Sandwich panels are lightweight structures used in the aerospace and the automobile industry. Global competition in these industries and the pressure to reduce material consumption and costs require ...new lightweight concepts and technologies to apply in sandwich panels. One of these new technologies is additive manufacturing (AM). The freedom of design provided by AM means that new structures such as strut-based lattices can be used as cores for sandwiches. These filigree structures cannot be fabricated using conventional manufacturing processes. Furthermore, fewer manufacturing steps are required through the use of additive manufacturing. Since all parts of the sandwich are manufactured in one step, the bonding process can be eliminated. However, the behavior of strut-based lattices as cores in sandwich panels is still unknown. Therefore, a new computational model is needed to predict all occurring stresses and displacements in sandwich panels to avoid failure of the sandwich structure. In the framework of linear elasticity, an analytical model for the calculation of stresses and displacements in cores of sandwich panels is developed in this study. By de-homogenization of the continuum core, the stress in lattice struts can be determined. In contrast to the most common laminate theories, the presented model enables the calculation of both transverse shear and normal stresses in the sandwich core since the transverse normal stress is of high importance for the design of the core when the sandwich is subjected to concentrated transverse forces. The obtained results can be used to optimize the design of lattice cores in sandwich panels employing additive manufacturing.
To compare muscle imaging findings in different subtypes of myofibrillar myopathies (MFM) in order to identify characteristic patterns of muscle alterations that may be helpful to separate these ...genetic heterogeneous muscular disorders.
Muscle imaging and clinical findings of 46 patients with MFM were evaluated (19 desminopathy, 12 myotilinopathy, 11 filaminopathy, 1 alphaB-crystallinopathy, and 3 ZASPopathy). The data were collected retrospectively in 43 patients and prospectively in 3 patients.
In patients with desminopathy, the semitendinosus was at least equally affected as the biceps femoris, and the peroneal muscles were never less involved than the tibialis anterior (sensitivity of these imaging criteria to detect desminopathy in our cohort 100%, specificity 95%). In most of the patients with myotilinopathy, the adductor magnus showed more alterations than the gracilis muscle, and the sartorius was at least equally affected as the semitendinosus (sensitivity 90%, specificity 93%). In filaminopathy, the biceps femoris and semitendinosus were at least equally affected as the sartorius muscle, and the medial gastrocnemius was more affected than the lateral gastrocnemius. The semimembranosus mostly showed more alterations than the adductor magnus (sensitivity 88%, specificity 96%). Early adult onset and cardiac involvement was most often associated with desminopathy. In patients with filaminopathy, muscle weakness typically beginning in the 5th decade of life was mostly pronounced proximally, while late adult onset (>50 years) with distal weakness was more often present in myotilinopathy.
Muscle imaging in combination with clinical data may be helpful for separation of distinct myofibrillar myopathy subtypes and in scheduling of genetic analysis.
Background and purpose
Post‐stroke immunodepression has been related to brain lesion size but not a specific lesion location. Here, we studied the influence of lesion location within middle cerebral ...artery (MCA) territory on parameters related to activation of sympathetic adrenomedullar pathway, immunodepression, and associated infection.
Methods
We analyzed clinical, brain imaging, and laboratory data of 384 patients (174 women; mean age 70.8 ± 12.9 years) consecutively admitted to the stroke unit no later than 24 h after onset of acute ischaemic stroke involving the MCA territory.
Results
Patients with lesion affecting >33% of MCA territory had increased serum metanephrine and normetanephrine levels, elevated neutrophil counts but decreased eosinophil, helper T lymphocyte, and cytotoxic T lymphocyte counts compared to patients with lesion in <33% of MCA territory. Patients with large infarctions had increased frequency of infections within 14 days after stroke, especially chest infections (P < 0.001). Considering only patients with non‐lacunar infarction in <33% of MCA territory, those with insular lesion had significantly higher normetanephrine levels, higher neutrophil but lower eosinophil and helper T lymphocyte counts than those with non‐insular lesion, despite similar lesion diameters. This coincided with an increased frequency of chest infections (P < 0.01) in patients with insular lesion. Whilst patients with right insular lesion showed decreased heart rate variability, lesion laterality had no impact on laboratory findings or infection frequency.
