What's black and white about the grey matter?

In 1873 Camillo Golgi discovered his eponymous stain, which he called la reazione nera. By adding to it the concepts of the Neuron Doctrine and the Law of Dynamic Polarisation, Santiago Ramon y Cajal was able to link the individual Golgi-stained neurons he saw down his microscope into circuits. This was revolutionary and we have all followed Cajal's winning strategy for over a century. We are now on the verge of a new revolution, which offers the prize of a far more comprehensive description of neural circuits and their operation. The hope is that we will exploit the power of computer vision algorithms and modern molecular biological techniques to acquire rapidly reconstructions of single neurons and synaptic circuits, and to control the function of selected types of neurons. Only one item is now conspicuous by its absence: the 21st century equivalent of the concepts of the Neuron Doctrine and the Law of Dynamic Polarisation. Without their equivalent we will inevitably struggle to make sense of our 21st century observations within the 19th and 20th century conceptual framework we have inherite

Sedimentary Bed Evolution as a Mean-Reverting Random Walk: Implications for Tracer Statistics

Sediment tracers are increasingly employed to estimate bed load transport and landscape evolution rates. Tracer trajectories are dominated by periods of immobility (“waiting times”) as they are buried and reexcavated in the stochastically evolving river bed. Here we model bed evolution as a random walk with mean-reverting tendency (Ornstein-Uhlenbeck process) originating from the restoring effect of erosion and deposition. The Ornstein-Uhlenbeck model contains two parameters, a and b, related to the particle feed rate and range of bed elevation fluctuations, respectively. Observations of bed evolution in flume experiments agree with model predictions; in particular, the model reproduces the asymptotic t−1 tail in the tracer waiting time exceedance probability distribution. This waiting time distribution is similar to that inferred for tracers in natural gravel streams and avalanching rice piles, indicating applicability of the Ornstein-Uhlenbeck mean-reverting model to many disordered transport systems with tracer burial and excavation

Ecology and Management Potential for Purple Loosestrife (Lythrum salicaria)

Purple loosestrife (Lythrum salicaria), an exotic wetland plant from Eurasia, has become widespread in the northeast and northcentral regions of the U.S. and Canada. When it becomes established in a wetland, it crowds out most native plant species, and can form dense stands either in standing water or on moist soil. This results in decreased plant diversity and the loss of food and cover species valuable to wildlife. Some attempted control methods, such as controlled burning and water-level manipulation have proven to be unsuccessful. Other control measures, including mechanical cutting, replacement, and cattail competition, have shown encouraging, but inconclusive, results. This study was therefore initiated to further explore the possibility of controlling purple loosestrife through competition with cattails (Typha angustifolia) in mixed stands. A competitive edge was given to Typha by cutting Lythrum and selectively fertilizing Typha. First-year results of the study showed a significant decrease in Lythrum biomass as a result of cutting treatments. Cutting did not significantly reduce resprouting Lythrum stems, as Lythrum resprouted in greater numbers than Typha, but Typha sprouts grew faster and increased in biomass more quickly than Lythrum sprouts. With carbohydrate replenishment to the roots reduced, it is expected that Lythrum biomass will be reduced in subsequent years. The stress caused by cutting, and increased shade by the Typha canopy, may help to control purple loosestrife spread

Radiation design criteria handbook

Radiation design criteria for electronic parts applications in space environments are provided. The data were compiled from the Mariner/Jupiter Saturn 1977 electronic parts radiation test program. Radiation sensitive device types were exposed to radiation environments compatible with the MJS'77 requirements under suitable bias conditions. A total of 189 integrated circuits, transistors, and other semiconductor device types were tested

Nanotechnology and the Developing World

How nanotechnology can be harnessed to address some of the world's most critical development problem

Public views on a wait time management initiative: a matter of communication

<p>Abstract</p> <p>Background</p> <p>Many countries have tried to reduce waiting times for health care through formal wait time reduction strategies. Our paper describes views of members of the public about a wait time management initiative - the Ontario Wait Time Strategy (OWTS) (Canada). Scholars and governmental reports have advocated for increased public involvement in wait time management. We provide empirically derived recommendations for public engagement in a wait time management initiative.</p> <p>Methods</p> <p>Two qualitative studies: 1) an analysis of all emails sent by the public to the (OWTS) email address; and 2) in-depth interviews with members of the Ontario public.</p> <p>Results</p> <p>Email correspondents and interview participants supported the intent of the OWTS. However they wanted more information about the Strategy and its actions. Interview participants did not feel they were sufficiently made aware of the Strategy and email correspondents requested additional information beyond what was offered on the Strategy's website. Moreover, the email correspondents believed that some of the information that was provided on the Strategy's website and through the media was inaccurate, misleading, and even dishonest. Interview participants strongly supported public involvement in the OWTS priority setting.</p> <p>Conclusions</p> <p>Findings suggest the public wanted increased communication from and with the OWTS. Effective communication can facilitate successful public engagement, and in turn fair and legitimate priority setting. Based on the study's findings we developed concrete recommendations for improving public involvement in wait time management.</p

