44 research outputs found
Dynamic Fuzzy c-Means (dFCM) Clustering and its Application to Calorimetric Data Reconstruction in High Energy Physics
In high energy physics experiments, calorimetric data reconstruction requires
a suitable clustering technique in order to obtain accurate information about
the shower characteristics such as position of the shower and energy
deposition. Fuzzy clustering techniques have high potential in this regard, as
they assign data points to more than one cluster,thereby acting as a tool to
distinguish between overlapping clusters. Fuzzy c-means (FCM) is one such
clustering technique that can be applied to calorimetric data reconstruction.
However, it has a drawback: it cannot easily identify and distinguish clusters
that are not uniformly spread. A version of the FCM algorithm called dynamic
fuzzy c-means (dFCM) allows clusters to be generated and eliminated as
required, with the ability to resolve non-uniformly distributed clusters. Both
the FCM and dFCM algorithms have been studied and successfully applied to
simulated data of a sampling tungsten-silicon calorimeter. It is seen that the
FCM technique works reasonably well, and at the same time, the use of the dFCM
technique improves the performance.Comment: 15 pages, 10 figures. It is accepted for publication in NIM
A Profile Likelihood Analysis of the Constrained MSSM with Genetic Algorithms
The Constrained Minimal Supersymmetric Standard Model (CMSSM) is one of the
simplest and most widely-studied supersymmetric extensions to the standard
model of particle physics. Nevertheless, current data do not sufficiently
constrain the model parameters in a way completely independent of priors,
statistical measures and scanning techniques. We present a new technique for
scanning supersymmetric parameter spaces, optimised for frequentist profile
likelihood analyses and based on Genetic Algorithms. We apply this technique to
the CMSSM, taking into account existing collider and cosmological data in our
global fit. We compare our method to the MultiNest algorithm, an efficient
Bayesian technique, paying particular attention to the best-fit points and
implications for particle masses at the LHC and dark matter searches. Our
global best-fit point lies in the focus point region. We find many
high-likelihood points in both the stau co-annihilation and focus point
regions, including a previously neglected section of the co-annihilation region
at large m_0. We show that there are many high-likelihood points in the CMSSM
parameter space commonly missed by existing scanning techniques, especially at
high masses. This has a significant influence on the derived confidence regions
for parameters and observables, and can dramatically change the entire
statistical inference of such scans.Comment: 47 pages, 8 figures; Fig. 8, Table 7 and more discussions added to
Sec. 3.4.2 in response to referee's comments; accepted for publication in
JHE
PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function.
Expansion of antigen-experienced CD8+ T cells is critical for the success of tumour-infiltrating lymphocyte (TIL)-adoptive cell therapy (ACT) in patients with cancer1. Interleukin-2 (IL-2) acts as a key regulator of CD8+ cytotoxic T lymphocyte functions by promoting expansion and cytotoxic capability2,3. Therefore, it is essential to comprehend mechanistic barriers to IL-2 sensing in the tumour microenvironment to implement strategies to reinvigorate IL-2 responsiveness and T cell antitumour responses. Here we report that prostaglandin E2 (PGE2), a known negative regulator of immune response in the tumour microenvironment4,5, is present at high concentrations in tumour tissue from patients and leads to impaired IL-2 sensing in human CD8+ TILs via the PGE2 receptors EP2 and EP4. Mechanistically, PGE2 inhibits IL-2 sensing in TILs by downregulating the IL-2Rγc chain, resulting in defective assembly of IL-2Rβ-IL2Rγc membrane dimers. This results in impaired IL-2-mTOR adaptation and PGC1α transcriptional repression, causing oxidative stress and ferroptotic cell death in tumour-reactive TILs. Inhibition of PGE2 signalling to EP2 and EP4 during TIL expansion for ACT resulted in increased IL-2 sensing, leading to enhanced proliferation of tumour-reactive TILs and enhanced tumour control once the cells were transferred in vivo. Our study reveals fundamental features that underlie impairment of human TILs mediated by PGE2 in the tumour microenvironment. These findings have therapeutic implications for cancer immunotherapy and cell therapy, and enable the development of targeted strategies to enhance IL-2 sensing and amplify the IL-2 response in TILs, thereby promoting the expansion of effector T cells with enhanced therapeutic potential
Compact Polyelectrolyte Complexes: “Saloplastic” Candidates for Biomaterials
Precipitates of polyelectrolyte complexes were transformed into rugged shapes suitable for bioimplants by ultracentrifugation in the presence of high salt concentration. Salt ions dope the complex, creating a softer material with viscous fluid-like properties. Complexes that were compacted under the centrifugal field (CoPECs) were made from poly(diallyldimethyl ammonium), PDADMA, as polycation, and poly(styrene sulfonate), PSS, or poly(methacrylic acid), PMAA, as polyanion. Dynamic mechanical testing revealed a rubbery plateau at lower frequencies for PSS/PDADMA with moduli that decreased with increasing salt concentration, as internal ion pair cross-links were broken. CoPECs had significantly lower modulii compared to similar polyelectrolyte complexes prepared by the “multilayering ” method. The difference in mechanical properties was ascribed to higher water content (located in micropores) for the former and, more importantly, to their nonstoichiometric polymer composition. The modulus of PMAA/PDADMA CoPECs, under physiological conditions, demonstrated dynamic mechanical properties that were close to those of the nucleus pulposus in an intervertebral disk