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Transforming growth factor beta (TGF-β) induced myofibroblast differentiation is central to the pathological scarring observed in Idiopathic Pulmonary Fibrosis (IPF) and other fibrotic diseases. Our lab has recently identified expression of GPR68 (Ovarian Cancer Gene Receptor 1, OGR1), a pH sensing G-protein coupled receptor, as a negative regulator of TGF-β induced profibrotic effects in primary human lung fibroblasts (PHLFs). We therefore hypothesized that small molecule activators of GPR68 would inhibit myofibroblast differentiation. Ogerin is a positive allosteric modulator (PAM) of GPR68, inducing a leftward shift of the dose response curve to proton induced signaling. Using PHLFs derived from patients with both non-fibrotic and IPF diagnoses, we show that Ogerin inhibits, and partially reverses TGF-β induced myofibroblast differentiation in a dose dependent manner. This occurs at the transcriptional level without inhibition of canonical TGF-β induced SMAD signaling. Ogerin induces PKA dependent CREB phosphorylation, a marker of Gαs pathway activation. The ability of Ogerin to inhibit both basal and TGF-β induced collagen gene transcription, and induction of Gαs signaling is enhanced at an acidic pH (pH 6.8). Similar findings were also found using fibroblasts derived from dermal, intestinal, and orbital tissue. The biological role of GPR68 in different tissues, cell types, and disease states is an evolving and emerging field. This work adds to the understanding of Gαs coupled GPCRs in fibrotic lung disease, the ability to harness the pH sensing properties of GPR68, and conserved mechanisms of fibrosis across different organ systems.

This perspective explores future research approaches on the use of noise characteristics of microelectromechanical systems (MEMS) devices as a diagnostic tool to assess their quality and reliability. Such a technique has been applied to electronic devices. In comparison to these, however, MEMS have much more diverse materials, structures, and transduction mechanisms. Correspondingly, we must deal with various types of noise sources and a means to separate their contributions. In this paper, we first provide an overview of reliability and noise in MEMS and then suggest a framework to link noise data of specific devices to their quality or reliability. After this, we analyze 13 classes of MEMS and recommend four that are most amenable to this approach. Finally, we propose a noise measurement system to separate the contribution of electrical and mechanical noise sources. Through this perspective, our hope is for current and future designers of MEMS to see the potential benefits of noise in their devices.

Pulmonary fibrosis is a devastating, progressive disease and carries a prognosis worse than most cancers. Despite ongoing research, the mechanisms that underlie disease pathogenesis remain only partially understood. However, the self-perpetuating nature of pulmonary fibrosis has led several researchers to propose the existence of pathological signalling loops. According to this hypothesis, the normal wound-healing process becomes corrupted and results in the progressive accumulation of scar tissue in the lung. In addition, several negative regulators of pulmonary fibrosis are downregulated and, therefore, are no longer capable of inhibiting these feed-forward loops. The combination of pathological signalling loops and loss of a checks and balances system ultimately culminates in a process of unregulated scar formation. This review details specific signalling pathways demonstrated to play a role in the pathogenesis of pulmonary fibrosis. The evidence of detrimental signalling loops is elucidated with regard to epithelial cell injury, cellular senescence and the activation of developmental and ageing pathways. We demonstrate where these loops intersect each other, as well as common mediators that may drive these responses and how the loss of pro-resolving mediators may contribute to the propagation of disease. By focusing on the overlapping signalling mediators among the many pro-fibrotic pathways, it is our hope that the pulmonary fibrosis community will be better equipped to design future trials that incorporate the redundant nature of these pathways as we move towards finding a cure for this unrelenting disease.

