Wild-type p53 protein undergoes cytoplasmic sequestration in undifferentiated neuroblastomas but not in differentiated tumors.

Neuroblastoma (NB), a tumor arising from the sympathetic nervous system, is one of the most common malignancies in childhood. Several recent reports on the p53 genotype found virtually exclusive wild-type status in primary tumors, and it was postulated that p53 plays no role in the development of NB. Here, however, we report that the vast majority of undifferentiated NBs exhibit abnormal cytoplasmic sequestration of wild-type p53. This inability of p53 to translocate to the nucleus presumably prevents the protein from functioning as a suppressor. Thirty of 31 cases (96%) of undifferentiated NB showed elevated levels of wild-type p53 in the cytoplasm of all tumor cells concomittant with a lack of nuclear staining. p53 immunoprecipitation from tumor tissues showed a 4.5- to 8-fold increase over normal protein levels. All of 10 tumors analyzed harbored wild-type p53 by direct sequencing of full-length cDNA and Southern blot. In addition, no MDM-2 gene amplification was seen in all 11 tumors analyzed. In contrast, no p53 abnormality was detected in 14 differentiated ganglioneuroblastomas and 1 benign ganglioneuroma. We conclude that loss of p53 function seems to play a major role in the tumorigenesis of undifferentiated NB. This tumor might abrogate the transactivating function of p53 by inhibiting its access to the nucleus, rather than by gene mutation. Importantly, our results suggest that (i) this could be a general mechanism for p53 inactivation not limited to breast cancer (where we first described it) and that (ii) it is found in a tumor previously not thought to be affected by p53 alteration.

The Future Direction of Delaware Law (Including a Brief Exegesis on Fee Shifting Bylaws)

Delaware sets the governance standards for most public companies. The ability to attract corporations could not be explained solely by the existence of a favorable statutory regime. Delaware was not invariably the first or the only state to implement management friendly provisions. Given the interpretive gaps in the statute and the critical importance of the common law in the governance process, courts played an outsized role in setting legal standards. The management friendly nature of the Delaware courts contributed significantly to the state’s attraction to public corporations. A current example of a management friendly trend in the case law had seen the recent decisions setting out the board’s authority to adopt bylaws under Section 109 of the Delaware General Corporation Law (DGCL), particularly those involving the shifting of fees in litigation against the corporation or its directors. The DGCL allows bylaws that address “the business of the corporation, the conduct of its affairs, and its rights or powers or the rights or powers of its stockholders, directors, officers or employees.” The broad parameters are, however, subject to limits. Bylaws cannot be inconsistent with the certificate of incorporation or “the law.” Law includes the common law. The Delaware courts have used the limitations imposed by “the law” to severely restrict the reach of shareholder inspired bylaws. The courts have not used the same principles to impose similar restraints on bylaws adopted by the board of directors. This can be seen with respect to bylaws that restrict or even eliminate the right of shareholders to bring actions against management and the corporation. In ATP Tour, Inc. v. Deutscher Tennis Bund the court approved a fee shifting bylaw that had littl relationship to the internal affairs of the corporation. The decision upheld the bylaw as facially valid.The decision ignored a number of obvious legal infirmities. Among other things, the decision did not adequately address the requirement in Section 109(b) that bylaws be consistent with “the law.” The decision obliquely acknowledged that the provisions would “by their nature, deter litigation” but otherwise made no effort to assess the impact of this deterrence on shareholders causes of action. The provision in fact had the practical effect of restricting, if not eliminating, litigation rights granted by the DGCL and the common law. Perhaps most significantly, however, the bylaws significantly limited common law rights of shareholders to bring actions against the corporation and the board. Given the high dismissal rates for these actions, fee shifting bylaws imposed a meaningful risk of liability on plaintiffs. Moreover, because judgments in derivative suits were paid to the corporation, shareholders serving as plaintiffs confronted the risk of liability without any offsetting direct benefit. By preventing suits in this area, the bylaw effectively insulated the behavior of boards from legal challenge. The ATP decision was poorly reasoned and overstepped acceptable boundaries. The management friendly decision threatened the preeminent role of Delaware in the development of corporate law. The decision raised the specter of federal intervention and the potential for meaningful competition from the states. Because the opinion examined the bylaw in the context of non-stock companies, the reasoning may remain applicable only to those entities and never make the leap to for-profit stock corporations. Nonetheless, the analysis reflects a management friendly approach that does not adequately take into account the impact of the provision on the rights of shareholders.

