Stellar clustering shapes the architectures of planetary systems

Planet formation is generally described in terms of a system containing the host star and a protoplanetary disc, of which the internal properties (e.g. mass and metallicity) determine the properties of the resulting planetary system. However, (proto)planetary systems are predicted and observed to be affected by the spatially-clustered stellar formation environment, either through dynamical star-star interactions or external photoevaporation by nearby massive stars. It is challenging to quantify how the architecture of planetary systems is affected by these environmental processes, because stellar groups spatially disperse within <1 billion years, well below the ages of most known exoplanets. Here we identify old, co-moving stellar groups around exoplanet host stars in the astrometric data from the Gaia satellite and demonstrate that the architecture of planetary systems exhibits a strong dependence on local stellar clustering in position-velocity phase space, implying a dependence on their formation or evolution environment. After controlling for host stellar age, mass, metallicity, and distance from the Sun, we obtain highly significant differences (with $p$-values of $10^{-5}{-}10^{-2}$) in planetary (system) properties between phase space overdensities and the field. The median semi-major axis and orbital period of planets in overdensities are 0.087 au and 9.6 days, respectively, compared to 0.81 au and 154 days for planets around field stars. 'Hot Jupiters' (massive, close-in planets) predominantly exist in stellar phase space overdensities, strongly suggesting that their extreme orbits originate from environmental perturbations rather than internal migration or planet-planet scattering. Our findings reveal that stellar clustering is a key factor setting the architectures of planetary systems

Spatiotemporal expansion of primary progenitor zones in the developing human cerebellum

We present histological and molecular analyses of the developing human cerebellum from 30 days after conception to 9 months after birth. Differences in developmental patterns between humans and mice include spatiotemporal expansion of both ventricular and rhombic lip primary progenitor zones to include subventricular zones containing basal progenitors. The human rhombic lip persists longer through cerebellar development than in the mouse and undergoes morphological changes to form a progenitor pool in the posterior lobule, which is not seen in other organisms, not even in the nonhuman primate the macaque. Disruptions in human rhombic lip development are associated with posterior cerebellar vermis hypoplasia and Dandy-Walker malformation. The presence of these species-specific neural progenitor populations refines our insight into human cerebellar developmental disorders

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

Surface Plasmon Resonance Reveals a Different Pattern of Proinsulin Autoantibodies Concentration and Affinity in Diabetic Patients

Type 1 diabetes mellitus (DM) is characterized by autoimmune aggression against pancreatic beta cells resulting in absolute deficiency of insulin secretion. The first detectable sign of emerging autoimmunity during the preclinical asymptomatic period is the appearance of diabetes-related autoantibodies. In children at risk for type 1 DM, high-affinity Insulin autoantibodies reactive to proinsulin, are associated with diabetes risk. Autoantibodies are usually measured by radioligand binding assay (RBA) that provides quasi-quantitative values reflecting potency (product between concentration and affinity) of specific autoantibodies. Aiming to improve the characterization of the specific humoral immune response, we selected surface plasmon resonance (SPR) as an alternative method to measure proinsulin autoantibodies (PAA). This novel technology has allowed real time detection of antibodies interaction and kinetic analysis. Herein, we have employed SPR to characterize the PAA present in sera from 28 childhood-onset (mean age 8.31±4.20) and 23 adult-onset diabetic patients (≥65 years old, BMI<30) in terms of concentration and affinity. When evaluating comparatively samples from both groups, childhood-onset diabetic patients presented lower PAA concentrations and higher affinities (median 67.12×10−9 M and 3.50×107 M−1, respectively) than the adults (median 167.4×10−9 M and 0.84×107 M−1, respectively). These results are consistent with those from the reference method RBA (Standard Deviation score median 9.49 for childhood-onset group and 5.04 for adult-onset group) where the binding can be directly related to the intrinsic affinity of the antibody, suggesting that there is a different etiopathogenic pathway between both types of clinical presentation of the disease. This technology has shown to be a useful tool for the characterization of PAAs parameters as an alternative to radioimmunoassay, with high versatility and reproducibility associated to low occupational and environmental risk. However, this technology is not eligible for routine marker screening, but this is a powerful technique for a fine description of the thermodynamic parameters of antigen-antibody interaction

