Diabetes mellitus is a metabolic disorder and affects nearly 10% of the population every year. The aim of present study was to investigate the histological changes in diabetic Induced Swiss albino mice, Mus norvegicus albinus on exposure to 1Deoxynojirimycin. 1-Deoxynojirimycin is known to be a potent antidiabetic compound. The study was conducted on mice Swiss albino male mice, the animals were divided into six equal groups and each group comprising 5 animals. The 1st group was given distilled water and used as a control group. The 2nd and 3rd groups were normal mice they were orally administered with only 1Deoxynojirimycin 40 mg/kg b.w. and 60 mg/kg b.w. respectively. The 4th group was used as a diabetic control which induced with Streptozotocin (STZ) to produce diabetes. The 5th and 6th groups were diabetic induced and administered 1-Deoxynojirimycin at the dose 40 mg/kg b.w. and 60 mg/kg b.w. respectively. The histological sectioning of tissue was followed as per the standard procedure. Photomicrograph of the section preparation was taken using Olympus (PM-6 Model) photomicrograph equipment. The results indicated that STZ treated mice exhibited severe liver degeneration and these changes were reversed on exposure to DNJ for a period of 30 days. The study exhibited that DNJ alleviated the hepatic histopathological changes induced by STZ.


Nucleosomes prepared from human placental nuclei and Escherichia coli DNA-dependent RNA polymerase (nucleoside triphosphate: RNA nucleotidyl transferase EC.188.8.131.52) form stable initiation complexes. This property is utilized as a probe of nucleosome structure. RNA polymerase initiation has been studied on purified nucleosomes, nucleosome cores, and nucleosomal DNA. The affinity of E. coli RNA polymerase for both nucleosome cores and monomers was 5-6 fold less than found for nucleosomal DNA. No difference in apparent initiation Km was found between cores and mononucleosomes. This suggests that initiation does not preferentially occur on the DNA tails of nucleosomes. Once initiated and allowed to form nascent RNA, these complexes are very stable to ionic strength changes. Under conditions in which free enzyme is inactivated with rifampicin, the enzyme in the complex retains activity as demonstrated by its ability to transcribe and reinitiate on both nucleosomes and free DNA. These complexes can be well resolved from free nucleosomes on preparative polyacrylamide gels and both can be eluted from gels for analysis of proteins and DNA sequence complexity. Studies using (125I) labelled nucleosomes show that histones are retained in the initiation complex, and are not dissociated by the enzyme during initiation.


Many plant aspartic proteases contain an additional sequence of ∼100 amino acids termed the plant-specific insert, which is involved in host defense and vacuolar targeting. Similar to all saposin-like proteins, the plant-specific insert functions via protein-membrane interactions; however, the structural basis for such interactions has not been studied, and the nature of plant-specific insert-mediated membrane disruption has not been characterized. In the present study, the crystal structure of the saposin-like domain of potato aspartic protease was resolved at a resolution of 1.9 Å, revealing an open V-shaped configuration similar to the open structure of human saposin C. Notably, vesicle disruption activity followed Michaelis-Menten-like kinetics, a finding not previously reported for saposin-like proteins including plant-specific inserts. Circular dichroism data suggested that secondary structure was pH-dependent in a fashion similar to influenza A hemagglutinin fusion peptide. Membrane effects characterized by atomic force microscopy and light scattering indicated bilayer solubilization as well as fusogenic activity. Taken together, the present study is the first report to elucidate the membrane interaction mechanism of plant saposin-like domains whereby pH-dependent membrane interactions resulted in bilayer fusogenic activity that probably arose from a viral type pH-dependent helix-kink-helix motif at the plant-specific insert N terminus.


Abstract.
 Foraging in a habitat with highly unpredictable availability of prey, breeding seabirds have to balance their investment in reproduction with their own energetic requirements, including their immune system. This study aimed to investigate the influence of breeding stage (incubation and chick rearing) and sex on body condition and leucocyte profiles in two sympatrically breeding tropical seabird species on Christmas Island, Indian Ocean: the strongly size-dimorphic, inshore-foraging brown booby (Sula leucogaster) and the monomorphic offshore-foraging red-tailed tropicbird (Phaethon rubricauda). Brown booby males were in poorer body condition than females. Male brown boobies had a higher heterophil/lymphocyte (H/L) ratio (indicating higher stress levels), and higher eosinophil numbers (suggesting higher intestinal parasite loads) than females, and sex differences in H/L ratio and body condition were more pronounced during chick rearing. The results suggest that in brown boobies, incubation was energetically less demanding for males than chick rearing, but that the smaller males were energetically more challenged than females during both breeding stages. In the monomorphic red-tailed tropicbird, there were no differences in body condition between sexes and breeding stage, and there was no influence of sex or breeding stage on the leucocyte profiles. The results suggest that incubation and chick rearing are equally demanding for males and females, and that the increased energetic demands of chick rearing are likely to be buffered by a bimodal foraging strategy by both sexes. Our results show that breeding stage as well as sex- and species-specific foraging behaviour can affect leucocyte profiles and particularly the H/L ratio differentially in sympatrically breeding seabird species.


A linear sensor system is defined as a sensor system in which the sensor measurements have a linear relationship to source variables that cannot be directly measured. Evaluation of the reliability of a general linear sensor system is a #P problem whose computational time increases exponentially with the increment of the number of sensors. To overcome the computational complexity, Monte Carlo methods are developed in this paper to approximate the sensor system's reliability. The crude Monte Carlo method is not efficient when the sensor system is highly reliable. A Monte Carlo method that has been improved for network reliability, known as the Recursive Variance Reduction (RVR) method, is further adapted for the reliability problem of linear sensor systems. To apply the RVR method, new methods are proposed to obtain minimal cut sets of the linear sensor system, particularly under the conditions where the states of some sensors are fixed as failed or functional. A case study in a multistage automotive assembly process is conducted to demonstrate the efficiency of the proposed methods.


Large language models with instruction-following capabilities open the door to a wider group of users. However, when it comes to information extraction - a classic task in natural language processing - most task-specific systems cannot align well with long-tail ad hoc extraction use cases for non-expert users. To address this, we propose a novel paradigm, termed On-Demand Information Extraction, to fulfill the personalized demands of real-world users. Our task aims to follow the instructions to extract the desired content from the associated text and present it in a structured tabular format. The table headers can either be user-specified or inferred contextually by the model. To facilitate research in this emerging area, we present a benchmark named InstructIE, inclusive of both automatically generated training data, as well as the human-annotated test set. Building on InstructIE, we further develop an On-Demand Information Extractor, ODIE. Comprehensive evaluations on our benchmark reveal that ODIE substantially outperforms the existing open-source models of similar size. Our code and dataset are released on https://github.com/yzjiao/On-Demand-IE.


We examine short- and the long-term price effect associated with the FTSE 100 index revisions. We control for both heteroskedastic nature of the residual and the change, between the estimation and the test period, in the beta coefficient of the standard market model. Our findings reveal no relationship between the long-term price reversals and the change in the discount rate, as approximated by the beta coefficient of the market model. Overall, we provide strong evidence in favour of the price pressure hypothesis, where the price increase (decrease) gradually starting before the announcement an inclusion (exclusion) and reverses completely in less than two weeks after the index revision date.


Scaling web applications such as e-commerce in cloud by adding or removing servers in the system is an important practice to handle workload variations, with the goal of achieving both high quality of service (QoS) and high resource efficiency. Through extensive scaling experiments of an n-tier application benchmark (RUBBoS), we have observed that scaling only hardware resources without appropriate adaptation of soft resource allocations (e.g., thread or connection pool size) of each server would cause significant performance degradation of the overall system by either under- or over-utilizing the bottleneck resource in the system. We develop a dynamic concurrency management (DCM) framework which integrates soft resource allocations into the system scaling management. DCM introduces a model which determines a near-optimal concurrency setting to each tier of the system based on a combination of operational queuing laws and online analysis of fine-grained measurement data. We implement DCM as a two-level actuator which scales both hardware and soft resources in an n-tier system on the fly without interrupting the runtime system performance. Our experimental results demonstrate that DCM can achieve significantly more stable performance and higher resource efficiency compared to the state-of-the-art hardware-only scaling solutions (e.g., Amazon EC2-AutoScale) under realistic bursty workload traces.


This paper investigates small and medium-sized software firms' success factors in the Japanese market. Findings of this study suggest that, due to the immaterial nature of software products, distribution and packaging has a less important role, while understanding Japanese business practices is ranked high along with customer satisfaction, honesty, and characteristics of a product. The findings also highlight the importance of distinguishing different kinds of software businesses based on their product strategies when analyzing success factors in a target country. For instance, the Japanese language assumed an important role in enterprise solution firms and in mass market software business, while its role in tailor-made software solution firms was less visible.


