Enhanced cosmic-ray flux toward zeta Persei inferred from laboratory study of H3+ - e- recombination rate

The H3+ molecular ion plays a fundamental role in interstellar chemistry, as it initiates a network of chemical reactions that produce many interstellar molecules. In dense clouds, the H3+ abundance is understood using a simple chemical model, from which observations of H3+ yield valuable estimates of cloud path length, density, and temperature. On the other hand, observations of diffuse clouds have suggested that H3+ is considerably more abundant than expected from the chemical models. However, diffuse cloud models have been hampered by the uncertain values of three key parameters: the rate of H3+ destruction by electrons, the electron fraction, and the cosmic-ray ionisation rate. Here we report a direct experimental measurement of the H3+ destruction rate under nearly interstellar conditions. We also report the observation of H3+ in a diffuse cloud (towards zeta Persei) where the electron fraction is already known. Taken together, these results allow us to derive the value of the third uncertain model parameter: we find that the cosmic-ray ionisation rate in this sightline is forty times faster than previously assumed. If such a high cosmic-ray flux is indeed ubiquitous in diffuse clouds, the discrepancy between chemical models and the previous observations of H3+ can be resolved.Comment: 6 pages, Nature, in pres

Artificial intelligence in cancer imaging: Clinical challenges and applications

Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care

Brain herniation in a patient with apparently normal intracranial pressure: a case report

Introduction Intracranial pressure monitoring is commonly implemented in patients with neurologic injury and at high risk of developing intracranial hypertension, to detect changes in intracranial pressure in a timely manner. This enables early and potentially life-saving treatment of intracranial hypertension. Case presentation An intraparenchymal pressure probe was placed in the hemisphere contralateral to a large basal ganglia hemorrhage in a 75-year-old Caucasian man who was mechanically ventilated and sedated because of depressed consciousness. Intracranial pressures were continuously recorded and never exceeded 17 mmHg. After sedation had been stopped, our patient showed clinical signs of transtentorial brain herniation, despite apparently normal intracranial pressures (less than 10 mmHg). Computed tomography revealed that the size of the intracerebral hematoma had increased together with significant unilateral brain edema and transtentorial herniation. The contralateral hemisphere where the intraparenchymal pressure probe was placed appeared normal. Our patient underwent emergency decompressive craniotomy and was tracheotomized early, but did not completely recover. Conclusions Intraparenchymal pressure probes placed in the hemisphere contralateral to an intracerebral hematoma may dramatically underestimate intracranial pressure despite apparently normal values, even in the case of transtentorial brain herniation

Baryons in the relativistic jets of the stellar-mass black-hole candidate 4U 1630-47

Accreting black holes are known to power relativistic jets, both in stellar-mass binary systems and at the centres of galaxies. The power carried away by the jets, and, hence, the feedback they provide to their surroundings, depends strongly on their composition. Jets containing a baryonic component should carry significantly more energy than electron–positron jets. Energetic considerations1, 2 and circular-polarization measurements3 have provided conflicting circumstantial evidence for the presence or absence of baryons in jets, and the only system in which they have been unequivocally detected is the peculiar X-ray binary SS 433 (refs 4, 5). Here we report the detection of Doppler-shifted X-ray emission lines from a more typical black-hole candidate X-ray binary, 4U 1630-47, coincident with the reappearance of radio emission from the jets of the source. We argue that these lines arise from baryonic matter in a jet travelling at approximately two-thirds the speed of light, thereby establishing the presence of baryons in the jet. Such baryonic jets are more likely to be powered by the accretion disk6 than by the spin of the black hole7, and if the baryons can be accelerated to relativistic speeds, the jets should be strong sources of γ-rays and neutrino emission

