bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural Transplantation for Neurodegenerative Diseases: Past, Present, and Futurea
Authors: REDMOND D. EUGENE , ROTH ROBERT H. , SPENCER DENNIS D. , NAFTOLIN FREDERICK , LERANTH CSABA , ROBBINS RICHARD J. , MAREK KENNETH L. , ELSWORTH JOHN D. , SASS KIMBERLEE J. , TAYLOR JANE R. , SLADEK JOHN R.
Published: December 2006

After almost 100 years of sporadic, and marginally successful, studies of neural transplantation in animals, we are now on the threshold of a clinical treatment of the damaged brain. The initial studies of neural transplantation have focused on Parkinson's disease, primarily as a model for a more general strategy of “repair by cellular replacement.” Parkinson's is known to result from the loss of a small population of cells that produce the essential neuromodulator, dopamine, for much of the brain. Further, the disease is improved significantly, during the early part of its course, by chemical augmentation of dopamine activity through drug therapies, such as l‐dopa. Finally, the disease is often fatal in spite of the best medical treatments, therefore justifying more radical therapeutic experiments. If transplantation of brain cells can be accomplished successfully in humans, as it has been in animals, then replacement of a small population of dopamine‐producing cells in Parkinson's disease should have important functional effects and possibly reverse the course and symptoms of the disease. Other useful applications will surely follow for conditions affecting millions of people for whom medicine now has only palliative and ineffective treatments.

Just as Parkinson's disease is a model clinical condition for testing cellular replacements, fetal neural tissue transplants are also a first step for a broader strategy of molecular and cellular therapies. Fetal cells are, in many respects, the best replacements one could imagine, since precursor cells have the capacity to develop into every cell found in the adult. So, the best replacement for a dopamine neuron would likely be a precursor dopamine neuron or “neuroblast.” Animal research through 1985 had demonstrated the unique properties of such fetal cells, but survivability after transplantation had not been attained with primate or human neural tissue. Our programs developed techniques to transplant monkey fetal neural tissue, to cryopreserve it, and to reverse functional effects of the neurotoxin, MPTP, in monkeys. This technique was applied to the collection and preservation of human tissue, and preliminary successful results have been obtained in patients with idiopathic Parkinson's disease. Others have reported success with different techniques in two MPTP‐Parkinsonian patients and a small number of patients with idiopathic disease. If the most dramatic improvements can be replicated consistently and the benefits last for a reasonable period without complications, a clinical treatment might develop using “random‐source” fetal cadaver cells.
The Use of the Computerized Neuropsychological Test Battery (CNTB) in an Efficacy and Safety Trial of BMY 21,502 in Alzheimer's Disease
Authors: CUTLER NEAL R. , SHROTRIYA RAJESH C. , SRAMEK JOHN J. , VEROFF AMY E. , SEIFERT RANDALL D. , REICH LINDA A. , HIRONAKA DENISE YEE
Published: December 2006

BMY 21,502 is a nootropic which protects memory and enhances long‐term potentiation according to preclinical findings. Alzheimer's disease (AD) patients who were diagnosed by DSM‐III‐R and NINCDS‐ADRDA criteria were enrolled in a 12‐week double‐blind investigation of BMY 21,502 vs. placebo at 300 mg tid. The study design included a 1‐week placebo lead‐in and a 4‐week placebo washout in addition to the 12‐week double‐blind treatment period. Efficacy was assessed with the Alzheimer's Disease Assessment Scale (ADAS) and the Computerized Neuropsychological Test Battery (CNTB) at weeks 4, 8, 12, and 16. Clinical Global Impression (CGI) assessments were also performed biweekly. Sixty‐nine patients (28M, 41F; mean age 72 years, range 54 to 92 years) were enrolled in the study. Baseline Mini‐Mental Status Examination (MMSE) scores ranged from 16 to 26 (mean 23.5) in patients on active drug (n = 34), and from 15 to 26 (mean 22.5) in placebo patients (n = 35). Baseline efficacy scores were comparable for drug and placebo patients (p > 0.05). Twelve (35%) patients who received BMY 21,502 withdrew from the study, 8 (24%) due to adverse events. Three (9%) patients who received placebo withdrew from the study, all due to adverse events. Patients on active drug who were valid for analysis of efficacy (n = 22) showed a mean decrease in ADAS of‐1.5 at week 12, vs. a mean change of‐0.5 in patients who received placebo (n = 32), although there was no significant difference between the two (p > 0.05). Correlations between the CNTB summary scores and ADAS cognitive subscores were, nevertheless, highly significant at baseline (r =−0.83, p= 0.0001) and week 12 (r =−0.83, p= 0.0001). Correlations between the word list learning, spatial, and naming subtests of the ADAS and CNTB were also highly significant (p= 0.0001). Although modest, the findings for active drug vs. placebo response in this study suggest that BMY 21,502 should be further investigated, with a larger study population, in order to fully determine the compound's potential efficacy.
THE STATUS OF ‘STANDARD’ SUSY
Authors: ZWIRNER FABIO
Published: December 2006

We summarize the present status of low‐energy supersymmetry, exemplified by the Minimal Supersymmetric extension of the Standard Model (MSSM). We review the searches for Supersymmetric particles and supersymmetric Higgs bosons. We conclude with some comments on the open theoretical problems related to spontaneous supersymmetry breaking in the underlying fundamental theory.
CONCLUDING SUMMARY
Authors: REES MARTIN J
Published: December 2006

We have heard a wide‐ranging set of talks on cosmology and high energy astrophysics at this conference. All I can really do in this short talk is to present my subjective impression of an arbitrary selection of highlights.
Topological Partition Relations of the Form ω*→(Y)12a
Authors: COMFORT W. W. , KATO AKIO , SHELAH SAHARON
Published: December 2006

