Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms

Proliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smoldering multiple myeloma (SMM), and 266 multiple myeloma (MM) patients. Ratio-PA of 0.77 ± 0.12, 1.94 ± 0.52, and 11.2 ± 0.7 (p < 0.0001) were observed in MGUS, SMM, and MM patients. Ten-year overall survival (10y-OS) rates for patients with low/high Ratio-PA were 93.5%/77.3% p < 0.0001) for MGUS, 82.5%/64.7% (p < 0.05) for SMM, and 62.3%/47.0% (p < 0.05) for MM. For patients with low, intermediate, and high risk, 10y-OS for low/high Ratio-PA were 95.5%/72.9% (p < 0.0001), 74.2%/50.4% (p < 0.0001), and 35.3%/20.0% (p = 0.836), respectively. Ratio-PA was an independent prognostic factor for OS (HR = 2.119, p < 0.0001, Harrell-C-statistic = 0.7440 ± 0.0194) when co-analyzed with sex, age, and standard risk. In patients with Ratio-PA^high, only first-line therapy with VRd/VTd, but not PAD/VCD, coupled with ASCT was associated with high 10y-OS (82.7%). Tumor cell Ratio-PA estimated at diagnosis offers a prognostic biomarker that complements standard risk stratification and helps to guide the clinical management of pre-malignant and symptomatic PCNs. Every effort should be made to provide first-line therapies including VTd or VRd associated with ASCT to patients with Ratio-PA^high at higher risk of progression and death.     

Deep Phenotyping of Superficial Epidermolytic Ichthyosis due to a Recurrent Mutation in KRT2

Superficial epidermolytic ichthyosis (SEI) is an autosomal dominant inherited ichthyosis. SEI is caused by mutations in KRT2 and frequently shows erythroderma and widespread blistering at birth. We report the clinical manifestations of two patients from a Japanese family with SEI caused by a hotspot mutation, p.Glu487Lys, in KRT2. In addition, we summarize previous reports on SEI patients with the identical mutation. One of the two patients had disease onset at the age of 7 months. The other patient’s age of onset is unknown, but it was in childhood. Neither of the two patients showed erythroderma. To perform deep phenotyping, we studied the age of onset and the frequency of erythroderma in 34 reported SEI cases with the p.Glu487Lys mutation, including the present cases. Among the cases with sufficient clinical information, 44.4% of the cases that were due to p.Glu487Lys in KRT2 occurred at birth. Erythroderma was observed in 11.1% of the cases with p.Glu487Lys in KRT2.     

Initiation and propagation of surface cracks in rolling fatigue of high hardness steel

Surface cracks initiating flaking failure observed by Sugino in rolling fatigue were further studied.Surface crack initiation was influenced by either running or material conditions, affecting the residual tensile stress just below the rolling contact surface. The fatigue crack is thought to initiate very near the surface by the stress cycle of small tensile residual stress and large compressive contact stress. The amount and direction of the tensile residual stress due to rolling contact varies with the contact geometry, which probably determines the direction of the surface crack and the appearance of flaking. The transition from the surface crack to flaking failure or complete section fracture is material and running condition dependent and is explained by a fracture mechanics concept.     

Te concentration dependent photoemission and inverse-photoemission study of FeSe1?xTex

We have characterized the electronic structure of FeSe_1−xTe_x for various x values using soft x-ray photoemission spectroscopy (SXPES), high-resolution photoemission spectroscopy (HRPES) and inverse photoemission spectroscopy (IPES). The SXPES valence band spectral shape shows that the 2 eV feature in FeSe, which was ascribed to the lower Hubbard band in previous theoretical studies, becomes less prominent with increasing x. HRPES exhibits systematic x dependence of the structure near the Fermi level (E_F): its splitting near E_F and filling of the pseudogap in FeSe. IPES shows two features, near E_F and approximately 6 eV above E_F; the former may be related to the Fe 3d states hybridized with chalcogenide p states, while the latter may consist of plane-wave-like and Se d components. In the incident electron energy dependence of IPES, the density of states near E_F for FeSe and FeTe has the Fano lineshape characteristic of resonant behavior. These compounds exhibit different resonance profiles, which may reflect the differences in their electronic structures. By combining the PES and IPES data the on-site Coulomb energy was estimated at 3.5 eV for FeSe.     

