Synchronous Phase Shift at LHC

The electron cloud in vacuum pipes of accelerators of positively charged particle beams causes a beam energy loss which could be estimated from the synchronous phase. Measurements done with beams of 75 ns, 50 ns, and 25 ns bunch spacing in the LHC for some fills in 2010 and 2011 show that the average energy loss depends on the total beam intensity in the ring. Later measurements during the scrubbing run with 50 ns beams show the reduction of the electron cloud due to scrubbing. Finally, measurements of the individual bunch phase give us information about the electron cloud build-up inside the batch and from batch to batch.Comment: Presented at ECLOUD'12: Joint INFN-CERN-EuCARD-AccNet Workshop on Electron-Cloud Effects, La Biodola, Isola d'Elba, Italy, 5-9 June 201

Protease-Specific Biomarkers to Analyse Protease Inhibitors for Emphysema Associated with Alpha 1-Antitrypsin Deficiency. An Overview of Current Approaches.

As a known genetic cause of chronic obstructive pulmonary disease (COPD), alpha1-antitrypsin deficiency (AATD) can cause severe respiratory problems at a relatively young age. These problems are caused by decreased or absent levels of alpha1-antitrypsin (AAT), an antiprotease which is primarily functional in the respiratory system. If the levels of AAT fall below the protective threshold of 11 µM, the neutrophil-derived serine proteases neutrophil elastase (NE) and proteinase 3 (PR3), which are targets of AAT, are not sufficiently inhibited, resulting in excessive degradation of the lung parenchyma, increased inflammation, and increased susceptibility to infections. Because other therapies are still in the early phases of development, the only therapy currently available for AATD is AAT augmentation therapy. The controversy surrounding AAT augmentation therapy concerns its efficiency, as protection of lung function decline is not demonstrated, despite the treatment's proven significant effect on lung density change in the long term. In this review article, novel biomarkers of NE and PR3 activity and their use to assess the efficacy of AAT augmentation therapy are discussed. Furthermore, a series of seven synthetic NE and PR3 inhibitors that can be used to evaluate the specificity of the novel biomarkers, and with potential as new drugs, are discussed

The molecular defect of albumin Tagliacozzo: 313 Lys → Asn

AbstractAlbumin Tagliacozzo is a fast-moving genetic variant of human serum albumin found in 19 unrelated families. The protein was isolated from the serum of a heterozygous healthy subject. Analysis of CNBr fragments by isoelectric focusing allowed us to localize the mutation to CNBr fragment IV (residues 299–329). This fragment was isolated on a preparative scale and subjected to tryptic digestion. Sequential analysis of the abnormal tryptic peptide, purified by RP-HPLC, revealed the variant was caused by 313 Lys → Asn substitution, probably due to a point mutation in the structural gene. The lack of a lysine residue accounts for the electrophoretic behavior of albumin Tagliacozzo

Driver Drowsiness Detection: A Machine Learning Approach on Skin Conductance

The majority of car accidents worldwide are caused by drowsy drivers. Therefore, it is important to be able to detect when a driver is starting to feel drowsy in order to warn them before a serious accident occurs. Sometimes, drivers are not aware of their own drowsiness, but changes in their body signals can indicate that they are getting tired. Previous studies have used large and intrusive sensor systems that can be worn by the driver or placed in the vehicle to collect information about the driver’s physical status from a variety of signals that are either physiological or vehicle-related. This study focuses on the use of a single wrist device that is comfortable for the driver to wear and appropriate signal processing to detect drowsiness by analyzing only the physiological skin conductance (SC) signal. To determine whether the driver is drowsy, the study tests three ensemble algorithms and finds that the Boosting algorithm is the most effective in detecting drowsiness with an accuracy of 89.4%. The results of this study show that it is possible to identify when a driver is drowsy using only signals from the skin on the wrist, and this encourages further research to develop a real-time warning system for early detection of drowsiness

Adapting Participatory Action Research to Include Individuals with Intellectual and Developmental Disabilities during the COVID-19 Global Pandemic

Participatory action research (PAR), or the inclusion of those affected by the issues being studied, is a growing area of emphasis in disability research. The principles of PAR align with those of the disability rights movement, such that full inclusion and “nothing about us without us” extends as much to research as it does to any other area of life. Moreover, PAR allows for meaningful input from people with intellectual and developmental disabilities (I/DD), which enhances the likelihood that research results are relevant and important to the disability community. As research activity resumes and is adapted to the context of a global pandemic, it is crucial that a balance is struck to optimize the safety of individuals with I/DD without taking steps backwards from the progress towards more meaningful inclusion in research. Lessons learned from past participatory research projects have demonstrated that accommodations to enable equitable participation of individuals with IDD in the research process are crucial. COVID-19 has significantly affected the lives of individuals with I/DD directly; however, COVID-19 has also affected those with I/DD indirectly through the disruption to critical intervention and other clinical research. As research processes are adapted to align with COVID-19 guidelines, the inclusion of individuals with I/DD via PAR needs to be adapted as well. Recommendations for the continuation of PAR in the context of COVID-19 will be discussed as well as ways in which accommodations can be modified to this new context

Methods of purification and application procedures of alpha1 antitrypsin: a long-lasting history

