305 research outputs found
A 107GHz LNA in 65nm CMOS with inductive neutralization and slow-wave transmission lines
This paper presents a 107GHz LNA prototype using TSMC 65nm CMOS technology. It explores the limit of the CMOS technology by effectively optimizing the active and passive devices. An improvement of 1.6dB higher maximum stable/available gain (MSG/MAG) on the transistor is achieved around 110GHz by layout optimization and inductor neutralization technique. A high quality factor co-planar waveguide (CPW) transmission line is designed utilizing the slow-wave effect. A quality factor of 23.6 is demonstrated by EM-simulations while taken the consideration of satisfying the stringent layout design rules. Based on the optimization on the active and passive devices, a dual-stage LNA is designed, with a simulated power gain of 10.2dB and noise figure of 8dB at 107GHz, verified by chip-level EM-simulations. The power consumption is 28.2mW
Еколого-геохімічні дослідження ґрунтів в зоні впливу підприємств чорної металургії м. Маріуполя
Вивчено закономірності розподілу і форми знаходження важких металів у ґрунтах і компонентах оточуючого середовища поблизу комбінатів чорної металургії м. Маріуполь.Изучены закономерности распределения и формы нахождения тяжелых металлов в почвах и компонентах окружающей среды вблизи комбинатов черной металлургии г. Мариуполь.There was done investigation of distribution and deportment form of heavy metals in soils and environmental components nearby the group of ferrous metallurgy enterprises of Mariupol
Proteasome-dependent protein quality control of the peroxisomal membrane protein Pxa1p
Peroxisomes are eukaryotic organelles that function in numerous metabolic pathways and defects in peroxisome function can cause serious developmental brain disorders such as adrenoleukodystrophy (ALD). Peroxisomal membrane proteins (PMPs) play a crucial role in regulating peroxisome function. Therefore, PMP homeostasis is vital for peroxisome function. Recently, we established that certain PMPs are degraded by the Ubiquitin Proteasome System yet little is known about how faulty/non-functional PMPs undergo quality control. Here we have investigated the degradation of Pxa1p, a fatty acid transporter in the yeast Saccharomyces cerevisiae. Pxa1p is a homologue of the human protein ALDP and mutations in ALDP result in the severe disorder ALD. By introducing two corresponding ALDP mutations into Pxa1p (Pxa1MUT), fused to mGFP, we show that Pxa1MUT-mGFP is rapidly degraded from peroxisomes in a proteasome-dependent manner, while wild type Pxa1-mGFP remains relatively stable. Furthermore, we identify a role for the ubiquitin ligase Ufd4p in Pxa1MUT-mGFP degradation. Finally, we establish that inhibiting Pxa1MUT-mGFP degradation results in a partial rescue of Pxa1p activity in cells. Together, our data demonstrate that faulty PMPs can undergo proteasome-dependent quality control. Furthermore, our observations may provide new insights into the role of ALDP degradation in ALD
Control of gluconeogenesis in rat liver cells. Flux control coefficients of the enzymes in the gluconeogenic pathway in the absence and presence of glucagon
A system for room acoustic simulation for one's own voice
The real-time simulation of room acoustical environments for one’s own voice, using generic software, has been difficult until very recently due to the computational load involved: requiring real-time convolution of a person’s voice with a potentially large number of long room impulse responses. This thesis is presenting a room acoustical simulation system with a software-based solution to perform real-time convolutions with headtracking; to simulate the effect of room acoustical environments on the sound of one’s own voice, using binaural technology. In order to gather data to implement headtracking in the system, human head- movements are characterized while reading a text aloud. The rooms that are simulated with the system are actual rooms that are characterized by measuring the room impulse response from the mouth to ears of the same head (oral binaural room impulse response, OBRIR). By repeating this process at 2o increments in the yaw angle on the horizontal plane, the rooms are binaurally scanned around a given position to obtain a collection of OBRIRs, which is then used by the software-based convolution system. In the rooms that are simulated with the system, a person equipped with a near- mouth microphone and near-ear loudspeakers can speak or sing, and hear their voice as it would sound in the measured rooms, while physically being in an anechoic room. By continually updating the person’s head orientation using headtracking, the corresponding OBRIR is chosen for convolution with their voice. The system described in this thesis achieves the low latency that is required to simulate nearby reflections, and it can perform convolution with long room impulse responses. The perceptual validity of the system is studied with two experiments, involving human participants reading aloud a set-text. The system presented in this thesis can be used to design experiments that study the various aspects of the auditory perception of the sound of one’s own voice in room environments. The system can also be adapted to incorporate a module that enables listening to the sound of one’s own voice in commercial applications such as architectural acoustic room simulation software, teleconferencing systems, virtual reality and gaming applications, etc
Normalized periprostatic fat MRI measurements can predict prostate cancer aggressiveness in men undergoing radical prostatectomy for clinically localised disease
Diagnostic DNA Methylation Biomarkers for Renal Cell Carcinoma:A Systematic Review