Idiopathic pulmonary fibrosis (IPF) is a disease characterized by irreversible scarring of the lung that is associated with significant mortality and morbidity. The pathophysiology is incompletely understood but it is well-established that fibroblast to myofibroblast differentiation is a key feature of pulmonary fibrosis. Our lab has established that a reduction in extracellular pH is one of several important pathways responsible for the activation of latent TGF-β in the extracellular space. TGF-β activation further decreases extracellular pH and creates a feed-forward mechanism that stimulates myofibroblast differentiation and activation of additional TGF-β. Given the importance of TGF-β and extracellular acidification to the progression of pulmonary fibrosis, we sought to identify novel mechanisms that are involved in pH-dependent fibrotic signaling. The proton sensing G-Protein Coupled family of receptors are activated in acidic environments, but their role in fibrotic signaling has not been studied. Here we report that the Ovarian Cancer G-Protein Coupled Receptor1 (OGR1 or GPR68), a member of the family of proton sensing G-Protein Coupled Receptors, negatively regulates pro-fibrotic signaling. We demonstrate that OGR1 expression is significantly reduced in lung tissue from patients with IPF and TGF-β decreases OGR1 expression. In fibroblasts, a reduction in expression of OGR1 (OGR knockout lung fibroblasts) and knockdown (OGR siRNA), promotes in vitro myofibroblast differentiation. In contrast, OGR1 overexpression inhibits myofibroblast differentiation. Finally, we demonstrate that OGR1 negatively regulates TGF-β stimulation through inhibition of focal adhesion kinase (FAK) phosphorylation. Our results suggest that preserving OGR1 expression may represent a novel therapeutic strategy in pulmonary fibrosis.

Pulmonary fibrosis is a chronic and irreversible scarring disease in the lung with poor prognosis. Few therapies are available; therefore it is critical to identify new therapeutic targets. Our lab has previously identified the enzyme lactate dehydrogenase-A (LDHA) as a potential therapeutic target in pulmonary fibrosis. We found increases in LDHA protein and its metabolic product, lactate, in patients with idiopathic pulmonary fibrosis (IPF). Importantly, we described lactate as a novel pro-fibrotic mediator by acidifying the extracellular space, and activating latent transforming growth factor beta (TGF-β1) in a pH-dependent manner. We propose a pro-fibrotic feed-forward loop by which LDHA produces lactate, lactate decreases pH in the extracellular space and activates TGF-β1 which can further perpetuate fibrotic signaling. Our previous work also demonstrates that the LDHA inhibitor gossypol inhibits TGF-β1-induced myofibroblast differentiation and collagen production in vitro. Here, we employed a mouse model of bleomycin-induced pulmonary fibrosis to test whether gossypol inhibits pulmonary fibrosis in vivo. We found that gossypol dose-dependently inhibits bleomycin-induced collagen accumulation and TGF-β1 activation in mouse lungs when treatment is started on the same day as bleomycin administration. Importantly, gossypol was also effective at treating collagen accumulation when delayed 7 days following bleomycin. Our results demonstrate that inhibition of LDHA with the inhibitor gossypol is effective at both preventing and treating bleomycin-induced pulmonary fibrosis, and suggests that LDHA may be a potential therapeutic target for pulmonary fibrosis.

Rationale: Neointimal hyperplasia characterized by abnormal accumulation of vascular smooth muscle cells (SMCs) is a hallmark of occlusive disorders such as atherosclerosis, postangioplasty restenosis, vein graft stenosis, and allograft vasculopathy. Cyclic nucleotides are vital in SMC proliferation and migration, which are regulated by cyclic nucleotide phosphodiesterases (PDEs). Objective: Our goal is to understand the regulation and function of PDEs in SMC pathogenesis of vascular diseases. Methods and Results: We performed screening for genes differentially expressed in normal contractile versus proliferating synthetic SMCs. We observed that PDE1C expression was low in contractile SMCs but drastically elevated in synthetic SMCs in vitro and in various mouse vascular injury models in vivo. In addition, PDE1C was highly induced in neointimal SMCs of human coronary arteries. More importantly, injury-induced neointimal formation was significantly attenuated by PDE1C deficiency or PDE1 inhibition in vivo. PDE1 inhibition suppressed vascular remodeling of human saphenous vein explants ex vivo. In cultured SMCs, PDE1C deficiency or PDE1 inhibition attenuated SMC proliferation and migration. Mechanistic studies revealed that PDE1C plays a critical role in regulating the stability of growth factor receptors, such as PDGF receptor β (PDGFRβ) known to be important in pathological vascular remodeling. PDE1C interacts with low-density lipoprotein receptor–related protein-1 and PDGFRβ, thus regulating PDGFRβ endocytosis and lysosome-dependent degradation in an low-density lipoprotein receptor–related protein-1–dependent manner. A transmembrane adenylyl cyclase cAMP-dependent protein kinase cascade modulated by PDE1C is critical in regulating PDGFRβ degradation. Conclusions: These findings demonstrated that PDE1C is an important regulator of SMC proliferation, migration, and neointimal hyperplasia, in part through modulating endosome/lysosome-dependent PDGFRβ protein degradation via low-density lipoprotein receptor–related protein-1.

