The 2021 Magnonics Roadmap.

Magnonics is a budding research field in nanomagnetism and nanoscience that addresses the use of spin waves (magnons) to transmit, store, and process information. The rapid advancements of this field during last one decade in terms of upsurge in research papers, review articles, citations, proposals of devices as well as introduction of new sub-topics prompted us to present the first roadmap on magnonics. This is a collection of 22 sections written by leading experts in this field who review and discuss the current status besides presenting their vision of future perspectives. Today, the principal challenges in applied magnonics are the excitation of sub-100 nm wavelength magnons, their manipulation on the nanoscale and the creation of sub-micrometre devices using low-Gilbert damping magnetic materials and its interconnections to standard electronics. To this end, magnonics offers lower energy consumption, easier integrability and compatibility with CMOS structure, reprogrammability, shorter wavelength, smaller device features, anisotropic properties, negative group velocity, non-reciprocity and efficient tunability by various external stimuli to name a few. Hence, despite being a young research field, magnonics has come a long way since its early inception. This roadmap asserts a milestone for future emerging research directions in magnonics, and hopefully, it will inspire a series of exciting new articles on the same topic in the coming years.

Localized mechanical stimulation of single cells with engineered spatio-temporal profile.

In vivo, cells are frequently exposed to multiple mechanical stimuli arising from the extracellular microenvironment, with a deep impact on many biological functions. On the other hand, current methods for mechanobiology do not allow one to easily replicate in vitro the complex spatio-temporal profile of such mechanical signals. Here we introduce a new platform for studying the mechanical coupling between single cells and a dynamic extracellular environment, based on active substrates for cell culture made of Fe-coated polymeric micropillars. Under the action of quasi-static external magnetic fields, each group of pillars produces synchronous mechanical stimuli at different points of the cell membrane, thanks to the highly controllable pillars' deflection. This method allows one to apply complex stress fields, resulting in the parallel application of localized forces with tunable intensity and temporal profile. The platform has been validated by studying the cellular response to periodic stimuli in NIH3T3 fibroblasts. We find that low-frequency mechanical stimulation affects the actin cytoskeleton, nuclear morphology, and H2B core-histone dynamics and induces MKL transcription-cofactor translocation from nucleus to cytoplasm. The unique capability of the proposed platform to apply stimuli with a tunable temporal profile and high parallelism on a cell culture holds great potential for the investigation of mechanotransduction mechanisms in cells and tissues.

Magnetic domain wall tweezers: a new tool for mechanobiology studies on individual target cells.

In vitro tests are of fundamental importance for investigating cell mechanisms in response to mechanical stimuli or the impact of the genotype on cell mechanical properties. In particular, the application of controlled forces to activate specific bio-pathways and investigate their effects, mimicking the role of the cellular environment, is becoming a prominent approach in the emerging field of mechanobiology. Here, we present an on-chip device based on magnetic domain wall manipulators, which allows the application of finely controlled and localized forces on target living cells. In particular, we demonstrate the application of a magnetic force in the order of hundreds of pN on the membrane of HeLa cells cultured on-chip, via manipulation of 1 µm superparamagnetic beads. Such a mechanical stimulus produces a sizable local indentation of the cellular membrane of about 2 µm. Upon evaluation of the beads' position within the magnetic field originated by the domain wall, the force applied during the experiments is accurately quantified via micromagnetic simulations. The obtained value is in good agreement with that calculated by the application of an elastic model to the cellular membrane.

Thermochemical scanning probe lithography of protein gradients at the nanoscale.

Patterning nanoscale protein gradients is crucial for studying a variety of cellular processes in vitro. Despite the recent development in nano-fabrication technology, combining nanometric resolution and fine control of protein concentrations is still an open challenge. Here, we demonstrate the use of thermochemical scanning probe lithography (tc-SPL) for defining micro- and nano-sized patterns with precisely controlled protein concentration. First, tc-SPL is performed by scanning a heatable atomic force microscopy tip on a polymeric substrate, for locally exposing reactive amino groups on the surface, then the substrate is functionalized with streptavidin and laminin proteins. We show, by fluorescence microscopy on the patterned gradients, that it is possible to precisely tune the concentration of the immobilized proteins by varying the patterning parameters during tc-SPL. This paves the way to the use of tc-SPL for defining protein gradients at the nanoscale, to be used as chemical cues e.g. for studying and regulating cellular processes in vitro.

