When it comes to modern design of turbomachinery, one of the most critical objectives is to achieve higher efficiency and performance by reducing weight, fuel consumption, and noise emissions. This ...implies the need for reducing the mass and number of the components, by designing thinner, lighter, and more loaded blades. These choices may lead to mechanical issues caused by the fluid–structure interaction, such as flutter and forced response. Due to the periodic aerodynamic loading in rotating components, preventing or predicting resonances is essential to avoid or limit the dangerous vibration of the blades; thus, simulation methods are crucial to study such conditions during the machine design. The purpose of this paper is to assess a numerical approach based on a topology optimization method for the innovative design of a compressor rotor. A fluid-structural optimization process has been applied to a rotor blisk which belongs to a one-and-a-half-stage aeronautical compressor including static and dynamic loads coming from blade rotation and fluid flow interaction. The fluid forcing is computed by some CFD TRAF code, and it is processed via time and space discrete Fourier transform to extract the pressure fluctuation components in a cyclic-symmetry environment. Finally, a topological optimization of the disk is performed, and the encouraging results are presented and discussed. The remarkable mass reduction in the component (≈32%), the mode-shape frequency shift from a fluid forcing frequency, and an overall relevant reduction in the dynamic response around Campbell’s crossing confirm the efficacy of the presented methodology.
blind sterile (bs) is a spontaneous autosomal-recessive mouse mutation discovered more than 30 years ago. Phenotypically, bs mice exhibit nuclear cataracts and male infertility; genetic analyses ...assigned the bs locus to mouse chromosome 2. In this study, we first positionally cloned the bs locus and identified a putative causative mutation in the Tbc1d20 gene. Functional analysis established the mouse TBC1D20 protein as a GTPase-activating protein (GAP) for RAB1 and RAB2, and bs as a TBC1D20 loss-of-function mutation. Evaluation of bs mouse embryonic fibroblasts (mEFs) identified enlarged Golgi morphology and aberrant lipid droplet (LD) formation. Based on the function of TBC1D20 as a RABGAP and the bs cataract and testicular phenotypes, we hypothesized that mutations in TBC1D20 may contribute to Warburg micro syndrome (WARBM); WARBM constitutes a spectrum of disorders characterized by eye, brain, and endocrine abnormalities caused by mutations in RAB3GAP1, RAB3GAP2, and RAB18. Sequence analysis of a cohort of 77 families affected by WARBM identified five distinct TBC1D20 loss-of-function mutations, thereby establishing these mutations as causative of WARBM. Evaluation of human fibroblasts deficient in TBC1D20 function identified aberrant LDs similar to those identified in the bs mEFs. Additionally, our results show that human fibroblasts deficient in RAB18 and RAB3GAP1 function also exhibit aberrant LD formation. These findings collectively indicate that a defect in LD formation/metabolism may be a common cellular abnormality associated with WARBM, although it remains unclear whether abnormalities in LD metabolism are contributing to WARBM disease pathology.
The paper describes a numerical method based on a modal work approach to evaluate the forced response of bladed disks and its validation against numerical results obtained by a commercial FEM code. ...Forcing functions caused by rotor–stator interactions are extracted from CFD unsteady solutions properly decomposed in time and space to separate the spinning perturbation acting on the bladed disk in a cyclic environment. The method was firstly applied on a dummy test case with cyclic symmetry where the forcing function distributions were arbitrarily selected: comparisons for resonance and out of resonance conditions revealed an excellent agreement between the two numerical methods. Finally, the validation was extended to a more realistic test case representative of a low-pressure turbine bladed rotor subjected to the wakes of two upstream rows: an IGV with low blade count and a stator row. The results show a good agreement and suggest computing the forced response problem on the finer CFD blade surface grid to achieve a better accuracy. The successful validation of the method, closely linked to the CFD environment, creates the opportunity to include the tool in an integrated multi-objective procedure able to account for aeromechanical aspects.
