Vectorial Transcellular Calcium Transport in Intestine: Integration of Current Models

In spite of decades of research, the exact subcellular pathway for calcium transport in intestine has not been elucidated. In this mini-review, we present three models for vectorial movement of calcium across the cell: facilitated (cytoplasmic) diffusion, vesicular/lysosomal transport, and tunneling through the endoplasmic reticulum compartment. We conclude by offering one way to integrate elements of these three models

Lessons from the Development of an Anomaly Detection Interface on the Mars Perseverance Rover using the ISHMAP Framework

While anomaly detection stands among the most important and valuable problems across many scientific domains, anomaly detection research often focuses on AI methods that can lack the nuance and interpretability so critical to conducting scientific inquiry. In this application paper we present the results of utilizing an alternative approach that situates the mathematical framing of machine learning based anomaly detection within a participatory design framework. In a collaboration with NASA scientists working with the PIXL instrument studying Martian planetary geochemistry as a part of the search for extra-terrestrial life; we report on over 18 months of in-context user research and co-design to define the key problems NASA scientists face when looking to detect and interpret spectral anomalies. We address these problems and develop a novel spectral anomaly detection toolkit for PIXL scientists that is highly accurate while maintaining strong transparency to scientific interpretation. We also describe outcomes from a yearlong field deployment of the algorithm and associated interface. Finally we introduce a new design framework which we developed through the course of this collaboration for co-creating anomaly detection algorithms: Iterative Semantic Heuristic Modeling of Anomalous Phenomena (ISHMAP), which provides a process for scientists and researchers to produce natively interpretable anomaly detection models. This work showcases an example of successfully bridging methodologies from AI and HCI within a scientific domain, and provides a resource in ISHMAP which may be used by other researchers and practitioners looking to partner with other scientific teams to achieve better science through more effective and interpretable anomaly detection tools

Relationship of vitamin D and parathyroid hormone with obesity and body composition in African Americans

Obesity disproportionately affects African Americans (AA) (especially women), and is linked to depressed 25-hydroxyvitamin D (25-OH D) and elevated parathyroid hormone (PTH). The relationship of 25-OH D and PTH with body composition and size in AA is not well known.To determine the relationship of 25-OH D and PTH levels with body composition and anthropometric measures.A cross-sectional study was conducted in 98 healthy, overweight, adult AA enrolled in an NIH/NIEHS-sponsored weight loss/salt-sensitivity trial.Multivariable linear regression analyses were used to explore the relationship of 25-OH D and PTH with body composition, determined by dual-energy X-ray absorptiometry, and anthropometric measures. Body composition and size were contrasted across vitamin D/PTH groups using general linear models: (i) normal (25-OH D >50 nmol/l, PTH ≤65 pg/ml), (ii) low 25-OH D and normal PTH and (iii) low 25-OH D and high PTH.Age, gender and season-adjusted regression analyses showed that PTH was directly correlated with total ( P  =   0·02), truncal ( P  =   0·03) and extremity ( P  =   0·03) fat mass, while 25-OH D was inversely related to truncal fat mass ( P  =   0·02). Total fat mass in groups 1–3, respectively, was 30·0, 34·0 and 37·4 kg ( P  =   0·008); truncal fat mass was 13·4, 15·9 and 17·6 kg ( P  =   0·006) and extremity fat mass was 15·8, 16·9 and 19·7 kg ( P  =   0·02). Lean mass did not differ across the three groups.Our findings show that lower 25-OH D and raised PTH are both correlated, though in opposite directions, with fat mass, fat distribution and anthropometric measures in adult AA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79084/1/j.1365-2265.2009.03676.x.pd

Геофизические закономерности локализации месторождений углеводородов Баренцево-Карского региона

Background: Rising serum levels of prostate-specific antigen (PSA) after radical prostatectomy are indicative of recurrent prostate cancer. This double-blind, placebo-controlled phase II study evaluated the anti-tumour activity of the anti-epithelial cell adhesion molecule (EpCAM) antibody adecatumumab in delaying biochemical disease progression. Patients and Methods: Prostate cancer patients with increasing serum PSA levels following radical prostatectomy were randomized to low- (2 mg/kg) or high-dose adecatumumab (6 mg/kg) or placebo. The primary efficacy endpoint was the mean change from baseline in total serum PSA at week 24. Secondary endpoints included PSA response rate, prolongation of serum PSA doubling time and time to biochemical disease progression. Results: The primary and secondary endpoints of the study were not met in the predefined analyses. In a retrospective analysis of patients with baseline PSA <= 1 ng/ml and a high EpCAM expression, both the mean increase in PSA from baseline to week 24 and the PSA doubling time at week 15 were significantly improved in the high-dose adecatumumab group compared with the placebo group. Most frequent treatment-related clinical adverse events were gastrointestinal (diarrhoea and nausea) or general events (chills), showing a dose dependency but no grade 3/4 intensity in any patient. Conclusion: In men with rising PSA levels after radical prostatectomy and no evidence of clinical relapse, adecatumumab delayed disease progression in a subgroup of patients with baseline PSA levels <= 1 ng/ml and high EpCAM-expressing tumours. Copyright (C) 2010 S. Karger AG, Base