ABSTRACT. THEOREM. The topological partition relation ω*→ (Y)12

(a) Fails for every space Y with |Y| |Mg 2c;

(b) Holds for Y discrete if and only if |Y| |Ml c;

(c) Holds for certain nondiscrete P‐spaces Y;

(d) Fails for Y=ω Imu {p} with p∉ω*;

(e) Fails for Y infinite and countably compact.
A Primer on Galois Connections
Authors: ERNÉ M. , KOSLOWSKI J. , MELTON A. , STRECKER G. E.
Published: December 2006

ABSTRACT. The rudiments of the theory of Galois connections (or residuation theory, as it is sometimes called) are provided, together with many examples and applications. Galois connections occur in profusion and are well known to most mathematicians who deal with order theory; they seem to be less known to topologists. However, because of their ubiquity and simplicity, they (like equivalence relations) can be used as an effective research tool throughout mathematics and related areas. If one recognizes that a Galois connection is involved in a phenomenon that may be relatively complex, then many aspects of that phenomenon immediately become clear, and thus, the whole situation typically becomes much easier to understand.
A History of the New York Branch of the American Psychological Association, 1903‐1935a
Authors: BENJAMIN LUDY T.
Published: December 2006

[The Eastern Psychological Association (EPA) held its 65th annual meeting in 1994. The numbering of those meetings began with a meeting of the New York Branch of the American Psychological Association in 1930, but the roots of the EPA are much deeper, beginning with the formation of the New York Branch in 1903. The branch began as a forum for the exchange of scientific information in psychology in the New York City area. It was initially successful, meeting three times per year for a one‐day program, and featured a Who's Who of speakers delivering some of the most important papers in the history of American psychology. After World War I its character, like that of psychology, began to change as the program reflected the growth in applied psychology and the membership began to be dominated by nonpsychologists. Its reorganization in 1930 restored control of the branch to university‐based psychologists and reestablished the scientific goals that characterize the EPA today.]
Some Generalizations of Pseudocompactness
Authors: GARCÍA‐FERREIRA SALVADOR
Published: December 2006

ABSTRACT: In this paper, we introduce the concepts of p‐boundedness for pɛω*, (α, M)‐pseudocompactness and (α, M)‐compactness, for a cardinal number α and Ø≠M⊆β(ω)\ω. We prove that Xα is pseudocompact (respectively, countably compact) iff X is (α, M)‐pseudocompact (respectively, (α, M)‐compact), for some Ø≠M⊆β(ω)\ω; the Rudin‐Keisler order on β(ω)\ω can be defined in terms of p‐boundedness and p‐pseudocompactness; and if pɛβ(ω)\ω then p is RK‐minimal (selective) iff the space ω∪T(p) is p‐pseudocompact, where T(p) is the type of p in β(ω)\ω.
Uniquely Representable Posets
Authors: GEHRKE MAI
Published: December 2006

ABSTRACT: It is known that a partially ordered set is uniquely representable, that is, it is order isomorphic to the order component of a Priestley space of a unique bounded distributive lattice whenever this lattice is generated by its doubly irreducible elements. In this case the interval topology on the poset is Hausdorff. Priestley has conjectured that the interval topology is always Hausdorff when the poset is uniquely representable. We consider this problem in topological terms. This allows us to see how the conjecture is a natural one and to broaden the class of lattices that are known to have uniquely representable spectral sets. Furthermore, we see that the theory of generalized continuous lattices ends up playing a crucial role, and that the conjecture perhaps should be strengthened to assert that for uniquely representable posets, the entire interval of admissible topologies collapses.
On Weaker Forms of Paracompactness, Countable Compactness, and Lindelöfness
Authors: HAMLETT T. R. , JANKOVIĆ DRAGAN
Published: December 2006

ABSTRACT: An ideal on a set X is a nonempty collection of subsets closed under the operations of finite union and subset. The concepts of parabounded and countably bounded subsets are defined as well as regularity with respect to an ideal I(i.e., I‐regular). The bounded subsets of a topological space are characterized as the subsets which are both parabounded and countably bounded. It is shown that if (X, τ) is a Hausdorff space and I is an ideal on X such that I∩τ={Ø}, then (X, τ) is compact modulo I iff (X, τ) is H‐closed and I‐regular. Examples are given which place e‐Lindelöfness in the hierarchy of known properties and it is shown that para‐Lindelöf e‐Lindelöf spaces are Lindelöf. It is shown that in the category of Hausdorff spaces, perfect images of e‐paracompact spaces are e‐paracompact. Posed as an open question is the following: What can be said about the closed continuous image of an e‐paracompact space?
On Complete Aronszajn Quasi‐metric Spaces and Subcompactness
Authors: ROMAGUERA SALVADOR
Published: December 2006

ABSTRACT: We show that every regular quasi‐developable complete Aronszajn space is a subcompact space. From this result we deduce, among other things, that every regular quasidevelopable left K‐sequentially complete quasi‐metric space is also subcompact. Finally, we prove that every Tychonoff Čech complete quasi‐metrizable space is a complete Aronszajn space.
Jordan Pairs of Adjacency Relations in Digital Spaces
Authors: HERMAN GABOR T.
Published: December 2006

