Frobenius Splittings

We give a gentle introduction to Frobenius splittings. Then we recall a few results that have been obtained with the method.Comment: 21 pages, typos correcte

Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation.

Ligation of the cell-surface Fas molecule by its ligand (Fas-L) or agonistic anti-Fas monoclonal antibodies results in the cleavage and activation of the cysteine protease procaspase 8 followed by the activation of procaspase 3 and by apoptosis. In some leukemia cell lines, cytotoxic drugs induce expression of Fas-L, which may contribute to cell killing through the ligation of Fas. The involvement of Fas, Fas-L, and caspase 8 was studied in the killing of B-cell chronic lymphocytic leukemia (B-CLL) cells by chlorambucil, fludarabine, or gamma radiation. Spontaneous apoptosis was observed at 24-hour incubation, with additional apoptosis induced by each of the cytotoxic treatments. Although Fas mRNA expression was elevated after exposure to chlorambucil, fludarabine, or gamma radiation, Fas protein levels only increased after irradiation. Therefore, Fas expression may be regulated by multiple mechanisms that allow the translation of Fas mRNA only in response to restricted cytotoxic stimuli. None of the cytotoxic stimuli studied here induced Fas-L expression. An agonistic anti-Fas monoclonal antibody (CH-11) did not significantly augment apoptosis induction by any of the death stimuli. A Fas-blocking antibody (ZB4) did not inhibit spontaneous, chlorambucil-, fludarabine-, or radiation-induced apoptosis. However, procaspase 8 processing was induced by all cytotoxic stimuli. These data suggest that the Fas/Fas-L signaling system does not play a major role in the induction of apoptosis in B-CLL cells treated with cytotoxic drugs or radiation. However, Fas-independent activation of caspase 8 may play a crucial role in the regulation of apoptosis in these cells

Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs.

We studied the actions of geldanamycin (GA) and herbimycin A (HMA), inhibitors of the chaperone proteins Hsp90 and GRP94, on B chronic lymphocytic leukemia (CLL) cells in vitro. Both drugs induced apoptosis of the majority of CLL isolates studied. Whereas exposure to 4-hour pulses of 30 to 100 nM GA killed normal B lymphocytes and CLL cells with similar dose responses, T lymphocytes from healthy donors as well as those present in the CLL isolates were relatively resistant. GA, but not HMA, showed a modest cytoprotective effect toward CD34+ hematopoietic progenitors from normal bone marrow. The ability of bone marrow progenitors to form hematopoietic colonies was unaffected by pulse exposures to GA. Both GA and HMA synergized with chlorambucil and fludarabine in killing a subset of CLL isolates. GA- and HMA-induced apoptosis was preceded by the up-regulation of the stress-responsive chaperones Hsp70 and BiP. Both ansamycins also resulted in down-regulation of Akt protein kinase, a modulator of cell survival. The relative resistance of T lymphocytes and of CD34+ bone marrow progenitors to GA coupled with its ability to induce apoptosis following brief exposures and to synergize with cytotoxic drugs warrant further investigation of ansamycins as potential therapeutic agents in CLL

Random Matrix Theory for the Hermitian Wilson Dirac Operator and the chGUE-GUE Transition

We introduce a random two-matrix model interpolating between a chiral Hermitian (2n+nu)x(2n+nu) matrix and a second Hermitian matrix without symmetries. These are taken from the chiral Gaussian Unitary Ensemble (chGUE) and Gaussian Unitary Ensemble (GUE), respectively. In the microscopic large-n limit in the vicinity of the chGUE (which we denote by weakly non-chiral limit) this theory is in one to one correspondence to the partition function of Wilson chiral perturbation theory in the epsilon regime, such as the related two matrix-model previously introduced in refs. [20,21]. For a generic number of flavours and rectangular block matrices in the chGUE part we derive an eigenvalue representation for the partition function displaying a Pfaffian structure. In the quenched case with nu=0,1 we derive all spectral correlations functions in our model for finite-n, given in terms of skew-orthogonal polynomials. The latter are expressed as Gaussian integrals over standard Laguerre polynomials. In the weakly non-chiral microscopic limit this yields all corresponding quenched eigenvalue correlation functions of the Hermitian Wilson operator.Comment: 27 pages, 4 figures; v2 typos corrected, published versio

The ordinary city trap

The paper is a critique of a critique, it explains why the most salient and influential critiques of the neo-Marxist world city and global city concepts, made by those arguing to further postcolonialize urban studies through such suppositions that all cities are ‘ordinary’, are misguided. First, it is explained how the charges of economism and ethnocentrism against the world city and global city concepts are ignoratio elenchi: they do not even begin to address or critique their neo-Marxist argument that, across the difference and diversity of the world’s cities, a few major cities have the necessary economic specialization and therefore extraordinary function of commanding and controlling neoliberal globalization. Second, the error made by advocates of ordinary cities of supposing that world-systems analysis and the world city concept are forms of developmentalism is understood as the source for a wider postcolonial mistake of conflating the neo-Marxist world city and global city literatures with the very neoliberal practices toward urban development that they have long attempted to disclose and counter. Finally, the charges against the world city and global city concepts as paradigmatic, peripheralizing, and normative are also rebutted, not only to highlight how those critiques are consequentialist and dependent on the respective charges of economism, ethnocentrism, and developmentalism having veracity, but to demonstrate how an acceptance of the ordinary cities argument for an idiographic, provincial, nominalist, and comparative approach to urban studies, as an alternative to the two neo-Marxist concepts, is only to fall into the trap of making the mistake of confusing evidence of absence for absence of evidence

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans

Methylphenidate significantly improves declarative memory functioning of adults with ADHD

Contains fulltext : 87790.pdf (publisher's version ) (Closed access)BACKGROUND: Declarative memory deficits are common in untreated adults with attention-deficit hyperactivity disorder (ADHD), but limited evidence exists to support improvement after treatment with methylphenidate. The objective of this study was to examine the effects of methylphenidate on memory functioning of adults with ADHD. METHODS: Eighteen adults with ADHD who were clinical responders to methylphenidate participated in this randomized crossover trial. After 3 days of no treatment, patients received in random order either their usual methylphenidate dose (mean: 14.7 mg; range: 10-30 mg) or placebo, separated by a 6-7-day washout period. Patients performed an immediate word recall test 1 h after treatment administration. Three hours after intake, patients performed the second part of the memory test (delayed word recall and a recognition test). RESULTS: Delayed recognition and immediate recall was similar on treatment and on placebo. Delayed word recall was significantly better in the methylphenidate than in the placebo condition (F (1, 17) = 7.0, p < 0.017). A significant correlation was found between prestudy CES-D depression scores and difference scores on delayed recall (r = 0.602, p < 0.008). CONCLUSION: Methylphenidate improves declarative memory functioning in patients with ADHD. New studies should further examine whether subclinical depressive symptoms mediate the effect of methylphenidate on declarative memory.1 oktober 201