Abstract 1941 Poster Board I-964 Multiple studies have repeatedly shown that loss of MHC II expression correlates with poor patient prognosis in diffuse large B-cell lymphoma (DLBCL). Major histocompatibility complex class II (MHCII) molecules present peptides for antigen recognition and are important for the adaptive immune response. Loss of MHCII expression is also one of the changes seen during normal B-cell differentiation into plasma cells. Plasmablastic lymphoma (PBL) is another B-cell lymphoma characterized by a proliferation of large B-cells with a plasma cell immunophenotype and very poor prognosis. In this study, we questioned whether DLBCL cases that have low MHCII expression have a similar gene expression pattern to PBL. Unstained cuts from formalin-fixed, paraffin-embedded tissue blocks of 101 DLBCL and 76 PBL cases were analyzed for gene expression using a quantitative nuclease protection assay (qNPA, ArrayPlate R ). The 42 genes on the array were previously identified as B-cell lineage-related or prognostically important in DLBCL. DLBCL cases were divided into low [MHCII(-)] and high [MHCII(+)] MHC II expression using a 20% cutoff for expression of HLA-DRB by qNPA, as previously described (L Rimsza et al, Blood 2008). Genes that differed significantly between lymphoma types were determined using the Partek Genomics Suite R software, using ANOVA tests with a false discovery rate of 0.05. Thirty of the 42 genes on the array (71%) were differentially expressed between DLBCL as a whole and PBL. As expected from the literature, the PBL cases had less expression of B-cell antigen, MHCII, and germinal center-related genes as compared to DLBCL. Of these 30 genes, 29 were also different between MHCII(+) and PBL. In contrast, only 21 genes of the 42 on the array (50%) were differentially expressed between MHCII(-) and PBL, indicating a less dissimilar expression pattern between these two sets of cases. Of the 21 genes, two were uniquely different between MHCII(-) and PBL. Both of these, FN1 and CTGF , are found in the extracellular matrix and were low in the MHCII(-) cases. This finding, that the MHCII(-) cases are similar, but not identical to PBL, agrees with our previous immunohistochemistry studies suggesting MHCII(-) cases may be invoking selected mechanisms of differentiation (S Wilkinson et al, AACR Annual Meeting 2009, #2712). Our findings confirm the hypothesis that MHCII(-) DLBCL have a more plasma cell-like expression pattern than MHCII(+) DLBCL. These findings may have implications for pathogenesis and treatment. Disclosures: Schwartz: High Throughput Genomics: Employment. Gascoyne: Roche Canada: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding. Rimsza: High Throughput Genomics: Memorandum of understanding with HTG to run qNPA assay at no cost..


The IETF's Next Steps in Signaling (NSIS) framework provides an up-to-date signaling protocol suite that can be used to dynamically install, maintain, and manipulate state in network nodes. In its two-layered architecture, the General Internet Signaling Transport (GIST) protocol is responsible for the transport and routing of signaling messages. The strong presence of Network Address Translation (NAT) gateways in today's Internet infrastructure causes some major challenges to signaling protocols like NSIS. The address translation mechanisms performed by common NAT gateways are primarily concerned with address information contained in the IP and transport layer headers. Messaging associations between two signaling peers do, however, rely on address information contained in GIST data units. If a non GIST-aware NAT gateway merely adapts addresses in the IP and transport headers, inconsistent state will finally be installed at the signaling nodes. In this paper we present the design, implementation, and evaluation of an application level gateway for the GIST protocol, that translates GIST messages in a way that allows for the establishment of messaging associations between any two GIST nodes across a NAT gateway.


The behavior of tracer particles in a concentrated suspension of non-colloidal spheres sheared in a parallel plate viscometer at low Reynolds number was investigated. The tracer particles were shown to migrate radially, with the tracer particles larger than those making up the suspension migrating radially outward. The migration velocity of the large tracer particles was measured, and found to be consistent with a shear-induced migration scaling (Leighton and Acrivos, 1987b), however the direction of the migration was the reverse of that suggested by the experiments of Abbot, et al. (1991) in a wide gap Couette device. The particle migration and segregation described here are interpreted in terms of the curvature of the flow geometry.


More than 20 weighting functions proposed for DLTS are critically compared. It is shown that the variety of DLTS peak widths of different weighting functions was primarily due to the variety of shapes of the high-temperature side of the peak. A refinement of the classification scheme of the weighting functions is proposed. It is shown that the high-temperature side of the DLTS peak can be made independent of the weighting function, by considering the delay time between the end of the filling pulse and the beginning of the weighting function as an integral part of each weighting function. An optimum delay time (specific for each weighting function) is obtained by maximizing the figure of merit defined as the signal-to-noise ratio of the correlator divided by the DLTS peak width. Using the concept of optimum delay time, the functions can be classified into several groups according to their selectivity. The functions from one group differ only by their sensitivity, making it easy to select the functions with the best signal-to-noise ratios. In the second part of the paper, several misunderstandings concerning exponential correlators and double boxcars that frequently appear in the literature are revealed.


ABSTRACT Erionite is a zeolite representing a well-known health hazard. In fact, exposure of humans to its fibers has been unequivocally associated with occurrence of malignant mesothelioma. For this reason, a multi-methodological approach, based upon field investigation, morphological characterization, scanning electron microscopy (SEM)/energy-dispersive spectroscopy (EDS) chemical analysis, and structure refinement through X-ray powder diffraction (XRPD), was applied to different samples of potentially carcinogenic erionite from Northern Italy. The studied crystals have a chemical composition ranging from erionite-Ca to erionite-Na and display variable morphologies, varying from prismatic, through acicular and fibrous, to extremely fibrous asbestiform habits. The fibrous samples were characterized by an unusual preferred partition of aluminum (Al) at tetrahedral site T1 instead of tetrahedral site T2. Further, a mismatch between the a-parameter of erionite-Ca and levyne-Ca that are intergrown in the asbestiform sample was detected. This misfit was coupled to a relevant micro-strain to maintain structure coherency at the boundary. Erionite occurs in 65% of the investigated sites, with an estimated quantity of 10 to 40 vol% of the associated minerals. The presence of this mineral is of concern for risk to human health, especially if one considers the vast number of quarries and mining-related activities that are operating in the zeolite host rocks. The discovery of fibrous and asbestiform erionite in Northern Italy suggests the need for a detailed risk assessment in all Italian areas showing the same potential hazard, with specific studies such as a quantification of the potentially respirable airborne fibers and targeted epidemiological surveillance.


This work is concerned with the space of alignments searched by word alignment systems. We focus on situations where word re-ordering is limited by syntax. We present two new alignment spaces that limit an ITG according to a given dependency parse. We provide D-ITG grammars to search these spaces completely and without redundancy. We conduct a careful comparison of five alignment spaces, and show that limiting search with an ITG reduces error rate by 10%, while a D-ITG produces a 31% reduction.


Ventilation tubes (VTs) have been extensively used to treat chronic serous otitis media over the last 30 years. However, it is not known if this practice has affected the incidence of cholesteatoma. A retrospective study was carried out at two Regional ENT Centres in Northern Ireland, examining the clinical notes of all patients undergoing major ear surgery between 1965 and 1988. The incidence of cholesteatoma per operatively in this period varied from 0.01 to 0.16 per 1,000 of population per year. The total number of cholesteatomas in the first five years of the study was exactly equal to the number in the last five years, despite an eight-fold increase in VT insertion over this period. These results indicate that the incidence of cholesteatoma remained stable between 1965 and 1988 despite a huge increase in the use of VTs.


The volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) is two to four times larger in male rats than in females; however, the mechanism for the establishment of sexual dimorphism and the function of this nucleus is almost unknown. Perinatal estrogen can cause sexual dimorphism via the estrogen receptor alpha (ERalpha). Recently, transgenic rats were generated that express enhanced green fluorescent protein (EGFP) under the control of the ERalpha gene promoter 0/B to tag ERalpha-positive neurons in the brain. In the present study, we examined whether this EGFP expression could be a marker for the SDN-POA in adults. EGFP-labeled cells were distributed in the core of the SDN-POA (0/B-SDN) of male and female transgenic rats, in accordance with the Nissl staining and immunoreactivity for the SDN marker, calbindin. They were also immunoreactive for ERalpha. The core was bigger in volume and contained more 0/B-SDN neurons in males than in females. The EGFP-tagged cells were packed more densely in the female core than that in males. Subcutaneous injection of 100 mug 17beta-estradiol to females on the day of birth, or orchidectomy of male neonates, reversed the sexually dimorphic phenotype of the volume of the 0/B-SDN, despite not affecting the cell number. We suggest that this EGFP expression in the SDN-POA could be a useful marker to clarify the sexual differentiation and function of the SDN-POA. Moreover, the ERalpha gene promoter 0/B plays a key role in the organization of the sexual differentiation of the SDN-POA.


Recent advances in social media have triggered a massive engagement of user population: a large part of people's lives has shifted to social media platforms and real events are reported while they are happening (e.g. in Twitter). As a result, such platforms have become an important source of information, being used by professionals as well, e.g. journalists, for fast access to news and events. Social media maintain an underlying network of social connections over which such information propagates. Information diffusion in social media has attracted attention, by analyzing how information is propagated from user to user and who is influenced by whom. Given the scale and speed of such information, systems that can keep up with such fast rates are required. In this poster, we present a system for real time reconstruction of information diffusion that encompass the challenges of analyzing fast data streams combined with large social graphs.


The sensitivities of a structural response due to variation of its design parameters are prerequisite in the majority of the algorithms used for fundamental problems in engineering as system uncertainties, identification and probabilistic assessments etc. The paper presents the concept of probabilistic sensitivity of suspension bridges with respect to near-fault ground motion. In near field earthquake ground motions, large amplitude spectral accelerations can occur at long periods where many suspension bridges have significant structural response modes. Two different types of suspension bridges, which are Bosporus and Humber bridges, are selected to investigate the near-fault ground motion effects on suspension bridges random response sensitivity analysis. The modulus of elasticity is selected as random design variable. Strong ground motion records of Kocaeli, Northridge and Erzincan earthquakes are selected for the analyses. The stochastic sensitivity displacements and internal forces are determined by using the stochastic sensitivity finite element method and Monte Carlo simulation method. The stochastic sensitivity displacements and responses obtained from the two different suspension bridges subjected to these near-fault strong-ground motions are compared with each other. It is seen from the results that near-fault ground motions have different impacts stochastic sensitivity responses of suspension bridges. The stochastic sensitivity information provides a deeper insight into the structural design and it can be used as a basis for decision-making.


