Culturing Pancreatic Islets in Microfluidic Flow Enhances Morphology of the Associated Endothelial Cells

Pancreatic islets are heavily vascularized in vivo with each insulin secreting beta-cell associated with at least one endothelial cell (EC). This structure is maintained immediately post-isolation; however, in culture the ECs slowly deteriorate, losing density and branched morphology. We postulate that this deterioration occurs in the absence of blood flow due to limited diffusion of media inside the tissue. To improve exchange of media inside the tissue, we created a microfluidic device to culture islets in a range of flow-rates. Culturing the islets from C57BL6 mice in this device with media flowing between 1 and 7 ml/24 hr resulted in twice the EC-density and -connected length compared to classically cultured islets. Media containing fluorescent dextran reached the center of islets in the device in a flow-rate-dependant manner consistent with improved penetration. We also observed deterioration of EC morphology using serum free media that was rescued by addition of bovine serum albumin, a known anti-apoptotic signal with limited diffusion in tissue. We further examined the effect of flow on beta-cells showing dampened glucose-stimulated Ca2+-response from cells at the periphery of the islet where fluid shear-stress is greatest. However, we observed normal two-photon NAD(P)H response and insulin secretion from the remainder of the islet. These data reveal the deterioration of islet EC-morphology is in part due to restricted diffusion of serum albumin within the tissue. These data further reveal microfluidic devices as unique platforms to optimize islet culture by introducing intercellular flow to overcome the restricted diffusion of media components

Pulsed quantum optomechanics

Studying mechanical resonators via radiation pressure offers a rich avenue for the exploration of quantum mechanical behavior in a macroscopic regime. However, quantum state preparation and especially quantum state reconstruction of mechanical oscillators remains a significant challenge. Here we propose a scheme to realize quantum state tomography, squeezing and state purification of a mechanical resonator using short optical pulses. The scheme presented allows observation of mechanical quantum features despite preparation from a thermal state and is shown to be experimentally feasible using optical microcavities. Our framework thus provides a promising means to explore the quantum nature of massive mechanical oscillators and can be applied to other systems such as trapped ions.Comment: 9 pages, 4 figure

On RAF Sets and Autocatalytic Cycles in Random Reaction Networks

The emergence of autocatalytic sets of molecules seems to have played an important role in the origin of life context. Although the possibility to reproduce this emergence in laboratory has received considerable attention, this is still far from being achieved. In order to unravel some key properties enabling the emergence of structures potentially able to sustain their own existence and growth, in this work we investigate the probability to observe them in ensembles of random catalytic reaction networks characterized by different structural properties. From the point of view of network topology, an autocatalytic set have been defined either in term of strongly connected components (SCCs) or as reflexively autocatalytic and food-generated sets (RAFs). We observe that the average level of catalysis differently affects the probability to observe a SCC or a RAF, highlighting the existence of a region where the former can be observed, whereas the latter cannot. This parameter also affects the composition of the RAF, which can be further characterized into linear structures, autocatalysis or SCCs. Interestingly, we show that the different network topology (uniform as opposed to power-law catalysis systems) does not have a significantly divergent impact on SCCs and RAFs appearance, whereas the proportion between cleavages and condensations seems instead to play a role. A major factor that limits the probability of RAF appearance and that may explain some of the difficulties encountered in laboratory seems to be the presence of molecules which can accumulate without being substrate or catalyst of any reaction.Comment: pp 113-12

Gender and sustainable livelihoods: linking gendered experiences of environment, community and self

In this essay I explore the economic, social, environmental and cultural changes taking place in Bolsena, Italy, where agricultural livelihoods have rapidly diminished in the last two decades. I examine how gender dynamics have shifted with the changing values and livelihoods of Bolsena through three women’s narratives detailing their gendered experiences of environment, community and self. I reflect on these changes with Sabrina, who is engaged in a feminist community-based organization; Anna, who is running an alternative wine bar; and Isabella, a jeweler, who is engaged in ecofeminist practices. My analysis is based on concepts developed by feminist political ecology: specifically, the theory of rooted networks from Dianne Rocheleau, Donna Haraway’s concept of naturecultures (and the work of J. K. Gibson-Graham on new economic imaginaries emerging from the politics of place. I aim to think with, reflect upon and provoke from the ‘‘otherwise’’, taking into account the lived relations entwining nature and gender. My article looks at the interconnections of gender, environment and livelihoods, attentive to the daily needs, embodied interactions and labours of these three women as part of a reappropriation, reconstruction and reinvention of Bolsena’s lifeworld. By listening to the stories of their everyday lives and struggles, I show the dynamic potential of the politics of place and the efforts to build diverse economies and more ethical economic and ecological relationships based on gender-aware subjectivities and values

Sideband Cooling Micromechanical Motion to the Quantum Ground State

The advent of laser cooling techniques revolutionized the study of many atomic-scale systems. This has fueled progress towards quantum computers by preparing trapped ions in their motional ground state, and generating new states of matter by achieving Bose-Einstein condensation of atomic vapors. Analogous cooling techniques provide a general and flexible method for preparing macroscopic objects in their motional ground state, bringing the powerful technology of micromechanics into the quantum regime. Cavity opto- or electro-mechanical systems achieve sideband cooling through the strong interaction between light and motion. However, entering the quantum regime, less than a single quantum of motion, has been elusive because sideband cooling has not sufficiently overwhelmed the coupling of mechanical systems to their hot environments. Here, we demonstrate sideband cooling of the motion of a micromechanical oscillator to the quantum ground state. Entering the quantum regime requires a large electromechanical interaction, which is achieved by embedding a micromechanical membrane into a superconducting microwave resonant circuit. In order to verify the cooling of the membrane motion into the quantum regime, we perform a near quantum-limited measurement of the microwave field, resolving this motion a factor of 5.1 from the Heisenberg limit. Furthermore, our device exhibits strong-coupling allowing coherent exchange of microwave photons and mechanical phonons. Simultaneously achieving strong coupling, ground state preparation and efficient measurement sets the stage for rapid advances in the control and detection of non-classical states of motion, possibly even testing quantum theory itself in the unexplored region of larger size and mass.Comment: 13 pages, 7 figure

