After-effects and after-effects and after-effects of after-effects: The multiple side effects of prospective memory

In a prospective memory task responding to a prospective memory target involves switching between ongoing and prospective memory task which can result in a slowing of subsequent ongoing task performance (i.e., an after-effect). Moreover, a slowing can also occur when prospective memory targets occur after the prospective memory task is deactivated (i.e., another after-effect). In this study, we investigated both after-effects within the same study. Moreover, we also tested whether the latter after-effects even occur on subsequent ongoing task trials. The results show, in fact, after-effects of all kinds. Thus, (1) correctly responding to prospective memory targets results in after-effects, a so far neglected cost on ongoing task performance, (2) responding to deactivated prospective memory targets also slows down performance, probably due to the involuntary retrieval of the intention, and (3) this slowing is present even on subsequent ongoing task trials, suggesting that even deactivated intentions are sufficient to induce a conflict that requires subsequent adaptation. Overall, these results indicate that performance slowing in a prospective memory experiment includes various kinds of sources, not only monitoring cost, and these sources may be understood best in terms of conflict adaptation.

Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures

Neuronal apoptosis was observed in the rat dentate gyrus in two experimental models of human limbic epilepsy. Five hours after one hippocampal kindling stimulation, a marked increase of in situ terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) of fragmented DNA was observed in nuclei located within and on the hilar border of the granule cell layer and in the polymorphic region. Forty kindling stimulations with 5-min interval produced higher numbers of labeled nuclei compared with one stimulation. The increase of TUNEL-positive nuclei was prevented by the protein synthesis inhibitor cycloheximide but not affected by the N-methyl-d-aspartate receptor antagonist MK-801. Kainic acid-induced seizures lead to a pattern of labeling in the hippocampal formation identical to that evoked by kindling. A large proportion of cells displaying TUNEL-positive nuclei was double-labeled by the neuron-specific antigen NeuN, demonstrating the neuronal identity of apoptotic cells. Either 1 or 40 kindling stimulations also gave rise to a marked increase of the number of cells double-labeled with the mitotic marker bromodeoxyuridine and NeuN in the subgranular zone and on the hilar border of the dentate granule cell layer. The present data show that single and intermittent, brief seizures induce both apoptotic death and proliferation of dentate gyrus neurons. We hypothesize that these processes, occurring early during epileptogenesis, are primary events in the development of hippocampal pathology in animals and possibly also in patients suffering from temporal lobe epilepsy.

Murine hematopoietic reconstitution after tagging and selection of retrovirally transduced bone marrow cells

A major problem facing the effective treatment of patients with cancer is how to get the specific antitumor agent into every tumor cell. In this report we describe the use of a strategy that, by using retroviral vectors encoding a truncated human CD5 cDNA, allows the selection of only the infected cells, and we show the ability to obtain, before bone marrow transplantation, a population of 5-fluouraci-treated murine bone marrow cells that are 100% marked. This marked population of bone marrow cells is able to reconstitute the hematopoietic system in lethally irradiated mice, indicating that the surface marker lacks deleterious effects on the functionality of bone marrow cells. No gross abnormalities in hematopoiesis were detected in mice repopulated with CD5-expressing cells. Nevertheless, a significant proportion of the hematopoietic cells no longer expresses the surface marker CD5 in the 9-month-old recipient mice. This transcriptional inactivity of the proviral long terminal repeat (LTR) was accompanied by de novo methylation of the proviral sequences. Our results show that the use of the CD5 as a retrovirally encoded marker enables the rapid, efficient, and nontoxic selection in vitro of infected primary cells, which can entirely reconstitute the hematopoietic system in mice. These results should now greatly enhance the power of studies aimed at addressing questions such as generation of cancer-negative hematopoiesis.

Elimination of residual metastatic prostate cancer after surgery and adjunctive cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade immunotherapy

Cancer relapse after surgery is a common occurrence, most frequently resulting from the outgrowth of minimal residual disease in the form of metastases. We examined the effectiveness of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade as an adjunctive immunotherapy to reduce metastatic relapse after primary prostate tumor resection. For these studies, we developed a murine model in which overt metastatic outgrowth of TRAMP-C2 (C2) prostate cancer ensues after complete primary tumor resection. Metastatic relapse in this model occurs reliably and principally within the draining lymph nodes in close proximity to the primary tumor, arising from established metastases present at the time of surgery. Using this model, we demonstrate that adjunctive CTLA-4 blockade administered immediately after primary tumor resection reduces metastatic relapse from 97.4 to 44%. Consistent with this, lymph nodes obtained 2 weeks after treatment reveal marked destruction or complete elimination of C2 metastases in 60% of mice receiving adjunctive anti-CTLA-4 whereas 100% of control antibody-treated mice demonstrate progressive C2 lymph node replacement. Our study demonstrates the potential of adjunctive CTLA-4 blockade immunotherapy to reduce cancer relapse emanating from minimal residual metastatic disease and may have broader implications for improving the capability of immunotherapy by combining such forms of therapy with other cytoreductive measures including surgery.

