A procedure for the determination of proteolytic activity

The difficulties introduced by the desire to maintain a constant pH during an enzyme-catalyzed hydrolysis of peptide-like substrates and at the same time to determine the extent of hydrolysis by an acid-base titration have been pointed out (1), but to date no completely satisfactory solution of the problem has been given. With those enzymes whose pH optima lie in the region between pH 7.5 to 8.5, e.g. trypsin and chymotrypsin, the poor buffering capacity of phosphate in this region prompted us, as it has others (2-5), to consider the use of organic amines whose pK’alpha values were near to or identical with the pH optimum of the enzyme being used. In the course of such studies it soon became evident that coincidental use of a suitable primary or secondary amine buffer system and a formol titration (1) would insure adequate buffering capacity with low buffer concentration during the hydrolysis and at the same time permit the final acid-base titration to be conducted under nearly ideal conditions. In this communication we shall limit the discussion to results obtained with chymotrypsin and specific acylated-a-amino acid amide substrates, since the application of the general method to other proteolytic enzymes and other types of substrates will be obvious

MAD Version 9

The program MAD is widely used for accelerator design and beam dynamics studies. For many years, its input language has been the nearest thing to a world-wide standard for describing accelerator structures. The new Version 9 is a complete rewrite using a systematic object-oriented methodology based on the CLASSIC classes [2] for accelerator physics. It provides many improvements over the previous MAD Version 8. These include: (i) support for multiple beam-lines simultaneously, facilitating, for example, matching constraints that couple the two rings of a two-ring collider, (ii) much improved Lie-algebraic map calculations, (iii) a uniform method and format for exchanging many kinds of structured data with other programs, (iv) an improved and more consistent input language. In addition, we report on a parallel 3D Poisson field solver for space charge calculations in high intensity particle beams. Applied to the PSI injector cyclotron, this shows the general nature of MAD Version 9 as a state-of- the-art problem-solving environment. We describe the current status of the program and how to get it, outline future plans and illustrate some of the new features

Beam Dynamics in High Intensity Cyclotrons Including Neighboring Bunch Effects: Model, Implementation and Application

Space charge effects, being one of the most significant collective effects, play an important role in high intensity cyclotrons. However, for cyclotrons with small turn separation, other existing effects are of equal importance. Interactions of radially neighboring bunches are also present, but their combined effects has not yet been investigated in any great detail. In this paper, a new particle in cell based self-consistent numerical simulation model is presented for the first time. The model covers neighboring bunch effects and is implemented in the three-dimensional object-oriented parallel code OPAL-cycl, a flavor of the OPAL framework. We discuss this model together with its implementation and validation. Simulation results are presented from the PSI 590 MeV Ring Cyclotron in the context of the ongoing high intensity upgrade program, which aims to provide a beam power of 1.8 MW (CW) at the target destination

Post-traumatic stress disorder in parturients delivering by caesarean section and the implication of anaesthesia: a prospective cohort study.

Post-traumatic stress disorder (PTSD) occurs in 1-7% of women following childbirth. While having a caesarean section (C-section) is known to be a significant risk factor for postpartum PTSD, it is currently unknown whether coexisting anaesthesia-related factors are also associated to the disorder. The aim of this study was to assess anaesthesia-linked factors in the development of acute postpartum PTSD. We performed a prospective cohort study on women having a C-section in a tertiary hospital in Switzerland. Patients were followed up six weeks postpartum. Patient and procedure characteristics, past morbidity or traumatic events, psychosocial status and stressful perinatal events were measured. Outcome was divided into two categories: full PTSD disease and PTSD profile. This was based on the number of DSM-IV criteria of the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) present. The PTSD Checklist Scale and the Clinician Administered PTSD Scale were used for measurement. Of the 280 patients included, 217 (77.5%) answered the questionnaires and 175 (62.5%) answered to an additional phone interview. Twenty (9.2%) had a PTSD profile and six (2.7%) a PTSD. When a full predictive model of risk factors for PTSD profile was built using logistic regression, maternal prepartum and intrapartum complications, anaesthetic complications and dissociative experiences during C-section were found to be the significant predictors for PTSD profile. This is the first study to show in parturients having a C-section that an anaesthesia complication is an independent risk factor for postpartum PTSD and PTSD profile development, in addition to known perinatal and maternal risk factors

Does implicit memory during anaesthesia persist in children?

Background Recent studies suggest that implicit memory (especially perceptual implicit memory) persists during adequate general anaesthesia in adults. Studies in children, however, have failed to demonstrate implicit memory during general anaesthesia, possibly because of differences in methodological design. We therefore designed a prospective study with the aim of evaluating implicit memory in children undergoing general anaesthesia, using a perceptual memory test based on the mere exposure effect, previously tested in a control group. Methods Twelve infrequent neutral words were played 12 times in a random sequence via headphones to 36 children aged 8-12 yr during elective or emergency surgery. The children were not premedicated, and general anaesthesia was maintained with isoflurane. The word presentation started immediately after the surgical incision. Within 36 h after the stimulus presentation, the memory was assessed by using a forced-choice preference judgement task. Time constraint and word deterioration with a low-pass filter were used to prevent the subjects from utilizing intentional retrieval. The implicit memory score was obtained by calculating the proportion of target words preferred, which was compared with the chance level (0.5). Results The percentage of correct responses given by the children was comparable with the chance level. The memory score was mean (sd) 0.48 (0.16) (95% CI 0.43-0.53). Conclusions The use of a perceptual implicit memory test based on the mere exposure procedure in children failed to reveal any evidence of implicit memory under general anaesthesi

Enhancement of antibody-dependent cellular cytotoxicity is associated with treatment response to extracorporeal photopheresis in Sézary syndrome.

Sézary syndrome (SS) is a rare, leukemic type of cutaneous T-cell lymphoma (CTCL), for which extracorporeal photopheresis (ECP) is a first-line therapy. Reliable biomarkers to objectively monitor the response to ECP in patients with SS are missing. We examined the quantitative and qualitative impact of ECP on natural killer (NK) cell activity in SS patients, and especially their functional ability for antibody-dependent cell-mediated cytotoxicity (ADCC). Further, we addressed the question whether the magnitude of the effect on ADCC can be associated with the anti-cancer efficacy of ECP in SS patients. We assessed numbers of NK cells, ADCC activity, and treatment response based on blood tumor staging in a cohort of 13 SS patients (8 women, 5 men) treated with ECP as a first-line therapy. Blood samples were collected before treatment start and after an average of 9 months of uninterrupted ECP treatment. NK cell numbers were reduced in SS patients compared to healthy individuals and showed a tendency of recovery after long-term ECP treatment, independent of the clinical response to treatment. Patients with marginal increase (≤1.5 AU-fold) or lack of increase in ADCC activity failed to respond clinically to treatment, while patients with an increased ADCC activity showed a reduction in blood tumor burden. NK-mediated ADCC is selectively enhanced and might be a mechanism underlying the effect of ECP while in addition it can possibly serve as a reliable biomarker to objectively monitor response to ECP in patients with SS