Conclusion
These findings suggest a specific role of insular lesion in the pathogenesis of stroke‐induced sympathetic hyperactivation and immunodepression. Neuroimaging studies applying lesion volume calculation techniques are warranted to confirm these findings.
The development of targeted inhibitors, vemurafenib and dabrafenib, has led to improved clinical outcome for melanoma patients with BRAF
mutations. Although the initial response to these inhibitors ...can be dramatic, sometimes causing complete tumor regression, the majority of melanomas eventually become resistant. Mitogen-activated protein kinase kinase (MEK) mutations are found in primary melanomas and frequently reported in BRAF melanomas that develop resistance to targeted therapy; however, melanoma is a molecularly heterogeneous cancer, and which mutations are drivers and which are passengers remains to be determined. In this study, we demonstrate that in BRAF
melanoma cell lines, activating MEK mutations drive resistance and contribute to suboptimal growth of melanoma cells following the withdrawal of BRAF inhibition. In this manner, the cells are drug-addicted, suggesting that melanoma cells evolve a 'just right' level of mitogen-activated protein kinase signaling and the additive effects of MEK and BRAF mutations are counterproductive. We also used a novel mouse model of melanoma to demonstrate that several of these MEK mutants promote the development, growth and maintenance of melanoma in vivo in the context of Cdkn2a and Pten loss. By utilizing a genetic approach to control mutant MEK expression in vivo, we were able to induce tumor regression and significantly increase survival; however, after a long latency, all tumors subsequently became resistant. These data suggest that resistance to BRAF or MEK inhibitors is probably inevitable, and novel therapeutic approaches are needed to target dormant tumors.
Background and purpose
Abnormalities of the lenticular nucleus (LN) on transcranial sonography (TCS) are a characteristic finding in idiopathic segmental and generalized dystonia. Our intention was ...to study whether TCS detects basal ganglia abnormalities also in spasmodic dysphonia, an extremely focal form of dystonia.
Methods
Transcranial sonography of basal ganglia, substantia nigra and ventricles was performed in 14 patients with spasmodic dysphonia (10 women, four men; disease duration 16.5 ± 6.1 years) and 14 age‐ and sex‐matched healthy controls in an investigator‐blinded setting.
Results
Lenticular nucleus hyperechogenicity was found in 12 spasmodic dysphonia patients but only in one healthy individual (Fisher's exact test, P < 0.001) whilst other TCS findings did not differ. The area of LN hyperechogenic lesions quantified on digitized image analysis correlated with spasmodic dysphonia severity (Spearman test, r = 0.82, P < 0.001).
Conclusion
Our findings link the underlying pathology of spasmodic dysphonia to that of more widespread forms of dystonia.
Bose-Einstein condensation has been achieved in a magnetic surface microtrap with 4 x 10(5) (87)Rb atoms. The strongly anisotropic trapping potential is generated by a microstructure which consists ...of microfabricated linear copper conductor of widths ranging from 3 to 30 microm. After loading a high number of atoms from a pulsed thermal source directly into a magneto-optical trap the magnetically stored atoms are transferred into the microtrap by adiabatic transformation of the trapping potential. In the microtrap the atoms are cooled to condensation using forced rf-evaporation. The complete in vacuo trap design is compatible with ultrahigh vacuum below 2 x 10(-11) mbar.
The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 ppm (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in ...2001, and is over an order of magnitude more precise than the previous measurement for the negative muon. The result a(mu(-))=11 659 214(8)(3) x 10(-10) (0.7 ppm), where the first uncertainty is statistical and the second is systematic, is consistent with previous measurements of the anomaly for the positive and the negative muon. The average of the measurements of the muon anomaly is a(mu)(exp)=11 659 208(6) x 10(-10) (0.5 ppm).
To study the use of brain parenchyma sonography (BPS) in discriminating between patients with corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP).
Thirteen patients with PSP and ...eight with CBD were studied with BPS according to a standardized protocol.
