The intersection between DNA damage response and cell death pathways

Apoptosis is a finely regulated process that serves to determine the fate of cells in response to various stresses. One such stress is DNA damage, which not only can signal repair processes but is also intimately involved in regulating cell fate. In this review we examine the relationship between the DNA damage/repair response in cell survival and apoptosis following insults to the DNA. Elucidating these pathways and the crosstalk between them is of great importance, as they eventually contribute to the etiology of human disease such as cancer and may play key roles in determining therapeutic response. This article is part of a Special Issue entitled “Apoptosis: Four Decades Later”

Body site colonization in patients with community-associated methicillin-resistant Staphylococcus aureus and other types of S. aureus skin infections

AbstractEfforts to control spread of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are often based on eradication of colonization. However, the role of nasal and non-nasal colonization in the pathogenesis of these infections remains poorly understood. Patients with acute S. aureus skin and soft tissue infection (SSTI) were prospectively enrolled. Each subject's nasal, axillary, inguinal and rectal areas were swabbed for S. aureus and epidemiological risk factors were surveyed. Among the 117 patients enrolled, there were 99 patients who had an SSTI and for whom data could be analysed. Sixty-five patients had a CA-MRSA SSTI. Among these patients, MRSA colonization in the nares, axilla, inguinal area and rectum was 25, 6, 11 and 13%, respectively, and 37% overall were MRSA colonized. Most (96%) MRSA colonization was detected using nose and inguinal screening alone. Non-nasal colonization was 25% among CA-MRSA patients, but only 6% among patients with CA-methicillin-susceptible S. aureus (MSSA) or healthcare-associated MRSA or MSSA. These findings suggest that colonization patterns in CA-MRSA infection are distinct from those in non-CA-MRSA S. aureus infections. The relatively high prevalence of non-nasal colonization may play a key role in CA-MRSA transmission and acquisition of infection

Array comparative genomic hybridization screening in IVF significantly reduces number of embryos available for cryopreservation

Objective During IVF, non-transferred embryos are usually selected for cryopreservation on the basis of morphological criteria. This investigation evaluated an application for array comparative genomic hybridization (aCGH) in assessment of surplus embryos prior to cryopreservation. Methods First-time IVF patients undergoing elective single embryo transfer and having at least one extra non-transferred embryo suitable for cryopreservation were offered enrollment in the study. Patients were randomized into two groups: Patients in group A (n=55) had embryos assessed first by morphology and then by aCGH, performed on cells obtained from trophectoderm biopsy on post-fertilization day 5. Only euploid embryos were designated for cryopreservation. Patients in group B (n=48) had embryos assessed by morphology alone, with only good morphology embryos considered suitable for cryopreservation. Results Among biopsied embryos in group A (n=425), euploidy was confirmed in 226 (53.1%). After fresh single embryo transfer, 64 (28.3%) surplus euploid embryos were cryopreserved for 51 patients (92.7%). In group B, 389 good morphology blastocysts were identified and a single top quality blastocyst was selected for fresh transfer. All group B patients (48/48) had at least one blastocyst remaining for cryopreservation. A total of 157 (40.4%) blastocysts were frozen in this group, a significantly larger proportion than was cryopreserved in group A (p=0.017, by chi-squared analysis). Conclusion While aCGH and subsequent frozen embryo transfer are currently used to screen embryos, this is the first investigation to quantify the impact of aCGH specifically on embryo cryopreservation. Incorporation of aCGH screening significantly reduced the total number of cryopreserved blastocysts compared to when suitability for freezing was determined by morphology only. IVF patients should be counseled that the benefits of aCGH screening will likely come at the cost of sharply limiting the number of surplus embryos available for cryopreservation

Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study

Background Single embryo transfer (SET) remains underutilized as a strategy to reduce multiple gestation risk in IVF, and its overall lower pregnancy rate underscores the need for improved techniques to select one embryo for fresh transfer. This study explored use of comprehensive chromosomal screening by array CGH (aCGH) to provide this advantage and improve pregnancy rate from SET. Methods First-time IVF patients with a good prognosis (age <35, no prior miscarriage) and normal karyotype seeking elective SET were prospectively randomized into two groups: In Group A, embryos were selected on the basis of morphology and comprehensive chromosomal screening via aCGH (from d5 trophectoderm biopsy) while Group B embryos were assessed by morphology only. All patients had a single fresh blastocyst transferred on d6. Laboratory parameters and clinical pregnancy rates were compared between the two groups. Results For patients in Group A (n=55), 425 blastocysts were biopsied and analyzed via aCGH (7.7 blastocysts/patient). Aneuploidy was detected in 191/425 (44.9%) of blastocysts in this group. For patients in Group B (n=48), 389 blastocysts were microscopically examined (8.1 blastocysts/patient). Clinical pregnancy rate was significantly higher in the morphology+aCGH group compared to the morphology-only group (70.9 and 45.8%, respectively; p=0.017); ongoing pregnancy rate for Groups A and B were 69.1 vs. 41.7%, respectively (p=0.009). There were no twin pregnancies. Conclusion Although aCGH followed by frozen embryo transfer has been used to screen at risk embryos (e.g., known parental chromosomal translocation or history of recurrent pregnancy loss), this is the first description of aCGH fully integrated with a clinical IVF program to select single blastocysts for fresh SET in good prognosis patients. The observed aneuploidy rate (44.9%) among biopsied blastocysts highlights the inherent imprecision of SET when conventional morphology is used alone. Embryos randomized to the aCGH group implanted with greater efficiency, resulted in clinical pregnancy more often, and yielded a lower miscarriage rate than those selected without aCGH. Additional studies are needed to verify our pilot data and confirm a role for on-site, rapid aCGH for IVF patients contemplating fresh SET

Proton tracking in a high-granularity Digital Tracking Calorimeter for proton CT purposes

Radiation therapy with protons as of today utilizes information from x-ray CT in order to estimate the proton stopping power of the traversed tissue in a patient. The conversion from x-ray attenuation to proton stopping power in tissue introduces range uncertainties of the order of 2-3% of the range, uncertainties that are contributing to an increase of the necessary planning margins added to the target volume in a patient. Imaging methods and modalities, such as Dual Energy CT and proton CT, have come into consideration in the pursuit of obtaining an as good as possible estimate of the proton stopping power. In this study, a Digital Tracking Calorimeter is benchmarked for proof-of-concept for proton CT purposes. The Digital Tracking Calorimeteris applied for reconstruction of the tracks and energies of individual high energy protons. The presented prototype forms the basis for a proton CT system using a single technology for tracking and calorimetry. This advantage simplifies the setup and reduces the cost of a proton CT system assembly, and it is a unique feature of the Digital Tracking Calorimeter. Data from the AGORFIRM beamline at KVI-CART in Groningen in the Netherlands and Monte Carlo simulation results are used to in order to develop a tracking algorithm for the estimation of the residual ranges of a high number of concurrent proton tracks. The range of the individual protons can at present be estimated with a resolution of 4%. The readout system for this prototype is able to handle an effective proton frequency of 1 MHz by using 500 concurrent proton tracks in each readout frame, which is at the high end range of present similar prototypes. A future further optimized prototype will enable a high-speed and more accurate determination of the ranges of individual protons in a therapeutic beam.Comment: 21 pages, 8 figure

Deformed Oscillator Algebras and Higher-Spin Gauge Interactions of Matter Fields in 2+1 Dimensions

We formulate a non-linear system of equations which describe higher-spin gauge interactions of massive matter fields in 2+1 dimensional space-time and explain some properties of the deformed oscillator algebra which underlies this formulation. In particular we show that the parameter of mass $M$ of matter fields is related to the deformation parameter in this algebra.Comment: LaTex, 12 pages, no figures; Invited talk at the International Seminar Supersymmetry and Quantum Field Theory dedicated to the memory of Dmitrij V. Volkov; Kharkov, January 1997; to appear in the proceeding

