The Hague Conference and the Main Issues of Private International Law for the Eighties

The Hague Conference on Private International Law has attempted, since its revitalization in the 1950, to unify the rules of private international law. The efforts of the Conference have in the past centered around the fields of civil procedure, conflict of laws, the international sale of goods, products liability and international family law. Messrs. Droz and Dyer review the history of the achievements of the Conference in these fields and reflect on the problems and opportunities the Conference will encounter in the 1980 s

The Hague Conference and the Main Issues of Private International Law for the Eighties

The Hague Conference on Private International Law has attempted, since its revitalization in the 1950, to unify the rules of private international law. The efforts of the Conference have in the past centered around the fields of civil procedure, conflict of laws, the international sale of goods, products liability and international family law. Messrs. Droz and Dyer review the history of the achievements of the Conference in these fields and reflect on the problems and opportunities the Conference will encounter in the 1980 s

Probing the outer vestibule of a sodium channel voltage sensor

The second and third basic residues of the S4 segment of domain 4 (D4:R2 and D4:R3) of the human skeletal muscle Na+ channel are known to be translocated from a cytoplasmic to an extracellular position during depolarization. Accessibilities of individual S4 residues were assayed by alteration of inactivation kinetics during modification of cysteine mutants by hydrophilic methanethiosulfonate reagents. The voltage dependences of the reaction rates are identical for extracellular application of cationic methanethiosulfonate-ethyltrimethylammonium (MTSET) and anionic methanethiosulfonate-ethylsulfonate (MTSES), suggesting that D4:R3C is situated outside the membrane electric field at depolarized voltages. The absolute rate of R3C modification is 281-fold greater for MTSET than for MTSES, however, suggesting that at depolarized voltages this S4 thiol resides in a negatively charged hydrophilic crevice. The two hydrophobic residues between D4:R2C and D4:R3C in the primary sequence (L1452 and A1453) are not externally exposed at any voltage. An alpha-helical representation of D4/S4 shows that the basic residues D4:R2 and D4:R3 are on the face opposite that of L1452 and A1453. We propose that in the depolarized conformation, the hydrophobic face of this portion of D4/S4 remains in contact with a hydrophobic region of the extracellular vestibule of the S4 channel

Factors determining hemoglobin carbamylation in renal failure

Factors determining hemoglobin carbamylation in renal failure. Carbamylated hemoglobin (carhb) is formed by the reaction of hemoglobin with cyanate, a product of in vivo urea dissociation. It is found in high levels in patients with renal failure and may be useful in their clinical evaluation. Accordingly, we measured carhb by HPLC after acid hydrolysis in 73 patients with renal failure and 11 controls. Mean carhb levels, (expressed as μg valine hydantoin/g Hb), were highest in chronic renal failure (CRF, 146 ± 13), intermediate in end-stage renal disease on hemodialysis (ESRD, 106 ± 7), and lowest in acute renal failure (ARF, 80 ± 12) when compared to normal subjects (27 ± 2). In all patients carhb was significantly correlated with BUN but not with creatinine, bicarbonate, or phosphate. For any level of BUN above 80 mg/dl, carhb was substantially higher in CRF than in ARF. Predialysis BUN and urea reduction ratio (URR) were significant predictors of carhb in ESRD. To investigate the effect of time of exposure and BUN level on the rate of carbamylation of hemoglobin, blood from normal subjects and dialysis patients was incubated in vitro with urea equivalent to BUN levels of 50, 100, 150, and 200 mg/dl and assayed for carhb at 0, 5, 9, and 14 days. Carhb increased linearly over the first nine days of urea exposure and leveled off thereafter. The rate of carbamylation increased as BUN increased and was significantly higher in hemoglobin from dialysis patients than from normal subjects. These results show that the higher the level of carhb at baseline, the higher the rate of carbamylation upon exposure to increasing urea concentrations. We conclude that carhb formation is dependent on urea concentration and length of exposure to urea. The rate of carhb formation for a given urea concentration is greater in hemoglobin already carbamylated, and this may explain why carhb is higher in CRF than in ARF at BUN levels greater than 80 mg/dl. Carhb may thus be a useful index of the duration and degree of exposure to high blood urea levels in patients with renal failure, and may potentially serve as an index of the adequacy of dialysis

