The Future of RICH Detectors through the Light of the LHCb RICH

The limitations in performance of the present RICH system in the LHCb experiment are given by the natural chromatic dispersion of the gaseous Cherenkov radiator, the aberrations of the optical system and the pixel size of the photon detectors. Moreover, the overall PID performance can be affected by high detector occupancy as the pattern recognition becomes more difficult with high particle multiplicities. This paper shows a way to improve performance by systematically addressing each of the previously mentioned limitations. These ideas are applied in the present and future upgrade phases of the LHCb experiment. Although applied to specific circumstances, they are used as a paradigm on what is achievable in the development and realisation of high precision RICH detectors

Building a Coalition in California: The 1911 Campaign for Women\u27s Suffrage

Women in California gained the right to vote in 1911 after a mass-organized campaign across the state. Suffrage, labor, and temperance organizations were driving forces behind the women’s suffrage proposition passing and being amended to the state constitution. The women figureheads and membership of these associations were responsible for organizing politically and reaching across class lines in order to build a coalition for women’s suffrage in the state. This research serves as a compilation and analysis of the female-driven clubs, leadership, and strategies behind the Campaign of 1911

Cold applications for recovery in adolescent athletes: a systematic review and meta analysis

Recovery and regeneration modalities have been developed empirically over the years to help and support training programmes aimed at maximizing athletic performance. Professional athletes undergo numerous training sessions, characterized by differing modalities of varying volumes and intensities, with the aim of physiological adaptation leading to improved performance. Scientific support to athletes focuses on improving the chances of a training programme producing the largest adaptive response. In competition it is mainly targeted at maximizing the chances of optimal performance and recovery when high performance levels are required repeatedly in quick succession (e.g. heats/finals). In recent years, a lot of emphasis has been put on recovery modalities. In particular, emphasis has been placed on the need to reduce the delayed onset of muscle soreness (DOMS) typically evident following training and competitive activities inducing a certain degree of muscle damage. One of the most used recovery modalities consists of cold-water immersion and/or ice/cold applications to muscles affected by DOMS. While the scientific literature has provided a rationale for such modalities to reduce pain in athletes and recreationally active adults, it is doubtful if this rationale is appropriate to aid training with adolescent athletes. In particular, since these methods have been suggested to potentially impair the muscle remodeling process leading to muscle hypertrophy. While this debate is still active in the literature, many coaches adopt such practices in youth populations, simply transferring what they see in elite sportspeople directly; without questioning the rationale, safety or effectiveness as well as the potential for such activity to reduce the adaptive potential of skeletal muscle remodeling in adolescent athletes. The aim of this review was to assess the current knowledge base on the use of ice/cold applications for recovery purposes in adolescent athletes in order to provide useful guidelines for sports scientists, medical practitioners, physiotherapists and coaches working with such populations as well as developing research questions for further research activities in this area. Based on the current evidence, it seems clear that evidence for acute benefits of such interventions are scarce and more work is needed to ascertain the physiological implications on a pre or peri-pubertal population

Intracellular targeting and functional analysis of single-chain Fv fragments in mammalian cells

In the past decade, intracellular antibodies have proven to be a useful tool in obtaining the phenotypic knock-out of selected gene function in different animal and plant systems. This strategy is based on the ectopic expression of recombinant forms of antibodies targeted towards different intracellular compartments, exploiting specific targeting signals to confer the new intracellular location. The functional basis of this technology is closely linked to the ability of intracellular antibodies to interact with their target antigens in vivo. This interaction allows either a direct neutralising effect or the dislodgement of the target protein from its normal intracellular location and, by this mechanism, the inactivation of its function. By using this approach, the function of several antigens has been inhibited in the cytoplasm, the nucleus, and the secretory compartments. In this article, we shall describe all the steps required for expressing single-chain Fv fragments in different subcellular compartments of mammalian cells and their subsequent use in knock-out experiments, starting from a cloned single-chain Fv fragment. This will include the analysis of the solubility properties of the new scFv fragment in transfected mammalian cells, the intracellular distribution of the antigen-antibody complex, and the resulting phenotype