Purpose: To evaluate the effectiveness of intravitreous bevacizumab (Avastin), intravitreous tissue plasminogen activator, and vitrectomy for the macular edema secondary to branch retinal vein occlusion. Methods: Retrospective, interventional case series. We studied 228 eyes of 228 patients. Forty-one eyes received 1.25 mg of intravitreous bevacizumab, 71 eyes received tissue plasminogen activator, and 116 eyes underwent vitrectomy. A reinjection of 1.25 mg of bevacizumab was based on the morphologic and functional findings. The main outcome measures were the best-corrected visual acuity and optical coherence tomography–determined foveal thickness. Results: The mean postoperative follow-up period was 32.2 months with a range of 12 months to 69 months. The mean number of intravitreous bevacizumab was 2.8 with a range of 1 to 5. The mean best-corrected visual acuity and foveal thickness significantly improved after all 3 treatments, and the differences in the best-corrected visual acuity between the 3 groups were not significant at 12 months. Fourteen eyes (34%) in the intravitreous bevacizumab group and 21 eyes (30%) in the tissue plasminogen activator group required additional surgeries. Conclusion: The 3 treatments appear to provide similar visual outcomes at 12 months. However, in some eyes treated with intravitreous bevacizumab or tissue plasminogen activator, additional surgeries were required, and a longer follow-up period was required to determine the final outcome.


For more than 60 years, soy-based infant formulas have been fed to millions of infants worldwide and studied in controlled clinical research. These products provide essential nutrients required for normal growth and development. The safety of isoflavones in soy-based products, including infant formulas, has been questioned recently owing to reports of possible endocrine effects in animals and in cultured cells. The literature offers no evidence of endocrine effects in humans from infant consumption of modern soy-based formulas. Growth is normal and no changes in the timing of puberty or in fertility rates have been reported in humans who consumed soy formulas as infants. Consequently, soy-based infant formulas continue to be a safe, nutritionally complete feeding option for most infants.


PURPOSE
Among patients in paediatric intensive care units (PICUs), death is sometimes inevitable despite advances in treatment. Some PICU patients may have irreversible cessation of all brain function, which is considered as brain death (BD). This study investigated demographic and clinical differences between PICU patients with BD and those with cardiopulmonary death.

METHODS
All children who died in the PICU at a university-affiliated trauma centre between October 2002 and October 2018 were included in this retrospective study. Demographics and clinical characteristics were compared between patients with BD and patients with cardiopulmonary death.

RESULTS
Of the 2784 patients admitted to the PICU during the study period, 127 died (4.6%). Of these 127 deaths, 22 (17.3%) were BD and 105 were cardiopulmonary death. Length of PICU stay was shorter for patients with cardiopulmonary death than for patients with BD (2 vs 8.5 days, P=0.0042). The most common mechanisms of injury in patients with BD were hypoxic-ischaemic injury (40.9%), central nervous system infection (18.2%), and traumatic brain injury (13.6%). The combined proportion of accident and trauma-related injury was greater in patients with BD than in patients with cardiopulmonary death (27.3% vs 3.8%, P<0.001). Organ donation was approved by the families of four of the 22 patients with BD (18.2%) and was performed successfully in three of these four patients.

CONCLUSIONS
These findings emphasise the importance of injury prevention in childhood, as well as the need for education of the public regarding acceptance of BD and support for organ donation.


Histori Artikel : Tgl. Masuk : 27-03-2020 Tgl. Diterima : 30-03-2020 Tersedia Online : 22-04-2020 This study aims to determine the effect of firm size, leverage, managerial ownership, listing age and audit committee on earnings persistence. The data used is data on banking companies listed on the Indonesia Stock Exchange (IDX) period 2015-2017. The sample selection uses a purposive sampling method. The samples that fit the criteria were 29 companies during the 2015-2017 observation period, so that the final number of observational data was 87 (3 × 29). Then data were analyzed using the SPSS 22 application.The results of this study indicate that firm size, managerial ownership and listing age do not affect earnings persistence. While leverage and audit committees negatively affect earnings persistence. Variables of company size, leverage, managerial ownership, listing age and audit committee jointly influence the persistence of earnings.


During levamisole therapy, 14 of 20 patients with previously unresponsive rheumatoid arthritis had significant improvement (P less than 0.05) in clinical measures of disease activity, erythrocyte sedimentation rate, and rheumatoid factor titer in a 32-week double-blind placebo controlled crossover trial. Levamisole was shown to alter antibody responses to tetanus and typhoid antigens, lymphocyte blastogenesis to phytohemagglutinins, and the number of null cells in peripheral blood. Agranulocytosis and rash resulted in discontinuation of the drug in one patient in each group. Though clearly effective, routine use of levamisole as a disease suppressant in rheumatoid arthritis must await more complete clarification of its association with agranulocytosis.


Controlling the structure of a material over a wide range of scales has been extensively pursued because the structure dictates its function. Here, we explore the formation of 3D structures at almost a millimetre scale using single-crystal complex oxides, which has been challenging because of the brittle nature of oxides. Our scheme is to release epitaxial oxide thin film heterostructures from the rigid substrate in order to utilise the elastic epitaxial strain as a driving force for self-shaping the flexible free-standing membrane in a controlled manner. Using an epitaxial free-standing LaAlO3/SrTiO3 membrane as a model system, we were able to create various 3D forms, such as cylindrically-rolled, spherically-bent, and helically-twisted structures, where the inversion-symmetry is broken by the strain gradient via flexoelectric effects. Our results will provide opportunities not only to broaden the application of functional oxides toward flexible electronics, but also to discover new functionalities driven by 3D architectures at various scales.


The concept of sustainability is increasingly being addressed theoretically by scholars and practically by managers and policymakers. With this growing focus on sustainability efforts, marketing is in a unique position to elevate its focus from managing relationships with customers to strategically managing a broader set of marketplace issues. Overall, an organization achieves market-based sustainability to the extent that it strategically aligns itself with the market-oriented product needs and wants of customers and the interests of multiple stakeholders concerned about social responsibility issues involving economic, environmental, and social dimensions. To set the stage for marketing's inquiry into sustainability efforts, I briefly review the concept of sustainability, compare it with corporate social responsibility, bring in stakeholders, argue for the notion of "market orientation plus," and consider the possibility that the notion of what sustainability encompasses is converging in the marketing literature.


Preliminary room temperature phosphorescence measurements of the highly buried Trp109 in E. coli alkaline phosphatase have been used to report on the kinetics of protein hydrogen-deuterium exchange. Upon dilution in D2O the phosphorescence lifetime increases (at 20 degrees C) in a biphasic manner with an immediate change (< 30 seconds) followed by a slow change occurring on an extremely long timescale (days). The immediate D2O-induced lifetime increase is similar to that observed upon dilution into glycerol, a known protein hydrating agent. On the other hand, the slow D2O-induced first order growth in Trp109 lifetime is due to exchange at highly protected protein groups. As the phosphorescence lifetime of Trp109 is dependent on local rigidity, this increase in lifetime reflects changes in alkaline phosphatase structure. This first use of room temperature phosphorescence to monitor proton exchange shows promise as a sensitive and selective probe of protein core dynamics.


The objective of this study was to quantify lactoferrin (Lfe) in buffalo milk and to examine the factors affecting milk Lfe, such as the lactation stage, daily milk yield, parity, and milk somatic cells count (SCC). Milk Lfe concentration was detected by the SDS-polyacrilamide gel electrophoresis (SDS-PAGE). The overall mean of Lfe concentration was 0.332±0.165 g/kg and ranged from 0.030 to 0.813 g/kg. Milk Lfe concentrations increased (P<0.01) with the increase of days in milk, but it was not affected by parity. Milk Lfe concentration was significantly affected by SCC. The differences became significant when the levels of SCC increased up to 200,000/mL. This is the first investigation on the levels of Lfe in buffalo milk in reference to daily milk production, lactation stage, parity and SCC. Further studies are needed to clarify the relationship between Lfe and SCC in buffalo milk.


The Mullins-Sekerka and the electric breakdown instabilities are well known to lead to the spontaneous formation of a variety of complex spatial structures, among them dendritic crystal shapes, and treelike electric discharge patterns. Controlling such systems by suppressing predominantly excited solutions offers the opportunity to manipulate and stabilize these patterns in a defined way for a wide range of technological applications. In this work, we employ a variational approach which enables one to systematically search for the ideal conditions under which the patterns grow, but where interfacial deformations are efficiently minimized. The effectiveness of our variational control method is illustrated via linear stability calculations on both two-dimensional and three-dimensional contour-dynamics models for crystal growth and electric discharge phenomena.


Determinate root growth is an important adaptation feature for seedling establishment in some Cactaceae. We show that seedlings of Pachycereus pringlei have primary roots with a stable determinate developmental program. How water stress affects determinate root growth and lateral root development has not been studied. Here we address this question. Root growth was analyzed in plants growing in vitro under well-watered and water-deficient (created by polyethylene glycol) growth conditions. Under severe water stress roots terminated their growth earlier and the rate of growth was significantly decreased as a result of inhibition of both cell elongation and cell production. Under severe water stress the number of lateral roots and primordia per millimeter of primary root was 1.5-1.7 times greater than under well-watered conditions; however, the total number of lateral roots and primordia was the same under all conditions. Lateral roots resembled root spurs found in some Opuntioideae. Analysis of the dynamics of meristem exhaustion indicated that initial-cell activities are required for the maintenance of proliferation before meristem exhaustion. We conclude that lateral root formation is a stable developmental process resistant to severe water stress and that water stress accelerates the determinate developmental program of the primary root. Both of these features appear to be important for successful seedling establishment in a desert.


Purpose
The purpose of this study is to identify the role played by external knowledge sources and intra-organizational collaboration as determinants of innovation in hotel firms. It proposes that local knowledge sources and intra-organizational collaboration determine the probability of producing incremental innovations, and that non-local knowledge sources determine the introduction of radical innovations.