We report the case of two siblings presenting with failure to thrive in early years, progressive microcephaly, moderate intellectual disability, developmental delay, ataxic gait and seizures with an ...identical EEG pattern, and minimal cerebellar atrophy. We ruled out the syndromic and metabolic causes of microcephaly and subsequently conducted a panel of genetic diagnostic tests, including the clinical exome sequencing which revealed compound heterozygous mutations in MED 17 gene in both patients. p.Glu16fs was found to be inherited from the mother and p.Gly253Arg from the father. This case along with review of the literature suggests that mutations in MED17 may define a phenotype characterized by progressive microcephaly, intellectual disability, seizures, cerebellar atrophy of variable degree, and ataxia. More cases are needed to define the phenotype–genotype correlation in MED17 mutations. However, basing on our findings, we recommend testing MED17 mutations in any patient presenting with two or more of the aforementioned signs and symptoms.
Aim
Forkhead Box G1 (FOXG1) syndrome is a developmental encephalopathy characterized by postnatal microcephaly, structural brain abnormalities, facial dysmorphisms, severe delay with absent language, ...defective social interactions, and epilepsy. Abnormal movements in FOXG1 syndrome have often been mentioned but not characterized.
Method
We clinically assessed and analysed video recordings of eight patients with different mutations or copy number variations affecting the FOXG1 gene and describe the peculiar pattern of the associated movement disorder.
Results
The age of the patients in the study ranged from 2 to 17 years old (six females, two males). They had severe epilepsy and exhibited a complex motor disorder including various combinations of dyskinetic and hyperkinetic movements featuring dystonia, chorea, and athetosis. The onset of the movement disorder was apparent within the first year of life, reached its maximum expression within months, and then remained stable.
Interpretation
A hyperkinetic–dyskinetic movement disorder emerges as a distinctive feature of the FOXG1‐related phenotype. FOXG1 syndrome is as an epileptic–dyskinetic encephalopathy whose clinical presentation bears similarities with ARX‐ and STXBP1‐gene related encephalopathies.
What this paper adds
Assessment of movement disorder in patients with FOXG1 mutations or copy number variations.
FOXG1 syndrome can be defined as an epileptic–dyskinetic encephalopathy.
This article is commented on by Parker on page 15 of this issue.
Post-traumatic cerebral infarction (PTCI) is common after traumatic brain injury (TBI). It is unclear what the occurrence of a PTCI is, how it impacts the long-term outcome, and whether it adds ...incremental prognostic value to established outcome predictors.
This was a prospective multicenter cohort study of moderate and severe TBI patients. The primary objective was to evaluate if PTCI was an independent risk factor for the 6-month outcome assessed with the Glasgow Outcome Scale (GOS). We also assessed the PTCI occurrence and if it adds incremental value to the International Mission for Prognosis and Clinical Trial design in TBI (IMPACT) core and extended models.
We enrolled 143 patients, of whom 47 (32.9%) developed a PTCI. In the multiple ordered logistic regression, PTCI was retained in both the core and extended IMPACT models as an independent predictor of the GOS. The predictive performances increased significantly when PTCI was added to the IMPACT core model (AUC = 0.73, 95% C.I. 0.66-0.82; increased to AUC = 0.79, 95% CI 0.71-0.83, p = 0.0007) and extended model (AUC = 0.74, 95% C.I. 0.65-0.81 increased to AUC = 0.80, 95% C.I. 0.69-0.85; p = 0.00008). Patients with PTCI showed higher ICU mortality and 6-month mortality, whereas hospital mortality did not differ between the two groups.
PTCI is a common complication in patients suffering from a moderate or severe TBI and is an independent risk factor for long-term disability. The addition of PTCI to the IMPACT core and extended predictive models significantly increased their performance in predicting the GOS.
The present study was registered in ClinicalTrial.gov with the ID number NCT02430324.
Warts Hypogammaglobulinemia Immunodeficiency Myelokathexis (WHIM) syndrome is a primary immunodeficiency characterized by recurrent bacterial infections, severe chronic neutropenia, with lymphopenia, ...monocytopenia and myelokathexis which is caused by heterozygous gain of functions mutations of the CXC chemokine receptor 4 (CXCR4). WHIM patients display an increased incidence of non-hematopoietic conditions, such as congenital heart disease suggesting that abnormal CXCR4 may put these patients at increased risk of congenital anomalies. Studies conducted on CXCR4 and SDF-1-deficient mice have demonstrated the role of CXCR4 signaling in neuronal cell migration and brain development. In particular, CXCR4 conditional knockout mice display abnormal cerebellar morphology and poor coordination and balance on motor testing.