Osseous erosion by herniated nucleus pulposus mimicking intraspinal tumor: a case report

Erosion of spinal osseous structure, so-called scalloping, has been rarely reported associated with herniated nucleus pulposus (HNP). We report a rare case of HNP causing erosion of the spinal osseous structure (including lamina). The patient was an 81-year-old woman with 3-year history of low-back pain and left leg radiating pain. Muscle weakness of the left leg was also apparent. Computed tomography following myelography showed severe compression of the dural sac at the level of L3–L4; furthermore, erosion of the lamina, pedicle, and vertebral body was noted, indicating that the space-occupying mass was most probably a tumorous lesion. The mass also showed calcification inside. During the surgery, the mass was confirmed to be an HNP with calcification. Following resection, the pain disappeared. Surgeons should be aware of the possibility of scalloping of the vertebrae caused by HNP mimicking a tumorous lesion

pp32 (ANP32A) Expression Inhibits Pancreatic Cancer Cell Growth and Induces Gemcitabine Resistance by Disrupting HuR Binding to mRNAs

The expression of protein phosphatase 32 (PP32, ANP32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, including gemcitabine. pp32 overexpression reduced the association of HuR with the mRNA encoding the gemcitabine-metabolizing enzyme deoxycytidine kinase (dCK), causing a significant reduction in dCK protein levels. Similarly, ectopic pp32 expression caused a reduction in HuR binding of mRNAs encoding tumor-promoting proteins (e.g., VEGF and HuR), while silencing pp32 dramatically enhanced the binding of these mRNA targets. Low pp32 nuclear expression correlated with high-grade tumors and the presence of lymph node metastasis, as compared to patients' tumors with high nuclear pp32 expression. Although pp32 expression levels did not enhance the predictive power of cytoplasmic HuR status, nuclear pp32 levels and cytoplasmic HuR levels associated significantly in patient samples. Thus, we provide novel evidence that the tumor suppressor function of pp32 can be attributed to its ability to disrupt HuR binding to target mRNAs encoding key proteins for cancer cell survival and drug efficacy

Resectable pancreatic small cell carcinoma

Primary pancreatic small cell carcinoma (SCC) is rare, with just over 30 cases reported in the literature. Only 7 of these patients underwent surgical resection with a median survival of 6 months. Prognosis of SCC is therefore considered to be poor, and the role of adjuvant therapy is uncertain. Here we report two institutions' experience with resectable pancreatic SCC. Six patients with pancreatic SCC treated at the Johns Hopkins Hospital (4 patients) and the Mayo Clinic (2 patients) were identified from prospectively collected pancreatic cancer databases and re-reviewed by pathology. All six patients underwent a pancreaticoduodenectomy. Clinicopathologic data were analyzed, and the literature on pancreatic SCC was reviewed. Median age at diagnosis was 50 years (range 27–60). All six tumors arose in the head of the pancreas. Median tumor size was 3 cm, and all cases had positive lymph nodes except for one patient who only had five nodes sampled. There were no perioperative deaths and three patients had at least one postoperative complication. All six patients received adjuvant therapy, five of whom were given combined modality treatment with radiation, cisplatin, and etoposide. Median survival was 20 months with a range of 9–173 months. The patient who lived for 9 months received chemotherapy only, while the patient who lived for 173 months was given chemoradiation with cisplatin and etoposide and represents the longest reported survival time from pancreatic SCC to date. Pancreatic SCC is an extremely rare form of cancer with a poor prognosis. Patients in this surgical series showed favorable survival rates when compared to prior reports of both resected and unresectable SCC. Cisplatin and etoposide appears to be the preferred chemotherapy regimen, although its efficacy remains uncertain, as does the role of combined modality treatment with radiation

Water Contaminants Detection Using Sensor Placement Approach in Smart Water Networks

