In this paper, we report how roadside cutting affect individuals of field gentian Gentianella campestris, a highly cutting tolerant grassland herb, and if roadsides could serve as refugia for this endangered species. Injured plants produced four times more branches located close to the ground and the plants were more than two times heavier compared to the uninjured ones. No differences in final reproductive parameters between the injured and uninjured plants were observed. Unsuccessful and slow allocation of belowground resources to reproductive organs to be the reason for the overcompensation injured plants, when measured in vegetative biomass, but not in reproductive output. However, because the injured plants either fully compensated, or even overcompensated, the damage in all parameters, our results suggest that substitutive habitats, such as the roadside in question, may provide temporary safe-sites for some species, and from these refugia they may disperse back to their original, restored habitats in the future.


Chromium is naturally occurring, but emission from anthropogenic sources can lead to increased soil concentrations. Information on its toxicokinetics is essential in order to understand the time needed to reach toxicity and the mechanisms of uptake/elimination. In this study the toxicokinetics of Cr(III) was evaluated using the soil standard species Enchytraeus crypticus. The animals were exposed to 180 mg Cr/kg dry soil, a sublethal concentration, in LUFA 2.2 natural soil. OECD guideline 317 was followed, with a 14-day uptake phase in spiked soil followed by a 14-day elimination in clean soil. Exposure to Cr led to fast uptake and elimination, with Ku = 0.012 kgsoil/kgorganism/day and Ke = 0.57 day−1. The bioaccumulation factor was 0.022, and DT50 for elimination was 1.2 days. The concentration of Cr reached an internal equilibrium in the animals after 10 days. Transfer to clean soil allowed body Cr concentrations to return to background levels after approximately 7 days. E. crypticus seemed able to efficiently regulate internal Cr concentrations by actively eliminating Cr (an essential element). Although Ku and Ke deviated from the values reported in other studies for other soil invertebrates, the bioaccumulation factors were similar. These findings show the importance of toxicokinetic studies in evaluating toxicity based on internal metal concentrations that can more accurately represent the bioavailable concentration.


Post-traumatic mortality rates are still very high and show an increasing tendency. Early identification of patients at high risk of severe complications has a significant impact on treatment outcomes. The aim of the study was to better understand the early pathological inflammatory response to injury and infection, and to determine the usefulness of the assessment of TNF-α and sTNFR1 concentrations in the peripheral blood as early indicators of severe post-traumatic complications. The study was carried out in a group of 51 patients after trauma, treated in the ED, including 32 patients who met the inclusion criteria for immunological analysis. Patients were divided into two groups using the ISS scale (A ISS ≥ 20, B ISS < 20). The highest TNF-α and sTNFR1 concentrations in both groups were recorded at admission and were significantly higher in group A compared to group B (A vs. B TNF-α 2.46 pg/ml vs. 1.78 pg/ml; sTNFR1 1667.5 pg/ml vs. 875.2 p < 0.005). The concentration of sTNFR1 in patients with severe complications was significantly higher compared to patients without complications and preceded clinical symptoms of complications (C+ vs. C– 1561.5 pg/ml vs. 930.6 pg/ml, p < 0,005). The high diagnostic sensitivity calculated from the ROC curves was found for the concentrations of both cytokines: TNF-α (AUC = 0.91, p = 0.004) and sTNFR1 (AUC = 0.86, p = 0.011). Elevated levels of sTNFR1, determined in the peripheral blood shortly after injury, are significantly associated with the occurrence of later complications, which in some patients lead to death. In contrast, high levels of TNF-α shortly after injury are associated with mortality.


A narrow-band adaptive multipass amplifier with four-wave phase-conjugating mirrors was developed. Pumping of these mirrors with radiations from two independent master oscillators was used in a three-pass CO2 amplifier with two four-wave mirrors operating on the basis of a thermal nonlinearity of a liquid (CCl4). The total gain achieved in this way was 2×1011. Two-pass and four-pass operation was also achieved and the corresponding gains were 1.5×107 and 5×109, respectively.


Background: Hospital semiprivate rooms may lead to coronavirus disease 2019 (COVID-19) patient exposures. We investigated the risk of COVID-19 patient-to-patient exposure in semiprivate rooms and the subsequent risk of acquiring COVID-19. Methods: The University of Iowa Hospitals & Clinics is an 811-bed tertiary care center. Overall, 16% of patient days are spent in semiprivate rooms. Most patients do not wear masks while in semiprivate rooms. Active COVID-19 surveillance included admission and every 5 days nasopharyngeal SARS-CoV-2 polymerase chain reaction (PCR) testing. We identified inpatients with COVID-19 who were in semiprivate rooms during their infectious periods during July–December 2020. Testing was repeated 24 hours after the first positive test. Cycle threshold (Ct) values of the two tests (average Ct <30), SARS-CoV-2 serology results, clinical assessment, and COVID-19 history were used to determine patient infectiousness. Roommates were considered exposed if in the same semiprivate room with an infectious patient. Exposed patients were notified, quarantined (private room), and follow-up testing was arranged (median seven days). Conversion was defined as having a negative test followed by a subsequent positive within 14 days after exposure. We calculated the risk of exposure: number of infectious patients in semiprivate rooms/number of semiprivate patient-days (hospitalization days in semiprivate rooms). Results: There were 16,427 semiprivate patient days during July–December 2020. We identified 43 COVID-19 inpatients who roommates during their infectious periods. Most infectious patients (77%) were male; the median age was 67 years; and 22 (51%) were symptomatic. Most were detected during active surveillance: admission testing (51%) and serial testing (28%). There were 57 exposed roommates. The risk of exposure was 3 of 1,000 semiprivate patient days. In total, 16 roommates (28%) did not complete follow-up testing. Of 41 exposed patients with follow-up data, 8 (20%) converted following their exposure. Median time to conversion was 5 days. The risk of exposure and subsequent conversion was 0.7 of 1,000 semiprivate patient days. Median Ct value of the source patient was 20 for those who converted and 23 for those who did not convert. Median exposure time was 45 hours (range, 3–73) for those who converted and 12 hours (range, 1–75) for those who did not convert. Conclusions: The overall risk of exposure in semiprivate rooms was low. The conversion rate was comparable to that reported for household exposures. Lower Ct values and lengthier exposures may be associated with conversion. Active COVID-19 surveillance helps early detection and decreases exposure time. Funding: No Disclosures: None


Traditional portfolio insurance strategies implement the insurance strategy all through the investment period.It does can obtain the insurance effect in the bearish market,but lose some return in the bullish market.The VaR-Based contingent portfolio insurance strategy,applying VaR technique and filter rule,however can offset the above drawback.And this portfolio insurance strategy can provide an efficient investment instrument for the insurance capital in China.


The present study tries to explain the anthropological assumptions implicitly contained in Michel Henrys ontology of corporality and specifically in his theory concerning the possibility of a subjectively determined body. In order to achieve this, we examine previously four paradigms regarding the theory of corporality (to be specific, those proposed by Descartes, Sartre, Merleau-Ponty and Heidegger), highlighting their respective tacit implications on the essence of man. From this criticism addressed by Henry to these four models of reflection concerning the corporal, derives a unitary conception of the human phenomenon, as well as a rehabilitation of the ontological status of subjectivity.


The insulin-like growth factors (IGF), IGF-I and IGF-II, influence ovarian follicular development. The IGF binding proteins (IGFBPs) comprise at least six distinct species which may modulate IGF action. We examined IGFBP profiles in follicular fluid (FF) from developing human ovarian follicles with aromatase activity as well as from androgen-dominant, atretic follicles. Western ligand blot analysis of FF from both atretic and active follicles revealed the presence of IGFBP-3 and IGFBP-2, confirmed by immunoprecipitation with specific antiserum, as well as 28 kilodalton (kDa) and 24 kDa IGFBPs. In FF specimens obtained during the follicular phase, IGFBP-2 and the 28 kDa and 24 kDa species were present in 3-, 6-, and 19-fold higher amounts in atretic compared to healthy developing follicles, respectively, and were present in greater amounts in atretic FF than in serum. In atretic FF obtained during the luteal phase, lower levels of IGFBP-2 and the 28 and 24 kDa IGFBPs were seen than in atretic follicles in the follicular phase. IGFBP-3 levels were comparable in all types of follicles and in serum. The 28 kDa IGFBP is glycosylated, and its level varied in parallel with the 24 kDa IGFBP, suggesting that these are variants of the recently identified IGFBP-4. IGFBP-1 was not detectable by immunoprecipitation and ligand blotting of FF obtained during the follicular phase. These data suggest that one or more IGFBPs present in higher levels in FF from atretic compared to healthy, developing follicles may play an important role in folliculogenesis and follicular atresia.


A failure of coronary blood flow to increase during cold pressor test has been shown in patients with coronary atherosclerosis and impaired metabolic coronary vasodilatation in response to atrial pacing has been demonstrated in diabetic patients without significant epicardial artery stenoses. This study was designed to evaluate coronary microvascular adaptation to increased myocardial oxygen demand in response to sympathetic stimulation in diabetic patients with angiographically normal coronary arteries. Microvascular coronary adaptation to increased myocardial oxygen demand due to sympathetic stimulation evoked by the cold pressor test has been examined in 22 type 2 diabetic patients and in 15 control subjects with angiographically normal coronary arteries and no other risk factors. Coronary blood flow was calculated by measuring mean flow velocity in left anterior descending coronary artery by intracoronary Doppler and cross sectional area of the artery by digital angiography. Results show that despite a similar increase in rate-pressure product in the 2 groups (+22.6 +/- 12.4% in diabetic patients and +31.8 +/- 8.2% in control subjects, NS), coronary blood flow increase in left anterior descending artery was significantly lower in diabetic patients than in control subjects (+14.7 +/- 19.8% vs +75.5 +/- 13.5%, respectively, p = 0.0001). In addition, when there was a positive correlation between the 2 parameters in control subjects (R = 0.651, p < 0.01), there was no relationship in diabetic patients (R = 0.054). In conclusion, this study demonstrates that vasodilatation of coronary microcirculation in response to sympathetic stimulation evoked by cold pressor test is impaired in type 2 diabetic patients without epicardial artery lesions. This microvascular impairment during sympathetic stimulation may explain exercise-induced myocardial perfusion abnormalities observed in these patients and may impair microcirculatory coronary vasodilatation during current life stress episodes such as exercise, mental stress or cold exposure.


Defects in the form of cylindrical amorphous tracks were introduced into YBa 2 Cu 3 O 7 crystals by irradiation with 5.3-GeV Pb ions. The columnar defects formed provide maximum possible pinning of flux lines parallel to the tracks and induce giant enhancement of magnetic irreversibility. However, even for this strong pinning, magnetic decay was measured at high temperatures. Relaxation is nonlogarithmic and exhibits an increase of the effective barrier for flux creep with decreasing persistent current. This behavior is interpreted in the framework of the nucleation creep model


What I cannot create, I do not understand" said the famous writing on Dr. Feynman's blackboard. The ability to create or to change objects requires us to understand their structure and factors of variation. For example, to draw a face an artist is required to know its composition and have a good command of drawing skills (the latter is particularly challenging for the presenter). Animation additionally requires the knowledge of rigid and non-rigid motion patterns of the object. This talk shows that generation, manipulation and animation skills of deep generative models substantially benefit from such understanding. Moreover we see, the better the models can explain the data they see during training, the higher quality content they are able to generate. Understanding and generation form a loop in which improved understanding improves generation, improving understanding even more. To show this, I detail our works in three areas: video synthesis and prediction, image animation by motion retargeting. I will further introduce a new direction in video generation which allows the user to play videos as they're generated. In each of these works, the internal representation was designed to facilitate better understanding of the task, resulting in improved generation abilities. Without a single labeled example, our models are able to understand factors of variation, object parts, their shapes, their motion patterns and perform creative manipulations previously only available to trained professionals equipped with specialized software and hardware.


Summary
Agricultural intensification is a major cause of reptile and amphibian decline world-wide, prompting concern on how to best protect biodiversity in commodity production landscapes and meet global food demands. Agri-environment schemes (AES) attempt to integrate biodiversity conservation in agricultural landscapes but are often compromised by a lack of baseline data, monitoring and evaluation. Few studies have examined the benefits of AES in protecting biodiversity relative to the wider farming landscape, and no studies have explicitly quantified the effectiveness of AES to increase herpetofaunal diversity.
To examine whether AES protect and increase herpetofauna, we established a landscape-wide biodiversity monitoring programme in threatened semi-arid and temperate woodland communities in south-eastern Australia.
With 31 species recorded, regional herpetofaunal diversity was relatively high, whereas local diversity was low. Herpetofaunal richness and reptile assemblage structure did not differ significantly between sites under AES and sites managed for livestock production. A gradient in species richness as a function of time-since-management intervention was not evident, although the abundance of one lizard species increased under vegetation management. Reptile richness and frog abundance differed significantly among vegetation types.
Herpetofaunal richness was positively related to native plant richness and bare ground cover, whereas Boulenger's skink Morethia boulengeri was negatively affected by bare ground cover. The ragged snake-eyed skink Cryptoblepharus pannosus was positively related to the amount of woody debris.
Synthesis and applications. In this system, strong habitat specificity implies local-scale management interventions under agri-environment schemes (AES) may not significantly increase herpetofaunal diversity in the short term. Vegetation management is likely to increase the abundance of common lizard species rather than increase local species richness due to barrier effects. Future incentive schemes should focus on improving habitat connectivity, enhancing pasture condition and increasing woody debris in the agricultural matrix to dissolve dispersal barriers and mitigate the legacy of historical land-use practices. We propose that AES, which manage mosaics of intergrading vegetation types at multiple spatial scales, will protect maximum herpetofaunal diversity. These recommendations have implications for AES world-wide, many of which currently do not adequately address the habitat requirements of herpetofauna.


It has been a more complex problem for water quality assessment. And its aim is to well and truly evaluate its degree of pollution for bodies of water, which will be easy to provide some principled projects and criterions for water resource's protection and their integration application. So, a water quality assessment method based on Multiclass Fuzzy Support Vector Machine is put forward. and a two-step cross-validation was used to search for the best combination of parameters to obtain an optimal training model. The test results show that the method proposed in this paper has an excellent performance on correct ratio compared to BP. It indicated that the performance of the proposed model is practically feasible in the application of water quality assessment.


In many inventory control contexts, inventory levels are only partially (i.e., not fully) observed. This may be due to nonobservation of demand, spoilage, misplacement, or theft of inventory. We study a partially observed inventory system where the demand is not observed, inventory level is noticed when it reaches zero, the unmet demand is lost, and replenishment orders must be decided so as to minimize the total discounted costs over an infinite horizon. This problem has an infinite-dimensional state space, and for it we establish the existence of a feedback policy when single-period costs are bounded or when the discount factor is sufficiently small. We also provide an approximately optimal feedback policy that uses a finite state representation.


Summary. The development of new technologies leads to the discovery of new viruses. For each of these new infectious agents, relevance to transfusion, including transmissibility by transfusion, pathogenicity, prevalence in blood donors, persistence and the availability of screening assays needs to be assessed. Since 1995, one virus and a new family of viruses have been identified. GB virus‐C/hepatitis G virus (GBV‐C/HGV), a flavi virus with some homology with and epidemiological features of HCV, is not related to post‐transfusion hepatitis but seems to positively interfere with human immunodeficiency virus replication. Human circoviruses include TT virus (TTV) and SEN‐V. Both are highly variable, constituting a large family of distantly related viruses. They appear ubiquitous, infecting humans very early in life and are largely persistent. No clinical symptoms or pathogenicity is associated with TTV, but SEN‐V might be associated with some non‐A–E post‐transfusion hepatitis. Parvovirus B19 has been known for many years, but its transmission to recipients of plasma derivatives despite viral inactivation raised the issue of screening plasma pools by nucleic acid testing. Most fractionators quantify B19 DNA in plasma pools to ensure a viral load of <104 IU mL−1.


The cholinergic hypothesis of Alzheimer's disease suggests that cholinergic agonists may have therapeutic potential for treating the attendant memory deficits of the disease. As part of a program aimed at preparing metabolically stable, nonquaternary analogs of muscarone, 1-oxa-2,8-dimethyl-8-azaspiro[4.5]decan-3-one, 2a, and related analogs have been synthesized and their in vitro muscarinic activity evaluated. The synthetic strategy in the formation of the 1-spiro[4.5]decan-3-one ring system of 2a involved cyclization of the diol 4 in the presence of Nafion-Hg. The spiromuscarone 2a was found to displace [3H]Oxo-M binding with a Ki value of 7 nM. Affinities of the oxime and hydrazone analogs of 2a were lower than 2a. The compounds in these series were partial muscarinic agonists as demonstrated by stimulation of phosphatidyl inositol hydrolysis assay, with 2a showing the highest intrinsic intrinsic activity (60% as compared with carbachol). The results from this study indicate that an exo double bond at the C-3 position is essential for the receptor binding.


Task graphs have been studied for decades as a foundation for scheduling irregular parallel applications and incorporated in many programming models including OpenMP. While many high-performance parallel libraries are based on task graphs, they also have additional scheduling requirements, such as synchronization within inner levels of data parallelism and internal blocking communications. In this paper, we extend task-graph scheduling to support efficient synchronization and communication within tasks. Compared to past work, our scheduler avoids deadlock and oversubscription of worker threads, and refines victim selection to increase the overlap of sibling tasks. To the best of our knowledge, our approach is the first to combine gang-scheduling and work-stealing in a single runtime. Our approach has been evaluated on the SLATE high-performance linear algebra library. Relative to the LLVM OMP runtime, our runtime demonstrates performance improvements of up to 13.82%, 15.2%, and 36.94% for LU, QR, and Cholesky, respectively, evaluated across different configurations related to matrix size, number of nodes, and use of CPUs vs GPUs.


This article publishes for the first time a selection of letters written to Mr Samuel Whiteley by William Smail, Theodore Haarhoff, Kenneth White, and Henry Tillyard, between 1923 and 1971. These letters were preserved among the papers and books donated by Whiteley to the Classics department at the University of KwaZulu- Natal (then the University of Natal), in Durban. The letters are set in their historical context and analysed. They illuminate the history of Classics in mid-20th-century South Africa in a very personal way.


Purpose. To conduct an in vitro strength test for the Joshi External Stabilising System (JESS) for stabilisation of tibial fractures using a cadaveric tibia and steel rods. Methods. The configuration of the JESS specimens was based on a 62-year-old man with a metaphyseal tibial fracture. Two types of JESS specimens were prepared, using either the tibia of an average male adult cadaver (n=1) or stainless steel cylindrical rods (n=3). The strength of the JESS rather than that of the rods was measured using a universal testing machine. The axial compressive load was gradually increased at 1 mm/min to 35 N. Axial deformation of the fracture fragment was recorded. Each experiment was repeated 3 times in identical manner. A finite element analysis of the JESS was developed. The axial compressive loads and corresponding interfragmentary displacement in the experimental specimens and in the finite element analysis were compared. Results. The mean strength of the JESS was 32.5 N/mm in experiments and 35.3 N/mm in finite element analysis; the difference was 8.4%. The interfragmentary displacement was directly proportional to the axial compressive load. Conclusion. The strength of the JESS is one fourth of that of the Ilizarov fixator, and therefore not suitable for full load bearing activities.


BACKGROUND
In animal studies, sialic acid supplementation is associated with increases of gangliosides in the brain and improved learning ability. Only limited data are available on the sialic acid content of human milk and infant formulas.

OBJECTIVE
We compared the concentrations of oligosaccharide-bound, protein-bound, and free sialic acid in milk from mothers of full-term and preterm infants and in a range of infant formulas.

DESIGN
The milk from 20 and 14 mothers of full-term and preterm infants (mean gestational age: 31 +/- 3 wk), respectively, was collected at 4 stages of lactation (colostrum, transition, 1 mo, and 3 mo) and compared with 21 different infant formulas.

RESULTS
Total sialic acid concentrations were highest in colostrum (x +/- SEM: 5.04 +/- 0.21 mmol/L in full term) and decreased by nearly 80% over the next 3 mo. Human milk from mothers of preterm infants contained 13-23% more sialic acid than did milk from mothers of full-term infants at 3 of the 4 lactation stages (P < 0.02). The sialic acid content of most formulas was <25% of that found in mature human milk (P < 0.01). Most of the sialic acid in the formulas ( approximately 70%) was bound to glycoproteins, whereas in human milk most sialic acid was bound to free oligosaccharides.