In order to evaluate a possible neurological involvement in WHIM syndrome subjects, we performed neurological examination, including International Cooperative Ataxia Rating Scale, cognitive and psychopathological assessment and brain Magnetic Resonance Imaging (MRI) in 6 WHIM patients (age range 8-51 years) with typical gain of functions mutations of CXCR4 (R334X or G336X). In three cases (P3, P5, P6) neurological evaluation revealed fine and global motor coordination disorders, balance disturbances, mild limb ataxia and excessive talkativeness. Brain MRI showed an abnormal orientation of the cerebellar folia involving bilaterally the gracilis and biventer lobules together with the tonsils in four subjects (P3, P4, P5, P6). The neuropsychiatric evaluation showed increased risk of internalizing and/or externalizing problems in four patients (P2, P3, P4, P6).
Taken together, these observations suggest CXCR4 gain of function mutations can be associated with cerebellar malformation, mild neuromotor and psychopathological dysfunction in WHIM patients.
Key Clinical Message
Baricitinib, a Janus kinase inhibitor (JAK‐inhibitor), seems to contribute to an improvement of a child affected by Aicardi‐Goutières syndrome (AGS), reducing the interferon ...score and determining a recovery of cognitive, communicative, and relational dysfunctions, while the gross motor deficit persisted.
We report the treatment response to baricitinib, a JAK‐inhibitor, in a 4‐year‐old girl affected by Aicardi‐Goutières syndrome (AGS2, RNASEH2B mutation). Using quantitative measures, we detected a significant amelioration characterized by a complete recovery of cognitive, communicative, and relational skills after 8 and 16 months from the beginning of therapy.
Background
Susceptibility-weighted imaging (SWI) is a relatively new magnetic resonance (MR) technique that exploits the magnetic susceptibility differences of various tissues, such as blood, iron ...and calcification, as a new source of contrast enhancement. This pictorial review is aimed at illustrating and discussing its main clinical applications.
Methods
SWI is based on high-resolution, three-dimensional (3D), fully velocity-compensated gradient-echo sequences using both magnitude and phase images. A phase mask obtained from the MR phase images is multiplied with magnitude images in order to increase the visualisation of the smaller veins and other sources of susceptibility effects, which are displayed at best after post-processing of the 3D dataset with the minimal intensity projection (minIP) algorithm.
Results
SWI is very useful in detecting cerebral microbleeds in ageing and occult low-flow vascular malformations, in characterising brain tumours and degenerative diseases of the brain, and in recognizing calcifications in various pathological conditions. The phase images are especially useful in differentiating between paramagnetic susceptibility effects of blood and diamagnetic effects of calcium. SWI can also be used to evaluate changes in iron content in different neurodegenerative disorders.
Conclusion
SWI is useful in differentiating and characterising diverse brain disorders.
Component reciprocal interaction and aero-thermal coupling are critical aspects in modern turbomachinery design. Combustors and highpressure turbine (HPT) interaction is extremely critical due to the ...compact and lightweight system design. In this context, computational and experimental analyses are thus necessary to study the interaction of the high temperature gas coming from combustor systems and entering the turbine in order to avoid engine mis-operations and to lower the indirect core noise generation. This paper presents a numerical study of pulsating temperature distortion (entropy wave) evolution within a high pressure turbine stage. Four different clocking positions between the 11 temperature spots and the 22 stators have been studied. The numerical results, obtained by URANS computations (TRAF code) and by a dedicated post-processing based on Fourier coefficients, have been compared with experimental measurements coming from the Laboratorio di Fluidodinamica delle Macchine (LFM) of the Politecnico di Milano (Italy) where the HP stage rig is located. The excellent agreement between numerical results and experimental acquisitions confirms the accuracy of the numerical approach. Such results also suggest recommendations for the thermal design of the rows and are the main prerequisite for the study of the indirect core noise generation.
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