Galaxy Orientations in the Coma Cluster

We have examined the orientations of early-type galaxies in the Coma cluster to see whether the well-established tendency for brightest cluster galaxies to share the same major axis orientation as their host cluster also extends to the rest of the galaxy population. We find no evidence of any preferential orientations of galaxies within Coma or its surroundings. The implications of this result for theories of the formation of clusters and galaxies (particularly the first-ranked members) are discussed.Comment: Accepted for publication in the Astrophysical Journal Letters. 4 pages, 4 figure

Osteoporosis in Celiac Disease: An Update

Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms such as diarrhea, bloating, or chronic abdominal pain, CD may also present a wide spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. This review aims to describe the role of CD in the development of skeletal alterations, underlying important clinical aspects and therapeutic implications. The etiopathology of bone lesions in CD is multifactorial and their management is challenging. Here, we provide gastroenterologists and orthopedics with an up-to-date overview on the link between CD and osteoporosis to improve the management of the CD condition

HIV/AIDS In Puerto Rican People Who Inject Drugs: Policy Considerations

We commend the important work of Deren et al. that underscores the high rates of HIV among Puerto Rican people who inject drugs (PRPWID) and highlights the health, social, and service disparities between Puerto Rico and the Northeast US region. As articulated in their article, HIV/AIDS risk and substance use are not individual problems with individual consequences—the epidemic impacts community and culture, across borders and boundaries. In addition to service disparities, various socioeconomic contextual factors are associated with and may exacerbate the spread of HIV/AIDS in PRPWID, including limited educational and employment opportunities, poverty, and political disenfranchisement. Efforts to reduce the incidence of HIV/AIDS and associated health risks and complications, including other infections, drug overdose, and social stigma, necessitate structural policy intervention in addition to programmatic improvements. Moreover, policy implementation that attends to contextual factors such as incarceration and impediments to culturally appropriate services is needed. We identify two contexts that represent opportunities for improvements in policy implementation that may curb the HIV/AIDS epidemic among PRPWID

EVALUATION OF A MICROIMMUNODIFUSION ASSAY FOR THE DIAGNOSIS OF ENZOOTIC BOVINE LEUKOSIS

O presente trabalho foi realizado com o objetivo de avaliar uma micro-IDGA usando protocolo simples para obtenção do antígeno comparativamente a uma macro-IDGA. Foram utilizadas 450 amostras de soro bovino provenientes de 92 rebanhos de 23 municípios que compõem a bacia leiteira do estado do Maranhão. O antígeno usado na micro-IDGA foi obtido por diálise frente ao polietilenoglicol de sobrenadante de células FLK infectadas pelo VLEB. Na micro-IDGA utilizou-se 10µL de antígeno e soro controle positivo e 30 µl do soro teste; na macro-IDGA 25 µl de todos os reagentes. Dos soros comparados, 57.56% (n=259) e 54.44% (n=245) apresentaram animais reagentes na micro-IDGA e macro-IDGA, respectivamente. Houve ótima concordância entre as duas técnicas (K=0,91), com sensibilidade e especificidade da macro-IDGA em relação à micro-IDGA de 93.43% e 98.43%, respectivamente. A micro-IDGA apresentou linhas mais claras que as observadas na macro-IDGA e a leitura pode ser feita 24 horas antes da macro-IDGA. Conclui-se que a micro-IDGA pode substituir à macro-IDGA no diagnóstico sorológico da LEB, com a vantagem de maior rapidez na emissão dos resultados e da obtenção do antígeno com técnica simples.  This work was developed to evaluate how a micro-AGID using simple protocol for obtaining the antigen compared to a macro-AGID. A total of 450 serum samples from 92 herds in 23 counties that make up the dairy herd of Maranhão were used. The antigen used in micro-AGID was obtained by desalting of supernatant of FLK cells infected with BLV against the polyethylenoglicol. In micro-AGID 10µL of antigen and positive serum control was used and 30 µl of test serum, in the macro-AGID 25 µl of all reagents were used. Of the compared sera, 57.56% (n=259) and 54.44% (n=245) showed positive animals reagents results in micro-AGID and macro-AGID, respectively. There was a very good agreement between both techniques (K=0.91), with sensitivity and specificity of the macro-AGID for micro-AGID of 93.43% and 98.43% with an accuracy of 95.96%. Micro-AGID showed clearer lines than those observed in the macro-AGID and reading can be made 24 hours before the macro-AGID. It is concluded that micro-AGID can be used successfully in the serological diagnosis of EBL, with the advantage of greater speed in issuing the results and obtaining the antigen with a simple technique

