Erratum: Lattice Dynamics of EuO: Evidence for Giant Spin-Phonon Coupling [Phys. Rev. Lett. 116, 185501 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.116.185501.

Anomalous Lattice Dynamics of EuSi_{2} Nanoislands: Role of Interfaces Unveiled.

We report a systematic lattice dynamics study of EuSi_{2} films and nanoislands by in situ nuclear inelastic scattering on ^{151}Eu and ab initio theory. The Eu-partial phonon density of states of the nanoislands exhibits anomalous excess of phonon states at low and high energies, not present in the bulk and at the EuSi_{2}(001) surface. We demonstrate that atomic vibrations along the island-substrate interface give rise to phonon states both at low and high energies, while atomic vibrations across the island-island interface result in localized high-energy phonon modes.

Lattice Dynamics of EuO: Evidence for Giant Spin-Phonon Coupling.

Comprehensive studies of lattice dynamics in the ferromagnetic semiconductor EuO have been performed by a combination of inelastic x-ray scattering, nuclear inelastic scattering, and ab initio calculations. A remarkably large broadening of the transverse acoustic phonons was discovered at temperatures above and below the Curie temperature T_{C}=69 K. This result indicates a surprisingly strong momentum-dependent spin-phonon coupling induced by the spin dynamics in EuO.

Nuclear forward scattering of synchrotron radiation by 99Ru.

We measured nuclear forward scattering spectra utilizing the (99)Ru transition, 89.571(3) keV, with a notably mixed E2/M1 multipolarity. The extension of the standard evaluation routines to include mixed multipolarity allows us to extract electric and magnetic hyperfine interactions from (99)Ru-containing compounds. This paves the way for several other high-energy Mössbauer transitions, E ∼ 90 keV. The high energy of such transitions allows for operando nuclear forward scattering studies in real devices.

Non-invasive stimulation of the vibrissal pad improves recovery of whisking function after simultaneous lesion of the facial and infraorbital nerves in rats.

We have recently shown that manual stimulation of target muscles promotes functional recovery after transection and surgical repair to pure motor nerves (facial: whisking and blink reflex; hypoglossal: tongue position). However, following facial nerve repair, manual stimulation is detrimental if sensory afferent input is eliminated by, e.g., infraorbital nerve extirpation. To further understand the interplay between sensory input and motor recovery, we performed simultaneous cut-and-suture lesions on both the facial and the infraorbital nerves and examined whether stimulation of the sensory afferents from the vibrissae by a forced use would improve motor recovery. The efficacy of 3 treatment paradigms was assessed: removal of the contralateral vibrissae to ensure a maximal use of the ipsilateral ones (vibrissal stimulation; Group 2), manual stimulation of the ipsilateral vibrissal muscles (Group 3), and vibrissal stimulation followed by manual stimulation (Group 4). Data were compared to controls which underwent surgery but did not receive any treatment (Group 1). Four months after surgery, all three treatments significantly improved the amplitude of vibrissal whisking to 30° versus 11° in the controls of Group 1. The three treatments also reduced the degree of polyneuronal innervation of target muscle fibers to 37% versus 58% in Group 1. These findings indicate that forced vibrissal use and manual stimulation, either alone or sequentially, reduce target muscle polyinnervation and improve recovery of whisking function when both the sensory and the motor components of the trigemino-facial system regenerate.

Perioperative steroid administration inhibits angiogenic host tissue response to porous polyethylene (Medpor) implants.