ABSTRACT: We define a digital space to be a pair consisting of an arbitrary nonempty set V and a symmetric binary relation π on V with respect to which V is connected. Our intent is to capture and investigate the notion of a boundary in this extremely general environment. Our motivation comes from practical applications, where boundaries need to be identified in multidimensional data sets with the further aim of displaying them on a computer screen. Our definitions are biased towards such applications. In particular, we refer to elements of V as spels (short for “spatial elements”). We call an arbitrary nonempty subset of a π surface and we define the notions of the interior and the exterior of a surface. We also introduce the notion of a near‐Jordan surface; its interior and exterior partition V. We call a symmetric binary relations on V that contains π a spel‐adjacency. For spel‐adjacencies κ and λ, we call a surface κλ‐Jordan if it is near‐Jordan, its interior is κ‐connected and its exterior is λ‐connected. Our first main result is that the surface between a κ‐connected set and any λ‐component of its complement is κλ‐Jordan. We introduce the notion of a binary picture in which there is an assignment of a 1 or a 0 to elements of V. A κλ‐boundary is defined as the surface between a λ‐component of 1‐spels and a λ‐component of 0‐spels. We discuss the notion of tightness for spel‐adjacencies. Our next main result is that for tight spel‐adjacencies κ and λ, the interior of a κλ‐boundary is κ‐connected, while its exterior is λ‐connected. We say that {κ, λ} is a Jordan pair, if κ and λ are tight spel‐adjacencies and every κλ‐boundary (equivalently, every λκ‐boundary) is near‐Jordan. It therefore follows from the previously stated result that if {κ, λ} is a Jordan pair, then a κλ‐boundary is κλ‐Jordan. We also show that if {κ, λ} is a Jordan pair and κ′ and λ′ are tight spel adjacencies containing κ and λ, respectively, then {κ′, λ′} is also a Jordan pair.
Covering Spaces, Boundary Sets, and Interconnection Networks
Authors: RICE MICHAEL D.
Published: December 2006

ABSTRACT: The paper introduces the ideas of algebraic mapping and boundary set as discrete analogues of the topological concepts of covering space mapping and boundary. These ideas are used to investigate various aspects of the theory of interconnection networks. Theorems 3 and 4 formalize and extend the discussion of group action graphs and Cayley graphs presented in [2]. Theorem 3 establishes the existence of a pair of adjoint functors between two special categories of interconnection networks. Theorem 4 characterizes the algebraic mappings with a universal lifting property. Using boundary sets, Theorems 6, 7, and 8 provide a mathematical foundation for the idea of wavefront computation discussed in [8] and [13].
Maximal Protori in Compact Topological Groups
Authors: AHDOUT SHAHLA , HURWITZ CAROL , ITZKOWITZ GERALD , ROTHMAN SHELDON , STRASSBERG HELEN
Published: December 2006

ABSTRACT: The analysis of Lie groups depends to a large extent on their maximal tori. For a compact connected topological group G, the subgroups analogous to the maximal tori are the maximal connected Abelian subgroups. As in Hofmann and Morris [7] we call them maximal protori. We sharpen some results of [7] by showing that each maximal protorus is in a natural way the projective limit of maximal tori Tα in the corresponding Gα, where G= projGα. This sharpened characterization together with some methods of Moskowitz [4], [10] will be used to show that a number of well‐known theorems concerning Lie groups extend in a natural way to all compact connected groups.
Noncoalescent Minimal Discrete Flows
Authors: SABBAGHAN MASOUD , WU TA‐SUN
Published: December 2006

ABSTRACT: The purpose of the present note is to give some general method of construction of noncoalescent minimal sets.
Topological and Algebraic Properties of the Subgroup Generated by the Involutions in a Compact Ring
Authors: COHEN JO‐ANN , KOH KWANGIL
Published: December 2006

ABSTRACT: An analogue, W, of the Weyl group for a compact ring A is defined. A description of the topological and algebraic properties of W is given, as well as an indication of how the structure of A reflects that of W.
Pathogenetic Mechanisms of Post‐Polio Syndrome: Morphological, Electrophysiological, Virological, and Immunological Correlations
Authors: DALAKAS MARINOS C.
Published: December 2006

To understand the mechanism of post‐poliomyelitis muscular atrophy (PPMA) and the post‐polio syndrome (PPS) in general, we performed the following studies: (1) histopathology in spinal cord sections from patients who died 9 days to 44 years after acute paralytic poliomyelitis; (2) enzyme histochemistry, immunocyto‐chemistry (for lymphocyte subsets, MHC antigens and N‐CAM) and polymerase chain reaction (PCR) for poliovirus RNA in the muscle biopsies from symptomatic or asymptomatic muscles of post‐polio patients; (3) determination of lymphocyte subsets and circulating IgG or IgM antibodies against GM1 and poliovirus; (4) virological studies in the spinal fluid for oligoclonal bands and search for poliovirus genome with PCR; (5) electrophysiological studies including single fiber EMG, fiber density and macro‐EMG; and (6) [31P] exercise MRS spectroscopy on previously affected muscles to search for a metabolic correlate of fatigue. These studies concluded that in PPS a continuing dysfunction is present in the spinal cord motor neurons, resulting in ongoing muscle denervation and reinnervation first evident at the axonal branch points. Symptoms are related to attrition of the oversprouting motor neurons which after a period of time cannot support all their axonal sprouts, resulting in failure of re‐reinnervation. In some patients with PPS there is also an ongoing immune activation and presence of defective viral particles in the spinal fluid. However, their role in the pathogenesis of PPS is presently unknown.
Amyotrophic Lateral Sclerosis and Polio: Is There an Association?
Authors: OKUMURA HITOSHI , KURLAND LEONARD T. , WARING STEPHEN C.
Published: December 2006