Australian water mass variations from GRACE data linked to Indo-Pacific climate variability

Time-variable gravity data from the Gravity Recovery And Climate Experiment (GRACE) mission are used to study total water content over Australia for the period 2002–2010. A time-varying annual signal explains 61% of the variance of the data, in good agreement with two independent estimates of the same quantity from hydrological models. Water mass content variations across Australia are linked to Pacific and Indian Ocean variability, associated with El Niño-Southern Oscillation (ENSO) and the Indian Ocean Dipole (IOD), respectively. From 1989, positive (negative) IOD phases were related to anomalously low (high) precipitation in southeastern Australia, associated with a reduced (enhanced) tropical moisture flux. In particular, the sustained water mass content reduction over central and southern regions of Australia during the period 2006–2008 is associated with three consecutive positive IOD events.

Community attributes determine facilitation potential in a semi-arid steppe

Studies on positive plant–plant relations have traditionally focused on pair-wise interactions. Conversely, the interaction with other co-occurring species has scarcely been addressed, despite the fact that the entire community may affect plant performance. We used woody vegetation patches as models to evaluate community facilitation in semi-arid steppes. We characterized biotic and physical attributes of 53 woody patches (patch size, litter accumulation, canopy density, vegetation cover, species number and identity, and phylogenetic distance), and soil fertility (organic C and total N), and evaluated their relative importance for the performance of seedlings of Pistacia lentiscus, a keystone woody species in western Mediterranean steppes. Seedlings were planted underneath the patches, and on their northern and southern edges. Woody patches positively affected seedling survival but not seedling growth. Soil fertility was higher underneath the patches than elsewhere. Physical and biotic attributes of woody patches affected seedling survival, but these effects depended on microsite conditions. The composition of the community of small shrubs and perennial grasses growing underneath the patches controlled seedling performance. An increase in Stipa tenacissima and a decrease in Brachypodium retusum increased the probability of survival. The cover of these species and other small shrubs, litter depth and community phylogenetic distance, were also related to seedling survival. Seedlings planted on the northern edge of the patches were mostly affected by attributes of the biotic community. These traits were of lesser importance in seedlings planted underneath and in the southern edge of patches, suggesting that constraints to seedling establishment differed within the patches. Our study highlights the importance of taking into consideration community attributes over pair-wise interactions when evaluating the outcome of ecological interactions in multi-specific communities, as they have profound implications in the composition, function and management of semi-arid steppes.

3D geometry of growth strata in a fault-propagation fold: insights into space–time evolution of the Crevillente Fault (Abanilla-Alicante sector), Betic Cordillera, Spain

This work presents a 3D geometric model of growth strata cropping out in a fault-propagation fold associated with the Crevillente Fault (Abanilla-Alicante sector) from the Bajo Segura Basin (eastern Betic Cordillera, southern Spain). The analysis of this 3D model enables us to unravel the along-strike and along-section variations of the growth strata, providing constraints to assess the fold development, and hence, the fault kinematic evolution in space and time. We postulate that the observed along-strike dip variations are related to lateral variation in fault displacement. Along-section variations of the progressive unconformity opening angles indicate greater fault slip in the upper Tortonian–Messinian time span; from the Messinian on, quantitative analysis of the unconformity indicate a constant or lower tectonic activity of the Crevillente Fault (Abanilla-Alicante sector); the minor abundance of striated pebbles in the Pliocene-Quaternary units could be interpreted as a decrease in the stress magnitude and consequently in the tectonic activity of the fault. At a regional scale, comparison of the growth successions cropping out in the northern and southern limits of the Bajo Segura Basin points to a southward migration of deformation in the basin. This means that the Bajo Segura Fault became active after the Crevillente Fault (Abanilla-Alicante sector), for which activity on the latter was probably decreasing according to our data. Consequently, we propose that the seismic hazard at the northern limit of the Bajo Segura Basin should be lower than at the southern limit.

