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1
Bolt, Bruce A. "Inge Lehmann. 13 May 1888—21 February 1993." Biographical Memoirs of Fellows of the Royal Society 43 (January 1997): 287–301. http://dx.doi.org/10.1098/rsbm.1997.0016.
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Dr Inge Lehmann was born on 13 May 1888 at Osterbro by the Lakes in Copenhagen. She grew up and lived much of her long life there, and for over 50 years, on Kastelvej, Copenhagen. The Lehmann family had its roots in Bohemia; the Danish branch had many influential members of high standing, including barristers, politicians and engineers. Inge Lehmann's paternal grandfather laid out the first Danish telegraph line (opened in 1854) and her great grandfather was Governor of the National Bank. Her mother's father, Hans Jakob T0rsleff, belonged to an old Danish family with a priest in every generation. A granddaughter, Anne Groes, was for a while Minister of Commerce. Inge's childhood was a happy one in the peaceful atmosphere of the 1890s. Her father, Alfred Lehmann, was a professor of psychology at the University of Copenhagen who pioneered the study of experimental psychology in Denmark. He was rarely seen except at mealtimes, though sometimes on Sunday he took the family for a walk. (A fund endowed by her estate makes a travel award each year alternatively to a psychologist and a geophysicist.) She had a sister, Harriet.
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Nze Ossima, Arnaud D., Jean-Pierre Daurès, Faiza Bessaoud, and Brigitte Trétarre. "The generalized Lehmann ROC curves: Lehmann family of ROC surfaces." Journal of Statistical Computation and Simulation 85, no. 3 (September 2, 2013): 596–607. http://dx.doi.org/10.1080/00949655.2013.831863.
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Gönen, Mithat, and Glenn Heller. "Lehmann Family of ROC Curves." Medical Decision Making 30, no. 4 (March 30, 2010): 509–17. http://dx.doi.org/10.1177/0272989x09360067.
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Receiver operating characteristic (ROC) curves evaluate the discriminatory power of a continuous marker to predict a binary outcome. The most popular parametric model for an ROC curve is the binormal model, which assumes that the marker, after a monotone transformation, is normally distributed conditional on the outcome. Here, the authors present an alternative to the binormal model based on the Lehmann family, also known as the proportional hazards specification. The resulting ROC curve and its functionals (such as the area under the curve and the sensitivity at a given level of specificity) have simple analytic forms. Closed-form expressions for the functional estimates and their corresponding asymptotic variances are derived. This family accommodates the comparison of multiple markers, covariate adjustments, and clustered data through a regression formulation. Evaluation of the underlying assumptions, model fitting, and model selection can be performed using any off-the-shelf proportional hazards statistical software package.
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Yakovlev, Roman V., Rob De Vos, Ramon Hulsbosch, and Vadim V. Zolotuhin. "Revision of the family Metarbelidae (Lepidoptera) of the Oriental Region. VIII. Genus Lutzkobesia Lehmann, 2019." Ecologica Montenegrina 52 (March 30, 2022): 49–52. http://dx.doi.org/10.37828/em.2022.52.7.
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In the eighth part of the revision on the Asian Metarbelidae (Lepidoptera) we consider the genus Lutzkobesia Lehmann, 2019, which includes two species, distributed in Western Indonesia (the islands of Sumatra and Java): L. hollowayi Lehmann, 2019 and L. tenera (Roepke, 1957) comb. n.
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Revell, E. J., and Israel Yeivin. "Yeivin, "Hebrew Manuscripts of the Lehmann Family"." Jewish Quarterly Review 84, no. 2/3 (October 1993): 348. http://dx.doi.org/10.2307/1455379.
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Jokiel-Rokita, Alicja, and Rafał Topolnicki. "Estimation of the ROC curve from the Lehmann family." Computational Statistics & Data Analysis 142 (February 2020): 106820. http://dx.doi.org/10.1016/j.csda.2019.106820.
