Amplitude and phase modulation techniques for an asymmetric multi-level outphasing transmitter

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2012.Cataloged from PDF version of thesis.Includes bibliographical references (p. 93-95).New techniques for improving outphasing transmitters show potential of breaking the traditional linearity-efficiency trade-off by using highly efficient non-linear switching Power Amplifiers (PAs). This work focuses on two of the main building blocks of modem outphasing systems, the power supply switching network and the phase modulator. Both are ubiquitous building blocks in modern RF transceivers, and both are especially critical in Asymmetric Multilevel Outphasing (AMO) systems. A design of the power supply network and control scheme is proposed for an implementation in mm-wave operating frequencies as part of a complete transmitter in 45nm SOI CMOS utilizing four discrete power supplies and achieving data rates of up to 4GS/s. The design includes analysis and simulation of the control signal data path requirements for optimal system operation as well as switch optimization and effects of the driving strength on overall system performance. A new design concept is proposed for a phase modulator utilizing the phase shifthing capabilities of a resonant tank and the ability to seperately control the circuit properties via its components. A prototype in 65nm CMOS achieves 12 bits of resolution, with an Effective Number Of Bits (ENOB) of 10.2 bits and very fast settling time of less than 5 carrier cycles. The chip is also tested as a stand alone transmitter showing an EVM of less than 5% for 8-PSK modulation at maximum data rate, meeting the requirements for operation at the Medical Implant Communication Services (MICS) band.by Gilad Yahalom.S.M

A Comprehensive Assessment of Qualitative and Quantitative Prodromal Parkinsonian Features in Carriers of Gaucher Disease-Identifying Those at the Greatest Risk

Carriers of GBA1 gene variants have a significant risk of developing Parkinson's disease (PD). A cohort study of GBA carriers between 40-75 years of age was initiated to study the presence of prodromal PD features. Participants underwent non-invasive tests to assess different domains of PD. Ninety-eight unrelated GBA carriers were enrolled (43 males) at a median age (range) of 51 (40-74) years; 71 carried the N370S variant (c.1226A > G) and 25 had a positive family history of PD. The Montreal Cognitive Assessment (MoCA) was the most frequently abnormal (23.7%, 95% CI 15.7-33.4%), followed by the ultrasound hyperechogenicity (22%, 95% CI 14-32%), Unified Parkinson's Disease Rating Scale part III (UPDRS-III) (17.2%, 95% CI 10.2-26.4%), smell assessment (12.4%, 95% CI 6.6-20.6%) and abnormalities in sleep questionnaires (11%, 95% CI 5.7-19.4%). Significant correlations were found between tests from different domains. To define the risk for PD, we assessed the bottom 10th percentile of each prodromal test, defining this level as "abnormal". Then we calculated the percentage of "abnormal" tests for each subject; the median (range) was 4.55 (0-43.5%). Twenty-two subjects had more than 15% "abnormal" tests. The limitations of the study included ascertainment bias of individuals with GBA-related PD in relatives, some incomplete data due to technical issues, and a lack of well-characterized normal value ranges in some tests. We plan to enroll additional participants and conduct longitudinal follow-up assessments to build a model for identifying individuals at risk for PD and investigate interventions aiming to delay the onset or perhaps to prevent full-blown PD

Analysis of common and rare VPS13C variants in late-onset Parkinson disease

Objective We aimed to study the role of coding VPS13C variants in a large cohort of patients with lateonset Parkinson disease (PD) (LOPD). Methods VPS13C and its untranslated regions were sequenced using targeted next-generation sequencing in 1,567 patients with PD and 1,667 controls from 3 cohorts. Association tests of rare potential homozygous and compound heterozygous variants and burden tests for rare heterozygous variants were performed. Common variants were analyzed using logistic regression adjusted for age and sex in each of the cohorts, followed by a meta-analysis. Results No biallelic carriers of rare VPS13C variants were found among patients, and 2 carriers of compound heterozygous variants were found in 2 controls. There was no statistically significant burden of rare (minor allele frequency [MAF] <1%) or very rare (MAF <0.1%) coding VPS13C variants in PD. A VPS13C haplotype including the p.R153H-p.I398I-p.I1132V-p.Q2376Q variants was nominally associated with a reduced risk for PD (meta-analysis of the tagging SNP p.I1132V [odds ratio = 0.48, 95% confidence interval = 0.28–0.82, p = 0.0052]). This haplotype was not in linkage disequilibrium with the known genome-wide association study top hit. Conclusions Our results do not support a role for rare heterozygous or biallelic VPS13C variants in LOPD. Additional genetic replication and functional studies are needed to examine the role of the haplotype identified here associated with reduced risk for PD

