Musings on Managing for the Long Term Zweig, Mark C; Liao, Sam S
Leadership and management in engineering,
07/2007, Volume:
7, Issue:
3
Journal Article
Peer reviewed
Open access
This article represents the juxtaposition of two vintage articles that originally appeared in The Zweig Letter: The Voice of Reason for Architecture, Engineering, & Environmental Consulting Firms. ...Though they were published several years apart, the articles complement each other in terms of thoughts on building A/E practices to endure for the long term. The essays are presented here back-to-back, and reprinted with permission from ZweigWhite Information Services, LLC. The first article, by Mark Zweig, is a whimsical observation regarding Frank Lloyd Wright, who despite the enormous legacy he left as an architect, was never terribly successful at building a real firm. The second article by Sam Liao presents some equally whimsical thoughts on the Zen of projects, and how they create the links that sustain and define a firm from day to day, week to week, year to year, and perhaps even century to century.
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FGGLJ, IZUM, KILJ, NUK, PILJ, SAZU, UL, UM, UPUK
Abstract There is much interest in targeting the activity in the oxytocin system to regulate social bonding. However, studies with exogenous administration of oxytocin face the caveats of its low ...stability, poor brain permeability and insufficient receptor specificity. The use of a small-molecule oxytocin receptor-specific agonist could overcome these caveats. Prior to testing the potential effects of a brain-penetrant oxytocin receptor agonist in clinical settings, it is important to assess how such an agonist would affect social bonds in animal models. The facultatively monogamous prairie voles ( Microtus ochrogaster ), capable of forming long-term social attachments between adult individuals, are an ideal rodent model for such testing. Therefore, in a series of experiments we investigated the effects of the recently developed oxytocin receptor-specific agonist LIT-001 on the acquisition and expression of partner preference, a well-established model of pair bonding, in prairie voles. LIT-001 (10 mg/kg, intraperitoneal), as expected, facilitated the acquisition of partner preference when administered prior to a 4hr cohabitation. In contrast, while animals injected with vehicle after the 4hr cohabitation exhibited significant partner preference, animals that were injected with LIT-001 did not show such partner preference. This result suggests that OXTR activation during expression of pair bonding can inhibit partner preference. The difference in effects of LIT-001 on acquisition versus expression was not due to basal differences in partner preference between the experiments, as LIT-001 had no significant effects on expression of partner preference if administered following a shorter (2hr-long) cohabitation. Instead, this difference agrees with the hypothesis that the activation of oxytocin receptors acts as a signal of presence of a social partner. Our results indicate that the effects of pharmacological activation of oxytocin receptors crucially depend on the phase of social attachments.
We have identified a natural Japanese macaque model of the childhood neurodegenerative disorder neuronal ceroid lipofuscinosis, commonly known as Batten Disease, caused by a homozygous frameshift ...mutation in the CLN7 gene (CLN7−/−). Affected macaques display progressive neurological deficits including visual impairment, tremor, incoordination, ataxia and impaired balance. Imaging, functional and pathological studies revealed that CLN7−/− macaques have reduced retinal thickness and retinal function early in disease, followed by profound cerebral and cerebellar atrophy that progresses over a five to six-year disease course. Histological analyses showed an accumulation of cerebral, cerebellar and cardiac storage material as well as degeneration of neurons, white matter fragmentation and reactive gliosis throughout the brain of affected animals. This novel CLN7−/− macaque model recapitulates key behavioral and neuropathological features of human Batten Disease and provides novel insights into the pathophysiology linked to CLN7 mutations. These animals will be invaluable for evaluating promising therapeutic strategies for this devastating disease.
•We have discovered a novel CLN7−/− macaque model of Batten disease (BD).•Affected BD macaques bear a frameshift mutation in the CLN7 gene (CLN7−/−).•CLN7−/− macaques display progressive locomotor deficits including ataxia and tremor.•Brains from CLN7−/− macaques show accumulation of autofluorescent storage material.•Brains from CLN7−/− macaques show robust cerebral and cerebellar atrophy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The University of California Santa Cruz Genome Browser Database (GBD) contains sequence and annotation data for the genomes of about a dozen vertebrate species and several major model organisms. ...Genome annotations typically include assembly data, sequence composition, genes and gene predictions, mRNA and expressed sequence tag evidence, comparative genomics, regulation, expression and variation data. The database is optimized to support fast interactive performance with web tools that provide powerful visualization and querying capabilities for mining the data. The Genome Browser displays a wide variety of annotations at all scales from single nucleotide level up to a full chromosome. The Table Browser provides direct access to the database tables and sequence data, enabling complex queries on genome-wide datasets. The Proteome Browser graphically displays protein properties. The Gene Sorter allows filtering and comparison of genes by several metrics including expression data and several gene properties. BLAT and In Silico PCR search for sequences in entire genomes in seconds. These tools are highly integrated and provide many hyperlinks to other databases and websites. The GBD, browsing tools, downloadable data files and links to documentation and other information can be found at http://genome.ucsc.edu/.