Guest editorial In the late 1850s, the whaling industry was in a veritable boom in the town of Lahaina on the Hawaiian island of Maui. Business was great, and many in the whaling industry believed that increased demand would continue for decades to come. But in 1859, oil was discovered in Titusville, Pennsylvania with a well drilled by Edwin Drake. The rest is history. That was 150 years ago. A small but increasing number of people around the world believe we are on a similar course, except this time it is the petroleum industry that might be threatened. As with any emerging technology, critical challenges must be overcome and a significant effort lies ahead to convince a world of skeptics that a new source of energy has been discovered and will be important. The potential new source of energy is low-energy nuclear reactions (LENR). With any discussion of a new technology, caution is advised. The world of LENR is filled with mystery, contradiction, gross speculation, misinformation, slippery timelines, and skepticism that sometimes spill over into outright denial. Healthy skepticism on LENR (or any new technology) is a good thing, but so is an open mind. If LENR is for real—and many well-qualified physicists believe it is—it will not only change the petroleum industry, but also significantly affect almost every aspect of our world. Some call it “the new fire.” In 1989 at the University of Utah, Stanley Pons and Martin Fleischmann announced they had discovered a cold fusion process that would ultimately result in cheap, limitless energy. The outcome from these cold fusion efforts became widely known and well documented, primarily because other researchers were unable to replicate the results from the initial experiments. Cold fusion was (and is) viewed as impossible by many in the scientific community. Although the research did not cease, it was largely ignored. For the past 20-plus years, a small number of scientists have been diligently working on what could eventually become a hugely disruptive technology. According to New Energy Times, “LENRs are weak interactions and neutron-capture processes that occur in nanometer-to-micron-scale regions on surfaces in condensed matter at room temperature. Although nuclear, LENRs are not based on fission or any kind of fusion, both of which primarily involve the strong interaction. LENRs produce energetic nuclear reactions and elemental transmutations, but do so without strong prompt radiation or long-lived radioactive waste.” (“Strong interaction” and “weak interaction” refer to the strong nuclear force and the weak nuclear force, which—along with electromagnetic force and gravity—make up the four basic forces in nature.)

“Low energy nuclear reactions” or LENR is the name now given to what was initially and poorly called “cold fusion”. Over twenty years of scientific research on LENR have resulted in some instances ...

We designed, fabricated and tested a novel compact fluorescence analysis system for quantification of uric acid (UA) in clinical samples at the point-of-care. To perform an analysis, diluted saliva, urine or blood samples are simply placed in a disposable thin-film sample holder using a dropper. A new enzyme immobilization technique was developed to retain within the sample holder two enzymes and a molecule, which transforms into a fluorescer in amounts depending on the UA concentration. The small instrument (7.5 cm × 5 cm × 5 cm) into which the sample holder is placed for analysis contains an LED, a narrow-band filter and an amplified photodiode. The analysis time is 30 s, and the dynamic range of the system is 4–400 μM of UA. The calibration curve for transparent saliva and urine was made using solutions of UA. The calibration curve for opaque blood was obtained with spiked samples of blood. The three different types of clinical samples were collected from three subjects and simply diluted before their measurements. Analysis with our instrument yielded UA concentrations within the expected concentration ranges. Development of instruments based on the current laboratory prototype is expected to result in products for clinical trials and point-of-care.

It is now well established that the protein BAD (a pro-apoptotic Bcl-2 family protein) plays a pivotal role in determining cell death and survival. The c-Jun N-terminal kinase (JNK) pathway has been hypothesized to be involved in regulation of BAD. To clarify the role of BAD within the JNK pathway, a randomized, controlled study was designed using a rabbit model of ischemic spinal cord injury [5,8]. Forty-five white adult New England rabbits were randomly assigned to one of the three groups: sham-operation group (n=5), vehicle group (n=20), and JNK inhibitor group (n=20). We examined alterations in spinal tissue morphology, local concentration and cellular locations of key regulatory proteins, and protein-protein interactions. Changes in spinal cord morphology were observed with hematoxylin and eosin (H&E) staining and electron microscopy. In the vehicle group, the amount of JNK phosphorylation, cytochrome c release, and the interaction between BAD and Bcl-XL or Bcl-2 were increased compared with the JNK inhibitor group. Similarly, the phosphorylation of BAD (Ser136) and the interaction between BAD and 14-3-3 were decreased in the vehicle group. Immunohistochemical studies showed that cytoplasmic location of 14-3-3 and p-BAD (Ser136) were decreased in the vehicle group compared with the JNK inhibitor group. In addition, mitochondrial morphology was better preserved and the percentage of apoptosis was lower when JNK was inhibited. These results indicate that the JNK pathway has a critical role in the survival of neurocytes by regulating the interaction between BAD and 14-3-3.

