julilili42/papers huggingface dataset:
Liquid biopsy: ready to guide therapy in advanced prostate cancer?
2016-07-19

The identification of molecular markers associated with response to specific therapy is a key step for the implementation of personalised treatment strategies in patients with metastatic prostate cancer. Only in a low proportion of patients biopsies of metastatic tissue are performed. Circulating tumour cells ( CTC ), cell‐free DNA (cf DNA ) and RNA offer the potential for non‐invasive characterisation of disease and molecular stratification of patients. Furthermore, a ‘liquid biopsy’ approach permits longitudinal assessments, allowing sequential monitoring of response and progression and the potential to alter therapy based on observed molecular changes. In prostate cancer, CTC enumeration using the CellSearch© platform correlates with survival. Recent studies on the presence of androgen receptor ( AR ) variants in CTC have shown that such molecular characterisation of CTC provides a potential for identifying patients with resistance to agents that inhibit the androgen signalling axis, such as abiraterone and enzalutamide. New developments in CTC isolation, as well as in vitro and in vivo analysis of CTC will further promote the use of CTC as a tool for retrieving molecular information from advanced tumours in order to identify mechanisms of therapy resistance. In addition to CTC , nucleic acids such as RNA and cf DNA released by tumour cells into the peripheral blood contain important information on transcriptomic and genomic alterations in the tumours. Initial studies have shown that genomic alterations of the AR and other genes detected in CTC or cf DNA of patients with castration‐resistant prostate cancer correlate with treatment outcomes to enzalutamide and abiraterone. Due to recent developments in high‐throughput analysis techniques, it is likely that CTC , cf DNA and RNA will be an important component of personalised treatment strategies in the future.
Interdisciplinary consensus statement on indication and application of a hydrogel spacer for prostate radiotherapy based on experience in more than 250 patients
2016-07-19

Abstract Background The aim of the study was to reach a consensus on indication and application of a hydrogel spacer based on multicentre experience and give new users important information to shorten the learning curve for this innovative technique. Methods The interdisciplinary meeting was attended by radiation oncologists and urologists, each with experience of 23 – 138 hydrogel injections (SpaceOAR®) in prostate cancer patients before dose-escalated radiotherapy. User experience was discussed and questions were defined to comprise practical information relevant for successful hydrogel injection and treatment. Answers to the defined key questions were generated. Hydrogel-associated side effects were collected to estimate the percentage, treatment and prognosis of potential risks. Results The main indication for hydrogel application was dose-escalated radiotherapy for histologically confirmed low or intermediate risk prostate cancer. It was not recommended in locally advanced prostate cancer. The injection or implantation was performed under transrectal ultrasound guidance via the transperineal approach after prior hydrodissection. The rate of injection-related G2-toxicity was 2% (n = 5) in a total of 258 hydrogel applications. The most frequent complication (n = 4) was rectal wall penetration, diagnosed at different intervals after hydrogel injection and treated conservatively. Conclusions A consensus was reached on the application of a hydrogel spacer. Current experience demonstrated feasibility, which could promote initiation of this method in more centres to reduce radiation-related gastrointestinal toxicity of dose-escalated IGRT. However, a very low rate of a potential serious adverse event could not be excluded. Therefore, the application should carefully be discussed with the patient and be balanced against potential benefits.
Signs of enhanced sleep and sleep-associated memory processing following the anti-inflammatory antibiotic minocycline in men
2016-07-19