College Book 4, 1686-1750

Regular recording of Corporation meetings began in College Book 4, which includes minutes from July 23, 1686 through September 5, 1750. Its spine title reads "College Book 4 & 5" due to a nineteenth century labeling error. The creation of College Book 4 was precipitated by the English Court of Chancery's October 1684 judgment, which annulled the Royal Charter of the Massachusetts Colony and seemed to render the College Charter of 1650 – and with it the Corporation and Board of Overseers – defunct. In May 1686, Joseph Dudley (Harvard AB 1665) received a commission as the President of the Council of New England, and on July 23, 1686, Dudley and the Council met in Boston to create a provisional College governing board led by Increase Mather as Rector of the College and John Leverett and William Brattle as Tutors. The "Rector and Tutors" mirrored in purpose if not in name the Corporation's "President and Fellows," and the agreements of President Dudley and the Council creating the new governing board comprise the first entry in College Book 4. In June 1692, a new act of incorporation for Harvard College was passed in the Massachusetts Legislature and signed by the Governor. The Charter of 1692 merged the functions of the Board of Overseers and the Corporation into one Corporation consisting of the President, Treasurer, and eight Fellows. As the Corporation created by this 1692 act (and modified in later versions of the Charter) grew unwieldy, its members met less frequently. As a result, the Faculty (known until 1825 as the "Immediate Government") assumed more responsibility in managing the College's daily operations and addressing student discipline. On December 6, 1707 the Massachusetts General Court restored the Charter of 1650, thus reestablishing the Board of Overseers and the Corporation as the governing bodies of Harvard College. The changes in name and composition of the Harvard Corporation between 1686 and 1707 are documented in the proceedings recorded in College Book 4.

Letter from William Prescott to Oliver Prescott, 1782 October 19

Two-page handwritten letter from Harvard undergraduate William Prescott to his classmate, Oliver Prescott, that chiefly describes, in florid language, the discipline received by John Rowe (Harvard AB 1783) and others from College officers for disorderly behavior.

III. Research materials used in William C. Lane's article, "Early Silver Belonging to Harvard College," [1923]

This folder contains transcriptions of archival materials used in Lane's research for the article, published by the Colonial Society of Massachusetts in 1923. Included are two letters from the papers of Harvard President Jared Sparks (1849-1853) regarding the christening basin and the role of the College steward in the care of the silver collection; and a 1781 inventory (see also in folder 7) and 1829 Corporation vote excerpted from College records. There are also two notes containing citations.

Reports of the Committee of commons, 1800

This collection contains two handwritten committee reports that provide a brief financial overview of the Harvard College Steward's accounts for the quarters ending February 27, 1800 and May 29, 1800. The February 27th statement is dated March 4, 1800, and the May 29th statement is dated June 2, 1800.

Back Bay, Boston, Massachusetts, 1861 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan of lands on the Back Bay : belonging to the Boston Water Power Co., the Commonwealth, and other parties, showing the system of streets & grades as laid out and recommended by the Back Bay Commissioners, compiled and surveyed under the direction of the Commissioners by James Slade ; H.M. Wightman, surveyor ; E.R. Brown, de. It was printed by A. Meisel, lith., Dec. 31st, 1861. Covers Back Bay and South End, Boston, Massachusetts, and portions of Roxbury and Brookline. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Massachusetts State Plane Coordinate System, Mainland Zone (in Feet) (Fipszone 2001). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, property owners, selected public buildings, parks, radial distances from City Hall, and more. This layer is part of a selection of digitally scanned and georeferenced historic maps of Massachusetts from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates (1755-1922), scales, and purposes. The digitized selection includes maps of: the state, Massachusetts counties, town surveys, coastal features, real property, parks, cemeteries, railroads, roads, public works projects, etc.