A special measurement system is developed to measure the combined noise and reliability of a three-axis micro-accelerometer. Three parametric tests are provided: gravitational, thermal and acoustical. The measurements were performed on both the in-plane and the out-of-plane axes. The temperature-dependence and acceleration-dependence of the noise was found, in agreement and contrast to the theories. The device is found to be very reliable when subjected to individual tests, but exhibits slight deviations during the combined tests.

In this work, a noise measurement of capacitive micro-accelerometers incorporating temperature effect is presented. In the setup, a hot plate is used to heat the device up to temperatures in the 75 degree C range. A thermo couple attached to the enclosure is used to assess its temperature. The data show that the noise power increases at high temperature, but not as significant as predicted by the theory.

The integration of electronics and optics with miniature fluidic systems has produced remarkable capabilities that have spawned a new industry, primarily in the past decade. Devices made by several companies, most of them start-ups, enable point-of-care analyses for clinical samples and on-site field studies, as well as providing instruments for research and development. The companies, the materials and processes they use to make devices, and the markets that are served, are the subjects of this overview of the microfluidics industry. Microfluidic chips are part of the field of microelectromechanical systems (MEMS). This is the case since they are made by the micromachining processes developed in the field of MEMS, whether or not they have moving parts. Instruments based on microfluidic chips are likely to become smaller and more widely used in the coming years. The chips themselves are candidates for even greater technical integration.

Noise measurements of micro-accelerometers were performed using a special measurement system. A common spectral behavior of noise is found, with 1/f noise dominating at low frequencies and white thermal noise being the limiting factor at higher frequencies. Unexpected resonances are also observed in the commercial devices. Most importantly, an acceleration dependent of the noise is found in analog devices and freescale accelerometers, in contrast to prevailing theory.

Microelectromechanical systems (MEMS) are devices that have static or movable components with dimensions on the scale of a micrometer. One particular device that is widely used commercially is the MEMS accelerometer. Such accelerometers typically contain some movable micro beams that measure acceleration in one or two orthogonal directions. Major markets for MEMS accelerometers are automobile airbag triggers, earthquake detection circuits and health care. MEMS accelerometers have advantages over conventional accelerometers because they are smaller, lighter and cheaper. Since MEMS accelerometers are used in many systems, the noise characteristics of these devices are very important. The noise characteristics will influence the performance of the accelerometers especially when operating at lower g conditions. In this work, we report on the noise characteristics and special measurement techniques for Analog Devices ADXL202, ADXL 105 and ADXL 190 accelerometers.

Resorufin is a fluorescent reporter molecule, the end product in a variety of biochemical analyses. In such assays, excitation sources with high intensity are desirable for fast and precise results. However, high intensity sources bleach resorufin. We report quantitative bleaching rates for resorufin subjected to green excitation over an irradiance range of 5 to about 600 mW/cm2.

A creative combination of hardware and software has produced a new digital noise spectroscopy system. It provides a low cost, user-friendly, rapid, non-destructive and non-invasive capability to acquire noise spectra. Thorough testing showed that the system has a very low noise floor (3×10−17 V2/Hz), as well as a broad frequency range (1 to 105 Hz). The system has been applied to survey solar cells with a variety of materials and geometries. In particular, we acquired noise spectra from (a) single junction Si and GaAs solar cells and (b) triple-junction solar cells that were heavily irradiated with 3 MeV protons. The results should make it possible to determine characteristics of solar cells, for example, trap densities, from the spectra. Later work will compare noise spectroscopy with normal means of characterizing solar cells.