Pro-inflammatory cytokines can promote sleep and neuronal processes underlying memory formation. However, this has mainly been revealed in animal studies. In this double-blind, placebo-controlled within-subject designed study, we examined how changes in the balance between pro- and anti-inflammatory signalling affect sleep and sleep-associated memory consolidation in humans. After learning declarative memory tasks (word pairs, texts) and a procedural memory task (finger tapping) in the evening, 21 healthy young men orally received either 200 mg of the anti-inflammatory antibiotic minocycline or placebo shortly before nocturnal sleep. Sleep was allowed between 23:00 and 07:00 h and recorded polysomnographically. Retrieval of memories was tested two days later. Because of outliers or missing data, final sample size was reduced to n = 14–19. Our data suggest that rather than weakening sleep as expected based on animal studies, the anti-inflammatory agent promoted sleep and memory consolidation. Specifically, minocycline increased slow-wave activity (0.68–4.0 Hz) during non-rapid eye movement sleep stage 2 and selectively enhanced episodic aspects in memory (i.e. memory for the temporal order of events in the texts). In combination with previous results, our findings indicate that, in humans, reducing pro-inflammatory signalling can act towards deepening non-rapid eye movement sleep and enhancing its memory forming efficacy.
The perception of ego-motion change in environments with varying depth: Interaction of stereo and optic flow
2016-07-19

When estimating ego-motion in environments (e.g., tunnels, streets) with varying depth, human subjects confuse ego-acceleration with environment narrowing and ego-deceleration with environment widening. Festl, Recktenwald, Yuan, and Mallot (2012) demonstrated that in nonstereoscopic viewing conditions, this happens despite the fact that retinal measurements of acceleration rate-a variable related to tau-dot-should allow veridical perception. Here we address the question of whether additional depth cues (specifically binocular stereo, object occlusion, or constant average object size) help break the confusion between narrowing and acceleration. Using a forced-choice paradigm, the confusion is shown to persist even if unambiguous stereo information is provided. The confusion can also be demonstrated in an adjustment task in which subjects were asked to keep a constant speed in a tunnel with varying diameter: Subjects increased speed in widening sections and decreased speed in narrowing sections even though stereoscopic depth information was provided. If object-based depth information (stereo, occlusion, constant average object size) is added, the confusion between narrowing and acceleration still remains but may be slightly reduced. All experiments are consistent with a simple matched filter algorithm for ego-motion detection, neglecting both parallactic and stereoscopic depth information, but leave open the possibility of cue combination at a later stage.
EPIGENETICS OF COLONIZING SPECIES? A STUDY OF JAPANESE KNOTWEED IN CENTRAL EUROPE
2016-07-19

Some of the world's most successful invasive plants have spread across large geographic areas while retaining little or no genetic diversity. Because of this lack of heritable variation, evolutionary hypotheses are usually not invoked when attempting to explain the success of these species. However, heritable trait variation within and among invasive populations could also be created through epigenetic or other nongenetic processes, particularly in clonal invaders where somatic changes can potentially persist indefinitely. We tested this possibility in a collection of 83 genetically identical clones of the invasive Japanese knotweed Fallopia japonica collected across Central Europe and propagated in a common environment for several years. Using regular as well as methylation-sensitive amplified fragment length polymorphism (AFLP) markers, we found that all clones indeed belonged to the same genotype but to 27 different epigenotypes. The different knotweed clones were also phenotypically differentiated. Path analysis indicated that among-clone phenotypic variation is partly correlated with epigenetic variation, as well as both directly and indirectly (through epigenetic variation) with climates of origin. Our results thus suggest a potential role of epigenetic variation in the geographic spread and invasion success of Japanese knotweed. More generally, our study highlights the need to incorporate large-scale epigenetic screens in studies of genetically uniform clonal invaders.
Does soil aging affect the N2O mitigation potential of biochar? A combined microcosm and field study
2016-07-20

