Comparative Conflict Resolution Procedures in Taxation: An Analytic Comparative Study

Tax administrators in well developed countries rarely have either occasion or opportunity to compare experiences or exchange opinions regarding procedures and practices utilized in administering complicated tax laws. Moreover, there is little comparative literature on the subject. Even the tax institutes which are internationally oriented usually focus on substantive tax principles, not procedures and practices. Hopefully, therefore, administrators in highly developed countries will find useful this analytic comparison of practices and procedures through which six of their number resolve disputable income tax questions -administratively and judicially. Concern for tax administrators in well developed countries, however, was not the prime motivation for this study. The initial conception grew out of the belief that administrators in countries just now developing would find especially useful an analytic comparison of diverse functioning models which had evolved out of long experience. Since these now developing countries differ from one another on many counts, it was imperative that there be equally wide dissimilarity among the several experienced countries selected as models. Thus, the choice of Belgium, France, West Germany, Great Britain, the Netherlands, and the United States. These countries differ in their size and population, the complexity and precision of their tax statutes, the degree their legislative bodies provide additional guidance through pre-enactment materials, the assessment system used (self- versus non-self-assessment systems), the standards of construction to which their courts traditionally conform, the theoretical status assigned by each to the doctrine of precedent, and the types of persons available to handle tax disputes-both within and without the government. Consequently, it was possible to determine whether such basic differences were relevant or irrelevant when choosing, from among the alternative functioning models, the structural arrangement and practices most appropriate for each level involved in the conflict resolution process. Also, the analytic comparison contained in the first four chapters should enable any given country to determine the extent to which diverse parts of different wholes are adaptable to its situation. The third purpose of this study is a byproduct of the first two. Practitioners engaged in international tax practice may gain a useful insight into the conflict resolution process followed in each of the six countries covered.https://repository.law.umich.edu/michigan_legal_studies/1005/thumbnail.jp

Comparative Conflict Resolution Procedures in Taxation: An Analytic Comparative Study

Tax administrators in well developed countries rarely have either occasion or opportunity to compare experiences or exchange opinions regarding procedures and practices utilized in administering complicated tax laws. Moreover, there is little comparative literature on the subject. Even the tax institutes which are internationally oriented usually focus on substantive tax principles, not procedures and practices. Hopefully, therefore, administrators in highly developed countries will find useful this analytic comparison of practices and procedures through which six of their number resolve disputable income tax questions -administratively and judicially. Concern for tax administrators in well developed countries, however, was not the prime motivation for this study. The initial conception grew out of the belief that administrators in countries just now developing would find especially useful an analytic comparison of diverse functioning models which had evolved out of long experience. Since these now developing countries differ from one another on many counts, it was imperative that there be equally wide dissimilarity among the several experienced countries selected as models. Thus, the choice of Belgium, France, West Germany, Great Britain, the Netherlands, and the United States. These countries differ in their size and population, the complexity and precision of their tax statutes, the degree their legislative bodies provide additional guidance through pre-enactment materials, the assessment system used (self- versus non-self-assessment systems), the standards of construction to which their courts traditionally conform, the theoretical status assigned by each to the doctrine of precedent, and the types of persons available to handle tax disputes-both within and without the government. Consequently, it was possible to determine whether such basic differences were relevant or irrelevant when choosing, from among the alternative functioning models, the structural arrangement and practices most appropriate for each level involved in the conflict resolution process. Also, the analytic comparison contained in the first four chapters should enable any given country to determine the extent to which diverse parts of different wholes are adaptable to its situation. The third purpose of this study is a byproduct of the first two. Practitioners engaged in international tax practice may gain a useful insight into the conflict resolution process followed in each of the six countries covered.https://repository.law.umich.edu/michigan_legal_studies/1005/thumbnail.jp

MCL-1 Inhibition Overcomes Anti-apoptotic Adaptation to Targeted Therapies in B-Cell Precursor Acute Lymphoblastic Leukemia

Multiple targeted therapies are currently explored for pediatric and young adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment. However, this new armamentarium of therapies faces an old problem: choosing the right treatment for each patient. The lack of predictive biomarkers is particularly worrying for pediatric patients since it impairs the implementation of new treatments in the clinic. In this study, we used the functional assay dynamic BH3 profiling (DBP) to evaluate two new treatments for BCP-ALL that could improve clinical outcome, especially for relapsed patients. We found that the MEK inhibitor trametinib and the multi-target tyrosine kinase inhibitor sunitinib exquisitely increased apoptotic priming in an NRAS-mutant and in a KMT2A-rearranged cell line presenting a high expression of FLT3, respectively. Following these observations, we sought to study potential adaptations to these treatments. Indeed, we identified with DBP anti-apoptotic changes in the BCL-2 family after treatment, particularly involving MCL-1 – a pro-survival strategy previously observed in adult cancers. To overcome this adaptation, we employed the BH3 mimetic S63845, a specific MCL-1 inhibitor, and evaluated its sequential addition to both kinase inhibitors to overcome resistance. We observed that the metronomic combination of both drugs with S63845 was synergistic and showed an increased efficacy compared to single agents. Similar observations were made in BCP-ALL KMT2A-rearranged PDX cells in response to sunitinib, showing an analogous DBP profile to the SEM cell line. These findings demonstrate that rational sequences of targeted agents with BH3 mimetics, now extensively explored in clinical trials, may improve treatment effectiveness by overcoming anti-apoptotic adaptations in BCP-ALL.JM acknowledges the Ramon y Cajal Program, Ministerio de Economia y Competitividad (RYC-2015-18357) and the Spanish National Plan “Retos Investigacion” I + D + i (RTI2018-094533-A-I00) from Ministerio de Ciencia, Innovación y Universidades. This work was supported by the CELLEX foundation and the Networking Biomedical Research Center (CIBER), Spain. CIBER is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III (RD16/0006/0012), with the support of the European Regional Development Fund (ERDF). This work was also partially funded by the CERCA Program and by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2017 SGR 1079). FS: Medical Faculty of Ulm University (Clinician Scientist Programme). K-MD and LM: German Research Foundation (DFG, SFB 1074)