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Schiaparelli, Stefano, Marco Oliverio, Marco Taviani, Huw Griffiths, Anne-Nina Lörz, and Giancarlo Albertelli. "Short Note: Circumpolar distribution of the pycnogonid-ectoparasitic gastropod Dickdellia labioflecta (Dell, ) (Mollusca: Zerotulidae)." Antarctic Science 20, no. 5 (May 16, 2008): 497–98. http://dx.doi.org/10.1017/s0954102008001302.
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The Antarctic gastropod Dickdellia labioflecta (Dell, 1990) (originally described as Laevilittorina (Corneolittorina) labioflecta) is an obligate parasite of pycnogonids, which exploits their body fluids through the cuticular gland holes (Lehmann et al. 2007) and lays its eggs on the pycnogonid's legs where embryos complete their life cycle (Hedgpeth 1964, Sirenko 2000, Lehmann et al. 2007). The ecology of D. labioflecta appears to be unique, as no other examples of such a specialized parasitic behaviour on pycnogonids are known. This life-style and the related anatomical specializations (gut and digestive gland morphology), prompted the erection of a new genus, Dickdellia Warén & Hain, 1996 provisionally included in the family Zerotulidae (Warén & Hain 1996). Although information is quite scant, to date, two pycnogonid host species are known for Dickdellia: Colossendeis megalonyx megalonyx Fry & Hedgpeth, 1969 (Lehmann et al. 2007) and Nymphon isabellae Turpaeva, 2000 (Sirenko 2000).
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Mutairi, Alya Al, and Muhammad Z. Arshad. "A New Odd Fréchet Lehmann Type II–G Family of Distributions: A Power Function Distribution With Theory and Applications." International Journal of Statistics and Probability 11, no. 2 (February 13, 2022): 29. http://dx.doi.org/10.5539/ijsp.v11n2p29.
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Modeling complex random phenomena frequently observed in reliability engineering and medical science once thought to be an enigma. Scientists and practitioners agree that an appropriate but simple model is the best choice for this investigation. We contribute a new family referred to as an odd Fréchet Lehmann type-II (OFrLII) G family of distributions to address these issues. This new family has involved a shape parameter that modulated the tails of new models. Furthermore, we develop a list of eight new sub-models for a new family and a power function distribution (OFrLII–PF) nominated for detailed discussion. We derive several complementary mathematical properties and explicit expressions for the moments, quantile function, and order statistics. We plot possible shapes of the density and the hazard rate functions over the particular choices of the model parameters. We follow a technique known as maximum likelihood estimation to estimate unknown model parameters and a simulation study established to assess the asymptotic behavior of these MLEs. The applicability of the OFrLII–G family, is evaluated via OFrLII –PF distribution. For this, we fit two engineering and one COVID–19 pandemic dataset. Supportive results of OFrLII–PF distribution declare it as a better fit model against the well-established competitor’s ones. A modified odd Fréchet Lehmann Type II–G Family of Distributions: A Power Function Distribution with Theory and Applications
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Petridou, Maria, Vasilios Kimiskidis, Konstantinos Deligiannis, and Aristides Kazis. "Borjeson-Forssman-Lehmann syndrome: two severely handicapped females in a family." Clinical Neurology and Neurosurgery 99, no. 2 (May 1997): 148–50. http://dx.doi.org/10.1016/s0303-8467(97)80014-5.
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Yakovlev, Roman V., and Vadim V. Zolotuhin. "Revision of the family Metarbelidae (Lepidoptera) of the Oriental Region. III. Genus Stueningeria Lehmann, 2019." Ecologica Montenegrina 43 (June 16, 2021): 16–29. http://dx.doi.org/10.37828/em.2021.43.2.
