Vibration analysis utilizing Mossbauer effect

Measuring instrument analyzes mechanical vibrations in transducers at amplitudes in the range of a few to 100 angstroms. This instrument utilizes the Mossbauer effect, the phenomenon of the recoil-free emission and resonant absorption of nuclear gamma rays in solids

The role of Fas and Fas ligand in apoptosis during regression of the corpus luteum

Apoptosis, a form of physiological cell death, has been found to occur during regression of the corpus luteum (Juengel etal, 1993; Dharmarajan etal, 1994). The pathways involved in this process, however, have yet to be specified. One possible mediator of corpus luteum regression is the Fas (or AP0-1 or CD95) receptor, a transmembrane protein which induces apoptosis in the cell when ligated. In order to further confirm this hypolhesis, the present study establishes and quantitates the presence and regulation of Fas receptor and Fas ligand (Fasl) in the rat corpus luteum during pregnancy and post-partum. The animals used were sexually mature (1 0-12 week old) female Wistar rats. The presence of Fas and Fasl in the rat corpus luteum at various stages of pregnancy and post-partum was investigated by immunohistochemistry using an anti-Fas monoclonal antibody and an anti-FasL polyclonal antibody. FasL was localised in corpora lutea throughout pregnancy, whilst Fas was localised at day 1 of pregnancy and at the time of luteolysis. Information on the steady state mRNA levels of Fasl was obtained using relative quantitative reverse transcription PCR (RT-PCR) analysis of RNA isolated from rat ovaries at various stages of pregnancy and post-partum. Expression of Fasl mRNA increased significantly at day 22 of pregnancy, just prior to parturition, and decreased by day 3 post-partum. The ability of an anti-rat Fas monoclonal antibody to block spontaneous apoptosis in corpora lutea placed in an in vitro culture model with serum-free medium was examined by analysis of extracted DNA using 3\u27-end labelling. Treatment with an anti-rat Fas monoclonal a11tibody demonstrated a reduction in the occurrence of spontaneous apoptosis. Roles for Fas receptor and Fas ligand in corpus luteum function were proposed, and the suitability of the in vitro corpus luteum culture model for future studies investigating molecular mechanisms of Fas-mediated apoptosis in the corpus luteum was discussed

Identification of a candidate CO2 sensor from Helicobacter pylori

Carbon dioxide (CO2) is a ubiquitous metabolite. It is fundamental in pathogenesis, involved in the activation of signalling pathways. Several species of human pathogens harbour CO2 sensing mechanisms that allow for the coupling of virulence factor expression to host CO2 levels, facilitating colonisation and persistence. Helicobacter pylori is an example of a human pathogen for which CO2 is especially important in its biology – requiring CO2 for growth and generating CO2 as a result of urease activity. However, what remains unclear are the details of the mechanisms underpinning CO2 sensing and the identity of CO2 sensors. A candidate mechanism by which CO2 sensing may occur is the direct modification of regulatory proteins, termed carbamylation, entailing the nucleophilic attack of a neutral N-terminal α-amino group or ε-amino group of Lys onto CO2, forming a carbamate. While carbamates observed to date, such as those in haemoglobin and RuBisCO, have significant functional roles, their systematic identification has been limited by their lability and the lack of a tool for their direct investigation, until recently. This thesis sought to assess the validity of the H. pylori nickel-responsive regulator (HpNikR) as a CO2 sensor, using carbamylation as a mechanism to achieve this, given its pleiotropic regulatory activity, the importance of Lys residues in its DNA binding, and its responsiveness to the environmental cues of Ni(II) availability and pH. Carbamylation would affect DNA binding, which in turn would affect gene expression and allow H. pylori to adapt to fluctuating CO2 levels, potentially in accordance with urease activity. Modification of a conserved Lys was detected, DNA binding assays showed this modification reduced DNA affinity, and this effect was reduced in a mutant insensitive to carbamate formation. This suggests that HpNikR may indeed behave as a CO2 sensor, potentially coupling gene transcription to this additional environmental cue

Public Wars, Private Warriors: An Analysis of Private Military Contractors in American Foreign and Domestic Policy

At the end of the Cold War, the global political arena was forever altered. One of the major changes was the introduction of private military contractors as legitimate actors of foreign policy. Despite this assertion made by scholars, private military contractors are an under studied political actor. This paper traces the historical, economic, and legal legacy of private military contractors in American history

The Relationship Between Course Delivery Mode and Location with Course Success for Dual Enrolled Students

