Miracle-dz/UniFAR-FTUs huggingface dataset:
Radiotherapy Dose and Late Failures in Prostate Cancer

Purpose— To quantify the impact of radiotherapy (RT) dose escalation on the timing of biochemical failure (BF) and distant metastasis (DM) for prostate cancer treated with RT alone. Methods and Materials— A total of 667 men with clinically localized intermediate and high risk prostate cancer treated with 3D-conformal RT alone were retrospectively analyzed. The interval hazard rates of DM and biochemical failure (BF), using ASTRO and Phoenix (Nadir+2) definitions, were determined. Median follow-up was 77 months. Results— Multivariate analysis showed that increasing RT dose was independently associated with decreased ASTRO BF ( P <.0001), Nadir+2 BF ( P =.001), and DM ( P =.006). The preponderance (85%) of ASTRO BF occurred at ≤ 4 years after RT, while Nadir+2 BF was more evenly spread over years 1-10, with 55% BF in ≤ 4 years. RT dose escalation caused a shift in the BF from earlier to later years. The interval hazard function for DM appeared to be biphasic (early and late peaks) overall and for the <74 Gy group. In patients receiving ≥ 74 Gy, there was a reduction in the risk of DM in both the early and late waves, although the late wave appears reduced to a greater degree. Conclusions— The ASTRO definition of BF systematically underestimates late BF due to backdating. RT dose escalation diminished and delayed BF; the delay suggests that there may still be local persistence in some patients. For DM, higher RT dose reduced both the early and late waves, suggesting that persistence of local disease contributes to both.
A User Perspective on Typification of Facade Features of 3D Building Models

Using detailed geometric city model may suffer from the capacity limitation and too high computing intensity during the visualization, especially when the model should be visualized with changing resolutions or map scales. One of the solutions to alleviate these drawbacks is to generalize the building models by means of operators such as simplification, aggregation and typification. This paper is dedicated to typification of facade features. Although typification has been frequently applied in 2D map generalization, much attention was paid on how to typify the features instead of whether the typification result pleases the user’s eyes. The authors present a user survey for the evaluation of different typification results under different constraints. The results showed that preserving the similarity after typification is the most important constraint for a reasonable typification process.
Tutorial Stimulus Control: Part I

In his effort to distinguish operant from respondent conditioning, Skinner stressed the lack of an eliciting stimulus and rejected the prevailing stereotype of Pavlovian "stimulus-response" psy-chology. But control by antecedent stimuli, whether classified as conditional or discriminative, is ubiquitous in the natural setting. With both respondent and operant behavior, symmetrical gradients of generalization along unrelated dimensions may be obtained following differential reinforcement in the presence and the absence of the stimulus. The slopes of these gradients serve as measures of stimulus control, and they can be steepened without applying differential reinforcement to any two points along the test dimension. Increases and decreases in stimulus control occur under the same conditions as those leading to increases and decreases in observing responses, indicating that it is the increasing frequency and duration of observation (and perhaps also of attention) that produces the separation in performances during discrimination learning. when conditioned reflexes are being established in dogs for the first time, it is found that the whole experimental environment, beginning with the introduction of the dog to the experimental room, acquires at first conditioned prop- erties. Later on, when the special reflex to a single definite and constant stimulus has ap- peared, all the other elements of the environment gradually lose their special conditioned signifi- cance. (Pavlov, 1927/1960, p. 115)
The presence of 19-kDa Bcl-2 in dividing cells

