Ideas that Change and Stay the Same

What will this building become? I interpret this to mean that initial design ideas are subject to various deforming forces at various distances in time from the original conception. Needless to say only a small portion of all built structures have any conscious theoretical content to speak of

Pure nuclear quadrupole resonance determination of the electric field gradient asymmetry for broad lines (and application to YBa2Cu3O7)

We present an angle dependent nuclear quadrupole resonance (ADNQR) method to determine the electric field gradient asymmetry parameter eta in systems where the resonance line is so broad that the radio frequency field can excite only a portion of the nuclear spins. In this situation the recently developed spectroscopic methods are not applicable. ADNQR is useful for single crystals and oriented powders, and, for small eta determines eta^4. Therefore, it can be used to evaluate fluctuations in eta due to inhomogeneities. We demonstrate the application of ADNQR experimentally to oriented superconducting YBa2Cu3O7 powder.Comment: 5 pages, 3 figure

Stress in tenure-track and non-tenure-track faculty : what we know and where we are going

A great deal of research has over the last fifty years has examined chronic stress in the workplace across numerous vocations. Relatively little has been studied in the context of university faculty, and even less still has been examined in non-tenure track faculty (NTTF), individuals who seek academic work contingently and fill teaching, supervising, researching, and mentoring roles. This report outlines the extant knowledge on chronic stress in university faculty, ultimately focusing on the experiences of NTTF. Research into professor stress in the following domains are outlined: workplace factors, multicultural and sexual minority concerns, gender, and disparities in treatment and payment. Additional stress factors may affect NTTF that are not experienced by all university professors, such as perceived social status (PSS), workplace isolation, and incivility from students. Exploratory research into and implications of NTTF stress are discussed, and future research directions and possible clinical interventions for NTTF stress are suggested.Educational Psycholog

Estimating Protein-Ligand Binding Affinity using High- Throughput Screening by NMR

Many of today’s drug discovery programs utilize high-throughput screening methods that rely on quick evaluations of protein activity to rank potential chemical leads. By monitoring biologically relevant protein-ligand interactions, NMR can provide a means to validate these discovery leads and to optimize the drug discovery process. NMR-based screens typically use a change in chemical shift or linewidth to detect a protein-ligand interaction. However, the relatively low throughput of current NMR screens and their high demand on sample requirements generally makes it impractical to collect complete binding curves to measure the affinity for each compound in a large and diverse chemical library. As a result, NMR ligand screens are typically limited to identifying candidates that bind to a protein and do not give any estimate of the binding affinity. To address this issue, a methodology has been developed to rank binding affinities for ligands based on NMR-based screens that use 1D 1H NMR line-broadening experiments. This method was demonstrated by using it to estimate the dissociation equilibrium constants for twelve ligands with the protein human serum albumin (HSA). The results were found to give good agreement with previous affinities that have been reported for these same ligands with HSA

Estimating Protein-Ligand Binding Affinity using High- Throughput Screening by NMR

Many of today’s drug discovery programs utilize high-throughput screening methods that rely on quick evaluations of protein activity to rank potential chemical leads. By monitoring biologically relevant protein-ligand interactions, NMR can provide a means to validate these discovery leads and to optimize the drug discovery process. NMR-based screens typically use a change in chemical shift or linewidth to detect a protein-ligand interaction. However, the relatively low throughput of current NMR screens and their high demand on sample requirements generally makes it impractical to collect complete binding curves to measure the affinity for each compound in a large and diverse chemical library. As a result, NMR ligand screens are typically limited to identifying candidates that bind to a protein and do not give any estimate of the binding affinity. To address this issue, a methodology has been developed to rank binding affinities for ligands based on NMR-based screens that use 1D 1H NMR line-broadening experiments. This method was demonstrated by using it to estimate the dissociation equilibrium constants for twelve ligands with the protein human serum albumin (HSA). The results were found to give good agreement with previous affinities that have been reported for these same ligands with HSA

