Towards tailoring non-invasive brain stimulation using real-time fMRI and Bayesian optimization

Non-invasive brain stimulation, such as transcranial alternating current stimulation (tACS) provides a powerful tool to directly modulate brain oscillations that mediate complex cognitive processes. While the body of evidence about the effect of tACS on behavioral and cognitive performance is constantly growing, those studies fail to address the importance of subjectspecific stimulation protocols. With this study here, we set the foundation to combine tACS with a recently presented framework that utilizes real-time fRMI and Bayesian optimization in order to identify the most optimal tACS protocol for a given individual. While Bayesian optimization is particularly relevant to such a scenario, its success depends on two fundamental choices: the choice of covariance kernel for the Gaussian process prior as well as the choice of acquisition function that guides the search. Using empirical (functional neuroimaging) as well as simulation data, we identified the squared exponential kernel and the upper confidence bound acquisition function to work best for our problem. These results will be used to inform our upcoming realtime experiments

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer

Individual and ethnic aspects of preoperative planning for posttraumatic rhinoplasty

The aim of this study was to compare the aesthetic results of post traumatic rhinoplasty among Europeans with populations of healthy Caucasians described in earlier reports, and to collate correct parameters of nasal shape in healthy representatives of both sexes and various races for improvement in aesthetic results of surgery. 3-D scanning of the face was performed in 54 patients after posttraumatic septorhinoplasty. Analysis of 3D model was based on two indices of the nasal proportions and four angles of the region from 18 anthropological points. Parameters of the nasal shape in addition to gender were compared to average values of healthy Caucasian population, described before. Normal characteristics of the nose among individuals of three races from previous studies were also compared to one another. In females, mean height and width of the nose as well as length of both nostrils was smaller. Neither were there any significant differences in width of the nostrils and length of the nasal pyramid nor nasal prominence. Nasal proportions were similar in both sexes. Some of the nasal angles differed in addition to gender. Posttraumatic rhinoplasty resulted in correct shape of the nose similar to the healthy Caucasian population. The aesthetic nose differ among healthy individuals of the three races analysed. While preoperative planning is important, knowledge of the normal values of parameters characterising shape in both genders is equally important as the individual differences in relation to the whole face

Laws of biology: why so few?

Finding fundamental organizing principles is the current intellectual front end of systems biology. From a hydrogen atom to the whole cell level, organisms manage massively parallel and massively interactive processes over several orders of magnitude of size. To manage this scale of informational complexity it is natural to expect organizing principles that determine higher order behavior. Currently, there are only hints of such organizing principles but no absolute evidences. Here, we present an approach as old as Mendel that could help uncover fundamental organizing principles in biology. Our approach essentially consists of identifying constants at various levels and weaving them into a hierarchical chassis. As we identify and organize constants, from pair-wise interactions to networks, our understanding of the fundamental principles in biology will improve, leading to a theory in biology

Supervolcanoes Within an Ancient Volcanic Province in Arabia Terra, Mars

Several irregularly shaped craters located within Arabia Terra, Mars represent a new type of highland volcanic construct and together constitute a previously unrecognized martian igneous province. Similar to terrestrial supervolcanoes, these low-relief paterae display a range of geomorphic features related to structural collapse, effusive volcanism, and explosive eruptions. Extruded lavas contributed to the formation of enigmatic highland ridged plains in Arabia Terra. Outgassed sulfur and erupted fine-grained pyroclastics from these calderas likely fed the formation of altered, layered sedimentary rocks and fretted terrain found throughout the equatorial region. Discovery of a new type of volcanic construct in the Arabia volcanic province fundamentally changes the picture of ancient volcanism and climate evolution on Mars. Other eroded topographic basins in the ancient Martian highlands that have been dismissed as degraded impact craters should be reconsidered as possible volcanic constructs formed in an early phase of widespread, disseminated magmatism on Mars

Influence of auxin and its polar transport inhibitor on the development of somatic embryos in Digitalis trojana

The present study reports the role of auxin and its transport inhibitor during the establishment of an efficient and optimized protocol for the somatic embryogenesis in Digitalis trojana Ivan. Hypocotyl segments (5 mm long) were placed vertically in the Murashige and Skoog medium supplemented with three sets [indole-3-acetic acid (IAA) alone or 2,3,5-triiodobenzoic acid (TIBA) alone or IAA-TIBA combination] of formulations of plant growth regulators, to assess their differential influence on induction and proliferation of somatic embryos (SEs). IAA alone was found to be the most effective, at a concentration of 0.5 mg/l, inducing similar to 10 SEs per explant with 52% induction frequency. On the other hand, the combination of 0.5 mg/l of IAA and 1 mg/l of TIBA produced significantly fewer (similar to 3.6 SEs) and abnormal (enlarged, oblong, jar and cup-shaped) SEs per explant with 24% induction frequency in comparison to that in the IAA alone. The explants treated with IAA-TIBA exhibited a delayed response along with the formation of abnormal SEs. Our study revealed that IAA induces high-frequency SE formation when used singly, but the frequency gradually declines when IAA was coupled with increasing levels of TIBA. Eventually, our findings bring new insights into the roles of auxin and its polar transport in somatic embryogenesis of D. trojana

Measuring the psychosocial burden in women with low-grade abnormal cervical cytology in the TOMBOLA trial: psychometric properties of the Process and Outcome Specific Measure (POSM)

Background There is a need for an instrument to measure the psychosocial burden of receiving an abnormal cervical cytology result which can be used regardless of the clinical management women receive. Methods 3331 women completed the POSM as part of baseline psychosocial assessment in a trial of management of low grade cervical cytological abnormalities. Factor analysis and reliability assessment of the POSM were conducted. Results Two factors were extracted from the POSM: Factor 1, containing items related to worry; and Factor 2 containing items relating to satisfaction with information and support received and change in the way women felt about themselves. Factor 1 had good reliability (Cronbach’s alpha 0.769), however reliability of the Factor 2 was poorer (0.482). Data collected at four subsequent time points demonstrated that the factor structure was stable over time. Conclusion This study demonstrates the presence and reliability of a scale measuring worries within the POSM. This analysis will inform its future use in this population and in other related contexts

Primary ovarian cancer chemotherapy: current standards of care

Chemotherapy has been regarded as standard therapy for the majority of women with advanced epithelial ovarian cancer for several decades, with this role filled largely by the alkylating agents — used as monotherapy — until the mid-1980s. The activity of cisplatin in this disorder was established during the 1970s, and combinations of cisplatin and an alkylating agent were widely used during the late 1980s. However, further research prompted by continuing concerns over poor survival and tolerability led to the adoption of paclitaxel in combination with either cisplatin or carboplatin as first-line therapy in ovarian cancer during the 1990s. Most recent research has focused on further optimisation of these regimens to maximise clinical benefit while minimising toxicity, and investigations into alternative taxanes (e.g. docetaxel), other novel agents and new treatment schedules are ongoing

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO