Terminal Arm Research Articles

Preclinical assessment of a noncooled MR thermometry-based neurosurgical laser therapy system.

MRI-guided laser interstitial thermal therapy (MRgLITT) has recently gained interest as an ablative stereotactic procedure for intractable epilepsy, movement disorders, and brain tumors. Conventionally, a LITT system consists of a laser generator and cooled laser applicator, which is a fiber optic core surrounded by a sheath through which cooled fluid is pumped. However, this footprint can make the system bulky and nonmobile, limit the maximum depth of targeting, and increase the chances of breakdown. Herein, the authors conduct a preclinical assessment of a noncooled MRgLITT system in a porcine model. Three-tesla MRI was used to guide the in vivo placement of noncooled laser applicators in the porcine brain. The study consisted of a survival arm and terminal arm. The laser was activated at a power of 4-7 W for ≤ 180 seconds. Temperature changes were monitored using the MR thermometry software ThermoGuide in the survival arm (n = 5) or both ThermoGuide software and adjacently inserted thermal probes in the terminal arm (n = 3). Thermal damage was determined by the software using the temperature-time relationship of cumulative equivalent minutes at 43°C (CEM43). Temperatures calculated by the software were compared with those recorded by the temperature probes. The dimensions of thermal damage thresholds (TDTs; 2-9, 10-59, 60-239, ≥ 240 CEM43 isolines) given by MR thermometry were compared with the dimensions of irreversible damage on histopathological analysis. There was a strong correlation between temperature recordings by ThermoGuide and those by thermal probes at both 4 mm (r = 0.96) and 8 mm (r = 0.80), with a mean absolute error of 0.76°C ± 2.13°C and 0.17°C ± 1.65°C at 4 and 8 mm, respectively. The area of 2-9 CEM43 was larger than the area of irreversible damage seen on histopathological analysis. The dimensions of the 10 and 60 CEM43 correlated well with dimensions of the lesion on histopathological analysis. A well-defined border (≤ 1 mm) was observed between the area of irreversible damage and healthy brain tissue. This preclinical assessment showed that the noncooled LITT system was able to precisely reach the target and create well-defined lesions within a margin of safety, without any adverse effects. MR thermometry software provided an accurate near-real-time temperature of the brain tissue, and dimensions of the lesion as visualized by the software correlated well with histopathological findings. Further studies to test the system's efficacy and safety in human subjects are in progress.

Evo-Devo in Ophiuroids: The Switch from Planktotrophy to Lecithotrophy in Ophionereis.

AbstractUnderstanding the evolution of development (evo-devo) in the Ophiuroidea and the pathways in the switch from a feeding to a nonfeeding larva is complicated by the variability in the phenotype of the metamorphic larva, being a reduced yolky ophiopluteus in some species (type I development) and a vitellaria larva in others (type II development). We investigated evo-devo in the family Ophionereididae, a group dominated by lecithotrophic development through a vitellaria larva. We reared the planktotrophic larvae of Ophionereis fasciata to settlement to determine the metamorphic phenotype. Counter to expectations, O. fasciata did not exhibit type II metamorphosis through a vitellaria, although it did exhibit transient vitellaria-like features. Resorption of the larval arms in the same interradial positions where the ciliary bands form in vitellariae gave them a fleeting vitellaria-like appearance. Development of O. fasciata exhibits heterochronic features in early formation of the skeletal primordium of the third pair (postoral) of larval arms and in the presettlement juvenile early appearance of the juvenile terminal arm plates on external view in parallel with larval arm resorption. Development of the fourth pair (posterodorsal) of larval arms, the last pair to be formed, is plastic, with 44% of larvae exhibiting partial arm growth. Heterochronic traits in development, as seen in O. fasciata, may have facilitated evolution of a lecithotrophic mode of development in Ophionereis. Comparison of the ophiopluteus of O. fasciata and the vestigial pluteus of O. schayeri provided insights into the simplification of larval form from the ancestral (feeding larva) state in Ophionereis. The diverse metamorphic phenotypes in ophiuroids indicate that type I and type II development may not be completely divergent lines of evo-devo and point to selective pressure in the pelagic-benthic transition in the evolution of ophiuroid development.