CONCLUSIONS
Human milk, including milk from mothers of preterm infants, is a rich source of oligosaccharide-bound sialic acid, which contrasts with the relatively small amounts found in infant formulas. The nutritional significance of sialic acid is presently unknown, but it is plausible that it is a conditional nutrient that contributes to sialic acid accretion in the brain.


Ginger rhizome rot disease, caused by the pathogen Bacillus pumilus GR8, could result in severe rot of ginger rhizomes and heavily threaten ginger production. In this study, we identified and characterized a new Bacillus velezensis strain, designated ATR2. Genome analysis revealed B. velezensis ATR2 harbored a series of genes closely related to promoting plant growth and triggering plant immunity. Meanwhile, ten gene clusters involved in the biosynthesis of various secondary metabolites (surfactin, bacillomycin, fengycin, bacillibactin, bacilysin, difficidin, macrolactin, bacillaene, plantazolicin, and amylocyclicin) and two clusters encoding a putative lipopeptide and a putative phosphonate which might be explored as novel bioactive compounds were also present in the ATR2 genome. Moreover, B. velezensis ATR2 showed excellent antagonistic activities against multiple plant pathogenic bacteria, plant pathogenic fungi, human pathogenic bacteria, and human pathogenic fungus. B. velezensis ATR2 was also efficacious in control of aphids. The antagonistic compound from B. velezensis ATR2 against B. pumilus GR8 was purified and identified as bacillomycin D. In addition, B. velezensis ATR2 exhibited excellent biocontrol efficacy against ginger rhizome rot disease on ginger slices. These findings showed the potential of further applications of B. velezensis ATR2 as a biocontrol agent in agricultural diseases and pests management.


IEEE 802.11ay defines new PHY and MAC specifications that enable 100 Gb/s communications in the 60 GHz millimeter-wave (mmWave) band. Among the various use cases supported by IEEE 802.11ay, fixed wireless access, a cost-efficient high-performance alternative and/ or complement to conventional fixed access, differentiates itself due to its unique requirements and characteristics. In this article, our goal is to identify and describe key elements incorporated into IEEE 802.11ay, including scheduling, beamforming, and link maintenance, that efficiently support fixed wireless access. IEEE 802.11ay is thus a viable and strong candidate to form the basis of future generations of standards-compliant (i.e., non-proprietary) mmWave fixed wireless access networks.


With the discovery of graphene, significant research has focused on the synthesis, characterization, and applications of ultrathin materials. Graphene has also brought into focus other ultrathin materials composed of organics, polymers, inorganics, and their hybrids. Together, these ultrathin materials have unique properties of broad significance. For example, ultrathin materials have a large surface area and high flexibility which can enhance conformal contact in wearables and sensors leading to improved sensitivity. When porous, the short transverse diffusion length in these materials allows rapid mass transport. Alternatively, when impermeable, these materials behave as an ultrathin barrier. Such controlled permeability is critical in the design of encapsulation and drug delivery systems. Finally, ultrathin materials often feature defect-free and single-crystal-like two-dimensional atomic structures resulting in superior mechanical, optical, and electrical properties. A unique property of ultrathin materials is their low bending rigidity, which suggests that they could easily be bent, curved, or folded into 3D shapes. In this Account, we review the emerging field of 2D to 3D shape transformations of ultrathin materials. We broadly define ultrathin to include materials with a thickness below 100 nm and composed of a range of organic, inorganic, and hybrid compositions. This topic is important for both fundamental and applied reasons. Fundamentally, bending and curving of ultrathin films can cause atomistic and molecular strain which can alter their physical and chemical properties and lead to new 3D forms of matter which behave very differently from their planar precursors. Shape change can also lead to new 3D architectures with significantly smaller form factors. For example, 3D ultrathin materials would occupy a smaller space in on-chip devices or could permeate through tortuous media which is important for miniaturized robots and smart dust applications. Our Account highlights several differences between ultrathin and traditional shape change materials. The latter is typically associated with hydrogels, liquid crystals, or shape memory elastomers. As compared to bulk materials, ultrathin materials can much more easily bend and fold due to the significantly reduced bending modulus. Consequently, it takes much less energy to alter the shape of ultrathin materials, and even small environmental stimuli can trigger a large response. Further, the energy barriers between different configurations are small which allow a variety of conformations and enhances programmability. Finally, due to their ultrathin nature, the shape changes are typically not slowed down by sluggish mass or thermal transport, and thus, responses can be much faster than those of bulk materials. The latter point is important in the design of high-speed actuators. Consequently, ultrathin materials could enable low-power, rapid, programmable, and complex shape transformations in response to a broad range of stimuli such as pH, temperature, electromagnetic fields, or chemical environments. The Account also includes a discussion of applications, important challenges, and future directions.


Background: The final treatment for castration-resistant prostate cancer (CRPC) is generally cabazitaxel treatment. However, once CRPC becomes resistant to cabazitaxel, the patients are obliged to best supportive care. Therefore, the elucidation of the mechanism of the cabazitaxel-resistance and the conquest are important themes to improve the prognosis of the patients. We already established paclitaxel/docetaxel-resistant prostate cancer, PC-3-TxR and DU145-TxR cells, and characterized those cell lines previously. Then we further tried to establish cabazitaxel-resistant prostate cancer cell lines, and characterized those cell lines. Materials and Methods: We established two cabazitaxel-resistant cell lines, PC-3-TxR/CxR and DU145-TxR/CxR by increasing concentration of cabazitaxel from 1 nM to 30 nM gradually when PC-3-TxR and DU145-TxR cells were passaged. We confirmed the IC50 of docetaxel and cabazitaxel of these cells. Next we purified total RNA and performed cDNA microarray (Agilent and compared gene expression profiles among these cells. Results and Conclusion: IC50 of PC-3-TxR and PC-3-TxR/CxR for cabazitaxel was 1.3 nM and 15.4 nM, respectively. IC50 of DU145-TxR and DU145-TxR/CxR was 7.0 nM and 30. 8 nM, respectively. Comparison of cDNA microarray between PC-3-TxR and PC-3-TxR/CxR cells or between DU145-TxR and DU145-TxR/CxR cells revealed that 4,470 genes in PC-3-TxR/CxR, and 1,345 genes in DU145-TxR/CxR cells were upregulated more than 3-fold and 4,683 genes PC-3-TxR/CxR and 1,537 genes were downregulated less than 0.3-fold, respectively. Especially, although expression of ABCB1 (MDR) gene was upregulated in DU145-TxR by 500-fold compared with DU145 cells, it was not upregulated in not upregulated in DU145-TxR/CxR cells any more. In contrast, expression of ABCB1 gene was upregulated in PC-3-TxR by 20-fold compared with PC-3 cells and it was further upregulated in PC-3-TxR/CxR by 40-fold compared with PC-3-TxR. In conclusion, various genes were regulated in cabazitaxel-resistant PCa cells and different mechanisms might be involved in this resistance in different cell lines. Citation Format: Atsushi Mizokami, Kazuaki Machioka, Kouji Izumi, Maolake Aerken, Ariunbold Natsagdorji, Yoshifumi Kadono, Yuta Takezawa, Hiroaki Iwamoto, Evan T. Keller. Establishment of cabazitaxel-resistant prostate cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 85. doi:10.1158/1538-7445.AM2017-85


Regulation of cell growth and proliferation has a fundamental role in animal and plant development and in the progression of cancer. In the context of development, it is important to understand the mechanisms that coordinate growth and patterning of tissues. Imaginal discs, which are larval precursors of fly limbs and organs, have provided much of what we currently know about these processes. Here, we consider the mechanism that is responsible for the observed uniformity of growth in wing imaginal discs, which persists in the presence of gradients in growth inducing morphogens in spite of the stochastic nature of cell division. The phenomenon of "cell competition," which manifests in apoptosis of slower-growing cells in the vicinity of faster growing tissue, suggests that uniform growth is not a default state but a result of active regulation. How can a patch of tissue compare its growth rate with that of its surroundings? A possible way is furnished by mechanical interactions. To demonstrate this mechanism, we formulate a mathematical model of nonuniform growth in a layer of tissue and examine its mechanical implications. We show that a clone growing faster or slower than the surrounding tissue is subject to mechanical stress, and we propose that dependence of the rate of cell division on local stress could provide an "integral-feedback" mechanism stabilizing uniform growth. The proposed mechanism of growth control is not specific to imaginal disc growth and could be of general relevance. Several experimental tests of the proposed mechanism are suggested.


Linear models with structured covariance matrices are applicable to a wide variety of longitudinal data sets. This paper presents a method for construct- ing simultaneous confidence bands for the growth or response curve. The bands can be defined on finite intervals and various other subsets of the real line. Previous re- sults on simultaneous confidence bands in linear regression with independent errors are generalized to include correlated errors when the covariance matrix depends on a finite number of unknown parameters. A correction for the additional variabil- ity arising from estimation of unknown covariance parameters is presented. The method is evaluated using data simulated from several different linear models, and it is applied to the analysis of pig metabolite concentrations after brief myocardial ischemia.


Many machine learning problems can be abstracted in solving game theory formulations and boil down to optimizing nested objectives, such as generative adversarial networks (GANs) and multi-agent reinforcement learning. Solving these games requires finding their stable fixed points or Nash equilibrium. However, existing algorithms for solving games suffer from empirical instability, hence demanding heavy ad-hoc tuning in practice. To tackle these challenges, we resort to the emerging scheme of Learning to Op-timize (L2O), which discovers problem-specific efficient optimization algorithms through data-driven training. Our customized L2O framework for differentiable game theory problems, dubbed "Learning to Play Games" (L2PG), seeks a stable fixed point solution, by predicting the fast update direction from the past trajectory, with a novel gradient stability-aware, sign-based loss function. We further incorporate curriculum learning and self-learning to strengthen the empirical training stability and generalization of L2PG. On test problems including quadratic games and GANs, L2PG can substantially accelerate the convergence, and demonstrates a remarkably more stable trajectory. Codes are available at https: //github.com/VITA-Group/L2PG .


AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

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Introduction: Pancreatic ductal carcinoma is one of unfavorable prognostic carcinomas. More than half of pancreatic carcinoma patients are diagnosed at advanced and inoperative stages, and consequently, depend on chemotherapy. However, almost all such cases are resistant to anticancer reagents. In this study, we attempted to establish a specific monoclonal antibody to chemoresistant pancreatic carcinomas. Method: Four female BALB/c mice were immunized live PANC-1 cells pretreated with an anti-cancer drug, gemcitabine. Splenocytes from the immunized mice were fused with myeloma cell line NS1/1-Ag4-1. After screening 615 clones, we established a monoclonal antibody 2G12 that reacted with the PANC-1 cells and pancreatic ductal carcinoma tissue, but not with normal pancreas tissue. The antigen of 2G12 was characterized by immunoblotting after pretreatment with several enzymes and reagents. In addition, distribution of the 2G12 antigen in various malignant tumors was also determined by immunohistochemistry. Results: Antibody 2G12 (IgG1) recognized the O-linked carbohydrate chains of 160-kDa glycoprotein localized on the plasma membrane and the cytoplasm in PANC-1 cells. Immunohistochemical investigation revealed that the 2G12 antigen was detected in 5 of 10 (50%) pancreatic carcinoma tissues. The 2G12 antigen was also distributed in various malignant tumors such as ovarian carcinomas (7 of 11, 64%), endometrial carcinomas (4 of 4, 100%), testicular germ cell tumors (10 of 16, 63%), renal bladder carcinoma (9 of 10, 90%), cholangiocarcinomas (5 of 10, 50%), breast carcinomas (7 of 8, 88%), RCC (5 of 11, 45%), esophageal carcinomas (3 of 11, 27%), HCC (2 of 10, 20%), gastric carcinomas (2 of 10, 20%), lung carcinomas (2 of 10, 20%), and thyroid carcinomas (1 of 10, 10%). In normal fetal and adult tissues, the 2G12 antigen was detected predominantly in the endothelium, the apical epithelial membrane of the uterine tube, and focal serous glands, but was absent in neuronal, myogenic, hematopoietic, and trophectodermal cells. Conclusion: Antibody 2G12 would be useful for the diagnosis of various malignant tumors.


Abstract Electrophysiological analysis of male antennal Sensilla trichodea in Xestia triangulum and X. ditrapezium showed that they contain the same five types of receptor cells in both species. These cells responded specifically to the (Z)-alkenyl acetates Z7-12:Ac, Z5-14:Ac, Z7-14:Ac, Z9-14:Ac and Z 11-14:Ac. Yet, in field trapping tests, male X. triangulum were highly attracted to pure Z5-14:Ac as a single compound, whereas male X. ditrapezium responded specifically to a ternary combination of Z5-/ Z7-/ Z9-14: Ac with the Z7 isomer as the major constituent. The four other "key compounds" in X. triangulum, and the other two in X. ditrapezium, inhibited trap captures. The results are considered in view of the close taxonomic relationship of the two species and their potential reproductive isolation from other, pheromonally-related noctuid moths.


Growth and allelism of arg-11 and adg Creative Commons License This work is licensed under a Creative Commons Attribution-Share Alike 4.0 License. This research note is available in Fungal Genetics Reports: http://newprairiepress.org/fgr/vol6/iss1/10 McDougall, K. J. and V. W. Woodword. Suppression of pyr-3 mutants of Neurospora. The mechanism by which pyr-3 mutants are suppressed has been described (IS fallows:carbamylphosphote (CAP) is synthesized in two independent pathways; one leoding to arginine synthesis and the other to pyrimidine synthesis. In the arginine pathway the enzyme carbumylphosphokinase (CPK ) catalyzes the synthesis of CAP, and the arg-3 mutation is the structural gene controlling CPK synthesis. Ornithine transcarbamylase (OTC ) catolyzesthecoupling of CAP with ornithine to yield citrullinc, and arg-12 is the structural gene for this WlZple. The enzyme catalyzing the synthesis of CAP in the pyrimidiawoy has not been described, yet certain of the pyr-3 mutants would appear to lack this enzyme activity. The enzyme asp&ate tronscarbamylase (ATC) c* CAP with aspartate to yield ureidceuccinic acid (US ); the pyr-3 locus serves also OS the structural gene for ATC. We have postulated, as has R. H. Davis, that the pyr-3 gene specifies one protein with two active sites, one site being the ATC and the other the CAP synthesiringsite. The mutation arg-12 is a leaky org-I2 mutation exhibiting about 3% of wild type OTC activity. This mutant has been known for many years to suppress certain of the pyr-3 mutants. Davis and Woodward (1962 Genetics 47: 1075 ) showed that those mutonk suppressed by erg-rive ATC activity but presumably lack the ability to synthesize CAP. We, therefore, postulate that-125 accumulates CAP which is then used by the pyr-3 component for pyrimidine synthesis. (Completes at the arg-I2 locus do not suppress pyr-3 mutants under these conditions because the required exogenous argininemts or represses CPK, shutting off the remaining scurce of CAP. ) In a search for alleles of arg-IB, four new pyr-3 suppressor mutations were found. These ore designated RU-I, 3, I2 and 20. Arginineadine double mutank were recovered after irradiating conidia of pyr-3 AT@ mutants and plating onto'minimol ogar. These double mutank were crossed to wild type and t&ads yielded the suppressed strains plus the individual components. In all cares it was shown that the arginine mutank possessed wild type OTC. The RU mutations are genetically distinct from arg-12. Wocdword and Schwarz (1964 Genetics 49: 846) hove shown that erg-I2 is located on linkage group II. RU-I is located on the right arm of linkage group V, 8 map units from2.8 map units from org-7, and 14.4 mop units from arg-8. The other three mutants are located on thmt arm of linkage grou-pproximately 29 map units dirtalto nit-I. Since these mutonk are intersterile, it is impossible to determine whether they comprise one or mxci. In 1952 the Mitchells (Proc. Natl. Acad. Sci. U. 5. 38:205) reported that arg-7 (orn-3) suppressed certain of the pyr-3 mutants. We have confirmed this and the fact that arg-6 (ormoes not suppress pyr-3. Collectively, these data would seem to complicate the above expmionppression. However, o paucity of ornithine substrate in the cell may have the same effect on pyr-3 as the accumulation of CAP. Either situation might make CAP available for pyrimidine synthesis. Studiesore now under way to analyze the concentrations of the arginine intermediates in the cells of these mutants. This work was supported by Public Health Service Grant No. GM 10216-02. Biology Deportment, Rice University, Houston, Texas. Newmeyer, D. Growth and ollelism The mutant arg-II (30820) was initially reported to of arg-II and adg. require argimor citrulline ) plus either o purine -or a pyrimidine (Srb 1950 @&an. Gaz. lll:470). It was subsequently mapped in linkage group VII, proximal to org-IO (Perkins 1959 Genetics 44: 1185 ). Mutant adg (44601 ), originally listed as "unknown requirement' 5s shown by Houlahan & al. (I949 Geneticsn:493) to segregate as (I single gene unlinked to sex (21 osci ). Subsequently J. Mauron (cited in G. Duber 1953 Ph. D. Thesis, California Institute of Technology) found adg to grow suboptimally on arginine plus either adenine or a pyrimidine. This result suggested o&&m with 30820, which proved to be the case (see below ). However, flask assays with these strains gave unexpected resulk. These results have been largely superseded by the recent report of Charles and Broodbent (1964 Nature 201: 1004) that 30820 will grow on minimal in the presence of 30% CO2 and that when CO2 is excluded both purine and pyrimidine become essential. However, as the relation of 30820 to the other CO2 mutants is still far from clear, our fragmentary results may be useful. Flask assays: (All results care based on 3 days growth at 25X in 20 ml of Vogel's Neurosporo minimal. ) It wZ&nm the growth requirements of 30820 are abnormally dependent on inoculum size. With very small inocula there is negligible growth unless arginine, odenine and uridine are all present, and optimal growth when all three ore added. (Alternative purines and pyrimidines were not tested.) As the inoculum size is increased, first uridine can be omitted; with a further increase in inoculum either adenine or uridine con be omitted; with still larger inoculo both odenine and uridine con be omitted.Tthe one experiment where conidia were counted, all three co=unds were essential at or below 2.2 x I@ conidia per flask. ) The growth of control cultures of arg-I (8369) and arg-3 (30300). which is also 0 co2 mutant, WCS essentially unaffected by a similar ranganoculum sizepreliminary tests mutant 44601 (odg ) behaved much like 30820, except that 44601 appeared to be a more extreme departure from wild type. Although with small inocula the requirements for adenine and uridine ore absolute, the concentrations required are very low. With 30820, essentially maximal growth was obtained with only 0.005 mg/ml each of adenine and uridine, compared with values in the literature of ca. 0.05 mg/ml for ordinary odenine mutants and ca. 0.075 mg/ml for ordinary pyrimidine mutants. The osnine requirement is also rather low (0.05 toll mg/ml ). It may be significant that the concentration of pyrimidine required by 30820 is similar to that which represses or inhibits the synthesis of pyrimidine-specific CAP, according to Charles's hypothesis (1964 J. Gen Microbial. 34: I31 ). Allelism tests: A cross of 30820 x 44601 gave no wild types among 268 random isolates and one true wild typeoutofanestimoted 4,000 oscospores plated (scored by early growth on minimal sorbcse, as in Lein et al. (1948 F'roc. Natl. Acod. Sci. U. S. 34:435). H owever, the results are complicated by the fact that rzgxly IO to 15% of the oscorpores also failed to grow on glycerol complete medium or on supplemented minimal. When isolated to complete slants, about half of these grew up in o few days; these will be called slows, and are not uncommon. The other half either did not grow et all, or grew so slowly that it took weeksxake a macrorcopically visible culture; these will be called near-lethols. Near-lethals were &o found among the random isolates. Since it was possible that wild type recombinants could occur preferentially among the near-lethols, via o pair of balanced lethols, four near-lethals from this cross were revived via prolonged growth and repeated s&culturing. These eventually attained a normal growth rate, and were then tested; ail failed to grow on minimal. (All I s ows tested also failed to grow on minimal. ) In addition, the balanced lethal hypothesis seems unlikely because a cross of wild type x 44601 also produced slows and near-lethals. (A cross of wild type x 30820 produced slows but no near-lethals among the small sample examined.) Allelism of 308x) and 44601 was also indicated by complementotion tests. Both mutants were backcrossed until strains were obtained which appeared fully compatible, in that each gave wild type heterocaryons with on arg-I tester. These strains did not complement each other. It is therefore concluded that 30820 and 4460l~alleles. It also seemed desirable to test for a functional relationship between arg-II and the rather closely linked arg-IO locus, despite their biochemical differences. Both org-II alleles wfierefore tested with a compatiblerain of B368, o non-complementing org-IO allele (J., personal communication via 0. Giilie). In each case, heterocaryons with wild type growth rate were obtained. Phenotypic variation: Among single-ascospore isolates from crosses of wild type x 44601, there is much variation in gravwnd morphology, even among the 44601+ segregonts; the near-lethols appear to be merely the mat extreme examples of this variation. The variation does not appear to be genotypic, since (a) it tends to diminish on subculture, and (b) even after four generations of back-crossing to wild type (each time selecting the most vigorws 44601segregant ), essentially the some range of variation was found. F'reliminory attempts to determine whether the variability is due to an unrelated gene with low penetrance or to a semidominant effect of 44601 (e.g., via threshold level(s) of limiting compound(s) in the mcospores) -have been unsuccessful. Mr. Oliver Gillie at the University of Edinburgh has obtained much more extensive data on the variable growth of both arg-II alleles. Department of Biolcgicol Sciences, Stanford University, Stanford, California.


