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Integration of renewable resources such as remote solar or wind farms and electricpower trading between neighbouring countries lead to new requirements on the development of thetransmission grids. Since AC grid expansion is limited by e.g. legislations issues, High VoltageDirect Current (HVDC) technology with its diverse benets compared to AC is being considered asappropriate alternative solution. The developed HVDC grid can be either embedded inside one ACgrid or connects several AC areas. In both architectures, the separate DC supervisory control can beproposed to control the HVDC grids using the interfacing information from AC Supervisory ControlAnd Data Acquisition (SCADA). The supervisory control is supposed to calculate the optimal power ow (OPF) in order to run the system in the most optimal situation. Based on the architecture, therequired information, boundary of the system and also objective function can vary. The aim of the thesis is to present the ndings of a feasibility study to implement a supervisorycontrol for bipolar Voltage Source Converter (VSC) HVDC grids in possible real time platforms. DCsupervisory control has a network topology manager to identify the grid conguration and employsan OPF calculator based on interior point optimization method to determine the set-point valuesfor all HVDC stations in a grid. OPF calculator takes into account the DC voltage, converter andDC line constraints.i

Rapidly progressive scoliosis in a patient with Marshall-Smith Syndrome

Case: Marshall-Smith syndrome is a rare genetic condition due to mutations in the NFIX gene resulting in a multitude of congenital abnormalities, including atlantoaxial instability and ligamentous laxity. This case report describes a patient with Marshall-Smith syndrome who developed atlantoaxial rotatory subluxation and subsequent rapidly progressive scoliosis after occiput-C2 fusion. She was treated with 4 weeks of halo traction, followed by an occiput to T3 posterior spinal fusion, segmental fixation, and magnetic growth rods from T3-L4. The thoracic curve was reduced from 125 to 34 degrees.Conclusion: The presence of atlantoaxial rotatory subluxation in the setting of generalized ligamentous laxity likely contributed to the rapid progression of scoliosis in this patient and should be recognized.https://scholarlycommons.henryford.com/merf2019caserpt/1066/thumbnail.jp

Disseminated non-segmental vitiligo with halo nevi and grey hair

HISTORY: A 20-year-old male with history of narcolepsy presented to the dermatology clinic for 5-month history of asymptomatic light spots on his trunk and graying of his hair. He initially noted acute onset of light spots slowly enlarging around moles on his chest and abdomen. Three months later, he developed slowly enlarging light spots disassociated with moles on his back and grey hairs on the back and top of his scalp. He denied new or changing moles and had no associated symptoms. Personal and family history was negative for vitiligo, autoimmune conditions, and skin cancers. EXAMINATION: On examination, the patient has numerous, isolated hypo- to depigmented macules and patches on the trunk and back, some are surrounding symmetric, evenly pigmented, well-demarcated 3-6-mm brown-black macules. The left upper inner arm had two small de-pigmented patches and the right inner thigh had one hypopigmented patch. The scalp is noted to have diffuse hypopigmentation with associated graying of hair. Wood’s lamp examination revealed enhancement and depigmentation of these macules and patches. COURSE AND THERAPY: The patient was started on topical betamethasone dipropionate 0.05% ointment twice daily to the hypopigmented and de-pigmented patches, and both Gingko biloba and alpha Lipoic acid capsules daily. DISCUSSION Halo nevi (HN, also known as Sutton\u27s nevus) are thought to be a benign finding affecting 1% of the population. The diameter of the depigmented halo may range fromcentimeters, just as the size of the nevi themselves may range from a few millimeters to centimeters. Males and females are equally affected, and the mean age of onset is 15 years. Patients with Turner’s syndrome have an increased tendency and a familial variant has been reported. While the exact pathophysiology of HN is poorly understood, melanocytes are absent under histopathology, suggesting an etiologic link to vitiligo. The inflammatory composition of halo nevi is predominantly T-lymphocytes (4:1 ratio of CD8:CD4) with scattered macrophages. Overall, an immunologic mechanism seems to be the cause of melanocyte destruction in HN, although the trigger and role of lymphocytes remains uncertain. Although usually benign, HN have two important significant associations: vitiligo and melanoma-associated leukoderma. In fact, approximately 20% of individuals with HN have vitiligo. A retrospective study of 101 patients with HN-associated vitiligo demonstrated that, under multivariate analysis, Koebner phenomenon, multiple HN, and family history of vitiligo are independent factors for HN appearance predicting vitiligo. Of these, our patient had only multiple HN. However, he also had premature hair graying (PHG). Lesional leukotrichia and family history of PHG are sometimes seen in patients with non-segmental HN-associated vitiligo. However, reports of PHG occurring concurrently in a patient with acute presentation of HN-associated vitiligo are lacking. Ezzedine and colleagues remark that PHG is an inherited trait, but an immunological factor may be implicated in a subset of cases. Nevertheless, PHG is an unusual finding in a patient with HN-associated vitiligo and should prompt all practitioners to search for melanoma. Thus, patients should be referred to dermatology for a full body skin and oral examination, ophthalmology to assess for uveal melanoma, and if appropriate, OBGYN to assess for mucosal melanoma. A thorough total body skin examination of our patient did not reveal lesions concerning for melanoma. He is pending examination by Ophthalmology. Thus, his acute clinical presentation of HN, non-segmental vitiligo, and PHG represents a rare triad.https://scholarlycommons.henryford.com/merf2020caserpt/1070/thumbnail.jp