Analysis and correction of the magnetic field effects in the Hybrid Photo-Detectors of the RICH2 Ring Imaging Cherenkov detector of LHCb

The Ring Imaging Cherenkov detectors of the LHCb experiment at the Large Hadron Collider at CERN are equipped with Hybrid Photo-Detectors. These vacuum photo-detectors are affected by the stray magnetic field of the LHCb magnet, which degrades their imaging properties. This effect increases the error on the Cherenkov angle measurement and would reduce the particle identification capabilities of LHCb. A system has been developed for the RICH2 Ring Imaging Cherenkov detector to perform a detailed characterisation of the magnetic distortion effects. It is described, along with the methods implemented to correct for these effects, restoring the optimal resolution.Comment: 16 pages, 11 figure

Association of a homozygous GCK missense mutation with mild diabetes

Background: Homozygous inactivating GCK mutations have been repeatedly reported to cause severe hyperglycemia, presenting as permanent neonatal diabetes mellitus (PNDM). Conversely, only two cases of GCK homozygous mutations causing mild hyperglycemia have been so far described. We here report a novel GCK mutation (c.1116G>C, p.E372D), in a family with one homozygous member showing mild hyperglycemia. Methods: GCK mutational screening was carried out by Sanger sequencing. Computational analyses to investigate pathogenicity and molecular dynamics (MD) were performed for GCK-E372D and for previously described homozygous mutations associated with mild (n = 2) or severe (n = 1) hyperglycemia, used as references. Results: Of four mildly hyperglycemic family-members, three were heterozygous and one, diagnosed in the adulthood, was homozygous for GCK-E372D. Two nondiabetic family members carried no mutations. Fasting glucose (p = 0.016) and HbA1c (p = 0.035) correlated with the number of mutated alleles (0–2). In-silico predicted pathogenicity was not correlated with the four mutations’ severity. At MD, GCK-E372D conferred protein structure flexibility intermediate between mild and severe GCK mutations. Conclusions: We present the third case of homozygous GCK mutations associated with mild hyperglycemia, rather than PNDM. Our in-silico analyses support previous evidences suggesting that protein stability plays a role in determining clinical severity of GCK mutations

From cell lines to pluripotent Stem Cells for Modelling Parkinson's Disease

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by loss of dopaminergic (DAergic) neurons in the substantia nigra that contributes to the main motor symptoms of the disease. At present, even if several advancements have been done in the last decades, the molecular and cellular mechanisms involved in the pathogenesis are far to be fully understood. Accordingly, the establishment of reliable in vitro experimental models to investigate the early events of the pathogenesis represents a key issue in the field. However, to mimic and reproduce in vitro the complex neuronal circuitry involved in PD-associated degeneration of DAergic neurons still remains a highly challenging issue. Here we will review the in vitro PD models used in the last 25 years of research, ranging from cell lines, primary rat or mice neuronal cultures to the more recent use of human induced pluripotent stem cells (hiPSCs) and, finally, the development of 3D midbrain organoids

An Online Interactive Video Vignette that Helps Students Learn Key Concepts of Fermentation and Respiration

Topics related to energy transformation and metabolism are important parts of an undergraduate biology curriculum, but these are also topics that students traditionally struggle with. To address this, we have created a short online Interactive Video Vignette (IVV) called To Ferment or Not to Ferment: That is the Question. This IVV is designed to help students learn important ideas related to cellular respiration and metabolism. Students in various courses across four institutions were assigned the IVV as an out-of-class preinstruction homework assignment. To test the effectiveness of this IVV on student learning, we collected and analyzed data from questions embedded in the IVV, open response reflection questions, and pre- and postassessments from IVV watchers and nonwatchers. Our analysis revealed that students who completed the IVV activity interacted productively with this online tool and made significant learning gains on important topics related to cellular respiration and metabolism. This IVV is freely available via https://www.rit.edu/cos/interactive/MINT for instructors to adopt for class use