A Simple Method for Rise-Time Discrimination of Slow Pulses from Charge-Sensitive Preamplifiers

Performance of a simple method of particle identification via pulse rise time discrimination is demonstrated for slow pulses from charge-sensitive preamplifiers with rise times ranging from 10 ns to 500 ns. The method is based on a comparison of the amplitudes of two pulses, derived from each raw preamplifier pulse with two amplifiers with largely differing shaping times, using a fast peak-sensing ADC. For the injected charges corresponding to energy deposits in silicon detectors of a few tens of MeV, a rise time resolution of the order of 1 ns can be achieved. The identification method is applicable in particle experiments involving large-area silicon detectors, but is easily adaptable to other detectors with a response corresponding to significantly different pulse rise times for different particle species.Comment: 10 pages, 7 figure

Liquid-Gas Coexistence and Critical Behavior in Boxed Pseudo-Fermi Matter

A schematic model is presented that allows one to study the behavior of interacting pseudo-Fermi matter locked in a thermostatic box. As a function of the box volume and temperature, the matter is seen to show all of the familiar charactersitics of a Van der Waals gas, which include the coexistence of two phases under certain circumstances and the presence of a critical point

The Role of Surface Entropy in Statistical Emission of Massive Fragments from Equilibrated Nuclear Systems

Statistical fragment emission from excited nuclear systems is studied within the framework of a schematic Fermi-gas model combined with Weisskopf's detailed balance approach. The formalism considers thermal expansion of finite nuclear systems and pays special attention to the role of the diffuse surface region in the decay of hot equilibrated systems. It is found that with increasing excitation energy, effects of surface entropy lead to a systematic and significant reduction of effective emission barriers for fragments and, eventually, to the vanishing of these barriers. The formalism provides a natural explanation for the occurrence of negative nuclear heat capacities reported in the literature. It also accounts for the observed linearity of pseudo-Arrhenius plots of the logarithm of the fragment emission probability {\it versus} the inverse square-root of the excitation energy, but does not predict true Arrhenius behavior of these emission probabilities

Proton Differential Elliptic Flow and the Isospin-Dependence of the Nuclear Equation of State

Within an isospin-dependent transport model for nuclear reactions involving neutron-rich nuclei, we study the first-order direct transverse flow of protons and their second-order differential elliptic flow as a function of transverse momentum. It is found that the differential elliptic flow of mid-rapidity protons, especially at high transverse momenta, is much more sensitive to the isospin dependence of the nuclear equation of state than the direct flow. Origins of these different sensitivities and their implications to the experimental determination of the isospin dependence of the nuclear equation of state by using neutron-rich heavy-ion collisions at intermediate energies are discussed.Comment: 15 pages, 6 figures. Phys. Rev. C (2001) in pres

Real-world experience of CPX-351 as first-line treatment for patients with acute myeloid leukemia

Abstract To investigate the efficacy and toxicities of CPX-351 outside a clinical trial, we analyzed 188 patients (median age 65 years, range 26–80) treated for therapy-related acute myeloid leukemia (t-AML, 29%) or AML with myelodysplasia-related changes (AML-MRC, 70%). Eighty-six percent received one, 14% two induction cycles, and 10% received consolidation (representing 22% of patients with CR/CRi) with CPX-351. Following induction, CR/CRi rate was 47% including 64% of patients with available information achieving measurable residual disease (MRD) negativity (<10−3) as measured by flow cytometry. After a median follow-up of 9.3 months, median overall survival (OS) was 21 months and 1-year OS rate 64%. In multivariate analysis, complex karyotype predicted lower response (p = 0.0001), while pretreatment with hypomethylating agents (p = 0.02) and adverse European LeukemiaNet 2017 genetic risk (p < 0.0001) were associated with lower OS. Allogeneic hematopoietic cell transplantation (allo-HCT) was performed in 116 patients (62%) resulting in promising outcome (median survival not reached, 1-year OS 73%), especially in MRD-negative patients (p = 0.048). With 69% of patients developing grade III/IV non-hematologic toxicity following induction and a day 30-mortality of 8% the safety profile was consistent with previous findings. These real-world data confirm CPX-351 as efficient treatment for these high-risk AML patients facilitating allo-HCT in many patients with promising outcome after transplantation

Mutations in KEOPS-Complex Genes Cause Nephrotic Syndrome with Primary Microcephaly

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms

Joint analysis of the energy spectrum of ultra-high-energy cosmic rays measured at the Pierre Auger Observatory and the Telescope Array