Consequences of an NFU1 Mutation in the Fe-­S Cluster Biosynthetic Pathway

Mathematical and Physical SciencesFe-S clusters are prosthetic groups found in several metalloproteins, and are conserved across all kingdoms of life (Lill, 2008). These clusters have essential yet diverse roles in the mechanics of the cell, including electron transfer, regulation of gene expression, and disulfide reduction (Johnson, 2005). Mutations in cluster-assembly and transfer proteins dramatically affect several crucial metabolic pathways (Ahting, 2015). Genetic mutations to a specific subset of mitochondrial cluster-delivery proteins are broadly categorized as a Multiple Mitochondrial Dysfunction Syndrome (MMDS), and symptoms include impairment of neurological development, lactic acidosis, failure to thrive, and ultimately early death (Invernizzi, 2014) (Navarro-Sastre, 2011). Multiple Mitochondrial Dysfunction Syndrome 1 (MMDS1) arises as a result of the missense mutation c.622G>T in NFU1, a cluster scaffold protein, which mutates a glycine near the Fe-S cluster binding pocket to a cysteine (G208C) (Navarro-Sastre, 2011). The connection between the mutation in NFU1 and MMDS1 has been recently discovered, and at this point, little is known about the role of NFU1 and why the point mutation results in such drastic consequences. A better understanding of the mechanism of disease and the dysfunction of the mutant NFU1 at a fundamental level is essential in order to find a potential cure. An investigation into the structural and functional consequences of an additional cysteine residue at the binding pocket will serve to characterize the mutant protein and examine the cause of disease at a biochemical level.Undergraduate Research OfficeNational Institutes of HealthOSU Chemistry-Biology Interface ProgramThe Ohio State Biochemistry ProgramThe Ohio State Biophysics ProgramA five-year embargo was granted for this item.Academic Major: Biochemistr

Dihydropyrimidine dehydrogenase deficiency as a cause of fatal 5-Fluorouracil toxicity

5-Fluorouracil (5-FU), in combination with other cytotoxic drugs, is commonly used to treat a variety of cancers. Dihydropyrimidine dehydrogenase (DPD) catalyzes the first catabolic step of the 5-FU degradation pathway, converting 80% of 5-FU to its inactive metabolite. Approximately 0.3% of the population demonstrate complete DPD deficiency, translating to extreme toxicity of 5-FU. Here we present a case of a patient who had a fatal outcome after treatment with 5-FU who was found to have an unknown DPD deficiency discovered at autopsy

A pediatric case of pigmented epithelioid melanocytoma with chromosomal copy number alterations in 15q and 17q and a novel NTRK3‐SCAPER gene fusion