New York, N.Y. and vicinity, 1961 : Paterson, N.J.-N.Y. (8 Sheet Set) (Raster Image)

This layer is a georeferenced raster image of the United States Geological Survey 7.5 minute topographic sheet map entitled: New York and vicinity : Paterson, N.J.-N.Y., 1955. It is part of an 8 sheet map set covering the metropolitan New York City area. It was published in 1961. Scale 1:24,000. The source map was prepared by the Geological Survey from 1:24,000-scale maps of Hackensack, Paterson, Orange, and Weehawken 1955 7.5 minute quadrangles. The Orange quadrangle was previously compiled by the Army Map Service. Culture revised by the Geological Survey. Hydrography compiled from USC&GS charts 287 (1954), 745 (1956), and 746 (1956). The image inside the map neatline is georeferenced to the surface of the earth and fit to the Universal Transverse Mercator (UTM) Zone 18N NAD27 projection. 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, index maps, legends, or other information associated with the principal map. USGS maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 10 and 20 feet; depths are shown with contours and soundings. Please pay close attention to map collar information on projections, spheroid, sources, dates, and keys to grid numbering and other numbers which appear inside the neatline. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

New York, N.Y. and vicinity, 1961 : Harlem, N.Y.-N.J. (8 Sheet Set) (Raster Image)

This layer is a georeferenced raster image of the United States Geological Survey 7.5 minute topographic sheet map entitled: New York and vicinity : Harlem, N.Y.-N.J., 1956. It is part of an 8 sheet map set covering the metropolitan New York City area. It was published in 1961. Scale 1:24,000. The source map was compiled from 1:24,000-scale maps of Mount Vernon 1956, Yonkers 1956, Central Park 1956, and Flushing 1955 7.5 minute quadrangles. Hydrography compiled from USC&GS charts 222 (1955), 223 (1954), 748 (1955), 226, 274, 745, 746, and 747 (1956). The image inside the map neatline is georeferenced to the surface of the earth and fit to the Universal Transverse Mercator (UTM) Zone 18N NAD27 projection. 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, index maps, legends, or other information associated with the principal map. USGS maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 10 and 20 feet; depths are shown with contours and soundings. Please pay close attention to map collar information on projections, spheroid, sources, dates, and keys to grid numbering and other numbers which appear inside the neatline. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

New York, N.Y. and vicinity, 1961 : Oyster Bay, N.Y.-Conn. (8 Sheet Set) (Raster Image)

This layer is a georeferenced raster image of the United States Geological Survey 7.5 minute topographic sheet map entitled: New York and vicinity : Oyster Bay, N.Y.-Conn., 1955. It is part of an 8 sheet map set covering the metropolitan New York City area. It was published in 1961. Scale 1:24,000. The source map was prepared by the Geological Survey from 1:24,000-scale maps of Bayville 1954, Mamaroneck 1955, Sea Cliff 1954, and Hicksville 1954 7.5 minute quadrangles compiled by the Army Map Service. The Mamaroneck quadrangle was previously compiled by the Geological Survey in 1933 and 1934. Culture revised by the Geological Survey. Hydrography compiled from USC&GS charts 222 (1955), 223 (1954, 1955), and 224 (1954). The image inside the map neatline is georeferenced to the surface of the earth and fit to the Universal Transverse Mercator (UTM) Zone 18N NAD27 projection. 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, index maps, legends, or other information associated with the principal map. USGS maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 10 and 20 feet; depths are shown with contours and soundings. Please pay close attention to map collar information on projections, spheroid, sources, dates, and keys to grid numbering and other numbers which appear inside the neatline. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

New York, N.Y. and vicinity, 1961 : Staten Island, N.Y.-N.J. (8 Sheet Set) (Raster Image)

This layer is a georeferenced raster image of the United States Geological Survey 7.5 minute topographic sheet map entitled: New York and vicinity : Staten Island, N.Y.-N.J., 1955. It is part of an 8 sheet map set covering the metropolitan New York City area. It was published in 1961. Scale 1:24,000. The source map was prepared by the Geological Survey from 1:24,000-scale maps of Jersey City, Elizabeth, Arthur Kill, and The Narrows, 1955 7.5 minute quadrangles. Hydrography compiled from USC&GS charts 285 (1955), 286 (1954), 287 (1954), 745 (1956), 369 (1956), 540 (1954), 541 (1955) and 745 (1956). The image inside the map neatline is georeferenced to the surface of the earth and fit to the Universal Transverse Mercator (UTM) Zone 18N NAD27 projection. 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, index maps, legends, or other information associated with the principal map. USGS maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 10 and 20 feet; depths are shown with contours and soundings. Please pay close attention to map collar information on projections, spheroid, sources, dates, and keys to grid numbering and other numbers which appear inside the neatline. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.