Miracle-dz/UniFAR-FTUs huggingface dataset:
Dabrafenib in the treatment of metastatic or unresectable melanoma

Dabrafenib is a potent inhibitor of mutant BRAF. Trials to date have shown it to be well tolerated, with significant activity in unresectable stage III or IV metastatic melanoma. Overall response rates of approximately 50% were seen in addition to improved progression-free and overall survival of 6 and 18 months, respectively. Preclinical studies suggested that combining BRAF and MEK inhibition would increase response rates and decrease toxicity. Clinical trials with the combination of dabrafenib and trametinib have improved progression-free and overall survival in interim analyses. Future improvements in responses and outcomes will depend on additional combination strategies, possibly employing immunotherapy.
The Response Regulator CpxR Directly Regulates Expression of Several Legionella pneumophila icm/dot Components as Well as New Translocated Substrates

ABSTRACT Legionella pneumophila has been shown to utilize the icm/dot type IV secretion system for pathogenesis. This system was shown to be composed of icm/dot complex components and accessory proteins, as well as a large number of translocated substrates. Bioinformatic analysis of the regulatory regions of all the genes revealed that several icm/dot genes, as well as two genes encoding icm/dot translocated substrates, contain the conserved CpxR regulatory element, a regulator that has been shown previously to control the expression of the icmR gene. An experimental analysis, which included a comparison of gene expression in a L. pneumophila wild-type strain and gene expression in a cpxR deletion mutant, construction of mutants with mutations in the CpxR conserved regulatory elements, controlled expression studies, and mobility shift assays, demonstrated the direct relationship between the CpxR regulator and the expression of the genes. Furthermore, genomic analysis identified nine additional genes that contain a putative CpxR regulatory element; five of these genes (two legA genes and three ceg genes) were suggested previously to be putative icm/dot translocated substrates. The three ceg genes identified, which were shown previously to contain a putative PmrA regulatory element, were found here to be regulated by both CpxR and PmrA. The other six genes (two legA genes and four new genes products were found to be regulated by CpxR. Moreover, using the CyaA translocation assay, these nine gene products were found to be translocated into host cells in an Icm/Dot-dependent manner. Our results establish that the CpxR regulator is a fundamental regulator of the icm/dot type IV secretion system in L. pneumophila.
Mortality in relation to smoking: 40 years' observations on male British doctors

Abstract Objective: To assess the hazards associated with long term use of tobacco. Design: Prospective study of mortality in relation to smoking habits assessed in 1951 and again from20time to time thereafter, with causes sought of deaths20over 40 years (to 1991). Continuation of a study that was last reported after 20 years' follow up (1951-71). Subjects: 34 439 British male doctors who replied20to a postal questionnaire in 1951, of whom 10 000 had died during the first 20 years and another 10 000 have died during the second 20 years. Results - Excess mortality associated with20smoking was about twice as extreme during the second half of the study as it had been during the first half. The death rate ratios during 1971-91 (comparing continuing cigarette smokers with lifelong20non-smokers) were approximately threefold at ages 45-64 and twofold at ages 65-84. The excess mortality was chiefly from diseases that can be caused by smoking. Positive associations with smoking were confirmed for death from cancers of the mouth, oesophagus, pharynx, larynx, lung, pancreas, and bladder; from chronic obstructive pulmonary disease and other respiratory diseases; from vascular diseases; from peptic ulcer; and (perhaps because of confounding by personality and alcohol use) from cirrhosis, suicide, and poisoning. A negative association was confirmed with death20from Parkinson's disease. Those who stopped20smoking before middle age subsequently avoided almost all of the excess risk that they would otherwise have suffered, but even those who stopped smoking in middle age were subsequently at substantially less risk than those who continued to smoke. Conclusion: Results from the first 20 years of this study, and of other studies at that time, substantially20underestimated the hazards of long term use of tobacco. It now seems that about half of all regular cigarette smokers will eventually be killed by their habit.
Endogenous glucose production following injury increases with age.