Design/methodology/approach
Descriptive statistics made it possible to evaluate the importance of each of the external sources as the origin of ideas for innovation. Principal component analysis was used to find homogeneous groups based on the different knowledge sources contemplated. Multiple regression analysis was used to determine which variables predict a hotel's capacity to introduce innovations.

Findings
The findings suggest a dissociation between innovations adopted by directly incorporating the specific knowledge provided by external agents and innovations that require the mediation of intra-organizational collaboration for their development.

Research limitations/implications
Future qualitative studies can provide data that would considerably improve the understanding of how innovation processes are produced in hotel companies based on the use of external knowledge and how hotel firms develop spaces to exchange and combine internal knowledge.

Practical implications
Hotel firms can adopt innovations by incorporating specific knowledge from external companies or by developing their own innovations based on information gathered from external agents or events (e.g. customers, attending trade fairs and professional conferences). The transformation of this information into innovations requires the establishment of internal communication channels that foment employees' collaboration and exchange of information.

Originality/value
The study provides empirical evidence for the relevant role played by both external agents and intra-organizational relationships as sources of knowledge to foster innovation in hotel firms. External agents are classified as local and non-local sources, and their effect on innovation is analyzed, distinguishing between incremental and radical innovations.


To face the advent of multicore processors and the ever increasing complexity of hardware architectures, programming models based on DAG-of-tasks parallelism regained popularity in the high performance, scientific computing community. In this context, enabling HPC applications to perform efficiently when dealing with graphs of parallel tasks that could potentially run simultaneously is a great challenge. Even if a uniform runtime system is used underneath, scheduling multiple parallel tasks over the same set of hardware resources introduces many issues, such as undesirable cache flushes or memory bus contention. In this paper, we show how runtime system-based scheduling contexts can be used to dynamically enforce locality of parallel tasks on multicore machines. We extend an existing generic sparse direct solver to use our mechanism and introduce a new decomposition method based on proportional mapping that is used to build the scheduling contexts. We propose a runtime-level dynamic context management policy to cope with the very irregular behaviour of the application. A detailed performance analysis shows significant performance improvements of the solver over various multicore hardware.


Purpose The outcome predictors of Kasai portoenterostomy (KPE) for biliary atresia (BA) are controversial. This study aimed to identify possible short-term outcome predictors of KPE for BA in infants. Methods This retrospective study included infants with BA who underwent KPE between January 2015 and December 2017 and were followed up for at least 6 months after surgery at the Pediatric Hepatology Unit, Cairo University Pediatric Hospital, Egypt. The short-term outcome was jaundice clearance within 6 months following surgery. All data were compared between the jaundice free group and those with persistent jaundice to identify the predictors of jaundice clearance. Results The study included 75 infants. The mean age at the time of surgery was 82.43±22.77 days (range, 37–150 days), and 28 (37.3%) infants cleared their jaundice within 6 months postoperative. Age at surgery did not significantly affect the outcome (p=0.518). Infants with persistent jaundice had significantly higher pre-operative levels of aspartate aminotransferase (AST) than those who were jaundice free (p=0.041). Receiver operating characteristic curve analysis showed that preoperative AST ≤180 IU/L was predictive of a successful KPE, with sensitivity 74.5% and specificity 60.7%. Infants with bile plugs in liver biopsy had a 6-fold higher risk of persistent jaundice than those without bile plugs (95% confidence interval: 1.59–20.75, p=0.008). Conclusion Jaundice clearance after KPE for BA can be predicted using preoperative AST and presence of bile plugs in liver biopsy.


Factors influencing the vertical driving force magnitude applied to screws during the process of driving the screws into faces of particleboard materials were investigated. In particular, the screw penetration depth and screwdriver air pressure were evaluated relative to critical torques, such as seating and stripping torques. Experimental results indicated that vertical driving forces significantly affected the magnitude of critical driving torques when no pilot hole was drilled, but this influence became non-significant when 3.2-mm diameter pilot holes were drilled. Screw-driving power had no significant effect on the magnitude of critical driving torques in particleboard materials if no pilot hole was drilled, but if pilot holes were drilled, increasing the screwdriver air pressure from 0.45 to 0.62 MPa led to increases in stripping torques. Increasing the screw penetration depth from 12.7 to 19.1 mm can significantly increase seating and stripping torques.


A total mean cordial labeling of a graph G = (V, E) is a function f : V (G) → {0, 1, 2} such that for each edge xy assign the label ⌈


BACKGROUND
Human epidermal growth factor receptor 2 (HER2)-targeted therapies have not been approved for patients with non-small-cell lung cancer (NSCLC). The efficacy and safety of trastuzumab deruxtecan (formerly DS-8201), a HER2 antibody-drug conjugate, in patients with HER2-mutant NSCLC have not been investigated extensively.

METHODS
We conducted a multicenter, international, phase 2 study in which trastuzumab deruxtecan (6.4 mg per kilogram of body weight) was administered to patients who had metastatic HER2-mutant NSCLC that was refractory to standard treatment. The primary outcome was objective response as assessed by independent central review. Secondary outcomes included the duration of response, progression-free survival, overall survival, and safety. Biomarkers of HER2 alterations were assessed.

RESULTS
A total of 91 patients were enrolled. The median duration of follow-up was 13.1 months (range, 0.7 to 29.1). Centrally confirmed objective response occurred in 55% of the patients (95% confidence interval [CI], 44 to 65). The median duration of response was 9.3 months (95% CI, 5.7 to 14.7). Median progression-free survival was 8.2 months (95% CI, 6.0 to 11.9), and median overall survival was 17.8 months (95% CI, 13.8 to 22.1). The safety profile was generally consistent with those from previous studies; grade 3 or higher drug-related adverse events occurred in 46% of patients, the most common event being neutropenia (in 19%). Adjudicated drug-related interstitial lung disease occurred in 26% of patients and resulted in death in 2 patients. Responses were observed across different HER2 mutation subtypes, as well as in patients with no detectable HER2 expression or HER2 amplification.

CONCLUSIONS
Trastuzumab deruxtecan showed durable anticancer activity in patients with previously treated HER2-mutant NSCLC. The safety profile included interstitial lung disease that was fatal in two cases. Observed toxic effects were generally consistent with those in previously reported studies. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Lung01 ClinicalTrials.gov number, NCT03505710.).


The research study of the Total Mobility Scheme, which provides reduced fares for taxi travel by people with disabilities, was undertaken to assist the government-funded Working Group on Transport Systems for Transport Disadvantaged in New Zealand in fulfilling its terms of reference. The study included a survey of users of the Total Mobility Scheme in Dunedin and Palmerston North, to provide more information about the scheme, especially to identify who uses it and the purposes of their trips. Summaries of the data analysis of the survey results are presented, and also a brief statement about possible future research that can be built on these results. (a)


Hydraulic fracturing operations in unconventional reservoirs are increasingly being monitored with fiber-optic (FO) Distributed Acoustic and Temperature Sensing (DAS/DTS). In this paper, we discuss how a single well equipped with fiber optics and DAS can be used as a diagnostic tool to better understand the completions program of three offset wells and the fiber instrumented well.
 Strain measurements were initially conducted for seismic studies, then followed by measurements of fluid injections from monitoring wells to better understand placement along the lateral section of the wellbore for programs such as hydraulic fracturing, water flooding, and steam injection. The broadband DAS signals have shown of value for the monitoring of microseismic, as well as thermal and mechanical strain of the fiber over the entire well-pad's completion process. During well stimulation, as a fracture propagates to an offset wellbore with fiber deployed, the DAS measurements can be used to monitor very small changes of strain on the fiber. Analysis of the Cross-Well Communication (CWC) strain measurements provide information about possible fracture numbers and locations, as well as the fracture propagating rate based on known well distance. Changes in the strain measurements are coupled with microseismic events that can be simultaneously monitored using the same interrogator unit and fiber optic cable.
 Here we present various diagnostic tools for DAS that help to better understand the completions program. A variety of physical effects, such as temperature, strain and micro seismicity are measured and correlated with the treatment program to aid in the analysis. Two of the offset wells were zipper-fractured first, then the fiber installed well was zipper-fractured with the third offset well. By monitoring CWC strain measurements we show that DAS can assess the treatment and performance of neighboring wells that are not instrumented with fiber optic cable. Low frequency strain events from neighboring wells provide direct measurements of the fracture density and possible fracture network post fiber well completion. CWC measurements can provide strain levels that can be analyzed in the context of the various completion parameters including stage length, clusters, and well spacing, etc. We also discuss the fluid and proppant allocations measurements that can be performed on the well with fiber installation. We show how DAS can be used as a tool for investigating cluster efficiency, diverter effectiveness, and for determining completions problems like screen-outs and stage communication.
 The analysis of the DAS data demonstrates that current fiber-optic technology can provide enough sensitivity to detect a significant number of frac events that can be used for an improved reservoir description and as an assessment of the completions program.


Sale and leaseback investment has been a growing trend among the Real Estate Investment Trust (REIT) Companies in Malaysia. This study is to determine the important elements in the concepts of the sale and leaseback transactions practiced by the REIT companies. The study uses the NVIVO software to analyze the data interviews with the REIT managers that adopt sale and leaseback investment transactions. With a response rate of 78%, results show there are three main elements namely location, type of lease, and rental. This study forms a useful guide to real estate managers in developing countries towards using the sale and leaseback as one of the alternative methods in property investment.


The capital structure policy by an entity is still a question specially in the context of investment policy and if related to market timing. The question is still exist because the entity faced by two options of financing which are internal financing (capital) and external financing (debt). This study is using data from the samples of 241 entities listed in Indonesia Stock Exchange in period of 2009 till 2012 making the total of observed data are 964. Conducting multiple regression analysis, this study conclude that, the effect of pecking order, trade off and market timing are not absolute for all conditions of entities, because the entities will take decision for capital structure policy based on its conditions such as internally or externally. In this case, the external condition is referring to capital market.