Porous polyethylene (Medpor) is an alloplastic biomaterial, which is commonly used in plastic and reconstructive surgery. In the present study, we analyzed the effect of perioperative steroid administration on the inflammatory and angiogenic host tissue response to implanted Medpor. For this purpose, Medpor was implanted into the dorsal skinfold chamber of prednisolone-treated and vehicle-treated (control) balb/c mice and analyzed by means of intravital fluorescence microscopy over a 14-day period. Incorporation of the implants was evaluated by histology. An aortic ring assay and Western blot analyses were performed to determine in vitro the effect of prednisolone on angiogenesis. Implantation of Medpor did not induce a leukocytic inflammatory host tissue response. However, in prednisolone-treated and control animals giant cells could be detected at the interface between the implants and the surrounding granulation tissue as a typical indicator for a chronic foreign body reaction. Interestingly, perioperative prednisolone administration inhibited vascularisation of the implants, as indicated by a significantly decreased functional density of newly developing capillary blood vessels. Accordingly, prednisolone suppressed in vitro endothelial sprouting and tube formation in the aortic ring assay and reduced proliferating cell nuclear antigen (PCNA), Tie2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 expression of murine endothelioma cells. In conclusion, prednisolone treatment inhibits the early vascularisation of Medpor implants due to direct inhibition of distinct angiogenic mechanisms. Therefore, perioperative steroid therapy should be avoided in case of Medpor implantation to achieve a rapid incorporation of the biomaterial at the implantation site.

GM1 Ganglioside role in the interaction of Alpha-synuclein with lipid membranes: Morphology and structure.

Alpha-Synuclein (AS) is the protein playing the major role in Parkinson's disease (PD), a neurological disorder characterized by the degeneration of dopaminergic neurons and the accumulation of AS into amyloid plaques. The aggregation of AS into intermediate aggregates, called oligomers, and their pathological relation with biological membranes are considered key steps in the development and progression of the disease. Here we propose a multi-technique approach to study the effects of AS in its monomeric and oligomeric forms on artificial lipid membranes containing GM1 ganglioside. GM1 is a component of functional membrane micro-domains, called lipid rafts, and has been demonstrated to bind AS in neurons. With the aim to understand the relation between gangliosides and AS, here we exploit the complementarity of microscopy (Atomic Force Microscopy) and neutron scattering (Small Angle Neutron Scattering and Neutron Reflectometry) techniques to analyze the structural changes of two different membranes (Phosphatidylcholine and Phosphatidylcholine/GM1) upon binding with AS. We observe the monomer- and oligomer-interactions are both limited to the external membrane leaflet and that the presence of ganglioside leads to a stronger interaction of the membranes and AS in its monomeric and oligomeric forms with a stronger aggressiveness in the latter. These results support the hypothesis of the critical role of lipid rafts not only in the biofunctioning of the protein, but even in the development and the progression of the Parkinson's disease.

Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations.

It is well documented that the aromatase inhibitors (AIs) are superior to tamoxifen as adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive breast cancer. However, compared with tamoxifen, an elevated incidence of arthralgia has been observed during AI treatment. Concerns have been raised that AI-induced arthralgia may dissuade patients from completing their full AI treatment course, and may also deter physicians from prescribing an AI if they feel that patients may be at risk of permanent joint damage. Patient education about the possibility of experiencing arthralgia, and effective management of symptoms if they appear, are important in helping patients adhere to AI treatment, and consequently improving breast cancer outcomes. In this paper, we discuss the potential mechanisms behind AI-induced arthralgia, review the frequency with which arthralgia occurs, and propose for the first time an algorithm specifically for the treatment of AI-induced arthralgia. As with joint pain in non-breast cancer patients, a sequential approach to disease management is recommended, involving modifying the patient's lifestyle in addition to taking a stratified approach to pharmacological intervention with analgesia and anti-inflammatory medication. Knowing that joint symptoms can be managed in most patients may encourage patient-physician communication and treatment compliance.

Twenty eight-day dietary toxicity study of Luo Han fruit concentrate in Hsd:SD rats.