Neointimal hyperplasia is associated with the development of diverse vascular diseases such as atherosclerosis, vein bypass graft disease and restenosis after percutaneous coronary interventions. Vascular injury-mediated neointimal hyperplasia involves the phenotypic modulation, migration and proliferation of vascular smooth muscle cells (VSMCs). Cyclic nucleotide is vital in regulating VSMC migration and proliferation, which are controlled by cyclic nucleotide phosphodiesterase (PDE) isozymes. To identify the regulation and function of PDEs in VSMC pathogenesis of vascular diseases, we performed systematic screening for all 22 known PDE genes in normal contractile VSMCs and proliferating synthetic VSMCs. Interestingly, we observed that expression of PDE1C was very low in normal contractile VSMCs but drastically elevated in synthetic VSMCs in vitro as well as in vivo in various mouse models of vascular injuries, including carotid artery ligation, femoral artery wire injury and vein bypass graft. Consistently, PDE1C is also highly induced in VSMCs in neointimal lesion of human coronary artery. More importantly, injury-induced neointimal formation was significantly attenuated in pde1c-deficient mice or by perivascular administration of PDE1 inhibitor. Furthermore, PDE1 inhibition also reduced the spontaneous vascular remodeling of human saphenous vein explant in an ex vivo culture model. Mechanistic studies revealed that PDE1C plays a critical role in regulating the stability of PDGF receptor beta (PDGFR-β). We found that PDE1C knockdown or inhibition markedly decreased the levels of PDGFR-β protein but not mRNA, which was blocked by endosome and lysosome inhibitors. Furthermore, PDE1C inhibition is capable of promoting PDGFR-β internalization and attenuating PDGFR-β membrane accumulation. Finally, we found that PDE1C co-localized with PDGFR-β on cell membrane, which was able to regulate PDGFR-β protein degradation through modulating a transmembrane adenylyl cyclase-cAMP-PKA signaling. Taken together, our present data demonstrated that PDE1C plays a critical role in regulating VSMC proliferation and neointimal hyperplasia, in part, through promoting endosome/lysosome dependent PDGFR-β protein degradation.

The advancement of science and technology normally occurs through evolutionary research and development. These activities and their fruits, knowledge and capabilities, might be very interesting and useful, but they normally do not challenge our overall view of the world. When something revolutionary comes to light, the potential paradigm shift, then we are forced to examine both our knowledge and our beliefs, which are intertwined. The topic called “cold fusion” caused reexamination of the physics of nuclear reactions and some aspects of the philosophy of science. We will consider these factors after a brief introductory survey of the complex experiments and results reported in the field, and the motivations for continued attention. “Cold fusion” is used here as an accepted label for the arena of interest, and not a statement about whatever processes might be involved. 1

Objective— The phenotypic modulation of vascular smooth muscle cells (VSMCs) to a synthetic phenotype is vital during pathological vascular remodeling and the development of various vascular diseases. An increase in type I collagen (collagen I) has been implicated in synthetic VSMCs, and cyclic nucleotide signaling is critical in collagen I regulation. Herein, we investigate the role and underlying mechanism of cyclic nucleotide phosphodiesterase 1 (PDE1) in regulating collagen I in synthetic VSMCs. Methods and Results— The PDE1 inhibitor IC86340 significantly reduced collagen I in human saphenous vein explants undergoing spontaneous remodeling via ex vivo culture. In synthetic VSMCs, high basal levels of intracellular and extracellular collagen I protein were markedly decreased by IC86340. This attenuation was due to diminished protein but not mRNA. Inhibition of lysosome function abolished the effect of IC86340 on collagen I protein expression. PDE1C but not PDE1A is the major isoform responsible for mediating the effects of IC86340. Bicarbonate-sensitive soluble adenylyl cyclase/cAMP signaling was modulated by PDE1C, which is critical in collagen I degradation in VSMCs. Conclusion— These data demonstrate that PDE1C regulates soluble adenylyl cyclase/cAMP signaling and lysosome-mediated collagen I protein degradation, and they suggest that PDE1C plays a critical role in regulating collagen homeostasis during pathological vascular remodeling.

MEMS accelerometers are extensively employed in various consumer applications due to their rapidly decreasing costs. In order to meet the low-cost requirements, manufacturers are forced to sacrifice some design parameters that may degrade their accelerometers' reliabilities. Interestingly, there is not much published works on the reliability aspects of MEMS accelerometers. Two reports detailed the reliability qualitative assessment on commercial devices [1–2]. Both works concluded that MEMS accelerometers are high reliable devices with low failure rates. In a recent study [3], a procedure to perform the quantitative accelerated life testing (QALT) on tri-axis accelerometer from STM was proposed, with a crude setup to vary the accelerations and temperatures. The purpose of this paper is to employ the QALT procedure on single axis accelerometers from Analog Device and Freescale. Laser-precision apparatus was designed, built, and employed to provide three types of excitations with great accuracy; mechanical (gravitational) test, thermal test and acoustical test. These tests are designed to mimic the operating conditions of the system, where the devices are employed.

