Science is perception: what can our sense of smell tell us about ourselves and the world around us?

Human sensory processes are well understood: hearing, seeing, perhaps even tasting and touch—but we do not understand smell—the elusive sense. That is, for the others we know what stimuli causes what response, and why and how. These fundamental questions are not answered within the sphere of smell science; we do not know what it is about a molecule that … smells. I report, here, the status quo theories for olfaction, highlighting what we do not know, and explaining why dismissing the perception of the input as ‘too subjective’ acts as a roadblock not conducive to scientific inquiry. I outline the current and new theory that conjectures a mechanism for signal transduction based on quantum mechanical phenomena, dubbed the ‘swipe card’, which is perhaps controversial but feasible. I show that such lines of thinking may answer some questions, or at least pose the right questions. Most importantly, I draw links and comparisons as to how better understanding of how small (10’s of atoms) molecules can interact so specially with large (10 000’s of atoms) proteins in a way that is so integral to healthy living. Repercussions of this work are not just important in understanding a basic scientific tool used by us all, but often taken for granted, it is also a step closer to understanding generic mechanisms between drug and receptor, for example

Could humans recognize odor by phonon assisted tunneling?

Our sense of smell relies on sensitive, selective atomic-scale processes that are initiated when a scent molecule meets specific receptors in the nose. However, the physical mechanisms of detection are not clear. While odorant shape and size are important, experiment indicates these are insufficient. One novel proposal suggests inelastic electron tunneling from a donor to an acceptor mediated by the odorant actuates a receptor, and provides critical discrimination. We test the physical viability of this mechanism using a simple but general model. Using values of key parameters in line with those for other biomolecular systems, we find the proposed mechanism is consistent both with the underlying physics and with observed features of smell, provided the receptor has certain general properties. This mechanism suggests a distinct paradigm for selective molecular interactions at receptors (the swipe card model): recognition and actuation involve size and shape, but also exploit other processes.Comment: 10 pages, 1 figur

People

Peopl

The VITAH Trial Vitamin D supplementation and cardiac autonomic tone in hemodialysis: a blinded, randomized controlled trial

BACKGROUND: Patients with end-stage kidney disease (ESKD) have a high rate of mortality and specifically an increased risk of sudden cardiac death (SCD). Impaired cardiac autonomic tone is associated with elevated risk of SCD. Moreover, patients with ESKD are often vitamin D deficient, which we have shown may be linked to autonomic dysfunction in humans. To date, it is not known whether vitamin D supplementation normalizes cardiac autonomic function in the high-risk ESKD population. The VITamin D supplementation and cardiac Autonomic tone in Hemodialysis (VITAH) randomized trial will determine whether intensive vitamin D supplementation therapies improve cardiac autonomic tone to a greater extent than conventional vitamin D supplementation regimens in ESKD patients requiring chronic hemodialysis. METHODS/DESIGN: A total of 60 subjects with ESKD requiring thrice weekly chronic hemodialysis will be enrolled in this 2x2 crossover, blinded, randomized controlled trial. Following a 4-week washout period from any prior vitamin D therapy, subjects are randomized 1:1 to intensive versus standard vitamin D therapy for 6 weeks, followed by a 12-week washout period, and finally the remaining treatment arm for 6 weeks. Intensive vitamin D treatment includes alfacalcidiol (activated vitamin D) 0.25mcg orally with each dialysis session combined with ergocalciferol (nutritional vitamin D) 50 000 IU orally once per week and placebo the remaining two dialysis days for 6 weeks. The standard vitamin D treatment includes alfacalcidiol 0.25mcg orally combined with placebo each dialysis session per week for 6 weeks. Cardiac autonomic tone is measured via 24 h Holter monitor assessments on the first dialysis day of the week every 6 weeks throughout the study period. The primary outcome is change in the low frequency: high frequency heart rate variability (HRV) ratio during the first 12 h of the Holter recording at 6 weeks versus baseline. Secondary outcomes include additional measures of HRV. The safety of intensive versus conventional vitamin D supplementation is also assessed. DISCUSSION: VITAH will determine whether an intensive vitamin D supplementation regimen will improve cardiac autonomic tone compared to conventional vitamin D supplementation and will assess the safety of these two supplementation regimens in ESKD patients receiving chronic hemodialysis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0177481

Numerical analysis of the radio-frequency single-electron transistor operation

We have analyzed numerically the response and noise-limited charge sensitivity of a radio-frequency single-electron transistor (RF-SET) in a non-superconducting state using the orthodox theory. In particular, we have studied the performance dependence on the quality factor Q of the tank circuit for Q both below and above the value corresponding to the impedance matching between the coaxial cable and SET.Comment: 14 page

A model of diffuse Galactic Radio Emission from 10 MHz to 100 GHz

Understanding diffuse Galactic radio emission is interesting both in its own right and for minimizing foreground contamination of cosmological measurements. Cosmic Microwave Background experiments have focused on frequencies > 10 GHz, whereas 21 cm tomography of the high redshift universe will mainly focus on < 0.2 GHz, for which less is currently known about Galactic emission. Motivated by this, we present a global sky model derived from all publicly available total power large-area radio surveys, digitized with optical character recognition when necessary and compiled into a uniform format, as well as the new Villa Elisa data extending the 1.4 GHz map to the entire sky. We quantify statistical and systematic uncertainties in these surveys by comparing them with various global multi-frequency model fits. We find that a principal component based model with only three components can fit the 11 most accurate data sets (at 10, 22, 45 & 408 MHz and 1.4, 2.3, 23, 33, 41, 61, 94 GHz) to an accuracy around 1%-10% depending on frequency and sky region. Both our data compilation and our software returning a predicted all-sky map at any frequency from 10 MHz to 100 GHz are publicly available at http://space.mit.edu/home/angelica/gsm .Comment: Accuracy improved with 5-year WMAP data. Our data, software and new foreground-cleaned WMAP map are available at https://ascl.net/1011.01