High and low performers in internal rotation after reverse total shoulder arthroplasty: a biplane fluoroscopic study.

Internal rotation in adduction is often limited after reverse total shoulder arthroplasty (rTSA), but the origins of this functional deficit are unclear. Few studies have directly compared individuals who can and cannot perform internal rotation in adduction. Little data on underlying 3D humerothoracic, scapulothoracic, and glenohumeral joint relationships in these patients are available. Individuals >1-year postoperative to rTSA were imaged with biplane fluoroscopy in resting neutral and internal rotation in adduction poses. Subjects could either perform internal rotation in adduction with their hand at T12 or higher (high, N=7), or below the hip pocket (low, N=8). Demographics, the American Shoulder and Elbow Surgeons score, Simple Shoulder Test, and scapular notching grade were recorded. Joint orientation angles were derived from model-based markerless tracking of the scapula and humerus relative to the torso. The 3D implant models were aligned to preoperative computed tomography models to evaluate bone-implant impingement. The Simple Shoulder Test was highest in the high group (11±1 vs. 9±2, P=.019). Two subjects per group had scapular notching (grades 1 and 2), and 3 high group and 4 low group subjects had impingement below the glenoid. In the neutral pose, the scapula had 7° more upward rotation in the high group (P=.100), and the low group demonstrated 9° more posterior tilt (P=.017) and 14° more glenohumeral elevation (P=.047). In the internal rotation pose, axial rotation was >45° higher in the high group (P≤.008) and the low group again had 11° more glenohumeral elevation (P=.058). Large rotational differences within subject groups arose from a combination of differences in the resting neutral and maximum internal rotation in adduction poses, not only the terminal arm position. Individuals who were able to perform high internal rotation in adduction after rTSA demonstrated differences in joint orientation and anatomic biases versus patients with low internal rotation. The high rotation group had 7° more resting scapular upward rotation and used a 15°-30° change in scapular tilt to perform internal rotation in adduction versus patients in the low group. The combination of altered resting scapular posture and restricted scapulothoracic range of motion could prohibit glenohumeral rotation required to reach internal rotation in adduction. In addition, inter-patient variation in humeral torsion may contribute substantially to postoperative internal rotation differences. These data point toward modifiable implant design and placement factors, as well as foci for physical therapy to strengthen and mobilize the scapula and glenohumeral joint in response to rTSA surgery.

Non-symmetrical bent-core homologous series bearing 1,2,4-oxadiazole core with a cholesterol terminal arm: Synthesis, characterization and their liquid crystalline properties

Nonsymmetric 1,2,4-oxadiazole derivatives with cholesteryl and alkoxy chain as end moieties exhibiting monotropic liquid crystalline behavior have been reported. The molecular structures have been confirmed by elemental analysis and spectroscopic studies. Differential scanning calorimetry (DSC) studies revealed multiple phase transitions and polarized optical microscopy (POM) investigations confirmed smectic A (SmA) and chiral nematic (N*) phases. The importance of alkyl chain length in mesophase formation is discussed. A comparison with other reported mesogenic materials possessing similar molecular structures is also discussed.

Externally initiated event in sequential risk assessment for the onshore LNG marine loading arm unit

This paper describes the failure assessment of the unloading arm unit that is connected to a Liquified Natural Gas (LNG) terminal. In this work, an external event, i.e., lightning, was simulated as the triggering event. A Temporal Fault Tree (TFT) analysis was developed, and sequential failures that function under the Priority AND (PAND) gate were assessed.The results show that the highest contributing factor to the failure of the terminal unloading arm was the sequential failure due to the loss of sensors which can happen before or after lightning strikes. The occurrence of failures for the loading arm was estimated using a Monte Carlo Simulation (MCS). For service years of 32.7, the sequential failures occurred 131 times when preventive maintenance was not considered. This work also presents that the failure distribution of the marine loading arm follows the Weibull distribution characteristic with the scale (α) and the shape (β) parameters values of 132,817.5 h-1 and 1.556, respectively.

LD-CNV: rapid and simple discovery of chromosomal translocations using linkage disequilibrium between copy number variable loci.