Can a "good death" be made better?: A preliminary evaluation of a patient-centred quality improvement strategy for severely ill in-patients

BACKGROUND: Prior studies attempting to improve end-of-life care have focused on specific outcomes deemed important to healthcare providers, with disappointing results. Improvement may be best achieved by identifying concerns important to individual patients, communicating the patients' concerns to the treating medical team, and repeating the process frequently until all concerns are addressed. Our objective was to conduct a preliminary evaluation of this innovative patient-centred quality improvement strategy. METHODS: Initial interviews elicited participants' ideas for improvement, which were then fed back to health care providers by the study investigator. A rapid-cycle change model ensured frequent reassessment and continued feedback. The study involved 36 seriously ill, hospitalized patients on teaching general medical inpatient units of a tertiary care hospital. The main outcome measure was participants' ratings of satisfaction within different domains of care on follow-up interviews. RESULTS: The proportion of participants who rated various aspects of their care as "excellent" or "very good" on initial interview was 72% for overall care, 64% for symptom control, 66% for level of support, and 75% for discussions about life sustaining treatments. Patients and families identified many actionable steps for improvement such as; better control of pain and shortness of breath, better access to physicians and medical information, more help with activities of daily living, improving the patient's environment, and shorter waits for nursing care, diagnosis, and treatment. Following feedback to the clinical team, participants reported improvement in overall care (32%), symptom control (44%), and support (40%). Only a minority had further discussions about life sustaining treatments. CONCLUSION: A patient-centred approach using rapid-cycle change was feasible and shows promise for improving the quality of end-of-life care. It should be evaluated on a larger sample in a controlled trial

Human endogenous retrovirus K106 (HERV-K106) was infectious after the emergence of anatomically modern humans.

HERV-K113 and HERV-K115 have been considered to be among the youngest HERVs because they are the only known full-length proviruses that are insertionally polymorphic and maintain the open reading frames of their coding genes. However, recent data suggest that HERV-K113 is at least 800,000 years old, and HERV-K115 even older. A systematic study of HERV-K HML2 members to identify HERVs that may have infected the human genome in the more recent evolutionary past is lacking. Therefore, we sought to determine how recently HERVs were exogenous and infectious by examining sequence variation in the long terminal repeat (LTR) regions of all full-length HERV-K loci. We used the traditional method of inter-LTR comparison to analyze all full length HERV-Ks and determined that two insertions, HERV-K106 and HERV-K116 have no differences between their 5' and 3' LTR sequences, suggesting that these insertions were endogenized in the recent evolutionary past. Among these insertions with no sequence differences between their LTR regions, HERV-K106 had the most intact viral sequence structure. Coalescent analysis of HERV-K106 3' LTR sequences representing 51 ethnically diverse individuals suggests that HERV-K106 integrated into the human germ line approximately 150,000 years ago, after the emergence of anatomically modern humans

Anomalies in Noncommutative Dipole Field Theories

We study chiral symmetries of fermionic non commutative dipole theories. By using Fujikawa's approach we obtain explicit expressions of the anomalies for Dirac and chiral fermions in 2 and 4 dimensions.Comment: 11pages, latex file. Comments adde

Metformin-mediated increase in DICER1 regulates microRNA expression and cellular senescence

Metformin, an oral hypoglycemic agent, has been used for decades to treat type 2 diabetes mellitus. Recent studies indicate that mice treated with metformin live longer and have fewer manifestations of age-related chronic disease. However, the molecular mechanisms underlying this phenotype are unknown. Here, we show that metformin treatment increases the levels of the microRNA-processing protein DICER1 in mice and in humans with diabetes mellitus. Our results indicate that metformin upregulates DICER1 through a post-transcriptional mechanism involving the RNA-binding protein AUF1. Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate. Consistent with the role of DICER1 in the biogenesis of microRNAs, we found differential patterns of microRNA expression in mice treated with metformin or caloric restriction, two proven life-extending interventions. Interestingly, several microRNAs previously associated with senescence and aging, including miR-20a, miR-34a, miR-130a, miR-106b, miR-125, and let-7c, were found elevated. In agreement with these findings, treatment with metformin decreased cellular senescence in several senescence models in a DICER1- dependent manner. Metformin lowered p16 and p21 protein levels and the abundance of inflammatory cytokines and oncogenes that are hallmarks of the senescence-associated secretory phenotype (SASP). These data lead us to hypothesize that changes in DICER1 levels may be important for organismal aging and to propose that interventions that upregulate DICER1 expression (e.g., metformin) may offer new pharmacotherapeutic approaches for age-related disease