A 28-day dietary study was conducted in Hsd:SD rats to evaluate the safety of PureLo, a non-caloric powdered concentrate of the Chinese fruit Luo Han Guo, which derives its sweetening properties from triterpene glycosides called mogrosides. Groups of 20 rats (10/sex/group) were fed diets containing 0, 10,000, 30,000, or 100,000 ppm PureLo for 28 days (OECD, Redbook 2000). PureLo was well tolerated and produced no significant adverse effects. Reduced body weight and body weight gain in high-dose animals of both sexes were related to sporadic reductions in food consumption; there were no overall differences in feed efficiency. Statistically significant changes in clinical chemistry (decreased bilirubin, increased total protein) and relative organ weights of liver, adrenals, ovaries and/or testes, and epididymides were not correlated with any histopathological findings and were not considered adverse. Although a few clinical and pathological findings suggest possible treatment-related effects, particularly in the high-dose group, these findings were transient, not dose-dependent, non-adverse, inconsistent, occurred only in one sex, and/or not supported by histopathological findings. Under the conditions of this study and based on the toxicological endpoints evaluated, the NOAEL for PureLo was 100,000 ppm in the diet, the highest level tested, equivalent to 7.07 and 7.48 g/kg bw/day for male and female rats, respectively.

Toxicologic evaluation of modified gum acacia: mutagenicity, acute and subchronic toxicity.

Modified gum acacia, produced from acacia gum by a process analogous to the production of modified food starch, was tested for mutagenicity in the microbial reverse mutation assay. The assay employed a wide range of dose levels, both with and without metabolic activation. Test results gave no indication that modified gum acacia possessed any mutagenic potential. The acute oral toxicity of modified gum acacia was determined in two studies employing Sprague-Dawley rats, and the LD50 values were found to be >2000 mg/kg. The primary dermal irritation potential of modified gum acacia was evaluated in rabbits by the Draize method. Test results indicated that modified gum acacia was slightly irritating by the Environmental Protection Agency (EPA) classification but not a primary irritant by Consumer Product Safety Commission (CPSC) guidelines. The subchronic toxicity of modified gum acacia was examined in Sprague-Dawley rats fed diets containing 0%, 1%, 2.5%, and 5% modified gum acacia for 13 weeks. No dose-related effects on survival, growth, hematology, blood chemistry, organ weights, or pathologic lesions were observed. Results of these studies indicate that modified gum acacia does not possess mutagenic potential and that animals are not adversely affected by acute or subchronic exposure to modified gum acacia.

Note: 4-bounce neutron polarizer for reflectometry applications.

A neutron polarizer using four successive reflections on m = 2.5 supermirrors was built and installed at the GINA neutron reflectometer at the Budapest Neutron Centre. This simple setup exhibits 99.6% polarizing efficiency with 80% transmitted intensity of the selected polarization state. Due to the geometry, the higher harmonics in the incident beam are filtered out, while the optical axis of the beam remains intact for easy mounting and dismounting the device in an existing experimental setup.

Asymmetric alloy formation at the Fe-on-Ti and Ti-on-Fe interfaces.

The Fe-on-Ti and Ti-on-Fe interfaces were studied experimentally by Mössbauer spectroscopy (MS), transmission electron microscopy (TEM) and x-ray reflectometry (XRR) on Ti/Fe/Ti trilayers grown on Si(1 1 1) substrates by vacuum evaporation. The nanoscale structure and composition were explored in cross sections using TEM, the layer structure and the interface widths by specular x-ray reflectometry. MS was applied to identify the interface alloy phases and to determine the pure and alloyed Fe layer fractions. The experimental results were compared with molecular dynamics (MD) simulations of layer growth on Fe or Ti underlayers of different orientations. The concentration distributions provided by MD simulations show an asymmetry at the interfaces in the layer growth direction. The transition is atomically sharp at the Ti-on-Fe interface for the (0 0 1) and (1 1 0) crystallographic orientations of the Fe underlayer, while it spreads over a few atomic layers for Fe(1 1 1) underlayer and for all studied Ti underlayer orientations at the Fe-on-Ti interface. MS and XRR data on Ti/Fe/Ti trilayers confirm the asymmetry between the bottom and top Fe interface, but the inferred interface widths considerable exceed those deduced from the MD simulations.