High school dual enrollment has increased dramatically in recent years, growing 75% nationally between academic years 2002-03 and 2010-11 (Borden, Taylor, Park, & Seiler, 2013). Proponents of dual enrollment programs cite long-term, positive student outcomes for dual enrollment students: higher GPAs in college as adults (Allen & Dadgar, 2012; Jones, 2014; Karp, Calcagno, Hughes, Jeong, & Bailey, 2007), higher first year persistence rates in college (Jones, 2014; Karp et al., 2007), faster time to degree completion (Allen & Dadgar, 2012; Ganzert, 2014; Hughes, 2016), and higher college graduation rates (Ganzert, 2014; Hughes, 2016). However, very little research has focused on short-term success for dual enrolled students. Course grades earned in dual enrollment programs become a part of the student’s official college transcript. As such, these grades can impact a student’s ability to be accepted at post-secondary institutions after graduation from high school. In addition, poor grades in dual enrollment courses can negatively affect satisfactory academic progress standards, thus impacting financial aid eligibility as an adult. Therefore, it is important to understand any factors which might improve the chances of student course-level success. This causal comparative study used ex post facto data from four community colleges to examine the correlation between course delivery location (high school or college campus) for college classes taken by dual enrolled students to student success as defined by final grades in those courses. In addition, this study examined the correlation between course delivery mode (face-to-face, hybrid, or online) for college classes taken by dual enrolled students to student success as defined by final grades in those courses. The study findings indicated dual enrolled students taking classes on high school sites had higher course grades compared to dual enrolled students taking classes on a college campus. A subset model utilizing data from just one college, however, indicated the opposite. The results also indicated that dual enrolled students taking classes delivered in face-to-face and hybrid modes had higher course grades compared to dual enrolled students taking classes delivered in a fully internet mode. Again, a subset model utilizing data from just one college indicated the opposite

Development of Computer-Aided Molecular Design Methods for Bioengineering Applications

Computer-aided molecular design (CAMD) offers a methodology for rational product design. The CAMD procedure consists of pre-design, design and post-design phases. CAMD was used to address two bioengineering problems: design of excipients for lyophilized protein formulations and design of ionic liquids for use in bioseparations. Protein stability remains a major concern during protein drug development. Lyophilization, or freeze-drying, is often sought to improve chemical stability. However, lyophilization can result in protein aggregation. Excipients, or additives, are included to stabilize proteins in lyophilized formulations. CAMD was used to rationally select or design excipients for lyophilized protein formulations. The use of solvents to aid separation is common in chemical processes. Ionic liquids offer a class of molecules with tunable properties that can be altered to find optimal solvents for a given application. CAMD was used to design ionic liquids for extractive distillation and in situ extractive fermentation processes. The pre-design phase involves experimental data gathering and problem formulation. When available, data was obtained from literature sources. For excipient design, data of percent protein monomer remaining post-lyophilization was measured for a variety of protein-excipient combinations. In problem formulation, the objective was to minimize the difference between the properties of the designed molecule and the target property values. Problem formulations resulted in either mixed-integer linear programs (MILPs) or mixed-integer non-linear programs (MINLPs). The design phase consists of the forward problem and the reverse problem. In the forward problem, linear quantitative structure-property relationships (QSPRs) were developed using connectivity indices. Chiral connectivity indices were used for excipient property models to improve fit and incorporate three-dimensional structural information. Descriptor selection methods were employed to find models that minimized Mallow's Cp statistic, obtaining models with good fit while avoiding overfitting. Cross-validation was performed to access predictive capabilities. Model development was also performed to develop group contribution models and non-linear QSPRs. A UNIFAC model was developed to predict the thermodynamic properties of ionic liquids. In the reverse problem of the design phase, molecules were proposed with optimal property values. Deterministic methods were used to design ionic liquids entrainers for azeotropic distillation. Tabu search, a stochastic optimization method, was applied to both ionic liquid and excipient design to provide novel molecular candidates. Tabu search was also compared to a genetic algorithm for CAMD applications. Tuning was performed using a test case to determine parameter values for both methods. After tuning, both stochastic methods were used with design cases to provide optimal excipient stabilizers for lyophilized protein formulations. Results suggested that the genetic algorithm provided a faster time to solution while the tabu search provides quality solutions more consistently. The post-design phase provides solution analysis and verification. Process simulation was used to evaluate the energy requirements of azeotropic separations using designed ionic liquids. Results demonstrated that less energy was required than processes using conventional entrainers or ionic liquids that were not optimally designed. Molecular simulation was used to guide protein formulation design and may prove to be a useful tool in post-design verification. Finally, prediction intervals were used for properties predicted from linear QSPRs to quantify the prediction error in the CAMD solutions. Overlapping prediction intervals indicate solutions with statistically similar property values. Prediction interval analysis showed that tabu search returns many results with statistically similar property values in the design of carbohydrate glass formers for lyophilized protein formulations. The best solutions from tabu search and the genetic algorithm were shown to be statistically similar for all design cases considered. Overall the CAMD method developed here provides a comprehensive framework for the design of novel molecules for bioengineering approaches

