A calorimeter for the study of photoproduction at high transverse momentum

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EXTENDING AND ENHANCING GT-ITM

GT-ITMis a topology generation tool. Since its release GTITMis widely used in the scientific community for network simulations. GTITM is extended to support routing on its topology. The routing algorithm used for interdomain routing attempts to emulate the BGP routing protocol seen on the internet. It uses a policy file if supplied to make routing decisions. An additional functionality provided with the tool is the ability to automatically generate policy file for large graphs

Development of novel carriers for transdermal delivery of peptides

Recent developments in genetic engineering and biotechnology have resulted in anincrease in availability of therapeutic peptides and small anti-cytokines. Oraladministration is inappropriate as these molecules are unstable in the gastrointestinaltract and are subject to hepatic first-pass effect. Transdermal delivery is an attractivealternative as the skin exhibits less enzymatic activity and allows for a controlled,sustained local therapeutic drug concentration over a prolonged period of time.However, the skin’s lipophilic stratum corneum acts as a major barrier to thedelivery of hydrophilic molecules, including peptides, resulting in lack of efficacy ofthese compounds if applied topically. Considerable research effort has beenfocussed on the development of skin penetration enhancement techniques. However,many of these techniques have been limited by insufficient penetration enhancementand/or induced irritancy.We have investigated three approaches to enhance the delivery of peptides that havetherapeutic or cosmetic effect in the skin. These approaches include the use ofphysical energy to enhance the delivery of Alanine-Tryptophan (Ala-Trp), lipoaminoacid (LAA) conjugation to increase the permeability of a HNE inhibitor Ala-Ala-Pro-Val (AAPV) and a cosmetic peptide, acetyl hexapeptide-3 and cyclisation to enhancethe delivery of a core peptide (CP) which has anti-inflammatory activity.In vitro permeation studies across human epidermis were performed in Pyrex glassFranz-type diffusion cells. Ala-Trp was selected as a small molecular weight modeldipeptide to study the penetration enhancement effects of Dermaportation, which is anewly developed pulsed electro magnetic field (PEMF) technology. The dipeptidewas found to be unstable on exposure to skin at 37°C and Dermaportation (Pulsedelectromagnetic field technology) significantly increased the in vitro permeabilitycoefficient of Ala-Trp across human epidermis from 7.7 x 10-4 cm/h with passivediffusion to 1.94 x 10-2 cm/h with Dermaportation over an 8 h period.Dermaportation thus may provide an effective means of delivering molecules that arehighly susceptible to degradation like dipeptides, in higher amounts and in arelatively short duration.The effectiveness of coupling a short chain lipoamino acid to enhance transepidermaldelivery of a model human neutrophil elastase (HNE) inhibitor (Ala-Ala-Pro-Val) was assessed. The optimal conjugate structure for skin penetration andbiological activity of this therapeutic peptide with anti-inflammatory activity wasdetermined. In order to enhance the trans-epidermal delivery of the peptide,lipophilic derivatives with LAAs of chain length C6, C8, and C10 were prepared bysolid phase synthesis. Conjugation to a C6-LAA enhanced epidermal permeability ofthe tetrapeptide. Stereoselective permeation of the lipopeptide diastereomers acrossthe human epidermis was observed. The amount of C6(D)-LAA-AAPV (467.94μg/cm2) was significantly higher than C6(L)–LAA-AAPV (123.04 μg/cm2). Thesame was observed with C8(D)-LAA-AAPV. The effect of donor concentration andskin hydration on skin permeability of C8(D,L)-LAA-AAPV and C10(D,L)-LAAAAPVwas also assessed and it was observed that there was higher permeation ofC10(D,L)-LAA-AAPV at a higher donor concentration. The lipoamino acid conjugates were more stable than the native tetrapeptide and biological activity was retained after coupling of the tetrapeptide to C6, C8 and C10 LAA.A cosmetic peptide, acetyl hexapeptide-3 was coupled to individual diastereomers ofC12 (A)-LAA and C12 (B)-LAA. The preliminary study was designed to assess theeffect of coupling of a LAA of higher molecular weight on the transepidermalpermeation and accumulation of this hexapeptide. Accumulation of these peptides inthe skin was also quantified. Detectable amounts of C12(A)-LAA-hexapeptide-3 andC12(B)-LAA-hexapeptide-3 were not found in the receptor solution but higherquantities of these conjugates were found to be retained in the skin. The amount ofC12(B)-LAA-hexapeptide-3 (59.92 μg/cm2 ± 10.64) in the epidermis was highestfollowed by C12(A)-LAA-hexapeptide-3 (33.06 μg/cm2 ± 3.70) and acetylhexapeptide-3 (12.64 μg/cm2 ± 1.48).Lastly, skin permeability and in skin stability of an anti-inflammatory peptide (corepeptide: CP) and two analogues that have demonstrated improved biological efficacyand specificity: a cyclic peptide sequence (C1) and its linear sequence counterpart(C1-L) were assessed. The stability of C1 and C1-L was significantly higher ascompared to CP when placed in contact with skin at 37ºC. The epidermal penetrationof the core anti-inflammatory peptide improved after cyclisation. The order of Lastly, skin permeability and in skin stability of an anti-inflammatory peptide (corepeptide: CP) and two analogues that have demonstrated improved biological efficacyand specificity: a cyclic peptide sequence (C1) and its linear sequence counterpart(C1-L) were assessed. The stability of C1 and C1-L was significantly higher ascompared to CP when placed in contact with skin at 37ºC. The epidermal penetrationof the core anti-inflammatory peptide improved after cyclisation. The order of permeation of the analogues was C1>C1-L>CP after 48h and 6 days. The amount of peptide retained in the skin was higher after 48h as compared to 8h due to greater partitioning of these peptides in the skin.This work demonstrates the enhancement effects of these three techniques tooptimize the transdermal/topical permeation of therapeutic and cosmetic peptides

