Neuro-Dynamic Programming for Radiation Treatment Planning

In many cases a radiotherapy treatment is delivered as a series of smaller dosages over a period of time. Currently, it is difficult to determine the actual dose that has been delivered at each stage, precluding the use of adaptive treatment plans. However, new generations of machines will give more accurate information of actual dose delivered, allowing a planner to compensate for errors in delivery. We formulate a model of the day-to-day planning problem as a stochastic linear program and exhibit the gains that can be achieved by incorporating uncertainty about errors during treatment into the planning process. Due to size and time restrictions, the model becomes intractable for realistic instances. We show how neuro-dynamic programming can be used to approximate the stochastic solution, and derive results from our models for realistic time periods. These results allow us to generate practical rules of thumb that can be immediately implemented in current planning technologies.\ud \ud This material is based on research partially supported by the National Science Foundation Grants ACI-0113051 and CCR-9972372, the Air Force Office of Scientific Research Grant F49620-01-1-0040, Microsoft Corporation and the Guggenheim Foundation

Calcification depth of deep-dwelling planktonic foraminifera from the eastern North Atlantic constrained by stable oxygen isotope ratios of shells from stratified plankton tows

Stable oxygen isotopes (delta O-18) of planktonic foraminifera are one of the most used tools to reconstruct environmental conditions of the water column. Since different species live and calcify at different depths in the water column, the delta O-18 of sedimentary foraminifera reflects to a large degree the vertical habitat and interspecies delta O-18 differences and can thus potentially provide information on the vertical structure of the water column. However, to fully unlock the potential of foraminifera as recorders of past surface water properties, it is necessary to understand how and under what conditions the environmental signal is incorporated into the calcite shells of individual species. Deep-dwelling species play a particularly important role in this context since their calcification depth reaches below the surface mixed layer. Here we report delta O-18 measurements made on four deep-dwelling Globorotalia species collected with stratified plankton tows in the eastern North Atlantic. Size and crust effects on the delta O-18 signal were evaluated showing that a larger size increases the delta O-18 of G. inflata and G. hirsuta, and a crust effect is reflected in a higher delta O-18 signal in G. truncatulinoides. The great majority of the delta O-18 values can be explained without invoking disequilibrium calcification. When interpreted in this way the data imply depth-integrated calcification with progressive addition of calcite with depth to about 300m for G. inflata and to about 500m for G. hirsuta. In G. scitula, despite a strong subsurface maximum in abundance, the vertical delta O-18 profile is flat and appears dominated by a surface layer signal. In G. truncatulinoides, the delta O-18 profile follows equilibrium for each depth, implying a constant habitat during growth at each depth layer. The delta O-18 values are more consistent with the predictions of the Shackleton (1974) palaeotemperature equation, except in G. scitula which shows values more consistent with the Kim and O'Neil (1997) prediction. In all cases, we observe a difference between the level where most of the specimens were present and the depth where most of their shell appears to calcify.Agência financiadora Portuguese Foundation for Science and Technology (FCT): SFRH/BD/78016/2011; UID/Multi/04326/2019 European Union Seventh Framework Programme (FP7/2007-2013): 228344-EUROFLEETS German Research Foundation (DFG): WA2175/2-1; WA2175/4-1 German Climate Modelling consortium PalMod - German Federal Ministry of Education and Research (BMBF)info:eu-repo/semantics/publishedVersio

Collaborative Preference: The Role of Homophily, Multiplexity, and Advantageous Network Position across Small and Medium-sized Organizations

The purpose of this paper is to examine collaboration between individuals across organizations. While both for profit and not-for-profit organizations utilize collaborative efforts, the factors that are important for bringing individuals and businesses together for collaboration still remain somewhat unresolved. In this paper, colleague similarity, the quality of pre-existing relationships, and the relative power of the other colleague are all examined for their correlation with the desirability of collaboration with that individual. In a study of pastors of small and medium sized churches in a southwestern protestant conference, we examined these areas through the lenses of homophily theory, multiplicity theories, and network positioning theories and found support for each of our hypotheses. Implications for management as well as future research directions are also presented

Analgesic and decongestant efficacy of the combination of aspirin with pseudoephedrine in patients with symptoms of upper respiratory tract infection