Foraging in semantic fields : how we search through memory

When searching for concepts in memory-as in the verbal fluency task of naming all the animals one can think of-people appear to explore internal mental representations in much the same way that animals forage in physical space: searching locally within patches of information before transitioning globally between patches. However, the definition of the patches being searched in mental space is not well specified. Do we search by activating explicit predefined categories (e.g., pets) and recall items from within that category (categorical search), or do we activate and recall a connected sequence of individual items without using categorical information, with each item recalled leading to the retrieval of an associated item in a stream (associative search), or both? Using semantic representations in a search of associative memory framework and data from the animal fluency task, we tested competing hypotheses based on associative and categorical search models. Associative, but not categorical, patch transitions took longer to make than position-matched productions, suggesting that categorical transitions were not true transitions. There was also clear evidence of associative search even within categorical patch boundaries. Furthermore, most individuals' behavior was best explained by an associative search model without the addition of categorical information. Thus, our results support a search process that does not use categorical information, but for which patch boundaries shift with each recall and local search is well described by a random walk in semantic space, with switches to new regions of the semantic space when the current region is depleted

Dynamic Remodeling of Individual Nucleosomes Across a Eukaryotic Genome in Response to Transcriptional Perturbation

The eukaryotic genome is packaged as chromatin with nucleosomes comprising its basic structural unit, but the detailed structure of chromatin and its dynamic remodeling in terms of individual nucleosome positions has not been completely defined experimentally for any genome. We used ultra-high–throughput sequencing to map the remodeling of individual nucleosomes throughout the yeast genome before and after a physiological perturbation that causes genome-wide transcriptional changes. Nearly 80% of the genome is covered by positioned nucleosomes occurring in a limited number of stereotypical patterns in relation to transcribed regions and transcription factor binding sites. Chromatin remodeling in response to physiological perturbation was typically associated with the eviction, appearance, or repositioning of one or two nucleosomes in the promoter, rather than broader region-wide changes. Dynamic nucleosome remodeling tends to increase the accessibility of binding sites for transcription factors that mediate transcriptional changes. However, specific nucleosomal rearrangements were also evident at promoters even when there was no apparent transcriptional change, indicating that there is no simple, globally applicable relationship between chromatin remodeling and transcriptional activity. Our study provides a detailed, high-resolution, dynamic map of single-nucleosome remodeling across the yeast genome and its relation to global transcriptional changes

The Soluble Proteome of the Drosophila Antenna

The olfactory system of Drosophila melanogaster is one of the best characterized chemosensory systems. Identification of proteins contained in the third antennal segment, the main olfactory organ, has previously relied primarily on immunohistochemistry, and although such studies and in situ hybridization studies are informative, they focus generally on one or few gene products at a time, and quantification is difficult. In addition, purification of native proteins from the antenna is challenging because it is small and encased in a hard cuticle. Here, we describe a simple method for the large-scale detection of soluble proteins from the Drosophila antenna by chromatographic separation of tryptic peptides followed by tandem mass spectrometry with femtomole detection sensitivities. Examination of the identities of these proteins indicates that they originate both from the extracellular perilymph and from the cytoplasm of disrupted cells. We identified enzymes involved with intermediary metabolism, proteins associated with regulation of gene expression, nucleic acid metabolism and protein metabolism, proteins associated with microtubular transport, 8 odorant-binding proteins, protective enzymes associated with antibacterial defense and defense against oxidative damage, cuticular proteins, and proteins of unknown function, which represented about one-third of all soluble proteins. The procedure described here opens the way for precise quantification of any target protein in the Drosophila antenna and should be readily applicable to antennae from other insects

Variant Histone H2A.Z Is Globally Localized to the Promoters of Inactive Yeast Genes and Regulates Nucleosome Positioning

H2A.Z is an evolutionary conserved histone variant involved in transcriptional regulation, antisilencing, silencing, and genome stability. The mechanism(s) by which H2A.Z regulates these various biological functions remains poorly defined, in part due to the lack of knowledge regarding its physical location along chromosomes and the bearing it has in regulating chromatin structure. Here we mapped H2A.Z across the yeast genome at an approximately 300-bp resolution, using chromatin immunoprecipitation combined with tiling microarrays. We have identified 4,862 small regions—typically one or two nucleosomes wide—decorated with H2A.Z. Those “Z loci” are predominantly found within specific nucleosomes in the promoter of inactive genes all across the genome. Furthermore, we have shown that H2A.Z can regulate nucleosome positioning at the GAL1 promoter. Within HZAD domains, the regions where H2A.Z shows an antisilencing function, H2A.Z is localized in a wider pattern, suggesting that the variant histone regulates a silencing and transcriptional activation via different mechanisms. Our data suggest that the incorporation of H2A.Z into specific promoter-bound nucleosomes configures chromatin structure to poise genes for transcriptional activation. The relevance of these findings to higher eukaryotes is discussed