Because polio and ALS are both manifestations of anterior horn cell disease, consideration of some etiologic or pathogenetic relationship continues to recur. Studies that show an association are infrequent and are greatly outnumbered by negative reports in spite of possible journal bias to report positive results. Our limited studies in Guam and Rochester, Minnesota, have added to the negative list, and support the conclusion that there is no etiologic association of these two distinct diseases. The role, if any, of nonparalytic polio and polio vaccines with respect to ALS is not clear. With such a high proportion of the population having antibodies to polio, it may not be feasible to differentiate ALS with respect to the presence or absence of polio antibodies. Although the results to date do not support a polio‐ALS relationship, further long‐term studies are desirable for both the classical and the Western Pacific forms of ALS with respect to past polio outbreaks and, for the future, the unknown effect of polio vaccines on the incidence of ALS.
Mice Homozygous for a Modified β‐Amyloid Precursor Protein (βAPP) Gene Show Impaired Behavior and High Incidence of Agenesis of the Corpus Callosuma
Authors: MÜLLER U. , CRISTINA N. , Li Z.‐W. , WOLFER D.P.Y. , LIPP H.‐P. , RÜLICKE T. , BRANDNER S. , AGUZZI A. , WEISSMAN C.
Published: December 2006

The amyloid precursor protein (βAPP) gene of the mouse was disrupted by homologous recombination; however, contrary to expectation, brain and other tissues still contained βAPP‐specific RNA, albeit at a level 5‐10 fold lower than wild‐type and lacking the disrupted exon, which had been spliced out. The brain contained shortened βAPP‐specific protein at a low level. Mutant mice were severely impaired in spatial learning and exploratory behavior and showed increased incidence of agenesis of the corpus callosum.
Tau Protein and the Neurofibrillary Pathology of Alzheimer's Disease
Authors: GOEDERT M.
Published: December 2006

Abundant neurofibrillary tangles, neuropil threads and senile plaque neurites constitute the neurofibrillary pathology of Alzheimer's disease. They form in the nerve cells that undergo degeneration in the disease, in which their regional distribution correlates with the degree of dementia. Each lesion contains the paired helical filament (PHF) as its major component. PHFs are composed of the microtubule‐associated protein tau in a hyperphosphorylated state. PHF‐tau is hyperphosphorylated on all six adult brain isoforms. As a consequence, tau is unable to bind to microtubules and is believed to self‐assemble into the PHF. Several candidate protein kinases and protein phosphatases have been identified through in vitro experiments.
M1 Agonists for the Treatment of Alzheimer's Disease.
Authors: FISHER A. , HELDMAN E. , GURWITZ D. , HARING R. , KARTON Y. , MESHULAM H. , PITTEL Z. , MARCIANO D. , BRANDEIS R. , SADOT E. , BARG Y. , PINKAS‐KRAMARSKI R. , VOGEL Z. , GINZBURG I. , TREVES T. A. , VERCHOVSKY R. , KLIMOWSKY S. , KORCZYN A.D.
Published: December 2006

The AF series compounds, AF102B and congeners of AF150(S), are functionally selective agonists for m1 muscarinic receptors (m1AChRs). This is shown in stable transfected CHO and PC12 cells (PC12M1) with m1‐m5AChRs and m1AChRs, respectively. AF102B and AF150(S) are partial agonists, but AF150, AF151, and AF151(S) are full agonists in stimulating phosphoinositides hydrolysis or arachidonic acid release in these cells. Yet, all these compounds behave as antagonists when compared with carbachol in elevating cAMP levels. In PC12M1 cells, unlike carbachol, the AF series compounds induce only minimal to moderate neurite outgrowth. Yet, these agonists synergize strongly with NGF, which by itself mediates only a mild response. Stimulation of m1AChRs by AF102B, AF150(S) and AF151(S) in PC12M1 cells enhances secretion of β/A4 amyloid precursor protein derivatives (APPs). The enhanced APPs secretion induced by AF102B is potentiated by NGF. AF102B also stimulates APPs secretion from rat cortical slices. Stimulation of m1AChR in PC12M1 cells with carbachol or AF102B decreases tau phosphorylation as indicated by specific tau‐1 mAb and alkaline phosphatase treatment. Due to the above mentioned properties m1 agonists may be of unique value in delaying the progression of Alzheimer's disease (AD). The AF series compounds show a wide safety margin and improve memory and learning deficits in animal models for AD. There is a dearth of clinical reports on m1 agonists. These include studies on AF102B and xanomeline, another m1 selective agonist. We tested AF102B in escalating doses of 20, 40, 60 mg, tid, po, (each dose for 2 weeks) for a total of 10 weeks. This was a single‐blind placebo‐controlled, parallel‐group study in patients with probable AD. AFl02B was signiticantly effective at 40 and 60 mg, tid in the ADAS, ADAS‐cognitive and ADAS‐word recognition scales.
High Affinity Choline Transporter Status in Alzheimer's Disease Tissue from Rapid Autopsya
Authors: BISSETTE G. , SEIDLER F. J. , NEMEROFF C. B. , SLOTKIN T. A.
Published: December 2006

The degeneration of nucleus basalis cholinergic neurons in Alzheimers disease (AD) has led to therapies that attempt to increase the synaptic availability of acetylcholine in the remaining cholinergic nerve terminals and to thereby reverse or slow the progressive dementia accompanying the disease process. The inadequacy of current choline‐replacement therapies suggests that utilization of choline may be disordered and the rate‐limiting step in acetylcholine synthesis, the high affinity choline transporter, may be involved. An adequate test of this hypothesis requires the use of fresh, unfrozen tissue, as the transporter activity declines rapidly after death. Using tissue acquired within two hours of death, the activity of the high affinity choline transporter was shown to be increased in cortical brain regions from AD patients compared to non‐AD controls. Further studies using frozen tissues with similar short postmortem acquisition times, revealed the expression of the high affinity uptake transporter to be increased in AD cortex as well. When the ratio of regional uptake activity or expression to the regional level of choline acetyltransferase was calculated, the increase in choline transporter activity and expression was clearly statistically significant. Further statistical significance in the choline transporter activity of the AD group was achieved when the putamen, a region without marked pathology in AD, was used as an internal standard to control for agonal state differences in the individual patients contributing tissue to this study. These increases in choline transporter expression and activity in AD indicate disordered regulation of this rate‐limiting component of acetylcholine synthesis above and beyond that required to compensate for the reduced cholinergic synaptic availability in AD.
Visual versus Auditory Memory Stimulation in Patients with Probable Alzheimer's Disease A PET Study with 18 FDGa
Authors: KESSLER J. , GHAEMI M. , MIELKE R. , HERHOLZ K. , HEISS W. D.
Published: December 2006