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In the third part of the revision of the family Metarbelidae (Lepidoptera) of South-Eastern Asia, we provide a revision of the genus Stueningeria Lehmann, 2019 with description of six new species: Stueningeria htetae sp. nov. (Type locality: Mynmar, 21 km E Putao), Stueningeria csovarii sp. nov. (Type locality: Thailand, Changwat Nan, 15 km N of Bo Luang), Stueningeria loeffleri sp. nov. (Type locality: Thailand, Sakhon Nakhon Prov., Phu Pan NP), Stueningeria ihlei sp. nov. (Type locality: Vietnam (C.), Prov. Thua-Thien-Hue, Kreis A Luoi, Gemeinde A Rong, Passastrasse ca. 30 km S A Luoi.), Stueningeria murzini sp. nov. (Type locality: China, SW Yunnan, Xishuanbanna, Guanping env., 60 km N Jinghong), and Stueningeria pinratanai sp. nov. (Type locality: NW Thailand, Chiangmai, Doi Pui Forest Res. Stat.) Two new combinations are established: Stueningeria campbelli (Hampson, 1910) comb. nov. and Stueningeria phaga (Swinhoe, 1894) comb. nov. Both species are redescribed. The type species of the genus Stueningeria nepalensis Lehmann, 2019 is reported for the first time for the fauna of India (Uttarakhand). We also give for the first time the description of female genitalia of the genus Stueningeria. The genus distribution map is provided.
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Gair, Susan, Jennifer Lehmann, and Rachael Sanders. "Editorial." Children Australia 41, no. 4 (November 29, 2016): 245–46. http://dx.doi.org/10.1017/cha.2016.42.
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Welcome to the final edition of Children Australia for 2016. For this edition, I am pleased to be guest co-editor along with regular editors Jennifer Lehmann and Rachael Sanders. Living in rural and remote Australia can bring a high level of satisfaction and many rewards, including a strong caring community, rich, longstanding social relationships, outdoor lifestyle, happy childhood memories and psychological, cultural, spiritual and economic connections to country. Rural living and working can also bring unique challenges including harsh climatic conditions and crises, a tyranny of distance, isolation, family hardships, limited services and infrastructure, reduced education and employment opportunities; and increased risk of mental health issues, family violence and child safety concerns. The demands of providing remote area health, welfare and other professional services include high visibility and trying to ‘fit in’, managing confidentiality, and dual and inter-relationships. These and other geographical and environmental challenges lead to low workforce retention rates that, in turn, leave significant gaps in service provision for children, families and communities, including Aboriginal communities (Jervis-Tracey et al., 2016; Lehmann, 2015; Robinson, Mares, & Arney, 2016).
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Jain, Kanchan, Savita Jain, and Suresh Sharma. "Generalized Lehmann family for meta analysis based upon summary receiver operating characteristic curves." Discussiones Mathematicae Probability and Statistics 36, no. 1-2 (2016): 115. http://dx.doi.org/10.7151/dmps.1186.
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Steen, Adam, and Lawrence S. Welch. "Dancing With Giants: Acquisition and Survival of the Family Firm." Family Business Review 19, no. 4 (December 2006): 289–300. http://dx.doi.org/10.1111/j.1741-6248.2006.00076.x.
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In this article, we examine the responses of family companies to the emerging environment of mergers and acquisitions, specifically within the international wine industry. At issue is the question of how the family perspective influences responses of a family firm to the prospect of merger or takeover. We examine the issue through a case study of the takeover of an Australian wine producer and family firm, Peter Lehmann Wines. The case study demonstrates ways in which the family perspective is critical in driving responses, for example, in the strength and forms of opposition to one of the potential acquirers in the case, indicating just how important the preservation of a family legacy was to key family members. However, the case also illustrates how in a takeover fight the dynamics of the takeover process itself become important in determining outcomes. In addition, the case demonstrates that family involvement and influence can be maintained in spite of takeover.
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Zakrevskaya, E. Yu. "The First Find of <i>Orbitolites</i> (Foraminifera: Family Soritidae) in the Eocene of Armenia." Палеонтологический журнал, no. 3 (May 1, 2023): 11–21. http://dx.doi.org/10.31857/s0031031x23030157.