Phase Stability and Segregation in Alloy 22 Base Metal and Weldments

The current design of the waste disposal containers relies heavily on encasement in a multi-layered container, featuring a corrosion barrier of Alloy 22, a Ni-Cr-Mo-W based alloy with excellent corrosion resistance over a wide range of conditions. The fundamental concern from the perspective of the Yucca Mountain Project, however, is the inherent uncertainty in the (very) long-term stability of the base metal and welds. Should the properties of the selected materials change over the long service life of the waste packages, it is conceivable that the desired performance characteristics (such as corrosion reistance) will become compromised, leading to premature failure of the system. To address this, we will study the phase stability and solute segregation characteristics of Alloy 22 base metal and welds. A better understanding of the underlying microstructural evolution tendencies, and their connections with corrosion behavior will (in turn) produce a higher confidence in the extrapolated behavior of the container materials over time periods that are not feasibly tested in a laboratory. Additionally, the knowledge gained here may potentially lead to cost savings through development of safe and realistic design constraints and model assumptions throughout the entire disposal system

Loopy: Programmable and Formally Verified Loop Transformations

Abstract. This paper presents a system, Loopy, for programming loop transformations. Manual loop transformation can be tedious and errorprone, while fully automated methods do not guarantee improvements. Loopy takes a middle path: a programmer specifies a loop transformation at a high level, which is then carried out automatically by Loopy, and formally verified to guard against specification and implementation mistakes. Loopy’s notation offers considerable flexibility with assembling transformations, while automation and checking prevent errors. Loopy is implemented for the LLVM framework, building on a polyhedral compilation library. Experiments show substantial improvements over fully automated loop transformations, using simple and direct specifications

Effect of blood storage on electrolyte levels

Background: Blood transfusion can be an immediate life saving measure in several acute conditions such as hemorrhage and anemia. However, various post transfusion complications are observed in patients which may be associated with the storage conditions of the collected blood. Electrolytes play a major role in maintaining homeostasis within the cells. Potassium is the most important extracellular cation responsible for maintenance of the cell integrity. Prolonged and improper storage of blood can lead to leakage of electrolytes, thus changing the cell morphology. This can adversely affect the patients who receive such blood. This study helps us analyze the effect of blood storage on electrolyte levels.Methods: For the study, 10ml of blood was collected from 30 blood bags containing CPDA-1 at the time of blood donation from 30 different volunteers. This blood containing the CPDA-1 was divided into 5 parts of 2ml and each 2ml sample was stored in plain bulbs. All the samples were stored at 4°C. Samples were tested to check for changes in the electrolyte (Na+, K+, Cl-) levels on day 0, 3, 7, 14 and 21. ANOVA was used to calculate the variance in the electrolyte levels.Results: Average sodium level on day 0 was 152.9±3.8 mEq/l. There was a significant decrease and it was measured at 139.5±4.8 mEq/l on day 21. Average potassium level on day 0 was 4.2±0.4 mEq/l. A significant spike was observed in potassium levels. The final reading of potassium level on day 21 was 15.2±0.7 mEq/l. Average chloride level on day 0 was 71.9±6.6 mEq/l which significantly declined to 67±5.9 mEq/l.Conclusions: Though blood is stored in proper conditions, a biochemical change occurs within the cells due to prolonged storage and thus affects its viability

Abstract Interpretation of Stateful Networks

Modern networks achieve robustness and scalability by maintaining states on their nodes. These nodes are referred to as middleboxes and are essential for network functionality. However, the presence of middleboxes drastically complicates the task of network verification. Previous work showed that the problem is undecidable in general and EXPSPACE-complete when abstracting away the order of packet arrival. We describe a new algorithm for conservatively checking isolation properties of stateful networks. The asymptotic complexity of the algorithm is polynomial in the size of the network, albeit being exponential in the maximal number of queries of the local state that a middlebox can do, which is often small. Our algorithm is sound, i.e., it can never miss a violation of safety but may fail to verify some properties. The algorithm performs on-the fly abstract interpretation by (1) abstracting away the order of packet processing and the number of times each packet arrives, (2) abstracting away correlations between states of different middleboxes and channel contents, and (3) representing middlebox states by their effect on each packet separately, rather than taking into account the entire state space. We show that the abstractions do not lose precision when middleboxes may reset in any state. This is encouraging since many real middleboxes reset, e.g., after some session timeout is reached or due to hardware failure