Neuroimaging has proved to be both sensitive and highly effective in detecting dopaminergic dysfunc-tion in Parkinsonian Syndromes. It can help establish the truth of the disorder when clinical features are incomplete or contradictory. Now the truth is out. Nycomed Amersham are proud to announce the first and only approved nuclear imaging product in Europe to help differentiate Essential Tremor from Parkinsonian Syndromes related to idiopathic Parkinson's disease, Multiple System Atrophy and Progressive Supranuclear Palsy. The images are easy to read and available the same day. DaTSCAN™ gives you clear diagnostic pictures that provide accurate visual differentiation of Parkinsonian Syndromes from Essential Tremor. Currently, diagnostic methods rely on the use of clinical criteria, with formal confirmation only possible at post mortem. DaTSCAN can reduce the time required to reach a diagnosis.With 97.5% sensitivity † , you can be more confident than ever that your diagnosis is correct and that the medication you prescribe will have the desired effect. DaTSCAN – another major step forward in the partnership of success between Neurology, Geriatrics, Nuclear Medicine and Nycomed Amersham. Abbreviated Prescribing Information Presentation: Vials containing 185 MBq ioflupane (123 I) at reference time. Uses: Detecting loss of functional dopaminergic neuron terminals in the striatum of patients with clinically uncertain Parkinsonian Syndromes in order to help differentiate Essential Tremor from Parkinsonian Syndromes related to idiopathic Parkinson's Disease (PD), Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP). DaTSCAN is unable to discriminate between PD, MSA and PSP. Dosage and Administration: DaTSCAN is a 5% (v/v) ethanolic solution for intravenous injection and should be used without dilution. Clinical efficiency has been demonstrated across the range of 111-185 MBq; do not use outside this range. Appropriate thyroid blocking treatment must be given prior to and post injection of DaTSCAN. SPECT imaging should take place 3-6 hours after injection of DaTSCAN. DaTSCAN is not recommended for use in children or adolescents. For use in patients referred by physicians experienced in the management of movement disorders. See SPC. Contraindications: Pregnancy and in patients with hypersensitivity to iodide or any of the excipients. Precautions: Radiopharmaceuticals should only be used by qualified personnel with appropriate government authorisation and should be prepared using aseptic and radiological precautions. DaTSCAN is not recommended in moderate to severe renal or hepatic impairment. Interactions: Consider current medication. Medicines that bind to the dopamine transporter may interfere with diagnosis; these include amphetamine, benzotropine, buproprion, cocaine, mazindol, methylphenidate, …


This paper presents the analysis of leakage current characteristics of outdoor polymer insulator due to pollution under wet conditions. In this work, laboratory based pollution performance tests were carried out on 11kv silicon rubber polymer insulator under AC voltage at different pollution levels with sodium chloride as a contaminant. Leakage current waveforms during the experimental studies were measured. Normally FFT spectrum estimation method used to find the harmonic spectrum in the leakage currents. But this method suffers from the major problem of resolution. So in this paper a higher order spectrum estimation method (Min-Norm) employed to understand the frequency domain characteristics of the leakage current signal. The results of the harmonic spectrum shows that has a good resolution than FFT spectrum and Reported results of this preliminary study on 11kv silicon rubber insulator shows that development of flashover due to pollution could be easily identified from the analysis of harmonic contents of leakage current signal.


Sensor elements employing fine filaments are often vulnerable to particulate fouling when used in certain operational field conditions. Depending on the size, attraction level, thermal and electrical conduction and charge accumulation properties of the particles, erroneous readings can be easily generated in such "dirty" environments. This paper describes the design, development and testing of an ultrasonic system which dynamically rejects highly tenacious electrostatically charged particles of a wide variety of sizes and even water. The paper starts with a brief introduction to the field of acoustic vector sensing, outlining its outstanding characteristics and history. Operational challenges including a statistical analysis of typical Middle-Eastern wind-blown desert sand and charge density are laid out. Several representative subscale hot-wire filaments were fouled with calibrated dust representing desert sand. The fouled elements were then exposed to airflows of 13 ft/s (4m/s) and showed highly erratic, shifted conduction levels with respect to baseline (clean) levels. An ultrasonic cleaning system was designed specifically resonate the filament and cantilever so as to mechanically reject foulants. When operated at resonance, the ultrasonic cleaning system showed 98.6% particulate rejection levels and associated restoration of uncorrupted filament resistance levels to within 2% of baseline resistance measurements. The study concludes with an assessment of such cleaning techniques in various environments.


: Speech processing area is wide area in computer science and telecommunication field. Speech recognition, speaker recognition and speech synthesis are prevalent tasks in speech processing area. This research work focuses on speaker identification part of speaker recognition. Deep learning shown significant performance in speech re3cogntiion area. This fact has motivated to analyze deep neural network .for another tasks like speaker recognition. Deep autoencoder has been proved good for feature representation purpose, this work has experimented deep autoencoder for speaker classification activity of speaker identification. Significant accuracy has been achieved for speaker classification. Speaker identity obtained used for extracting speeches of interested speaker from mixed speaker videos.


The discrepancy between the anomaly found by Bousso and Hawking and that of other workers is explained by the omission of a zero-mode contribution to the effective action.


Preparation‐free and skin compliant biopotential electrodes with high recording quality enable wearables for future healthcare and the Internet of Humans. Here, super‐soft and self‐adhesive electrodes are presented for use on dry and hairy skin without skin preparation or attachment pressure. The electrodes show a skin‐contact impedance of 50 kΩ cm2 at 10 Hz that is comparable to clinical standard gel electrodes and lower than existing dry electrodes. Microstructured electrodes inspired by grasshopper feet adhere repeatedly to the skin with a force of up to 0.1 N cm−2 without further attachment even during strong movement or deformation of the skin. Skin compliance and adhesive properties of the electrodes result in reduction of noise and motion artifacts superior to other dry electrodes reaching the performance of commercial gel electrodes. The signal quality is demonstrated by recording a high‐fidelity electrocardiograms of a swimmer in water. Furthermore, an electrode with soft macropillars is used to detect alpha activity in the electroencephalograms from the back of the head through dense hair. Compared to gel electrodes, the soft biopotential electrodes are nearly imperceptible to the wearer and cause no skin irritations even after hours of application. The electrodes presented here could combine unobtrusive and long‐term biopotential recordings with clinical‐grade signal performance.


We present here two letters of Voetius to Maarten Schoock, professor of philosophy at the university of Groningen. They almost exclusively treat both men's dispute with Descartes, and especially the proceedings the French philosopher instituted against Schoock because of his anti-Cartesian work Admiranda methodus (Utrecht 1643). The first letter (April 1644, published here for the first time), is of particular interest, for Voetius described in detail the reasons for publishing Admiranda methodus in it. The second one (21 January 1645 o.s., only partly known) is a letter of advice, or, as Descartes saw it, a shameless attempt to entice Schoock to give false evidence before his judges (AT VIIIB 248-249). The last document published here is Schoock's Corte memorie. The margins of this manuscript show Voetius's own comments.


Based on more than 3 years of moored current-meter records, this study examined seasonal variability of near-inertial kinetic energy (NIKE) as well as all large (greater than one standard deviation from the mean) NIKE events related to storms and eddies in the northwestern South China Sea. The NIKE in the subsurface layer (30-450 m) exhibited obvious seasonal variability with larger values in autumn (herein defined as August, September, and October). All large NIKE events during the observation period were generated by passing storms. Most of the NIKE events had an e-folding timescale longer than 7 d. The phase velocity, vertical wavelength, and frequency shift of these events were examined. The maximum NIKE, induced by typhoon Neoguri, was observed in April 2008. Normal mode analysis suggested that the combined effects of the first four modes determined the vertical distribution of NIKE with higher NIKE below 70 m but lower NIKE from 30 to 70 m. Another near-inertial oscillation event observed in August 2007 had the longest e-folding timescale of 13.5 d. Moreover, the NIKE propagated both upward and downward during this event. A ray-tracing model indicated that the smaller Brunt-Vaisala frequency and the stronger vertical shear of horizontal currents in an anticyclonic eddy and the near-inertial wave with larger horizontal scale facilitated the unusual propagation of the NIKE and the long decay timescale. Although the NIKE originated from wind, the water column structure affected by diverse oceanographic processes contributed substantially to its complex propagation and distribution.


Pulitzer Prize-winner David Brion Davis here provides a penetrating survey of slavery and emancipation from ancient times to the twentieth century. His trenchant analysis puts the most recent international debates about freedom and human rights into much-needed perspective. Davis shows that slavery was once regarded as a form of human progress, playing a critical role in the expansion of the western world. It was not until the eighteenth and nineteenth centuries that views of slavery as a retrograde institution gained far-reaching acceptance. Davis illuminates this momentous historical shift from "progressive" enslavement to "progressive" emancipation, ranging over an array of important developments--from the slave trade of early Muslims and Jews to twentieth-century debates over slavery in the League of Nations and the United Nations. In probing the intricate connections among slavery, emancipation, and the idea of progress, Davis sheds new light on two crucial issues: the human capacity for dignifying acts of oppression and the problem of implementing social change.


CSR (Corporate Social Responsibility) is an increasingly important area of corporate and legal concern. In addition to problems defining the meaning of the term and understanding the implications for, there is a lack of understanding how it can, does and should interact with law. This paper answers this gap using a method used in the sociology of law, systems theory. The paper argues that CSR can be understood as a response to social costs and law's apparent failure to curb those costs. It focuses the examination on social costs generated by large industrial organisations and how they are regulated by public and private regulatory systems. It concludes with an innovative suggestion integrating ideas from ecological economic systems with both new and traditional regulatory solutions.