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Paleogene genus Orbitolites (family Soritidae) was found in Armenia as well as in former USSR firstly. The largest species O. cotentinensis Lehmann prevails in population of this genus in Rind section of Southern Armenia. The systematic description of three species of discovered Orbitolites is given. The aсcompanying assemblage of larger benthic foraminifera allowed to define the stratigraphic position of layers with Orbitolites in lower Priabonian, SB18C subzone. Distribution of Orbitolites and miliolids show on back-reef lagoon paleoenvironment, unusual for Priabonian of Southern Armenia.
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Khan, Sadaf, Oluwafemi Samson Balogun, Muhammad Hussain Tahir, Waleed Almutiry, and Amani Abdullah Alahmadi. "An Alternate Generalized Odd Generalized Exponential Family with Applications to Premium Data." Symmetry 13, no. 11 (November 1, 2021): 2064. http://dx.doi.org/10.3390/sym13112064.
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In this article, we use Lehmann alternative-II to extend the odd generalized exponential family. The uniqueness of this family lies in the fact that this transformation has resulted in a multitude of inverted distribution families with important applications in actuarial field. We can characterize the density of the new family as a linear combination of generalised exponential distributions, which is useful for studying some of the family’s properties. Among the structural characteristics of this family that are being identified are explicit expressions for numerous types of moments, the quantile function, stress-strength reliability, generating function, Rényi entropy, stochastic ordering, and order statistics. The maximum likelihood methodology is often used to compute the new family’s parameters. To confirm that our results are converging with reduced mean square error and biases, we perform a simulation analysis of one of the special model, namely OGE2-Fréchet. Furthermore, its application using two actuarial data sets is achieved, favoring its superiority over other competitive models, especially in risk theory.
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Kim, Joungyoun, Sung-Cheol Yun, Johan Lim, Moo-Song Lee, Won Son, and Dohwan Park. "ROC Estimation from Clustered Data with an Application to Liver Cancer Data." Cancer Informatics 15s4 (January 2016): CIN.S40299. http://dx.doi.org/10.4137/cin.s40299.
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In this article, we propose a regression model to compare the performances of different diagnostic methods having clustered ordinal test outcomes. The proposed model treats ordinal test outcomes (an ordinal categorical variable) as grouped-survival time data and uses random effects to explain correlation among outcomes from the same cluster. To compare different diagnostic methods, we introduce a set of covariates indicating diagnostic methods and compare their coefficients. We find that the proposed model defines a Lehmann family and can also introduce a location-scale family of a receiver operating characteristic (ROC) curve. The proposed model can easily be estimated using standard statistical software such as SAS and SPSS. We illustrate its practical usefulness by applying it to testing different magnetic resonance imaging (MRI) methods to detect abnormal lesions in a liver.
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Holling, Heinz, Walailuck Böhning, and Dankmar Böhning. "Meta-analysis of diagnostic studies based upon SROC-curves: a mixed model approach using the Lehmann family." Statistical Modelling: An International Journal 12, no. 4 (August 2012): 347–75. http://dx.doi.org/10.1177/1471082x1201200403.
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Lower, Karen M., Göran Solders, Marie-Louise Bondeson, John Nelson, Arne Brun, Joanna Crawford, Gunilla Malm, et al. "1024C>T (R342X) is a recurrent PHF6 mutation also found in the original Börjeson–Forssman–Lehmann syndrome family." European Journal of Human Genetics 12, no. 10 (July 7, 2004): 787–89. http://dx.doi.org/10.1038/sj.ejhg.5201228.
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Gomaa, Rabab S., Alia M. Magar, Najwan Alsadat, Ehab M. Almetwally, and Ahlam H. Tolba. "The Unit Alpha-Power Kum-Modified Size-Biased Lehmann Type II Distribution: Theory, Simulation, and Applications." Symmetry 15, no. 6 (June 19, 2023): 1283. http://dx.doi.org/10.3390/sym15061283.