Pigmented epithelioid melanocytoma (PEM) represents a group of rare, heavily pigmented melanocytic tumors encompassing lesions previously designated as “animal‐type melanomas” and “epithelioid blue nevi.” Despite the association of multiple such tumors in the setting of Carney complex, most cases of PEM occur spontaneously as solitary neoplasms in otherwise healthy patients. PEM may arise in both children and adults, and has a known propensity to spread to the regional lymph nodes. Despite this latter finding, recurrence at the biopsy site or spread beyond the lymph node basin is exceptionally uncommon. Although the molecular basis for PEM continues to be characterized, findings to date suggest that this category of melanocytic neoplasia has genetic alterations distinct from those seen in common nevi, dysplastic nevi, Spitz nevi, and melanoma. Herein, we present an in‐depth clinical, histopathologic, and molecular analysis of a case of PEM occurring on the scalp of a young African American girl found to have a novel NTRK3‐SCAPER gene fusion.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152480/1/cup13566.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152480/2/cup13566_am.pd

A pediatric case of pigmented epithelioid melanocytoma with chromosomal copy number alterations in 15q and 17q and a novel NTRK3‐SCAPER gene fusion

Pigmented epithelioid melanocytoma (PEM) represents a group of rare, heavily pigmented melanocytic tumors encompassing lesions previously designated as “animal‐type melanomas” and “epithelioid blue nevi.” Despite the association of multiple such tumors in the setting of Carney complex, most cases of PEM occur spontaneously as solitary neoplasms in otherwise healthy patients. PEM may arise in both children and adults, and has a known propensity to spread to the regional lymph nodes. Despite this latter finding, recurrence at the biopsy site or spread beyond the lymph node basin is exceptionally uncommon. Although the molecular basis for PEM continues to be characterized, findings to date suggest that this category of melanocytic neoplasia has genetic alterations distinct from those seen in common nevi, dysplastic nevi, Spitz nevi, and melanoma. Herein, we present an in‐depth clinical, histopathologic, and molecular analysis of a case of PEM occurring on the scalp of a young African American girl found to have a novel NTRK3‐SCAPER gene fusion.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152480/1/cup13566.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152480/2/cup13566_am.pd

Dihydropyrimidine dehydrogenase deficiency as a cause of fatal 5-Fluorouracil toxicity

5-Fluorouracil (5-FU), in combination with other cytotoxic drugs, is commonly used to treat a variety of cancers. Dihydropyrimidine dehydrogenase (DPD) catalyzes the first catabolic step of the 5-FU degradation pathway, converting 80% of 5-FU to its inactive metabolite. Approximately 0.3% of the population demonstrate complete DPD deficiency, translating to extreme toxicity of 5-FU. Here we present a case of a patient who had a fatal outcome after treatment with 5-FU who was found to have an unknown DPD deficiency discovered at autopsy

PufQ regulates porphyrin flux at the haem/bacteriochlorophyll branchpoint of tetrapyrrole biosynthesis via interactions with ferrochelatase

Facultative phototrophs such as Rhodobacter sphaeroides can switch between heterotrophic and photosynthetic growth. This transition is governed by oxygen tension and involves the large-scale production of bacteriochlorophyll, which shares a biosynthetic pathway with haem up to protoporphyrin IX. Here, the pathways diverge with the insertion of Fe(2+) or Mg(2+) into protoporphyrin by ferrochelatase or magnesium chelatase, respectively. Tight regulation of this branchpoint is essential, but the mechanisms for switching between respiratory and photosynthetic growth are poorly understood. We show that PufQ governs the haem/bacteriochlorophyll switch; pufQ is found within the oxygen-regulated pufQBALMX operon encoding the reaction centre-light harvesting photosystem complex. A pufQ deletion strain synthesises low levels of bacteriochlorophyll and accumulates the biosynthetic precursor coproporphyrinogen III; a suppressor mutant of this strain harbours a mutation in the hemH gene encoding ferrochelatase, substantially reducing ferrochelatase activity. FLAG-immunoprecipitation experiments retrieve a ferrochelatase-PufQ-carotenoid complex, proposed to regulate the haem/bacteriochlorophyll branchpoint by directing porphyrin flux towards bacteriochlorophyll production under oxygen-limiting conditions. The co-location of pufQ and the photosystem genes in the same operon ensures that switching of tetrapyrrole metabolism towards bacteriochlorophyll is coordinated with the production of reaction centre and light harvesting polypeptides. This article is protected by copyright. All rights reserved