Large-scale structural variations, such as chromosomal translocations, can have profound effects on fitness and phenotype, but are difficult to identify and characterize. Here, we describe a simple and effective method aimed at identifying translocations using only the dosage of sequence reads mapped on the reference genome. We binned reads on genomic segments sized according to sequencing coverage and identified instances when copy number segregated in populations. For each dosage-polymorphic 1 Mb bin, we tested independence, effectively an apparent linkage disequilibrium (LD), with other variable bins. In nine potato (Solanum tuberosum) dihaploid families translocations affecting pericentromeric regions were common and in two cases were due to genomic misassembly. In two populations, we found evidence for translocation affecting euchromatic arms. In cv. PI 310467, a nonreciprocal translocation between chromosomes (chr.) 7 and 8 resulted in a 5-3 copy number change affecting several Mb at the respective chromosome tips. In cv. "Alca Tarma," the terminal arm of chr. 4 translocated to the tip of chr. 1. Using oligonucleotide-based fluorescent in situ hybridization painting probes (oligo-FISH), we tested and confirmed the predicted arrangement in PI 310467. In 192 natural accessions of Arabidopsis thaliana, dosage haplotypes tended to vary continuously and resulted in higher noise, while apparent LD between pericentromeric regions suggested the effect of repeats. This method, LD-CNV, should be useful in species where translocations are suspected because it tests linkage without the need for genotyping.

Clinical and molecular characterization of an almost complete ring chromosome 4 in two sisters, with recurrence due to gonadal mosaicism.

Autosomal ring chromosomes are rare cytogenetic findings that arise from breakage and fusion of the chromosome ends. Rings are mitotically unstable, usually sporadic and associated with a 'ring syndrome', characterized by a variable phenotype: growth retardation, no significant dysmorphisms and normal to moderately disabled intelligence. We describe the clinical features and molecular characterization of two sisters with ring chromosome 4. Karyotype analysis was performed on both sisters and parents. Chromosome microarray was performed on both sisters to delineate the breakpoint imbalance. Both sisters had a large ring 4 chromosome in the majority of cells analyzed on karyotype. Microarray results were identical in the sisters, showing a 55.8 kb duplication on the terminal 4p arm and a 1.5 Mb deletion on the terminal 4q arm. No genes of interest were identified in these regions. Parental karyotypes on lymphocytes and fibroblasts were normal, with no finding of mosaicism for the ring 4 chromosome. Polymorphic marker analysis revealed the maternal origin of the ring. To our knowledge, this is the first reported instance of a ring 4 chromosome recurring in siblings after extensive parental testing, which suggests this was due to maternal gonadal mosaicism.

Molecular cytogenetic analysis and genetic counseling: a case report of eight 46,XX males and a literature review

Background46,XX male syndrome is a rare disorder that usually causes infertility. This study was established to identify the genetic causes of this condition in a series of 46,XX males through the combined application of cytogenetic and molecular genetic techniques.Case presentationWe identified eight azoospermic 46,XX males who underwent infertility-related consultations at our center. They all presented normal male phenotypes. In seven of the eight 46,XX males (87.5%), translocation of the SRY gene to the terminal short arm of the X chromosome was clearly involved in their condition, which illustrated that this translocation is the main mechanism of 46,XX sex reversal, in line with previous reports. However, one patient presented a homozygous DAX1 mutation (c.498G > A, p.R166R), which was not previously reported in SRY-negative XX males.ConclusionsWe proposed that this synonymous DAX1 mutation in case 8 might not be associated with the activation of the male sex-determining pathway, and the male phenotype in this case might be regulated by some unidentified genetic or environmental factors. Hence, the detection of genetic variations associated with sex reversal in critical sex-determining genes should be recommended for SRY-negative XX males. Only after comprehensive cytogenetic and molecular genetic analyses can genetic counseling be offered to 46,XX males.

EPO and TMBIM3/GRINA Promote the Activation of the Adaptive Arm and Counteract the Terminal Arm of the Unfolded Protein Response after Murine Transient Cerebral Ischemia.