This research is motivated by the implementation of the vision and mission of the school is less a reflection of the in shaping the culture of a good school, to the achievement of the goals of the school effectively. The purpose of this study was to determine the formulation of the vision and mission of the school is reflected in the culture of the school. The method used is qualitative research with descriptive approach exploratory. Population in this research is primary School Cluster Pasirjambu, Ciwidey, Bandung. Sampling technique in this research is purposive. The instrument used was a questionnaire, interviews, observation and analysis of documentation.
Conclusion the results of the research are (1) Formulation of vision and mission that owned the school made with the editor that is clear, interesting, adapted to the conditions of the school, describe the expectations/ ideals of the school, and contains the results of the expected performance. (2) Criteria for the formulation of the vision and mission have not all met by the school, because has not contain instructions about the target service vision, mission and haven't made the acronym a vision that is meaningful. (3) The Procedures for the formulation of the vision and mission has not been pursued comprehensively by the school. (4) The Culture of the school is not consistent with the vision and mission set by the school. From the above findings, the results of ths study have implications for schools to carry out the vision and mission accordingly the formulation procedure has an academic code of ethics code and has a motto/slogan as if it can encourage the school culture in accordance with the relevance and material of the study of the vision and formulating concept of the school and school culture.


In this paper, we work with a diffusion-perturbed risk model comprising a surplus generating process and an investment return process. The investment return process is of standard a Black–Scholes type, that is, it comprises a single risk-free asset that earns interest at a constant rate and a single risky asset whose price process is modelled by a geometric Brownian motion. Additionally, the company is allowed to purchase noncheap proportional reinsurance priced via the expected value principle. Using the Hamilton–Jacobi–Bellman (HJB) approach, we derive a second-order Volterra integrodifferential equation which we transform into a linear Volterra integral equation of the second kind. We proceed to solve this integral equation numerically using the block-by-block method for the optimal reinsurance retention level that minimizes the ultimate ruin probability. The numerical results based on light- and heavy-tailed individual claim amount distributions show that proportional reinsurance and investments play a vital role in enhancing the survival of insurance companies. But the ruin probability exhibits sensitivity to the volatility of the stock price.


The present investigation is carried out to study the genetic divergence among 35
finger millet genotypes for fourteen morphological characters using Mahalanobis
D2 statistics during kharif, 2014. D2 statistics indicated that the genotypes studied
were genetically diverse. The 35 genotypes of finger millet were grouped into 6
clusters irrespective of geographical diversity, indicating no parallelism between
geographic and genetic diversity. Clusters I and VI were highest number of 8
genotypes, followed by cluster II and V with 7 genotypes and cluster III with 4
genotypes. Cluster IV was monogenotypic. The highest inter-cluster distances was
observed between cluster IV and V followed by cluster IV and VI, cluster II and
IV, cluster I and IV, cluster III and V and cluster III and IV suggesting the use of
genotypes from these clusters to serve as potential parents for hybridization.
Considering cluster mean and genetic distance the crossing of entry of clusters IV
with entries of cluster V and those genotypes of cluster VI would be fruitful for
obtaining transgrassive segregants for developing high yielding and better quality
finger millet varieties.


Early laboratory research has shown that when people are faced with a stressfull situation they prefer the company of those facing the same unpleasant event. In this paper we extend this work by examining the impact that peer support group membership has on the mental health of participants, individuals who have sought the help of similarly afflicted others. We present a theoretical argument which proposes that needs for evaluating the appropriateness of one's emotional reactions to victimization are not likely to be met through normal social interactions, leading to feelings of perceived self deviance which could contribute to depression. We suggest that needs for validation, however, could be fulfilled when a victim is able to share emotional reactions with those having similar experiences in peer support groups. Indirect evidence from other research and relevant data from our pilot study on peer support for rape victims indicates that feelings of deviance do tend to decline after group participation. The findings on the reduction of negative affect of group members are rather limited, but positive outcomes generally have been obtained in groups facilitated by professionals. We conclude by suggesting some of the functions that peer support groups may serve for participants in the hopes of increasing their general effectiveness as vehicles for depression reduction.


Background: Drug addiction is a drastic problem in women's life which is growing rapidly and has attracted a lot of attention in Iran's academic community who investigate addiction. Process of addiction in women highly differs with men; moreover, individual, familial and social consequences of addiction for women are much more intense than that of the men. Objectives: This study aimed at achieve a holistic view on the onset of drug addiction and factors related to the continuation of drug abuse in female drug addicts in Hamadan province, Iran. Patients and Methods: Fifty nine addicted women who were admitted to the only rehabilitation and treatment center for addicted women in Hamadan and volunteered to participate in this cross-sectional survey were chosen. Following clinical interviewing and completing the health questionnaire, they were asked to fill up a standard questionnaire to obtain demographic information including complete and comprehensive questions about sociodemographic and familial states which were effective in onset, continuation and cession of drug abuse. Results: The most common drug used by 48 women (81.35%) was th eopium, followed by crack (8.47%), heroin (1.69%), methadone (1.69%) and cannabis (1.69%). Mean age of the first time experience of cigarette smoking was 17.11 ± 9.22 years. Also, the mean age of the first time drug substance use was 27.62 ± 10.46 years and the mean duration of drug use was 5.2 ± 12.0 years. Among studied women, 74.57% used drugs on a regular basis. General Health Questionnaire results indicated that 74.6% of the studied women had suboptimal general health. Twenty six women (44.6%) were referred to a psychologist or psychiatrist. The main reason for referring to a psychologist or psychiatrist was addiction withdrawal in 19.35%, depression and anxiety in 5.06%, and familial problems in 12.9% and headache in 9.68%. Among the examined individuals, 50.8% had once decided to quit, 23.7% for two times, 11.9% for three times, 8.5% for four times and 1.7% for sixteen times. Conclusions: Significant differences are expected regarding the various patterns of onset, continuation and cession of drug abuse between the women and men. There are also different incentives for participation of women in the treatment processes which is dependent on the country's social and cultural features.


Abstract Purpose To compare the fit and assess the accuracy of tooth-supported single and multi-unit FDPs in cobalt chromium fabricated using different manufacturing techniques. Materials and methods A systematic search was performed in three databases; PubMed, Scopus, and Web of Science, using clearly specified search terms and inclusion criteria. The search yielded 1071 articles and included 18 articles in the analysis. Data regarding the fit analyses and the methods of manufacturing were extracted and the accuracy was defined as the fit result minus the pre-set cement spacer. Internal gap (IntG) was the mean of all the internal measuring points and total gap (TotG) was the mean of all measuring points (marginal, cervical, chamfer, axial, occlusal). Results The total gap results for fit and accuracy irrespective of manufacturing technique were 96 μm and 54 μm for single crowns, 107 μm and 54 μm for multi-unit FDPs, and 98 μm and 54 μm for both single crowns and multi-unit FDPs combined. For total gap of single crowns soft milling had the highest accuracy, for multi-unit FDPs additive manufactured restorations had the highest accuracy. With the results grouped by impression technique, the accuracy for total gap was highest for digital impressions and lower for conventional impressions. Conclusions Due to the inherent limitations of this systematic review, it still remains unclear what effect the manufacturing technique has on the fit of FDPs. However, the descriptive results suggest that the marginal fit of cobalt chromium FDPs is not negatively affected by the manufacturing technique.


Acremonium zeae has been characterized as a protective endophyte of maize and displays antifungal activity against other fungi. Pyrrocidines A and B were discovered to be the metabolites accounting for this activity. During a population survey of A. zeae isolates from maize seeds produced in nine states to determine their ability to produce pyrrocidines, another metabolite of A. zeae, unrelated to the pyrrocidines, was found to have widespread occurrence (105 of 154 isolates) and to be produced in amounts comparable to the pyrrocidines. Further chemical studies of fermentation extracts of an A. zeae isolate (NRRL 45893) from maize led to the identification of a new compound, dihydroresorcylide, the saturated analogue of cis-resorcylide. Also identified were the two diastereomers of 7-hydroxydihydroresorcylide. Dihydroresorcylide and pyrrocidines A and B were detected by LC-APCI-MS in symptomatic maize kernels from ears that were wound-inoculated in the milk stage with A. zeae NRRL 34559.


Anomaly detection in online social networks (OSNs) is an important data mining task that aims to detect unexpected and suspicious users. To enhance anomaly exploration, anomaly ranking is used to assess the degree of user anomaly rather than applying binary detection methods, which depend on identifying users as either anomalous users or normal users. In this paper, we propose a community-based anomaly detection approach called Community ANOMaly detection (CAnom). Our approach aims to detect anomalous users in an OSN community and rank them based on their degree of deviation from normal users. Our approach measures the level of deviation in both the network structure and a subset of the attributes, which is defined by the context selection. The approach consists of two phases. First, we partition the network into communities. Then, we compute the anomaly ranking score, which is composed of a community-structure-based score and an attribute-based score. Experiments on real-world benchmark datasets show that CAnom detects ground-truth groups and outperforms baseline algorithms on accuracy. On synthetic datasets, the results show that CAnom has high AUC and ROC curves even when the attribute number increases; therefore, our model is suitable for today's applications, where the number of attributes is rising.


In membrane processes, a spacer is known to play a key role in the mitigation of membrane fouling. In this study, the effect of electric polarization on a graphene-blended polymer spacer (e.g., poly(lactic acid), PLA) for organic fouling on membrane surfaces was investigated. A pristine PLA spacer (P-S), a graphene-blended spacer (G-S), and an electrically polarized graphene-blended spacer (EG-S) were successfully fabricated by 3D printing. Organic fouling tests were conducted by the 5-h filtration of CaCl2 and a sodium alginate solution through commercially available membranes, which were placed together with the fabricated spacers. Membranes utilizing P-S, G-S, and EG-S were characterized in terms of the fouling amount on the membrane surface and fouling roughness. Electrostatic forces of EG-S provided 70% less and 90% smoother fouling on the membrane surface, leading to an only 14% less water flux reduction after 5 h of fouling. The importance of nanomaterial blending and polarization was successfully demonstrated herein.