ABSTRACT Introduction: The patent foramen ovale (PFO) is a common anatomical variant in humans (prevalence 25%). Most often asymptomatic, it may engender paradoxically embolic strokes, myocardial infarctions, or visceral or peripheral ischemia. It is causatively related to migraine, positional or exertional hypoxemia with dyspnea, diving incidents, high altitude edema, and sleep apnea. Percutaneous closure of atrial septal defects was first performed in the seventies. A dedicated PFO occluder (Amplatzer PFO Occluder) was first used on 10 September 1997 by Kurt Amplatz and Bernhard Meier. Since, percutaneous PFO closure has evolved into one of the most common and the simplest and safest catheter-based intervention in adult cardiology. Randomized studies have proved its benefit for prevention of recurrent ischemic events (particularly strokes) in patients without competing stroke etiology. There are also supportive clinical data for PFO closure in other situations. Areas covered: The Amplatzer PFO Occluder, the first, most implanted, and best-studied PFO occluder, is reviewed, presenting implantation technique, possible complications, and pertinent scientific data of efficacy and safety. Expert commentary: Percutaneous PFO closure has grown to one of the most common procedures in interventional cardiology. Implantation of the Amplatzer PFO Occluder is simple, safe, and effective.


Co50Pt50 nanoparticles were co-deposited on thermally oxidized Si substrates by electron beam evaporation, at a substrate temperature between RT and 750°C. The co-deposition led to formation of nanoparticles which exhibit a mean diameter between 2 and 20 nm depending on the nominal thickness of the layer and on the substrate temperature. Different processing conditions resulted in different structural and morphological properties of the samples, which led to superparamagnetic and ferromagnetic behaviours. The post-annealing treatment of the CoPt nano-grains, performed in-situ soon after the deposition in the crystallization of the L10 ordered phase and consequently in the progressive magnetic hardening of the samples with a maximum coercivity of ∼7.4 kOe.


Survival times are rarely intrinsically discrete (an important counterexample being time to pregnancy, which is naturally measured in menstrual cycles). If times are recorded in intervals, grouped survival times methods may be relevant, but it is alternatively sometimes preferable to consider time as discrete. This leads to various forms of generalized linear models, notably repeated logistic regressions or discrete proportional hazards (complementary log–log link functions). Smoothing methods are considered.

Generalizations to competing risks and to frailty models have also been studied.

Keywords:

survival analysis;
life table;
logistic regression;
discrete proportional hazard;
generalized linear models;
frailty;
complementary log–log link;
competing risks


Elastic-plastic fracture mechanics (EPFM) is the name given to a body of fracture technology that includes parameters, test methods, and analysis techniques. EPFM began in the 1960s, soon after it was recognized that the linear elastic approach to fracture mechanics was too limited to cover many engineering applications. It began in response to real engineering problems and continues to develop in the same application-driven mode. The development of EPFM spans more than three decades. It involved many people and a multitude of good ideas. Some of the people have gone on to other pursuits, and many of the ideas have been set aside or discarded in the never-ending debate about which is the best approach. The development of EPFM is not complete, nor is the controversy ended. It is important to look back at the factors that influenced such a vast development of technology before trying to forge ahead. This paper takes a look at the area of fracture mechanics called EPFM. It considers the development of a technology that involved people, places, and a seemingly inexhaustible supply of technical ideas. It considers what happened in the past, what is going on in the present, and speculates about what will happen for the future. Its purpose is to stop for a moment and consider for EPFM: Where has it been? Where is it going?


Patients presenting for surgical stabilisation of an unstable cervical spine are at risk of sustaining a further iatrogenic spinal cord injury during intubation of the trachea. Controversy exists regarding the optimal anaesthetic technique for securing the airway. We reviewed the techniques employed for intubating the trachea in our hospital over a five year period. Tracheal intubation was achieved using two different techniques: awake fibre-optic intubation with local anaesthesia, and general anaesthesia via the intravenous or inhalational route with neuromuscular blockade. Forty five patients were included. 16 patients demonstrated a pre-operative neurological deficit. Awake fibre-optic intubation was used in 27 cases, general anaesthesia was employed via the intravenous route in 17 cases and the inhalational route in 1 case. Weighted traction was employed in all cases to immobilize the cervical spine during intubation. There was no new neurological sequelae with any of these techniques. Our study suggests that there is no optimal anaesthetic technique for intubating the trachea in patients with cervical spine injuries and it is noteworthy that in line traction was used in every case.


Service level agreement (SLA) is a contract between service provider and user about the quality of service (QoS) in cloud computing. The cost value and benefit value of SLA monitoring systems is a concerned issue in cloud computing. The trustable SLA monitoring model is important to assess SLA validation in cloud computing. The optimization of monitoring interval is another objective of study to economize SLA monitoring system. Therefore in this paper the SLA monitoring tools is developed to evaluate the proposed dynamic interval in actual testbed of cloud computing. The experiment design described in this paper presents the cloud configuration and environmental setup for testbed experiment.


Recent changes in information systems technology, combined with the postulates of open access to information, are causing the processes of knowledge production and dissemination to change. The necessity of the democratization of science, scientific openness, social orientation of science and the involvement of stakeholders from outside the scientific community in conducting research becomes a necessity for researchers. This is also in line with the guidelines of the European Commission's Community Research and Development Information Service, according to which academics are expected to change the ways of creating knowledge, be oriented towards solving social problems or transgress traditional disciplinary boundaries. Crowdsourcing in science is a collaborative online process through which scientists involve a group of self-selected individuals of varying, diverse knowledge and skills, via an open call to the Internet and/or online platforms, to undertake a specified research task or set of tasks. While research efforts to date have focused on the benefits of crowdsourcing in science, its typology has yet to mature. Typologies are important in describing complex, multidisciplinary organizational forms such as crowdsourcing in science. The main purpose of this article is to identify and provide a typology of crowdsourcing in science. Based on the thematic analysis of publications collected in a systematic manner and focused group interviews, 12 types of crowdsourcing in science are identified. The proposed crowdsourcing in science typology matrix may be a starting point for future research and decision-making by practitioners regarding the choice of a specific type of crowdsourcing in science.


Context/objective: Herbal preparations derived from various species and parts of Echinacea (Asteraceae) have been advocated for various medical applications, as a result of the many antimicrobial and immunomodulatory activities attributed to them. Materials and methods: In order to investigate their effects on parasites, four preparations of Echinacea, with distinct chemical compositions, were evaluated for growth inhibition of three species of trypanosomatids: Leishmania donovani, Leishmania major, and Trypanosoma brucei. In addition one Echinacea preparation was tested for anti-inflammatory activity in cell culture models designed to measure pro-inflammatory cytokines induced by L. donovani. Results and discussion: All Echinacea preparations inhibited growth of the organisms, though with different relative potencies, and in some cases morphological changes were observed. However, there was no obvious correlation with the composition of the marker compounds, alkylamides, caffeic acid derivatives, and polysaccharides. L. donovani stimulated the production of the pro-inflammatory cytokines IL-6 and IL-8 in human bronchial epithelial cells and in human skin fibroblasts, but in both cases the standardized ethanol extract of E. purpurea (L.) Moench (Echinaforce®) abolished the stimulation, indicating anti-inflammatory activity of this extract. Conclusions: Thus various Echinacea extracts can inhibit the proliferation of these parasites and at least one can reverse the pro-inflammatory activity of Leishmania donovani.


Background: The provision of supportive care is increasingly a priority of quality care in pediatric oncology settings. In China, the quality of supportive care services may vary among regions because of differences in social and health indicators. Objectives: To evaluate Chinese pediatric oncology practitioners' pain management practices, and identify barriers to optimal pain control in children with cancer undergoing invasive procedures in China. Methods: Oncology practitioners were recruited from pediatric cancer centers and professional groups in Hong Kong and mainland China through convenience sampling. Respondents completed a paper-based or electronic structured questionnaire. Chi-square test was conducted to compare practitioners' responses across geographical regions of their practices. Results: The sample (n=304) consisted of pediatric oncologist/hematologists (n=149, 49%) and allied health professional (n=155, 51%), who practiced in the South China region (n=189, 62%) and North China/other regions (n=115, 38%). As compared to practitioners from the South China region, practitioners from the North/other regions were less likely to administer procedural sedation during lumbar puncture (78% vs 48%; P<0.0001) and bone marrow aspiration (72% vs 46%; P=0.0012). Regardless of region, practitioners identified the lack of formal training (72%) and dedicated staff (77%), and restricted access to sedative drugs (70%), as major barriers to adopting procedural sedation. Physicians who practiced in South China were more likely than those in North China/ other regions to report the use of opioids for moderate-to-severe pain, such as morphine (70% vs 49%; P=0.013) which is the recommended first-line strong opioid for persistent pain in children. Practitioners indicated parents' concerns with opioid addiction (73%), safety (76%) and stigma (63%). Practitioners also reported inadequate knowledge in dosing opioids (48%) and side effects management (48%). Overall, 37% of practitioners perceived that even with existing measures, children still experienced severe pain (pain score of 5-10) during procedures. Conclusion: Our results suggest the relative inadequacy of procedural control in certain regions of China. We


Nigeria's harsh economic situation in 2016 has led major industries to look inwards to resolve supply deficits occasioned majorly by foreign exchange scarcity. In the electricity sector, however, the influx of imported electrical components leaves so much to be desired and hurts domestic companies. This article argues that potentials exist in the Nigerian electricity market, and with the right mix of research, policy and investments, Nigeria would be positioned to fulfil these potential and ensure job creation in the process.