Ischemic stroke is known to cause the accumulation of misfolded proteins and loss of calcium homeostasis leading to impairment of endoplasmic reticulum (ER) function. The unfolded protein response (UPR) is an ER-located and cytoprotective pathway that aims to resolve ER stress. Transmembrane BAX inhibitor-1 motif-containing (TMBIM) protein family member TMBIM3/GRINA is highly expressed in the brain and mostly located at the ER membrane suppressing ER calcium release by inositol-1,4,5-trisphosphate receptors. GRINA confers neuroprotection and is regulated by erythropoietin (EPO) after murine cerebral ischemia. However, the role of GRINA and the impact of EPO treatment on the post-ischemic UPR have not been elucidated yet. We subjected GRINA-deficient (Grina−/−) and wildtype mice to transient (30 min) middle cerebral artery occlusion (tMCAo) followed by 6 h or 72 h of reperfusion. We administered EPO or saline 0, 24 and 48 h after tMCAo/sham surgery. Oxygen–glucose deprivation (OGD) and pharmacological stimulation of the UPR using Tunicamycin and Thapsigargin were carried out in primary murine cortical mixed cell cultures. Treatment with the PERK-inhibitor GSK-2606414, IRE1a-RNase-inhibitor STF-083010 and EPO was performed 1 h prior to either 1 h, 2 h or 3 h of OGD. We found earlier and larger infarct demarcations in Grina−/− mice compared to wildtype mice, which was accompanied by a worse neurological outcome and an abolishment of EPO-mediated neuroprotection after ischemic stroke. In addition, GRINA-deficiency increased apoptosis and the activation of the corresponding PERK arm of the UPR after stroke. EPO enhanced the post-ischemic activation of pro-survival IRE1a and counteracted the pro-apoptotic PERK branch of the UPR. Both EPO and the PERK-inhibitor GSK-2606414 reduced cell death and regulated Grina mRNA levels after OGD. In conclusion, GRINA plays a crucial role in post-ischemic UPR and the use of both GSK-2606414 and EPO might lead to neuroprotection.

64. CAN FISH PROBE STRATEGIES INFLUENCE MOSAIC EMBRYO RATES IN ROBERTSONIAN TRANSLOCATION PGD?

Introduction Robertsonian translocation (RT) results from centric fusion of two acrocentric chromosomes. RT carriers are phenotypically normal, but they are known to be at increased risk of repeated miscarriages or of pregnancies resulting in the birth of a child with congenital anomalies, mental retardation. Preimplantation Genetic Diagnosis (PGD) is therefore a solution for RT carriers. A suitable probe strategy on cleavage stage allows us to differentiate balanced embryos, unbalanced embryos, mosaic and chaotic embryos. According to ESHRE recommendations, only balanced embryos are considered for transfer. However, transfer of some mosaic embryos has resulted in live births. We performed the first comparative analysis between a two or a three probes FISH strategies, in order to enhance the safety and security of embryos transferred and to establish the best reliable and low-cost strategy for RT PGD management. Material and methods Retrospective analysis of 253 preimplantation genetic diagnosis (PGD) cycles were performed on 91 men and 42 women carriers of different Robertsonian translocations t(13;14), t(14;21), t(14;15), t(15;21), t(13;15), t(13;21), t(14;22), t(15;22), t(21;22), t(13;13). The first strategy involved two relevant probes use. Each probe is located within the terminal long arm. The second strategy required a third probe addition on one of the two translocated chromosomes. The additional probe is located close to centromeric regions. Result(s) Regardless of probe strategies, 253 PGD cycles were performed in the aim to exclude imbalances in both carriers. On a total of 1,549 biopsied cells, 1,458 were successfully analyzed. Among these, 232 were transferred. Clinical pregnancy was achieved in 108 patients, and 85 healthy babies were delivered. No significant difference was observed in the balanced embryo rates (40.5% and 40.4% in a two probes and a three probe strategies respectively). Among these balanced embryos, diagnostic established on single or two mononucleate cells, wasn't affected by the probe strategies. However, a significant difference (p Conclusion(s) According to the present findings, concerning balanced embryo rates, the two probes strategy seems more suitable for Robertsonian translocation PGD analysis, firstly because it led to similar results as the three probes strategy. Secondly, this study also highlighted an increase mosaic embryo rate observed with the two probes strategy. Recent data indicated that mosaic embryos may represent a second category to transfer after balanced embryos. Obviously, balanced embryos must be transferred in priority. However in absence of balanced embryos, transfer of a mosaic embryo should be considered. In this case, genetic counseling about risks and potential benefits is of utmost importance to ensure informed decision-making by patients.