In this study, we compare the results for vibrational, reorientational and hydrogen bond dynamics of ethanol in water and in hexane across the whole concentration range. Water and hexane are both commonly used as solvents, but so far, it has been unclear to what extent they modify the solute dynamics. Ethanol is chosen as the solute because it is an aliphatic molecule that is miscibile with both solvents. It is known that ethanol forms micelle-like domains in water and cyclic clusters resembling loops in hexane. This structural micro-heterogeneity is well known both in experiments and in simulations. The main question we raise here is: is there a signature of micro-heterogeneity in the dynamical quantities of ethanol? We focus on quantities such as the vibrational spectra, the reorientational correlation functions, the self-diffusion coefficients, the ethanol-ethanol hydrogen bond correlation functions and the corresponding hydrogen bond histograms. For the first time ever, we compute the van Hove functions to reveal the dynamical variations of spatial correlations in these systems. All these results complement each other and provide a unifying dynamical description of ethanol in binary mixtures.


From the trial investigation of human to identify facial expressions, the contrast of facial expression recognition between human and computer is analyzed. The phenomena that one expression may arise from several emotions ("one to more") and various expressions may reflect one emotion ("more to one") result in the problem that facial expression recognition is a difficult task because of these mapping uncertainties. In this paper, some points on understanding facial expression recognition are raised and several important aspects of the feature research are also discussed


The article presents the MRI symptoms of spinal tumors. We examined 44 patients with spinal gliomas. The diagnosis was confirmed during operation and verified morphologically. The study showed that tumor form significantly depended on its histological type: in patients with ependymomas we more often revealed elongate ellipsoid tumor with distinct contours on MRI with contrast enhancement and in patients with astrocytomas we found unformed tumors without clear borders. Siryngomyelic cists were found more often in patients with ependymomas. MRI sings of bleeding were revealed in 37,5% of patients with ependymomas and in 16,7 % patients with astrocytomas. The study showed that complex analysis of MRI symptoms can help to distinguish dendritic cell ependymomas from diffuse (fibrillar and protoplasmic) forms of astrocytomas. K e y w o r d s: spinal cord tumors, differential diagnosis, MRI


The effect of the geometry dependence of spin-orbit splitting on transition state theory (TST) predictions for radical-radical recombination rate coefficients is examined. The effects are illustrated with direct ab initio variable-reaction-coordinate (VRC)-TST calculations for the reactions of two types of hydrocarbon radicals (R = CH(3) and CH(2)CHCH(2)) with three halogen atoms (X = F, Cl, and Br). These halogen atoms exhibit a range of spin-orbit interaction strengths, while their interactions with the two hydrocarbon radicals exhibit a range of attractiveness. The transition state dividing surfaces for these barrierless reactions occur over a range of R-X fragment separations ( approximately 3-7 A) where the magnitude of the spin-orbit splitting is strongly geometry dependent. Perturbative models for incorporating the energetic effect of spin-orbit splitting into barrierless kinetics are presented and tested. Simply neglecting the variation in the spin-orbit splitting is demonstrated to contribute an error of less than 15% to the predicted rate coefficients for all but the CH(2)CHCH(2) + Br reaction, where its neglect increases the rate by up to a factor of 2. For the CH(2)CHCH(2) + Br reaction, the effect of spin-orbit splitting is not perturbative and instead qualitatively changes the long-range interaction potential and association dynamics. The present theoretical predictions are compared with available experimental measurements and previous theoretical work. For the CH(3) + F association reaction, the errors associated with limitations in the basis set and in the active space are studied, and a detailed comparison is made between VRC-TST and rigid rotor-harmonic oscillator variational TST.


Boron (B) and Tungsten (W) are often found enriched in high-temperature geothermal waters associated with the development of subduction-related mafic to felsic arc magma. However, knowledge about the sourcing and transportation of these elements from such hydrothermal systems is sparse and ambiguous. Being the only active continental collision site in the world, the Trans-Himalaya offers a unique chance to study how continental collision sources the high boron and tungsten concentrations in geothermal fluids. This study investigated the distribution of trace elements, major cations, and anions in three physicochemically distinct hotspring sites in the Ladakh region. The results were integrated with the existing geochemical and isotopic data to address the research problem more effectively. This study exhibits that the extreme concentrations of boron, sodium, chlorine, potassium, and tungsten in the hotspring waters were primarily governed by magmatic fluid inputs. In addition, this study recorded the highest-ever chlorine and boron concentrations for the Trans-Himalayan hotspring waters. The highest-ever boron and chlorine concentrations in the hotspring waters probably represented an increase in magmatic activity in the deeper source zone.


Green tea is a popular beverage around the world and possesses a unique flavor. The flavor qualities of green tea are closely related to its grade and this relationship has not yet been studied. Three baked green teas with similar flavor were studied, namely, Huangshan Maofeng, Taiping Houkui, and Shucheng Xiaolanhua. A total of 34 odor compounds were identified by solid phase microextraction (SPME) combined with two-dimensional comprehensive gas chromatography–olfactometry–mass spectrometry analysis (GC×GC-O-MS). The results of the clustering analysis showed that the content of D-limonene and linalool in the high-grade (Grade A) tea was much higher than the content in other grades, so they were identified as odor markers of Grade A baked green tea. The taste components of different grades of green tea infusion were analyzed by high-performance liquid chromatography–mass spectrometry (HPLC–MS) and HPLC. A combination of clustering analysis, principal component analysis (PCA), and orthogonal partial least squares discrimination analysis (OPLS-DA) indicated that galloylglucose, digalloylglucose, trigalloyglucose, strictinin, and gallic acid could be used as taste markers of Grade A baked green tea. Therefore, the results in this paper reveal the substances responsible for the odor and taste markers of high-grade baked green tea.


How to counter the false perception of science as cold facts devoid of human interest is a problem that has exercised many minds in recent years. Richard Brennan presents pen portraits of eight men who have shaped our modern understanding of physics. He writes explicitly for the `intelligent layperson', convinced that the physicists' insights can be explained in simple terms and that their personalities are important in understanding their achievements. It is the dramatic and exciting story of modern physics that he sets out to tell. Seven of the eight are twentieth-century physicists - Einstein, Planck, Rutherford, Bohr, Heisenberg, Feynman and Gell-Mann. The eighth is Newton. His were the ideas that the modern physicists tested up to, and beyond, their limits, but he is included more because of who he is than because the story of his life and work contributes to the main thrust of the book. To distil the life and work of such important figures into a few short pages is a tall order, and Brennan's success is uneven. The discussion of some concepts, such as simultaneity in the context of Einstein's theory of relativity, is not totally convincing. Only those parts of a subject's work that help to weave a continuous thread through the eight chapters are treated in any detail. The basic concepts of relativity, atomic physics and quantum mechanics have been known for sufficiently long to be more easily accepted, but Feynman's diagrams and the gamut of particles foreshadowed by Gell-Mann's work have not yet been assimilated. Brennan's explanations give some inkling of what they are, but less about how and why they are so important. The accounts of the lives of the chosen physicists are conventional and pay little attention to the nuances of academic historians. Brennan accepts the story of Newton being inspired by an apple falling because Newton told it to his first biographer many years later. Historians can point to many instances where the recollections of old age are demonstrably incorrect. Brennan does point out that achievements have to be seen in the context of the times, but he does not attain this consistently. He does not always succeed in conveying how reasonable it was that other scientists should not accept immediately ideas like Einstein's relativity, the Rutherford - Bohr atom or Heisenberg's uncertainty. The personal lives of the eight men are described dispassionately, unpleasant features are neither ignored nor recounted in unnecessary detail. Five of the physicists lived through the Second World War and were radically affected by the conflict: it shattered hitherto close relationships between some of them. It is here one sees most clearly that scientists are not cocooned in ivory towers, but are caught up inextricably in the events surrounding them. The format of the book does not permit an integrated discussion of this vast topic, and in any case it is almost impossible to balance the conflicting pressures of morality, patriotism and reality. The unashamedly journalistic style of the book ignores many subtleties. Its American origin is obvious, and the author fails to appreciate some cultural distinctions. The description of Faraday as `the Thomas Edison of his day' will seem bizarre to British readers. Where figures are quoted they are in imperial units, which will dismay British science educators. The book is marred by occasional carelessness over details such as the spelling of names. There is a chronology of physics but it is so short that it omits too many significant events, and it gives an unusual date in at least one case (Thomson's discovery of the electron). The glossary is also short and of restricted value, and the bibliography looks as though a page or two has been omitted since it ends at the letter P. The index is not comprehensive, omitting some significant names. The reader with no background in science should find the book interesting, though there are parts that will not be understood fully. It is more likely to be read by someone with at least a basic knowledge of science, who could find it glib in places. No book of this length intended for a lay audience can do more than skim the surface, and there is a dearth of material about the human side of science. Though imperfect, it is worth using with care, and there is a need for more books of this type.


Can frictionless small open economy models driven solely by technology shocksaccount for business cycles in developing countries? We don't find evidence of it. We build a DSGE model that jointly includes a variety of real perturbations in addition to technology shocks, such as procyclical fiscal policies; terms of trade fluctuations; and perturbations to the foreign interest rate coupled with financial frictions and estimate it using Bayesian methods on high and low frequency data from a developing -and "tropical"- country, Colombia. We find interest rate shocks to be crucial andthat financial frictions play a central role as propagating mechanisms of transitory technology shocks. These two driving forces alone can account well for the observed properties of the Colombian business cycle. Other structural shocks such as terms of trade fluctuations and level shifts in the technology process do not appear to be relevant in the past decade and a half, but their importance increases when a longer span of data is considered.