We consider Coulomb gas models for which the empirical measure typically concentrates, when the number of particles becomes large, on an equilibrium measure minimizing an electrostatic energy. We study the behavior when the gas is conditioned on a rare event. We first show that the special case of quadratic confinement and linear constraint is exactly solvable due to a remarkable factorization, and that the conditioning has then the simple effect of shifting the cloud of particles without deformation. To address more general cases, we perform a theoretical asymptotic analysis relying on a large deviations technique known as the Gibbs conditioning principle. The technical part amounts to establishing that the conditioning ensemble is an I-continuity set of the energy. This leads to characterizing the conditioned equilibrium measure as the solution of a modified variational problem. For simplicity, we focus on linear statistics and on quadratic statistics constraints. Finally, we numerically illustrate our predictions and explore cases in which no explicit solution is known. For this, we use a Generalized Hybrid Monte Carlo algorithm for sampling from the conditioned distribution for a finite but large system.


PERHAPS THE MOST IMPORTANT TREND in conservation science this decade is "ecosystem services," typically defined as economic benefits derived from species and ecosystems. Ecosystem services form the basis of new market-centric mechanisms for conservation sometimes referred to as the "new conservation." The logic underlying this movement is that if we could properly quantify the economic value of nature, decision makers would suddenly recognize the folly of environmental destruction. In the words of key proponents of this so-called new conservation, conservationists must "jettison their idealized notions of nature, parks, and wilderness" and "partner with corporations in a science-based effort to integrate the value of nature's benefits into their operations and cultures."


Advances that could accrue from the introduction of photometric methods into cytochemical staining practice include the investigation, by cytophotometry, of the mechanism of enzyme action in situ and the possible identification of closely similar enzymes by the direct determination of their Michaelis-Menten constants in the cell or tissue. After brief mention of the fundamental limitations of stain cytochemistry associated with (i) enzyme specificity, and (ii) the need for preliminary treatment such as fixation, a study is made of the theoretical basis of those staining methods which can be classified under the scheme substrate enzymic → reaction stain precursor 'capture reaction' → with developing agent stain. These are considered in relation to a radially symmetrical model in which the enzyme is taken to be uniformly distributed in a spherical site, selected as the simplest that approximates to many actual sites. The overall process is simplified, without undue error, by division into stages. A brief survey of substrate penetration is followed by detailed study of the production, diffusion, and chemical removal of the stain precursor. Little is known about the mechanism of stain immobilization, but on the assumption of non-diffusibility, the stain density patterns are given for various values of the (first order) velocity constant of the capture reaction, diffusion coefficient of the stain precursor, and enzyme-site radius. A localization factor (degree of localization, F) is defined, which gives an indication of the intrinsic localization possibilities of any cytochemical method. This has value in both theoretical and experimental study. Values for F have been calculated, corresponding to the kinetic and geometrical parameters mentioned above. In order to satisfy the objective requirements that emerge from the theory, certain generalizations may be made concerning the properties of prospective substrates. The substrate itself should not associate with protein, except possibly the specific enzyme species, but it should yield a stain precursor and a stain, both of which should associate strongly with protein, i. e. be highly substantive molecules. Unless precursor-protein association occurs, extremely high capture reaction velocities are necessary for precise enzyme mapping in small sites.


During infectious disease outbreaks, some infected individuals may spread the disease widely and amplify risks in the community. People whose daily activities bring them in close proximity to many others can unknowingly become superspreaders. The use of contact tracking based on social networks, GPS, or mobile tracking data can help to identify superspreaders and break the chain of transmission. We propose a model that aims at providing insight into risk factors of superspreading events. Here, we use a social force model to estimate the superspreading potential of individuals walking in a bidirectional corridor. First, we applied the model to identify parameters that favor exposure to an infectious person in scattered crowds. We find that low walking speed and high body mass both increase the expected number of close exposures. Panic events exacerbate the risks while social distancing reduces both the number and duration of close encounters. Further, in dense crowds, pedestrians interact more and cannot easily maintain the social distance between them. The number of exposures increases with the density of person in the corridor. The study of movements reveals that individuals walking toward the center of the corridor tend to rotate and zigzag more than those walking along the edges, and thus have higher risks of superspreading. The corridor model can be applied to designing risk reduction measures for specific high volume venues, including transit stations, stadiums, and schools.


REASONS FOR PERFORMING THE STUDY
Yellow fat disease or steatitis is characterised by a local or general inflammation of fat tissue and is occasionally found in horses. Diagnosis is challenging because of the wide range of nonspecific clinical signs.

OBJECTIVES
To describe clinical signs, treatment, outcome and ultrasonographic findings in horses with steatitis.

STUDY DESIGN
Retrospective study (January 2008 to January 2015).

METHODS
History, clinical signs, ultrasonographic findings, diagnosis, treatment and outcome were recorded.

RESULTS
Twenty cases (18 horses, 2 donkeys; 9 mares, 9 stallions, 2 geldings) were retrieved from 13,707 patient records. Mean age was 1.6 (± 0.8) years (range 1 month-3.5 years). All cases appeared between October and February except for one (August). History included dullness, recumbency, decreased appetite and weight loss. Fever, ventral oedema, stiff/painful gait and painful neck were found. Low haematocrit, low vitamin E and selenium and increased levels of creatinine kinase and particularly lactate dehydrogenase were almost consistent findings. On ultrasound, ventral oedema was found. Subperitoneal, perirenal, mesenteric, coronary and caudal mediastinal fat showed homogenously increased echogenicity. Especially the subperitoneal fat was surrounded by oedema or free fluid. Increased amounts of abdominal, thoracic and pericardial fluid were often found. Fat biopsies were taken in the neck or from the retroperitoneal fat in the ventral flank. In all horses where fat biopsy was taken (n = 13), steatitis was confirmed. Treatment consisted of selenium and vitamin E (intra-muscular injection followed by oral treatment) supplementation and anti-inflammatory treatment (dexamethasone or prednisolone parenteral or oral) for at least 1-4 weeks. Fourteen animals (70%) survived. Full recovery took about 2-6 months.

CONCLUSIONS
Yellow fat disease may be underdiagnosed because of the nonspecific clinical signs. Ultrasound was extremely helpful for making a diagnosis. Recovery was rather slow but was achieved in 70% of the animals. Ethical animal research: Research ethics committee oversight not currently required by this conference: retrospective study of clinical records. Explicit owner informed consent for inclusion of animals in this study was not stated.

SOURCE OF FUNDING
Ghent University (institutional). Competing interests: None declared.


This paper is derived from a study of Physical Education curriculum in 99 preschools, with 60 head teachers, 60 parents and 4 County Early Childhood Education officers from Nairobi and Nyeri counties. The study comparatively evaluated the sustainability of the implementation of the preschool Physical Education (PE) curriculum in Nairobi and Nyeri counties. Its purpose was to establish the extent to which the implementation of PE is sustainably done in these two counties. Unlike in the traditional African society where play was embedded in every day's life, today, PE does not enjoy prominent status like the other examinable subjects. Schools do not meet the legal policy requirements for PE. This could partly be attributed to pressure for academic excellence geared towards examination performance. In so doing, children are denied their right to psychomotor and life skills, a situation that may affect the sustainability of the implementation of the PE curriculum yet physical inactivity is leading to a global risk of noncommunicable diseases. The results of the study show how key different stakeholders supported the implementation of PE curriculum with the aim of addressing this risk of non-communicable diseases besides the communicable diseases as health is central to the country's present and future development.


A radioimmunoassay (RIA), to quantitate nonenzymatically glucosylated albumin (GA), was established. Antiserum A was obtained by immunizing guinea pigs with reduced glucosylated guinea pig albumin (RedGlc-GPA), and antiserum B was obtained by immunizing with reduced glucosylated human albumin (RedGlc-HA) and absorbing the antibody against human native albumin. For antiserum A; RedGlc-GPA and NaBH4-reduced guinea pig serum, in which epsilon-N-1-(1-deoxy glucitol) lysine (GL) was present, were effective competitors. But NaBH4-reduced human serum, NaBH4-reduced human hemoglobin, and RedGlc-HA, in which GL were also present, were not so effective competitors. For antiserum B; RedGlc-HA, and RedGlc-GPA, in which GL were present, and GL were equally effective competitors. Thus it seemed that for antiserum A, the antigenic region was not only GL, and for antiserum B, the antigenic region was GL almost specifically. So we used antiserum B for this RIA, and GA in NaBH4-reduced human albumin was quantitated by measuring its ability to compete for antibody binding, compared with that of GL as a standard. Reproducibility of GA-values with this RIA was a enough to use for clinical purpose. With this RIA method, the following results were obtained: 1) These GA values were correlated with GA values, measured by boronate-affinity chromatographic method. 2) Average of GA values in 44 diabetics was significantly higher than that of 24 normal subjects. 3) These GA values were also correlated with HbA1, HbA1c, and fasting blood sugar (FBS). 4) These GA values were more closely correlated with FBS, 2 weeks before, than with FBS, at the same time, and with FBS, 4 weeks before. 5) After insulin treatment to untreated diabetics, these GA values were more rapidly decreased than HbA1c. These result indicated that GA values quantitated in this RIA was available for monitoring blood sugar level for shorter period than that represented by HbA1c.