Seamless Fault-Tolerant Operation of a Modular Multilevel Converter With Switch Open-Circuit Fault Diagnosis in a Distributed Control Architecture

Modularity and high reliability from redundancy are the two attractive advantages of modular multilevel converters (MMCs). This paper elaborates a switch open-circuit fault diagnosis and a fault-tolerant operation scheme for MMCs with distributed control. The proposed fault diagnosis and fault-tolerant control method can significantly improve the reliability of the MMC while maintaining the modularity of its software implementation. By distributing fault diagnosis into submodules, its local controller is capable of identifying the switching devices in open-circuit fault without extra hardware circuitry. Based on the real-time measurements of submodule terminal voltage and arm current, single, or multiple faulty switches can be identified within 3.5 ms without triggering faulty alarms. Furthermore, a new fault-tolerant operation is proposed to maintain the output current, internal dynamics, and switching harmonics unchanged after the faulty submodule is bypassed. This is achieved by resetting the period and phase registers in the local controller according to the information of bypassed submodules. The control loops of the MMC are not influenced by the proposed fault diagnosis and fault-tolerant operation, making the operation transition seamless and reliable. Experimental results show that fault identification and system reconfiguration can be completed within 5 ms, and the MMC can seamlessly and smooth ride through the switch open-circuit faults without severe malfunction and catastrophic damages.

Dichotomous On-Surface Self-Assembly of Tripod Molecules with Anchor Like Interaction Pattern

Recent development of methods to fabricate low dimensional molecular structures has enabled tailoring their architecture using building blocks with suitably encoded structural and chemical properties. In this contribution we study structure formation in adsorbed assemblies comprising model tripod molecules equipped with terminal arm segments providing short-range directional interactions. The interaction directions were assigned in a specific anchor like pattern which enabled the creation of diverse intermolecular connections. To explore the on-surface self-assembly of these functional units the coarse grained lattice Monte Carlo simulation method was used in which the molecules were represented as collections of interconnected segments adsorbed on a triangular lattice. Our theoretical investigations focus on the effect of symmetry and size of molecular backbone on the outcome of the 2D self-assembly. The simulations revealed the formation of complex superstructures of two types including porous networks with diverse nanocavities and nanoribbons characterized by a constant width. Occurrence of these different assemblies was found to be strongly dependent on the molecular symmetry and aspect ratio, highlighting the decisive role of the arm length distribution in the tripod building block. The theoretical results of this study can be helpful in designing new low-dimensional superstructures which are stabilized be weak intermolecular interactions as well as by covalent bonds formed in on-surface reactions such as the Ullmann coupling.

New mesogenic materials bearing 1,2,4-oxadiazole moiety: Synthesis, characterization and investigation their mesomorphic behaviors

ABSTRACTIn this work, two series containing a 1,2,4-oxadiazole ring as a central core were synthesized and characterized by common spectroscopic techniques, including FT-IR, 1H-NMR, and elemental analysis. The first series was 3-(4-alkoxyphenyl)-5-(p-methylphenyl)-1,2,4-oxadiazole (Cn), which consisted of alkoxy group in the terminal arm and a methyl group in the other, while, the oxidation reaction of methyl group in a series (Cn) to the carboxy group was the method used to synthesize the second series in this work, 4-(3-(4-alkoxyphenyl)-1,2,4-oxadiazol-5-yl)benzoic acid (Dn). The mesophase behaviors of these two series were studied by optical polarized microscopy (OPM) and differential scanning calorimetry (DSC). The liquid crystalline investigations of the compounds (Cn and Dn) show that the last six homologeus of the series (Cn), (C6–C11), have a monotropic nematic phase, while only the intermediate compounds in the series (Dn), (D3–D9), displayed monotropic nematic phase, also, the liquid crystalline properties in the first and last two compounds in this series (D1, D2, D10, and D11) had disappeared. The differences in liquid crystalline properties between the two series, (Cn and Dn), were discussed through the influences of the different terminal groups (–CH3 and –COOH) in addition to the effect of the 1,2,4-oxadiazole ring and the length of the terminal alkyl chain.