Abstract The application of biochar as a soil amendment to improve soil fertility has been suggested as a tool to reduce soil‐borne CO 2 and non‐ CO 2 greenhouse gas emissions, especially nitrous oxide (N 2 O). Both laboratory and field trials have demonstrated N 2 O emission reduction by biochar amendment, but the long‐term effect (&gt;1 year) has been questioned. Here, we present results of a combined microcosm and field study using a powdered beech wood biochar from slow pyrolysis. The field experiment showed that both CO 2 and N 2 O emissions were still effectively reduced by biochar in the third year after application. However, biochar did not influence the biomass yield of sunflower for biogas production ( Helianthus annuus L.). Biochar reduced bulk density and increased soil aeration and thus reduced the water‐filled pore space ( WFPS ) in the field, but was also able to suppress N 2 O emission in the microcosms experiment conducted at constant WFPS . For both experiments, biochar had limited impact on soil mineral nitrogen speciation, but it reduced the accumulation of nitrite in the microcosms. Extraction of soil DNA and quantification of functional marker genes by quantitative polymerase chain reaction showed that biochar did not alter the abundance of nitrogen‐transforming bacteria and archaea in both field and microcosm experiments. In contradiction to previous experiments, this study demonstrates the long‐term N 2 O emission suppression potential of a wood biochar and thus highlights its overall climate change mitigation potential. While a detailed understanding of the underlying mechanisms requires further research, we provide evidence for a range of biochar‐induced changes to the soil environment and their change with time that might explain the often observed N 2 O emission suppression.
Whole-Genome Sequencing to Evaluate the Resistance Landscape Following Antimalarial Treatment Failure With Fosmidomycin-Clindamycin
2016-07-20

Novel antimalarial therapies are needed in the face of emerging resistance to artemisinin combination therapies. A previous study found a high cure rate in Mozambican children with uncomplicated Plasmodium falciparum malaria 7 days after combination treatment with fosmidomycin-clindamycin. However, 28-day cure rates were low (45.9%), owing to parasite recrudescence. We sought to identify any genetic changes underlying parasite recrudescence. To this end, we used a selective whole-genome amplification method to amplify parasite genomes from blood spot DNA samples. Parasite genomes from pretreatment and postrecrudescence samples were subjected to whole-genome sequencing to identify nucleotide variants. Our data did not support the existence of a genetic change responsible for recrudescence following fosmidomycin-clindamycin treatment. Additionally, we found that previously described resistance alleles for these drugs do not represent biomarkers of recrudescence. Future studies should continue to optimize fosmidomycin combinations for use as antimalarial therapies.
High cut-off dialysis in chronic haemodialysis patients reduces serum procalcific activity
2016-07-20

The use of HCO dialysis membranes in chronic dialysis patients reduces the procalcific effects of serum on VSMC in vitro. The mechanisms of the strong effect of HCO on in vitro calcification are not completely understood. One factor may be lower levels of VCAM-1 in HCO serum samples, since VCAM-1 was able to induce vascular calcification in our experiments. Neither sTNFR 1, sTNFR 2 nor sIL2R enhance vascular calcification in vitro. Regardless of the mechanisms, our results encourage further studies of highly permeable filters in chronic dialysis patients.
Spatiotemporal variation in local adaptation of a specialist insect herbivore to its long-lived host plant
2016-07-20

Local adaptation of interacting species to one another indicates geographically variable reciprocal selection. This process of adaptation is central in the organization and maintenance of genetic variation across populations. Given that the strength of selection and responses to it often vary in time and space, the strength of local adaptation should in theory vary between generations and among populations. However, such spatiotemporal variation has rarely been explicitly demonstrated in nature and local adaptation is commonly considered to be relatively static. We report persistent local adaptation of the short-lived herbivore Abrostola asclepiadis to its long-lived host plant Vincetoxicum hirundinaria over three successive generations in two studied populations and considerable temporal variation in local adaptation in six populations supporting the geographic mosaic theory. The observed variation in local adaptation among populations was best explained by geographic distance and population isolation, suggesting that gene flow reduces local adaptation. Changes in herbivore population size did not conclusively explain temporal variation in local adaptation. Our results also imply that short-term studies are likely to capture only a part of the existing variation in local adaptation.
Growth and annealing kinetics of α-sexithiophene and fullerene C60mixed films
2016-07-20

