Cladribine and Fludarabine Nucleoside Change the Levels of CD Antigens on B-Lymphoproliferative Disorders

The purine analogs, fludarabine nucleoside (FdA), and cladribine (CdA) (1 μM, 24 hours), significantly changed the levels of some surface antigens on the human B-cell lines MEC2 and Raji. Changes in the surface proteins were identified using a Cluster of Differentiation (CD) antibody microarray that captures live cells and confirmed by flow cytometry. For Raji cells, CdA up-regulated CD10, CD54, CD80, and CD86, with repression of CD22, while FdA up-regulated CD20, CD54, CD80, CD86 and CD95. For MEC2 cells, CdA up-regulated CD11a, CD20, CD43, CD45, CD52, CD54, CD62L, CD80, CD86, and CD95, but FdA had no effect. Up-regulation of particular CD antigens induced on a B-cell lymphoproliferative disorder by a purine analog could provide targets for therapeutic antibodies with synergistic cell killing

Classical electromagnetic field theory in the presence of magnetic sources

Using two new well defined 4-dimensional potential vectors, we formulate the classical Maxwell's field theory in a form which has manifest Lorentz covariance and SO(2) duality symmetry in the presence of magnetic sources. We set up a consistent Lagrangian for the theory. Then from the action principle we get both Maxwell's equation and the equation of motion of a dyon moving in the electro-magnetic field.Comment: 10 pages, no figure

Height-diameter models for maritime pine in Portugal: a comparison of basic, generalized and mixed-effects models

Tree height is a key variable in forest monitoring studies and for forest management. However, tree height measurement is time consuming, and the recommended procedure is to use estimates from height-diameter models. Here, we compare height-diameter model forms and approaches for predicting tree height (h) as a function of tree diameter at breast height (d) and additional stand level covariates. Four model forms were evaluated: (i) basic models (which only used d as predictor variable); (ii) generalized models (which used d and stand-level predictor variables); (iii) a mixed-effects model based on the best basic model; and (iv) a mixed-effects model based on the best generalized model. Several alternatives aimed at minimizing height measurement effort were tested in terms of accuracy and applicability. From a practical point of view, the selected generalized model is recommended for estimating the height of maritime pine in Portugal. The results also show that a calibrated basic mixed model provides more accurate results than a basic model locally fitted when the number of h-d observations is limited.S

XRCC2 R188H (rs3218536), XRCC3 T241M (rs861539) and R243H (rs77381814) single nucleotide polymorphisms in cervical cancer risk

Human Papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesions. Transformation may be induced by several mechanisms, including oncogene activation and genome instability. Individual differences in DNA damage recognition and repair have been hypothesized to influence cervical cancer risk. The aim of this study was to evaluate whether the double strand break gene polymorphisms XRCC2 R188H G>A (rs3218536), XRCC3 T241M C>T (rs861539) and R243H G>A (rs77381814) are associated to cervical cancer in Argentine women. A case control study consisting of 322 samples (205 cases and 117 controls) was carried out. HPV DNA detection was performed by PCR and genotyping of positive samples by EIA (enzyme immunoassay). XRCC2 and 3 polymorphisms were determined by pyrosequencing. The HPV-adjusted odds ratio (OR) of XRCC2 188 GG/AG genotypes was OR = 2.4 (CI = 1.1-4.9, p = 0.02) for cervical cancer. In contrast, there was no increased risk for cervical cancer with XRCC3 241 TT/CC genotypes (OR = 0.48; CI = 0.2-1; p = 0.1) or XRCC3 241 CT/CC (OR = 0.87; CI = 0.52-1.4; p = 0.6). Regarding XRCC3 R243H, the G allele was almost fixed in the population studied. In conclusion, although the sample size was modest, the present data indicate a statistical association between cervical cancer and XRCC2 R188H polymorphism. Future studies are needed to confirm these findings.Fil: Perez, Luis Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Crivaro, Andrea Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Barbisan, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Poleri, Lucía Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Golijow, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentin

Time Variation of the Fine Structure Constant Driven by Quintessence

There are indications from the study of quasar absorption spectra that the fine structure constant $\alpha$ may have been measurably smaller for redshifts $z>2.$ Analyses of other data ($^{149}$Sm fission rate for the Oklo natural reactor, variation of $^{187}$Re $\beta$-decay rate in meteorite studies, atomic clock measurements) which probe variations of $\alpha$ in the more recent past imply much smaller deviations from its present value. In this work we tie the variation of $\alpha$ to the evolution of the quintessence field proposed by Albrecht and Skordis, and show that agreement with all these data, as well as consistency with WMAP observations, can be achieved for a range of parameters. Some definite predictions follow for upcoming space missions searching for violations of the equivalence principle.Comment: Final version, to be published in Phys Rev