Seven (88%) of the eight CBD patients showed marked hyperechogenicity of the substantia nigra (SN) but none of eleven PSP patients (Mann-Whitney U test, p < 0.001). This finding indicated CBD with a positive predictive value of 100%. Marked dilatation of the third ventricle (width > 10 mm) was found in 10 (83%) of 12 PSP patients, but in none of the CBD patients (p < 0.005). BPS measurements of ventricle widths closely matched MRI measurements (Pearson correlation, r = 0.90, p < 0.001). The presence of at least one of the BPS findings 1) marked SN hyperechogenicity and 2) third-ventricle width < 10 mm indicated CBD with a sensitivity of 100%, a specificity of 83%, and a positive predictive value of 80%. Other BPS findings such as echogenicity of lentiform and caudate nuclei and widths of the frontal horns did not discriminate between CBD and PSP. One PSP patient could not be assessed because of insufficient acoustic temporal bone windows.
Substantia nigra hyperechogenicity, reported earlier as characteristic brain parenchyma sonography finding in idiopathic Parkinson disease, is also typical for corticobasal degeneration.
Progressive supranuclear palsy (PSP) is the most common atypical parkinsonian syndrome and an important differential diagnosis of parkinson’s disease (PD). The clinical diagnosis of PSP relies on ...characteristic symptoms. There is evidence of clinical subgroups within the entity of PSP interfering with making the firm diagnosis. It was the aim of the study to clarify the differences between phenotypical subtypes of PSP and PD focusing on transcallosal inhibition (TI). A systematic chart review of 67 patients supposed to have probable PSP was done in a standardized diagnostic work-up. As only complete data sets were included into further analysis, 26 PSP patients (mean age 68.6 ± 7.1 years) could be evaluated and subdivided into Richardson’s syndrome (RS) (
n
= 15) or PSP of parkinsonian type (PSP-P) (
n
= 11). Fifteen PD patients served as controls. TI was evaluated by investigation of the ipsilateral silent period (iSP) with transcranial magnetic stimulation (TMS). Cognition was assessed by the Addenbrooke′s cognitive examination (ACE-R). TMS revealed a significantly more severe affection of TI in RS patients as compared to PSP-P and PD patients who showed similar neurophysiological findings. 47 % of RS patient displayed an iSP loss, whereas PSP-P and PD did not. There was a significant correlation between iSP latency and ACE-R (Spearman’s coefficient −0.369,
P
= 0.010). In conclusion, RS patients—contrary to PSP-P and PD patients—had pathological TI at least in one hemisphere indicating more severe involvement of transcallosally projecting output neurons in RS.
We have evaluated the effect of NaCl concentration on the mode of binding of poly- l -lysine to DNA and the resulting structural and functional features of the condensed DNA particles using DNA ...precipitation,
DNase I resistance, electron microscopy, and receptor-mediated gene transfer assays. At a high concentration of NaCl and in
the presence of excess DNA, poly- l -lysine interacted with DNA cooperatively, fully condensing some of the DNA and leaving the rest of the DNA unbound. At low
NaCl concentrations, poly- l -lysine molecules interacted with DNA in a noncooperative fashion, i.e. they bind randomly to the whole population of DNA molecules. Cooperative binding of poly- l -lysine to DNA occurred over a narrow range of NaCl concentrations, and the specific salt concentration depended on the length
of the poly- l -lysine. The ability of condensed DNA to withstand digestion by DNase I was correlated with the structural features of the
condensed DNA as determined by electron microscopy. Using our condensation procedure, cooperative binding of poly- l -lysine to DNA is a necessary prerequisite for the preparation of condensed DNA having a spherical shape and a diameter of
15â30 nm. Condensed DNA, containing galactosylated poly- l -lysine, was evaluated further for the extent and specificity of receptor-mediated gene transfer into HuH-7 human hepatoma
cells via the asialoglycoprotein receptor. Efficient receptor-mediated transfection occurred only when condensed DNA complexes
had a spherical shape with a diameter of 15â30 nm; asialofetuin, a natural ligand for the asialoglycoprotein receptor, inhibited
this process by up to 90%. Our results support the importance of appropriate DNA condensation for the uptake and ultimate
expression of DNA in hepatic cells.
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