Patients with probable Alzheimer's disease were either stimulated with a continuous visual recognition task (n = 18) or with a continuous auditory recognition task during PET measurement with 18 FDG. The PET scanner was a Siemens CTI, ECAT EXACT with 5 mm transaxial and 6 mm axial resolution. The global stimulation effects were nearly identical in both groups and increased of 4.17 ± 8.14% in the auditory stimulated group and of 4.03 ± 11.78% in the visual stimulated group. Beyond regional stimulation effects in both groups a common cerebellar stimulation effect was measured. It is concluded that the cerebellar stimulation effect reflects a modality independent cognitive process and that the only small enhancement of global glucose metabolism indicates disturbed stimuli processes and finally explained the patient's failure in memory tasks.
Computer‐based Cognitive Training in Alzheimer's Disease Patients
Authors: HOFMANN M. , HOCK C. , MÜLLER‐SPAHN F.
Published: December 2006

Memory training programs for cognitively impaired patients have often been criticized for their lack of relevance to everyday activities. We therefore report our experience with four patients suffering from probable Alzheimer's disease, who were trained with a new computer based program recently developed by our research group. An everyday task of personal relevance to the patient is simulated and trained on a PC‐touch‐screen using personal photographs of the patient's surroundings and biography. According to the degree of cognitive impairment, training has three major aspects 1) social competence in patients with beginning deficiencies, 2) orientation in patients with moderate disease, and 3) emotional aspects in patients with advanced deficiencies. The patient's training performance improved substantially. While psychopathometric tests showed no significant effects with regard to general cognitive performance, levels of motivation were high and there was a positive acceptance of the training and signs of emotional activation.
ApoE2 Allele, Down's Syndrome, and Dementiaa
Authors: ROYSTON M. C. , MANN D. , PICKERING‐BROWN S. , OWEN F. , PERRY R. , RAGBHAVAN R. , KHIN‐NU C. , TYNER S. , DAY K. , CROOK R. , HARDY J. , ROBERTS G. W.
Published: December 2006

All individuals with Down's syndrome (trisomy 21‐DS) develop the pathogenic hallmarks of Alzheimer's disease in old age (+40 years).1‐4 The extent of pathology is variable, but it has been shown that the amount of β‐amyloid pathology is variable and related to age and the degree of dementia.3 Thus, in DS, growing old is associated with a progressive pathological process which results in cognitive decline. However, neuropsychological studies of older DS subjects have identified a clinical dementia in only a proportion of cases.1‐4These contradictory observations could be reconciled if some factor existed which modulated the rate and amount of β‐amyloid pathology. Recent studies demonstrate an association between the apolipoprotein E4 (ApoE4) allele and the earlier age of onset in both sporadic8‐9 and familial10 AD. Increased amounts of βamyloid pathology can also be related to the E4 allele. However, at present there are no data documenting the effects of ApoE genotype on the expression or degree of clinical symptoms of the disease. We have examined the ApoE genotype in a cohort of clinically evaluated elderly patients with DS in order to examine the effects of ApoE genotype on the clinical symptoms of dementia. We report here that, despite the presence of an active disease process, the ApoE E2 allele is associated with longevity and preservation of cognitive functioning.
Amyloid β‐Protein, APOE Genotype and Head Injury
Authors: NICOLL J. A. R. , ROBERTS G. W. , GRAHAM D. I.
Published: December 2006

Deposition of amyloid β‐protein (Aβ) in the brain plays a key role in the pathogenesis of Alzheimer's disease. Head injury is an epidemiological risk factor for Alzheimer's disease, and deposition of Aβ occurs in approximately one third of individuals dying shortly after a severe head injury. Of the three common apolipoprotein E alleles (APOE‐ε2, ε3, and ε4) APOE‐ε4 allele is a strong risk factor for both sporadic and some familial cases of Alzheimer's disease and there is in vitro evidence that apolipoprotein E is directly involved in Aβ deposition. We have examined the frequency of APOE‐ε4 in those individuals with Aβ deposition following head injury and found that the APOE‐ε4 frequency (0.52) is higher than in most studies of sporadic Alzheimer's disease. In those head‐injured individuals without amyloid deposition the APOE‐ε4 frequency (0.16) is similar to that in non‐Alzheimer's disease controls (p < 0.00001). Our data indicate an interaction between known environmental and genetic risk factors for Alzheimer's disease and underlines the importance of convergence of data around the common mechanism of Aβ deposition. Furthermore, it indicates a genetic susceptibility to the effects of a head injury which may be of significance both to those who have recently sustained such an injury and to those whose activities put them at risk of trauma.
Apolipoprotein E Polymorphism Is Associated with Both Senile Plaque Load and Alzheimer‐Type Neurofibrillary Tangle Formationa
Authors: MÄRZ W. , SCHARNAGL H. , KIRÇA M. , BOHL J. , GROß W. , OHM T. G.
Published: December 2006

