why3, au travers de nombreux exemples.
Fractionated but Not Single-Dose Radiotherapy Induces an Immune-Mediated Abscopal Effect when Combined with Anti–CTLA-4 Antibody

Purpose: This study tested the hypothesis that the type of dose fractionation regimen determines the ability of radiotherapy to synergize with anti–CTLA-4 antibody. Experimental Design: TSA mouse breast carcinoma cells were injected s.c. into syngeneic mice at two separate sites, defined as a “primary” site that was irradiated and a “secondary” site outside the radiotherapy field. When both tumors were palpable, mice were randomly assigned to eight groups receiving no radiotherapy or three distinct regimens of radiotherapy (20 Gy × 1, 8 Gy × 3, or 6 Gy × 5 fractions in consecutive days) in combination or not with 9H10 monoclonal antibody against CTLA-4. Mice were followed for tumor growth/regression. Similar experiments were conducted in the MCA38 mouse colon carcinoma model. Results: In either of the two models tested, treatment with 9H10 alone had no detectable effect. Each of the radiotherapy regimens caused comparable growth delay of the primary tumors but had no effect on the secondary tumors outside the radiation field. Conversely, the combination of 9H10 and either fractionated radiotherapy regimens achieved enhanced tumor response at the primary site (P < 0.0001). Moreover, an abscopal effect, defined as a significant growth inhibition of the tumor outside the field, occurred only in mice treated with the combination of 9H10 and fractionated radiotherapy (P < 0.01). The frequency of CD8+ T cells showing tumor-specific IFN-γ production was proportional to the inhibition of the secondary tumor. Conclusions: Fractionated but not single-dose radiotherapy induces an abscopal effect when in combination with anti–CTLA-4 antibody in two preclinical carcinoma models. (Clin Cancer Res 2009;15(17):5379–88)
Effective capacity optimization for multiuser diversity systems with adaptive transmission

The effective capacity (EC) for a wireless system expresses the maximum arrival source rate that the system can reliably transmit over the wireless channel while fulfilling a probabilistic delay constraint. This paper presents an EC optimization for a multiuser diversity system exploiting proportional opportunistic scheduling at the medium access control layer in conjunction with adaptive modulation and coding (AMC) at the physical layer. We consider the downlink of a time‐slotted multiuser system with two different types of channel state information (CSI) at the transmitter, that is, (i) full CSI, whereby each user feeds back its normalized signal‐to‐noise ratio to the transmitter and (ii) quantized CSI, where each user feeds back the AMC mode for transmission. For each case, we first derive the EC function of the queue service process for the individual users at the medium access control layer. We then design the AMC scheme with power control aiming at maximizing the said function subject to a target packet‐error rate constraint. Both independent and identically distributed and time‐correlated fading channels are considered. The results illustrate the superior performance of the proposed schemes, when compared with the previous systems such as opportunistic scheduling with single‐rate transmission and round‐robin scheduling with AMC. Copyright © 2012 John Wiley & Sons, Ltd.