The work presented in this thesis focused on bone tissue engineering approach as an alternative treatment for bone repair and losses resulting from injury or disease. This multidisciplinary field combines biology, engineering, physics, materials sciences, and medicine, to develop bone tissue like substitutes. This is achieved through a specific interaction between scaffolds, cells and growth factors. Thus, there are three key issues that lead to the design of successfully engineered bone tissue, and must be carefully investigated. The main objective proposed in this thesis addresses the fabrication of artificial bone tissue, and in vitro and in vitro tests to confirm the suitability of the fabricated bone tissue. The research works were divided into three parts. The results obtained in each part contributed significantly to engineering area of bone tissue. The first part was directed towards the development of a new scaffold used in bone tissue engineering. The second part of this work focused on bone cell attachment and growth on the scaffold in vitro. The third part focused on the post-implantation biological evaluation of the implanted newly developed scaffold in vivo. Three-dimensional novel porous biodegradable scaffolds were fabricated with micro and macro-architectures. For the first time, a unique blend of cockle shell, dextrin, dextran and gelatin were studied in order to design an ideal bone scaffolds with an adequate degradation rate. Five different ratios of bone scaffolds were rabricated and two different processing methods were used to develop the scaffolds. The processing methods used in this study allowed the preparation of 3D-Scaffolds with controlled porosity and adequate pore size with good mechanical strength. The newly developed scaffolds have the following characteristics: (i) good biocompatibility and biodegradability, (ii) suitable surface chemistry and (iii) highly porous, with interconnected pore net work. In vitro study on rabbit bone marrow osteoblastic differentiation of stromal cells (MSC) was assessed on scaffolding. The MSCs was cultured for 10 to 16 days using fresh cells of bone marrow under osteogenic differentiation conditions. The cells were sub-cultured for 5 weeks on different compositions of the scaffolds. The capability of cells to proliferate and form extracellular matrix on these scaffolds was assessed by a significantly increased activity of alkaline phosphatase and calcium deposits at 21 days. Light and scanning electron microscopy revealed the presence of numerous osteoblasts-like cells with the development of calcification of the dense network of collagen fibrils and bone matrix-like tissues were observed in the different area of scaffolds, resulting in the formation of bone like tissue containing osteocyte-like cells. In this process the manual delivery of nutrients and disposal of waste were applied. In vivo study was about evaluating the new bioceramic scaffolf. Various micro-macropores scaffolds were implanted into 1.5 cm critical size defect created on the radial bone of rabbits. Bone regrowth in the bioceramics was obtained using an established model of bone formation in vitro by exogenously added osteoprogenitor cells. Radiographic examination revealed new bone image representing the bone construct was formed at the margin and centre of the defect, which involved osteogenesis that diffused from the central region and the margin of the scaffold implant. Histological analysis of samples at 8 weeks revealed the amount of mature bone had increased to form completer bone. The mass of the implanted scaffold was completely dissolved and absorbed during this time. A little cartilage tissue was detected in some of the implanted scaffolds. Bone formation showed a centripetal pattern, and the new bone always appeared as a replacement to the implanted matrix. As far as we know, the time of complete restore the lost bone in this study represents a major break through in the artificial bone graft healing.


Woods and Gardner (2011) open debate on the challenge of policy application by geographers. Their contribution begs extension to consider the shifting multi-scalar forces that condition the application of scholarship. These include both endogenous and exogenous influences. The former have evolved swiftly in recent decades with the rise of managerialism in the higher education sectors of western nations. Most recently the emergence and implementation of national research assessment frames has provided a powerful conditioning force around applied scholarship. The liberal view of the independent scholar is deeply problematised by these influences. The role of the contemporary public intellectual exposes these problems and bears more discussion than has been the case up to now.


The core thesis is that postnormal science, a discourse on scientific methodology and its related techniques, can be understood as a realization of the new modality of science that Marcuse predicted in One-Dimensional Man, where: "pacified existence...the repressed final cause behind the scientific enterprise... were [it] to materialize and become effective, [is accompanied by a situation where] the Logos of technics would open a universe of qualitatively different relations between man and man, and man and nature."


Scottish philosophy and intellectual history have become the increasingly fashionable fields of academic studies. Alexander Broadie, one of the pioneers and an accomplished scholar of the Scottish Enlightenment, returns to the basic question, namely, "what is Scottish philosophy?", and presents a comprehensive work on the history of Scottish philosophy. Broadie successfully elucidates the nature and significance of Scottish philosophy both historically and philosophically. He argues that Scottish philosophy must be studied in its historical context, for it is not only a philosophical enterprise but also a persistent tradition which has united the Scottish nation for centuries. The advancements in science, literature, politics, and culture in Scotland would be extremely unlikely, if not impossible, without such an intellectual culture established by thinkers in that tradition. This article is intended as a review of Broadie's A History of Scottish Philosophy in the background of his shifting academic interests from philosophy to history while he holds the professorship in University of Glasgow. His commitment to Scottish philosophical culture deserves the attention of contemporary historians and philosophers, for his work opens up a space for MA Candidate in the History of Political Thought and Intellectual History, Queen Mary University of London and University College London. 評 Alexander Broadie, A History of Scottish Philosophy 179 dialogue between intellectual history and history of philosophy, an issue addressed at the end of this paper.


Background and hypothesis: CD25 (IL2RA) represents the α chain of the interleukin 2 receptor on T cells and plays an important role in the maintenance of regulatory T (Treg) cells, hence preventing T cell autoimmunity. In a comprehensive gene expression analysis, we found that CD25 is specifically upregulated by pre-B cell receptor (pre-BCR) signaling during early B cell development and oncogenic tyrosine kinase that mimic pre-BCR signaling (e.g. in Ph+ ALL and Ph-like ALL). In adults with Ph+ ALL (ECOG; MDACC) and children with Ph-like ALL (P9906) patients with CD25 expression at the time of diagnosis have a particularly poor outcome (n=416; P=0.005). For these reasons, we studied the function of CD25 in B cell development and leukemia in a series of genetic experiments. Results: Unlike T cells, CD25 (IL2RA) does not function as IL2 receptor chain in B cells and B-lineage ALL: CD25 expressed on B-lineage cells did not pair with IL2Rb and g-chains and was not responsive to IL2. Il2ra-/- B cells were arrested at the pre-B cell stage with hyperactive pre-BCR downstream signaling including SRC, BTK and ERK. In the presence of CD25, Il2ra+/+ B cells responded to engagement of the pre-BCR with phosphorylation of pre-BCR downstream tyrosine kinases and coordinated release of Ca2+ from cytoplasmic stores. In the absence of CD25 (Il2ra-/-), the pre-BCR signals autonomously, resulting in uncoordinated Ca2+ oscillations of variable duration. While CD25 does not function as IL2 receptor chain in B cells, it coordinates pre-BCR-dependent signal transduction and regulates its intensity. The pre-BCR related tyrosine kinase BTK is phosphorylated by BCR-ABL1 in Ph+ ALL and other tyrosine kinase oncogenes in Ph-like ALL (Chen et al., 2015). Interestingly, overexpression of a constitutively active form of BTK resulted in strong upregulation of CD25 surface expression. Conversely, the BTK-inhibitor ibrutinib abolished CD25 expression suggesting that feedback control between pre-BCR signaling and CD25 requires BTK. The ability of CD25 to stabilize oncogenic signaling strength in Ph+ ALL and Ph-like ALL was important for leukemia-initiation and development of fatal disease. In the absence of CD25, Il2ra-/- ALL cells showed impaired proliferation and colony formation. Serial transplantation experiments revealed a profound defect of Il2ra-/- ALL cells to initiate leukemia. 100-times more cells were required to cause fatal disease. In addition, CD25 expression mediated drug-resistance in ALL cells: In patient-derived pre-B ALL cells with heterogeneous CD25 expression, vincristine selectively induced apoptosis in CD25Low cells but spared CD25High ALL cells. Combination with an anti-CD25 immunotoxin efficiently eradiated CD25High leukemia cells and sensitized the ALL cell population to treatment with vincristine. To elucidate the mechanism of how CD25 coordinates negative feedback control of pre-BCR signaling or its oncogenic mimics, we focused on its short (13aa) cytoplasmic tail, which includes two phosphorylation sites (S268 and T271) that are known substrates for serine/threonine protein kinase, PKCα. To identify cytoplasmic interaction partners of CD25, we overexpressed a Flag-tagged truncated form of CD25 including a myristoylation signal for constitutive membrane localization, transmembrane domain and cytoplasmic tail. Immunoprecipitation (IP; Flag) followed by 2D mass spectrometry revealed strong interactions of PP2A with cytoplasmic tail of CD25. Western blots showed additional strong interactions of the cytoplasmic tail of CD25 with inhibitory phosphatases PTEN, SHP1 and SHIP1. Importantly, reconstitution of myristoylated CD25 tail but not a mutant construct lacking the serine/threonine motif (S268A/T271A) rescued proliferation and survival defects of Il2ra-/- ALL cells. Conclusion: We identified CD25 as a surface receptor that mediates membrane recruitment of PP2A, PTEN, SHP1 and SHIP1, which balances fluctuations in signaling output from a pre-B cell receptor or its oncogenic mimic in ALL cells (e.g. BCR-ABL1 in Ph+ ALL). We propose that CD25-mediated negative feedback control stabilizes oncogenic tyrosine kinase signaling and mediates drug-resistance in Ph+ ALL and Ph-like ALL cells. Targeted inhibition using CD25-directed immunotoxins may be useful in new approaches to overcome drug-resistance in Ph+ ALL and Ph-like ALL. Disclosures No relevant conflicts of interest to declare.