The centrosome neither persistently leads migration nor determines the site of axonogenesis in migrating neurons in vivo

In vivo analysis of subcellular dynamics in the zebrafish cerebellum provides new insights into centrosome positioning during vertebrate brain differentiation

Role of vitamin D-binding protein in isocyanate-induced occupational asthma

The development of a serological marker for early diagnosis of isocyanate-induced occupational asthma (isocyanate-OA) may improve clinical outcome. Our previous proteomic study found that expression of vitamin D-binding protein (VDBP) was upregulated in the patients with isocyanate-OA. In the present study, we evaluated the clinical relevance of VDBP as a serological marker in screening for isocyanate-OA among exposed workers and its role in the pathogenesis of isocyanate-OA. Three study groups including 61 patients with isocyanate-OA (group I), 180 asymptomatic exposed controls (AECs, group II), 58 unexposed healthy controls (NCs, group III) were enrolled in this study. The baseline serum VDBP level was significantly higher in group I compared with groups II and III. The sensitivity and specificity for predicting the phenotype of isocyanate-OA with VDBP were 69% and 81%, respectively. The group I subjects with high VDBP (≥ 311 µg/ml) had significantly lower PC20 methacholine levels than did subjects with low VDBP. The in vitro studies showed that TDI suppressed the uptake of VDBP into RLE-6TN cells, which was mediated by the downregulation of megalin, an endocytic receptor of the 25-hydroxycholecalciferol-VDBP complex. Furthermore, toluene diisocyanate (TDI) increased VEGF production and secretion from this epithelial cells by suppression of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] production. The findings of this study suggest that the serum VDBP level may be used as a serological marker for the detection of isocyanate-OA among workers exposed to isocyanate. The TDI-induced VEGF production/secretion was reversed by 1,25(OH)2D3 treatment, which may provide a potential therapeutic strategy for patients with isocyanate-OA

Rediscovering vitamin D

Over the past 2 years there has been a radical change in standard clinical practice with respect to vitamin D. As a result of a growing body of knowledgeable physicians are assessing the vitamin D nutritional status of their patients and prescribing aggressive repletion regimens of a vitamin D supplement. The present paper summarizes some basic information about this essential nutrient and reviews some of the more recent data implicating vitamin D deficiency in disease etiology with an emphasis on cardiovascular disease and cancer. Finally a rational approach to the dosing of vitamin D in different patient populations is provided

A phase II trial of the vitamin D analogue Seocalcitol (EB1089) in patients with inoperable pancreatic cancer

Inoperable cancer of the exocrine pancreas responds poorly to most conventional anti-cancer agents, and new agents are required to palliate this disease. Seocalcitol (EB1089), a vitamin D analogue, can inhibit growth, induce differentiation and induce apoptosis of cancer cell lines in vitro and can also inhibit growth of pancreatic cancer xenografts in vivo. Thirty-six patients with advanced pancreatic cancer received once daily oral treatment with seocalcitol with dose escalation every 2 weeks until hypercalcaemia occurred, following which patients continued with maintenance therapy. The most frequent toxicity was the anticipated dose-dependent hypercalcaemia, with most patients tolerating a dose of 10–15 μg per day in chronic administration. Fourteen patients completed at least 8 weeks of treatment and were evaluable for efficacy, whereas 22 patients were withdrawn prior to completing 8 weeks' treatment and in 20 of these patients withdrawal was due to clinical deterioration as a result of disease progression. No objective responses were observed, with five of 14 patients having stable disease in whom the duration of stable disease was 82–532 days (median=168 days). The time to treatment failure (n=36) ranged from 22 to 847 days, and with a median survival of approximately 100 days. Seocalcitol is well tolerated in pancreatic cancer but has no objective anti-tumour activity in advanced disease. Further studies are necessary to determine if this agent has any cytostatic activity in this malignancy in minimal disease states

Health potential of soy isoflavones for menopausal women

OBJECTIVE: To review the current literature on the effects of soy isoflavones, one class of phyto-oestrogens, on cardiovascular diseases, osteoporosis, cancer and climacteric symptoms. DESIGN: Many study designs were employed in the reports reviewed here, including prospective human trials, observational human studies, animal experiments and in vitro cell studies that explored the protective or preventive effects of soy isoflavones (genistein, daidzein and glycitein alone or mixed). SETTING: Diverse settings were employed, depending on study design. SUBJECTS: Human subjects, mostly menopausal or postmenopausal, were included, as were animal models and specific cell types. RESULTS: The findings were: (i) isoflavones plus soy protein together were needed to obtain the highly significant beneficial results on blood lipids and arterial dimensions; (ii) isoflavone treatments alone at high doses (relative to above) consistently improved bone parameters in rodent ovariectomized models, but not in humans or primates; (iii) isoflavones were not consistent in exerting positive effects regarding the prevention or treatment of cancers of the mammary glands, uterus and colon; and (iv) the effects of isoflavones on climacteric symptoms were not clear-cut. CONCLUSIONS: The promise of soy isoflavones reducing chronic disease risk seems to be non-uniform, with the most conclusive benefits occurring in the prevention of cardiovascular diseases, but other organ systems, such as skeletal and reproductive tissues, may also benefit from the consumption of soy and soy-derived products