To evaluate the influence of aging on the increase in endogenous glucose production that follows injury, we studied 22 fully resuscitated, clinically stable, previously healthy patients aged < or = 30 yr or > or = 60 yr admitted to hospital following injury, and 11 healthy volunteers in the same age groups. Endogenous glucose production was determined using a primed constant infusion of D-glucose-6,6-2d2. Urine cortisol and C-peptide were markedly higher in patients than volunteers (both P < 0.01), and urine C-peptide was lower in older than in younger patients (P < 0.05). Urine cortisol increased as a function of the interaction of age and Injury Severity Score (ISS) (r2 = 0.40, P < 0.001). Intracellular water was markedly lower and extracellular water greater in patients compared with volunteers (both P < 0.001), reflecting the loss of body cell mass and expansion of the extracellular space following injury. Endogenous glucose production (milligrams per minute per liter intracellular water) was best described as a function of ISS and age-ISS interaction (r2 = 0.35, all P < 0.05), and was increased 56% and 78% in younger and older patients, respectively, in comparison with the respective volunteer groups. Endogenous glucose production following injury increases in relation to the severity of injury and patient age. Greater cortisol elaboration and diminished insulin secretion in older patients may contribute to this age effect.
Partial Dual-Relay Selection Protocols in Two-Way Relayed FSO Networks

In this paper, we present relay selection protocols for parallel relayed free-space optical (FSO) communication network, which consists of two non-line-of-sight terminal nodes and multiple two-way relays (TWR). The TWRs use the two time-phase decode-and-forward relaying protocol to establish a bidirectional link between the terminals. For the considered system, we propose a partial dual-relay selection (P-DRS) scheme, in which two TWRs are selected to participate in the communication process. By using two TWRs, the advantages of cooperative diversity are achieved. For the proposed relay selection scheme and assuming Gamma-Gamma fading channels with pointing errors and path loss, we derive an exact closed form expression for the system outage. Further, we derive an asymptotic expression for average error probability. The diversity order of the system is also presented. It is shown by numerical analysis that by using the proposed P-DRS scheme, the system performance can be significantly improved.
Control of Contact Interactions with Acatastatic Nonholonomic Constraints

A robot arm performs many tasks by interacting with objects or other robots in the environment. It is important for the robot arm to be able to exhibit controlled interactions with the objects and other robots. The contact motion between the robot arm and an object can be rolling, sliding, or separation. In this article, we address the problem of maintaining rolling contact between the robot arm and an external moving object. We assume that a nominal model of the motion of the moving object is available. The dynamic system that characterizes the motion of the robot arm and the moving object in this case is acatastatic and nonholonomic. We have designed a nonlinear feedback for the control of such a system that successfully maintains rolling contact. Simulation results are presented to demonstrate the effectiveness of the system.
Disulfide analysis reveals a role for macrophage migration inhibitory factor (MIF) as thiol-protein oxidoreductase.

The molecular mechanism of action of macrophage migration inhibitory factor (MIF), a cytokine with a critical role in the immune and inflammatory response, has not yet been identified. Here we report that MIF can function as an enzyme exhibiting thiol-protein oxidoreductase activity. Using a decapeptide fragment of MIF (MF1) spanning the conserved cysteine sequence motif Cys57-Ala-Leu-Cys60 (CALC), Cys-->Ser mutants (C57S MIF, C60S MIF, and C57S/C60S MIF) of human MIF (wtMIF), and alkylated wtMIF, we show that this activity is mediated by the CALC region and is important for the macrophage-activating properties of MIF. Both wtMIF and MF1 were demonstrated to form an intramolecular disulfide bridge. Using two common oxidoreductase assays, MIF was shown to enzymatically catalyze the reduction of insulin and 2-hydroxyethyldisulfide (HED). Examination of wtMIF and the mutants by far-UV circular dichroism spectroscopy (CD) together with denaturation studies showed that substituting or reducing the cysteine residues of CALC led to a reduced conformational stability of MIF but did not significantly change its overall conformation. A functional role for the CALC region was revealed by subjecting the mutants and alkylated wtMIF to the enzymatic assays. Mutant C60S did not have any enzymatic activity while mutant C57S had a reduced activity. Thiol-modified wtMIF that was alkylated under oxidizing conditions was found to have full enzymatic activity, whereas alkylation of wtMIF under reducing conditions completely eliminated MIF-mediated redox activity. Importantly, further physiological relevance of the disulfide motif was obtained by examining the mutants and alkylated MIF in an immunological assay that involved the macrophage-activating properties of MIF. In this test, mutant C60S was essentially inactive and mutant C57S was partly active, indicating together that at least some of the cytokine-like biological activities of MIF are dependent on the presence of cysteine 57 and 60. Again, use of the alkylated MIF species confirmed the role of the cysteine motif for this MIF activity. In conclusion, our results argue (a) that MIF exhibits enzymatic oxidoreductase activity, (b) that this activity is dependent on the presence of the catalytic center that is formed by cysteine residues 57 and 60, and (c) that certain MIF-mediated immune processes are due to the cysteine-mediated redox mechanism.
UBER DEN ZUSAMMENHANG ZWISCHEN DEM VERBLAUEN DES HOLZES UND DEN INSEKTEN

