260 research outputs found
Can people guess what happened to others from their reactions?
Are we able to infer what happened to a person from a brief sample of his/her behaviour? It has been proposed that mentalising skills can be used to retrodict as well as predict behaviour, that is, to determine what mental states of a target have already occurred. The current study aimed to develop a paradigm to explore these processes, which takes into account the intricacies of real-life situations in which reasoning about mental states, as embodied in behaviour, may be utilised. A novel task was devised which involved observing subtle and naturalistic reactions of others in order to determine the event that had previously taken place. Thirty-five participants viewed videos of real individuals reacting to the researcher behaving in one of four possible ways, and were asked to judge which of the four βscenariosβ they thought the individual was responding to. Their eye movements were recorded to establish the visual strategies used. Participants were able to deduce successfully from a small sample of behaviour which scenario had previously occurred. Surprisingly, looking at the eye region was associated with poorer identification of the scenarios, and eye movement strategy varied depending on the event experienced by the person in the video. This suggests people flexibly deploy their attention using a retrodictive mindreading process to infer events
Analysis of Transcriptional Regulatory Pathways of Photoreceptor Genes by Expression Profiling of the Otx2-Deficient Retina
In the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. We previously reported that Otx2 conditional knockout (CKO) mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome of the Otx2 CKO retina, we compared expression profile of Otx2 CKO and wild-type retinas at P1 and P12 using microarray. We observed that expression of 101- and 1049-probe sets significantly decreased in the Otx2 CKO retina at P1 and P12, respectively, whereas, expression of 3- and 4149-probe sets increased at P1 and P12, respectively. We found that expression of genes encoding transcription factors involved in photoreceptor development, including Crx, Nrl, Nr2e3, Esrrb, and NeuroD, was markedly down-regulated in the Otx2 CKO at both P1 and P12. Furthermore, we identified three human retinal disease loci mapped in close proximity to certain down-regulated genes in the Otx2 CKO retina including Ccdc126, Tnfsf13 and Pitpnm1, suggesting that these genes are possibly responsible for these diseases. These transcriptome data sets of the Otx2 CKO retina provide a resource on developing rods and cones to further understand the molecular mechanisms underlying photoreceptor development, function and disease
Observation of the Smallest Metal Nanotube with Square-cross-section
Understanding the mechanical properties of nanoscale systems requires a range
of measurement techniques and theoretical approaches to gather the relevant
physical and chemical information. The arrangements of atoms in nanostructures
and macroscopic matter can be different, principally due to the role of surface
energy, but the interplay between atomic and electronic structure in
association with applied mechanical stress can also lead to surprising
differences. For example, metastable structures such as suspended chains of
atoms and helical wires have been produced by the stretching of metal
junctions. Here we report the spontaneous formation of the smallest possible
metal nanotube with a square cross-section during the elongation of silver
nanocontacts. Ab initio calculations and molecular simulations indicate that
the hollow wire forms because this configuration allows the surface energy to
be minimized, and also generates a soft structure capable of absorbing a huge
tensile deformation
Development of a method for environmentally friendly chemical peptide synthesis in water using water-dispersible amino acid nanoparticles
Due to the vast importance of peptides in biological processes, there is an escalating need for synthetic peptides to be used in a wide variety of applications. However, the consumption of organic solvent is extremely large in chemical peptide syntheses because of the multiple condensation steps in organic solvents. That is, the current synthesis method is not environmentally friendly. From the viewpoint of green sustainable chemistry, we focused on developing an organic solvent-free synthetic method using water, an environmentally friendly solvent. Here we described in-water synthesis technology using water-dispersible protected amino acids
On the power and the systematic biases of the detection of chromosomal inversions by paired-end genome sequencing
One of the most used techniques to study structural variation at a genome level is paired-end mapping (PEM). PEM has the advantage of being able to detect balanced events, such as inversions and translocations. However, inversions are still quite difficult to predict reliably, especially from high-throughput sequencing data. We simulated realistic PEM experiments with different combinations of read and library fragment lengths, including sequencing errors and meaningful base-qualities, to quantify and track down the origin of false positives and negatives along sequencing, mapping, and downstream analysis. We show that PEM is very appropriate to detect a wide range of inversions, even with low coverage data. However, % of inversions located between segmental duplications are expected to go undetected by the most common sequencing strategies. In general, longer DNA libraries improve the detectability of inversions far better than increments of the coverage depth or the read length. Finally, we review the performance of three algorithms to detect inversions -SVDetect, GRIAL, and VariationHunter-, identify common pitfalls, and reveal important differences in their breakpoint precisions. These results stress the importance of the sequencing strategy for the detection of structural variants, especially inversions, and offer guidelines for the design of future genome sequencing projects
The stellar and sub-stellar IMF of simple and composite populations
The current knowledge on the stellar IMF is documented. It appears to become
top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr
pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing
metallicity and in increasingly massive early-type galaxies. It declines quite
steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars
having their own IMF. The most massive star of mass mmax formed in an embedded
cluster with stellar mass Mecl correlates strongly with Mecl being a result of
gravitation-driven but resource-limited growth and fragmentation induced
starvation. There is no convincing evidence whatsoever that massive stars do
form in isolation. Various methods of discretising a stellar population are
introduced: optimal sampling leads to a mass distribution that perfectly
represents the exact form of the desired IMF and the mmax-to-Mecl relation,
