Angioedema is a localized, non-pitting, non-dependent, submucosal, and subcutaneous swelling resulting from the extravasation of fluid into the interstitium due to the increased production of plasma kinins and histamine. It can present with urticaria or anaphylaxis and is usually associated with angiotensin-converting enzyme inhibitors (ACEis), complement deficiencies, or the side effects of tissue plasminogen activator (tPA). Orolingual angioedema following tPA for acute ischemic stroke is a transient, self-resolving hemifacial swelling contralateral to neurological deficits that can rarely progress to the airway, compromising it and leading to a life-threatening situation if not managed promptly.

Although optical fibers and specialty waveguides are the base of majority of today's telecom and light delivery applications, fabrication deformation, nonlinearity and attenuation limit the bandwidth of the data being transmitted or the amount of power carried by these systems. One-way to overcome these limitations without changing the fibers design or fabrication is to engineer the input light in order to excite a certain mode or a group of modes with unique optical properties. Diffractive and micro optics are highly effective for selectively coupling light to specific modes. Using micro optics, mode selective coupling can be achieved through several matching schemes: phase only, phase and amplitude, or phase, amplitude and polarization. The main scope of this work is the design and fabrication of novel optical elements that overcome the limitations of these light delivery systems, as well as the characterization and analysis of their performance both experimentally and using numerical simulation

Over a wide range of applications, optical systems have utilized conventional optics in order to provide the ability to engineer the properties of incident infra-red fields in terms of the transmitted field spectral, spatial, amplitude, phase, and polarization characteristics. These micro/nano-optical elements that provide specific optical functionality can be categorized into subcategories of refractive, diffractive, multi-layer thin film dichroics, 3-D photonic crystals, and polarization gratings. The feasibility of fabrication, functionality, and level of integration which these elements can be used in an optical system differentiate which elements are more compatible with certain systems than others. With enabling technologies emerging allowing for a wider range of options when it comes to lithographic nano/micro-patterning, dielectric growth, and transfer etching capabilities, optical elements that combine functionalities of conventional optical elements can be realized. Within this one class of optical elements, it is possible to design and fabricate components capable of tailoring the spectral, spatial, amplitude, phase, and polarization characteristics of desired fields at different locations within an optical system. Optical transmission filters, polarization converting elements, and spectrally selective reflecting components have been investigated over the course of this dissertation and have been coined  MOSSE,' which is an acronym for micro-optic-spectral-spatial-elements. Each component is developed and fabricated on a wafer scale where the thin film deposition, lithographic exposure, and transfer etching stages are decoupled from each other and performed in a sequential format. This facilitates the ability to spatially vary the optical characteristics of the different MOSSE structures across the surface of the wafer itself.

Aufgrund des rasanten technischen Fortschritts, unter anderem bedingt durch Megatrends wie Funktionsintegration, Individualisierung oder Digitalisierung, sind die Produkte aber auch die Prozesse einem stetigen Wandel unterworfen. Die ehemals systembestimmende Mechanik wird auch in Zukunft noch das Grundgerüst stellen, das elektrisch angetrieben und durch komplexe informationstechnische Einheiten gesteuert wird. Längst ist die Software jedoch zu einem wesentlichen Innovationstreiber im Maschinen- und Anlagenbau geworden.

