Law Libraries and Laboratories: The Legacies of Langdell and His Metaphor

Law Librarians and others have often referred to Harvard Law School Dean C.C. Langdell’s statements that the law library is the lawyer’s laboratory. Professor Danner examines the context of what Langdell through his other writings, the educational environment at Harvard in the late nineteenth century, and the changing perceptions of university libraries generally. He then considers how the “laboratory metaphor” has been applied by librarians and legal scholars during the twentieth century and into the twenty-first. The article closes with thoughts on Langdell’s legacy for law librarians and the usefulness of the laboratory metaphor

Comparative Network Analysis of Preterm vs. Full-Term Infant-Mother Interactions

Several studies have reported that interactions of mothers with preterm infants show differential characteristics compared to that of mothers with full-term infants. Interaction of preterm dyads is often reported as less harmonious. However, observations and explanations concerning the underlying mechanisms are inconsistent. In this work 30 preterm and 42 full-term mother-infant dyads were observed at one year of age. Free play interactions were videotaped and coded using a micro-analytic coding system. The video records were coded at one second resolution and studied by a novel approach using network analysis tools. The advantage of our approach is that it reveals the patterns of behavioral transitions in the interactions. We found that the most frequent behavioral transitions are the same in the two groups. However, we have identified several high and lower frequency transitions which occur significantly more often in the preterm or full-term group. Our analysis also suggests that the variability of behavioral transitions is significantly higher in the preterm group. This higher variability is mostly resulted from the diversity of transitions involving non-harmonious behaviors. We have identified a maladaptive pattern in the maternal behavior in the preterm group, involving intrusiveness and disengagement. Application of the approach reported in this paper to longitudinal data could elucidate whether these maladaptive maternal behavioral changes place the infant at risk for later emotional, cognitive and behavioral disturbance

New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell death

New fluorinated and methoxylated di(hetero)arylethers and di(hetero)arylamines were prepared functionalizing the 7-position of the thieno[3,2-blpyridine, using copper (C-O) or palladium (C N) catalyzed couplings, respectively, of the 7-bromothieno[3,2-blpyridine, also prepared, with ortho, meta and para fluoro or methoxy phenols and anilines. The compounds obtained were evaluated for their growth inhibitory activity on the human tumor cell lines MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), HCI15 (colon carcinoma), HepG2 (hepatocellular carcinoma) and HeLa (cervical carcinoma). The most active compounds, a di(hetero)arylether with a methoxy group in the meta position relative to the ether function and two di(hetero)arylamines with a methoxy group either in the ortho or in the meta position relative to the NH, were further tested at their GI(50) concentrations on NCI-H460 cells causing pronounced alterations in the cell cycle profile and a strong and significant increase in the programmed death of these cells. The fluorinated and the other methoxylated compounds did not show important activity, presenting high GI(50) values in all the cell lines tested. Furthermore, the hepatotoxicity of the compounds was assessed using porcine liver primary cells (PLP2), established by some of us. Results showed that one of the most active compounds was not toxic to the non-tumor cells at their GI(50) concentrations showing to be the most promising as antitumoral.The authors would like to thank to the Foundation for the Science and Technology (PCT Portugal) for financial support through the NMR Portuguese network (Bruker 400 Avance III-Univ Minho); to FCT and FEDER-COMPETE/QREN/EU for financial support through the research unities PEst-C/QUI/UI686/2011 and PEst-OE/AGR/UI0690/2011, the research project PTDC/QUI-QUI/111060/2009 and the post-Doctoral grants attributed to R.C.C. (SFRH/BPD/68344/2010) and R.T.L. (SRH/BPD/68787/2010). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

Validation of control genes and a standardised protocol for quantifying gene expression in the livers of C57BL/6 and ApoE−/− mice

The liver plays a critical role in food and drug metabolism and detoxification and accordingly influences systemic body homeostasis in health and disease. While the C57BL/6 and ApoE−/− mouse models are widely used to study gene expression changes in liver disease and metabolism, currently there are no validated stably expressed endogenous genes in these models, neither is it known how gene expression varies within and across liver lobes. Here we show regional variations in the expression of Ywhaz, Gak, Gapdh, Hmbs and Act-β endogenous genes across a liver lobe; Using homogeneous samples from the four liver lobes of 6 C57BL/6 mice we tested the stability of 12 endogenous genes and show that Act-β and Eif2-α are the most stably expressed endogenous genes in all four lobes and demonstrate lobular differences in the expression of Abca1 cholesterol efflux gene. These results suggest that sampling from a specified homogeneous powdered liver lobe is paramount in enhancing data reliability and reproducibility. The stability of the 12 endogenous genes was further tested using homogeneous samples of left liver lobes from 20 ApoE−/− mice on standard or high polyphenol diets. Act-β and Ywhaz are suitable endogenous genes for gene expression normalisation in this mouse model

