Symmetry violation in weak decays

Our current knowledge of particle physics is described by the Standard Model (SM). This model, however, leaves important observations unexplained. To answer these outstanding questions, as of yet, unknown physics is required. In the search for new physics, symmetries and their breaking play a guiding role. This dissertation combines experimental results to find to which extent nature is described by our current theory. For this the breaking of the discrete symmetries: parity, charge-conjugation and time-reversal invariance is studied. In addition the possible breakdown of Lorentz symmetry is considered. The breaking of this fundamental symmetry, that lies at the foundation of both the SM and general relativity, is possible in some of the theoretical models that try to unify the SM and gravity. The breaking of the discrete symmetries in beta decay played a major role in development of the SM. Nowadays, beta-decay experiments also search for new interactions. In this dissertation the significance of beta decay compared to experiments at the Large Hadron Collider and to searches for electric dipole moments is studied. This allowed us to make important recommendations for future beta-decay experiments. There have been many tests of Lorentz invariance, but these left the weak interaction relatively unexplored. In this dissertation, Lorentz-symmetry breaking is studied in a number of weak decays. This allowed us to put limits on the effects of Lorentz-symmetry breaking and to make recommendations for future experiments to further test Lorentz invariance in the weak interaction

QCD factorization of the four-lepton decay B−→ℓνˉℓℓ(′)ℓˉ(′)B^-\rightarrow \ell \bar{\nu}_\ell \ell^{(\prime)} \bar{\ell}^{(\prime)}

Motivated by the first search for the rare charged-current $B$ decay to four leptons, $\ell \bar{\nu}_\ell \ell^{(\prime)} \bar{\ell}^{(\prime)}$, we calculate the decay amplitude with factorization methods. We obtain the $B\to \gamma^*$ form factors, which depend on the invariant masses of the two lepton pairs, at leading power in an expansion in $\Lambda_{\rm QCD}/m_b$ to next-to-leading order in $\alpha_s$, and at $\mathcal{O}(\alpha_s^0)$ at next-to-leading power. Our calculations predict branching fractions of a few times $10^{-8}$ in the $\ell^{(\prime)} \bar{\ell}^{(\prime)}$ mass-squared bin up to $q^2=1~\text{GeV}^2$ with $n_+q>3~$GeV. The branching fraction rapidly drops with increasing $q^2$. An important further motivation for this investigation has been to explore the sensitivity of the decay rate to the inverse moment $\lambda_B$ of the leading-twist $B$ meson light-cone distribution amplitude. We find that in the small-$q^2$ bin, the sensitivity to $\lambda_B$ is almost comparable to $B^- \rightarrow \ell^- \bar{\nu}_\ell\gamma$ when $\lambda_B$ is small, but with an added uncertainty from the light-meson intermediate resonance contribution. The sensitivity degrades with larger $q^2$.Comment: 22 pages, 7 figures; v2: study of the sensitivity to the shape of the B-LCDA added (Sec. 4.4). Matches published versio

Use of multiparametric MRI to characterize uterine fibroid tissue types

Background: Although the biological characteristics of uterine fibroids (UF) have implications for therapy choice and effectiveness, there is limited MRI data about these characteristics. Currently, the Funaki classification and Scale

Rationale and design of the PRAETORIAN-COVID trial:A double-blind, placebo-controlled randomized clinical trial with valsartan for PRevention of Acute rEspiraTORy dIstress syndrome in hospitAlized patieNts with SARS-COV-2 Infection Disease

There is much debate on the use of angiotensin receptor blockers (ARBs) in severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2)–infected patients. Although it has been suggested that ARBs might lead to a higher susceptibility and severity of SARS-CoV-2 infection, experimental data suggest that ARBs may reduce acute lung injury via blocking angiotensin-II–mediated pulmonary permeability, inflammation, and fibrosis. However, despite these hypotheses, specific studies on ARBs in SARS-CoV-2 patients are lacking. Methods: The PRAETORIAN-COVID trial is a multicenter, double-blind, placebo-controlled 1:1 randomized clinical trial in adult hospitalized SARS-CoV-2–infected patients (n = 651). The primary aim is to investigate the effect of the ARB valsartan compared to placebo on the composite end point of admission to an intensive care unit, mechanical ventilation, or death within 14 days of randomization. The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160 mg bid, and the placebo arm will receive matching placebo. Treatment duration will be 14 days, or until the occurrence of the primary end point or until hospital discharge, if either of these occurs within 14 days. The trial is registered at clinicaltrials.gov (NCT04335786, 2020). The PRAETORIAN-COVID trial is a double-blind, placebo-controlled 1:1 randomized trial to assess the effect of valsartan compared to placebo on the occurrence of ICU admission, mechanical ventilation, and death in hospitalized SARS-CoV-2–infected patients. The results of this study might impact the treatment of SARS-CoV-2 patients globally

