Color responses and their adaptation in human superior colliculus and lateral geniculate nucleus

We use an fMRI adaptation paradigm to explore the selectivity of human responses in the lateral geniculate nucleus (LGN) and superior colliculus (SC) to red–green color and achromatic contrast.We measured responses to red–green (RG) and achromatic (ACH) high contrast sinewave counter-phasing rings with and without adaptation, within a block design. The signal for the RG test stimulus was reduced following both RG and ACH adaptation, whereas the signal for the ACH test was unaffected by either adaptor. These results provide compelling evidence that the human LGN and SC have significant capacity for color adaptation. Since in the LGN red–green responses are mediated by P cells, these findings are in contrast to earlier neurophysiological data from non-human primates that have shown weak or no contrast adaptation in the P pathway. Cross-adaptation of the red–green color response by achromatic contrast suggests unselective response adaptation and points to a dual role for P cells in responding to both color and achromatic contrast. We further show that subcortical adaptation is not restricted to the geniculostriate system, but is also present in the superior colliculus (SC), an oculomotor region that until recently, has been thought to be color-blind. Our data show that the human SC not only responds to red–green color contrast, but like the LGN, shows reliable but unselective adaptation.published_or_final_versio

Methane Production Pathway Regulated Proximally by Substrate Availability and Distally by Temperature in a High-Latitude Mire Complex

Projected 21st century changes in high-latitude climate are expected to have significant impacts on permafrost thaw, which could cause substantial increases in emissions to the atmosphere of carbon dioxide (CO2) and methane (CH4, which has a global warming potential 28 times larger than CO2 over a 100-year horizon). However, predicted CH4 emission rates are very uncertain due to difficulties in modeling complex interactions among hydrological, thermal, biogeochemical, and plant processes. Methanogenic production pathways (i.e., acetoclastic [AM] and hydrogenotrophic [HM]) and the magnitude of CH4 emissions may both change as permafrost thaws, but a mechanistic analysis of controls on such shifts in CH4 dynamics is lacking. In this study, we reproduced observed shifts in CH4 emissions and production pathways with a comprehensive biogeochemical model (ecosys) at the Stordalen Mire in subarctic Sweden. Our results demonstrate that soil temperature changes differently affect AM and HM substrate availability, which regulates magnitudes of AM, HM, and thereby net CH4 emissions. We predict very large landscape-scale, vertical, and temporal variations in the modeled HM fraction, highlighting that measurement strategies for metrics that compare CH4 production pathways could benefit from model informed scale of temporal and spatial variance. Finally, our findings suggest that the warming and wetting trends projected in northern peatlands could enhance peatland AM fraction and CH4 emissions even without further permafrost degradation

The Tevatron at the Frontier of Dark Matter Direct Detection

Direct detection of dark matter (DM) requires an interaction of dark matter particles with nucleons. The same interaction can lead to dark matter pair production at a hadron collider, and with the addition of initial state radiation this may lead to mono-jet signals. Mono-jet searches at the Tevatron can thus place limits on DM direct detection rates. We study these bounds both in the case where there is a contact interaction between DM and the standard model and where there is a mediator kinematically accessible at the Tevatron. We find that in many cases the Tevatron provides the current best limit, particularly for light dark matter, below 5 GeV, and for spin dependent interactions. Non-standard dark matter candidates are also constrained. The introduction of a light mediator significantly weakens the collider bound. A direct detection discovery that is in apparent conflict with mono-jet limits will thus point to a new light state coupling the standard model to the dark sector. Mono-jet searches with more luminosity and including the spectrum shape in the analysis can improve the constraints on DM-nucleon scattering cross section.Comment: 20 pages, 8 figures, final version in JHE

A Multivariate Analysis of United States and Global Real Estate Investment Trusts

Using daily data for the period February 2006 to July 2013 we examine the return and volatility linkages between the two main United States REIT sub-sectors and global linkages between the Americas, Europe and the Asia Pacific regions using the BEKK-GARCH and the DCC-GARCH models. We find that there is no evidence of any volatility spillovers between the US sub-sectors. By contrast, we find evidence of volatility spillovers between the Asia Pacific and the Americas, the Asia Pacific and Europe but no spillovers between the United States and Europe. Our results suggest that the REIT market is becoming increasingly globalized and that investors need to consider time varying volatility and correlations across different regions of the world when forming their optimal portfolio-allocations

The strong emergence of molecular structure

One of the most plausible and widely discussed examples of strong emergence is molecular structure. The only detailed account of it, which has been very influential, is due to Robin Hendry and is formulated in terms of downward causation. This paper explains Hendry’s account of the strong emergence of molecular structure and argues that it is coherent only if one assumes a diachronic reflexive notion of downward causation. However, in the context of this notion of downward causation, the strong emergence of molecular structure faces three challenges that have not been met and which have so far remained unnoticed. First, the putative empirical evidence presented for the strong emergence of molecular structure equally undermines supervenience, which is one of the main tenets of strong emergence. Secondly, it is ambiguous how the assumption of determinate nuclear positions is invoked for the support of strong emergence, as the role of this assumption in Hendry’s argument can be interpreted in more than one way. Lastly, there are understandings of causation which render the postulation of a downward causal relation between a molecule’s structure and its quantum mechanical entities, untenable

Fatal miliary Coccidioidomycosis in a patient receiving infliximab therapy: a case report