Rationale: Cyclic nucleotide phosphodiesterases (PDEs) through the degradation of cGMP play critical roles in maintaining cardiomyocyte homeostasis. Ca 2+ /calmodulin (CaM)-activated cGMP-hydrolyzing PDE1 family may play a pivotal role in balancing intracellular Ca 2+ /CaM and cGMP signaling; however, its function in cardiomyocytes is unknown. Objective: Herein, we investigate the role of Ca 2+ /CaM-stimulated PDE1 in regulating pathological cardiomyocyte hypertrophy in neonatal and adult rat ventricular myocytes and in the heart in vivo. Methods and Results: Inhibition of PDE1 activity using a PDE1-selective inhibitor, IC86340, or downregulation of PDE1A using siRNA prevented phenylephrine induced pathological myocyte hypertrophy and hypertrophic marker expression in neonatal and adult rat ventricular myocytes. Importantly, administration of the PDE1 inhibitor IC86340 attenuated cardiac hypertrophy induced by chronic isoproterenol infusion in vivo. Both PDE1A and PDE1C mRNA and protein were detected in human hearts; however, PDE1A expression was conserved in rodent hearts. Moreover, PDE1A expression was significantly upregulated in vivo in the heart and myocytes from various pathological hypertrophy animal models and in vitro in isolated neonatal and adult rat ventricular myocytes treated with neurohumoral stimuli such as angiotensin II (Ang II) and isoproterenol. Furthermore, PDE1A plays a critical role in phenylephrine-induced reduction of intracellular cGMP- and cGMP-dependent protein kinase (PKG) activity and thereby cardiomyocyte hypertrophy in vitro. Conclusions: These results elucidate a novel role for Ca 2+ /CaM-stimulated PDE1, particularly PDE1A, in regulating pathological cardiomyocyte hypertrophy via a cGMP/PKG-dependent mechanism, thereby demonstrating Ca 2+ and cGMP signaling cross-talk during cardiac hypertrophy.

It has been well established over recent years that synchrotron radiation possesses some unique features as a source of primary x-rays for x-ray fluorescence analysis. Advantage has been taken of the high intensity emanating from the bending magnets of storage rings to develop x-ray microprobes utilizing apertures or focussing optics, or both, to provide a beam spot at the specimen of the order of micrometers. The use of insertion devices wigglers and undulatora, can further increase the available intensity, especially for the high energy photons. Beam Line X-17C at the National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory, accepts the unmodified continuum radiation from a superconducting wiggler in the storage ring. Some initial XRF measurements have been made on this beam line using apertures in the 10 to 100 micrometer range. The fluorescent radiation was measured by an intrinsic Ge detector having an energy resolution of 300 eV at 15 kev, and located at 90° to the incident beam in the plane of the electron orbit. In samples containing many elements, detection limits of a few ppm were achieved with 100 μm beams.

The integration of semiconductor electronics and diverse optics with miniature MEMS fluidic systems has produced remarkable capabilities, which have spawned a new industry, primarily in the past decade. Microfluidics devices made by several companies, most of them start-ups, enable point-of-care analyses for clinical samples and on-site field studies, as well as instruments for research and development. The companies, the materials and processes they use to make devices, the techniques employed for detection, and the markets are the subjects of this overview of the microfluidics industry.

The authors performed the low frequency noise measurement (LFNM) technique to study noise characteristics of commercial accelerometers with single and dual axis. In this work, we studied the noise characteristics of a three-axis accelerometer using an improved and sensitive test setup to avoid cross-axis distortion.

Appling security to messages traveling over wireless links in sensor nodes requires additional energy. This paper describes our suggestions on balancing the level of security and energy consumption based on our measurements using CrossBow and Ember sensor nodes. It was found that the node microcontroller's CPU operates for substantially longer times for both hashing and encryption operations compared to the time for handling messages without any security. However, this has little overall impact on energy consumption. The longer high-power radio transmission times due to hashing were especially costly. For the full operational mode, with CPU processing and also radio transmission of messages, our results indicate that the lifetime of a transmitting node in a security regime is only about one-half of the lifetime without security. Hence, we provided design guidelines to apply security with energy consideration for WSN. They include 2 to 8 bytes MACs for integrity and authentication instead of SHA-1, and the size of messages should match the steps of encryption algorithms.