Use of multiparametric MRI to characterize uterine fibroid tissue types

Background Although the biological characteristics of uterine fibroids (UF) have implications for therapy choice and effectiveness, there is limited MRI data about these characteristics. Currently, the Funaki classification and Scaled Signal Intensity (SSI) are used to predict treatment outcome but both screening-tools appear to be suboptimal. Therefore, multiparametric and quantitative MRI was studied to evaluate various biological characteristics of UF. Methods 87 patients with UF underwent an MRI-examination. Differences between UF tissues and myometrium were investigated using T2-mapping, Apparent Diffusion Coefficient (ADC) maps with different b-value combinations, contrast-enhanced T1-weighted and T2-weighted imaging. Additionally, the Funaki classification and SSI were calculated. Results Significant differences between myometrium and UF tissue in T2-mapping (p = 0.001), long-TE ADC low b-values (p = 0.002), ADC all b-values (p < 0.001) and high b-values (p < 0.001) were found. Significant differences between Funaki type 3 versus type 1 and 2 were observed in SSI (p < 0.001) and T2-values (p < 0.001). Significant correlations were found between SSI and T2-mapping (p < 0.001; rho(s) = 0.82), ADC all b-values (p = 0.004; rho(s) = 0.31), ADC high b-values (p < 0.001; rho(s) = 0.44) and long-TE ADC low b-values (p = 0.004; rho(s) = 0.31). Conclusions Quantitative MR-data allowed us to distinguish UF tissue from myometrium and to discriminate different UF tissue types and may, therefore, be a useful tool to predict treatment outcome/determine optimal treatment modality

OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors.

This phase I/IIa study (NCT02737475) evaluated the safety and activity of BMS-986178, a fully human OX40 agonist IgG1 mAb, ± nivolumab and/or ipilimumab in patients with advanced solid tumors. Patients (with non-small cell lung, renal cell, bladder, other advanced cancers) received BMS-986178 (20-320 mg) ± nivolumab (240-480 mg) and/or ipilimumab (1-3 mg/kg). The primary endpoint was safety. Additional endpoints included immunogenicity, pharmacodynamics, pharmacokinetics, and antitumor activity per RECIST version 1.1. Twenty patients received BMS-986178 monotherapy, and 145 received combination therapy in various regimens (including two patients receiving nivolumab monotherapy). With a follow-up of 1.1 to 103.6 weeks, the most common (≥5%) treatment-related adverse events (TRAEs) included fatigue, pruritus, rash, pyrexia, diarrhea, and infusion-related reactions. Overall, grade 3-4 TRAEs occurred in one of 20 patients (5%) receiving BMS-986178 monotherapy, six of 79 (8%) receiving BMS-986178 plus nivolumab, zero of two receiving nivolumab monotherapy, six of 41 (15%) receiving BMS-986178 plus ipilimumab, and three of 23 (13%) receiving BMS-986178 plus nivolumab plus ipilimumab. No deaths occurred. No dose-limiting toxicities were observed with monotherapy, and the MTD was not reached in either the monotherapy or the combination escalation cohorts. No objective responses were seen with BMS-986178 alone; objective response rates ranged from 0% to 13% across combination therapy cohorts. In this study, BMS-986178 ± nivolumab and/or ipilimumab appeared to have a manageable safety profile, but no clear efficacy signal was observed above that expected for nivolumab and/or ipilimumab

Tuning of the optical and electrochemical properties of the primary donor bacteriochlorophylls in the reaction centre from Rhodobacter sphaeroides: spectroscopy and structure

A series of mutations have been introduced at residue 168 of the L-subunit of the reaction centre from Rhodobacter sphaeroides. In the wild-type reaction centre, residue His L168 donates a strong hydrogen bond to the acetyl carbonyl group of one of the pair of bacteriochlorophylls (BChl) that constitutes the primary donor of electrons. Mutation of His L168 to Phe or Leu causes a large decrease in the mid-point redox potential of the primary electron donor, consistent with removal of this strong hydrogen bond. Mutations to Lys, Asp and Arg cause smaller decreases in redox potential, indicative of the presence of weak hydrogen bond and/or an electrostatic effect of the polar residue. A spectroscopic analysis of the mutant complexes suggests that replacement of the wild-type His residue causes a decrease in the strength of the coupling between the two primary donor bacteriochlorophylls. The X-ray crystal structure of the mutant in which His L168 has been replaced by Phe (HL168F) was determined to a resolution of 2.5 Å, and the structural model of the HL168F mutant was compared with that of the wild-type complex. The mutation causes a shift in the position of the primary donor bacteriochlorophyll that is adjacent to residue L168, and also affects the conformation of the acetyl carbonyl group of this bacteriochlorophyll. This conformational change constitutes an approximately 27° through-plane rotation, rather than the large into-plane rotation that has been widely discussed in the context of the HL168F mutation. The possible structural basis of the altered spectroscopic properties of the HL168F mutant reaction centre is discussed, as is the relevance of the X-ray crystal structure of the HL168F mutant to the possible structures of the remaining mutant complexes