Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy

Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a heterogeneous disorder characterized by profound hypoglycemia due to inappropriate hypersecretion of insulin. An important diagnostic goal is to distinguish patients with a focal hyperplasia of islet cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets (DiPHHI) because management strategies differ significantly. 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated. Selective pancreatic venous sampling coupled with peroperative surgical examination and analysis of extemporaneous frozen sections allowed us to identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases of FoPHHI, but not those of DiPHHI, there was specific loss of maternal alleles of the imprinted chromosome region 11p15 in cells of the hyperplastic area of the pancreas but not in normal pancreatic cells. This somatic event is consistent with a proliferative monoclonal lesion. It involves disruption of the balance between monoallelic expression of several maternally and paternally expressed genes. Thus, we provide the first molecular explanation of the heterogeneity of sporadic forms of PHHI such that it is possible to perform only partial pancreatectomy, limited to the focal somatic lesion, so as to avoid iatrogenic diabetes in patients with focal adenomatous hyperplasia.     

Preferential exclusion of sucrose from recombinant interleukin-1 receptor antagonist: role in restricted conformational mobility and compaction of native state

Understanding the mechanism for sucrose-induced protein stabilization is important in many diverse fields, ranging from biochemistry and environmental physiology to pharmaceutical science. Timasheff and Lee [Lee, J. C. & Timasheff, S. N. (1981) J. Biol. Chem. 256, 7193-7201] have established that thermodynamic stabilization of proteins by sucrose is due to preferential exclusion of the sugar from the protein's surface, which increases protein chemical potential. The current study measures the preferential exclusion of 1 M sucrose from a protein drug, recombinant interleukin 1 receptor antagonist (rhIL-1ra). It is proposed that the degree of preferential exclusion and increase in chemical potential are directly proportional to the protein surface area and that, hence, the system will favor the protein state with the smallest surface area. This mechanism explains the observed sucrose-induced restriction of rhIL-1ra conformational fluctuations, which were studied by hydrogen-deuterium exchange and cysteine reactivity measurements. Furthermore, infrared spectroscopy of rhlL-1ra suggested that a more ordered native conformation is induced by sucrose. Electron paramagnetic resonance spectroscopy demonstrated that in the presence of sucrose, spin-labeled cysteine 116 becomes more buried in the protein's interior and that the hydrodynamic diameter of the protein is reduced. The preferential exclusion of sucrose from the protein and the resulting shift in the equilibrium between protein states toward the most compact conformation account for sucrose-induced effects on rhIL-1ra.     

Epithelial marker genes are expressed in cultured embryonic rat lung and in vivo with similar spatial and temporal patterns

Explants of embryonic lung are often used to characterize lung growth, bronchial tree pattern, and cell differentiation. Most investigators culture lungs for 3-7 days in defined media lacking, e.g., added growth factors or hormones. If growth and differentiation are comparable to that in vivo, these cultures show considerable promise for identifying developmental regulatory molecules and target genes, and for elucidating molecular responses. We used in situ hybridization and RT-PCR to compare times and sites of expression of mRNAs of six epithelial genes in cultured and uncultured fetal rat lungs. These genes, expressed in distal lung of adult rats, are surfactant proteins (SP) A, B, and C; LAR, a receptor-type tyrosine phosphatase; Clara cell secretory protein (CC10, CCSP); and T1alpha. SP-A, SF-B, LAR, and CC10 are expressed by both Clara and Type II cells in adult animals. SP-C and T1alpha are unique markers for Type II and Type I cells, respectively. SP-C, LAR, and T1alpha are expressed before the lung is explanted (Day 13.5); SP-A, -B, and CC10 mRNAs are first detected later. The onset of expression is similar in vivo and in vitro. Although the patterns of expression differ for each mRNA, their sites of expression in culture match those in vivo relative to the bronchial tree. The explanted embryonic lung appears to be an excellent experimental model.     

Characterization method of thermomechanical parameters for microelectronic materials

Reliability of thermomechanical simulations is critically linked to the accuracy of the mechanical properties that govern the behaviour of structure, like Young's modulus (E) and coefficient of thermal expansion (CTE). For many cases, the values found in literatures are dealing with bulk properties without detailed information on temperature effects. To address such issues, it is necessary to measure the materials parameters as a function of temperature. The measurement of CTE is usually accomplished by evaluating the thermal deflections of a subjected material layer deposited on a substrate, providing that E is known at a specific temperature of experiment. A bilayer method, based on theory of elasticity, is proposed to determine both E and CTE for a given temperature with a good resolution. This paper presents the theoretical analysis, the design and process of the microsystem test structures, and the main calculation results.     

End-User Computing in a CASE Environment

Computer-aided software engineering (CASE) tools are currently being used by IS professionals rather than by users. No matter how effective these tools may be, however, they will not be able to assist in the reduction of application backlogs without supporting user-driven applications. This article examines characteristics of a CASE environment from the various perspectives of decision support, identifies the advantages and limitations of end-user computing in this environment, and suggests how IS managers can realize the potentials of CASE for user applications.     

Use of polymers for cement-based structural materials

Cement-based materials are widely used in the civil infrastructure. Polymers as admixtures can improve the properties, particularly in relation to water absorption reduction, toughness enhancement, vibration damping and increase of the bond strength of cement to reinforcements. Polymeric admixtures include particles, short fibers and organic liquids. Latex in the form of an aqueous particle dispersion is most common. Other than being used as admixtures, polymers are used as partial replacement of fine aggregate, for coating, sealing and repairing concrete and for coating steel reinforcing bars for corrosion protection.     

High performance biofilm process for treating wastewater discharged from coal refining plants containing nitrogen, cyanide and thiocyanate.

Wastewater discharge from coal refining plants contains a number of biologically toxic compounds; 2000-2500 mg/l of COD of which 40% is composed of phenol, 100-400 mg/l of thiocyanate, 10-40 mg/l of cyanide, 100-250 mg/l of NH4+-N and 150-300 mg/l of total nitrogen. In order to treat this kind of high strength wastewater, we have developed a high performance biofilm process using fluidizing bio-carriers of the tube chip type. The fluidizing biofilm carriers are made of a composite of polyethylene and several inorganic materials, whose density is controlled at 0.97-0.98 g/ml. The fluidizing biofilm carriers show sound fluidization characteristics inside bioreactors. The wastewater is treated using three consecutive series reactors in oxic-anoxic-oxic arrangement. Each reactor is charged with the fluidizing biofilm carriers of 50 vol%. Furthermore, newly cultured active microorganisms for the thiocyanate biodegradation are added in the biofilm process. At total hydraulic retention time of 2.2 days, this process can achieve steady state removal efficiencies: COD, 99%; thiocyanate, 99%; NH4+-N, 99% and total nitrogen, 90%.