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In order to represent the data with non-monotonic failure rates and produce a better fit, a novel distribution is created in this study using the alpha power family of distributions. This distribution is called the alpha-power Kum-modified size-biased Lehmann type II or, in short, the AP-Kum-MSBL-II distribution. This distribution is established for modeling bounded data in the interval (0,1). The proposed distribution’s moment-generating function, mode, quantiles, moments, and stress–strength reliability function are obtained, among other attributes. To estimate the parameters of the proposed distribution, estimation methods such as the maximum likelihood method and Bayesian method are employed to estimate the unknown parameters for the AP-Kum-MSBL-II distribution. Moreover, the confidence intervals, credible intervals, and coverage probability are calculated for all parameters. The symmetric and asymmetric loss functions are used to find the Bayesian estimators using the Markov chain Monte Carlo (MCMC) method. Furthermore, the proposed distribution’s usefulness is demonstrated using three real data sets. One of them is a medical data set dealing with COVID-19 patients’ mortality rate, the second is a trade share data set, and the third is from the engineering area, as well as extensive simulated data, which were applied to assess the performance of the estimators of the proposed distribution.
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Lehmann, Maike, and Alexandra Oberländer. "Introduction: Socialism to Be Embodied." East European Politics and Societies: and Cultures 34, no. 4 (June 7, 2020): 802–16. http://dx.doi.org/10.1177/0888325420921917.
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This article belongs to the special cluster, “Family, Gender and (dis)Abled Bodies after 1953”, guest-edited by Maike Lehmann and Alexandra Oberländer. While the ideal of the New Socialist Wo/Man was never fully realized and seems to have been abandoned across the Eastern Bloc after 1953, the question still arises what role individuals were to play within the socialist system. As dichotomous conceptualizations of state and society have been repeatedly criticized in recent years, we propose to look at how the role of the individual was imagined by different actors in Eastern European countries and how the ideals inherent in these imaginations were (to be) embodied. One possible avenue would be to explore the role of official language for subjectivization processes as they have been discussed during the last twenty years in Soviet studies. We, however, want to turn the attention towards the body and its role in shaping the individual in a cluster dealing with the impact family, gender, and dis/ability (were meant to) have on the formation of an individual body and its place within broader society. This is to explore some of the ways in which anybody could become somebody in socialist Eastern Europe and might help to shift the attention from dichotomous conceptualizations of political dogma and social practice towards an exploration of socialism as a diverse, yet specific cultural system.
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Young, Virginia R. "Discussion of Christofides' Conjecture Regarding Wang's Premium Principle." ASTIN Bulletin 29, no. 2 (November 1999): 191–95. http://dx.doi.org/10.2143/ast.29.2.504610.
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Christofides (1998) studies the proportional hazards (PH) transform of Wang (1995) and shows that for some parametric families, the PH premium principle reduces to the standard deviation (SD) premium principle. Christofides conjectures that for a parametric family of distributions with constant skewness, the PH premium principle reduces to the SD principle. I will show that this conjecture is false in general but that it is true for location-scale families and for certain other families.Wang's premium principle has been established as a sound measure of risk in Wang (1995, 1996), Wang, Young, and Panjer (1997), and Wang and Young (1998). Determining when the SD premium principle is a special case of Wang's premium principle is important because it will help identify circumstances under which the more easily applied SD premium principle is a reliable measure of risk.First, recall that a distortion g is a non-decreasing function from [0, 1] onto itself. Wang's premium principle, with a fixed distortion g, associates the following certainty equivalent with a random variable X, (Wang, 1996) and (Denneberg, 1994):in which Sx is the decumulative distribution function (ddf) of X, Sx(t) = Pr(X > t), t ∈ R. If g is a power distortion, g(p) = pc, then Hg is the proportional hazards (PH) premium principle (Wang, 1995).Second, recall that a location-scale family of ddfs is , in which Sz is a fixed ddf. Alternatively, if Z has ddf Sz, then {X = μ + σZ: μ∈ R, σ > 0} forms a location-scale family of random variables, and the ddf of . Examples of location-scale families include the normal, Cauchy, logistic, and uniform families (Lehmann, 1991, pp. 20f). In the next proposition, I show that Wang's premium principle reduces to the SD premium principle on a location-scale family. Christofides (1998) observes this phenomenon in several special cases.