The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model

Malignant glioma is characterised by extensive neovascularisation, principally influenced by vascular endothelial growth factor (VEGF). ZD6474 is a potent inhibitor of VEGF-R2 tyrosine kinase activity, but with additional inhibitory effects on other growth factors. In this study, we have investigated the effects of ZD6474 with regard to tumour growth, neovascularisation, proliferation and apoptosis in the intracerebral rat glioma model, BT4C. ZD6474 (50 and 100 mg kg−1) was given as a daily oral gavage. Animals were killed on day 19 and tumour volume was measured. Sections were stained for factor VIII, Ki-67 and for apoptosis. The ability of ZD6474 to inhibit cell growth directly was examined in vitro, using the glioma cell line BT4C and the transformed rat brain endothelial cell line RBE4. Cell growth was analysed with fluorometric microculture cytotoxicity assay to quantify the cytotoxic effects. ZD6474 significantly decreased tumour volume compared to controls. Microvascular density increased after treatment with ZD6474, and tumour cell proliferation index was reduced. There was also an increase in tumour cell apoptosis. In vitro, the growth of both cell lines was significantly reduced. The results reported justify further experimental investigations concerning the effects of ZD6474 in malignant glioma alone or in combination with other modalities

Multi-Level Communication of Human Retinal Pigment Epithelial Cells via Tunneling Nanotubes

Background: Tunneling nanotubes (TNTs) may offer a very specific and effective way of intercellular communication. Here we investigated TNTs in the human retinal pigment epithelial (RPE) cell line ARPE-19. Morphology of TNTs was examined by immunostaining and scanning electron microscopy. To determine the function of TNTs between cells, we studied the TNT-dependent intercellular communication at different levels including electrical and calcium signalling, small molecular diffusion as well as mitochondrial re-localization. Further, intercellular organelles transfer was assayed by FACS analysis. Methodology and Principal Findings: Microscopy showed that cultured ARPE-19 cells are frequently connected by TNTs, which are not attached to the substratum. The TNTs were straight connections between cells, had a typical diameter of 50 to 300 nm and a length of up to 120 µm. We observed de novo formation of TNTs by diverging from migrating cells after a short time of interaction. Scanning electron microscopy confirmed characteristic features of TNTs. Fluorescence microscopy revealed that TNTs between ARPE-19 cells contain F-actin but no microtubules. Depolymerisation of F-actin, induced by addition of latrunculin-B, led to disappearance of TNTs. Importantly, these TNTs could function as channels for the diffusion of small molecules such as Lucifer Yellow, but not for large molecules like Dextran Red. Further, organelle exchange between cells via TNTs was observed by microscopy. Using Ca2+ imaging we show the intercellular transmission of calcium signals through TNTs. Mechanical stimulation led to membrane depolarisation, which expand through TNT connections between ARPE-19 cells. We further demonstrate that TNTs can mediate electrical coupling between distant cells. Immunolabelling for Cx43 showed that this gap junction protein is interposed at one end of 44% of TNTs between ARPE-19 cells. Conclusions and Significance: Our observations indicate that human RPE cell line ARPE-19 cells communicate by tunneling nanotubes and can support different types of intercellular traffic

Long-Lasting Consequences of Neonatal Maternal Separation on Social Behaviors in Ovariectomized Female Mice

Maternal separation (MS) stress is known to induce long-lasting alterations in emotional and anxiety-related behaviors, but effects on social behaviors are not well defined. The present study examined MS effects on female social behaviors in the social investigation (SIT) and social preference (SPT) tests, in addition to non-social behaviors in the open-field (OFT) and light-dark transition (LDT) tests in C57BL/6J mice. All females were tested as ovariectomized to eliminate confounding effects of endogenous estrogen during behavioral testing. Daily MS (3 hr) from postnatal day 1 to 14 did not affect anxiety levels in LDT, but were elevated in OFT with modified behavioral responses to the novel environment. Furthermore, MS altered social investigative behaviors and preference patterns toward unfamiliar stimulus mice in SIT and short- and long-term SPT paradigms. In SIT, MS reduced social investigation duration and increased number of stretched approaches towards both female and male unfamiliar stimulus mice, suggesting increased social anxiety levels in MS females. Similarly, MS heightened levels of social anxiety during short-term SPT but no MS effect on social preference was found. On the other hand, MS females displayed a distinctive preference for female stimuli, unlike control females, when tested for long-term SPT over a prolonged period of 5 days. Evaluation of FosB expression in the paraventricular nucleus, medial and central amygdala following stimulus exposure demonstrated greater number of FosB immunopositive cells in all three brain regions in MS females compared to control females. These results suggest that MS females might differ in neuroendocrine responses toward unfamiliar female and male opponents, which may be associated with modifications in social behaviors found in the present study. Taken together, this study provides new evidence that early life stress modifies female social behaviors by highlighting alterations in behavioral responses to situations involving social as well as non-social novelty