WSN nodes are usually powered by batteries. Energy consumption during node operation determines battery life. Power consumption depends on the different hardware and software components in a WSN node and their various activities. In order to determine the life of the battery, we must measure the energy consumption of a node that is active in a network. That is, we must know the power consumption and time duration for node activities including computations, and RF transmission and reception. In this paper, we introduce an easy and accurate method for dynamic energy measurements without disturbing the node or network. The method consists of an oscilloscope, which can stream digitized voltages into a PC, which calculates the profile of energy consumption. We employed this capability to determine energy consumption for different security algorithms in CrossBow MICA2 nodes.

Both correct transmission using hashing and protection of messages using encryption in sensor nodes require additional energy. This paper describes our measurement results for energy consumption in CrossBow and Ember sensor nodes for the process of exchanging data messages between nodes both in the clear and in a protected form. Full strength algorithms were loaded into and executed in nodes. It was found that the CPU operates for substantially longer times for both hashing and encryption operations compared to the time for handling messages without any security. The longer radio transmission times due to hashing were especially costly. Hence, security algorithms have great impacts on energy consumption in sensor nodes. For the full operational mode, with CPU processing and also radio transmission of messages, our results indicate that the lifetime of a transmitting node in a security regime is only about one-half of the lifetime without security.

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK), which plays a pivotal role in cell apoptosis. To determine the mechanism of ASK1 induction during reperfusion of ischemic spinal tissue, we used a model of rabbit spinal cord ischemia and reperfusion. To assess the role of ASK1 in spinal cord ischemia-reperfusion injuries, we examined alterations in spinal tissue morphology, protein–protein interactions, and activation of key members of the ASK1-mediated signaling pathway. Changes in spinal cord morphology were observed with hematoxylin and eosin (H&E) staining and electron microscopy. The phosphorylation levels of ASK1, JNK, and p38 were assessed by immunoblotting proteins from animals that received 30 min of ischemia followed by 1 or 24 h of reperfusion. We observed increased phosphorylation of ASK1, JNK, and p38 after reperfusing ischemic spinal cords. Immunohistochemical studies were performed to determine the cellular localization of phosphorylated ASK1 (pASK1) and 14-3-3. Following reperfusion for 24 h, we observed increased cytoplasmic localization of pASK1 and decreased cytoplasmic localization of 14-3-3. Immunoprecipitation analyses suggested that 14-3-3 dissociates from ASK1 during reperfusion of ischemic spinal cords. These results indicate that activation of ASK1 may play an important role in the apoptotic signaling mechanisms that occur in reperfused spinal cord injuries.

Sensors are systems or devices that provide signals, which are correlated to some physical, chemical, or biological condition in their neighborhood. The signals can be transformed, by use of a calibration curve, into information about the environment of a sensor. There are two classes of sensors, point sensors that provide information only from their immediate surroundings and volume sensors (imagers or cameras) that can give information on conditions in an extended region. Sensors are old, but recent advances in miniaturization technologies have been leading to very small and capable sensors. Micromachining processes, which grew out of the microelectronics industry, have been used for about two decades to make microelectromechanical systems (MEMS) that are relative cheap and extraordinarily reliable. Microsensors for pressure and acceleration are now sold by the tens of millions annually. In the past decade, processes have been developed to grow nano-materials, which have structures on the scale of molecules. They are proving to be very useful for small sensors, especially for chemical and biological applications. Two-dimensional arrays of bio-sensors, based on DNA or antibodies to recognize the target molecules in a sample, are especially important. They, and other small sensors, enable almost immediate diagnostics at the point of care, rather than sending samples to a central laboratory. Small sensors make it possible to put diagnostic equipment inside the body. They are expected to have an increasing impact on biomedical engineering and clinical medicine. Keywords: sensors; microsensors; nano-sensors; microtechnology; nano-technology; chemical sensors; bio-sensors; clinical medicine