A 78-year-old white male from Iowa in the United States of America receiving the anti- tumor necrois factor (TNF) agent infliximab therapy for rheumatoid arthritis developed a cheek ulcer which failed to respond to empiric antibiotic therapy. He subsequently presented with progressive respiratory failure from miliary coccidioidomycosis which proved fatal. The patient vacationed in Arizona 6 months previously and likely contracted the organism there as Iowa is not an endemic area for coccidioidomycosis. Respiratory failure from miliary infiltration is an uncommon presentation of coccidioidomycosis. Physicians should be aware of the importance of travel history and potential for life-threatening coccidioidomycosis in patients receiving tumor necrosis factor inhibitors

Short- and long-term cause-specific survival of patients with inflammatory breast cancer

BACKGROUND: Inflammatory breast cancer (IBC) had been perceived to have a poor prognosis. Oncologists were not enthusiastic in the past to give aggressive treatment. Single institution studies tend to have small patient numbers and limited years of follow-up. Most studies do not report 10-, 15- or 20-year results. METHODS: Data was obtained from the population-based database of the Surveillance, Epidemiology, and End Results program of the National Cancer Institute from 1975–1995 using SEER*Stat5.0 software. This period of 21 years was divided into 7 periods of 3 years each. The years were chosen so that there was adequate follow-up information to 2000. ICD-O-2 histology 8530/3 was used to define IBC. The lognormal model was used for statistical analysis. RESULTS: A total of 1684 patients were analyzed, of which 84% were white, 11% were African Americans, and 5% belonged to other races. Age distribution was < 30 years in 1%, 30–40 in 11%, 40–50 in 22%, 50–60 in 24%, 60–70 in 21%, and > 70 in 21%. The lognormal model was validated for 1975–77 and for 1978–80, since the 10-, 15- and 20-year cause-specific survival (CSS) rates, could be calculated using the Kaplan-Meier method with data available in 2000. The data were then used to estimate the 10-, 15- and 20-year CSS rates for the more recent years, and to study the trend of improvement in survival. There were increasing incidences of IBC: 134 patients in the 1975–77 period to 416 patients in the 1993–95 period. The corresponding 20-year CSS increased from 9% to 20% respectively with standard errors of less than 4%. CONCLUSION: The improvement of survival during the study period may be due to introduction of more aggressive treatments. However, there seem to be no further increase of long-term CSS, which should encourage oncologists to find even more effective treatments. Because of small numbers of patients, randomized studies will be difficult to conduct. The SEER population-based database will yield the best possible estimate of the trend in improvement of survival for patients with IBC

Ultrasonic NDE of Adhesive Bonds: The Inverse Problem

Over the past quarter century, a wide variety of ultrasonic techniques have been developed to determine the phase velocity and thickness of elastic plates. Techniques to measure the phase velocity include toneburst [1–4], separable pulse methods [5–7], and spectroscopy [8–11]. These classical methods require that the specimen be thick enough such that two successive echoes from the front and the back faces of the specimen, respectively, be separable in the time domain. Kinra and Dayal [12], developed a through transmission technique which removes this particular limitation of the classical methods. This technique works satisfactorily for the measurement of the phase velocity for specimens whose thickness is greater than one-half of the wavelength; for thinner specimens, however, their numerical algorithm runs into convergence problems. Moreover, their numerical algorithm cannot be used to determine thickness at any wavelength. The reasons for their convergence problems are discussed in detail by Iyer, Hanneman and Kinra [13]. They demonstrated that a detailed sensitivity analysis is a necessary pre-requisite for the development of a robust inversion algorithm. Accordingly, a new inversion scheme based on the method of least squares was developed by Iyer and Kinra to determine thickness from the measurements of phase, magnitude and complex spectrum, respectively, [14–17]. In all of the above ultrasonic methods only one parameter can be determined i.e., an accurate knowledge of thickness is required to determine the wavespeed and vice versa. This defines the central objective of the present work: In this paper we present a technique for determining, simultaneously, the thickness and wavespeed of a thin layer

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

Approaches for estimating minimal clinically important differences in systemic lupus erythematosus.

A minimal clinically important difference (MCID) is an important concept used to determine whether a medical intervention improves perceived outcomes in patients. Prior to the introduction of the concept in 1989, studies focused primarily on statistical significance. As most recent clinical trials in systemic lupus erythematosus (SLE) have failed to show significant effects, determining a clinically relevant threshold for outcome scores (that is, the MCID) of existing instruments may be critical for conducting and interpreting meaningful clinical trials as well as for facilitating the establishment of treatment recommendations for patients. To that effect, methods to determine the MCID can be divided into two well-defined categories: distribution-based and anchor-based approaches. Distribution-based approaches are based on statistical characteristics of the obtained samples. There are various methods within the distribution-based approach, including the standard error of measurement, the standard deviation, the effect size, the minimal detectable change, the reliable change index, and the standardized response mean. Anchor-based approaches compare the change in a patient-reported outcome to a second, external measure of change (that is, one that is more clearly understood, such as a global assessment), which serves as the anchor. Finally, the Delphi technique can be applied as an adjunct to defining a clinically important difference. Despite an abundance of methods reported in the literature, little work in MCID estimation has been done in the context of SLE. As the MCID can help determine the effect of a given therapy on a patient and add meaning to statistical inferences made in clinical research, we believe there ought to be renewed focus on this area. Here, we provide an update on the use of MCIDs in clinical research, review some of the work done in this area in SLE, and propose an agenda for future research