Fundamental partial compositeness

We construct renormalizable Standard Model extensions, valid up to the Planck scale, that give a composite Higgs from a new fundamental strong force acting on fermions and scalars. Yukawa interactions of these particles with Standard Model fermions realize the partial compositeness scenario. Under certain assumptions on the dynamics of the scalars, successful models exist because gauge quantum numbers of Standard Model fermions admit a minimal enough 'square root'. Furthermore, right-handed SM fermions have an SU(2)$_R$-like structure, yielding a custodially-protected composite Higgs. Baryon and lepton numbers arise accidentally. Standard Model fermions acquire mass at tree level, while the Higgs potential and flavor violations are generated by quantum corrections. We further discuss accidental symmetries and other dynamical features stemming from the new strongly interacting scalars. If the same phenomenology can be obtained from models without our elementary scalars, they would reappear as composite states.Comment: 36 pages, 3 figures, 5 tables. v2: final published version, expanded discussion about neutrino masses, dark matter and flavou

Analysis of Helicopter Activities in Forest Fire-Fighting

In Southern European countries wildfires are the most natural threat to forests and wooded areas. Over the last decade, public and scientific debates on forest fire management have increased. Helicopters and airtankers are extremely effective fire suppression means, but they are also very expensive. Studies on the improved performance of suppression for the enhancement of firefighting organization are still needed. Consequently to make a plan for the distribution of financial resources to be divided between fire suppression and fire prevention actions in terms of fuel management is not possible. The aim of this study is to compare the helicopter’s forest fire-fighting activity in Tuscany (central Italy) over two periods: between 1998–2000 and 2001–2005 when five and ten helicopters were respectively assigned. For both periods (1998–2000 and 2001–2005) the following were analyzed: the number of forest fires and the burned area with or without helicopter intervention and the position of the helicopter bases in relation to the fire. The results showed that a fleet of 10 helicopters is oversized, in relation to the fire regime of Tuscany, suggesting the need to evaluate a reduction in the fleet. Financial resources may be thus made available for more profitable fire prevention activities, such as, active fuel management. The results also showed where there is the need to improve the helicopter efficiency via the re–management as regards the positioning of their bases

Metabolic response of Insulinoma 1E cells to glucose stimulation studied by fluorescence lifetime imaging

A cascade of highly regulated biochemical processes connects glucose stimulation to insulin secretion in specialized cells of mammalian pancreas, the β-cells. Given the importance of this process for systemic glucose homeostasis, noninvasive and fast strategies capable to monitor the response to glucose in living cells are highly desirable. Here, we use the phasor-based approach to Fluorescence Lifetime IMaging (FLIM) microscopy to quantify the ratio between protein-bound and free Nicotinamide adenine dinucleotide (phosphate) species in their reduced form (NAD(P)H), and the Insulinoma cell line INS-1E as a β-like cellular model. Phasor-FLIM analysis shows that the bound/free ratio of NAD(P)H species increases upon pulsed glucose stimulation. Such response is impaired by 48-hours preincubation of cells under hyperglycemic conditions. Phasor-FLIM concomitantly monitors the appearance of long-lifetime species (LLS) as characteristic products of hyperglycemia-induced oxidative stress

Optical Nanoscopy of Cytokine-Induced Structural Alterations of the Endoplasmic Reticulum and Golgi Apparatus in Insulin-Secreting Cells

first_pagesettingsOrder Article Reprints Open AccessArticle Optical Nanoscopy of Cytokine-Induced Structural Alterations of the Endoplasmic Reticulum and Golgi Apparatus in Insulin-Secreting Cells by Licia Anna Pugliese 1,*,Valentina De Lorenzi 1ORCID,Marta Tesi 2,Piero Marchetti 2 andFrancesco Cardarelli 1,*ORCID 1 NEST Laboratory—Scuola Normale Superiore, Piazza San Silvestro 12, 56127 Pisa, Italy 2 Islet Cell Laboratory, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy * Authors to whom correspondence should be addressed. Int. J. Mol. Sci. 2024, 25(19), 10391; https://doi.org/10.3390/ijms251910391 Submission received: 9 August 2024 / Revised: 20 September 2024 / Accepted: 25 September 2024 / Published: 27 September 2024 (This article belongs to the Section Molecular Biology) Downloadkeyboard_arrow_down Browse Figures Versions Notes Abstract Pro-inflammatory cytokines play a role in the failure of β cells in type 1 and type 2 diabetes. While existing data from ‘omics’ experiments allow for some understanding of the molecular mechanisms behind cytokine-induced dysfunction in β cells, no report thus far has provided information on the direct imaging of the β cell landscape with nanoscale resolution following cytokine exposure. In this study, we use Airyscan-based optical super-resolution microscopy of Insulinoma 1E (INS-1E) cells to investigate the structural properties of two subcellular membranous compartments involved in the production, maturation and secretion of insulin-containing granules, the endoplasmic reticulum (ER) and the Golgi apparatus (GA). Our findings reveal that exposure of INS-1E cells to IL-1β and IFN-γ for 24 h leads to significant structural alterations of both compartments. In more detail, both the ER and the GA fragment and give rise to vesicle-like structures with markedly reduced characteristic area and perimeter and increased circularity with respect to the original structures. These findings complement the molecular data collected thus far on these compartments and their role in β cell dysfunction and lay the groundwork for future optical microscopy-based ex vivo and in vivo investigations