Power transformer field drying is becoming a habitual practice because water is damaging for transformer insulation, and its presence increases the probability of unexpected failures. Different drying methods are currently being used by electrical companies but sometimes without a profound knowledge of the drying processes involved, and consequently drying is not as effective as would be desirable. Physical models have been developed by the authors in order to study power transformer drying processes. The use of the models will help to plan more effective drying processes, tailoring the drying times and drying conditions for each particular case. The models have been tested in a test transformer fitted with sensors. In order to monitor the process, insulation samples were extracted from the transformer before and after the process. In this article, several transformer drying procedures are described. Theoretical models and their experimental validation processes are reported. Finally, some general recommendations about transformer drying in the field are provided.


Back-translation has been proven to be effective in unsupervised domain adaptation of neural machine translation (NMT). However, the existing back-translation methods mainly improve domain adaptability by generating in-domain pseudo-parallel data that contains sentence-structural knowledge, paying less attention to the in-domain lexical knowledge, which may lead to poor translation of unseen in-domain words. In this paper, we propose an Iterative Constrained Back-Translation (ICBT) method to incorporate in-domain lexical knowledge on the basis of BT for unsupervised domain adaptation of NMT. Specifically, we apply lexical constraints into back-translation to generate pseudo-parallel data with in-domain lexical knowledge, and then perform round-trip iterations to incorporate more lexical knowledge. Based on this, we further explore sampling strategies of constrained words in ICBT to introduce more targeted lexical knowledge, via domain specificity and confidence estimation. Experimental results on four domains show that our approach achieves state-of-the-art results, improving the BLEU score by up to 3.08 compared to the strongest baseline, which demonstrates the effectiveness of our approach.


ABSTRACT Propaganda has been increasingly digitized, popularized, and aestheticized globally. This article focuses on the restyling of propaganda in China, particularly the role of Chinese state-run media in the making of soft propaganda – propagandistic content packaged in sleek and entertaining formats. Building upon Bourdieu's field theory, this article illuminates Chinese state-run media's capacity to refract external pressures, such as digitization, to enhance their status and the resilience of the political regime. It reveals their brokering role in a heterogeneous 'thought work' network, comprised of state-affiliated units and private actors, where different forms of capital are exchanged. Drawing on in-depth interviews with online news staff in three central-level state-run outlets in China, my analysis challenges the discourse of digital technologies as inherently liberating forces and accentuates their multivocality, namely the flexible ways in which technological innovation is interpreted and practiced in concrete institutional contexts, serving pre-existing priorities and interests. It shows how innovation can function as a legitimation device serving organizations' and individuals' quests for political and symbolic capital within bureaucratic systems.


The aim of this paper is to compare two different methods of measuring the Modulation Transfer Functions (MTF) and the corresponding derived STI-RASTI indices to a ssessing intelligibility. The first method uses, as test signal, a band filtered (500 and 2000 Hz) amplitude modulated noise. The second one uses MLS signals to obtain the impulse response of the system; further post processing allows us to calculate the MTF and STI-RASTI indices from this filtered response.


In survival analysis, the semiparametric accelerated failure time model is an important alternative to the widely used Cox proportional hazard model. The existing methods for accelerated failure time models include least-squares, log rank-based estimating equations and approximations to the nonparametric error distribution. In this paper, we propose another fitting method for the accelerated failure time model, formulated from the hazard function of the exponential error term. Our method can handle partly interval-censored data which contains event time, as well as left, right and interval censoring time. We adopt the maximum penalized likelihood method to estimate all the parameters in the model, including the nonparametric component. The penalty function is used to regularize the nonparametric component of the accelerated failure time model. Asymptotic properties of the penalized likelihood estimate are developed. A simulation study is conducted to investigate the performance of the proposed method and an application of this method to an AIDS study is presented as an example.


Over the last decades, various researches have been done to evaluate how and why people are different. People are eager to know why they are different. This is an important subject in daily life as these differences cause different attitude towards life, relationships and jobs. Hence, researchers are psychologist have done several tests to determine some criteria to study people based on them. However, some of these factors are more valid and reliable. This paper proposes a study of personality and intelligence as two main universal factors that cause differences in people. Some of the personality tests are discussed over time to specify their flaws and main factors in intelligence are studied alongside the brief study of the IQ test. Furthermore, some of the most effective and well-known aspects of self in relationships are studied to help people first understand themselves better and then, to have more intimate and efficient relationships with others including the loved ones, friends, co-workers. Therefore, the main purpose of this paper is to discuss how and why people are different from one another.


Elderly patients are perceived as a high-risk group for procedural sedation. Procedural sedation analgesia (PSA) is generally safe in older adults. What is not acceptable is undertreating pain or inadequately sedating a stable patient. All the usual precautions should be taken. One should consider any comorbidities that could make the patient more at risk of adverse reactions or complications. Older patients may be at higher risk for oxygen desaturation, but they usually respond quickly to supplemental oxygen. Geriatric patients usually require lower doses of medications. They tend to be more sensitive to medications, with slower metabolism, less physiologic reserve to handle side effects, and a smaller volume of distribution. The use of drugs for sedation in elderly patients requires careful consideration of their age-related changes in physiology and pharmacokinetics. The choice of drug should be based on the patient's medical condition, comorbidities, and potential adverse effects. Moreover, the administration should be done by trained personnel with close monitoring of vital signs and level of consciousness to prevent complications such as respiratory depression.


Predicting 3D structure of protein from its amino acid sequence is one of the most important unsolved problems in biophysics and computational biology. This paper attempts to give a comprehensive introduction of the most recent effort and progress on protein structure prediction. Following the general flowchart of structure prediction, related concepts and methods are presented and discussed. Moreover, brief introductions are made to several widely-used prediction methods and the community-wide critical assessment of protein structure prediction (CASP) experiments.


OBJECTIVE
The prognosis of first episodes of HIV-associated PCP has markedly improved. The knowledge about the reasons for this progress could bear important implications for the management of HIV-infected patients.

PATIENTS AND METHODS
Clinical and laboratory parameters, as well as therapy and clinical course were documented. Prognostic analysis was performed using a logistic regression model. Early (1985-1988) and late (1989-1994) episodes were compared with regard to the results of the prognostic analysis.

RESULTS
67 patients (61 male, six female, mean age 35 +/- 12 years) without any prophylaxis presenting with a first episode of PCP were treated from 1985 until 1994. 95% of patients had a known HIV-serostatus prior to the diagnosis of PCP. Hemoglobin, percentage of neutrophils in BALF as well as AaDO2 were variables significantly associated with lethal outcome. The prognosis of late episodes was significantly improved (7 versus 32% lethal outcomes, log rank p < 0.01). AaDO2 as the only parameter found to be significantly associated with outcome was significantly lower in the late episodes, accordingly. The mean time until diagnosis of PCP was five days shorter in this group. Moreover, CD8 cell-count and serum albumin were found to be significantly higher, and mean loss of weight prior to diagnosis of PCP significantly lower.

CONCLUSIONS
The prognosis of first episodes of PCP without any prophylaxis is most closely associated to the severity of pneumonia as reflected by AaDO2. Causes for a minor severity of PCP include an earlier diagnosis as well as better immunity and a better clinical performance at the time of PCP. The improved prognosis therefore results from the experience of the treatment center. A known HIV-serostatus and regular medical care by an experienced treatment center contributes significantly to improved outcome of PCP also in the group non-compliant to distinctive recommendations with regard to prophylaxis for PCP.


Abstract Hairball buster (HB) (also called node-neighbor centrality or NNC) is an approach to graph analytic triage that uses simple calculations and visualization to quickly understand and compare graphs. Rather than displaying highly interconnected graphs as 'hairballs' that are difficult to understand, HB provides a simple standard visual representation of a graph and its metrics, combining a monotonically decreasing curve of node metrics with indicators of each node's neighbors' metrics. The HB visual is canonical, in the sense that it provides a standard output for each node-link graph. It helps analysts quickly identify areas for further investigation, and also allows for easy comparison between graphs of different data sets. The calculations required for creating an HB display is order M plus N log N, where N is the number of nodes and M is the number of edges. This paper includes examples of the HB approach applied to four real-world data sets. It also compares HB to similar visual approaches such as degree histograms, adjacency matrices, blockmodeling, and force-based layout techniques. HB presents greater information density than other algorithms at lower or equal calculation cost, efficiently presenting information in a single display that is not available in any other single display.


Abstract Mortality and morbidity rate among cancer patients is at an alarming rate and its ratio of incidence is increasing as a result of its effects of metastasis and recurrence in its patients. Anesthetists are faced with the challenges daily of handling and treating cancer patients, for surgical resection to removal of the primary tumor. Retrospective analyses and studies have proposed a link between anesthetic technique and cancer outcomes. In this mini-review, we will give a summary of some of the available effects of anesthetic and analgesic techniques on cancer metastasis as derived from experimental cell culture and live animal data and also from clinical studies.


PURPOSE
Brimonidine, an alpha-2 adrenoceptor agonist, is an effective and safe medication that is widely used in glaucoma treatment. Although it is known that it is quickly taken up by the cornea following topical administration and that the cornea has alpha-2 adrenoceptors, there are only few studies available on the impact brimonidine has on the cornea.

METHODS
Twenty healthy test persons (12 female and 8 male subjects)-mean age about 33 years (22 to 38 years)-were tested in a double-blind, prospective, randomized study. Intraocular pressure as well as epithelial, stromal, and endothelial thickness was measured before, at 25 days while, and at 5 days after administration of brimonidine 0.1% eye drops twice daily. To check the impact of this medication, placebo (proper solution of preservative) eye drops were administered to the other eye twice daily.

RESULTS
Administration of brimonidine 0.1% resulted in a reduction of intraocular pressure from an initial value of 14 to 9 mmHg after 5 days (P=0.001) as well as an increase in total corneal thickness from 556 μm from the time of the baseline examination to 578 μm (P=0.001), an increase of epithelial thickness from 58 to 66 μm (P<0.001), and stromal thickness from 488 to 502 μm (P=0.008) after 2 days each. Another 2 days later, total corneal thickness was 559 μm (P=0.276), epithelial thickness 56 μm (P=0.561), and stromal thickness 493 μm (P=0.315), which means that the values had returned more or less toward the initial values measured. In contrast, endothelial thickness did not vary following administration of brimonidine 0.1% (P=0.965). With treatment with brimonidine 0.1%, mean intraocular pressure in thin corneas (<556 μm) was lower than in the thick corneas (>556 μm, P=0.018).