Renormalization of the Inverse Square Potential

The quantum-mechanical D-dimensional inverse square potential is analyzed using field-theoretic renormalization techniques. A solution is presented for both the bound-state and scattering sectors of the theory using cutoff and dimensional regularization. In the renormalized version of the theory, there is a strong-coupling regime where quantum-mechanical breaking of scale symmetry takes place through dimensional transmutation, with the creation of a single bound state and of an energy-dependent s-wave scattering matrix element.Comment: 5 page

Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology1,2. The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tumorigenesis and drug resistance3-7. Furthermore, PSC activation occurs very early during PDAC tumorigenesis8-10, and activated PSCs comprise a substantial fraction of the tumour mass, providing a rich source of readily detectable factors. Therefore, we hypothesized that the communication between PSCs and PCCs could be an exploitable target to develop effective strategies for PDAC therapy and diagnosis. Here, starting with a systematic proteomic investigation of secreted disease mediators and underlying molecular mechanisms, we reveal that leukaemia inhibitory factor (LIF) is a key paracrine factor from activated PSCs acting on cancer cells. Both pharmacologic LIF blockade and genetic Lifr deletion markedly slow tumour progression and augment the efficacy of chemotherapy to prolong survival of PDAC mouse models, mainly by modulating cancer cell differentiation and epithelial-mesenchymal transition status. Moreover, in both mouse models and human PDAC, aberrant production of LIF in the pancreas is restricted to pathological conditions and correlates with PDAC pathogenesis, and changes in the levels of circulating LIF correlate well with tumour response to therapy. Collectively, these findings reveal a function of LIF in PDAC tumorigenesis, and suggest its translational potential as an attractive therapeutic target and circulating marker. Our studies underscore how a better understanding of cell-cell communication within the tumour microenvironment can suggest novel strategies for cancer therapy

Contribution of common and rare variants to bipolar disorder susceptibility in extended pedigrees from population isolates.

Current evidence from case/control studies indicates that genetic risk for psychiatric disorders derives primarily from numerous common variants, each with a small phenotypic impact. The literature describing apparent segregation of bipolar disorder (BP) in numerous multigenerational pedigrees suggests that, in such families, large-effect inherited variants might play a greater role. To identify roles of rare and common variants on BP, we conducted genetic analyses in 26 Colombia and Costa Rica pedigrees ascertained for bipolar disorder 1 (BP1), the most severe and heritable form of BP. In these pedigrees, we performed microarray SNP genotyping of 838 individuals and high-coverage whole-genome sequencing of 449 individuals. We compared polygenic risk scores (PRS), estimated using the latest BP1 genome-wide association study (GWAS) summary statistics, between BP1 individuals and related controls. We also evaluated whether BP1 individuals had a higher burden of rare deleterious single-nucleotide variants (SNVs) and rare copy number variants (CNVs) in a set of genes related to BP1. We found that compared with unaffected relatives, BP1 individuals had higher PRS estimated from BP1 GWAS statistics (P = 0.001 ~ 0.007) and displayed modest increase in burdens of rare deleterious SNVs (P = 0.047) and rare CNVs (P = 0.002 ~ 0.033) in genes related to BP1. We did not observe rare variants segregating in the pedigrees. These results suggest that small-to-moderate effect rare and common variants are more likely to contribute to BP1 risk in these extended pedigrees than a few large-effect rare variants

Renormalized Path Integral for the Two-Dimensional Delta-Function Interaction

A path-integral approach for delta-function potentials is presented. Particular attention is paid to the two-dimensional case, which illustrates the realization of a quantum anomaly for a scale invariant problem in quantum mechanics. Our treatment is based on an infinite summation of perturbation theory that captures the nonperturbative nature of the delta-function bound state. The well-known singular character of the two-dimensional delta-function potential is dealt with by considering the renormalized path integral resulting from a variety of schemes: dimensional, momentum-cutoff, and real-space regularization. Moreover, compatibility of the bound-state and scattering sectors is shown.Comment: 26 pages. The paper was significantly expanded and numerous equations were added for the sake of clarity; the main results and conclusions are unchange