A planar multipole ion trap

We report on the realisation of a chip-based multipole ion trap manufactured using micro-electromechanical systems (MEMS) technology. It provides ion confinement in an almost field-free volume between two planes of radiofrequency electrodes, deposited on glass substrates, which allows for optical access to the trap. An analytical model of the effective trapping potential is presented and compared with numerical calculations. Stable trapping of argon ions is achieved and a lifetime of 16s is measured. Electrostatic charging of the chip surfaces is studied and found to agree with a numerical estimate

Formation of ultracold RbCs molecules by photoassociation

The formation of ultracold metastable RbCs molecules is observed in a double species magneto-optical trap through photoassociation below the ^85Rb(5S_1/2)+^133Cs(6P_3/2) dissociation limit followed by spontaneous emission. The molecules are detected by resonance enhanced two-photon ionization. Using accurate quantum chemistry calculations of the potential energy curves and transition dipole moment, we interpret the observed photoassociation process as occurring at short internuclear distance, in contrast with most previous cold atom photoassociation studies. The vibrational levels excited by photoassociation belong to the 5th 0^+ or the 4th 0^- electronic states correlated to the Rb(5P_1/2,3/2)+Cs(6S_1/2) dissociation limit. The computed vibrational distribution of the produced molecules shows that they are stabilized in deeply bound vibrational states of the lowest triplet state. We also predict that a noticeable fraction of molecules is produced in the lowest level of the electronic ground state

Phospho-CRKL monitoring for the assessment of BCR-ABL activity in imatinib-resistant chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia patients treated with nilotinib

n/

Ideal Multipole Ion Traps from Planar Ring Electrodes

We present designs for multipole ion traps based on a set of planar, annular, concentric electrodes which require only rf potentials to confine ions. We illustrate the desirable properties of the traps by considering a few simple cases of confined ions. We predict that mm-scale surface traps may have trap depths as high as tens of electron volts, or micromotion amplitudes in a 2-D ion crystal as low as tens of nanometers, when parameters of a magnitude common in the field are chosen. Several example traps are studied, and the scaling of those properties with voltage, frequency, and trap scale, for small numbers of ions, is derived. In addition, ions with very high charge-to-mass ratios may be confined in the trap, and species of very different charge-to-mass ratios may be simultaneously confined. Applications of these traps include quantum information science, frequency metrology, and cold ion-atom collisions.Comment: Section on trapping of a single ion added, two figures added, one formula corrected, otherwise minor change

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Azimuthal asymmetry in the risetime of the surface detector signals of the Pierre Auger Observatory

The azimuthal asymmetry in the risetime of signals in Auger surface detector stations is a source of information on shower development. The azimuthal asymmetry is due to a combination of the longitudinal evolution of the shower and geometrical effects related to the angles of incidence of the particles into the detectors. The magnitude of the effect depends upon the zenith angle and state of development of the shower and thus provides a novel observable, $(\sec \theta)_\mathrm{max}$, sensitive to the mass composition of cosmic rays above $3 \times 10^{18}$ eV. By comparing measurements with predictions from shower simulations, we find for both of our adopted models of hadronic physics (QGSJETII-04 and EPOS-LHC) an indication that the mean cosmic-ray mass increases slowly with energy, as has been inferred from other studies. However, the mass estimates are dependent on the shower model and on the range of distance from the shower core selected. Thus the method has uncovered further deficiencies in our understanding of shower modelling that must be resolved before the mass composition can be inferred from $(\sec \theta)_\mathrm{max}$.Comment: Replaced with published version. Added journal reference and DO

Ultrahigh-energy neutrino follow-up of Gravitational Wave events GW150914 and GW151226 with the Pierre Auger Observatory

On September 14, 2015 the Advanced LIGO detectors observed their first gravitational-wave (GW) transient GW150914. This was followed by a second GW event observed on December 26, 2015. Both events were inferred to have arisen from the merger of black holes in binary systems. Such a system may emit neutrinos if there are magnetic fields and disk debris remaining from the formation of the two black holes. With the surface detector array of the Pierre Auger Observatory we can search for neutrinos with energy above 100 PeV from point-like sources across the sky with equatorial declination from about -65 deg. to +60 deg., and in particular from a fraction of the 90% confidence-level (CL) inferred positions in the sky of GW150914 and GW151226. A targeted search for highly-inclined extensive air showers, produced either by interactions of downward-going neutrinos of all flavors in the atmosphere or by the decays of tau leptons originating from tau-neutrino interactions in the Earth's crust (Earth-skimming neutrinos), yielded no candidates in the Auger data collected within $\pm 500$ s around or 1 day after the coordinated universal time (UTC) of GW150914 and GW151226, as well as in the same search periods relative to the UTC time of the GW candidate event LVT151012. From the non-observation we constrain the amount of energy radiated in ultrahigh-energy neutrinos from such remarkable events.Comment: Published version. Added journal reference and DOI. Added Report Numbe