Die Insekten spielen an und fur sich eine sehr wichtige Rolle als Schadlinge des Waldes und des Holzmaterials. Dazu kommen aber noch die oft sehr bedeutenden Schaden, welche die Insekten indirekt verursachen, indem sie als Ubertrager von Pilzsporen, welche sich dann in dem Holze selbstandig weiterentwickeln konnen, mitwirken. Mehrere Beispiele fur ein solches Zusammenspiel zwischen Insekten und Pilzen odter Bakterien sind bekannt. Eine ausgezeichnete tVbersicht uiber unsere ge-genwartigen Kenntnisse auf diesem Gebiete ist von dem amerikanischen Forscher LEACH (1940) zusammengestellt worden. Ein gutes Beispiel fur ein derartiges Zusammenwirken von Insekten und Pilzen ist das Verblauen bei den Nadelholzern. Das Splintholz versehiedener Koniferen wird leicht von Blauepilzen angegriffen. Das Verblauen tritt vor allem an den aufgearbeiteten Stammen auf, aber es kann manchmal auch a.n lebenden Baumen vorkommen, besonders wenn diese infolge von Trockenheit, Feuerschaden usw. geschwacht sind. Die Borke bildet an und ffir sich einen guten Schutz gegen die Blauepilze, deren Sporen nicht durch die unbeschadigte Rinde ei-ndringen konnen. Schon von SCHRENCK (1903) vermutete jedoch, dass die Insekten Vermittler bei der ETbertragung der Pilzsporen in das Holz wren, und dass dies tatsachlich der Fall ist, ist spater durch eine Reihe Untersuchungen bestatigt worden (CRAIGHEAD 1928, NELSON and BEAL 1929, NELSON 1934 u. a.). Durch spezielle Versuche wiesen LEACH, ORR und CHRISTENSEN (1934) nach, dass die Blauepilzsporen durch Insekten in das Holz eingefuihrt wurden, und dass sie kaum irgendwelche Moglichkeiten hatten, es auf eine andere Weise zu infizieren. Es hat sich erwiesen, dass verschiedene Insekten Blauesporen mit sich fiihren. In Nordamerika iberfiuhren Dendroctonus-Arten Blaue auf Kiefern,
Cytomegalovirus Quantitation by Real-Time PCR Is Unaffected by Delayed Separation of Plasma from Whole Blood

ABSTRACT A previous study suggested that delayed sample preparation can cause a false-positive plasma cytomegalovirus (CMV) PCR. We evaluated 78 samples submitted for CMV testing, and we report that a 24-h delay in plasma separation did not affect viral quantitation by real-time PCR. Laboratories should evaluate specimen handling requirements for their own PCR technology.
Association of D 4-GDI expression with breast cancer progression

D4-GDI is a key regulator of Rho GTPases that have been implicated in several aspects of breast tumorigenesis. We have previously found that D4-GDI was selectively expressed in breast cancer cell lines over normal mammary epithelial cells [45]. In this study, we investigated the expression level of D4-GDI in breast tumor specimens (n = 165) by immunohistochemistry using a validated antibody that specifically recognizes the full-length D4-GDI protein. D4-GDI was predominantly expressed in the luminal cells of the duct in contrast to the myoepithelial cells of the outer layer. The percentage of D4-GDI positive samples were found to be higher in the early stages of breast cancers followed by a significant decrease in malignant tumors and metastatic lesions when compared to normal breast tissues (p < 0.01). Analysis of matched samples confirmed the lower expression of D4-GDI in malignant tumors than normal adjacent tissues, while there was no further decrease in metastatic lesions. These results suggest that D4-GDI may function as a biphasic regulator of breast cancer progression and metastasis.
SERUM PROTEINS AND BIOCHEMICAL PARAMETERS IN CATTLE WITH THEILERIOSIS 137