Nanopatterning reconfigurable magnetic landscapes via thermally assisted scanning probe lithography.

The search for novel tools to control magnetism at the nanoscale is crucial for the development of new paradigms in optics, electronics and spintronics. So far, the fabrication of magnetic nanostructures has been achieved mainly through irreversible structural or chemical modifications. Here, we propose a new concept for creating reconfigurable magnetic nanopatterns by crafting, at the nanoscale, the magnetic anisotropy landscape of a ferromagnetic layer exchange-coupled to an antiferromagnetic layer. By performing localized field cooling with the hot tip of a scanning probe microscope, magnetic structures, with arbitrarily oriented magnetization and tunable unidirectional anisotropy, are reversibly patterned without modifying the film chemistry and topography. This opens unforeseen possibilities for the development of novel metamaterials with finely tuned magnetic properties, such as reconfigurable magneto-plasmonic and magnonic crystals. In this context, we experimentally demonstrate spatially controlled spin wave excitation and propagation in magnetic structures patterned with the proposed method.

Electric control of magnetism at the Fe/BaTiO3 interface.

Interfacial magnetoelectric coupling is a viable path to achieve electrical writing of magnetic information in spintronic devices. For the prototypical Fe/BaTiO3 system, only tiny changes of the interfacial Fe magnetic moment upon reversal of the BaTiO3 dielectric polarization have been predicted so far. Here, by using X-ray magnetic circular dichroism in combination with high-resolution electron microscopy and first principles calculations, we report on an undisclosed physical mechanism for interfacial magnetoelectric coupling in the Fe/BaTiO3 system. At this interface, an ultrathin oxidized iron layer exists, whose magnetization can be electrically and reversibly switched on and off at room temperature by reversing the BaTiO3 polarization. The suppression/recovery of interfacial ferromagnetism results from the asymmetric effect that ionic displacements in BaTiO3 produces on the exchange coupling constants in the interfacial-oxidized Fe layer. The observed giant magnetoelectric response holds potential for optimizing interfacial magnetoelectric coupling in view of efficient, low-power spintronic devices.

Conditions for efficient on-chip magnetic bead detection via magnetoresistive sensors.

A commonly used figure of merit of magnetoresistive sensors employed to detect magnetic beads labeling biomolecules in lab-on-chip applications is the sensor sensitivity (S0) to external magnetic fields in the linear region of the sensor. In this paper we show that, in case of lock-in detection and bead excitation by a small AC magnetic field, S0 is not the good figure of merit to optimize. Indeed, the highest sensitivity to the magnetic beads is achieved biasing the sensor in the region of its characteristics where the product between the DC bias field and the second derivative of the resistance with respect to the magnetic field is maximum. The validity of this criterion, derived from a phenomenological model of bead detection, is proved in case of magnetic tunneling junction sensors detecting magnetic beads with 250nm diameter. This work paves the way to the development of a new generation of sensors properly designed to maximize the bead sensitivity.

Conjugated equine estrogen, raloxifene and arterial stiffness in postmenopausal women.