CONCLUSIONS
Topical administration of brimonidine 0.1% results in a reversible increase in corneal thickness. The question whether this increase is of clinical significance and whether it is the result of epithelial and/or endothelial receptor stimulation cannot be finally answered at the present time.


The presence of gas in dusty debris disks around main-sequence stars is reviewed. We present new observational results for the most prominent representative of the class, viz. the southern naked-eye star β Pictoris. The spatial and spectral distribution of observed atomic lines from the disk around the star is reproducable by a Keplerian rotation model to a high degree of accuracy. The expected velocity dispersion due to radiation pressure in resonance lines is not observed. Modeling the motion of different atomic species under the influence of gravity, radiation pressure and gas friction leads to the conclusion that an underlying decelerating component must be present in the disk. This braking agent is most likely hydrogen, with inferred average densities n H > 10 6 cm −3. This could support the observational result of Thi et al. (2001) which indicated the presence of appreciable amounts of H 2 around the star β Pic.


Bandwidth selection is crucial in the kernel estimation of density level sets. A risk based on the symmetric difference between the estimated and true level sets is usually used to measure their proximity. In this paper we provide an asymptotic $L^p$ approximation to this risk, where $p$ is characterized by the weight function in the risk. In particular the excess risk corresponds to an $L^2$ type of risk, and is adopted to derive an optimal bandwidth for nonparametric level set estimation of $d$-dimensional density functions ($d\geq 1$). A direct plug-in bandwidth selector is developed for kernel density level set estimation and its efficacy is verified in numerical studies.


Secondary non-Hodgkin's lymphoma of the central nervous system is typically a late manifestation of systemic T-cell lymphoma, with a 2-month median survival time after the development of neurological disease. Of the reported patients with this late complication, only 1% manifest spread of the disease to the brain parenchyma. The authors report a patient with an unusual initial neurological presentation of systemic T-cell lymphoproliferative disorder and associated space-occupying lesions of the brain parenchyma. The diagnosis was supported by extensive molecular, immunological, and histopathological analysis. Neurological symptoms appeared early in the course of systemic disease and were characterized by spontaneous exacerbations and remissions. The patient has survived for more than 5 years since the onset of his neurological symptoms. Histopathological characterization including immunoperoxidase staining for T-cell markers, DNA content, and cell-cycle analysis of brain tissue obtained at stereotactic biopsy were compared to those of atypical lymphoid cells of peripheral blood, bone marrow, and liver. The neurological manifestations and possible etiologies of T-cell lymphoma are discussed.


Background: Cancer cells with deleterious mutations in breast cancer susceptibility genes 1 and 2 (BRCA1/2) are deficient in the DNA double-strand break repair mechanism, rendering them highly dependent on the single-strand break repair pathway, which is initiated by poly-(ADP-ribose) polymerase (PARP) [1-3]. In cells with deleterious BRCA1/2 mutations, PARP inhibition is synthetically lethal because of accumulation of irreparable DNA damage [1-3]. Talazoparib (BMN 673) exhibits a novel two-pronged approach in treating BRCA1/2-mutant tumors: 1) potent catalytic inhibition of the PARP enzyme; and 2) trapping of PARP at sites of DNA damage [4-7]. The capacity to trap PARP-DNA complexes varies widely across PARP inhibitors and is not correlated with catalytic inhibition potency [4-7]. In preclinical models, trapping PARP on DNA is more potent at inducing cancer cell death than enzymatic inhibition of PARP alone [4,7]. Talazoparib is the most potent clinical-stage PARP inhibitor tested to date with the highest efficacy at trapping PARP-DNA complexes [7]. Talazoparib has shown single-agent antitumor efficacy in several solid tumor types and was generally well tolerated in a phase 1/2 clinical study [8]. Methods: This 2-stage, 2-cohort, phase 2 international study (ABRAZO) evaluates the safety and efficacy of talazoparib in patients with a deleterious germline BRCA1 or BRCA2 mutation with locally advanced and/or metastatic breast cancer. Eligible subjects will be assigned to one of two cohorts based on prior chemotherapy for metastatic disease. Cohort 1 (n=70) includes patients with a complete response (CR) or partial response (PR) to platinum-containing regimens for metastatic disease. Cohort 2 (n=70) includes patients who have received >2 prior chemotherapy regimens in the metastatic setting but have not had prior platinum therapy for locally advanced or metastatic disease (prior adjuvant or neoadjuvant therapy with a platinum is allowed). The primary objective is objective response rate (ORR). Secondary objectives include clinical benefit response (CBR) rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Health-related quality of life (QoL) assessments are an exploratory objective. Eligible subjects will receive oral talazoparib (1 mg/day, 21-day cycles) until disease progression or unacceptable toxicity. This trial is currently enrolling patients from the United States and Europe (NCT02034916). This study is funded by BioMarin Pharmaceutical Inc. References: 1. Ashworth A. J Clin Oncol. 2008;26:3785-3790; 2. Jalve M, Curtin NJ. Ther Adv Med Oncol. 2011;3:257-267; 3. Helleday T. Mol Oncol. 2011;5:387-393; 4. Murai J et al. Cancer Res. 2012;72:5588-5599; 5. Rouleau M et al. Nat Rev Cancer. 2010;10:293-301; 6. Shen Y et al. Clin Cancer Res. 2013;19:5003-5015; 7. Murai J et al. Mol Cancer Ther. 2014;13:433-443; 8. Wainberg ZA et al. J Clin Oncol. 2014;32(suppl):5. Abstract 7522. Citation Format: Turner NC, Balmana J, Fasching PA, Hurvitz SA, Rugo HS, Telli ML, Visco F, Wardley AM, Yang X, Lokker NA, Lounsbury DL, Robson ME. ABRAZO: An international phase 2 (2-stage, 2-cohort) study of the oral PARP inhibitor talazoparib (BMN 673) in BRCA mutation subjects with locally advanced and/or metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-03-17.


The development of information technology has led to a significant increase in the share of multimedia traffic in data networks. This has necessitated to solve the following information security tasks in relation to multimedia data: protection against leakage of confidential information, as well as identifying the source of the leak; ensuring the impossibility of unauthorized changes; copyright protection for digital objects. To solve such kind of problems, methods of steganography and watermarking are designed that implement embedding in digital objects hidden information sequences for various purposes. In this paper, an overview of promising research in the specified area is provided. First of all, we provide basic information about this field of research and consider the main applications of its methods. Next, we review works demonstrating current trends in the development of methods and algorithms for data hiding in digital images. This review is not exhaustive; it focuses on contemporary works illustrating current research directions in the field of information embedding in digital images. This is the main feature of review, which distinguishes it from previously published reviews. The paper concludes with an analysis of identified problems in the field of digital steganography and digital watermarking.


This essay argues that Arundhati Roy's inclusion of numerous Indian vernacular words and phrases in her fiction is carefully calibrated to serve the author's activist political agenda. This is true not only of her first novel, The God of Small Things, but also of the more recent Ministry of Utmost Happiness. Both feature a Bakhtinian or dialogic interplay of linguistic modes. The earlier work poses two languages against each other: Malayalam, the primary language of Kerala, and English, the medium of narration and the preferred tongue of the prominent Ipe family. The outcome of this contest highlights the Ipes' imprisonment within a life-denying straitjacket of outworn prejudices and conventions. In The Ministry of Utmost Happiness the linguistic terrain broadens to include several tongues of the subcontinent, along with English. Roy gives special exposure to two: Urdu and Kashmiri, to reclaim them from the oppression both of them, along with their speakers, are undergoing at the hands of the dominant Hindi-speaking majority. Tilo, a pivotal character, is enthusiastically polyglot, a trait which accords with her more general adaptability and freedom from sectarian narrowness. The other central figure, the transgender Anjum, resembles Tilo in her resistance to strict definitions of her fluid selfhood, but must endure forms of verbal as well as physical violence. Like her first novel, but on a more capacious stage, Roy's second aims at speaking multilingual truth to monolingual power.


The paper studies the impact of market integration on investment incentives in non-competitive industries. It distinguishes between investment in transportation and production cost-reducing technologies. Each domestic firm is controlled by a national regulator in a common market made of two countries. When public funds are costly, and production costs in the two countries are not very different, business stealing effect decreases welfare in both countries. Welfare increases in both countries when the difference in production costs is large enough. Market integration tends to increase the level of sustainable investment in cost-reducing technology compared to autarky. This is in contrast with the systematic underinvestment problem arising for transportation facilities. Free-riding reduces the incentives to invest in these public-good components, while business-stealing reduces the capacity for financing new investment.


Fizeau sensors constitute a large proportion of the fiber optic interferometric type sensors in use today. These include EFPI, FFPI, certain MEMS devices and in-line fiber intrinsic dual-reflector type sensors. The vast majority of the published literature covering these sensor types models them with a "2-beam" interferometer approximation, and implement interrogation approaches considering the same. Analysis performed and results presented show that the 2-beam model is not sufficient when reflection coefficients exceed 1% and traditional quadrature interrogation can result in linearity or distortion errors roughly in directly proportion to the reflectivity coefficients of the Fizeau sensor. A 4-beam multi-path interferometer model is developed and exercised to demonstrate this problem. Further this model shows that the "errors" in comparison to an ideal 2-beam interferometer model are symmetric across the unit circle and suggests that linear interrogation may be accomplished if orthonormal sample sets over the entire unit circle are used to replace the traditional (simple) quadrature sampling. This is shown to be true in both modeling and lab evaluations. The resulting approach has capabilities of remote, passive sensor operation, high frequency response, large, linear dynamic range and low noise. The interrogation technique demonstrated involves a phase generated carrier with full fringe sampling and quadrature determination which cancels the errors experienced from simple quadrature determination. Such an improvement enables higher reflectivity, higher SNR, high-fidelity fiber Fizeau sensor designs. Applications include embedded sensors, line sensors, or mechanically adapted for acoustic, pressure, vibration, acceleration or seismic sensing.