Analog-digital co-existence in 3D-IC

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2016.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 231-246).Ubiquitous mobile communication creates an increasing demand for high data rates, complex modulation schemes and low power design. The cost and performance benefits of conventional lithographic scaling are diminishing as process cost increases exponentially. 3D integration has the potential to keep driving performance forward while keeping cost down. The possibility to integrate separate dies with low-parasitic, dense interconnect and shorter routing provides area and power benefits. However, new challenges must be addressed in order to enable design in this new dimension and provide system level improvements. This thesis explores the impact, challenges and advantages of using 3D integration for combining digital and analog circuits for RF applications. The use of a vertical solenoid inductor in a Voltage Controlled Oscillator (VCO) is proposed. The inductor design utilizes the through-silicon-vias of the 3D stack as part of its geometry. The solenoid inductor exhibits a 28%larger inductance and a 6 dB higher quality factor compared to a conventional planar inductor occupying the same area. The VCO circuit phase noise is improved by 6 dB and exhibits an improved immunity to coupling from adjacent digital clock lines routed on the bottom tier of the 3D stack. An efficient hardware implementation is presented for an LTE uplink channel. The proposed design processes input data for cellular transmission. The core of the computation includes a variable-length, high-order, mixed-radix FFT and IFFT blocks. The use of energy efficient circuits and algorithms enables achieving an energy efficiency of up to 95 pJ/Sample and additional power savings of up to 24% for different operation modes. Both designs are combined along with digital-to-analog conversion to create a partial cellular transmitter in 3D-IC. Highly flexible and configurable design allows for various partitioning of the system. The 3D design has a digital link energy efficiency of up to 0.37 pJ/bit, compared to the 33.3 pJ/bit consumed in a multiple die partitioning and 0.83 pJ/bit for a 2.5D interposer emulated design. The use of the solenoid VCO along with digital-analog partitioning between the die tiers enables high immunity to noise and reduction of spurs at the VCO output.by Gilad Yahalom.Ph. D

Therapeutic Approach to Botulinum Injections for Hemifacial Spasm, Synkinesis and Blepharospasm

The aim of this study was to show our therapeutic outcome of botulinum injection to the facial muscles and thereby to find the best therapeutic concept which should be embraced. The decision to treat the lower eyelid with 1-point or 2-points injection was randomly taken as there is no consensus regarding this debate. Injections of the lateral end of the upper eyelid were performed more laterally to the conventional injection point, just lateral to the conjunction of the upper and lower eyelids. Twenty-three patients (12 hemifacial spasm, 6 blepharospasm, 5 post facial palsy synkinesis) were enrolled. Data were retrieved from 112 visits between 2019 and 2022. Overall, 84.9% of the treatments had moderate or marked improvement. The most common side effect was facial weakness (11.8%). Neither ptosis nor diplopia were noted. Two-points regimen in the lower eyelid was associated with a lower risk of facial weakness (p = 0.01), compared to 1-point regimen, with a better therapeutic outcome as reflected by more favorable PGI-C scores (p = 0.04). Injection of the pretarsal segment of the upper eyelid, just onto or even lateral to the conjunction of the upper and lower eyelids, lowers the risk of ptosis

Neuro-Ophthalmic Manifestations of Costeff Syndrome (.pdf)

Type III 3-methylglutaconic aciduria (OPA III) is a neuro-ophthalmologic syndrome consisting of early-onset bilateral optic atrophy caused by mutation c.143-1G>C variant. Since Costeff described phenotype of 19 patients in 1989 several reports described approximately 40 patients, but most of them lack details about neuro-ophthalmic phenotype. Our aim was to characterize the clinical course of the neuro-ophthalmic manifestations of this syndrome

Automated stage discrimination of Parkinson’s disease

International audienceTreament plans for Parkinson’s disease are based on a disease stage scale, which is generally determined using a manual, observational procedure. Automated, sensor based discrimination saves labour and cost in clinical settings and may offer augmented stage determination accuracy. Previous automated devices were either cumbersome or costly and were not suitable for individuals who cannot walk without support.Since 2017, a device has been available that successfully detects Parkinson’s disease and operates for people who cannot walk without support. In the present study, the suitability of this device for automated discrimination of Parkinson’s disease stages is tested. The device consists of a walking frame fitted with sensors to simultaneously support walking and monitor patient gait. Sixty-five Parkinson’s disease patients in HYstages 1 to 4 and twenty-four heathy controls were subjected to supported timed up and go (TUG) tests, while using the walking frame. The walking trajectory, velocity, acceleration and force were recorded by the device throughout the tests. These physical parameters were converted into symptomic spatio-temporal quanitities that are conventionaly used in Parksinon’s disease gait assessment. An ANOVA Test extended by a confidence interval analysis indicated statistically significant seperability between HYstages for the following spatio-temporal quantities: TUG time (p<0.001), straight like walking time (p<0.001), turning time (p<0.001) and step count (p<0.001). A negative correlation was obtained for mean step velocity (p<0.001) and mean step length (p<0.001). Moreover, correlations were established between these, as well as additional spatio-temporal quanitities, and disease duration, levodopa dose, motor fluctuation, dyskinesia and the mobile part of the unified Parkinson’s disease rating scale. We have proven that stage discrimination of Parkinson’s disease can be automated, even to patients who cannot support themselves. A similar method might be successfully applied to other gait disorders

Expert opinion on diagnosing, treating and managing patients with cerebrotendinous xanthomatosis (CTX): a modified Delphi study

Background Cerebrotendinous xanthomatosis (CTX) is a rare, chronic, progressive, neurodegenerative disorder requiring life-long care. Patients with CTX often experience a diagnostic delay. Although early diagnosis and treatment initiation can improve symptoms and prognosis, a standardised approach to diagnosis, treatment and management of patients is not yet established. Aim To assess expert opinion on best care practices for patients with CTX using a modified Delphi method. Methods A multidisciplinary group of healthcare professionals with expertise in CTX responded to a 3-round online questionnaire (n = 10 in Rounds 1 and 2; n = 9 in Round 3), containing questions relating to the diagnosis, treatment, monitoring, multidisciplinary care and prognosis of patients with CTX. Determination of consensus achievement was based on a pre-defined statistical threshold of >= 70% Delphi panellists selecting 1-2 (disagreement) or 5-6 (agreement) for 6-point Likert scale questions, or >= 70% Delphi panellists choosing the same option for ranking and proportion questions. Results Of the Round 1 (n = 22), Round 2 (n = 32) and Round 3 (n = 26) questions for which consensus was assessed, 59.1%, 21.9% and 3.8% reached consensus, respectively. Consensus agreement that genetic analyses and/or determination of serum cholestanol levels should be used to diagnose CTX, and dried bloodspot testing should facilitate detection in newborns, was reached. Age at diagnosis and early treatment initiation (at birth, where possible) were considered to have the biggest impact on treatment outcomes. All panellists agreed that chenodeoxycholic acid (CDCA) is a lifetime replacement therapy which, if initiated early, can considerably improve prognosis as it may be capable of reversing the pathophysiological process in CTX. No consensus was reached on the value of cholic acid therapy alone. Monitoring patients through testing plasma cholestanol levels and neurologic examination was recommended, although further research regarding monitoring treatment and progression of the disease is required. Neurologists and paediatricians/metabolic specialists were highlighted as key clinicians that should be included in the multidisciplinary team involved in patients' care. Conclusions The results of this study provide a basis for standardisation of care and highlight key areas where further research is needed to inform best practices for the diagnosis, treatment and management of patients with CTX

<i>GBA1</i>-Associated Parkinson’s Disease Is a Distinct Entity

GBA1-associated Parkinson’s disease (GBA1-PD) is increasingly recognized as a distinct entity within the spectrum of parkinsonian disorders. This review explores the unique pathophysiological features, clinical progression, and genetic underpinnings that differentiate GBA1-PD from idiopathic Parkinson’s disease (iPD). GBA1-PD typically presents with earlier onset and more rapid progression, with a poor response to standard PD medications. It is marked by pronounced cognitive impairment and a higher burden of non-motor symptoms compared to iPD. Additionally, patients with GBA1-PD often exhibit a broader distribution of Lewy bodies within the brain, accentuating neurodegenerative processes. The pathogenesis of GBA1-PD is closely associated with mutations in the GBA1 gene, which encodes the lysosomal enzyme beta-glucocerebrosidase (GCase). In this review, we discuss two mechanisms by which GBA1 mutations contribute to disease development: ‘haploinsufficiency,’ where a single functional gene copy fails to produce a sufficient amount of GCase, and ‘gain of function,’ where the mutated GCase acquires harmful properties that directly impact cellular mechanisms for alpha-synuclein degradation, leading to alpha-synuclein aggregation and neuronal cell damage. Continued research is advancing our understanding of how these mechanisms contribute to the development and progression of GBA1-PD, with the ‘gain of function’ mechanism appearing to be the most plausible. This review also explores the implications of GBA1 mutations for therapeutic strategies, highlighting the need for early diagnosis and targeted interventions. Currently, small molecular chaperones have shown the most promising clinical results compared to other agents. This synthesis of clinical, pathological, and molecular aspects underscores the assertion that GBA1-PD is a distinct clinical and pathobiological PD phenotype, necessitating specific management and research approaches to better understand and treat this debilitating condition