The measurement of the energy spectrum of ultra-high-energy cosmic rays (UHECRs) is of crucial importance to clarify their origin and acceleration mechanisms. The Pierre Auger Observatory in Argentina and the Telescope Array (TA) in the US have reported their measurements of UHECR energy spectra observed in the southern and northern hemisphere, respectively. The region of the sky accessible to both Observatories ([−15,+24] degrees in declination) can be used to cross-calibrate the two spectra. The Auger-TA energy spectrum working group was organized in 2012 and has been working to understand the uncertainties in energy scale in both experiments, their systematic differences, and differences in the shape of the spectra. In previous works, we reported that there was an overall agreement of the energy spectra measured by the two observatories below 10 EeV while at higher energies, a remaining significant difference was observed in the common declination band. We revisit this issue to understand its origin by examining the systematic uncertainties, statistical effects, and other possibilities. We will also discuss the differences in the spectra in different declination bands and a new feature in the spectrum recently reported by the Auger Collaboration

The UHECR dipole and quadrupole in the latest data from the original Auger and TA surface detectors

The sources of ultra-high-energy cosmic rays are still unknown, but assuming standard physics, they are expected to lie within a few hundred megaparsecs from us. Indeed, over cosmological distances cosmic rays lose energy to interactions with background photons, at a rate depending on their mass number and energy and properties of photonuclear interactions and photon backgrounds. The universe is not homogeneous at such scales, hence the distribution of the arrival directions of cosmic rays is expected to reflect the inhomogeneities in the distribution of galaxies; the shorter the energy loss lengths, the stronger the expected anisotropies. Galactic and intergalactic magnetic fields can blur and distort the picture, but the magnitudes of the largest-scale anisotropies, namely the dipole and quadrupole moments, are the most robust to their effects. Measuring them with no bias regardless of any higher-order multipoles is not possible except with full-sky coverage. In this work, we achieve this in three energy ranges (approximately 8--16 EeV, 16--32 EeV, and 32--∞ EeV) by combining surface-detector data collected at the Pierre Auger Observatory until 2020 and at the Telescope Array (TA) until 2019, before the completion of the upgrades of the arrays with new scintillator detectors. We find that the full-sky coverage achieved by combining Auger and TA data reduces the uncertainties on the north-south components of the dipole and quadrupole in half compared to Auger-only results

The UHECR dipole and quadrupole in the latest data from the original Auger and TA surface detectors

The sources of ultra-high-energy cosmic rays are still unknown, but assuming standard physics, they are expected to lie within a few hundred megaparsecs from us. Indeed, over cosmological distances cosmic rays lose energy to interactions with background photons, at a rate depending on their mass number and energy and properties of photonuclear interactions and photon backgrounds. The universe is not homogeneous at such scales, hence the distribution of the arrival directions of cosmic rays is expected to reflect the inhomogeneities in the distribution of galaxies; the shorter the energy loss lengths, the stronger the expected anisotropies. Galactic and intergalactic magnetic fields can blur and distort the picture, but the magnitudes of the largest-scale anisotropies, namely the dipole and quadrupole moments, are the most robust to their effects. Measuring them with no bias regardless of any higher-order multipoles is not possible except with full-sky coverage. In this work, we achieve this in three energy ranges (approximately 8--16 EeV, 16--32 EeV, and 32--∞ EeV) by combining surface-detector data collected at the Pierre Auger Observatory until 2020 and at the Telescope Array (TA) until 2019, before the completion of the upgrades of the arrays with new scintillator detectors. We find that the full-sky coverage achieved by combining Auger and TA data reduces the uncertainties on the north-south components of the dipole and quadrupole in half compared to Auger-only results

UHECR arrival directions in the latest data from the original Auger and TA surface detectors and nearby galaxies

The distribution of ultra-high-energy cosmic-ray arrival directions appears to be nearly isotropic except for a dipole moment of order $6 \times (E/10~\mathrm{EeV})$ per cent. Nonetheless, at the highest energies, as the number of possible candidate sources within the propagation horizon and the magnetic deflections both shrink, smaller-scale anisotropies might be expected to emerge. On the other hand, the flux suppression reduces the statistics available for searching for such anisotropies. In this work, we consider two different lists of candidate sources: a sample of nearby starburst galaxies and the 2MRS catalog tracing stellar mass within 250 Mpc. We combine surface-detector data collected at the Pierre Auger Observatory until 2020 and the Telescope Array until 2019, and use them to test models in which UHECRs comprise an isotropic background and a foreground originating from the candidate sources and randomly deflected by magnetic fields. The free parameters of these models are the energy threshold, the signal fraction, and the search angular scale. We find a correlation between the arrival directions of $11.8\%_{-3.1\%}^{+5.0\%}$ of cosmic rays detected with $E \ge 38~\mathrm{EeV}$ by Auger or with $E \gtrsim 49~\mathrm{EeV}$ by TA and the position of nearby starburst galaxies on a ${15.5^\circ}_{-3.2^\circ}^{+5.3^\circ}$ angular scale, with a 4.2σ post-trial significance, as well as a weaker correlation with the overall galaxy distribution