On special quadratic birational transformations of a projective space

A birational map from a projective space onto a not too much singular projective variety with a single irreducible non-singular base locus scheme (special birational transformation) is a rare enough phenomenon to allow meaningful and concise classification results. We shall concentrate on transformations defined by quadratic equations onto some varieties (especially projective hypersurfaces of small degree), where quite surprisingly the base loci are interesting projective manifolds appearing in other contexts; for example, exceptions for adjunction theory, small degree or small codimensional manifolds, Severi or more generally homogeneous varieties. In particular, we shall classify: quadro-quadric transformations into a quadric hypersurface; quadro-cubic transformations into a del Pezzo variety; transformations whose base locus (scheme) has dimension at most three.Comment: This is my Ph.D. thesis, with the addition of a few other example

Single-cell imaging of α and β cell metabolic response to glucose in living human Langerhans islets

Here we use a combination of two-photon Fluorescence Lifetime Imaging Microscopy (FLIM) of NAD(P)H free/bound ratio in living HIs with post-fixation, immunofluorescence-based, cell-type identification. FLIM allowed to measure variations in the NAD(P)H free/bound ratio induced by glucose; immunofluorescence data allowed to identify single α and β cells; finally, matching of the two datasets allowed to assign metabolic shifts to cell identity. 312 α and 654 β cells from a cohort of 4 healthy donors, 15 total islets, were measured. Both α and β cells display a wide spectrum of responses, towards either an increase or a decrease in NAD(P)H free/bound ratio. Yet, if single-cell data are averaged according to the respective donor and correlated to donor insulin secretion power, a non-random distribution of metabolic shifts emerges: robust average responses of both α and β cells towards an increase of enzyme-bound NAD(P)H belong to the donor with the lowest insulin-secretion power; by contrast, discordant responses, with α cells shifting towards an increase of free NAD(P)H and β cells towards an increase of enzyme-bound NAD(P)H, correspond to the donor with the highest insulin-secretion power. Overall, data reveal neat anti-correlation of tissue metabolic responses with respect to tissue insulin secretion power

Corpus luteum vascularization and progesterone production in Autumn and Winter cycles of the mare: relationship between ultrasonographic characteristics of corpora lutea and plasma progesterone concentration in the last cycles before anestrus

In 20 estrus cycles of 15 mares, Color Doppler ultrasound of corpora lutea and plasma progesterone concentration ([P4]) were analyzed on days 6, 10, 14, 16 and 18 after ovulation. [P4] was positively correlated with corpora lutea cross sectional area (CSA), vascularized area (VA) and index of vascularization (IV=VA/CSA) (P 1 ng/ml. Mares with CSA <3473 pixels, VA<25.5 pixels and a IV <7.6% were prone to express [P4] <1 ng/ml 25.4, 7.9 and 7.6 times more than mares with higher values, respectively. CLs analyzed parameters differed significantly between last cycles of the breeding season and previous cycles until day 14 after ovulation (P<0.05). No significant differences were found in [P4] between last cycles and previous ones

Determinants of Mechanical Dysfunction in Myocardium with Reduced Density of T-Tubules

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Eteplirsen Treatment for Duchenne Muscular Dystrophy: A Qualitative Patient Experience Study.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is characterized by rapid functional decline. Current available treatment options aim to delay disease progression or stabilize physical function. To aid in healthcare providers understanding of the symptoms of disease that impact patients experience, this study explored childrens physical functioning, activities of daily living (ADLs), and health-related quality of life (HRQoL) after receiving eteplirsen, a weekly infusion indicated for individuals with DMD with exon&nbsp;51 skip-amenable mutations. METHODS: Fifteen caregivers of male individuals with DMD participated in a 60-min, semi-structured interview. Open-ended questioning explored changes in the childrens condition or maintenance in abilities since eteplirsen initiation. RESULTS: Children with DMD (age 7-15&nbsp;years [mean 10.9]; steroid treatment at interview, n = 8; time since eteplirsen initiation 3-24&nbsp;months [mean 14.9]) were described by caregivers as ambulatory (n = 9) and non-ambulatory (n = 6). Caregivers of ambulatory children reported improvements or maintenance of walking ability (n = 7/9), running (n = 6/9), and using stairs (n = 4/9). Continued decline in using stairs was reported by two caregivers. In upper-limb functioning, improvements or maintenances in fine-motor movements were reported by nearly half of all caregivers (n = 7/15), with one caregiver noting a continued decline. Subsequent improvements or maintenances in ADLs were described. Improvements or maintenances in fatigue (n = 9/15), muscle weakness (n = 7/15), and pain (n = 6/15) were reported, although some caregivers described a continued decline (n = 3/15 fatigue, n = 1/15 muscle weakness, n = 2/15 pain). Importantly, most caregivers who reported maintenances in ability perceived this as a positive outcome (n = 6/9). CONCLUSION: This exploratory study indicated that most caregivers perceived improvements or maintenances in aspects of their childs physical functioning, ADLs, and HRQoL since eteplirsen initiation, which they perceived to be a positive outcome