METHODS: We analyzed the influence of conjugated equine estrogen (CEE) and raloxifene on arterial stiffness. Sixty-seven healthy, normotensive women 1-10 years into menopause were assigned to receive oral placebo, conjugated equine estrogen 0.625 mg, or raloxifene 60 mg. Arterial stiffness was evaluated by measuring the carotid-femoral and femoral-dorsalis pedis pulse wave velocity (CF PWV, FP PWV). Systolic pressure augmentation index (AI) at the carotid artery was obtained with applanation tonometry. RESULTS: Arterial stiffness was not affected by any treatment regimen: placebo (CF PWV before vs. after: 644 vs. 626 cm/s, p = 0.09; FP PWV before vs. after: 1006 vs. 1012 cm/s,p = 0.77; AI before vs. after = 30 vs. 29%, p = 0.55), CEE (CF PWV before vs. after: 642 vs. 600 cm/s, p = 0.11; FP PWV before vs. after: 952 vs. 971 cm/s, p = 0.66; AI before vs. after: 25 vs. 32%, p = 0.82), and raloxifene (CF PWV before vs. after: 636 vs. 601 cm/s, p = 0.12; FP PWV before vs. after: 964 vs. 941 cm/s, p = 0.62; AI before vs. after: 25 vs. 25%, p = 0.65). A correlation occurred between basal stiffness and the degree of reduction in indexes measured, indicating that the higher the basal stiffness, the greater the degree of reduction, particularly in the CEE group: CF PWV (r = - 0.602, p = 0.001); FP PWV (r = - 0.455, p = 0.022); AI (r = - 0.410, p = 0.042). CONCLUSIONS: Conjugated equine estrogen and raloxifene do not seem to affect arterial stiffness of healthy normotensive women less than 10 years since menopause. Reduction in arterial stiffness seems related to its basal level.

Traumatized rat striatum produces neurite-promoting and neurotrophic activities in vitro.

We have previously reported that ciliary neurotrophic factor (CNTF) mRNA is upregulated in the rat striatum following trauma and that its peak is coincident with a peak in the number of GFAP-positive astrocytes. CNTF, or other neurotrophic factors present in the traumatized striatum, may be involved in the dopaminergic fiber sprouting seen following cavitation or graft implantation in animal models of Parkinson's disease. This study was undertaken in order to further characterize the neurotrophic activity present following trauma through the use of bioassays. Adult rats underwent stereotaxic biopsy of the right striatum, and gelatin sponge [gelfoam (GF)] was placed in the resultant cavity. GF was collected from 1 to 30 days following trauma and homogenized. GF extracts (with equal protein concentrations) were assayed using dorsal root ganglion (DRG) explants, dissociated ciliary ganglia (CG), and human dopaminergic neuroblastoma cell (SH-SY5Y) cultures. The GF extracts had significant neurite-promoting activity (NPA) for DRG, CG, and SH-SY5Y cells, with the maximum effect seen 7 days after trauma. NPA was not blocked by anti-nerve growth factor (NGF) Ab, but anti-brain-derived neurotrophic factor (BDNF) Ab significantly blocked the activity for DRG. The GF extracts protected the SH-SY5Y cells from the neurotoxins 6-OHDA and MPP+, as did NGF and BDNF. This neuroprotective effect of GF was not blocked by anti-NGF Ab. This study suggests that the neurotrophic activity in GF extracts has CNTF-like and BDNF-like components as well as another, undefined component.

[Breast cancer in the pregnancy-puerperal cycle]. / Câncer de mama no ciclo grávido-puerperal.

From 1978 to 1988, 611 cases of breast cancer were seen by the Mastology Department of the Beneficência Portuguesa Hospital in São Paulo, Brazil. Thirteen (2.12%) cases were associated to pregnancy, and nine (2.4%) became pregnant after treatment. The patients were submitted to surgery and the authors waited till the end of pregnancy to perform the Rt and/or Qt. Two cases could not be submitted to any kind of treatment. Whenever tests indicated fetal maturity, the option was to perform a caesarean section, and oophorectomy was performed in the most advanced cases. Among patients who became pregnant after treatment, initial cases were predominant and their pregnancies went to term with no problem. The authors compare their results to data found in literature and draw attention to anticonception in mastectomized patients.

[Dermatologic drill biopsy (punch): diagnostic procedures in advanced carcinoma of the breast]. / Pinça de biópsia dermatológica ("punch"): procedimento diagnóstico no carcinoma avançado da mama.