Theileriosis, caused by Theileria protozoa and infected by ticks, is a disease with high mortality rate. The most common species found in tropical and subtropical regions are T. annulata and T. parva. Theileriosis is often seen in cattle in the Eastern Anatolia Region, especially in the Van region. Clinical symptoms such as high fever, anaemia and haemoglobinuria are detected with this disease. Besides, the blood-shaped elements, especially the volume of red blood cells, are reduced. Diagnosis can be made accurately when blood protozoan is seen in erythrocyte in blood smear.
First results of the Piton de la Fournaise STRAP 2015 experiment: multidisciplinary tracking of a volcanic gas and aerosol plume

Abstract. The STRAP (Synergie Transdisciplinaire pour Repondre aux Aleas lies aux Panaches volcaniques) campaign was conducted over the entire year of 2015 to investigate the volcanic plumes of Piton de La Fournaise (La Reunion, France). For the first time, measurements at the local (near the vent) and at the regional scales were conducted around the island. The STRAP 2015 campaign has become possible thanks to strong cross-disciplinary collaboration between volcanologists and meteorologists. The main observations during four eruptive periods (85 days) are summarised. They include the estimates of SO2, CO2 and H2O emissions, the altitude of the plume at the vent and over different areas of La Reunion Island, the evolution of the SO2 concentration, the aerosol size distribution and the aerosol extinction profile. A climatology of the volcanic plume dispersion is also reported. Simulations and measurements show that the plumes formed by weak eruptions have a stronger interaction with the surface of the island. Strong SO2 mixing ratio and particle concentrations above 1000 ppb and 50 000 cm−3 respectively are frequently measured over a distance of 20 km from Piton de la Fournaise. The measured aerosol size distribution shows the predominance of small particles in the volcanic plume. Several cases of strong nucleation of sulfuric acid have been observed within the plume and at the distal site of the Maido observatory. The STRAP 2015 campaign provides a unique set of multi-disciplinary data that can now be used by modellers to improve the numerical parameterisations of the physical and chemical evolution of the volcanic plumes.
A comparison of the effects of desflurane and isoflurane on arterial oxygenation during one‐lung ventilation

In a randomised prospective cross‐over study, we compared the effects of desflurane and isoflurane on arterial oxygenation, heart rate and mean arterial pressure during one‐lung anaesthesia. Thirty patients scheduled for oesophagogastrectomy were randomly assigned to one of two groups. One group of 15 patients received desflurane to an end‐tidal concentration of 6% in oxygen from induction until the end of 30 min of open chest one‐lung ventilation in the lateral position. This was followed by isoflurane to an end‐tidal concentration of 1.1% in oxygen for the next 30 min of one‐lung ventilation. The other group of 15 patients received the two anaesthetic agents in the reverse order. We found no significant difference in arterial oxygenation, heart rate or mean arterial pressure between the two inhalational agents. In the subgroup of 10 patients with pulmonary artery catheters, we found no significant differences in mixed venous saturation, derived shunt or cardiac output. We conclude that during one‐lung ventilation, the choice between desflurane and isoflurane does not significantly influence arterial oxygenation.
Auditory hallucinations inhibit exogenous activation of auditory association cortex