Thin films of α-sexithiophene (6T) and C 60 mixtures deposited on nSiO substrates at 303 and 373 K were investigated in real time and in situ during the film growth using X-ray diffraction. The mixtures are observed to contain the well known 6T low-temperature crystal phase and the β phase, which usually coexist in pure 6T films. The addition of C 60 modifies the structure to almost purely β-phase-dominated films if the substrate is at 303 K. In contrast, at 373 K the low-temperature crystal phase of 6T dominates the film growth of the mixtures. Post-growth annealing experiments up to 373 K on equimolar mixtures and pure 6T films were also performed and followed in real time with X-ray diffraction. Annealing of pure 6T films results in a strong increase of film ordering, whereas annealing of equimolar 6T:C 60 mixed films does not induce any significant changes in the film structure. These results lend further support to theories about the important influence of C 60 on the growth behaviour and structure formation process of 6T in mixtures of the two materials.
Propeller effect in two brightest transient X-ray pulsars: 4U 0115+63 and V 0332+53
2016-07-21

Aims. We present the results of the monitoring programmes performed with the Swift/XRT telescope and aimed specifically to detect an abrupt decrease of the observed flux associated with a transition to the propeller regime in two well-known X-ray pulsars 4U 0115+63 and V 0332+53. Methods. Both sources form binary systems with Be optical companions and undergo so-called giant outbursts every 3−4 years. The current observational campaigns were performed with the Swift/XRT telescope in the soft X-ray band (0.5−10 keV) during the declining phases of the outbursts exhibited by both sources in 2015. Results. The transitions to the propeller regime were detected at the threshold luminosities of (1.4 ± 0.4) × 1036 erg s-1 and (2.0 ± 0.4) × 1036 erg s-1 for 4U 0115+63 and V 0332+53, respectively. Spectra of the sources are shown to be significantly softer during the low state. In both sources, the accretion at rates close to the aforementioned threshold values briefly resumes during the periastron passage following the transition into the propeller regime. The strength of the dipole component of the magnetic field required to inhibit the accretion agrees well with estimates based on the position of the cyclotron lines in their spectra, thus excluding presence of a strong multipole component of the magnetic field in the vicinity of the neutron star
Chromium geochemistry of the ca. 1.85 Ga Flin Flon paleosol
2016-07-21

Abstract Fractionation of stable Cr isotopes has been measured in Archaean paleosols and marine sedimentary rocks and interpreted to record the terrestrial oxidation of Cr( III ) to Cr( VI ), providing possible indirect evidence for the emergence of oxygenic photosynthesis. However, these fractionations occur amidst evidence from other geochemical proxies for a pervasively anoxic atmosphere. This study examined the Cr geochemistry of the ca. 1.85 Ga Flin Flon paleosol, which developed under an atmosphere unambiguously oxidising enough to quantitatively convert Fe( II ) to Fe( III ) during pedogenesis. The paleosol shows an extreme range in Cr isotope composition of 2.76 ‰ δ 53/52 Cr. The protolith greenstone (δ 53/52 Cr: −0.23 ‰), the deepest weathering horizon (δ 53/52 Cr: −0.15 to −0.23 ‰) and a residual corestone in the upper paleosol (δ 53/52 Cr: −0.01 ‰) all exhibit Cr isotopic compositions comparable to unaltered igneous rocks. The most significant isotopic fractionation is preserved in the areas influenced by oxidative subaerial weathering (i.e. increase in Fe( III )/Fe( II )) and the greatest loss of mobile elements. The uppermost paleosol horizon is both Cr and Mn depleted and offset to significantly 53 Cr‐enriched compositions (δ 53/52 Cr values between +1.50 and +2.38 ‰), which is not easily modelled with the oxidation of Cr( III ) and loss of isotopically heavy Cr( VI ). Instead, the currently preferred model for these data invokes the open‐system removal of isotopically light aqueous Cr( III ) during either pedogenesis or subsequent hydrothermal/metamorphic alteration. The 53 Cr enrichment would then represent the preferential dissolution or complexation of isotopically light aqueous Cr( III ) species (enhanced by lower pH conditions and possibly the presence of complexing ligands) and/or the residual signature from preferential adsorption of isotopically heavy Cr( III ). Both scenarios would contradict the widely held assumption that only redox reactions of Cr can generate large magnitude isotopic fractionations and, if substantiated, non‐redox isotope effects would complicate the conclusive fingerprinting of ancient atmospheric O 2 from Cr isotope data alone.
Precipitation δ18O over the Himalaya‐Tibet orogen from ECHAM5‐wiso simulations: Statistical analysis of temperature, topography and precipitation
2016-07-21

