Neutron Scattering as a Powerful Tool to Investigate Magnetic Shape Memory Alloys: A Review

Magnetic shape memory alloys (MSMAs) are an interesting class of smart materials characterized by undergoing macroscopic deformations upon the application of a pertinent stimulus: temperature, stress and/or external magnetic fields. Since the deformation is rapid and contactless, these materials are being extensively investigated for a plethora of applications, such as sensors and actuators for the medical, automotive and space industries, energy harvesting and damping devices, among others. These materials also exhibit a giant magnetocaloric effect, whereby they are very promising for magnetic refrigeration. The applications in which they can be used are extremely dependent on the material properties, which are, in turn, greatly conditioned by the structure, atomic ordering and magnetism of a material. Particularly, exploring the material structure is essential in order to push forward the current application limitations of the MSMAs. Among the wide range of available characterization tools, neutron scattering techniques stand out in acquiring advanced knowledge about the structure and magnetism of these alloys. Throughout this manuscript, a comprehensive review about the characterization of MSMAs using neutron techniques is presented. Several elastic neutron scattering techniques will be explained and exemplified, covering neutron imaging techniques—such as radiography, tomography and texture diffractometry; diffraction techniques—magnetic (polarized neutron) diffraction, powder neutron diffraction and single crystal neutron diffraction, reflectometry and small angle neutron scattering. This will be complemented with a few examples where inelastic neutron scattering has been employed to obtain information about the phonon dispersion in MSMAs.This work has been carried out with the financial support of the Spanish Ministry of Science, Innovation and Universities (project RTI2018-094683-B-C53-54) and Basque Government Department of Education (project IT1245-19). N.A.R.-L. wants to thank the Basque Government (Department of Education) for providing funding under the specific investigation PFPI grant

Testing the Applicability of 119Sn Mössbauer Spectroscopy for the Internal Stress Study in Ternary and Co-Doped Ni-Mn-Sn Metamagnetic Alloys

The influence of both the Co addition and the internal stress on the atomic level magnetism is comparatively studied in Ni50Mn37Sn13 and Ni45Mn38Sn13Co4 alloys by magnetic measurements and 119Sn Mössbauer spectroscopy. The results show that the saturation magnetization and the hyperfine field follow the same temperature trend. The internal stress state is investigated by subjecting the samples to milling and annealing treatments, and tracking the singlet component revealed by 119Sn Mössbauer spectroscopy. Contrary to what was expected, in the Co-doped Ni-Mn-Sn sample the singlet component can be resolved between the milled and annealed states in both martensite and austenite phases. Therefore, the results demonstrate the feasibility of tracking the singlet component upon the structural recovery in Co-doped Ni-Mn-Sn alloys in a much wider range than in ternary alloys. In addition, it is concluded that the transferred dipolar field at Sn from the neighbor magnetic atoms depends very strongly on the stress field and on the microstructural order surrounding Sn atoms. The observed sensitivity of Sn Mössbauer probe atoms to slight microstructural distortions make 119 Sn a powerful technique for the characterization of the stress present in Sn containing metamagnetic shape memory alloys.This research was funded by Projects RTI2018-094683-B-C5 (4,5) (MCIU/AEI/FEDER, UE) and Basque Government Grant IT-1005–16

Atypical carcinoid tumours of the lung: prognostic factors and patterns of recurrence

Background: Atypical carcinoids (AC) of the lung are rare intermediate-grade neuroendocrine neoplasms. Prognostic factors for these tumours are undefined. Methods: Our cooperative group retrieved data on 127 patients operated between 1980 and 2009 because of an AC. Several clinical and pathological features were studied. Results: In a univariable analysis, T-status (p=0.005), N-status (p=0.021), preoperative M-status (previously treated) (p=0.04), and distant recurrence developed during the outcome (p<0.001) presented statistically significant differences related to survival of these patients. In a multivariable analysis, only distant recurrence was demonstrated to be an independent risk factor for survival (p<0.001; HR: 13.1). During the monitoring, 25.2% of the patients presented some kind of recurrence. When we studied recurrence factors in a univariable manner, sublobar resections presented significant relationship with locoregional recurrence (p<0.001). In the case of distant recurrence, T and N status presented significant differences. Patients with preoperative M1 status presented higher frequencies of locoregional and distant recurrence (p=0.004 and p<0.001, respectively). In a multivariable analysis, sublobar resection was an independent prognostic factor to predict locoregional recurrence (p=0.002; HR: 18.1). Conclusions: Complete standard surgical resection with radical lymphadenectomy is essential for AC. Sublobar resections are related to locoregional recurrence, so they should be avoided except for carefully selected patients. Nodal status is an important prognostic factor to predict survival and recurrence. Distant recurrence is related to poor outcome

Influence of Structural Defects on the Properties of Metamagnetic Shape Memory Alloys