Percepts unaccompanied by a veridical stimulus, such as hallucinations, provide an opportunity for mapping the neural correlates of conscious perception. Functional magnetic resonance imaging (fMRI) can reveal localized changes in blood oxygenation in response to actual as well as imagined sensory stimulation. The safe repeatability of fMRI enabled us to study a patient with schizophrenia while he was experiencing auditory hallucinations and when hallucination-free (with supporting data from a second case). Cortical activation was measured in response to periodic exogenous auditory and visual stimulations using time series regression analysis. Functional brain images were obtained in each hallucination condition both while the patient was on and off antipsychotic drugs. The response of the temporal cortex to exogenous auditory stimulation (speech) was markedly reduced when the patient was experiencing hallucinating voices addressing him, regardless of medication. Visual cortical activation (to flashing lights) remained normal over four scans. From the results of this study and previous work on visual hallucinations we conclude that hallucinations coincide with maximal activation of the sensory and association cortex, specific to the modality of the experience.
Hybrid AC Power Source Based on Modular Multilevel Converter and Linear Amplifier

This paper presents a hybrid amplifier for an ac power source (ACPS). The topology is composed of a modular multilevel converter (MMC), operating as main amplifier, connected in series with a linear power amplifier (LPA), which operates as correction amplifier. This way, it is possible to gather the modularity, reliability, and high efficiency provided by the MMC and the high waveform fidelity provided by the LPA. Additionally, it is possible to reproduce a voltage waveform with a high bandwidth and, differently from previous works, with a topology that requires a unique dc voltage source for the main amplifier. The inner current and the submodule capacitor voltages are controlled in the MMC. Meanwhile, the LPA is controlled to define the output voltage. A design methodology and experimental results are included to demonstrate the operation of the ACPS topology.
Changes in Aleut Concerns Following the Stakeholder‐Driven Amchitka Independent Science Assessment

There is widespread agreement that stakeholders should be included in the problem‐formulation phase of addressing environment problems and, more recently, there have been attempts to include stakeholders in other phases of environmental research. However, there are few studies that evaluate the effects of including stakeholders in all phases of research aimed at solving environmental problems. Three underground nuclear blasts were detonated on Amchitka Island from 1965 to 1971. Considerable controversy developed when the Department of Energy (DOE) decided to “close” Amchitka. Concerns were voiced by subsistence Aleuts living in the region, resource trustees, and the State of Alaska, among others. This article evaluates perceptions of residents of three Aleutian village before (2003) and after (2005) the Consortium for Risk Evaluation with Stakeholder Participation's (CRESP) Amchitka Independent Science Assessment (AISA). The CRESP AISA provided technical information on radionuclide levels in biota to inform questions of seafood safety and food chain health. CRESP used the questions asked at public meetings in the Aleut communities of Atka, Nikolski, and Unalaska to evaluate attitudes and perceptions before and after the AISA. Major concerns before the AISA were credibility/trust of CRESP and the DOE, and information about biological methodology of the study. Following the AISA, people were most concerned about health effects and risk reduction, and trust issues with CRESP declined while those for the DOE remained stable. People’s relative concerns about radionuclides declined, while their concerns about mercury (not addressed in the AISA) increased, and interest in ecological issues (population changes of local species) and the future (continued biomonitoring) increased from 2003 to 2005. These results suggest that questions posed at public meetings can be used to evaluate changes in attitudes and perceptions following environmental research, and the results are consistent with the hypothesis that the AISA answered questions about radionuclides, and lowered overall concern about radionuclides, but left unanswered concerns about the health effects of mercury.
Uncovering the Boundary-Spanning Role of Information Systems Research in Trans-Disciplinary Knowledge Advancement

Intrigued by the important yet underexplored inter-disciplinary impact of IS discipline, this study investigates the inter-disciplinary role played by IS discipline in trans-disciplinary knowledge advancement. To achieve this objective, this study firstly advanced a Model of Trans-Disciplinary Knowledge Advancement that posits a process that consists of three stages of thesis, antithesis, and synthesis with two transitions, namely knowledge liquidization and crystallization, in two modes, namely boundary-reinforcing and boundary-spanning. In light of this model, this study conducted an algorithmic historiographic citation analysis on 114767 articles in four distinct research areas, including technology acceptance, IT system success, trust, and knowledge management, extracted from ISI Web of Science database. 64 central articles in main paths of liquidization and crystallization were elicited. Results from an in-depth bibliographic analysis on these central articles shed light on four distinct trans-disciplinary roles (i.e., spanner, innovator, aggregator, and reinforcer) and trans-disciplinary characteristics of IS research.