Abstract Variations in oxygen isotope compositions (δ 18 O) provide insight into modern climate and past changes in climate and topography. In addition, in regions such as Tibet, geologic archives of isotope ratios record climate change driven by plateau uplift and therefore also provide information about the surface uplift history. A good understanding of modern‐day controls on δ 18 O is crucial for interpreting geologic δ 18 O in this context. We use the ECHAM5‐wiso global atmospheric general circulation model to calculate δ 18 O in precipitation (δ 18 O p ) for the present‐day climate. In the region of the Tibetan Plateau, spatial variations of monthly means of δ 18 O p are statistically related to spatial variations of 2 m air temperature and precipitation rate, as well as to topography. The size and location of investigated regions are varied in our study to capture regional differences in these relationships and the processes governing the modern δ 18 O p . In addition to correlation analyses, a cross‐validated stepwise multiple regression is carried out using δ 18 O p as the predictand, and topography and atmospheric variables (temperature and precipitation amount) as predictors. The 2 m air temperature and topography yield the highest spatial correlation coefficients of &gt;0.9 and &lt; −0.9, respectively, throughout most of the year. Particularly high correlation coefficients are calculated for the region along the Himalayan orogeny and parts of western China. The predictors explain &gt;90% of the δ 18 O p spatial variance in the same regions. The 2 m air temperature is the dominant predictor and contributes 93.6% to the total explained spatial variance on average. The results demonstrate that most of the δ 18 O p pattern on and around the Tibetan Plateau can be explained by variation in 2 m air temperature and altitude. Correlation of the dependent predictors indicate that in low‐altitude regions where topography does not determine temperature variability, the high correlation of temperature and δ 18 O p may partially be explained by variations in precipitation rates.
Experimental investigation of transverse mixing in porous media under helical flow conditions
2016-07-22

Plume dilution and transverse mixing can be considerably enhanced by helical flow occurring in three-dimensional heterogeneous anisotropic porous media. In this study, we perform tracer experiments in a fully three-dimensional flow-through chamber to investigate the effects of helical flow on plume spiraling and deformation, as well as on its dilution. Porous media were packed in angled stripes of materials with different grain sizes to create blocks with macroscopically anisotropic hydraulic conductivity, which caused helical flows. Steady-state transport experiments were carried out by continuously injecting dye tracers at different inlet ports. High-resolution measurements of concentration and flow rates were performed at 49 outlet ports. These measurements allowed quantifying the spreading and dilution of the solute plumes at the outlet cross section. Direct evidence of plume spiraling and visual proof of helical flow was obtained by freezing and slicing the porous media at different cross sections and observing the dye-tracer distribution. We simulated flow and transport to interpret our experimental observations and investigate the effects of helical flow on mixing-controlled reactive transport. The simulation results were evaluated using metrics of reactive mixing such as the critical dilution index and the length of continuously injected steady-state plumes. The results show considerable reaction enhancement, quantified by the remarkable decrease of reactive plume lengths (up to four times) in helical flows compared to analogous scenarios in uniform flows.
Voluntary Disclosure and Analyst Forecast
2016-07-22

Empiricists document that firms more often voluntarily disclose bad news than good news and link this pessimism to managers’ increased incentives not to fall short of earnings expectations. This paper analyzes the voluntary disclosure of a manager’s private information by explicitly considering her incentives to meet or beat an analyst’s earnings forecast. The model predicts that managers who face strong incentives to meet or beat these forecasts more frequently disclose bad news than good news in order to guide analysts’ expectations about future earnings downward. This pessimism is higher in markets with less informed managers and may hold even if the manager has strong incentives for high stock prices and meet-or-beat incentives are comparably low.