Hard-Loop Effective Action for Anisotropic Plasmas

We generalize the hard-thermal-loop effective action of the equilibrium quark-gluon plasma to a non-equilibrium system which is space-time homogeneous but for which the parton momentum distribution is anisotropic. We show that the manifestly gauge-invariant Braaten-Pisarski form of the effective action can be straightforwardly generalized and we verify that it then generates all n-point functions following from collisionless gauge-covariant transport theory for a homogeneous anisotropic plasma. On the other hand, the Taylor-Wong form of the hard-thermal-loop effective action has a more complicated generalization to the anisotropic case. Already in the simplest case of anisotropic distribution functions, it involves an additional term that is gauge invariant by itself, but nontrivial also in the static limit.Comment: 12 pages. Version 3: typo in (15) corrected, note added discussing metric conventions use

Neutron beam test of CsI crystal for dark matter search

We have studied the response of Tl-doped and Na-doped CsI crystals to nuclear recoils and $\gamma$'s below 10 keV. The response of CsI crystals to nuclear recoil was studied with mono-energetic neutrons produced by the $^3$H(p,n)$^3$He reaction. This was compared to the response to Compton electrons scattered by 662 keV $\gamma$-ray. Pulse shape discrimination between the response to these $\gamma$'s and nuclear recoils was studied, and quality factors were estimated. The quenching factors for nuclear recoils were derived for both CsI(Na) and CsI(Tl) crystals.Comment: 21pages, 14figures, submitted to NIM

Charmonium states in QCD-inspired quark potential model using Gaussian expansion method

We investigate the mass spectrum and electromagnetic processes of charmonium system with the nonperturbative treatment for the spin-dependent potentials, comparing the pure scalar and scalar-vector mixing linear confining potentials. It is revealed that the scalar-vector mixing confinement would be important for reproducing the mass spectrum and decay widths, and therein the vector component is predicted to be around 22%. With the state wave functions obtained via the full-potential Hamiltonian, the long-standing discrepancy in M1 radiative transitions of $J/\psi$ and $\psi^{\prime}$ are alleviated spontaneously. This work also intends to provide an inspection and suggestion for the possible $c\bar{c}$ among the copious higher charmonium-like states. Particularly, the newly observed X(4160) and X(4350) are found in the charmonium family mass spectrum as $M(2^1D_2)= 4164.9$ MeV and $M(3^3P_2)= 4352.4$ MeV, which strongly favor the $J^{PC}=2^{-+}, 2^{++}$ assignments respectively. The corresponding radiative transitions, leptonic and two-photon decay widths have been also predicted theoretically for the further experimental search.Comment: 16 pages,3 figure

Green manure in coffee systems in the region of Zona da Mata, Minas Gerais: characteristics and kinetics of carbon and nitrogen mineralization.

The use of green manure may contribute to reduce soil erosion and increase the soil organic matter content and N availability in coffee plantations in the Zona da Mata, State of Minas Gerais, in Southeastern Brazil. The potential of four legumes (A. pintoi, C. mucunoides, S. aterrimum and S. guianensis)to produce above-ground biomass, accumulate nutrients and mineralize N was studied in two coffee plantations of subsistence farmers under different climate conditions. The biomass production of C. mucunoides was influenced by the shade of the coffee plantation.C. mucunoides tended to mineralize more N than the other legumes due to the low polyphenol content and polyphenol/N ratio. In the first year, the crop establishment of A. pintoi in the area took longer than of the other legumes, resulting in lower biomass production and N2 fixation. In the long term, cellulose was the main factor controlling N mineralization. The biochemical characteristics, nutrient accumulation and biomass production of the legumes were greatly influenced by the altitude and position of the area relative to the sun