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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.

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.

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.

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.

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.

Optical fluorescence and absorption are two of the primary techniques used for analytical microfluidics. We provide a thorough yet tractable method for computing the performance of diverse optical micro-analytical systems. Sample sizes range from nano- to many micro-liters and concentrations from nano- to milli-molar. Equations are provided to trace quantitatively the flow of the fundamental entities, namely photons and electrons, and the conversion of energy from the source, through optical components, samples and spectral-selective components, to the detectors and beyond. The equations permit facile computations of calibration curves that relate the concentrations or numbers of molecules measured to the absolute signals from the system. This methodology provides the basis for both detailed understanding and improved design of microfluidic optical analytical systems. It saves prototype turn-around time, and is much simpler and faster to use than ray tracing programs. Over two thousand spreadsheet computations were performed during this study. We found that some design variations produce higher signal levels and, for constant noise levels, lower minimum detection limits. Improvements of more than a factor of 1,000 were realized.

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.

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.

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

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.

Facile, integrated and comprehensive software is needed for the design of processes, models and simulation, which are required for effective production of MEMS and microsystems. The characteristics of computer-aided design software now available from seven companies are reviewed. Three of the firms have roots in microelectronics, and three were formed specifically for MEMS design. Electronic, mechanical, thermal and fluidic mechanisms are commonly included. One company is especially strong in microfluidics. Two of the design suites permit computational coupling between a MEMS device and its package. High spatial- and temporal- resolution optical diagnostics are now producing detailed data that will challenge design and simulation software for MEMS and microsystems. Near and far term prospects for the CAD of MEMS and microsystems are projected.

This review provides a comprehensive survey of noise research in MEMS. Some background on noise and on MEMS is provided. We review noise production mechanisms, and highlight work on the theory and modeling of noise in MEMS. Then noise measurements in the specific types of MEMS are reviewed. Inertial MEMS (accelerometers and angular rate sensors), pressure and acoustic sensors, optical MEMS, RF MEMS, surface acoustic wave devices, flow sensors, and chemical and biological MEMS, as well as data storage devices and magnetic MEMS, are reviewed. We indicate opportunities for additional experimental and computational research on noise in MEMS.

A high vacuum soft x-ray source has been coupled to a large volume experimental chamber to provide a versatile facility for x-ray investigations in the energy range of 0.1 to 10 kev. The source chamber presently contains a modified Herike tube, but can employ any of a variety of source designs. The large experimental chamber is equipped with a kinematic mount to position a number of x-ray optical instruments. The source and experimental chambers are connected through a high vacuum valve/shutter, and are pumped separately with provision for a thin window to isolate one from the other, single and double crystal spectrometers have been used in the experimental chamber. A variable chord diffractometer/reflectometer using double crystal monnotiromatization has been designed, in addition, the facility has been used to expose photoresists in x-ray lithography tests.