High-sensitivity microfluidic calorimeters for biological and chemical applications

High-sensitivity microfluidic calorimeters raise the prospect of achieving high-throughput biochemical measurements with minimal sample consumption. However, it has been challenging to realize microchip-based calorimeters possessing both high sensitivity and precise sample-manipulation capabilities. Here, we report chip-based microfluidic calorimeters capable of characterizing the heat of reaction of 3.5-nL samples with 4.2-nW resolution. Our approach, based on a combination of hard- and soft-polymer microfluidics, provides both exceptional thermal response and the physical strength necessary to construct high-sensitivity calorimeters that can be scaled to automated, highly multiplexed array architectures. Polydimethylsiloxane microfluidic valves and pumps are interfaced to parylene channels and reaction chambers to automate the injection of analyte at 1 nL and below. We attained excellent thermal resolution via on-chip vacuum encapsulation, which provides unprecedented thermal isolation of the minute microfluidic reaction chambers. We demonstrate performance of these calorimeters by resolving measurements of the heat of reaction of urea hydrolysis and the enthalpy of mixing of water with methanol. The device structure can be adapted easily to enable a wide variety of other standard calorimeter operations; one example, a flow calorimeter, is described

Evolutionary prisoner's dilemma game on hierarchical lattices

An evolutionary prisoner's dilemma (PD) game is studied with players located on a hierarchical structure of layered square lattices. The players can follow two strategies [D (defector) and C (cooperator)] and their income comes from PD games with the ``neighbors.'' The adoption of one of the neighboring strategies is allowed with a probability dependent on the payoff difference. Monte Carlo simulations are performed to study how the measure of cooperation is affected by the number of hierarchical levels (Q) and by the temptation to defect. According to the simulations the highest frequency of cooperation can be observed at the top level if the number of hierarchical levels is low (Q<4). For larger Q, however, the highest frequency of cooperators occurs in the middle layers. The four-level hierarchical structure provides the highest average (total) income for the whole community.Comment: appendix adde

Conditional strategies and the evolution of cooperation in spatial public goods games

The fact that individuals will most likely behave differently in different situations begets the introduction of conditional strategies. Inspired by this, we study the evolution of cooperation in the spatial public goods game, where besides unconditional cooperators and defectors, also different types of conditional cooperators compete for space. Conditional cooperators will contribute to the public good only if other players within the group are likely to cooperate as well, but will withhold their contribution otherwise. Depending on the number of other cooperators that are required to elicit cooperation of a conditional cooperator, the latter can be classified in as many types as there are players within each group. We find that the most cautious cooperators, such that require all other players within a group to be conditional cooperators, are the undisputed victors of the evolutionary process, even at very low synergy factors. We show that the remarkable promotion of cooperation is due primarily to the spontaneous emergence of quarantining of defectors, which become surrounded by conditional cooperators and are forced into isolated convex "bubbles" from where they are unable to exploit the public good. This phenomenon can be observed only in structured populations, thus adding to the relevance of pattern formation for the successful evolution of cooperation.Comment: 7 two-column pages, 7 figures; accepted for publication in Physical Review

Evolution of Coordination in Social Networks: A Numerical Study

Coordination games are important to explain efficient and desirable social behavior. Here we study these games by extensive numerical simulation on networked social structures using an evolutionary approach. We show that local network effects may promote selection of efficient equilibria in both pure and general coordination games and may explain social polarization. These results are put into perspective with respect to known theoretical results. The main insight we obtain is that clustering, and especially community structure in social networks has a positive role in promoting socially efficient outcomes.Comment: preprint submitted to IJMP

Hereditary sensory and autonomic neuropathies: types II, III, and IV

The hereditary sensory and autonomic neuropathies (HSAN) encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception) and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating). Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that identification and classification are ongoing. As a group, the HSAN are rare diseases that affect both sexes. HSAN III is almost exclusive to individuals of Eastern European Jewish extraction, with incidence of 1 per 3600 live births. Several hundred cases with HSAN IV have been reported. The worldwide prevalence of HSAN type II is very low. This review focuses on the description of three of the disorders, HSAN II through IV, that are characterized by autosomal recessive inheritance and onset at birth. These three forms of HSAN have been the most intensively studied, especially familial dysautonomia (Riley-Day syndrome or HSAN III), which is often used as a prototype for comparison to the other HSAN. Each HSAN disorder is likely caused by different genetic errors that affect specific aspects of small fiber neurodevelopment, which result in variable phenotypic expression. As genetic tests are routinely used for diagnostic confirmation of HSAN III only, other means of differentiating between the disorders is necessary. Diagnosis is based on the clinical features, the degree of both sensory and autonomic dysfunction, and biochemical evaluations, with pathologic examinations serving to further confirm differences. Treatments for all these disorders are supportive

Probable Gravitational Microlensing towards the Galatic Bulge

The MACHO project carries out regular photometric monitoring of millions of stars in the Magellanic Clouds and Galactic Bulge, to search for very rare gravitational microlensing events due to compact objects in the galactic halo and disk. A preliminary analysis of one field in the Galactic Bulge, containing {$\sim430,000$} stars observed for 190 days, reveals four stars which show clear evidence for brightenings which are time-symmetric, achromatic in our two passbands, and have shapes consistent with gravitational microlensing. This is significantly higher than the $\sim 1$ event expected from microlensing by known stars in the disk. If all four events are due to microlensing, a 95\% confidence lower limit on the optical depth towards our bulge field is $1.3 \times 10^{-6}$, and a ``best fit" value is $\tau \approx 1.6 \times 10^{-6}/\epsilon$,where $\epsilon$ is the detection efficiency of the experiment, and $\epsilon < 0.4$. If the true optical depth is close to the ``best fit" value, possible explanations include a ``maximal" disk which accounts for most of the galactic circular velocity at the solar radius, a halo which is centrally concentrated, or bulge-bulge microlensing.Comment: submitted to Astrophysical Journal Letters, 10 pages text as uuencoded compressed PostScript, 5 figures and paper also available via anonymous ftp from merlin.anu.edu.au in /pub/kcf/mach