The 26-kDa bcl-2 gene product inhibits apoptosis and cell proliferation. Cleavage of Bcl-2 into a 22-kDa fragment inactivates its anti-apoptotic activity and is a key event in apoptosis. Here, and in recent work, we describe massive 19-kDa Bcl2 immunoreactivity in non-apoptotic cells, suggesting a link with viability rather than cell death. Loss of 19 kDa Bcl-2 in adriamycin-induced apoptotic cells underlines this. G 2 /M-phase accumulation of cells by nocodazole-treatment also results in loss of 19 kDa Bcl-2. Next to its well-documented cytoplasmic localization, a substantial pool of Bcl-2 resides in nuclei. Hampered nuclear localization of Bcl-2 leads to a loss of cell cycle repression. This has led us to point at a pivotal role for nuclear Bcl-2 in cellular proliferation. In this report, cellular fractionation of bcl-2 transfected cells in various phases of the cell cycle reveals a constitutive cytoplasmic pool of 19 kDa Bcl-2. Nuclear 19-kDa Bcl-2 immunoreactivity is far more pronounced in rapidly dividing nuclei compared with more quiescent nuclear fractions. This implicates that ongoing cell proliferation involves cleavage of nuclear Bcl-2 with a 19-kDa fragment.
Pre- to Post-operative Changes in Physical Activity: Report from the Longitudinal Assessment of Bariatric Surgery-2

Background— Numerous studies report that bariatric surgery patients report more physical activity (PA) after surgery than before, but the quality of PA assessment has been questionable. Methods— The Longitudinal Assessment of Bariatric Surgery-2 is a 10-center longitudinal study of adults undergoing bariatric surgery. Of 2458 participants, 455 were given an activity monitor, which records steps/minute, and an exercise diary before and 1 year after surgery. Mean step/day, active minutes/day, and high-cadence minutes/week were calculated for 310 participants who wore the monitor at least 10 hours/day for at least 3 days at both time points. Pre- and post-surgery PA were compared for differences using the Wilcoxon signed-rank test. Generalized Estimating Equations identified independent pre-operative predictors of post-operative PA. Results— PA increased significantly (p<.0001) pre- to post-operative for all PA measures. Median values pre- and post-operative were: 7563 and 8788 steps/day; 309 and 340 active minutes/day; and 72 and 112 high-cadence minutes/week, respectively. However, depending on the PA measure, 24–29% of participants were at least 5% less active post-operative than preoperative. Controlling for surgical procedure, sex, age and BMI, higher PA preoperative independently predicted higher PA post-operative (p<.0001, all PA measures). Less pain, not having asthma and self-report of increasing PA as a weight loss strategy pre-operative also independently predicted more high-cadence minutes/week post-operative (p<.05). Conclusion— The majority of adults increase their PA level following bariatric surgery. However, most remain insufficiently active and some become less active. Increasing PA, addressing pain and treating asthma prior to surgery may have a positive impact on post-operative PA.
Retinoic Acid Regulation of Hemogenic Endothelial Cell Specification Requires c-Kit, Notch Signaling and p27-mediated Cell Cycle Control

SUMMARY Delineating the mechanism(s) that regulate the specification of hemogenic endothelial cells from primordial endothelium is critical for optimizing their derivation from human stem cells for clinical therapies. We previously determined that retinoic acid (RA) is required for hemogenic specification, as well as cell cycle control, of endothelium during embryogenesis. Herein, we define the molecular signals downstream of RA that regulate hemogenic endothelial cell development, and demonstrate that cell cycle control is required for this process. We found that reexpression of c-Kit in RA-deficient ( Raldh2 −/− ) primordial endothelium induced Notch signaling and p27 expression, which restored cell cycle control and rescued hemogenic endothelial cell specification and function. Re-expression of p27 in RA-deficient and Notch-inactivated primordial endothelial cells was sufficient to correct their defects in cell cycle regulation and hemogenic endothelial cell development. Thus, RA regulation of hemogenic endothelial cell specification requires c-Kit, notch signaling and p27-mediated cell cycle control.
Cellular stress upregulates indole signaling metabolites in E. coli.