Recent work provided evidence that the apolipoprotein (apo) E polymorphism is associated with late‐onset sporadic Alzheimer's disease. The major histological hallmarks of Alzheimer's disease are the extraneuronal deposition of A4/β‐amyloid and the intraneuronal formation of neurofibrillary tangles, the latter correlating strongly with the psychometric status. We examined the relationship between the apo E polymorphism and Alzheimer's disease‐related histological changes using a staging system which accounts for the progression of the disease over time and correlates well with the cognitive decline ante mortem. We observed a significant positive correlation between both neurofibrillary changes and A4/β‐amyloid deposits and the ε4 gene dose. We estimated that the presence of one apo E4 allele leads to an earlier onset of the histopathological process of about one decade. The association of both types of Alzheimer's disease‐related changes with the prevalence of the ε4‐allele suggests that the apo E polymorphism causally contributes to the development of Alzheimer's disease.
The Role of Arachidonic Acid in the Secretion of the Amyloid Precursor Protein (APP)a
Authors: EMMERLING M. R. , DUDLEY D. T. , DYER R. D. , CARROLL R. T. , DOYLE P. D. , DAVIS R. E.
Published: December 2006

We have studied the activation of human ml‐muscarinic receptors in a genetically engineered Chinese hamster ovary cell line (CHO‐ml) to determine which second messenger systems affect the secretion of APP via the non‐amyloidogenie route. Carbachol activation of the signaling pathways in CHO‐ml cells promotes APP secretion by activation of both protein kinase C (PKC)‐dependent or Ca++ ‐dependent second messenger pathways. Both pathways converge to increase the enzyme activity of phospholipase A2 (PLA2), the enzyme that releases arachidonic acid from cellular stores. Directly activating PLA2 with melittin, a peptide from bee venom, or by adding arachidonic acid directly to cultured cells increases the secretion of APP. Thus, our results indicate that arachidonic acid is yet another cellular second messenger involved in regulating the metabolism of APP in addition to PKC and cytoplasmic Ca++. Moreover, activation of PLA2 appears to be an obligatory event in increasing the secretion of APP from CHO‐ml cells by the various methods of activation that we have tried thus far.
Metabotropic Glutamate Receptors Regulate APP Processing in Hippocampal Neurons and Cortical Astrocytes Derived from Fetal Ratsa
Authors: LEE R. K. K. , JIMENEZ J. , COX A. J. , WURTMAN R. J.
Published: December 2006

It has previously been shown that stimulation of muscarinic m1 or m3 receptors can, by generating diacylglycerol (DAG) and activating protein kinase C (PKC), accelerate the breakdown of the amyloid precursor protein (APP) to form soluble, non‐amyloidogenic peptides (APPs). This relationship has been demonstrated in human glioma and neuroblastoma cells as well as in transfected human embryonic kidney (HEK) cells and PC12 cells.1,2

We now provide evidence that stimulation of metabotropic glutamate receptors (mGluRs), which also are coupled to DAG and PKC, similarly accelerates processing of APP into non‐amyloidogenic APPs in hippocampal neurons and cortical astrocytes derived from normal fetal rats. The mGluR antagonist, L(+)‐2‐amino‐3‐phosphonopropionic acid (L‐AP3), and GF 109203X, an inhibitor of PKC, both blocked the release of APPs from hippocampal neurons and astrocytes evoked by glutamate receptor stimulation. Inasmuch as glutamatergic neurons in cortex and hippocampus are known to be damaged in Alzheimer's disease, our findings suggest that amyloid formation may be enhanced by the resulting glutamate deficiency and that selective mGluR agonists may be useful in facilitating synaptic efficacy and treating the disease.
Nicotine‐induced Protection Against Glutamate Cytotoxicity
Authors: SHIMOHAMA S. , AKAIKE A. , KIMURA J.
Published: December 2006

Cortical neurodegeneration in Alzheimer's disease (AD) is suggested to be attributable not only to β‐protein but also to glutamate. Although degeneration of cholinergic projection to the cerebral cortex is recognized to be one of the most prominent pathological changes in AD, there is only limited information concerning the cholinergic interaction with the cortical neurodegeneration. This study was performed to examine the protective effect of nicotine against glutamate‐induced cytotoxicity using rat cultured cortical neurons. The cell viability was significantly reduced when cultures were briefly exposed to glutamate or N‐methyl‐d‐aspartate (NMDA). The simultaneous addition of nicotine did not reduce glutamate cytotoxicity. In contrast, the simultaneous application of NMDA receptor antagonists such as MK‐801 reduced glutamate cytotoxicity. Incubating the cultures with nicotine (10 μM) for 0.5‐24 h prior to glutamate exposure reduced its cytotoxicity. Neuroprotection by nicotine was dependent on both the concentration and incubation period. In contrast to nicotine, muscarine (10 μM) weakly potentiated glutamate cytotoxicity. The neuroprotective effect of nicotine against glutamate cytotoxicity was antagonized by hexamethonium but not by artopinc. Nicotine prevented NMDA cytotoxicity but did not affect cytotoxicity induced by either kainate or α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA). Cell viability was significantly reduced by a brief exposure of cultures to ionomycin, a calcium ionophore. Ionomycin‐induced cytotoxicity was abolished by removing Ca2+ from incubating medium. S‐nitrosocysteine (SNOC), which spontaneously releases nitric oxide (NO), also induced delayed cell death. Nicotine prevented ionomycin‐induced cytotoxicity without affecting SNOC‐induced cytotoxicity. These results suggest that nicotinic cholinergic receptor stimulation induces neuroprotection against glutamate cytotoxicity by its inhibitory action on NO‐formation. Therefore, we propose that acetylcholine, acting through nicotinic cholinergic receptors, can function as a putative neuroprotective factor against neurodegeneration caused by the excessive release of glutamate and/or NMDA receptor activation.
The Effect of Cholinesterase Inhibitors on the Secretion of APPS from Rat Brain Cortexa
Authors: GIACOBINI E. , MORI F. , LAI C‐C.
Published: December 2006