Coupling carbon nanotube mechanics to a superconducting circuit

The quantum behaviour of mechanical resonators is a new and emerging field driven by recent experiments reaching the quantum ground state. The high frequency, small mass, and large quality-factor of carbon nanotube resonators make them attractive for quantum nanomechanical applications. A common element in experiments achieving the resonator ground state is a second quantum system, such as coherent photons or superconducting device, coupled to the resonators motion. For nanotubes, however, this is a challenge due to their small size. Here, we couple a carbon nanoelectromechanical (NEMS) device to a superconducting circuit. Suspended carbon nanotubes act as both superconducting junctions and moving elements in a Superconducting Quantum Interference Device (SQUID). We observe a strong modulation of the flux through the SQUID from displacements of the nanotube. Incorporating this SQUID into superconducting resonators and qubits should enable the detection and manipulation of nanotube mechanical quantum states at the single-phonon level

Microwave amplification with nanomechanical resonators

Sensitive measurement of electrical signals is at the heart of modern science and technology. According to quantum mechanics, any detector or amplifier is required to add a certain amount of noise to the signal, equaling at best the energy of quantum fluctuations. The quantum limit of added noise has nearly been reached with superconducting devices which take advantage of nonlinearities in Josephson junctions. Here, we introduce a new paradigm of amplification of microwave signals with the help of a mechanical oscillator. By relying on the radiation pressure force on a nanomechanical resonator, we provide an experimental demonstration and an analytical description of how the injection of microwaves induces coherent stimulated emission and signal amplification. This scheme, based on two linear oscillators, has the advantage of being conceptually and practically simpler than the Josephson junction devices, and, at the same time, has a high potential to reach quantum limited operation. With a measured signal amplification of 25 decibels and the addition of 20 quanta of noise, we anticipate near quantum-limited mechanical microwave amplification is feasible in various applications involving integrated electrical circuits.Comment: Main text + supplementary information. 14 pages, 3 figures (main text), 18 pages, 6 figures (supplementary information

Fate specification and tissue-specific cell cycle control of the <i>Caenorhabditis elegans</i> intestine

Coordination between cell fate specification and cell cycle control in multicellular organisms is essential to regulate cell numbers in tissues and organs during development, and its failure may lead to oncogenesis. In mammalian cells, as part of a general cell cycle checkpoint mechanism, the F-box protein β-transducin repeat-containing protein (β-TrCP) and the Skp1/Cul1/F-box complex control the periodic cell cycle fluctuations in abundance of the CDC25A and B phosphatases. Here, we find that the Caenorhabditis elegans β-TrCP orthologue LIN-23 regulates a progressive decline of CDC-25.1 abundance over several embryonic cell cycles and specifies cell number of one tissue, the embryonic intestine. The negative regulation of CDC-25.1 abundance by LIN-23 may be developmentally controlled because CDC-25.1 accumulates over time within the developing germline, where LIN-23 is also present. Concurrent with the destabilization of CDC-25.1, LIN-23 displays a spatially dynamic behavior in the embryo, periodically entering a nuclear compartment where CDC-25.1 is abundant

Quantum nondemolition measurement of mechanical motion quanta

The fields of opto- and electromechanics have facilitated numerous advances in the areas of precision measurement and sensing, ultimately driving the studies of mechanical systems into the quantum regime. To date, however, the quantization of the mechanical motion and the associated quantum jumps between phonon states remains elusive. For optomechanical systems, the coupling to the environment was shown to preclude the detection of the mechanical mode occupation, unless strong single photon optomechanical coupling is achieved. Here, we propose and analyse an electromechanical setup, which allows to overcome this limitation and resolve the energy levels of a mechanical oscillator. We find that the heating of the membrane, caused by the interaction with the environment and unwanted couplings, can be suppressed for carefully designed electromechanical systems. The results suggest that phonon number measurement is within reach for modern electromechanical setups.Comment: 8 pages, 5 figures plus 24 pages, 11 figures supplemental materia

Critical Role of Gap Junction Coupled K(ATP) Channel Activity for Regulated Insulin Secretion

Pancreatic β-cells secrete insulin in response to closure of ATP-sensitive K(+) (K(ATP)) channels, which causes membrane depolarization and a concomitant rise in intracellular Ca(2+) (Ca(i)). In intact islets, β-cells are coupled by gap junctions, which are proposed to synchronize electrical activity and Ca(i) oscillations after exposure to stimulatory glucose (>7 mM). To determine the significance of this coupling in regulating insulin secretion, we examined islets and β-cells from transgenic mice that express zero functional K(ATP) channels in approximately 70% of their β-cells, but normal K(ATP) channel density in the remainder. We found that K(ATP) channel activity from approximately 30% of the β-cells is sufficient to maintain strong glucose dependence of metabolism, Ca(i), membrane potential, and insulin secretion from intact islets, but that glucose dependence is lost in isolated transgenic cells. Further, inhibition of gap junctions caused loss of glucose sensitivity specifically in transgenic islets. These data demonstrate a critical role of gap junctional coupling of K(ATP) channel activity in control of membrane potential across the islet. Control via coupling lessens the effects of cell–cell variation and provides resistance to defects in excitability that would otherwise lead to a profound diabetic state, such as occurs in persistent neonatal diabetes mellitus