Arabidopsis thaliana infection assays. H.B. P. contributed to paraquat stress and time-course analyses. A.G. contributed to analysis of indolokine production from Gram-positive and Gram-negative bacteria. A.D. and N.K. C. performed the Arabidopsis thaliana callose response assays. R.W. , T.P.W. , and G.P. contributed to BioMAP® Phenotypic Profiling Assay analysis. J.M. C. conceived the study, oversaw experiments, and wrote the defense response. We show that the indolokines are produced in a convergent evolutionary manner relative to plants, enhance E. coli persister cell formation, outperform ICN protection in an Arabidopsis thaliana-Pseudomonas syringae infection model, trigger a hallmark plant innate immune response, and activate distinct immunological responses in primary human tissues. Our molecular studies link a family of cellular stress-induced metabolites to defensive responses across bacteria, plants, and humans. Abstract Kim, Li, et al. describe the characterization of cellular stress-induced, bacterial indole-functionalized metabolites termed “indolokines. ” The indolokines are found in diverse bacteria, enhance persister formation in E. coli, and activate innate immune responses in both plant and human tissues. interleukin-8 (IL-8) in venular endothelial cells co-cultured with PBMCs, caused a decrease in proliferation in dermal fibroblasts, and decreased eotaxin-3 (CCL26) in both venular endothelial cells (mono-culture) and bronchial epithelial cells co-cultured with dermal fibroblasts. These results suggest the role of indolokine A4 ( 2 ) in affecting immunomodulatory and inflammation-related activities. Indolokine B4 ( 6 ) caused a decrease in matrix metallopeptidase 9 (MMP-9), urokinase-type plasminogen activator receptor (CD87), plasminogen activator inhibitor-1 (PAI-1), and C-X-C chemokine 11 (CXCL-11), all of which are with tissue remodeling. experiments were performed in the absence of either L -Cys or I3P and both L -Cys and I3P in M9 or LB media.
Reproductive and metabolic determinants of granulosa cell dysfunction in normal-weight polycystic ovary syndrome women

Objective— To determine the degree to which estradiol (E2) hyperresponsiveness to follicle-stimulating hormone (FSH) and anti-mullerian hormone (AMH) overproduction in normal-weight women with polycystic ovary syndrome (PCOS) correlate with increased antral follicle number (AFN), hyperandrogenism and/or metabolic dysfunction. Design— Prospective cohort study Setting— Academic medical center Patients— Seven normal-weight PCOS women (1990 NIH criteria) ages 20–34 years and 13 age-and body mass index (BMI, 18.5–25 kg/m 2 )-matched normoandrogenic ovulatory women were studied. Intervention(s)— All women underwent basal serum hormone and metabolic measurements, FSH stimulation testing with transvaginal ovarian sonography, frequently-sampled intravenous glucose tolerance testing and whole-body dual-energy x-ray absorptiometry. Main Outcome Measure(s)— Serum hormone/metabolite levels, 24-hour serum E2 response to 150 IU recombinant human (rh) FSH infusion, AFN, insulin sensitivity and body mass measurements. Results— Serum E2 responsiveness to rhFSH and AMH levels were all women combined, serum E2 responsiveness to rhFSH was associated with AFN. Serum AMH levels, however, positively correlated with AFN but remained positively correlated with serum luteinizing hormone and free testosterone levels and negatively correlated with total body fat and percent body fat, adjusting for AFN. Conclusion— In normal-weight PCOS women, serum E2 hyperresponsiveness to rhFSH represents increased AFN, while elevated serum AMH levels reflect opposing effects of stimulatory reproductive (hyperandrogenism and increased AFN) versus inhibitory metabolic (body fat) factors. Given the small number of subjects reported, additional follow-up studies are required to confirm these data.
18 F-FES PET/CT In ﬂ uences the Staging and Management of Patients with Newly Diagnosed Estrogen Receptor-Positive Breast Cancer: A Retrospective Comparative Study with 18 F-FDG PET/CT

breast cancer con ﬁ rmed that 18F-FES scans led to change in management in 26.3% of the 19 patients with newly diagnosed ER positive breast cancer. This retrospective study indicates the potential impact of 18F-FES PET/CT on intended management of patients with newly diagnosed estrogen receptor positive breast cancer in comparison to 18F- ﬂ uoro-2-deoxy-D-glucose PET/CT.
Intercellular Bridge Mediates Ca 2 D Signals between Micropatterned Cells via IP 3 and Ca 2 D Diffusion

