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We expand our understanding of the training transfer process by developing the Dynamic Transfer Model (DTM). We develop and examine linkages between intentions to transfer, the initial attempts to utilize training, and the integration of feedback received from the transfer attempt. We propose that this process repeats itself over time in subsequent transfer attempts to impact work behavior and performance. Implications for transfer criteria, the dynamic interaction between the trainee and context, and the personalization of transfer are discussed. Based on the DTM, we suggest future research directions that can enrich our understanding of transfer as well as derive practical implications for improving training effectiveness.

Histone variant H2A.Z occupies the promoters of active and poised, bivalent genes in embryonic stem cells (ESCs) to regulate developmental programs, yet how it contributes to these contrasting states is poorly understood. Here, we investigate the function of H2A.Z.1 monoubiquitylation (H2A.Z.1ub) by mutation of the PRC1 target residues (H2A.Z.1[superscript K3R3]). We show that H2A.Z.1[superscript K3R3] is properly incorporated at target promoters in murine ESCs (mESCs), but loss of monoubiquitylation leads to de-repression of bivalent genes, loss of Polycomb binding, and faulty lineage commitment. Using quantitative proteomics, we find that tandem bromodomain proteins, including the BET family member BRD2, are enriched in H2A.Z.1 chromatin. We further show that BRD2 is gained at de-repressed promoters in H2A.Z.1[superscript K3R3] mESCs, whereas BRD2 inhibition restores gene silencing at these sites. Together, our study reveals an antagonistic relationship between H2A.Z.1ub and BRD2 to regulate the transcriptional balance at bivalent genes to enable proper execution of developmental programs., National Institutes of Health (U.S.) (Pre-doctoral Training Grant T32GM007287), Massachusetts Institute of Technology. School of Science (Fellowship in Cancer Research), National Cancer Institute (U.S.) (Core Grant Award P30-CA14051), National Heart, Lung, and Blood Institute. Bench to Bassinet Program (U01HL098179), Massachusetts Life Sciences Center

Long noncoding RNAs (lncRNAs) are often expressed in a development-specific manner, yet little is known about their roles in lineage commitment. Here, we identified Braveheart (Bvht), a heart-associated lncRNA in mouse. Using multiple embryonic stem cell (ESC) differentiation strategies, we show that Bvht is required for progression of nascent mesoderm toward a cardiac fate. We find that Bvht is necessary for activation of a core cardiovascular gene network and functions upstream of mesoderm posterior 1 (MesP1), a master regulator of a common multipotent cardiovascular progenitor. We also show that Bvht interacts with SUZ12, a component of polycomb-repressive complex 2 (PRC2), during cardiomyocyte differentiation, suggesting that Bvht mediates epigenetic regulation of cardiac commitment. Finally, we demonstrate a role for Bvht in maintaining cardiac fate in neonatal cardiomyocytes. Together, our work provides evidence for a long noncoding RNA with critical roles in the establishment of the cardiovascular lineage during mammalian development., Damon Runyon Cancer Research Foundation (DRG 2032-09), Damon Runyon Cancer Research Foundation (DFS 04-12), European Molecular Biology Organization (Long-term Fellowship), National Heart, Lung, and Blood Institute. Bench to Bassinet Program (U01HL098179), National Heart, Lung, and Blood Institute. Bench to Bassinet Program (U01HL098188), Smith Family Foundation, Pew Charitable Trusts. Program in the Biomedical Sciences

Precise control of gene expression patterns is critical for the specification of cellular diversity during metazoan development. Polycomb group (PcG) proteins comprise a class of transcriptional modifiers that have dynamic and essential roles in regulating a number of key processes including lineage commitment. How this is accomplished during mammalian development is incompletely understood. Here, we discuss recent studies in embryonic stem cells (ESCs) that provide critical new insights into how PcG proteins may be targeted to genomic sites as well as the mechanisms by which these regulators influence gene expression and multilineage differentiation in mammals.

A series of 6-bicycloaryloxynicotinamides were identified as opioid receptor antagonists at mu, kappa, and delta receptors. Compounds in the 6-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide scaffold exhibited potent in vitro functional antagonism at all three receptors.

The phenolic hydroxy group of opiate-derived ligands is of known importance for biological activity. We have developed a SAR study around LY255582 by comparing the effect of the hydroxy group in the 2- and 4-position of the phenyl ring. Also, we have proved that the 3-position of the phenyl ring is optimal for opioid activity. Furthermore, we have successfully replaced the hydroxy group in LY255582 by carbamate and carboxamide groups. The new analogs have high affinity for the opioid receptors comparable to the corresponding phenol. Carboxamide analog 12 has an improved metabolism profile and proved to be efficacious in in vivo studies.