Gantry Robot Dynamic Analysis Based on Lagrange’s Motion Equation

The dynamic problem is defined as the way the motion of the robot arises due to the torques and forces applied at the joint by the actuators. The motion undergone by robotic mechanical system should be as, a rule, as smooth as possible, abrupt changes in position, velocity, and acceleration should be avoided. Indeed, abrupt motions require unlimited amounts of power to be implemented, which the motors cannot supply because of their physical limitations. In this paper an analytical solution for the dynamics of 3 DOF gantry robot presented to achieve those goals, so our aims is to model the dynamics of gantry Robot for simple pick and place application. Equations of motion are derived using the Lagrange equations of the second order, the dynamical model of robot was developed, and the gantry robot system was modeled in SOLIDWORKS software environment and it was simulated using ADAMS software. The manipulator is composed by four basic modules defined as module X, module Y, module Z and terminal arm, where is connected the end-effector.

Synthesis and Covalent Grafting of Tripod‐Shaped Oligo(p‐phenylene)s End‐Capped with Azide Groups

AbstractHere we report the synthesis and characterization of several tripod‐shaped oligo(p‐phenylene)s molecules with legs composed of five and three phenylene units, compounds 1 and 2, respectively. In these structures, each leg is end‐capped with an azide group and the terminal functional arm contains an acetylene or bromine group. The presented synthesis has as the key step a Pd‐catalyzed Suzuki cross‐coupling reaction. In particular, the iodine derivative from the silicon core molecule reacts with the appropriate oligo(p‐phenylene) boron derivative, thus generating the final tripod‐shaped structure. The azide end‐capped leg is specifically designed for its covalent incorporation on alkynyl terminated silicon surfaces in an easy and reproducible way. As a preliminary study, we present the nanostructuration of tripod 2 a on alkynyl‐functionalized silicon wafers through copper‐catalyzed alkyne‐azide cycloaddition (CuAAC) click reaction.

Genetic analysis and molecular mapping of Pitb with broad-spectrum resistance to Magnaporthe oryzae in rice

Zixuan 2 is a broad spectrum-resistance indica subspecies (Oryza sativa ssp. indica) with a high resistance to 15 Magnaporthe oryzae strains from ZA, ZB, and ZC. The F1 generation of hybrid between Zixuan 2 and Lijiangxintuanheigu showed significant resistance to rice-blast pathogen ZB13, and the ratio of resistant plants to susceptible plants was 3:1, indicating that the resistance of Zixuan 2 to rice blast is controlled by a single dominant karyogene or a quantitative trait locus, designated here as Pitb. Molecular marker analysis showed that the rice blast-resistance gene is located on the terminal short arm of chromosome 12 between IN936 and IN950, with a genetic distance of 3.0 cM and physical distance of 143 kbp. In addition, the localization found that Pitb was coseparated with marker IN937. The genetic data and recombination populations provided in this study will enable further fine-mapping and cloning of the resistance gene.

Robust Ordered Bundles of Porous Helical Nanotubes Assembled from Fully Rigid Ionic Benzene-1,3,5-tricarboxamides.

Size-controlled and ordered assemblies of artificial nanotubes are promising for practical applications; however, the supramolecular assembly of such systems remains challenging. A novel strategy is proposed that can be used to reinforce intermolecular noncovalent interactions to construct hierarchical supramolecular structures with fixed sizes and long-range ordering by introducing ionic terminals and fully rigid arms into benzene-1,3,5-tricarboxamide (BTA) molecules. A series of similar BTA molecules with distinct terminal groups and arm lengths are synthesized; all form hexagonal bundles of helical rosette nanotubes spontaneously in water. Despite differences in molecular packing, the dimensions and bundling of the supramolecular nanotubes show almost identical concentration dependence for all molecules. The similarities of the hierarchical assemblies, which tolerate certain molecular irregularities, can extend to properties such as the void ratio of the nanotubular wall. This is a rational strategy that can be used to achieve supramolecular nanotubes in aqueous environments with precise size and ordering at the same time as allowing molecular modifications for functionality.