The study investigated the efficacy and safety of a combination therapy of 1,000 mg aspirin (ASA) and 60 mg pseudoephedrine (PSE) on the symptoms of pain (combined score for headache and sore throat) and nasal congestion in 833 patients with acute upper respiratory tract viral infection (URTI), over 4 hours after a single dose in the clinic and over 3 days with multiple doses at home. The study demonstrated that over 4 hours in the clinic the combination ASA plus PSE was superior to PSE or placebo for relief of pain symptoms measured subjectively with pain scores, and was superior to ASA or placebo for relief of nasal congestion as measured objectively with rhinomanometry and subjectively with congestion scores. After 3 days of treatment, ASA plus PSE was superior to PSE but not to placebo or ASA for global pain assessments, and ASA plus PSE was superior to ASA and placebo but not to PSE for congestion assessments. No unexpected adverse events occurred and no serious adverse events were attributed to study medicines. This study demonstrates that a combination therapy of ASA plus PSE provides safe and effective relief of both common cold pain related symptoms and nasal congestion

A functional genomic screen in Saccharomyces cerevisiae reveals divergent mechanisms of resistance to different alkylphosphocholine chemotherapeutic agents

The alkylphosphocholine (APC) class of antineoplastic and antiprotozoal drugs, such as edelfosine and miltefosine, are structural mimics of lyso-phosphatidylcholine (lyso-PC), and are inhibitory to the yeast Saccharomyces cerevisiae at low micromolar concentrations. Cytotoxic effects related to inhibition of phospholipid synthesis, induction of an unfolded protein response, inhibition of oxidative phosphorylation, and disruption of lipid rafts have been attributed to members of this drug class, however, the molecular mechanisms of action of these drugs remain incompletely understood. Cytostatic and cytotoxic effects of the APCs exhibit variability with regard to chemical structure, leading to differences in effectiveness against different organisms or cell types. We now report the comprehensive identification of S. cerevisiae titratableessential gene and haploid nonessential gene deletion mutants that are resistant to the APC drug miltefosine (hexadecyl-O-phosphocholine). Fifty-eight strains out of~5600 tested displayed robust and reproducible resistance to miltefosine. This gene set was heavily enriched in functions associated with vesicular transport steps, especially those involving endocytosis and retrograde transport of endosome derived vesicles to the Golgi or vacuole, suggesting a role for these trafficking pathways in transport of miltefosine to potential sites of action in the endoplasmic reticulum and mitochondrion. In addition, we identified mutants with defects in phosphatidylinositol-4-phosphate synthesis (TetO::STT4) and hydrolysis (sac1Δ), an oxysterol binding protein homolog (osh2Δ), a number of ER-resident proteins, and multiple components of the eisosome. These findings suggest that ER-plasma membrane contact sites and retrograde vesicle transport are involved in the interorganelle transport of lyso-PtdCho and related lyso-phospholipid-like analogs to their intracellular sites of cytotoxic activity

Factors controlling the depth habitat of planktonic foraminifera in the subtropical eastern North Atlantic

Planktonic foraminifera preserved in marine sediments archive the physical and chemical conditions under which they built their shells. To interpret the paleoceano-graphic information contained in fossil foraminifera, the recorded proxy signals have to be attributed to the habitat and life cycle characteristics of individual species. Much of our knowledge on habitat depth is based on indirect methods, which reconstruct the depth at which the largest portion of the shell has been calcified. However, habitat depth can be best studied by direct observations in stratified plankton nets. Here we present a synthesis of living planktonic foraminifera abundance data in vertically resolved plankton net hauls taken in the eastern North Atlantic during 12 oceanographic campaigns between 1995 and 2012. Live (cytoplasm-bearing) specimens were counted for each depth interval and the vertical habitat at each station was expressed as average living depth (ALD). This allows us to differentiate species showing an ALD consistently in the upper 100m (e.g., Globigerinoides ruber white and pink), indicating a shallow habitat; species occurring from the surface to the subsurface (e.g., Globigerina bulloides, Globorotalia inflata, Globorotalia truncatulinoides); and species inhabiting the subsurface (e.g., Globorotalia scitula and Globorotalia hirsuta). For 17 species with variable ALD, we assessed whether their depth habitat at a given station could be predicted by mixed layer (ML) depth, temperature in the ML and chlorophyll a concentration in the ML. The influence of seasonal and lunar cycle on the depth habitat was also tested using periodic regression. In 11 out of the 17 tested species, ALD variation appears to have a predictable component. All of the tested parameters were significant in at least one case, with both seasonal and lunar cyclicity as well as the environmental parameters explaining up to >50% of the variance. Thus, G. truncatulinoides, G. hirsuta and G. scitula appear to descend in the water column towards the summer, whereas populations of Trilobatus sacculifer appear to descend in the water column towards the new moon. In all other species, properties of the mixed layer explained more of the observed variance than the periodic models. Chlorophyll a concentration seems least important for ALD, whilst shoaling of the habitat with deepening of the ML is observed most frequently. We observe both shoaling and deepening of species habitat with increasing temperature. Further, we observe that temperature and seawater density at the depth of the ALD were not equally variable among the studied species, and their variability showed no consistent relationship with depth habitat. According to our results, depth habitat of individual species changes in response to different environmental and ontogenetic factors and consequently planktonic foraminifera exhibit not only species-specific mean habitat depths but also species-specific changes in habitat depth.Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/78016/2011]; MARUM - Center for Marine Environmental Sciences; European Union [228344-EUROFLEETS]; DFG (German Research Foundation) [WA2175/2-1, WA2175/4-1]; German Climate Modeling consortium PalMod - German Federal Ministry of Education and Research (BMBF); CANIGO project (EU) [MAS-CT96-0060]; DFGinfo:eu-repo/semantics/publishedVersio