Intercellular bridges are plasma continuities formed at the end of the cytokinesis process that facilitate intercellular mass transport between the two daughter cells. However, it remains largely unknown how the intercellular bridge mediates Ca 2 þ communication between postmitotic cells. In this work, we utilize BV-2 microglial cells planted on dumbbell-shaped micropatterned assemblies to resolve spatiotemporal characteristics of Ca 2 þ signal transfer over the intercellular bridges. With the use of such micropatterns, considerably longer and more regular intercellular bridges can be obtained than in conventional cell cultures. The initial Ca 2 þ signal is evoked by mechanical stimulation of one of the daughter cells. A considerable time delay is observed between the arrivals of passive Ca 2 þ diffusion and endogenous Ca 2 þ response in the intercellular-bridge-connected cell, indicating two different pathways of the Ca 2 þ communication. Extracellular Ca 2 þ and the paracrine pathway have practically no effect on the endogenous Ca 2 þ response, demonstrated by application of Ca 2 þ -free medium, exogenous ATP, and P2Y 13 receptor antagonist. In contrast, the endoplasmic reticulum Ca 2 þ -ATPase inhibitor thapsigargin and inositol trisphosphate (IP 3 ) receptor blocker 2-aminoethyl diphenylborate signiﬁcantly inhibit the endogenous Ca 2 þ increase, which signiﬁes involve-ment of IP 3 -sensitive calcium store release. Notably, passive Ca 2 þ diffusion into the connected cell can clearly be detected when IP 3 -sensitive calcium store release is abolished by 2-aminoethyl diphenylborate. Those observations prove that both passive Ca 2 þ diffusion and IP 3 -mediated endogenous Ca 2 þ response contribute to the Ca 2 þ increase in intercellular-bridge-connected cells. Moreover, a simulation model agreed well with the experimental observations. utilize BV-2 microglial cells planted on specially designed micropatterned assemblies to resolve the spatiotemporal characteristics of Ca 2 þ communication over the intercellular bridge. We show that both passive Ca 2 þ diffusion and inositol-triphosphate-mediated endogenous Ca 2 þ response contribute to the signal transfer.
Left Atrial Volumes and Reservoir Function Are Associated With Subclinical Cerebrovascular Disease: The Cardiovascular Abnormalities and Brain Lesions (CABL) Study

Objectives— To assess the relationship of left atrial (LA) phasic volumes and LA reservoir function with subclinical cerebrovascular disease in a stroke-free community-based cohort. Background— An increase in LA size is associated with cardiovascular events including stroke. However, it is not known whether LA phasic volumes and reservoir function are associated with subclinical cerebrovascular disease. Methods— LA minimum (LAV min ) and maximum (LAV max ) volumes, and LA reservoir function, measured as total emptying volume (LAEV) and total emptying fraction (LAEF), were assessed by real-time three-dimensional echocardiography in 455 stroke-free participants from the community-based Cardiovascular Abnormalities and Brain Lesions (CABL) study. Subclinical cerebrovascular disease was assessed as silent brain infarcts (SBI) and white matter hyperintensity volume (WMHV) by brain magnetic resonance imaging (MRI). Results— SBI prevalence was 15.4%; mean WMHV was 0.66±0.92%. Participants with SBI showed greater LAV min (17.1±9.3 vs. 12.5±5.6 ml/m 2 , p<0.01) and LAV max (26.6±8.8 vs. 23.3±7.0 ml/m 2 , p<0.01) compared to those without SBI. LAEV (9.5±3.4 vs. 10.8±3.9 ml/m 2 , p<0.01) and LAEF (38.7±14.7% vs. 47.0±11.9%, p<0.01) were also reduced in participants with SBI. In univariate analyses, greater LA volumes and smaller reservoir function were significantly associated with greater WMHV. In multivariate analyses, LAV min remained significantly associated with SBI [adjusted odds ratio (OR) per SD increase: 1.37, 95% confidence intervals (CI) 1.04–1.80, p<0.05] and with WMHV ( β =0.12, p<0.01), whereas LAV max was not independently associated with either. Smaller LAEF was independently associated with SBI (adjusted OR=0.67, 95% CI 0.50–0.90, p<0.01) and WMHV ( β =−0.09, p<0.05). Conclusions— Greater LA volumes and reduced LA reservoir function are associated with subclinical cerebrovascular disease detected by brain MRI in subjects without history of stroke. LAV min and LAEF, in particular, are more strongly associated with SBI and WMHV than the more commonly measured LAV max , and their relationship with subclinical brain lesions is independent of other cardiovascular risk factors.
OF TOROIDAL LIE ALGEBRAS ARISING FROM φ ǫ -COORDINATED OF