The Research of Grouting Sandblasting Carrying Manipulator Based Wax Casting-Line

Mechanization and automation are the general trend of Investment casting in the world. The paper briefly discusses the sandblasting process of investment, and introduces the shell casting process. Carrying manipulator design is proposed to complete the investment casting process. The terminal arm and other major components of structural design are discussed. The terminal clamping structure is modeled. The parameters of the terminal clamping structure are designed. The research can provide some reference for the development and design of grouting sandblasting carrying manipulator based wax casting-line.

Genome rearrangements of Streptomyces albus J1074 lead to the carotenoid gene cluster activation

Streptomyces albus J1074 is a derivative of the S. albus G1 strain defective in SalG1 restriction-modification system. Genome sequencing of S. albus J1074 revealed that the size of its chromosome is 6.8 Mb with unusually short terminal arms of only 0.3 and 0.4 Mb. Here we present our attempts to evaluate the dispensability of subtelomeric regions of the S. albus J1074 chromosome. A number of large site-directed genomic deletions led to circularization of the S. albus J1074 chromosome and to the overall genome reduction by 307 kb. Two spontaneous mutants with an activated carotenoid cluster were obtained. Genome sequencing and transcriptome analysis indicated that phenotypes of these mutants resulted from the right terminal 0.42 Mb chromosomal region deletion, followed by the carotenoid cluster amplification. Our results indicate that the right terminal 0.42 Mb fragment is dispensable under laboratory conditions. In contrast, the left terminal arm of the S. albus J1074 chromosome contains essential genes and only 42 kb terminal region is proved to be dispensable. We identified overexpressed carotenoid compounds and determined fitness costs of the large genomic rearrangements.

Utility of SNP Microarray in the Diagnosis of MDS

AbstractAbstract 4806A series of 206 bone marrow aspirates/blood submitted for diagnostic testing for possible MDS/MPN was studied by high resolution SNP microarray to determine the efficacy of this technology for detecting clonal copy number alterations and copy neutral loss of heterozygosity. The latter, acquired uniparental disomy (aUPD), is associated with oncogene mutations that through mitotic recombination have converted to the homozygous state, offering additional selective advantage to daughter cells. Of the 206 patient samples classified as possible MDS, 76 were abnormal by the array. Thirty one of these were either copy neutral or demonstrated copy number alterations below the resolution of cytogenetics. Twenty-three cases demonstrated aUPD and in 14 of these it was the only abnormality detected. Two of these 14 had multiple aUPD (9q/14q and 1p/4q/14q). When the aUPD clones were accompanied by copy number alterations, they could be seen as either the early primary alteration or as a later evolutionary event. The most common segmental UPD regions in MDS were 4q(9), 7q(4),11q(4) and 14q(4) while 9p(4) was the most common a(UPD in the patients with MPN which was likely to be associated with a homozygous JAK2 mutation (confirmed in two cases). The small MPN group (12 cases) demonstrated eight clones with aUPD, only three of which had copy number alterations. All the aUPDs found in this study involved terminal chromosome arm exchange and almost all involved a percentage of the DNA tested, consistent with an acquired change. Whole chromosome aUPD was not seen in these patients. There were three instances of possible interstitial LOH which were not included in this report until normal patient DNA can be obtained to confirm this uncommon observation. Two of these three showed mosaic LOH consistent with an acquired change. The most common deletions below the resolution of cytogenetics involved the RUNX1 and TET2 genes. In summary, the SNP microarray increased the abnormal clone detection from 45 by cytogenetics to 76 in cases of MDS and from 4 to 8 in the small MPN cohort, underscoring the utility of the testing while laying the groundwork for the discovery of new driver genes in the aUPD regions in the pathogenesis of MDS. Disclosures:Papenhausen:LabCorp: Employment. Schwartz:LabCorp: Employment. Thomason:LabCorp: Employment.