Electrogenerated Chemiluminescence Of Luminophores And Enhancement With Melatonin

The photoluminescent (PL), electrochemical, and electrogenerated chemiluminescent (ECL) properties of 1,5-I-Aedans (N-(iodoacetylaminotheyl)-1-naphthylamine-5-sulfonic acid) in aqueous buffered (KH2PO4) and 50:50 (v/v) acetonitrile:KH2PO4 solutions were obtained. Tri-n-propylamine (TPrA) was used as the oxidative-reductive coreactant. The PL efficiencies (em) were 1.83 in KH2PO4 and 4.81 in mixed solvent compared to Ru(bpy)32+ standard solutions (em = 1.0). 1,5-I-Aedans displayed quasi-reversible oxidative electrochemistry in aqueous solutions and irreversible to quasi-reversible oxidation in mixed solvent. ECL efficiencies (ecl) were obtained by comparison to a Ru(bpy)32+/TPrA (bpy = 2,2\u27-bipyridine) standard (ecl = 1) and were higher in KH2PO4 (ecl = 6.8 x 10-4) than in the mixed solvent system (ecl = 0.072 x 10-4). A second project studied the ECL of the Ru(bpy)32+/TPrA system when melatonin (N-acetyl-5-methoxytryptamine; MLT) is present in aqueous buffered solution. MLT displays weak ECL when TPrA is used as the oxidative-reductive coreactant, but when micromolar concentrations of MLT were added to the system, up to 2.5-fold enhancement was seen. PL efficiencies did not change in the presence of MLT unless the solution underwent electrochemical bulk oxidation. Spectroscopic, electrochemical and spectro-electrochemical studies indicate that the mechanism involves oxygen scavenging by MLT oxidation products. This scavenging prevents quenching of the *Ru(bpy)32+ excited states

Quality of life in the five years after intensive care : a cohort study

Peer reviewedPublisher PD

The Effect of Temperature on the Oxygen-linked Ionizations of Hemoglobin

Abstract On the assumption that only two of the acid groups per heme are affected by oxygenation, the difference in electrical charge, ΔX, between oxygenated and deoxygenated hemoglobin (O2Hb and Hb) at the same pH (as determined from the difference in their titration curves) is given by the equation. [see PDF for equation] where h = hydrogen ion concentration and Ko, K'o, Kr, and K'r are the ionization constants of these "Bohr groups" in O2Hb and Hb, respectively. The above equation has been found to fit (within the limits of experimental error) the data on the "difference" titration curves for bovine, human, and horse O2Hb and Hb over the pH range 5.0 to 9.3 at 25–37°; "best" (i.e. least mean square) values of the ionization constants have been estimated statistically by means of an automatic computer program, written in Fortran language. Thus, for human hemoglobin at 25°, pKr = 7.84 (±0.006), pKo = 6.84 (±0.009), pK'r = 5.13 (±0.04), and pK'o = 5.60 (±0.03). These figures differ by up to 0.7 pK unit from those obtained by other recent workers, who did not, however, analyze their data statistically. Values for the corresponding heats of ionization, Qo, Q'o, Qr and Q'r, have been calculated from the effect of temperature on the respective ionization constants. The most accurate results have been obtained in the case of human hemoglobin, wherein it is found that (Qr - Qo) is 5,000 (±800) cal. The actual value of Qr is of the order of 11,000 cal and thus lies outside the usual range for the heat of ionization of imidazole and its derivatives. These conclusions are based upon the experimental data not only of the present paper but also of the recent paper (11) of Antonini, Wyman, Brunori, Fronticelli, Bucci, and Rossi-Fanelli, the concordance between these two independent sets of results, when statistically analyzed, being very satisfactory. (Q'o - Q'r) has also been found to be of the order of 5000 cal, but this figure is subject to a wide margin of uncertainty, owing to the difficulty in obtaining accurate estimates of pK'o and pK'r from data in the acid pH range, wherein hemoglobin is unstable. Preliminary experiments have shown that at pH below 6.2 "rapid" titration figures (i.e. within 10 msec) differ significantly from the results obtained by the customary slow titration procedure, which takes several minutes. The results of this paper are discussed in light of current views on the chemical and x-ray structure of O2Hb and Hb