This hypothetical case study provides a vehicle for illustrating typical project cash flows and the day-to-day events that can influence these flows. The case study also shows the interaction between ...project cash flows and a firm's overall financial condition. As the title implies, it is a simplified caricature of what actually happens in more complex and realistic setting, where a project manager has to worry about a multitude of problems, including the concerns of project scope schedule, and budget, plus the technical challenges of getting the job done. Isolating the management of the cash flow from the rest of these concerns allows an examination of what a project manager might need to contend with respect to cast and financial management of a project. Three industry experts-Robert J. Berg, Francis D. Leathers (Member ASCE), and Mark C. Zweig-provide analysis of the case study.
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DOBA, FGGLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We investigated functional responses of benthic invertebrates to deposited sediment in four Missouri USA streams. In each stream, invertebrates were sampled along continuums of deposited sediment ...(particles <2 mm in size) from 0 to 100% surface cover in reaches of fairly homogeneous substrate composition, current velocity, and water depths. Correlations, graphical representations, and the cumulative response curves of feeding and habit groups provided strong empirical support for distinct community functional changes due to deposited sediment. Feeding groups were more sensitive to deposited sediment than habit groups. Densities of all the feeding groups decreased significantly with increasing deposited sediment, while relative densities of gatherers increased significantly. Taxa richness also decreased significantly for all the feeding groups except for the shredders. Increases in deposited sediment were related to significant density decreases for only the clingers and sprawlers in the habit group, resulting in significant increases in the relative densities of both burrowers and climbers. Clingers, sprawlers, and swimmers also showed significant decreases in taxa richness.PUBLICATION ABSTRACT
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ribosomal protein (RP) expression in higher eukaryotes is regulated translationally through the 5′TOP sequence. This mechanism evolved to more rapidly produce RPs on demand in different tissues. Here ...we show that 40S ribosomes, in a complex with the mRNA binding protein LARP1, selectively stabilize 5′TOP mRNAs, with disruption of this complex leading to induction of the impaired ribosome biogenesis checkpoint (IRBC) and p53 stabilization. The importance of this mechanism is underscored in 5q− syndrome, a macrocytic anemia caused by a large monoallelic deletion, which we found to also encompass the LARP1 gene. Critically, depletion of LARP1 alone in human adult CD34+ bone marrow precursor cells leads to a reduction in 5′TOP mRNAs and the induction of p53. These studies identify a 40S ribosome function independent of those in translation that, with LARP1, mediates the autogenous control of 5′TOP mRNA stability, whose disruption is implicated in the pathophysiology of 5q− syndrome.
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•LARP1 controls the stability but not the translation of 5′TOP mRNAs•The 40S ribosome is required for LARP1 stabilization of 5′TOP mRNAs•Disruption of 5′TOP stability elicits the IRBC response and p53 stabilization•LARP1 is lost in 5q− syndrome, and its deficit mirrors the pathology
Ribosomal proteins (RPs) are essential components of the translational machinery. Gentilella et al. show that the 40S ribosome and LARP1 form a complex that has a high affinity for 5′TOP mRNAs, particularly RPs. This association preserves 5′TOP mRNA stability, constituting an anabolic reservoir that can be utilized upon demand.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Clinical teaching does not fit neatly into traditional teaching-learning models. The interaction between a resident and an attending physician is of particular interest because it has several ...functions including education, supervision, socialization, and quality control. The purpose of this study was to observe, classify, and record verbal teaching and learning behaviors in the resident-attending physician interaction. During a 12-month period, 125 observations of resident-attending physician interactions were recorded; the average length of the interactions was 4.27 minutes. The six most frequent resident verbal behaviors compared by postgraduate year level did not vary significantly. Only one of the six most frequent attending physician verbal behaviors varied significantly. In the average interaction of about 4 minutes, three fourths of the interaction was on patient care issues, leaving little time for teaching. There are many unanswered questions about the resident-attending physician interaction and its contribution to the training of a physician.
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