Adaptive Significance of the Formation of Multi-Species Fish Spawning Aggregations near Submerged Capes

BACKGROUND: Many fishes are known to spawn at distinct geomorphological features such as submerged capes or "promontories," and the widespread use of these sites for spawning must imply some evolutionary advantage. Spawning at these capes is thought to result in rapid offshore transport of eggs, thereby reducing predation levels and facilitating dispersal to areas of suitable habitat. METHODOLOGY/PRINCIPAL FINDINGS: To test this "off-reef transport" hypothesis, we use a hydrodynamic model and explore the effects of topography on currents at submerged capes where spawning occurs and at similar capes where spawning does not occur, along the Mesoamerican Barrier Reef. All capes modeled in this study produced eddy-shedding regimes, but specific eddy attributes differed between spawning and non-spawning sites. Eddies at spawning sites were significantly stronger than those at non-spawning sites, and upwelling and fronts were the products of the eddy formation process. Frontal zones, present particularly at the edges of eddies near the shelf, may serve to retain larvae and nutrients. Spawning site eddies were also more predictable in terms of diameter and longevity. Passive particles released at spawning and control sites were dispersed from the release site at similar rates, but particles from spawning sites were more highly aggregated in their distributions than those from control sites, and remained closer to shore at all times. CONCLUSIONS/SIGNIFICANCE: Our findings contradict previous hypotheses that cape spawning leads to high egg dispersion due to offshore transport, and that they are attractive for spawning due to high, variable currents. Rather, we show that current regimes at spawning sites are more predictable, concentrate the eggs, and keep larvae closer to shore. These attributes would confer evolutionary advantages by maintaining relatively similar recruitment patterns year after year

Materials Characterization Using Acoustic Nonlinearity Parameters and Harmonic Generation: Effects of Crystalline and Amorphous Structures

The importance of nonlinearity in the description of material behavior is gaining widespread attention. Nonlinearity plays a major, if not dominating, role in a number of material properties. For example, properties that are important in engineering design such as thermal expansion or the pressure dependence of optical refraction are inherently nonlinear [1]. New assembley techniques such as the use of ultrasonic gauges to determine the loading of critical fasteners depend upon nonlinear properties of the fasteners [2]. Areas of considerable fundamental interest in nonlinearity include lattice dynamics [3], radiation stress in solids [4,5], and nonlinear optics [6

Mechanisms Involved in Alleviation of Intestinal Inflammation by Bifidobacterium Breve Soluble Factors

Objectives: Soluble factors released by Bifidobacterium breve C50 (Bb) alleviate the secretion of pro-inflammatory cytokines by immune cells, but their effect on intestinal epithelium remains elusive. To decipher the mechanisms accounting for the cross-talk between bacteria/soluble factors and intestinal epithelium, we measured the capacity of the bacteria, its conditioned medium (Bb-CM) and other Gram(+) commensal bacteria to dampen inflammatory chemokine secretion. Methods: TNFa-induced chemokine (CXCL8) secretion and alteration of NF-kB and AP-1 signalling pathways by Bb were studied by EMSA, confocal microscopy and western blotting. Anti-inflammatory capacity was also tested in vivo in a model of TNBS-induced colitis in mice. Results: Bb and Bb-CM, but not other commensal bacteria, induced a time and dose-dependent inhibition of CXCL8 secretion by epithelial cells driven by both AP-1 and NF-kB transcription pathways and implying decreased phosphorylation of p38-MAPK and IkB-a molecules. In TNBS-induced colitis in mice, Bb-CM decreased the colitis score and inflammatory cytokine expression, an effect reproduced by dendritic cell conditioning with Bb-CM. Conclusions: Bb and secreted soluble factors contribute positively to intestinal homeostasis by attenuating chemokine production. The results indicate that Bb down regulate inflammation at the epithelial level by inhibiting phosphorylation