Exploring impulsive solar magnetic energy release and particle acceleration with focused hard X-ray imaging spectroscopy

How impulsive magnetic energy release leads to solar eruptions and how those eruptions are energized and evolve are vital unsolved problems in Heliophysics. The standard model for solar eruptions summarizes our current understanding of these events. Magnetic energy in the corona is released through drastic restructuring of the magnetic field via reconnection. Electrons and ions are then accelerated by poorly understood processes. Theories include contracting loops, merging magnetic islands, stochastic acceleration, and turbulence at shocks, among others. Although this basic model is well established, the fundamental physics is poorly understood. HXR observations using grazing-incidence focusing optics can now probe all of the key regions of the standard model. These include two above-the-looptop (ALT) sources which bookend the reconnection region and are likely the sites of particle acceleration and direct heating. The science achievable by a direct HXR imaging instrument can be summarized by the following science questions and objectives which are some of the most outstanding issues in solar physics (1) How are particles accelerated at the Sun? (1a) Where are electrons accelerated and on what time scales? (1b) What fraction of electrons is accelerated out of the ambient medium? (2) How does magnetic energy release on the Sun lead to flares and eruptions? A Focusing Optics X-ray Solar Imager (FOXSI) instrument, which can be built now using proven technology and at modest cost, would enable revolutionary advancements in our understanding of impulsive magnetic energy release and particle acceleration, a process which is known to occur at the Sun but also throughout the Universe

Kidney Function, Albuminuria and Life Expectancy

Background: Lower estimated glomerular filtration rate is associated with reduced life expectancy. Whether this association is modified by the presence or absence of albuminuria, another cardinal finding of chronic kidney disease, is unknown. Objective: Our objective was to estimate the life expectancy of middle-aged men and women with varying levels of eGFR and concomitant albuminuria. Design: A retrospective cohort study. Setting: A large population-based cohort identified from the provincial laboratory registry in Alberta, Canada. Participants: Adults aged ≥30 years who had outpatient measures of serum creatinine and albuminuria between May 1, 2002 and March 31, 2008. Measurements: Predictor : Baseline levels of kidney function identified from serum creatinine and albuminuria measurements. Outcomes : all cause mortality during the follow-up. Methods: Patients were categorized based on their estimated glomerular filtration rate (eGFR) (≥60, 45–59, 30–44, and 15–29 mL/min/1 · 73 m 2 ) as well as albuminuria (normal, mild, and heavy) measured by albumin-to-creatinine ratio or urine dipstick. The abridged life table method was applied to calculate the life expectancies of men and women from age 40 to 80 years across combined eGFR and albuminuria categories. We also categorized participants by severity of kidney disease (low risk, moderately increased risk. high risk, and very high risk) using the combination of eGFR and albuminuria levels. Results: Among men aged 50 years and with eGFR ≥60 mL/min/1.73 m 2 , estimated life expectancy was 24.8 (95% CI: 24.6–25.0), 17.5 (95% CI: 17.1–17.9), and 13.5 (95% CI: 12.6–14.3) years for participants with normal, mild and heavy albuminuria respectively. Life expectancy for men with mild and heavy albuminuria was 7.3 (95% CI: 6.9–7.8) and 11.3 (95% CI: 10.5–12.2) years shorter than men with normal proteinuria, respectively. A reduction in life expectancy was associated with an increasing severity of kidney disease; 24.8 years for low risk (95% CI: 24.6–25.0), 19.1 years for moderately increased risk (95% CI: 18.7–19.5), 14.2 years for high risk (95% CI: 13.5–15.0), and 9.6 years for very high risk (95% CI: 8.4–10.8). Among women of similar age and kidney function, estimated life expectancy was 28.9 (95% CI: 28.7–29.1), 19.8 (95% CI: 19.2–20.3), and 14.8 (95% CI: 13.5–16.0) years for participants with normal, mild and heavy albuminuria respectively. Life expectancy for women with mild and heavy albuminuria was 9.1 (95% CI: 8.5–9.7) and 14.2 (95% CI: 12.9–15.4) years shorter than the women with normal proteinuria, respectively. For women also a graded reduction in life expectancy was observed across the increasing severity of kidney disease; 28.9 years for low risk (95% CI: 28.7–29.1), 22.5 years for moderately increased risk (95% CI: 22.0–22.9), 16.5 years for high risk (95% CI: 15.4–17.5), and 9.2 years for very high risk (95% CI: 7.8–10.7). Limitations: Possible misclassification of long-term kidney function categories cannot be eliminated. Possibility of confounding due to concomitant comorbidities cannot be ruled out. Conclusion: The presence and degree of albuminuria was associated with lower estimated life expectancy for both gender and was especially notable in those with eGFR ≥30 mL/min/1.73 m 2 . Life expectancy associated with a given level of eGFR differs substantially based on the presence and severity of albuminuria