Destination Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a prototypical neurodegenerative disease characterized by progressive degeneration of motor neurons both in the brain and spinal cord. The constantly evolving nature of ALS represents a fundamental dimension of individual differences that underlie this disorder, yet it involves multiple levels of functional entities that alternate in different directions and finally converge functionally to define ALS disease progression. ALS may start from a single entity and gradually becomes multifactorial. However, the functional convergence of these diverse entities in eventually defining ALS progression is poorly understood. Various hypotheses have been proposed without any consensus between the for-and-against schools of thought. The present review aims to capture explanatory hierarchy both in terms of hypotheses and mechanisms to provide better insights on how they functionally connect. We can then integrate them within a common functional frame of reference for a better understanding of ALS and defining future treatments and possible therapeutic strategies. Here, we provide a philosophical understanding of how early leads are crucial to understanding the endpoints in ALS, because invariably, all early symptomatic leads are underpinned by neurodegeneration at the cellular, molecular and genomic levels. Consolidation of these ideas could be applied to other neurodegenerative diseases (NDs) and guide further critical thinking to unveil their roadmap of destination ALS

Destination Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a prototypical neurodegenerative disease characterized by progressive degeneration of motor neurons both in the brain and spinal cord. The constantly evolving nature of ALS represents a fundamental dimension of individual differences that underlie this disorder, yet it involves multiple levels of functional entities that alternate in different directions and finally converge functionally to define ALS disease progression. ALS may start from a single entity and gradually becomes multifactorial. However, the functional convergence of these diverse entities in eventually defining ALS progression is poorly understood. Various hypotheses have been proposed without any consensus between the for-and-against schools of thought. The present review aims to capture explanatory hierarchy both in terms of hypotheses and mechanisms to provide better insights on how they functionally connect. We can then integrate them within a common functional frame of reference for a better understanding of ALS and defining future treatments and possible therapeutic strategies. Here, we provide a philosophical understanding of how early leads are crucial to understanding the endpoints in ALS, because invariably, all early symptomatic leads are underpinned by neurodegeneration at the cellular, molecular and genomic levels. Consolidation of these ideas could be applied to other neurodegenerative diseases (NDs) and guide further critical thinking to unveil their roadmap of destination ALS

Olivocochlear efferent contributions to speech-in-noise recognition across signal-to noise ratios

The medial olivocochlear (MOC) efferent system modifies cochlear output to aid signal detection in noise, but the precise role of efferents in speech-in-noise understanding remains unclear. The current study examined the contribution of the MOC reflex for speech recognition in noise in 30 normal-hearing young adults (27 females, mean age = 22.7 yr). The MOC reflex was assessed using contralateral inhibition of transient-evoked otoacoustic emissions. Speech-in-noise perception was evaluated using the coordinate response measure presented in ipsilateral speech-shaped noise at signal-to-noise ratios (SNRs) ranging from −12 to 0 dB. Performance was assessed without and with the presence of contralateral noise to activate the MOC reflex. Performance was significantly better with contralateral noise only at the lowest SNR. There was a trend of better performance with increasing contralateral inhibition at the lowest SNR. Threshold of the psychometric function was significantly correlated with contralateral inhibition. Response time on the speech task was not significantly correlated with contralateral inhibition. Results suggest that the MOC reflex contributes to listening in low SNRs and the relationship between the MOC reflex and perception is highly dependent upon the task characteristics.American Speech-Language-Hearing Foundation (2017 New Investigators Research Grant)Office of the Vice Chancellor for Research, University of Illinois at Urbana-Champaign (Arnold O. Beckman Award)Ope

The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression

Neuroblastoma is the most common solid tumor during early childhood. One of the key features of neuroblastoma is extensive tumor-driven angiogenesis due to hypoxia. However, the mechanism through which neuroblastoma cells drive angiogenesis is poorly understood. Here we show that the long noncoding RNA MALAT1 was upregulated in human neuroblastoma cell lines under hypoxic conditions. Conditioned media from neuroblastoma cells transfected with small interfering RNAs (siRNA) targeting MALAT1, compared with conditioned media from neuroblastoma cells transfected with control siRNAs, induced significantly less endothelial cell migration, invasion and vasculature formation. Microarray-based differential gene expression analysis showed that one of the genes most significantly downregulated following MALAT1 suppression in human neuroblastoma cells under hypoxic conditions was fibroblast growth factor 2 (FGF2). RT-PCR and immunoblot analyses confirmed that MALAT1 suppression reduced FGF2 expression, and Enzyme-Linked Immunosorbent Assays revealed that transfection with MALAT1 siRNAs reduced FGF2 protein secretion from neuroblastoma cells. Importantly, addition of recombinant FGF2 protein to the cell culture media reversed the effects of MALAT1 siRNA on vasculature formation. Taken together, our data suggest that up-regulation of MALAT1 expression in human neuroblastoma cells under hypoxic conditions increases FGF2 expression and promotes vasculature formation, and therefore plays an important role in tumor-driven angiogenesis