CONTEXT: The 5-yr survival of early-stage renal cell carcinoma (RCC) is approximately 93%, but once metastasised, the 5-yr survival plummets to 12%, indicating that early RCC detection is crucial to improvement in survival. DNA methylation biomarkers have been suggested to be of potential diagnostic value; however, their current state of clinical translation is unclear and a comprehensive overview is lacking. OBJECTIVE: To systematically review and summarise all literature regarding diagnostic DNA methylation biomarkers for RCC. EVIDENCE ACQUISITION: We performed a systematic literature review of PubMed, EMBASE, Medline, and Google Scholar up to January 2019, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. Included studies were scored according to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forest plots were generated to summarise diagnostic performance of all biomarkers. Level of evidence (LoE) and potential risk of bias were determined for all included studies. EVIDENCE SYNTHESIS: After selection, 19 articles reporting on 44 diagnostic DNA methylation biomarkers and 11 multimarker panels were included; however, only 15 biomarkers were independently validated. STARD scores varied from 4 to 13 out of 23 points, with a median of 10 points. Large variation in subgroups, methods, and primer locations was observed. None of the reported biomarkers exceeded LoE III, and the majority of studies reported inadequately. CONCLUSIONS: None of the reported biomarkers exceeded LoE III, indicating their limited clinical utility. Moreover, study reproducibility and further development of these RCC biomarkers are greatly hampered by inadequate reporting. PATIENT SUMMARY: In this report, we reviewed whether specific biomarkers could be used to diagnose the most common form of kidney cancer. We conclude that due to limited evidence and reporting inconsistencies, none of these biomarkers can be used in clinical practice, and further development towards clinical use is hindered
ACBD5 deficiency causes a defect in peroxisomal very long-chain fatty acid metabolism
Background
Acyl-CoA binding domain containing protein 5 (ACBD5) is a peroxisomal membrane protein with a
cytosolic acyl-CoA binding domain. Because of its acyl-CoA binding domain, ACBD5 has been
assumed to function as an intracellular carrier of acyl-CoA esters. In addition, a role for ACBD5 in
pexophagy has been suggested. However, the precise role of ACBD5 in peroxisomal metabolism
and/or functioning has not yet been established. Previously, a genetic ACBD5 deficiency was
identified in three siblings with retinal dystrophy and white matter disease. We identified a pathogenic
mutation in ACBD5 in another patient and studied the consequences of the ACBD5 defect in patient
material and in ACBD5-deficient HeLa cells to uncover this role.
Methods
We studied a girl who presented with progressive leukodystrophy, syndromic cleft palate, ataxia and
retinal dystrophy. We performed biochemical, cell biological and molecular studies in patient material
and in ACBD5-deficient HeLa cells generated by CRISPR-Cas9 genome editing.
Results
We identified a homozygous deleterious indel mutation in ACBD5, leading to complete loss of ACBD5
protein in the patient. Our studies showed that ACBD5 deficiency leads to accumulation of very longchain
fatty acids (VLCFAs) due to impaired peroxisomal beta-oxidation. No effect on pexophagy was
found.
Conclusions
Our investigations strongly suggest that ACBD5 plays an important role in sequestering C26-CoA in
the cytosol and thereby facilitates transport into the peroxisome and subsequent beta-oxidation.
Accordingly, ACBD5 deficiency is a novel single peroxisomal enzyme deficiency caused by impaired
VLCFA metabolism and leading to retinal dystrophy and white matter disease.Supported in part by funding through the Marie Curie Initial Training Networks (ITN) action to
KDF, MS and HRW (FP7-2012-PERFUME-316723). MS is supported by the Biotechnology and
Biological Sciences Research Council (BB/K006231/1; BB/N01541X/1)
Periprostatic fat measured on computed tomography as a marker for prostate cancer aggressiveness
Contains fulltext :
89797.pdf (publisher's version ) (Closed access)OBJECTIVE: Several reports found that obesity was associated with prostate cancer (PC) aggressiveness among men treated with radical prostatectomy or radiotherapy. Studies concerning this issue have basically relied on body mass index (BMI), as a marker for general obesity. Because visceral fat is the most metabolic active fat, we sought to evaluate if periprostatic fat measured on a computed tomography (CT) is a better marker than BMI to predict PC aggressiveness in a Dutch population who underwent brachytherapy for localized PC. PATIENTS AND METHODS: Of the 902 patients who underwent brachytherapy, 725 CT scans were available. Subcutaneous fat thickness (CFT), periprostatic fat area (cm(2)) and fat-density (%) were determined on the CT scan. Patients were stratified into three groups: 75 percentile of the fat-density. Associations between the three fat-density subgroups and BMI and PC aggressiveness were examined. RESULTS: 237 patients were classified as having normal weight (37.2%), 320 as overweight (50.2%) and 80 as obese (12.6%). There was a strong significant association between BMI and fat-density and CFT. The strongest correlation was seen between BMI and CFT (Pearson r coefficient = 0.71). Logistic regression analysis revealed no statistically significant association between the different fat measurements and the risk of having a high-risk disease. CONCLUSIONS: Periprostatic fat and fat-density as measured with CT were not correlated with PC aggressiveness in patients receiving brachytherapy. However, 31% of the patients with a normal BMI had a fat-density of >75 percentile of the periprostatic fat-density.01 december 201
- …