In this study we examined the question whether cholinesterase inhibitors (ChEI) could alter the release of amyloid precursor protein (APP) from superfused brain cortical slices of the rat following electrical as well as pharmacological stimulation with bethanechol (BETHA). Three ChEI, both reversible and irreversible were tested for their ability to enhance the release of non‐amyloidogenic soluble derivatives (APPs). These included physostigmine (PHY), heptyl‐physostigmine (HEP) and 2,2‐dichlorovinyldimethyl phosphate (DDVP), at the concentrations producing cholinesterase (ChE) inhibition ranging from 5% to 95%. All three ChEI elevated APPs release significantly above control levels. Electrical field stimulation significantly increased the release of APPs within 50 min. Similar increase was observed after muscarinic receptor stimulation with BETHA. Tetrodotoxin (TTX) completely blocked the effect of electrical stimulation. These findings suggest that long‐term administration of ChEI to Alzheimer's disease (AD) patients may have a neuroprotective effect by activating normal APP processing and decreasing the formation of amyloidogenic APP products.
HWA 285 (Propentofylline)—A New Compound for the Treatment of Both Vascular Dementia and Dementia of the Alzheimer Type
Authors: ROTHER M. , KITTNER B. , RUDOLPHI K. , RÖßNER M. , LABS K.‐H.
Published: December 2006

The pharmacological profile of HWA 285 favors its use in patients with both Alzheimer's disease (PDD) and/or vascular dementia (MID). Clinical trials showed clinically relevant, statistically significant efficacy in the domains of cognitive function, global function and activities of daily living (ADL) in both PDD and MID. HWA 285 had a prolonged symptomatic effect for at least 12 months, although therapeutic effects were seen already after the first 3 months of treatment. HWA 285 was very well tolerated for at least 1 year.
Mice Deficient for the Amyloid Precursor Protein Gene
Authors: ZHENG H. , JIANG M. , TRUMBAUER M. E. , HOPKINS R. , SIRINATHSINGHJI D. J. S. , STEVENS K. A. , CONNER M. W. , SLUNT H. H. , SISODIA S. S. , CHEN H. Y. , VAN DER PLOEG L. H. T.
Published: December 2006

To understand the in vivo function of the amyloid precursor protein (APP) we generated an APP null mutation in mice by homologous recombination in embryonic stem (ES) cells. We show here that homozygous APP deficient mice were produced at expected frequencies. Neither APP mRNA nor protein could be detected in these animals. Yet the homozygous APP mutant mice are fertile and do not show overt abnormalities at up to 12 weeks of age. Neuroanatomical studies of the brain did not reveal significant differences in the knockout mice as compared to the wild‐type controls. These results argue against an essential function of APP in mouse embryonic and early neuronal development.
The Jordan Curve‐type Theorems for the Funnel in 2‐dimensional Semiflows
Authors: CIESIELSKI KRZYSZTOF
Published: December 2006

We investigate “the past” of a nonstationary point x in a semiflow π: ℝ+ x M→M on a 2‐manifold M. In a natural way there are defined two boundary trajectories Ta and Tb; by the funnel we mean F(x) ={y:π(t, y) =x for some t} and we put D(x) ≈F(x)\(Ta∪Tb). We show that if x is not a point of negative unicity, then D(x) is homeomorphic to ℝ2. Also, if T is a nonboundary trajectory through x, then D(x)\T has two components for a regular point x and D(x)\T has two or three components for a periodic point x.
Iwasawa‐type Decomposition in Compact Groups
Authors: ITZKOWITZ GERALD , WU TA SUN
Published: December 2006

Iwasawa in his famous paper “On some types of topological groups,” proved a number of decomposition theorems for compact groups. Among them is the theorem stating that a compact connected group G can be written as G=Z(G) · [G, G], where Z(G) is the center of G and [G, G] is the commutator subgroup of G. Later authors have refined this result to the statement that G=Z(G)o· [G, G], where Z(G)o is the component of the identity of Z(G). In the present paper we show that these theorems may be further strenghthened to the following statement: Let G be a compact group and let N be a compact normal subgroup of G. If either G=A·N, where A is a compact connected Abelian group, or if G/N is connected, then G=ZG(N)o·N, where ZG(N)o is the component of the identity of the centralizer in G of N. The proof of this result has a number of interesting corollaries.
Intersection Properties of Open Sets. IIe
Authors: JUHÁSZ I. , NAGY ZS , SOUKUP L. , SZENTMIKLÓSSY Z.
Published: December 2006

A topological space is called P2 (P3, P<ω) if and only if it does not contain two (three, finitely many) uncountable open sets with empty intersection. We show that (i) there are 0‐dimensional P<ω spaces of size 2ω, (ii) there are compact P<ω spaces of size ω1, (iii) the existence of a Ψ‐like examples for (ii) is independent of ZFC, (iv) it is consistent that 2ω is as large as you wish but every first countable (and so every compact) P2 space has cardinality ≤ω1.
Free Topological Groups over (Semi) Group Actions
Authors: MEGRELISHVILI MICHAEL
Published: December 2006

We study equivariant embeddability into G‐groups. A new regionally proximal type relation introduced in the paper gives a necessary condition providing some counter‐examples. We establish also some sufficient conditions (for locally compact acting semigroups G, for instance) improving results of M.Eisenberg and J. de Vries.
On the Product of a Compact Space with an Absolutely Countably Compact Space
Authors: VAUGHAN JERRY E.
Published: December 2006