Marine and hydrokinetic (MHK) energy, including ocean waves, tidal current, ocean current and river current, has been recognized as a promising power source due to its full-day availability and high energy potential. At this stage, ocean current energy, tidal energy and ocean wave energy are currently the most competitive sourves among all the categories of MHK. The state of art MHK energy harvesting technology mainly focus on harvesting either ocean wave energy or current energy, but not both. However, a significant amount of ocean waves and tidal/ ocean current coexist in many sites and traditional devices that harvest from a single form of MHK energy, cannot make full use of the coexisting ocean energy. Furthermore, MHK energy harvesting devices need to advance to be cost-effective and competitive with other energy sources. This is difficult to achieve. Ocean wave excitation is irregular, which means that ocean wave height and wave periods are unpredictable and excitation forces on energy harvesting devices can have large variance in amplitude and frequency. Such problems/ restrictions can be possibly addressed by the concept of a hybrid energy converter. In this sense, a hybrid wave-current ocean energy conveter (HWCEC) that simutaneously harvests energy from current and wave with one single power takeoff (PTO) is designed.The wave energy is extracted through relative heaving motion between a floating buoy and a submerged second body, while the current energy is extracted using a marine current turbine (MCT). Energy from both sources are integrated by a hybrid PTO whose concept is based on a mechanical motion rectifier (MMR). In this study, different working modes are investigated together with switching criteria.Simulations were conducted with hydrodynamic coefficients obtained from computational fluid dynamics analysis and boundary element method. Tank tests were conducted for a HWCEC under co-existing wave and current inputs. For comparison, separate baseline tests of a turbine and a two-body point absorber, each acting in isolation, are conducted. Experimental results validate the dynamic modeling and show that a HWCEC can increase the output power with a range between 29-87 percent over either current turbine and wave energy converter acting individually, and it can reduce by up to 70 percent the peak-to-average power ratio compared with the wave energy converter on the tested conditions.Such results demonstrate the potential of the HWCEC as an efficient and cost-effective design. / Master of Science / Ocean energy has been recognized as a promising power source due to its full-day availability and high energy potential. At this stage, ocean current energy, tidal energy and ocean wave energy are currently the most competitive sources among all the categories of ocean energy. The state of art ocean energy harvesting technology mainly focus on harvesting either ocean wave energy or current energy, but not both. However, a significant amount of ocean waves and tidal/ ocean current coexist in many sites and traditional devices that harvest from a single form of ocean energy, cannot make full use of the coexisting energy resource. Furthermore, MHK energy harvesting devices need to advance to be cost-effective and competitive with other energy sources. This is difficult to achieve. Ocean wave height and wave periods are unpredictable and excitation forces on energy harvesting devices can have large variance in amplitude and frequency. Such restrictions can be possibly addressed by the concept of a hybrid energy converter. In this sense, a hybrid wave-current ocean energy converter (HWCEC) that simultaneously harvests energy from current and wave with one single power takeoff (PTO), which consists of ball screw, gearbox, and generator, is designed.The wave energy is extracted through relative heaving motion between a floating buoy and a submerged second body, while the current energy is extracted using a marine current turbine (MCT). Energy from both sources are integrated by a hybrid PTO whose concept is based on a mechanical motion rectifier (MMR). In this study, different working modes are investigated together with switching criteria.Simulations were conducted with hydrodynamic coefficients obtained from computational fluid dynamics analysis and boundary element method. Tank tests were conducted for a HWCEC under co-existing wave and current inputs. For comparison, separate baseline tests of a turbine and a two-body, wave-energy-harvesting structure, each acting in isolation, are conducted. Experimental results validate the dynamic modeling and show that a HWCEC can increase the output power with a range between 29-87 percent over either current turbine and wave energy converter acting individually, and it can reduce by up to 70 percent the peak-to-average power ratio compared with the wave energy converter on the tested conditions.Such results demonstrate the potential of the HWCEC as an efficient and cost-effective design.

No / Quality by design (QbD) is an essential part of the modern approach to pharmaceutical quality. This study was conducted in the framework of a QbD project involving ramipril tablets. Preliminary work included identification of the critical quality attributes (CQAs) and critical process parameters (CPPs) based on the quality target product profiles (QTPPs) using the historical data and risk assessment method failure mode and effect analysis (FMEA). Compendial and in-house specifications were selected as QTPPs for ramipril tablets. CPPs that affected the product and process were used to establish an experimental design. The results thus obtained can be used to facilitate definition of the design space using tools such as design of experiments (DoE), the response surface method (RSM) and artificial neural networks (ANNs). The project was aimed at discovering hidden knowledge associated with the manufacture of ramipril tablets using a range of artificial intelligence-based software, with the intention of establishing a multi-dimensional design space that ensures consistent product quality. At the end of the study, a design space was developed based on the study data and specifications, and a new formulation was optimized. On the basis of this formulation, a new laboratory batch formulation was prepared and tested. It was confirmed that the explored formulation was within the design space.

No description available.

Thesis (Ph. D.)--Ohio State University, 2007. / Full text release at OhioLINK's ETD Center delayed at author's request