Differences in the anorectic activity of morphinan (e.g., naltrexone) and 3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (4PP) opioid receptor antagonists have been described. In an attempt to explain these differences, the influence of Na(+) on opioid binding affinity and functional activity of 4PP antagonists was compared to other opioid antagonists. The binding affinities of neutral antagonists were unaffected by the addition of Na(+), whereas that for the peptide, inverse agonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI174864) was increased. Similarly, the binding affinities of the 4PP antagonist (3R,4R)-1-((S)-3-hydroxy-3-cyclohexylpropyl)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidine (LY255582) and other 4PP antagonists were increased in the presence of Na(+) with the greatest effects at the delta opioid receptor followed by the mu and kappa opioid receptors, respectively. Similar to ICI174864, 4PP antagonists were found to inhibit basal GTPgamma[(35)S] binding at the delta opioid receptor indicating inverse agonist activity. A correlation was observed between the binding affinities in the presence of Na(+), the inverse agonist potency, and the anorectic potency of 4PP antagonists. These data suggest that 4PP antagonists differ from morphinan antagonists in their inverse agonist activity and suggest a relationship between inverse agonism and anorectic activity.

C/EBP-alpha binds a C/EBP consensus site in the leptin promoter and activates transcription in vitro. We assessed adipose tissue expression of C/EBP-alpha, leptin and beta-actin in Sprague Dawley rats under conditions that modulate leptin mRNA abundance in order to study the relationship between leptin and C/EBP-alpha expression patterns. During acute fasting, which decreased the level of leptin and beta-actin mRNA, C/EBP-alpha mRNA expression was unaltered. In leptin-treated and pair-fed animals, C/EBP-alpha mRNA was unaltered compared to ad libitum fed controls, while leptin and beta-actin mRNA expression was again decreased. These results indicate that changes in the level of leptin gene expression are not directly associated with changes in the level of C/EBP-alpha abundance.

To characterize the flow patterns of wastewater through subsurface-flow rock-reed filters, a combination of tracer studies and specific conductance measurements were used. Neither the tracer study nor the specific conductance measurements alone provided the necessary information to understand the flow of wastewater through the system. However, the data taken together indicate that preferential flow occurred due to density effects and surface flow. In gravel substrates, dense wastewater flowed beneath the less dense rainwater and influent, resulting in a decrease in the residence time. Sand-and-gravel substrates, which experienced a great deal of surface flow as a result of clogging, were shown to have very little, if any, flow through the subsurface. The results of this study indicate that both preferential and overland flow should be taken into account for the proper design of rock-reed filters.

Phragmites australis (common reed) grew well in the presence of high concentrations of NH4+-N (300 mg/1), BOD (300 mg/1), Fe (30 mg/1), Mn (1.5 mg/1) and K (500 mg/1). Other metals were not particularly elevated with the pH of the landfill leachate being 7-7.2. Reed standing crop continued to increase in the two years after leachate applications began, ranging to about 1100, 100, and 1000 g/m2 dry wt. for shoots, roots and rhizomes, respectively. Nutrient elements like N, K, Ca, and Mg were absorbed to normally sufficient levels, while tissue P was low at 0.04%. Metals were not translocated to and accumulated by shoots or rhizomes, but exhibited elevated levels in roots. Fe, Cu, Zn, Pb, and Cd were at levels of 3700, 65, 45, 12 and 0.2 mg/kg respectively, but the roots acted as effective filters for transport of metals to the shoots and rhizomes. Only P and Zn accumulation by plants approached total amounts in leachate entering the constructed beds. SEM and X-ray microanalysis showed Fe accumulation on root surfaces, with Fe and other metals at lower concentrations inside the root tissue. The rhizosphere may provide a particularly effective, locally oxidized environment for metal precipitation and adsorption outside the root.

Long-term use of a constructed wetland to treat landfill leachate requires that the saturated hydraulic conductivity be maintained and clogging avoided to prevent overland flow, which bypasses the treatment process. This paper describes the application of an equation developed for prediction of cumulative drainage volume from hillslopes to measure the saturated hydraulic conductivity (Ks) of substrates used in rock-reed filters. Outflow was measured at five intervals during the first 26 months of operation. The values of Ks) obtained by the drainage equation compared favorably with values calculated from a more dificult method based on Darcy's law. Results indicate that the finest substrate (a sand-and-gravel mixture) became almost completely clogged, and that the presence of reeds (Phragmites australis) did not maintain or increase the conductivity. Hydraulic conductivity of pea-gravel (0.5-cm diameter) and coarse-gravel (3-cm diameter) substrates with reeds did decrease in the 26-month period.

The aim of this study was to compare growth hormone (GH) response of barrows and gilts to porcine growth hormone-releasing hormone (pGRH) at the pituitary level. Anterior pituitary cells from barrows and gilts responded to pGRH in a dose-dependent manner. The median effective pGRH concentration (EC50) which stimulated GH release from cells of barrows was greater (P less than .05) than that for cells obtained from intact female siblings. Maximal pGRH mediated GH secretion from barrows was not different (P greater than 0.05) than that from gilt stimulated cells. These data demonstrate that somatotrophs of growing peripubertal gilts are more responsive to pGRH stimulation than are cells from their castrated male siblings. This difference could be caused by castration of the neonatal male.