We show that the product of a compact sequential T2‐space, with an absolutely countably compact T3‐space, is absolutely countably compact, and give several related results. For example, we show that every countably compact GO‐space is absolutely countably compact, and that the product of a compact T2‐space of countable tightness with an absolutely countably compact, ω‐bounded T3‐space (in particular a countably compact GO‐space) is absolutely countably compact.
Involvement of Mitochondrial Gene Abnormalities in the Pathogenesis of Diabetes Mellitus
Authors: ODAWARA MASATO
Published: December 2006

SUMMARY
Another Possibility
Authors: Malabou Catherine
Published: December 2006

We try to explore here the Derridean concept of "possibility." Such a concept has no contraries. It does not oppose effectivity or necessity, or even impossibility, but stays what it is in any case: possible. Trying to negate it or to contradict it only leads to denial. To Derrida, this strange status of possibility is addressed as the question of faith as such, as it appears in "Faith and Knowledge." Every belief is always, at its foundation, belief in the possibility of a completely different history altogether, in what Derrida calls the "utterly other chance." Is deconstruction the legible form of this otherness?
The Events of Morality and Forgiveness: From Kant to Derrida
Authors: Lotz Christian
Published: December 2006

In this paper, I will perform a "step back" by showing how Derrida's analysis of forgiveness is rooted in Kantian moral philosophy and in Derrida's interpretation of Kierkegaard's concept of decision. This will require a discussion of the distinction that Kant draws in his Groundwork between price (the economic) and dignity (the incomparable), as well as a discussion of the underlying notion of singularity in Kant's text. In addition, Derrida universalizes Kierkegaard's concept of the agent so that, with this perspective in view, the interpretation of Kantian morality as something that must be described in a paradoxical way, becomes fully transparent. Whereas the interpretation of Kantian morality will provide us with a concept of morality that remains a "blind spot" for the agent, with the help of Derrida's Kierkegaard interpretation we can see that the concept of decision remains ultimately ambivalent. In conclusion, both (a) the deconstructed concept of morality and (b) the concept of decision will finally (c) let us understand Derrida's radical concept of forgiveness, which is both a non-economic act of morality in the sense explained and an unpredictable, uncontrollable decision and event.
Reading: Derrida in Hegel's Understanding
Authors: Russon John
Published: December 2006

Hegel's dialectic "Consciousness," Part A from the Phenomenology of Spirit, is interpreted in light of the concept of "reading." The logic of reading is especially helpful for interpreting the often misunderstood dialectic of understanding, as that is described in chapter 3 of the Phenomenology, "Force and Understanding: Appearance and the Supersensible World." Hegel's concept of "the Inverted World" in particular is clarified, and from it Hegel's notion of originary difference is developed. Derrida's notion of "differance" is used to illuminate Hegel's use of difference and to interpret the Hegelian metaphysics that is developed in "Force and Understanding" and in the opening moves of Hegel's Science of Logic. It is argued that the philosophical projects of Hegel and Derrida are ultimately indistinguishable.
Deconstruction and Translation: The Passage into Philosophy
Authors: Crépon Marc
Published: December 2006

In taking up the question of translation as its guiding thread, this essay considers the extent to which deconstruction consists in a radical calling into question of the type of thought and practice of translation implied in what Derrida has called "the passage into philosophy." At the same time, a whole other thought of translation—of the very kind that Derrida put into practice—is demanded insofar as something like the survival of works and the very possibility of a tradition are at stake.
Crimes of the Tongue: The Inquisitorial Trials of Cristóbal Duarte Ballester
Authors: Surtz Ronald E.
Published: December 2006

Cristóbal Duarte Ballester was tried twice by the Spanish Inquisition. To the principal accusation of blasphemy the prosecutor added Ballester's faulty observance of the basic precepts of Christianity: eating meat on days forbidden by the church, not confessing his sins, and not attending mass. The Inquisition assigned a moral value to what came out of Ballester's mouth—oaths—as well as to what entered it—certain foods at forbidden moments. The defendant's oral crimes of blasphemy and nonobservance of fasts were compounded by such suspicion-provoking verbal behaviors as Ballester's fluency in Arabic and his love of singing songs in that language.
Alejo de Venegas's Agonía del Tránsito de la Muerte: A Morisco Treatise on the Art of Dying?
Authors: Vázquez Miguel Ángel
Published: December 2006

The mostly clandestine nature of Morisco literature both in Spanish and Aljamiado has prompted critics to inquire to what extent and how it was influenced by the canonical literature of the Golden Age. Indeed, there are many interesting examples of how the literary trends of the times influenced the Moriscos. The question of whether Morisco literature influenced the more canonical tradition, on the other hand, is especially interesting if one considers a work such as Agonía del tránsito de la muerte (1537) by the Toledan Alejo de Venegas (1498/99-1562) as a Morisco text. Álvaro Galmés de Fuentes proposed just such a reading, but I argue that the evidence does not fully support his hypothesis, which must be revised along the lines I propose.
Mudejar: An Alternative Architectural System in the Castilian Urban Repopulation Model
Authors: Borrás Gualis Gonzalo M.
Published: December 2006

This essay takes the city of Toledo as an example of the adaptation of mudejar architecture to the repopulation efforts of conquered territories throughout Castile. Considering architectural developments from the twelfth to the sixteenth centuries, it explains the ways in which adaptation and innovation occurred in response to changes in population as well as the expansion of the Castilian state. The essay models a methodological alternative to the more traditional strategy of art history, which is to focus on regional aesthetic choices.