Thirty-seven patients with breast tumors in stage III and IV were selected, and a new method to remove fragments of tissue for anatomopathologic study was used. The "punch" of Keyes was introduced towards the tumor, under strong pressure, with clockwise and counter-clockwise rotational movements. In thirty-eight biopsies, the anatomopathologic study allowed the authors to make a perfect evaluation of the structure, and the diagnosis made was of infiltrating carcinoma of the breast. This method proved to be a quick, safe and simple procedure, free of complications, and it allows for anatomopathologic diagnosis in 100% of the cases.

The effects of 8-hydroxy-2-(di-n-propylamino)tetralin and other serotonergic agonists on performance in a radial maze: a possible role for 5-HT1A receptors in memory.

A group of ten rats was trained to obtain food pellets in an 8-arm radial maze. The effects of pretreatment with (+)-Lysergic acid diethylamide (+)-tartrate (LSD), m-trifluoromethylphenylpiperazine (TFMPP), 5-methoxy-N,N-dimethyltryptamine oxalate (5-MeO-DMT), racemic 8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT), and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU 24969) were then evaluated. All drugs were administered IP 15 min before testing. With the exception of an increased rate of responding at a dose of 0.1 mg/kg of 8-OH-DPAT, all drugs produced a dose-related decline in response rate. In addition, LSD, RU 24969, and 8-OH-DPAT caused a statistically significant decrease in efficiency of responding. Of the three, 8-OH-DPAT was clearly the most active. Doses of 0.3, 1.0, and 3.0 mg/kg resulted in efficiencies of 61%, 53%, and 44%, respectively. The present results taken in light of 8-OH-DPAT's preferential binding to 5-HT1A receptors, the high density of these receptors in hippocampus, and the observation that the number of 5-HT1A receptors is decreased in Alzheimer's disease, suggest a possible role for this serotonergic receptor subtype in memory.

Endometrial damage in acute salpingitis.

Histologic and bacteriologic analyses of endometrium were performed before and on day 15 after minocycline treatment of 20 patients with acute salpingitis. Endometritis was diagnosed in 15 patients before and in nine after treatment. Neisseria gonorrhoeae was recovered from the cervix and endometrium of seven patients but was not isolated after treatment. Chlamydia trachomatis was recovered from the cervix of eight, and from the endometrium of three patients, two of whom had negative cervical cultures. After treatment C. trachomatis was recovered from the cervix of three patients, although two of them had taken aluminum hydroxide for gastric symptomatology during minocycline treatment. Culture of an endometrial specimen revealed no growth of C. trachomatis. The histologic study revealed plasma cell infiltrates in specimens from patients who had cultures positive for C. trachomatis. The results showed that although endometritis is an important manifestation of acute salpingitis, there is no correlation between severity of endometritis and degree of tubal damage.

Procedimentos de diagnostico e ensaio terapeutico com tinidazol na leucorreia por Gardnerella vaginalis. / Diagnostic procedures and therapeutic assay with tinidazole in leukorrhea by Gardnerella vaginalis

Foram estudadas 71 pacientes portadoras de leucorreia vaginal que apresentavam caracteristicas clinicas compativeis com a presenca de Gardnerella vaginalis. O estudo incluia procedimentos para diagnostico clinico e laboratorial; na terapeutica ulitizou-se o tinidazol administrado em dose unica de 2,0g, sendo tambem tratados os parceiros sexuais destas pacientes com esta mesma dose. Das 71 pacientes incluidas, em 18 (25,3%) foi confirmado o diagnostico da vaginite por Gardnerella atraves de esfregaco e cultura de secrecao vaginal. Do ponto de vista clinico, 72 horas apos administracao do medicamento, 56% das pacientes estavam curadas; no 7o. dia, 72% e ao termino da 2a. semana 100%. Microbiologicamente, ja no 7o. dia, 83% das pacientes apresentavam culturas negativas e na avaliacao do 14o dia, 100% das pacientes analisadas estavam curadas.Com relacao a reacoes adversas foram observados dois casos de nauseas e dois de epigastralgia, todos com desaparecimento espontaneo. O tinidazol mostrou um elevado grau de eficacia e uma boa tolerabilidade no tratamento da vaginite por Gardnerella vaginalis, constituindo-se em fundamentada escolha no tratamento deste tipo de vaginite