In response to biological and mechanical injury, or in vitro culturing, vascular smooth muscle cells (VSMCs) undergo phenotypic modulation from a differentiated “contractile” phenotype to a dedifferentiated “synthetic” one. This results in the capacity to proliferate, migrate, and produce extracellular matrix proteins, thus contributing to neointimal formation. Cyclic nucleotide phosphodiesterases (PDEs), by hydrolyzing cAMP or cGMP, are critical in the homeostasis of cyclic nucleotides that regulate VSMC growth. Here, we demonstrate that PDE1A, a Ca 2+ -calmodulin–stimulated PDE preferentially hydrolyzing cGMP, is predominantly cytoplasmic in medial “contractile” VSMCs but is nuclear in neointimal “synthetic” VSMCs. Using primary VSMCs, we show that cytoplasmic and nuclear PDE1A were associated with a contractile marker (SM-calponin) and a growth marker (Ki-67), respectively. This suggests that cytoplasmic PDE1A is associated with the “contractile” phenotype, whereas nuclear PDE1A is with the “synthetic” phenotype. To determine the role of nuclear PDE1A, we examined the effects loss-of-PDE1A function on subcultured VSMC growth and survival using PDE1A RNA interference and pharmacological inhibition. Reducing PDE1A function significantly attenuated VSMC growth by decreasing proliferation via G 1 arrest and inducing apoptosis. Inhibiting PDE1A also led to intracellular cGMP elevation, p27 Kip1 upregulation, cyclin D1 downregulation, and p53 activation. We further demonstrated that in subcultured VSMCs redifferentiated by growth on collagen gels, cytoplasmic PDE1A regulates myosin light chain phosphorylation with little effect on apoptosis, whereas inhibiting nuclear PDE1A has the opposite effects. These suggest that nuclear PDE1A is important in VSMC growth and survival and may contribute to the neointima formation in atherosclerosis and restenosis.

Pd employed as cathodes in cold fusion experiments contains various defects, each of which has an associated energy. In principle, some of the energy in Pd due to defects that exist before a cold fusion experiment could be released as apparent excess heat during the experiment. Energy densities were computed for high concentrations of vacancies, impurities (both substitutional and interstitial atoms), dislocations and grain boundaries, as well as for strains. It is concluded that pre-existing defects and strains cannot account for the energies released during cold fusion experiments. Nonetheless, defects may play other supporting or central roles in cold fusion.

This chapter provides an overview of micro electro mechanical systems (MEMS). The sequential steps in their production are then reviewed, namely design, simulation, fabrication, packaging, and testing. The reliability of MEMS is considered from the viewpoint of their performance in actual applications. The applications of micromachined static MEMS, micromechanical MEMS sensors and actuators, and functional MEMS systems are also surveyed. Micro electro mechanical systems are devices that have static or moveable components with some dimensions on the scale of a micrometer to nanometer. MEMS combine microelectronics and micromechanics and sometimes microoptics and micromagnetics. MEMS are already important devices in several major industries. Both the variety of available mechanical microdevices and their applications grow rapidly in the foreseeable future.

This chapter illustrates a framework for relating and comparing technologies for the transfer of patterns and materials with micrometer and nanometer resolution. It discusses the basic concepts for each technology by providing some references and examples. Methods for the production and assembly of parts vary widely. The micrometer scale involves parallel production of objects, using pattern transfer and other methods, with layering or bonding being primary methods of assembly. In the nanometer regime, a different approach to the production of objects is followed. The bottom-up approach of chemistry and biology dominates nanometer technology. Molecular synthesis and self-assembly are used as primary approaches for making functional systems on the nanometer scale. The chapter provides an overview of self assembly, in which both the material and pattern are effectively transferred at once. The material essentially contains its own patterning information, which may or may not be expressed, depending on conditions at the time of transfer and subsequently.

Programmable methods for transferring materials to surfaces in patterns can produce structures with micrometer and nanometer scale features. All such technologies involve combinations of information, materials and energy. The materials in additive technologies can originate in the vapor phase, as liquids or suspensions, or as solids. The energy can come from laser, electron or ion beams, or the pressures used in writing, dispensing, jetting or flow methods. Many of the programmable techniques do not require high temperatures, so they can be used to make fine-scale structures of organic and bio-materials, and even live biologicals. Quantitative comparisons of both additive and subtractive programmable methods show that only a few, based on electron or ion beams, or on proximal probes, are capable of making nanometer-scale structures. Assembly methods, notably self- and directed-assembly, should prove to be central to the realization of manufacturable nanotechnology. Programmable deposition technologies may be used to supply materials for, and otherwise control self-assembly processes. The four sets of technologies, namely masked lithography, direct-write techniques, self-assembly and directed-assembly, provide a versatile and powerful toolbox for making micro-and nano-meter scale devices and systems.