A boron-coated CCD camera for direct detection of Ultracold Neutrons (UCN)

A new boron-coated CCD camera is described for direct detection of ultracold neutrons (UCN) through the capture reactions $^{10}$B (n,$\alpha$0$\gamma$)$^7$Li (6%) and $^{10}$B(n,$\alpha$1$\gamma$)$^7$Li (94%). The experiments, which extend earlier works using a boron-coated ZnS:Ag scintillator, are based on direct detections of the neutron-capture byproducts in silicon. The high position resolution, energy resolution and particle ID performance of a scientific CCD allows for observation and identification of all the byproducts $\alpha$, $^7$Li and $\gamma$ (electron recoils). A signal-to-noise improvement on the order of 10$^4$ over the indirect method has been achieved. Sub-pixel position resolution of a few microns is demonstrated. The technology can also be used to build UCN detectors with an area on the order of 1 m$^2$. The combination of micrometer scale spatial resolution, few electrons ionization thresholds and large area paves the way to new research avenues including quantum physics of UCN and high-resolution neutron imaging and spectroscopy.Comment: 10 pages, 8 figure

Parkinson's disease may disrupt overlapping subthalamic nucleus and pallidal motor networks.

There is an ongoing debate about differential clinical outcome and associated adverse effects of deep brain stimulation (DBS) in Parkinson's disease (PD) targeting the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi). Given that functional connectivity profiles suggest beneficial DBS effects within a common network, the empirical evidence about the underlying anatomical circuitry is still scarce. Therefore, we investigate the STN and GPi-associated structural covariance brain patterns in PD patients and healthy controls. We estimate GPi's and STN's whole-brain structural covariance from magnetic resonance imaging (MRI) in a normative mid- to old-age community-dwelling cohort (n = 1184) across maps of grey matter volume, magnetization transfer (MT) saturation, longitudinal relaxation rate (R1), effective transversal relaxation rate (R2*) and effective proton density (PD*). We compare these with the structural covariance estimates in patients with idiopathic PD (n = 32) followed by validation using a reduced size controls' cohort (n = 32). In the normative data set, we observed overlapping spatially distributed cortical and subcortical covariance patterns across maps confined to basal ganglia, thalamus, motor, and premotor cortical areas. Only the subcortical and midline motor cortical areas were confirmed in the reduced size cohort. These findings contrasted with the absence of structural covariance with cortical areas in the PD cohort. We interpret with caution the differential covariance maps of overlapping STN and GPi networks in patients with PD and healthy controls as correlates of motor network disruption. Our study provides face validity to the proposed extension of the currently existing structural covariance methods based on morphometry features to multiparameter MRI sensitive to brain tissue microstructure

Quantum Theory and Time Asymmetry

The relation between quantum measurement and thermodynamically irreversible processes is investigated. The reduction of the state vector is fundamentally asymmetric in time and shows an observer-relatedness which may explain the double interpretation of the state vector as a representation of physical states as well as of information about them. The concept of relevance being used in all statistical theories of irreversible thermodynamics is shown to be based on the same observer-relatedness. Quantum theories of irreversible processes implicitly use an objectivized process of state vector reduction. The conditions for the reduction are discussed, and I speculate that the final (subjective) observer system might even be carried by a spacetime point.Comment: Latex version of a paper published in 1979 (with minor revisions), 18 page

Quantifying decoherence in continuous variable systems

We present a detailed report on the decoherence of quantum states of continuous variable systems under the action of a quantum optical master equation resulting from the interaction with general Gaussian uncorrelated environments. The rate of decoherence is quantified by relating it to the decay rates of various, complementary measures of the quantum nature of a state, such as the purity, some nonclassicality indicators in phase space and, for two-mode states, entanglement measures and total correlations between the modes. Different sets of physically relevant initial configurations are considered, including one- and two-mode Gaussian states, number states, and coherent superpositions. Our analysis shows that, generally, the use of initially squeezed configurations does not help to preserve the coherence of Gaussian states, whereas it can be effective in protecting coherent superpositions of both number states and Gaussian wave packets.Comment: Review article; 36 pages, 19 figures; typos corrected, references adde

The Reality of Pervasive Transcription

Despite recent controversies, the evidence that the majority of the human genome is transcribed into RNA remains strong

Prediction of Anisotropic Single-Dirac-Cones in Bi1−x{}_{1-x}Sbx{}_{x} Thin Films

The electronic band structures of Bi${}_{1-x}$Sb${}_{x}$ thin films can be varied as a function of temperature, pressure, stoichiometry, film thickness and growth orientation. We here show how different anisotropic single-Dirac-cones can be constructed in a Bi${}_{1-x}$Sb${}_{x}$ thin film for different applications or research purposes. For predicting anisotropic single-Dirac-cones, we have developed an iterative-two-dimensional-two-band model to get a consistent inverse-effective-mass-tensor and band-gap, which can be used in a general two-dimensional system that has a non-parabolic dispersion relation as in a Bi${}_{1-x}$Sb${}_{x}$ thin film system