In this paper, for every ǫ ∈ Z , we introduce an extension of the 2-toroidal Lie algebra by certain derivations. Based on the φ ǫ -coordinated modules theory for vertex algebras, we give an explicit realization of a class of irreducible highest weight modules for this extended toroidal Lie algebra. When ǫ = 1, this aﬀords a realization of certain irreducible modules for the toroidal extended aﬃne Lie algebras ﬁrst constructed by Billig.
Protein Kinase B/Akt Is Present in Activated Form throughout the Entire Replicative Cycle of (cid:2) U S 3 Mutant Virus but Only at Early Times after Infection with Wild-Type Herpes Simplex Virus 1

The product of the herpes simplex virus 1 (HSV-1) US3 gene is a multifunctional serine-threonine protein kinase that can block apoptosis induced by proapoptotic cellular proteins, exogenous agents, or replication-defective viruses. Earlier studies showed that the U S 3 kinase activates and functionally overlaps cellular protein kinase A (PKA). In this study we examined the status of phosphatidylinositol 3-kinase [PI(3)K] and of its effector, protein kinase B/Akt (PKB/Akt), a component of a major pathway of mammalian antiapoptotic signaling systems. We report the following. (i) Infection of target cells with HSV-1 induces transient phosphorylation of serine 473 of PKB/Akt early in infection, with a mechanism that is dependent on PI(3)K. Inhibition of PI(3)K induced apoptosis in mock-infected or (cid:1) U S 3 mutant-virus-infected but not in wild-type-virus-infected cells and reduced the accumulation of speciﬁc viral gene products, including the U S 3 protein kinase, but had a marginal effect on virus yields. (ii) At later times after infection, the total amounts of PKB/Akt decreased and phosphorylated PKB/Akt forms disappeared in a U S 3-dependent and protein phos- phatase 2A-independent manner. (iii) Activation of PKA by forskolin did not mediate signiﬁcant dephosphorylation of PKB/Akt. Our results are consistent with the model that PKB/Akt is activated early in infection and acts to block apoptosis in infected cells prior to the accumulation of U S 3 protein kinase and that it persists and continues to function as an antiapoptotic protein in the absence of U S 3 but becomes redundant or even inimical once U S 3 protein kinase accumulates in effective amounts.
Cost of Intensive care: General principles

In general, there are two methods of costing described as top down[4] and bottom-up[5] method, each having its advantages and disadvantages that are outside the context of this article. In order to improve comparison of costing data from different Intensive Care Units (ICU) in United Kingdom (UK), a working group identiÞ ed six cost blocks i.e. costs of staff, clinical support services, consumables, estates, non-clinical support services and capital equipment. [6] Subsequently it was adapted for the development of IPOC (The International Programme for resource use in Critical care). [7] The three UK cost blocks i.e. staff; support services and consumables were used along with an additional block for major capital equipment. The addition of a major capital equipment block was to allow understanding of the differences in resource use between countries. The costs were converted to international dollars, using the Purchasing Power Parity (PPP) exchange rates developed by the World Health Organization. This allowed, for the Þ rst time, the comparison of ICU costs from one country to another using a common reference point. The cost of critical care is widely recognized as being both expensive and increasing. [1] It remains a challenge to accurately assess the cost of intensive care due to lack of standardized methodology. There is also considerable heterogeneity between countries and even within the country in allocation of resources and distribution of critical care services[2] and cost of personnel and price of drugs. The indivisibility and intangibility of several health care outcomes is also a concern, particularly while evaluating cost effectiveness. More importantly, when it comes to health care needs, the emotions and ethics of the society is often compelling and most are willing to accept the cost even in situations where effectiveness is not clearly established. The objective of this article is to review these issues and develop a framework through which cost of Intensive care in India can be analyzed.