Ambidextrous strategy and execution in entrepreneurial project-oriented organizations: The case of Pagani supercars

This research explores the dynamics underpinning entrepreneurial project-oriented organizations. Specifically, it focuses on how strategy and execution by projects are managed and how ambidexterity – a firm's ability to exploit old certainties while exploring new possibilities – operates as a logic. The empirical findings from an explorative longitudinal research of supercar maker Pagani Automobili in the period 2007–2019, offer an insight of a complex entrepreneurially led project-oriented organization and suggest three integrative mechanisms that describe the ambidextrous management of the interplay within and between strategy and project levels. Additionally, this research recognizes the critical role of projects also in entrepreneurial environments and suggests that the accomplishment of ambidexterity is unique in nature as it is aimed at reconciling the uniqueness of competitive propositions and that of projects within a unique entrepreneurial environment, opening avenues for more theoretical and empirical studies at the intersection of project management and entrepreneurship.     

Boolean-based fractional order SMC for switching systems: application to a DC-DC buck converter

The combination of sliding mode control and fractional order control (FOC) has received a considerable attention in the last years due to the advances and effectiveness of FOC solving robust control problems. This paper collects different methods to apply FOC in sliding mode problems through the use of fractional order surfaces and proposes a direct boolean control (BC) strategy based on this kind of surfaces. The application of BC is novel and takes advantage of avoiding the use of PWM. Simulation results for a DC-DC buck converter application are given to show the goodness of the proposed approach.     

A novel magneto‐impedance sensor model based on the zeros of Bessel functions

Nowadays, the design of magneto‐impedance (MI) sensors requires the development of lumped circuit models that can be simulated through equivalent impedance circuits relied on Bessel functions. A new impedance model based on Senani's equivalent using the zeros of Bessel functions is developed in this paper. The model allows to describe the impedance as a transfer function that can be easily synthesized by means of current conveyor circuits and passive elements. The mathematical representation was verified under simulation of transfer functions involving different number of poles and zeros. Moreover, the model has been verified using SPICE simulations and measurement results from a fabricated prototype demonstrating its scope and validity. Finally, a study of finite tracking errors of CCIIs used in the implementation of magneto‐impedance sensor has been realized. Copyright © 2014 John Wiley & Sons, Ltd.     

Estimation of soil water repellency of different particle size fractions in relation with carbon content by different methods

The water repellency of soils with different texture under different types of plant cover was determined by applying the WDPT and MED methods to both whole samples and the following size fractions: 2-1, 1-0.5, 0.5-0.25, 0.25-0.05 and <0.05 mm. Based on the results, the soils under maize crop and grassland, which were mostly wettable in the whole samples, exhibited water repellency in the finest fraction (<0.05 mm) as a result of its higher organic carbon content. On the other hand, all fractions in the forest soils, which were extremely water repellent, contributed to the overall repellency; in any case, the MED test revealed that the finest fraction was strongly repellent in the forest soils as well.     

On a branch-and-bound approach for a Huff-like Stackelberg location problem

Modelling the location decision of two competing firms that intend to build a new facility in a planar market can be done by a Huff-like Stackelberg location problem. In a Huff-like model, the market share captured by a firm is given by a gravity model determined by distance calculations to facilities. In a Stackelberg model, the leader is the firm that locates first and takes into account the actions of the competing chain (follower) locating a new facility after the leader. The follower problem is known to be a hard global optimisation problem. The leader problem is even harder, since the leader has to decide on location given the optimal action of the follower. So far, in literature only heuristic approaches have been tested to solve the leader problem. Our research question is to solve the leader problem rigorously in the sense of having a guarantee on the reached accuracy. To answer this question, we develop a branch-and-bound approach. Essentially, the bounding is based on the zero sum concept: what is gain for one chain is loss for the other. We also discuss several ways of creating bounds for the underlying (follower) sub-problems, and show their performance for numerical cases. This work has been supported by the Ministry of Education and Science of Spain through grant SEJ2005/06273/ECON. M. Elena Sáz was supported by a junior research grant of Mansholt Graduate School (Wageningen Universiteit).