The transcriptome of utricle hair cell regeneration in the avian inner ear

Sensory hair cell loss is the major cause of hearing and balance disorders. Mammals are incapable of sustained hair cell regeneration, but lower vertebrates can regenerate these mechano-electrical transducers. We present the first comprehensive transcriptome (by mRNA-Seq) of hair cell regeneration in the chick utricle. We provide pathway and pattern annotations and correlate these with the phenotypic events that occur during regeneration. These patterns are surprisingly synchronous and highly punctuated. We show how these patterns are a new resource for identifying components of the hair cell transcriptome and identify 494 new putative hair-cell-specific genes and validate three of these (of three tested) by immunohistochemical staining. We describe many surprising new components and dynamic expression patterns, particularly within NOTCH signaling. For example, we show that HES7 is specifically expressed during utricle hair cell regeneration and closely parallels the expression of HES5. Likewise, the expression of ATOH1 is closely correlated with HEYL and the HLH inhibitory transcription factors ID1, ID2, and ID4. We investigate the correlation between fibroblast growth factor signaling and supporting cell proliferation and show that FGF20 inhibits supporting cell proliferation. We also present an analysis of 212 differentially expressed transcription factor genes in the regenerative time course that fall into nine distinct gene expression patterns, many of which correlate with phenotypic events during regeneration and represent attractive candidates for future analysis and manipulation of the regenerative program in sensory epithelia and other vertebrate neuroepithelia

Combining remote sensing techniques and field surveys for post‑earthquake reconnaissance missions

Remote reconnaissance missions are promising solutions for the assessment of earthquake induced structural damage and cascading geological hazards. Space-borne remote sensing can complement in-field missions when safety and accessibility concerns limit post-earthquake operations on the ground. However, the implementation of remote sensing techniques in post-disaster missions is limited by the lack of methods that combine different techniques and integrate them with field survey data. This paper presents a new approach for rapid post-earthquake building damage assessment and landslide mapping, based on Synthetic Aperture Radar (SAR) data. The proposed texture-based building damage classification approach exploits very high resolution post-earthquake SAR data integrated with building survey data. For landslide mapping, a backscatter intensity-based landslide detection approach, which also includes the separation between landslides and flooded areas, is combined with optical-based manual inventories. The approach was implemented during the joint Structural Extreme Event Reconnaissance, GeoHazards International and Earthquake Engineering Field Investigation Team mission that followed the 2021 Haiti Earthquake and Tropical Cyclone Grace

La dimensión democrática de la nueva gestión pública

El eje temático de este nuevo número de la revista GAPP ha estado injustamente marginado de los apasionados debates que ha suscitado la modernización de la administración pública. La atracción que ha ejercido la gestión empresarial, las modas privatizadoras y desreguladoras o, más genéricamente, el desprestigio del gobierno y de la cosa pública contribuyen a explicar por qué, durante la última década, la dimensión democrática de la administración pública ha aparecido únicamente en algunas eruditas notas a pie de página. Esta marginación, sin embargo, no ha conseguido reducir la importancia del tema. Ha conseguido, en cambio, distorsionar peligrosamente el discurso de la modernización administrativa