The production of μ-particles of Metamagnetic Shape Memory Alloys by crushing and subsequent ball milling process has been analyzed. The high energy involved in the milling process induces large internal stresses and high density of defects with a strong influence on the martensitic transformation; the interphase creation and its movement during the martensitic transformation produces frictional contributions to the entropy change (exothermic process) both during forward and reverse transformation. The frictional contribution increases with the milling time as a consequence of the interaction between defects and interphases. The influence of the frictional terms on the magnetocaloric effect has been evidenced. Besides, the presence of antiphase boundaries linked to superdislocations helps to understand the spin-glass behavior at low temperatures in martensite. Finally, the particles in the deformed state were introduced in a photosensitive polymer. The mechanical damping associated to the Martensitic Transformation (MT) of the particles is clearly distinguished in the produced composite, which could be interesting for the development of magnetically-tunable mechanical dampers.This research was funded by Projects RTI2018-094683-B-C5 (4,5) (MCIU/AEI/FEDER,UE); ASACTEI Pcia.Santa Fe IO-2017-00138, PID-UNR ING 575 and ING 612 (2018–202

Lateral flow glyco‐assays for the rapid and low‐cost detection of lectins–polymeric linkers and particle engineering are essential for selectivity and performance

Lateral flow immuno‐assays, such as the home pregnancy test, are rapid point‐of‐care diagnostics that use antibody‐coated nanoparticles to bind antigens/analytes (e.g., viruses, toxins or hormones). Ease of use, no need for centralized infrastructure and low‐cost, makes these devices appealing for rapid disease identification, especially in low‐resource environments. Here glycosylated polymer‐coated nanoparticles are demonstrated for the sensitive, label‐free detection of lectins in lateral flow and flow‐through. The systems introduced here use glycans, not antibodies, to provide recognition: a “lateral flow glyco‐assay,” providing unique biosensing opportunities. Glycans are installed onto polymer termini and immobilized onto gold nanoparticles, providing colloidal stability but crucially also introducing assay tunability and selectivity. Using soybean agglutinin and Ricinus communis agglutinin I (RCA120) as model analytes, the impact of polymer chain length and nanoparticle core size are evaluated, with chain length found to have a significant effect on signal generation—highlighting the need to control the macromolecular architecture to tune response. With optimized systems, lectins are detectable at subnanomolar concentrations, comparable to antibody‐based systems. Complete lateral flow devices are also assembled to show how these devices can be deployed in the “real world.” This work shows that glycan‐binding can be a valuable tool in rapid diagnostics

A bicyclic α-iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration

I2 receptors (I2-IR) are widely distributed in the central nervous system. I2-IR ligands are associated with a neuroprotective effect but, as I2-IR structure remains unknown, the discovery of better and more selective ligands is necessary to understand the pharmacological and molecular implications of I2-IR. Recently, we described a new imidazoline-structure family which showed high affinity and selectivity for I2-IR. In vivo studies in mice indicated a neuroprotective role and revealed beneficial effects in behaviour and cognition with a murine model of neurodegeneration, senescence-accelerated prone mouse (SAMP8). Herein, we report a novel non-imidazoline-structure of bicyclic α-iminophosphonates family with high affinities for I2-IR. In vivo studies in 5X-FAD mice (a transgenic representative model of AD) and SAMP8 mice (a model of neurodegeneration linked to aging) showed an improvement in behaviour and cognition, a reduction of AD hallmarks and of neuroinflammation markers for the mice treated with the lead compound B06. After evaluating several pathways associated with neurodegeneration, we demonstrated that CaN pathway plays a critical role on the neuroprotective effects of I2-IR ligands on SAMP8 mice model. To rule out warnings of the novel family, we calculated DMPK and physicochemical properties for the novel bicyclic α-iminophosphonates. As well, we carried out drug metabolism, safety studies and in vivo pharmacokinetics for lead compound B06. In summary, we present a novel family of I2-IR ligands, its effectiveness in in vivo models and the possible neuroprotective molecular mechanism mediated by them. This highlights that the modulation of I2-IR by bicyclic α-iminophosphonates may open a new therapeutic venue for unmet neurodegenerative conditions

Bicyclic alfa-iminophosphonates as high affinity imidazoline I2 receptor ligands for Alzheimer's disease

Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffered from neurodegenerative disorders, are orphan from the structural point of view and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and 3D-QSAR studies of a new family of bicyclic α-iminophosphonates endowed with relevant affinities for human brain I2-IR. Acute treatment in mice with a selected compound significantly decreased the FADD protein in the hippocampus, a key marker in neuroprotective actions. Additionally, in vivo studies in the familial Alzheimer's disease 5xFAD murine model revealed beneficial effects in behavior and cognition. These results are supported by changes in molecular pathways related to cognitive decline and Alzheimer's disease. Therefore bicyclic α-iminophosphonates are tools that may open new therapeutic avenues for I2-IR, particularly for unmet neurodegenerative conditions

Cushing's Syndrome and Fetal Features Resurgence in Adrenal Cortex–Specific Prkar1a Knockout Mice

Carney complex (CNC) is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD), a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 α-regulatory subunit (R1α) of the cAMP–dependent protein kinase (PKA) have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1α loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO). AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1α loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1α is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD