3D flash memory cube design utilizing COTS for space

With the rapid growth in scope for space missions, the computing capabilities of on-board spacecraft is becoming a major limiting factor for future missions. This thesis is part of a project that designs a radiation hardened NAND Flash memory cube for use in space. The main focus of this thesis is on presenting a new NAND Flash memory cube design with features to allow the cube to be used in space. Another goal of the thesis is to show proof of concept of the cube. Thus, a preliminary RTL was designed for the memory controllerportion of the design and simulated results are shown in the later part of the thesis.M.S

Eosinophilic gastroenteritis in an 18-year-old male with prolonged nephrotic syndrome

Eosinophilic gastroenteritis is a rare disease characterized by prominent eosinophilic tissue infiltration of the gastrointestinal tract. Here, we report a case of eosinophilic gastroenteritis in an 18-year-old patient with prolonged nephrotic syndrome who presented with abdominal pain and peripheral hypereosinophilia. During the previous 2 years, he had visited local Emergency Department several times because of epigastric pain and nausea. He had been treated with steroid-dependent nephrotic syndrome since 3 years of age. Tests ruled out allergic and parasitic disease etiologies. Gastroduodenoscopy with biopsy revealed marked eosinophilic infiltration in the duodenum. Renal biopsy findings indicated minimal change disease spectrum without eosinophilic infiltration. The oral deflazacort dosage was increased, and the patient was discharged after abdominal pain resolved. To our knowledge, this is the first report of eosinophilic gastroenteritis in a patient with minimal change disease

Decreased Exosomal Acetylcholinesterase Activity in the Plasma of Patients With Parkinson’s Disease

Exosomes, which are small extracellular vesicles produced from various cell types, contain a variety of molecular constituents, such as proteins, lipids, and RNA. Recently, exosomal biomarkers have been investigated to probe the understanding and diagnosis of neurodegenerative disorders. Previous reports have demonstrated increased exosomal α-synuclein (α-syn) in patients with Parkinson’s disease (PD) in comparison to healthy controls (HC). Interestingly, the cholinergic loss was revealed in the central and peripheral nervous systems in histopathology and molecular neuroimaging. Thereby, we simultaneously examined acetylcholinesterase (AChE) with α-syn as exosomal markers. Exosomes were isolated from the plasma of 34 FP-CIT PET proven patients with PD and 29 HC. Exosomal α-syn and AChE activity were quantified andthe relationship with clinical parameters was analyzed. Remarkably, exosomal AChE activity was significantly decreased in PD compared to HC (P = 0.002). Moreover, exosomal AChE activity in PD revealed a strong negative correlation with disease severity, including H&Y (P = 0.007) and UPDRS part III (P = 0.047) scores. By contrast, no significant difference in exosomal α-syn concentration was observed between groups. These results support the occurrence of cholinergic dysfunction in PD, and they could be implicated with disease progression, especially motor deficits. Exosomal AChE activity with advanced exosome isolation techniques may be a reliable biomarker for the early diagnosis and prognosis of PD

Prenatal Diagnosis of Uniparental Disomy in Cases of Rare Autosomal Trisomies Detected Using Noninvasive Prenatal Test: A Case of Prader–Willi Syndrome

Rare autosomal trisomies (RATs) other than common aneuploidies can be detected using noninvasive prenatal testing (NIPT). However, conventional karyotyping is insufficient for evaluating diploid fetuses with uniparental disomy (UPD) due to trisomy rescue. Using the diagnostic process for Prader–Willi syndrome (PWS), we aim to describe the need for additional prenatal diagnostic testing for confirming UPD in fetuses diagnosed with RATs via NIPT and its clinical implications. NIPT was performed using the massively parallel sequencing (MPS) method, and all pregnant women with RATs underwent amniocentesis. After confirming the normal karyotype, short tandem repeat (STR) analysis, methylation-specific PCR (MS-PCR), and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were performed to detect UPD. Overall, six cases were diagnosed with RATs. There was a suspicion of trisomies of chromosomes 7, 8, and 15 in two cases each. However, these cases were confirmed to have a normal karyotype using amniocentesis. In one of six cases, PWS caused by maternal UPD 15 was diagnosed using MS-PCR and MS-MLPA. We propose that in cases where RAT is detected by NIPT, UPD should be considered following trisomy rescue. Even if amniocentesis confirms a normal karyotype, UPD testing (such as MS-PCR and MS-MLPA) should be recommended for accurate assessment, as an accurate diagnosis can lead to appropriate genetic counseling and improved overall pregnancy management

Prenatal Diagnosis of Uniparental Disomy in Cases of Rare Autosomal Trisomies Detected Using Noninvasive Prenatal Test: A Case of Prader–Willi Syndrome

Rare autosomal trisomies (RATs) other than common aneuploidies can be detected using noninvasive prenatal testing (NIPT). However, conventional karyotyping is insufficient for evaluating diploid fetuses with uniparental disomy (UPD) due to trisomy rescue. Using the diagnostic process for Prader–Willi syndrome (PWS), we aim to describe the need for additional prenatal diagnostic testing for confirming UPD in fetuses diagnosed with RATs via NIPT and its clinical implications. NIPT was performed using the massively parallel sequencing (MPS) method, and all pregnant women with RATs underwent amniocentesis. After confirming the normal karyotype, short tandem repeat (STR) analysis, methylation-specific PCR (MS-PCR), and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were performed to detect UPD. Overall, six cases were diagnosed with RATs. There was a suspicion of trisomies of chromosomes 7, 8, and 15 in two cases each. However, these cases were confirmed to have a normal karyotype using amniocentesis. In one of six cases, PWS caused by maternal UPD 15 was diagnosed using MS-PCR and MS-MLPA. We propose that in cases where RAT is detected by NIPT, UPD should be considered following trisomy rescue. Even if amniocentesis confirms a normal karyotype, UPD testing (such as MS-PCR and MS-MLPA) should be recommended for accurate assessment, as an accurate diagnosis can lead to appropriate genetic counseling and improved overall pregnancy management

A Possible Pathogenic PSEN2 Gly56Ser Mutation in a Korean Patient with Early-Onset Alzheimer’s Disease

Early-onset Alzheimer’s disease (EOAD) is characterized by the presence of neurological symptoms in patients with Alzheimer’s disease (AD) before 65 years of age. Mutations in pathological genes, including amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2), were associated with EOAD. Seventy-six mutations in PSEN2 have been found around the world, which could affect the activity of γ-secretase in amyloid beta processing. Here, a heterozygous PSEN2 point mutation from G to A nucleotide change at position 166 (codon 56; c.166G>A, Gly56Ser) was identified in a 64-year-old Korean female with AD with progressive cognitive memory impairment for the 4 years prior to the hospital visit. Hippocampal atrophy was observed from magnetic resonance imaging-based neuroimaging analyses. Temporal and parietal cortex hypometabolisms were identified using fluorodeoxyglucose positron emission tomography. This mutation was at the N-terminal portion of the presenilin 2 protein on the cytosolic side. Therefore, the serine substitution may have promoted AD pathogenesis by perturbing to the mutation region through altered phosphorylation of presenilin. In silico analysis revealed that the mutation altered protein bulkiness with increased hydrophilicity and reduced flexibility of the mutated region of the protein. Structural changes were likely caused by intramolecular interactions between serine and other residues, which may have affected APP processing. The functional study will clarify the pathogenicity of the mutation in the future