Contribution of biobanks to care services

Approaches to the management of patients with cancer have been revolutionised by the ability to examine tumours at a genetic and molecular level and tailor treatments accordingly. Underpinning this work is the need for large numbers of high-quality human biospecimens for use in translational research studies to identify new biomarkers for the prediction, diagnosis and treatment of cancer. Biobanking has subsequently emerged as a dedicated activity to provide the infrastructure required for the standardised collection, storage and distribution of high quality human biospecimens for research purposes. This article provides an overview of the role of biobanks and the vital contribution they make to the delivery of cancer care for patients now and in the future

Molecular classification of non-invasive breast lesions for personalised therapy and chemoprevention

Breast cancer screening has led to a dramatic increase in the detection of pre-invasive breast lesions. While mastectomy is almost guaranteed to treat the disease, more conservative approaches could be as effective if patients can be stratified based on risk of co-existing or recurrent invasive disease.Here we use a range of biomarkers to interrogate and classify purely non-invasive lesions (PNL) and those with co-existing invasive breast cancer (CEIN). Apart from Ductal Carcinoma In Situ (DCIS), relative homogeneity is observed. DCIS contained a greater spread of molecular subtypes. Interestingly, high expression of p-mTOR was observed in all PNL with lower expression in DCIS and invasive carcinoma while the opposite expression pattern was observed for TOP2A.Comparing PNL with CEIN, we have identified p53 and Ki67 as predictors of CEIN with a combined PPV and NPV of 90.48% and 43.3% respectively. Furthermore, HER2 expression showed the best concordance between DCIS and its invasive counterpart.We propose that these biomarkers can be used to improve the management of patients with pre-invasive breast lesions following further validation and clinical trials. p53 and Ki67 could be used to stratify patients into low and high-risk groups for co-existing disease. Knowledge of expression of more actionable targets such as HER2 or TOP2A can be used to design chemoprevention or neo-adjuvant strategies. Increased knowledge of the molecular profile of pre-invasive lesions can only serve to enhance our understanding of the disease and, in the era of personalised medicine, bring us closer to improving breast cancer care.

Pathologie et thérapeutique chirurgicales générales (2e édition française complètement remaniée et très augmentée, traduite d'après la 12e édition allemande) / par Th. Billroth,... Alex. von Winiwarter,...

Titre original : Die allgemeine chirurgische Pathologie und Therapie

Structural determinants of subunit -subunit interactions and subcellular localization of the calcium /calmodulin -dependent protein kinase II

The multifunctional Ca$\sp{2+}$/calmodulin-dependent protein kinase II (CaM kinase) is a Ser/Thr directed protein kinase that participates in diverse Ca$\sp{2+}$ signaling pathways in neurons. The function of CaM kinase depends upon the ability of subunits to form oligomers and to interact with other proteins. Oligomerization is required for autophosphorylation which produces significant functional changes that include Ca$\sp{2+}$/calmodulin-independent activity and calmodulin trapping. Associations with other proteins localize CaM kinase to specific substrates and effectors which serves to optimize the efficiency and speed of signal transduction. In this thesis, we investigate the interactions that underlie the appropriate positioning of CaM kinase activity in cells. We demonstrate that the subcellular distribution of CaM kinase is dynamic in hippocampal slices exposed to anoxic/aglycemic insults and to high K$\sp{+}$-induced depolarization. We determine the localization of CaM kinase domains expressed in neurons and PC-12 cells and find that the C-terminal domain of the $\alpha$ subunit is necessary for localization to dendrites. Moreover, monomeric forms of the enzyme gain access to the nucleus. Attempts made to identify novel CaM kinase binding proteins using the yeast two-hybrid system resulted in the isolation of hundreds of positive clones. Those that have been sequenced are identical to CaM kinase isoforms. Finally, we report the discovery of specific regions within the C-terminal domain that are necessary and sufficient for subunit-subunit interactions. Differences between the $\alpha$ and $\beta$ isoforms were discovered that indicate unique structural requirements for oligomerization. A model for how CaM kinase subunits interact to form holoenzymes and how structural heterogeneity might influence CaM kinase function is presented. ^

Relacion puntual de la gloriosa recuperacion de la ciudad de Valencia por las armas del Rey... mandadas por... el señor Duque de Orleans y el señor Mariscal Duque de Bervick ..

Palau fecha la obra en 1707

Docket and fees book / 1791-1797

Records of cases heard in the Massachusetts Court of Common Pleas (Middlesex Co.) in Cambridge, Mass., and the New Hampshire Inferior Court of Common Pleas (Hillsborough Co.) in Amherst, N.H and matters brought before justices of the peace. Records identify the litigants, with some notes on fees and settlements; many of the cases concern debts. Justices of the peace include: Israel Atherton (Lancaster, Mass.); Samuel Dana (Amherst, N.H.); Joshua Longley (Shirley, Mass.); Nathaniel Paine (Worcester, Mass.); James Prescott (Westford, Mass.); Jeremiah Stiles (Keene, N.H.); William Swan (Groton, Mass.); Sampson Tuttle (Littleton, Mass.); and Henry Woods (Pepperell, Mass.).

" Lines upon the late proceedings of the College Government" collection, 1787-1917

This collection contains various manifestations of a humorous poem, most often called "Lines upon the late proceedings of the College Government," written by classmates John Quincy Adams and John Murray Forbes in 1787. Both Adams and Forbes were members of the class of 1787, and the poem recounts events surrounding the pranks and ensuing punishment of two members of the class behind them, Robert Wier and James Prescott. Wier and Prescott had been caught drinking wine and making "riotous noise," and they were publicly reprimanded by Harvard President Joseph Willard and several professors and tutors, including Eliphalet Pearson, Eleazar James, Jonathan Burr, Nathan Read, and Timothy Lindall Jennison. The poem mocks these authority figures, but it spares Samuel Williams, whom it suggests was the only professor to find their antics humorous.

Historical essays, being selections from "Short studies on great subjects".

Mode of access: Internet.