Acute and subchronic oral toxicity studies in rats of a hydrolyzed chicken sternal cartilage preparation.

Two acute and subchronic oral toxicity studies were conducted in rats to evaluate safety of a patented preparation of hydrolyzed chicken sternal cartilage (BioCell Collagen II) containing collagen type II, chondroitin sulfate, and hyaluronic acid. In the acute oral toxicity study, five males and five females of Sprague-Dawley rats were administered a single dose of 5000 mg of the test product per kg body weight and observed for 14 days. All animals survived and exhibited normal body weight gain throughout the study. Macroscopic necropsy examination conducted on day 15 revealed no gross pathological lesions in any of the animals. In the subchronic study, Sprague-Dawley rats (40 males, 40 females) were divided into four same-sex groups (10 animals/group). Animals in each group were administered daily either 0, 30, 300 or 1000 mg of the test product per kg of body weight for over 90 days. All animals survived and showed no significant changes in their body weights and histopathology. Although some differences were observed between the treated and control animals in several parameters, they were generally not dose-related or considered to be of toxicological significance. In conclusion, the results from the two oral toxicity studies with male and female young adult rats indicated that the test preparation from hydrolyzed chicken sternal cartilage collagen (BioCell Collagen II) was well tolerated at all four doses tested.

Prognostic implications of ploidy and proliferative activity in diffuse large cell lymphomas.

Paraffin-embedded surgical biopsies from 50 patients with newly diagnosed diffuse large cell lymphoma (DLCL) were examined for proliferative activity and DNA aneuploidy by flow cytometry. These results were correlated with the clinical characteristics of these patients and the course of their disease. High proliferative activity, defined as less than 80% of cells in G0 or G1, was found to be the single most important pretreatment adverse prognostic factor in these patients. This relationship remained significant after correcting for poor performance status and advanced Ann Arbor stage, the other factors found to be associated with a shortened survival. DLCLs with high proliferative activity were more probable to present with extranodal involvement than those with lower proliferative activity. The mitotic count as determined by light microscopy did not correlate with flow cytometry-defined proliferative activity and may be a less accurate method for assessing this important biological characteristic in DLCL. DNA aneuploidy was detected in 62% of cases but did not appear to have any prognostic significance. Biopsies from patients who presented with lymphomatous bone marrow involvement, however, invariably demonstrated an aneuploid stemline. These results suggest that differences in proliferative activity may be an important biological basis for the variable prognosis seen in DLCL.

Flow cytometry, cellular DNA content, and prognosis in human malignancy.

The use of flow cytometry to analyze the cellular DNA content of human malignancies has become increasingly commonplace. The relationship between abnormalities in DNA content or proliferative characteristics and prognosis is becoming clear for a variety of malignancies in part through new techniques that permit analysis of archival material. High- and low-risk groups of patients with early breast and bladder carcinomas, non-small-cell lung cancer, and colorectal, ovarian, and cervical carcinoma can be distinguished on the basis of abnormal stemline DNA content. In several hematologic and common pediatric malignancies, the prognostic relevance of DNA content flow cytometry has been similarly established. Though the interpretation of tumor cell cycle analyses is less certain, this characteristic may also be prognostically important. However, generalizations cannot be made when applying flow cytometric DNA analysis to clinical decision making. The prognostic importance of an abnormal DNA histogram for an individual patient must be assessed on the basis of the relevant data base for that particular tumor type. The current extent of this data base for various malignancies is reviewed.

Electrophoretic analysis of 248 clinical breast cancer specimens for P-glycoprotein overexpression or gene amplification.