Angiotensin converting enzyme (ACE) catalyzes the conversion of angiotensin I (Ang I) to angiotensin II (AngII). ACE also cleaves the terminal dipeptide of vasodilating hormone bradykinin (a nonapeptide) to its inactive form. Therefore, inhibition of ACE is one of the treatments of hypertension. A number of ACE inhibitory antihypertensive drugs are known. ‘Oxidative stress’ is another disease state caused by an imbalance in the production of oxidants and antioxidants in the body. A number of studies suggest that hypertension and oxidative stress are interdependent. Therefore, ACE inhibitors having antioxidant property are considered beneficial for the treatment of hypertension. Generally, selenium compounds exhibit better antioxidant behavior than their sulfur analogues. Therefore, we have synthesized a number of selenium analogues of captopril, an ACE inhibitor used as antihypertensive drug. Similar to captopril, the selenium analogues of captopril exhibited excellent ACE inhibition property. It was observed that these compounds are very good scavengers of peroxynitrite (PN), a strong oxidizing as well as nitrating agent found in vivo. The orientation of the chiral centers in these compounds was found to be very important for their ACE inhibition behavior. A number of selenocysteine- and cysteine-containing dipeptides and tripeptides were synthesized as inhibitors of ACE. It was observed that the ACE inhibition properties of these compounds depend on various factors such as orientation of the amino functionality, substitution at the C-terminal of the inhibitor, ring size of the proline moiety or the availability of the terminal acid group in carboxylate form etc. A structure-function correlation was drawn for the ACE inhibition properties of the peptide-based selenium-or sulfur-containing compounds. These studies reveal that the antioxidant properties do not depend on the side-chain functional groups, but they depend on the availability of selenium or sulfur centers. Selenium-based compounds were found to be better antioxidants than those containing sulfur moieties. In conclusion, the present study reveals that the replacement of sulfur atom in captopril and its analogues by selenium enhances the antioxidant activity. The reaction products of lactoperoxidase (LPO)-catalyzed iodination of Ang II were separated and characterized. It was observed that LPO-catalyzed iodination of Ang II takes place preferentially at the tyrosine residue. LPO-catalyzed iodination of Ang II is inhibited by commonly used antithyroid drugs such as MMI, MTU, PTU and also by antihypertensive drug captopril. It was also observed that the monoiodo Ang I is a better substrate for ACE compared to the natural substrate Ang I. The site of nitration of Ang II by PN was also determined by MS-MS analyses. This study reveals that the nitration takes place at the tyrosine residue.

Obesity is strongly associated with hypertension and cardiovascular diseases. An activated renin-angiotensin system (RAS) has long been suggested as a critical contributor to elevated blood pressure with obesity. Angiotensin II (AngII), the main effector of an activated RAS, can be catabolized by angiotensin-converting enzyme 2 (ACE2) to form angiotensin-(1-7) (Ang-(1-7)), which, acting through the mas receptor (MasR), has been shown to oppose the effects of an activated RAS. Therefore, further understanding of the mechanisms of this counter-regulatory arm, called the ACE2/Ang-(1-7)/MasR axis, may lead to new therapies for obesity-induced hypertension. Previously, we demonstrated that differences in the regulation of ACE2 in a tissue-specific manner contribute to sexual dimorphism of diet-induced obesity-hypertension in mice. Whereas male mice fed a high fat (HF) diet developed hypertension, HF-fed female mice were protected from obesity-hypertension, and this was associated with increased activity of ACE2 in adipose tissue of females. Both upregulation of adipose ACE2 and protection against obesity-hypertension were lost when females were ovariectomized (OVX). We hypothesized that estrogen-mediated increases in adipose ACE2 reduce the AngII/Ang-(1-7) peptide balance and protect females from obesity-hypertension. To test this hypothesis, we first determined if estrogen restores protection of Ovx female mice from obesity-hypertension, and therapeutically protects male mice from obesity-hypertension. We demonstrated that estrogen administration to Ovx HF-fed females activates adipose ACE2, reduces plasma Ang II concentrations, and decreases blood pressure in wildtype, but not of ACE2-deficient obese females. In contrast, estrogen administration to HF-fed male mice had no on the development of obesity-hypertension, regardless of genotype. These results demonstrate that estrogen protects female mice from obesity-hypertension through an ACE2-dependent mechanism. Next we defined the role of MasR deficiency on the development of obesity-hypertension in male and female mice. In HF-fed MasR-deficient female mice, diastolic blood pressure (DBP) was significantly elevated compared to LF-fed controls, suggesting that protection from obesity-hypertension was abolished by MasR deficiency. In contrast, HF-fed male mice with MasR deficiency exhibited reduced blood pressure compared to wildtype controls which was associated with reduced cardiac function. Overall, these studies indicate that the ACE2/Ang-(1-7)/MasR axis plays an important role in sexual dimorphism of obesity-hypertension, and in the regulation of cardiac function. Moreover, these studies suggest that the effects of this counter-regulatory arm of the RAS may be sex-specific.