A Classic Type 2 QSO

In the Chandra Deep Field South 1Msec exposure we have found, at redshift 3.700 +- 0.005, the most distant Type 2 AGN ever detected. It is the source with the hardest X-ray spectrum with redshift z>3. The optical spectrum has no detected continuum emission to a 3sigma detection limit of ~3 10^{-19} ergs/s/cm^2/AA and shows narrow lines of Ly_alpha, CIV, NV, HeII, OVI, [OIII], and CIII]. Their FWHM line widths have a range of ~700-2300 km/s with an average of approximately ~1500 km/s. The emitting gas is metal rich (Z ~2.5-3 Z_solar). In the X-ray spectrum of 130 counts in the 0.5-7 keV band there is evidence for intrinsic absorption with N_H > 10^{24} cm^{-2}. An iron K_alpha line with rest frame energy and equivalent width of ~6.4 keV and ~1 keV, respectively, in agreement with the obscuration scenario, is detected at a 2sigma level. If confirmed by our forthcoming XMM observations this would be the highest redshift detection of FeK_alpha. Depending on the assumed cosmology and the X-ray transfer model, the 2-10 keV rest frame luminosity corrected for absorption is ~10^{45 +- 0.5} ergs/s, which makes our source a classic example of the long sought Type 2 QSOs. From standard population synthesis models, these sources are expected to account for a relevant fraction of the black-hole-powered QSO distribution at high redshift.Comment: 24 LaTeX pages including 6 postscript figures. Revised version, accepted by Ap

Modulation of LISA free-fall orbits due to the Earth-Moon system

We calculate the effect of the Earth-Moon (EM) system on the free-fall motion of LISA test masses. We show that the periodic gravitational pulling of the EM system induces a resonance with fundamental frequency 1 yr^-1 and a series of periodic perturbations with frequencies equal to integer harmonics of the synodic month (9.92 10^-7 Hz). We then evaluate the effects of these perturbations (up to the 6th harmonics) on the relative motions between each test masses couple, finding that they range between 3mm and 10pm for the 2nd and 6th harmonic, respectively. If we take the LISA sensitivity curve, as extrapolated down to 10^-6 Hz, we obtain that a few harmonics of the EM system can be detected in the Doppler data collected by the LISA space mission. This suggests that the EM system gravitational near field could provide an absolute calibration for the LISA sensitivity at very low frequencies.Comment: 15 pages, 5 figure

An Engineered IFNγ-Antibody Fusion Protein with Improved Tumor-Homing Properties

Interferon-gamma (IFNγ) is one of the central cytokines produced by the innate and adaptive immune systems. IFNγ directly favors tumor growth control by enhancing the immunogenicity of tumor cells, induces IP-10 secretion facilitating (CXCR3+) immune cell infiltration, and can prime macrophages to an M1-like phenotype inducing proinflammatory cytokine release. We had previously reported that the targeted delivery of IFNγ to neoplastic lesions may be limited by the trapping of IFNγ-based products by cognate receptors found in different organs. Here we describe a novel fusion protein consisting of the L19 antibody, specific to the alternatively spliced extra-domain B of fibronectin (EDB), fused to a variant of IFNγ with reduced affinity to its cognate receptor. The product (named L19-IFNγ KRG) selectively localized to tumors in mice, showed favorable pharmacokinetic profiles in monkeys and regained biological activity upon antigen binding. The fusion protein was investigated in two murine models of cancer, both as monotherapy and in combination with therapeutic modalities which are frequently used for cancer therapy. L19-IFNγ KRG induced tumor growth retardation and increased the intratumoral concentration of T cells and NK cells in combination with anti-PD-1

A combined microRNA-based targeted therapeutic approach to eradicate glioblastoma stem-like cells

A minor population of glioblastoma stem-like cells (GSCs) has been implicated in the relapse and resistance of glioblastoma to therapeutic treatments. Based on knowledge of the involvement of multiple microRNAs in GSC propagation, we designed a combinational approach to target the GSC population with multiple miRNA-based therapeutics. As carriers for the targeted delivery we took advantage of two aptamers that bind to, and inhibit, the receptor tyrosine kinases, Axl and PDGFRβ. We showed that the aptamer conjugates are transported through an in vitro blood-brain barrier (BBB) model. Furthermore, combining miR-137 and antimiR-10b synergizes with the receptor inhibitory function of aptamer carriers and prevents GSC expansion. Results highlighted the potential of combining multifunctional RNA-based therapeutics for selective targeting of GSCs and offer a proof of principle strategy to potentially fulfill the still unmet need for effective and safe treatment of glioma

Application of nnU-Net for Automatic Segmentation of Lung Lesions on CT Images and Its Implication for Radiomic Models.

Radiomics investigates the predictive role of quantitative parameters calculated from radiological images. In oncology, tumour segmentation constitutes a crucial step of the radiomic workflow. Manual segmentation is time-consuming and prone to inter-observer variability. In this study, a state-of-the-art deep-learning network for automatic segmentation (nnU-Net) was applied to computed tomography images of lung tumour patients, and its impact on the performance of survival radiomic models was assessed. In total, 899 patients were included, from two proprietary and one public datasets. Different network architectures (2D, 3D) were trained and tested on different combinations of the datasets. Automatic segmentations were compared to reference manual segmentations performed by physicians using the DICE similarity coefficient. Subsequently, the accuracy of radiomic models for survival classification based on either manual or automatic segmentations were compared, considering both hand-crafted and deep-learning features. The best agreement between automatic and manual contours (DICE = 0.78 ± 0.12) was achieved averaging 2D and 3D predictions and applying customised post-processing. The accuracy of the survival classifier (ranging between 0.65 and 0.78) was not statistically different when using manual versus automatic contours, both with hand-crafted and deep features. These results support the promising role nnU-Net can play in automatic segmentation, accelerating the radiomic workflow without impairing the models' accuracy. Further investigations on different clinical endpoints and populations are encouraged to confirm and generalise these findings