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Mapping and Phenotyping Genes in the Del(13)Svea36H Region of Mouse Chromosome 13
Del(13)Svea36H (also known as Del36H) is a 12.7Mb gene-rich region that has been deleted in mouse chromosome 13. It contains numerous disease loci as well as showing conserved synteny to two regions of human chromosome 6p which can be missing in some deletion syndromes. The mouse deletion causes homozygous embryonic lethality but is hemizygously viable. It has therefore been used as a tool to screen for lethal recessive mutations that could help to identify developmental genes that are responsible for the symptoms of the associated human diseases.
A Physical map of the region was constructed in order to facilitate the mapping of mutations arising from the lethal screen. Eleven lethal lines have been mapped to varying degrees of accuracy, including one lethal mutation that exhibited circulation defects which localised to Sox4.
The forkhead transcription factor Foxf2 was considered a potential candidate for embryonic lethal mutations within the interval. To complement the lethal recessive screen, an attempt was made to identify an allelic series of mutations in the gene. ENU mutagenised mouse archives were screened for novel Foxf2 mutations. Three potential functional mutations were discovered - two coding mutations (Foxf2W174R and Foxf2V412F), and a splice site mutation.
Foxf2W174R heterozygotes exhibited thinning of the iris stroma, alongside hypoplasia of the trabecular meshwork and canal of Schlemm and a reduction in the iridocorneal angle. Homozygote eyes at E18.5 show no signs of the developing ciliary body which were seen in wildtype littermates.
Homozygote carriers survive for several days, significantly longer than the 18hr survival time observed in the knockout, suggesting a hypomorphic mutation. In contrast to Foxf2 knockouts, homozygotes for the W174R mutation do not possess a cleft palate or malformed tongue
Shrink and squeeze: today\u27s teaching pressures and its effect on teaching social studies
Social studies education is one of the four core subjects taught to students in elementary schools. Teaching social studies provides students with the content knowledge and ways of thinking to allow them to be participating members in their communities. Although there are many skills students learn from social studies, due to federal legislation starting with No Child Left Behind, social studies has been put on the back burner while math and reading take the forefront. The goal of this study was to explore the perceptions and experiences of teachers regarding their social studies teaching. Semi-structured interviews were conducted with veteran teachers about their current approach to teaching social studies and changes they have made given the increasing marginalization of this subject area. Major themes related to social studies in fifth grade classes included a lack of emphasis on social studies, reduced instructional time, a changed instructional approach, gaps in student learning, a changed teaching response, and increased teacher advocacy
Measurement of air temperatures and velocities in the fiber glass forming environment
Thesis (S.M. and S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1999.Includes bibliographical references (leaves 81-82).The manufacture of continuous strand fiber glass is accomplished by draining molten glass through an array of small orifices in a heated bushing plate and then drawing the glass onto a winder. Upon exiting the orifices, the fibers pass through a cloud of atomized water to assist in the cooling of the fibers and then over a surfactant applicator before they are wound. The rate at which the cooling of the fibers occurs relies heavily on the operating conditions used in the process. This report deals with measurements made in a scaled-down process using a variety of different operating conditions. Experimental data on air temperatures and velocities were recorded within the forming environment without water sprays. Trials were run using an apparatus similar to one used in production, but of a much smaller scale. In production, a granular batch is continuously fed into a furnace, melted, mixed, and sent down a slightly downward sloping channel, via gravity. A series of electrically heated bushings, each with hundreds of tips, lies below the channel, allowing the molten glass to drain. The apparatus used in this study, however, consisted of one isolated nine-tip bushing with a small well above it. Glass marbles were placed in the well, and the system was electrically heated, melting the glass and allowing it to drain from the well through the bushing tips. The speed at which the fiber was drawn was varied, as was the bushing temperature. It was found that fiber diameter, which is information essential for predicting cooling rates, varies with both of these parameters, but is more heavily influenced by bushing temperature. By running the process at a constant bushing temperature, while using a series of fiber speeds, it was found that varying the speed of the fiber noticeably changes the temperature field in the forming environment. By increasing the fiber speed from 12.2 m/s to 21.3 m/s there are more noticeable temperature peaks surrounding the individual fibers, indicating significant differences in convective cooling rates as fiber speed is varied. Similar trends are seen for a constant fiber speed as the bushing temperature is increased from 1505 K to 1533 K, though the differences are not as dramatic. In addition it was necessary to correct temperature measurements using a theoretical heat transfer model, to account for error due to radiative heating of the thermocouple from the bushing plate and conductive heat loss through the thermocouple leads. Air velocity measurements were also taken using the same series of operating conditions. Increasing the fiber speed resulted in noticeably higher air velocities; increasing the bushing temperature also raised air velocity, although the change was less significant.by Brett M. McKeone.S.M.and S.B
Two Asymmetries between Clitic Left and Clitic Right Dislocation in Bulgarian
The paper discusses some subtle points of the syntax of clitic left dislocation and clitic right dislocation in Bulgarian
A Novel Mutation in Chronic Granulomatous Disease: Treating the Family, Not Just the Patient
Chronic Granulomatous Disease (CGD) is caused by genetic defects in the phagocyte NADPH oxidase leading to potentially severe infections with catalase positive micro-organisms. With the innate immune system being affected this disease usually presents before the age of 5 years with infections involving the skin, lung, liver or lymphnodes. Infections with specific catalase positive organisms, especially Burkholderia cepacia, Serratia, Nocardia and Chromobacterium violaceum prompt a workup for CGD in affected patients. In addition, a family history of CGD also warrants testing. The pattern of inheritance of CGD varies across geographic regions of the world and societies, with X-linked inheritance being most prevalent in the United States and Europe. Affected patients require life-long therapy with prophylactic antibiotics, antifungals, and possibly interferon-gamma. Hematopoietic Stem Cell Transplantation is the only curative therapy known to date. Identification, diagnosis and management of patients with CGD usually involves a multi-specialty team including Pediatrics, Immunology, Infectious Diseases, Hematology/Oncology and often also Pulmonology and GI/Hepatology. Frequent follow up is paramount for good outcomes; infections have to be recognized and treated promptly and often preemptively. This is challenging for most patients and their families but presents a significant barrier for patients with limited access to care, limited resources or other challenging social situations. This case report describes the difficulties of managing a family with a novel mutation and multiple affected family members in different custody arrangements. It highlights the importance of close contact and communication with the family in deciding on management and treatment options. Educating the family and patient is critical to avoid complications of the disease and allow shared decision making that ultimately leads to better outcomes
Case Report: Successful avoidance of etoposide for primary hemophagocytic lymphohistiocytosis-induced multiple organ dysfunction syndrome using emapalumab
We describe the case of an infant who presented with simple rhinovirus/enterovirus bronchiolitis whose condition worsened with rapid progression to multiple organ dysfunction syndrome (MODS). The patient was presumed to have either primary or secondary hemophagocytic lymphohistiocytosis (HLH), and treatment was initiated using dexamethasone, anakinra, and intravenous immunoglobulin to modulate the immune system. Due to the organ dysfunction, the use of etoposide was avoided and instead, emapalumab, an interferon gamma antagonist, was administered at a dose of 6 mg/kg. The patient's organ failure improved, and the levels of inflammatory markers decreased. The flow cytometry analysis revealed that cytotoxic cells lacked perforin expression, and subsequent genetic analysis confirmed homozygous pathogenic mutations in the perforin gene. This case highlights the potential avoidance of etoposide in cases of primary HLH, the possible benefit of an elevated initial dose of emapalumab, and the contribution offered by a multi-specialty team approach to complex diagnosis
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