Beef manual for 4-H club members

Cover title

The Cost of Jointness and How to Manage It

Although joint programs are typically formed to reduce costs, recent studies have suggested that joint programs experience larger cost growth than non-joint programs. To explain this phenomenon, we present a model that attributes joint program cost growth to agencies’ actions to maintain or regain their autonomy. We use this model to motivate principles for architecting joint programs and outline a process that can be used to identify opportunities for reforming current joint programs or for establishing new ones. Finally, we apply our approach to analyze joint program options for NOAA’s low-earth orbiting weather satellite program and in doing so, identify several risks facing NOAA’s current program and strategies for mitigating them.Massachusetts Institute of Technology (Sandia Corporation Excellence in Engineering Graduate Fellowship)Skolkovo Institute of Science and Technolog

Nonergodic Behavior of Interacting Bosons in Harmonic Traps

We study the time evolution of a system of interacting bosons in a harmonic trap. In the low-energy regime, the quantum system is not ergodic and displays rather large fluctuations of the ground state occupation number. In the high energy regime of classical physics we find nonergodic behavior for modest numbers of trapped particles. We give two conditions that assure the ergodic behavior of the quantum system even below the condensation temperature.Comment: 11 pages, 3 PS-figures, uses psfig.st

Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6.

Senescent cells may exert detrimental effect on microenvironment through the secretion of soluble factors and the release of extracellular vesicles, such as microparticles, key actors in ageing and cardiovascular diseases. We previously reported that sirtuin-1 (SIRT1) deficiency drives accelerated senescence and dysfunction of endothelial colony-forming cells (ECFC) in PT neonates. Because preterm birth (PT) increases the risk for cardiovascular diseases during neonatal period as well as at adulthood, we hypothesized that SIRT1 deficiency could control the biogenesis of microparticles as part of a senescence-associated secretory phenotype (SASP) of PT-ECFC and investigated the related molecular mechanisms. Compared to control ECFC, PT-ECFC displayed a SASP associated with increased release of endothelial microparticles (EMP), mediating a paracrine induction of senescence in naïve endothelial cells. SIRT1 level inversely correlated with EMP release and drives PT-ECFC vesiculation. Global transcriptomic analysis revealed changes in stress response pathways, specifically the MAPK pathway. We delineate a new epigenetic mechanism by which SIRT1 deficiency regulates MKK6/p38 <sup>MAPK</sup> /Hsp27 pathway to promote EMP biogenesis in senescent ECFC. These findings deepen our understanding of the role of ECFC senescence in the disruption of endothelial homeostasis and provide potential new targets towards the control of cardiovascular risk in individuals born preterm

The temporal dynamics of Arc expression regulate cognitive flexibility

YesNeuronal activity regulates the transcription and translation of the immediate-early gene Arc/Arg3.1, a key mediator of synaptic plasticity. Proteasomedependent degradation of Arc tightly limits its temporal expression, yet the significance of this regulation remains unknown. We disrupted the temporal control of Arc degradation by creating an Arc knockin mouse (ArcKR) where the predominant Arc ubiquitination sites were mutated. ArcKR mice had intact spatial learning but showed specific deficits in selecting an optimal strategy during reversal learning. This cognitive inflexibility was coupled to changes in Arc mRNA and protein expression resulting in a reduced threshold to induce mGluR-LTD and enhanced mGluR-LTD amplitude. These findings show that the abnormal persistence of Arc protein limits the dynamic range of Arc signaling pathways specifically during reversal learning. Our work illuminates how the precise temporal control of activity-dependent molecules, such as Arc, regulates synaptic plasticity and is crucial for cognition.Open access funded by Biotechnology and Biological Sciences Research Counci

Dental Caries Experience in the Deciduous Dentition of Rural Guatemalan Children Ages 6 Months to 7 Years

A study of 528 Guatemalan children indicated that caries prevalence in the deciduous dentition was twice as great as but in the permanent dentition was similar to that for US white children. This is a repeated observation for children of some preindustrial societies. Caries experience was significantly greater in boys. Until 4 years of age, caries attack was greater in the anterior segment of the oral cavity; linear enamel hypoplasia was a predisposing factor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68238/2/10.1177_00220345760550064501.pd