Multiple drug resistance (MDR), consisting of acquired cross resistance to anthracyclines, vinca alkyloids, and other antineoplastic antibiotics, has been described in a variety of cell lines. This MDR phenotype is associated with overexpression and sometimes amplification of a gene coding for a 170 kDa glycoprotein, termed P-glycoprotein. To understand the role of this mechanism in clinical breast cancer, 248 breast cancer specimens representing both untreated primary and refractory relapsing disease were probed for evidence of P-glycoprotein gene amplification or overexpression using Southern, Northern, or Western blot techniques. In no case was an increase in P-glycoprotein gene copy number or expression detected. Though these findings do not necessarily rule out a role for P-glycoprotein in mediating drug resistance in breast cancer, electrophoretic analysis of clinical specimens is unlikely to provide useful predictive information. More sensitive assays must be developed to overcome the difficulties inherent in analyzing heterogenous tissue samples.

Docetaxel combined with trastuzumab is an active regimen in HER-2 3+ overexpressing and fluorescent in situ hybridization-positive metastatic breast cancer: a multi-institutional phase II trial.

PURPOSE: To determine the efficacy and safety of weekly docetaxel and trastuzumab as first- or second-line therapy in women with HER-2-overexpressing metastatic breast cancer and to correlate the efficacy of trastuzumab with HER-2 status as determined by immunohistochemistry assay and fluorescent in situ hybridization (FISH). PATIENTS AND METHODS: Twenty-six women with HER-2-positive (HercepTest [Dako Corp, Carpenteria, CA]2 to 3+) metastatic breast cancer were enrolled onto this study of trastuzumab (4 mg/kg load; 2 mg/kg/wk administered intravenously) and docetaxel (35 mg/m2/wk for 6 weeks). RESULTS: Using an intent-to-treat analysis, the overall response rate was 50% (13 of 26 patients). Eight patients (31%) had a period of stable disease posttherapy. Among HER-2 3+ patients, the overall response rate was 63% (12 of 19 patients) compared with a 14% response rate (one of seven patients) for HER-2 2+ patients (P=.07). Patients with FISH-positive tumors experienced an overall response rate of 64%. Median time to progression was 12.4 months for the entire cohort (HER-2 3+ tumors, 12.3 months; HER-2 2+ lesions, 9.5 months) and median survival was 22.1 months. All HER-2 3+ patients were FISH-positive; the only HER-2 2+ patient responding to treatment was also FISH-positive. Grade 4 toxicities occurred in four patients; most toxicities were mild. CONCLUSION: Trastuzumab plus docetaxel is an active and well-tolerated regimen in women with HER-2 3+ overexpressing or FISH-positive metastatic breast cancer.

Evolution of magnetism on a curved nano-surface.

To design custom magnetic nanostructures, it is indispensable to acquire precise knowledge about the systems in the nanoscale range where the magnetism forms. In this paper we present the effect of a curved surface on the evolution of magnetism in ultrathin iron films. Nominally 70 Å thick iron films were deposited in 9 steps on 3 different types of templates: (a) a monolayer of silica spheres with 25 nm diameter, (b) a monolayer of silica spheres with 400 nm diameter and (c) for comparison a flat silicon substrate. In situ iron evaporation took place in an ultrahigh vacuum chamber using the molecular beam epitaxy technique. After the evaporation steps, time differential nuclear forward scattering spectra, grazing incidence small angle X-ray scattering images and X-ray reflectivity curves were recorded. In order to reconstruct and visualize the magnetic moment configuration in the iron cap formed on top of the silica spheres, micromagnetic simulations were performed for all iron thicknesses. We found a great influence of the template topography on the onset of magnetism and on the developed magnetic nanostructure. We observed an individual magnetic behaviour for the 400 nm spheres which was modelled by vortex formation and a collective magnetic structure for the 25 nm spheres where magnetic domains spread over several particles. Depth selective nuclear forward scattering measurements showed that the formation of magnetism begins at the top region of the 400 nm spheres in contrast to the 25 nm particles where the magnetism first appears in the region where the spheres are in contact with each other.