Resume In part I of this work, we studied the application of a third order perturbation theory to c(2 × 2) overlayers. Here, this approach is applied to some calculations of rotation diagrams and energy profiles, for Ni(001)−c(2 × 2)−S. First, we compare our results and those of an exact calculation, in the framework of the isotropic scatterer, and find them to be in fairly good agreement. So we can proceed to calculations with more realistic anisotropic scatterers. Here, we only consider the nickel-sulfur system, which has been studied very carefully, experimentally and theoretically. We ascertain a very important shortening of computation time owing to our perturbative method and, at the same time, the agreement with experiment is comparable for an exact calculation and for our approach.

Dynamics of glomerular ultrafiltration: VI. Studies in the primate. Pressures and flows were measured in accessible surface glomeruli of the squirrel monkey under conditions of normal hydropenia. Mean glomerular capillary hydrostatic pressure and the mean glomerular transcapillary hydrostatic pressure difference (ΔP) averaged approximately 45 mm Hg and 35 mm Hg, respectively. These findings are in close accord with recent direct estimates in the rat. The net driving force for ultrafiltration was found to decline from a maximum value of about 12 mm Hg at the afferent end of the glomerular capillary network essentially to zero by the efferent end, indicating that, in the monkey as in the rat, filtration pressure equilibrium is achieved under normal hydropenic conditions. The monkey differs from the rat in one important respect, however, in that, as has long been recognized, the monkey tends to have higher systemic total plasma protein concentrations (CA) than the rat. This is of interest since monkey, like man, is found to have lower filtration fractions than the rat. Since ΔP is found to be essentially similar in monkey and rat, and since, at filtration pressure equilibrium, filtration fraction is determined by ΔP and CA, these observed differences in filtration fraction between rodent and primate must therefore be due to these differences in CA.

We present some experimental and theoretical LEED results obtained from the (001) surface of aluminum. The experimental curves were obtained with a new goniometer which allows us to set any incidence conditions, and to measure all the diffracted beams. We show that rotation diagrams are more interesting than energy profiles for studying the dynamical interactions and testing various LEED theories. We use several models to compute such diagrams. As a first step, we compare the results obtained in the S-wave approximation with the three following models: One Dimensional Multiple Scattering Model, Inelastic Collision Model, and the Kambe-McRae Multiple Scattering approach. As a second step, we use more elaborate potentials to calculate LEED intensities according to the Kambe-McRae Multiple Scattering approach, and the Band Structure-Matching formalism; the results are discussed and compared with experiment.

Some businessmen believe that universities could be run more efficiently if they copied corporation techniques. Some expertise can indeed be transferred, but the author believes that the university can never be run as a corporation. The university's constraints are quite different from those of the business firm in at least five major areas: ownership, the chief executive, the governing board, the time frame commitment, and the measurement of results. Abolishing faculty tenure and recentralizing authority would provide the university president with authority more comparable to that of the corporate chief executive. Such a reform would be vigorously resisted, however, and would be contrary to the university's mission.

It has been shown by Loeb 2 that one function of the well developed corpus luteum in the mammalian reproductive cycle is to inhibit ovulation. This fact appears to be firmly established for mammals by his observations and experiments. Ruge's 3 observations seem also essentially to confirm this result. This suggestion was also made earlier by Prenant 4 and Sandes and Skrobansky. 5 In connection with die series of studies in progress in this laboratory on the physiology of avian reproduction it seemed a matter of considerable interest to determine whether an extract of mammalian corpus luteum substance would exercise a similar inhibitory action on ovulation in a bird, where, of course, there is normally nothing connected with the ovary which is either morphologically or physiologically homologous to the corpus luteum of the mammalian ovary. The experiments here reported were undertaken for the purpose of throwing light upon this question. In the complete paper …

This work investigated the chemical and electrochemical mechanisms of localised corrosion triggered by CaS·xMgO·yAl2O3·TiN complex inclusions in high strength low alloy steel (HSLAS) under a simulated marine environment. Special focus was given to the role of the TiN portion of the inclusion on the initiation and growth of the corrosion pits. The thermodynamic process of pitting initiation was investigated by Gibbs free energy, Pourbaix diagram and first principle calculation. Localised corrosion is mainly induced by inclusions and triggered by dissolution of adjacent distorted matrix. Chemical dissolution of CaS portion in CaS·xMgO·yAl2O3·TiN complex inclusion creates an acidic aggressive environment that accelerates the further dissolution of inclusion and matrix. Galvanic coupling effect between TiN inclusion and matrix is directly verified. TiN covered with a TiO2 film acts as the cathodic phase in galvanic corrosion, although it has a lower Volta potential than the matrix. This is an unusual correlation with the scanning Kelvin probe force microscopy result, which has been explained for this special system.