Rock map of the Yellow River (Huang He) expedition, China, 1925-1927 : Sheet 2

This layer is part of a set of georeferenced, raster images of the manuscript, paper map set entitled: Ch'ing-Hai upper Yellow River expedition : Rock and Simpson, 1925-27, [cartography by J.F. Rock]. Scale 1:250,000. This layer image is of Sheet II [of 10] covering a portion of the Yellow River (Huang He) region in eastern Qinghai Sheng and southern Gansu Sheng, China. The map set details the route and surrounding environs of the Arnold Arboretum's "Western China" expedition led by Joseph Rock, 1924-1927. The set covers a portion of the Yellow River (Huang He) region in south central China (Qinghai, Gansu, and Sichuan shengs (a portion of historic Tibet)). It shows features, labeled variously in English, Chinese, Wade-Giles transliteration, and Tibetan, including: rivers, streams, lakes, mountains, gorges, valleys, plateaus, plains, cities, towns, villages, provincial capitals, county seats, passes, monasteries, ruin sites, native tribe locations, and more. Relief is shown by hachures, spot heights, and landform drawings. The original manuscript map set is part of the Harvard College Library, Harvard Map Collection. "Joseph Rock traced his travels for the [Arnold] Arboretum's [Western China] 1924-1927 expedition in a colorful, hand-drawn map entitled 'Ch'ing-Hai upper Yellow River expedition.' The pen-and-ink drawing was made on ten sheets that when joined form a single, irregularly-shaped map, approximately six by eight feet in size. The individual sheets are numbered, using roman numerals; on sheet VII is a second title, 'Choni Territory, Upper and Lower T'ieh-Pu country and route to Sung-Pan, J. F. Rock, 1925-1927.' Topographical and other features are identified using a combination of English, Chinese characters, Wade-Giles transliterations and Tibetan script. Rock's attractive cursive style and use of hachures, spot heights, and landform drawings to depict relief add character to the map." -- Text from the Arnold Arboretum Web site.

Rock map of the Yellow River (Huang He) expedition, China, 1925-1927 : Sheet 3

This layer is part of a set of georeferenced, raster images of the manuscript, paper map set entitled: Ch'ing-Hai upper Yellow River expedition : Rock and Simpson, 1925-27, [cartography by J.F. Rock]. Scale 1:250,000. This layer image is of Sheet III [of 10] covering a portion of the Yellow River (Huang He) region in eastern Qinghai Sheng and southern Gansu Sheng, China. The map set details the route and surrounding environs of the Arnold Arboretum's "Western China" expedition led by Joseph Rock, 1924-1927. The set covers a portion of the Yellow River (Huang He) region in south central China (Qinghai, Gansu, and Sichuan shengs (a portion of historic Tibet)). It shows features, labeled variously in English, Chinese, Wade-Giles transliteration, and Tibetan, including: rivers, streams, lakes, mountains, gorges, valleys, plateaus, plains, cities, towns, villages, provincial capitals, county seats, passes, monasteries, ruin sites, native tribe locations, and more. Relief is shown by hachures, spot heights, and landform drawings. The original manuscript map set is part of the Harvard College Library, Harvard Map Collection. "Joseph Rock traced his travels for the [Arnold] Arboretum's [Western China] 1924-1927 expedition in a colorful, hand-drawn map entitled 'Ch'ing-Hai upper Yellow River expedition.' The pen-and-ink drawing was made on ten sheets that when joined form a single, irregularly-shaped map, approximately six by eight feet in size. The individual sheets are numbered, using roman numerals; on sheet VII is a second title, 'Choni Territory, Upper and Lower T'ieh-Pu country and route to Sung-Pan, J. F. Rock, 1925-1927.' Topographical and other features are identified using a combination of English, Chinese characters, Wade-Giles transliterations and Tibetan script. Rock's attractive cursive style and use of hachures, spot heights, and landform drawings to depict relief add character to the map." -- Text from the Arnold Arboretum Web site.