Incidents of water pollution or contamination have occurred repeatedly in recent years, causing significant disasters and negative health impacts. Water quality sensors need to be installed in the water distribution system (WDS) to allow real-time water contamination detection to reduce the risk of water contamination. Deploying sensors in WDS is essential to monitor and detect any pollution incident at the appropriate time. However, it is impossible to place sensors on all nodes of the network due to the relatively large structure of WDS and the high cost of water quality sensors. For that, it is necessary to reduce the cost of deployment and guarantee the reliability of the sensing, such as detection time and coverage of the whole water network. In this paper, a dynamic approach of sensor placement that uses an Evolutionary Algorithm (EA) is proposed and implemented. The proposed method generates a multiple set of water contamination scenarios in several locations selected randomly in the WDS. Each contamination scenario spreads in the water networks for several hours, and then the proposed approach simulates the various effect of each contamination scenario on the water networks. On the other hand, the multiple objectives of the sensor placement optimization problem, which aim to find the optimal locations of the deployed sensors, have been formulated. The sensor placement optimization solver, which uses the EA, is operated to find the optimal sensor placements. The effectiveness of the proposed method has been evaluated using two different case studies on the example of water networks: Battle of the Water Sensor Network (BWSN) and another real case study from Madrid (Spain). The results have shown the capability of the proposed method to adapt the location of the sensors based on the numbers and the locations of contaminant sources. Moreover, the results also have demonstrated the ability of the proposed approach for maximising the coverage of deployed sensors and reducing the time to detect all the water contaminants using a few numbers of water quality sensor

Androgen receptor expression in metastatic adenocarcinoma in females favors a breast primary

BACKGROUND: The differential diagnosis of metastatic mammary adenocarcinoma and adenocarcinomas from other primary sites can be challenging, particularly in tumors that are poorly differentiated and negative for Estrogen/Progesterone receptors (ER/PR). With progression of disease, Androgen receptors (AR) are preserved with higher frequency than ER/PR in metastatic mammary carcinoma. This study was undertaken to evaluate the diagnostic significance of AR expression in adenocarcinoma of breast and other morphologically similar adenocarcinomas. DESIGN: Formalin-fixed paraffin-embedded tissue sections of 113 primary adenocarcinoma of various sites [breast (34, all females), lung (23, M- 6, F-17), colon (9, M-2, F-7), stomach (6, M-4, F-2), liver and bile duct (11, M-5, F-6), pancreas (7, M-2, F-5), ovary (10), endometrium (7), and cervix (6)] were immunostained with monoclonal antibody for AR. Except for well differentiated lobular carcinoma of breast (5) and bronchoalveolar carcinoma of lung (10), majority of the tumors were moderately to poorly differentiated. Tumors immunoreactive for ≥ 10% of nuclei were considered AR positive. However, AR immunoreactivity in the cytoplasm only was also recorded. RESULTS: 56% (19/34) mammary carcinoma and 20% (2/10) adenocarcinoma of ovary were positive for AR. Remaining 69 adenocarcinomas did not show nuclear immunoreactivity for AR in ≥ 10% nuclei; however, 52% (36/69) showed variable cytoplasmic immunoreactivity. CONCLUSION: Significant proportion of mammary carcinomas and some ovarian carcinomas express AR in the nuclei of more than 10% tumor cells. If metastatic tumor with unknown primary in a female is AR positive, breast and ovary are the most likely primary sites. Cytoplasmic immunoreactivity alone without nuclear immunoreactivity for AR was non-specific for this differential diagnosis

R2P from Below: Does the British Public View Humanitarian Interventions as Ethical and Effective?

One of the major barriers to the implementation of the Responsibility to Protect principle is the lack of a political will. Public attitudes towards intervention will have a crucial impact on elite willingness to prevent mass atrocities, yet we have little understanding of the factors that influence those attitudes. This article provides the first examination of UK public perceptions about the moral justifiability and effectiveness of humanitarian interventions. The article shows that decisions about justifiability and effectiveness are very different. Attitudes towards justification were more easily explained suggesting that judgements about effectiveness are more contextual and less easily accounted for by individuals’ background characteristics and attitudes. Experiences with both Iraq and Afghanistan have contaminated public perceptions of both the ethics and effectiveness of humanitarian interventions. Although the public is broadly supportive about the justifiability of humanitarian interventions they are extremely sceptical about the likelihood that those interventions will be successful