The aim of the present report is to review the literature addressing the methods developed for the purification of alpha1-antitrypsin (AAT) from the 1950s to the present. AAT is a glycoprotein whose main function is to protect tissues from human neutrophil elastase (HNE) and other proteases released by neutrophils during an inflammatory state. The lack of this inhibitor in human serum is responsible for the onset of alpha1-antitrypsin deficiency (AATD), which is a severe genetic disorder that affects lungs in adults and for which there is currently no cure. Being used, under special circumstances, as a medical treatment of AATD in the so-called "replacement" therapy (consisting in the intravenous infusion of the missing protein), AAT is a molecule with a lot of therapeutic importance. For this reason, interest in AAT purification from human plasma or its production in a recombinant version has grown considerably in recent years. This article retraces all technological advances that allowed the manufacturers to move from a few micrograms of partially purified AAT to several grams of highly purified protein. Moreover, the chronic augmentation and maintenance therapy in individuals with emphysema due to congenital AAT deficiency (current applications in the clinical setting) is also presented.Pathogenesis and treatment of chronic pulmonary disease

Production of serine chymotrypsin - like elastase by aspergillus fumigatus strains

Thirty-four Aspergillus fumigatus strains isolated from air, horse-hair; agricultural soil and human samples were screened to evaluate the production of elastase. Aspergillus fumigatus strains were grown in elastin solid medium, showing a widespread elastin solubilization. However, isolates from human and agricultural soil samples were found to be the highest elastase producers. Then, eight out of 34 strains were grown in four different liquid media, on wich we investigated total and specific proteolytic activity. Results from this experiments suggest that the elastase production is induced by the presence of elastin as a substrate and that the elastase is a chymotrypsin like enzyme. Inhibitory profile showed that the A.fumigatus elastase is a serine proteinase

Protease-specific biomarkers to analyse protease inhibitors for emphysema associated with alpha 1-antitrypsin deficiency. an overview of current approaches

As a known genetic cause of chronic obstructive pulmonary disease (COPD), alpha1-antitrypsin deficiency (AATD) can cause severe respiratory problems at a relatively young age. These problems are caused by decreased or absent levels of alpha1-antitrypsin (AAT), an antiprotease which is primarily functional in the respiratory system. If the levels of AAT fall below the protective threshold of 11 mu M, the neutrophil-derived serine proteases neutrophil elastase (NE) and proteinase 3 (PR3), which are targets of AAT, are not sufficiently inhibited, resulting in excessive degradation of the lung parenchyma, increased inflammation, and increased susceptibility to infections. Because other therapies are still in the early phases of development, the only therapy currently available for AATD is AAT augmentation therapy. The controversy surrounding AAT augmentation therapy concerns its efficiency, as protection of lung function decline is not demonstrated, despite the treatment's proven significant effect on lung density change in the long term. In this review article, novel biomarkers of NE and PR3 activity and their use to assess the efficacy of AAT augmentation therapy are discussed. Furthermore, a series of seven synthetic NE and PR3 inhibitors that can be used to evaluate the specificity of the novel biomarkers, and with potential as new drugs, are discussed.Pathogenesis and treatment of chronic pulmonary disease

A New Luminescence Assay for Autoantibodies to Mammalian Cell–Prepared Insulinoma-Associated Protein 2

OBJECTIVE—Insulinoma-associated protein 2 (IA-2) is a major autoantigen in type 1 diabetes, and IA-2 autoantibodies are routinely detected by a liquid-phase radioimmunoprecipitation assay. The present experiments were initiated to develop a new assay that does not require the use of radioisotopes or autoantigens prepared in bacteria or by in vitro transcription/translation

Anti-HTLV antibody profiling reveals an antibody signature for HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)

<p>Abstract</p> <p>Background</p> <p>HTLV-I is the causal agent of adult T cell leukemia (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Biomarkers are needed to diagnose and/or predict patients who are at risk for HAM/TSP or ATLL. Therefore, we investigated using luciferase immunoprecipitation technology (LIPS) antibody responses to seven HTLV-I proteins in non-infected controls, asymptomatic HTLV-I-carriers, ATLL and HAM/TSP sera samples. Antibody profiles were correlated with viral load and examined in longitudinal samples.</p> <p>Results</p> <p>Anti-GAG antibody titers detected by LIPS differentiated HTLV-infected subjects from uninfected controls with 100% sensitivity and 100% specificity, but did not differ between HTLV-I infected subgroups. However, anti-Env antibody titers were over 4-fold higher in HAM/TSP compared to both asymptomatic HTLV-I (<it>P </it>< 0.0001) and ATLL patients (<it>P </it>< 0.0005). Anti-Env antibody titers above 100,000 LU had 75% positive predictive value and 79% negative predictive value for identifying the HAM/TSP sub-type. Anti-Tax antibody titers were also higher (<it>P </it>< 0.0005) in the HAM/TSP compared to the asymptomatic HTLV-I carriers. Proviral load correlated with anti-Env antibodies in asymptomatic carriers (<it>R </it>= 0.76), but not in HAM/TSP.</p> <p>Conclusion</p> <p>These studies indicate that anti-HTLV-I antibody responses detected by LIPS are useful for diagnosis and suggest that elevated anti-Env antibodies are a common feature found in HAM/TSP patients.</p