Rock map of the Yellow River (Huang He) expedition, China, 1925-1927 : Sheet 5

This layer is part of a set of georeferenced, raster images of the manuscript, paper map set entitled: Ch'ing-Hai upper Yellow River expedition : Rock and Simpson, 1925-27, [cartography by J.F. Rock]. Scale 1:250,000. This layer image is of Sheet V [of 10] covering a portion of the Yellow River (Huang He) region in eastern Qinghai Sheng and southern Gansu Sheng, China. The map set details the route and surrounding environs of the Arnold Arboretum's "Western China" expedition led by Joseph Rock, 1924-1927. The set covers a portion of the Yellow River (Huang He) region in south central China (Qinghai, Gansu, and Sichuan shengs (a portion of historic Tibet)). It shows features, labeled variously in English, Chinese, Wade-Giles transliteration, and Tibetan, including: rivers, streams, lakes, mountains, gorges, valleys, plateaus, plains, cities, towns, villages, provincial capitals, county seats, passes, monasteries, ruin sites, native tribe locations, and more. Relief is shown by hachures, spot heights, and landform drawings. The original manuscript map set is part of the Harvard College Library, Harvard Map Collection. "Joseph Rock traced his travels for the [Arnold] Arboretum's [Western China] 1924-1927 expedition in a colorful, hand-drawn map entitled 'Ch'ing-Hai upper Yellow River expedition.' The pen-and-ink drawing was made on ten sheets that when joined form a single, irregularly-shaped map, approximately six by eight feet in size. The individual sheets are numbered, using roman numerals; on sheet VII is a second title, 'Choni Territory, Upper and Lower T'ieh-Pu country and route to Sung-Pan, J. F. Rock, 1925-1927.' Topographical and other features are identified using a combination of English, Chinese characters, Wade-Giles transliterations and Tibetan script. Rock's attractive cursive style and use of hachures, spot heights, and landform drawings to depict relief add character to the map." -- Text from the Arnold Arboretum Web site.

Valorização da flora de Cusseque e Caiúndo no centro e sul de Angola e avaliação da biomassa lenhosa utilizada para combustível e construção

Tese de mestrado em Biologia da Conservação, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2016

Why the EU must reengage with Turkey. EPC Commentary, 29 September 2014

Democratic values and basic rights in Turkey are hanging by a thread. Over the past eighteen months the rule of law, civil liberties and freedoms have been eroded which has left many Turks anxious over the direction in which their country is heading. With Turkey’s accession negotiations de facto frozen, the EU finds itself with little leverage over Ankara. Calls of concern have fallen on deaf ears as Turkey’s leadership has become increasingly belligerent, with its EU related narrative overflowing with resentment. Because Turkey’s accession negotiations are irreversibly intertwined with Turkey-EU cooperation in other areas, this has had a negative impact on the broader relationship between both sides. Recent examples include the issue of foreign fighters traveling from Europe to Syria via Turkey. Each side has accused the other of not doing enough to stem the flow. Likewise, following the decision of Russian President, Vladimir Putin, to ban the import of agricultural goods from countries that have placed sanctions on Moscow, the EU asked Turkey to demonstrate solidarity, as a “candidate country”, and not to increase exports of agricultural products to Russia. Turkey rejected this request and is reportedly working on strengthening trade ties with Moscow. Turkey remains an important partner in a number of key areas including trade, energy, foreign and security policy and migration. At a time when the EU faces crises in both its Eastern and Southern neighbourhoods, a reliable and predictable Turkey, with which it can cooperate in the Black Sea and Middle East neighbourhoods is crucial. Hence the vision and plans of the EU’s new leadership, in particular new Foreign Policy Chief, Federica Mogherini, and Commissioner for European Neighbourhood Policy and Enlargement Negotiations, Johannes Hahn, how to shape relations with Ankara is particularly significant. The Union’s current policy is counterproductive and is further eroding trust and cooperation rather than enhancing it. It needs to be turned around.