while random sampling results in statistical variations of the shape of the
IMF. The observed mmax-to-Mecl correlation and the small spread of IMF
power-law indices together suggest that optimally sampling the IMF may be the
more realistic description of star formation than random sampling from a
universal IMF with a constant upper mass limit. Composite populations on galaxy
scales, which are formed from many pc scale star formation events, need to be
described by the integrated galactic IMF. This IGIMF varies systematically from
top-light to top-heavy in dependence of galaxy type and star formation rate,
with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and
Galactic Structure, Vol.5, Springer. This revised version is consistent with
the published version and includes additional references and minor additions
to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-
Tuning the Mammalian Circadian Clock: Robust Synergy of Two Loops
The circadian clock is accountable for the regulation of internal rhythms in most living organisms. It allows the anticipation of environmental changes during the day and a better adaptation of physiological processes. In mammals the main clock is located in the suprachiasmatic nucleus (SCN) and synchronizes secondary clocks throughout the body. Its molecular constituents form an intracellular network which dictates circadian time and regulates clock-controlled genes. These clock-controlled genes are involved in crucial biological processes including metabolism and cell cycle regulation. Its malfunction can lead to disruption of biological rhythms and cause severe damage to the organism. The detailed mechanisms that govern the circadian system are not yet completely understood. Mathematical models can be of great help to exploit the mechanism of the circadian circuitry. We built a mathematical model for the core clock system using available data on phases and amplitudes of clock components obtained from an extensive literature search. This model was used to answer complex questions for example: how does the degradation rate of Per affect the period of the system and what is the role of the ROR/Bmal/REV-ERB (RBR) loop? Our findings indicate that an increase in the RNA degradation rate of the clock gene Period (Per) can contribute to increase or decrease of the period - a consequence of a non-monotonic effect of Per transcript stability on the circadian period identified by our model. Furthermore, we provide theoretical evidence for a potential role of the RBR loop as an independent oscillator. We carried out overexpression experiments on members of the RBR loop which lead to loss of oscillations consistent with our predictions. These findings challenge the role of the RBR loop as a merely auxiliary loop and might change our view of the clock molecular circuitry and of the function of the nuclear receptors (REV-ERB and ROR) as a putative driving force of molecular oscillations
Mechanism of resistance to trastuzumab and molecular sensitization via ADCC activation by exogenous expression of HER2-extracellular domain in human cancer cells
Trastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive breast and gastric cancers; however, acquired resistance presents a formidable obstacle to long-term tumor responses in the majority of patients. Here, we show the mechanism of resistance to trastuzumab in HER2-positive human cancer cells and explore the molecular sensitization by exogenous expression of HER2-extracellular domain (ECD) in HER2-negative or trastuzumab-resistant human cancer cells. We found that long-term exposure to trastuzumab induced resistance in HER2-positive cancer cells; HER2 expression was downregulated, and antibody-dependent cellular cytotoxicity (ADCC) activity was impaired. We next examined the hypothesis that trastuzumab-resistant cells could be re-sensitized by the transfer of non-functional HER2-ECD. Exogenous HER2-ECD expression induced by the stable transfection of a plasmid vector or infection with a replication-deficient adenovirus vector had no apparent effect on the signaling pathway, but strongly enhanced ADCC activity in low HER2-expressing or trastuzumab-resistant human cancer cells. Our data indicate that restoration of HER2-ECD expression sensitizes HER2-negative or HER2-downregulated human cancer cells to trastuzumab-mediated ADCC, an outcome that has important implications for the treatment of human cancers
Estimation of physician supply by specialty and the distribution impact of increasing female physicians in Japan
<p>Abstract</p> <p>Background</p> <p>Japan has experienced two large changes which affect the supply and distribution of physicians. They are increases in medical school enrollment capacity and in the proportion of female physicians. The purpose of this study is to estimate the future supply of physicians by specialty and to predict the associated impact of increased female physicians, as well as to discuss the possible policy implications.</p> <p>Methods</p> <p>Based on data from the 2004 and 2006 National Survey of Physicians, Dentists and Pharmacists, we estimated the future supply of physicians by specialty, using multistate life tables. Based on possible scenarios of the future increase in female physicians, we also estimated the supply of physicians by specialty.</p> <p>Results</p> <p>Even if Japan's current medical school enrollment capacity is maintained in subsequent years, the number of physicians per 1000 population is expected to increase from 2.2 in 2006 to 3.2 in 2036, which is a 46% increase from the current level. The numbers of obstetrician/gynecologists (OB/GYNs) and surgeons are expected to temporarily decline from their current level, whereas the number of OB/GYNs per 1000 births will still increase because of the declining number of births. The number of surgeons per 1000 population, even with the decreasing population, will decline temporarily over the next few years. If the percentage of female physicians continues to increase, the overall number of physicians will not be significantly affected, but in specialties with current very low female physician participation rates, such as surgery, the total number of physicians is expected to decline significantly.</p> <p>Conclusion</p> <p>At the current medical school enrollment capacity, the number of physicians per population is expected to continue to increase because of the skewed age distribution of physicians and the declining population in Japan. However, with changes in young physicians' choices of medical specialties and as the percentage of female physicians increases, patterns of physician supply will vary between specialties. Specialties less often chosen by young physicians and where males have dominated will face a decline in physician supply. These results highlight the necessity for developing a work environment that attracts female physicians to these types of specialties. This will also lead to improved gender equality in the workforce and more effective use of human resources.</p
- β¦