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Dubois, D., H. Fargier, and H. Prade. "Ordinal and Probabilistic Representations of Acceptance." Journal of Artificial Intelligence Research 22 (July 1, 2004): 23–56. http://dx.doi.org/10.1613/jair.1265.
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An accepted belief is a proposition considered likely enough by an agent, to be inferred from as if it were true. This paper bridges the gap between probabilistic and logical representations of accepted beliefs. To this end, natural properties of relations on propositions, describing relative strength of belief are augmented with some conditions ensuring that accepted beliefs form a deductively closed set. This requirement turns out to be very restrictive. In particular, it is shown that the sets of accepted belief of an agent can always be derived from a family of possibility rankings of states. An agent accepts a proposition in a given context if this proposition is considered more possible than its negation in this context, for all possibility rankings in the family. These results are closely connected to the non-monotonic 'preferential' inference system of Kraus, Lehmann and Magidor and the so-called plausibility functions of Friedman and Halpern. The extent to which probability theory is compatible with acceptance relations is laid bare. A solution to the lottery paradox, which is considered as a major impediment to the use of non-monotonic inference is proposed using a special kind of probabilities (called lexicographic, or big-stepped). The setting of acceptance relations also proposes another way of approaching the theory of belief change after the works of Gärdenfors and colleagues. Our view considers the acceptance relation as a primitive object from which belief sets are derived in various contexts.
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Morishita, Takashi, Yasuhiro Tsutsui, Hiroshi Iwasaki, and Hideo Shinagawa. "The Schizosaccharomyces pombe rad60 Gene Is Essential for Repairing Double-Strand DNA Breaks Spontaneously Occurring during Replication and Induced by DNA-Damaging Agents." Molecular and Cellular Biology 22, no. 10 (May 15, 2002): 3537–48. http://dx.doi.org/10.1128/mcb.22.10.3537-3548.2002.
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ABSTRACT To identify novel genes involved in DNA double-strand break (DSB) repair, we previously isolated Schizosaccharomyces pombe mutants which are hypersensitive to methyl methanesulfonate (MMS) and synthetic lethals with rad2. This study characterizes one of these mutants, rad60-1. The gene that complements the MMS sensitivity of this mutant was cloned and designated rad60. rad60 encodes a protein with 406 amino acids which has the conserved ubiquitin-2 motif found in ubiquitin family proteins. rad60-1 is hypersensitive to UV and γ rays, epistatic to rhp51, and defective in the repair of DSBs caused by γ-irradiation. The rad60-1 mutant is also temperature sensitive for growth. At the restrictive temperature (37°C), rad60-1 cells grow for several divisions and then arrest with 2C DNA content; the arrested cells accumulate DSBs and have a diffuse and often aberrantly shaped nuclear chromosomal domain. The rad60-1 mutant is a synthetic lethal with rad18-X, and expression of wild-type rad60 from a multicopy plasmid partially suppresses the MMS sensitivity of rad18-X cells. rad18 encodes a conserved protein of the structural maintenance of chromosomes (SMC) family (A. R. Lehmann, M. Walicka, D. J. Griffiths, J. M. Murray, F. Z. Watts, S. McCready, and A. M. Carr, Mol. Cell. Biol. 15:7067-7080, 1995). These results suggest that S. pombe Rad60 is required to repair DSBs, which accumulate during replication, by recombination between sister chromatids. Rad60 may perform this function in concert with the SMC protein Rad18.
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Hallama, Peter. "Struggling for a Socialist Fatherhood: “Re-educating” Men in East Germany, 1960–1989." East European Politics and Societies: and Cultures 34, no. 4 (June 7, 2020): 817–36. http://dx.doi.org/10.1177/0888325419891200.
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This article belongs to the special cluster, “Family, Gender and (dis)Abled Bodies after 1953”, guest-edited by Maike Lehmann and Alexandra Oberländer. Research on the history of masculinities and fatherhood during state socialism in East Central Europe is still rare. Therefore, scholars in the field of women’s and gender studies sometimes reproduce the idea of men in that region as stable characters across the period of socialist rule. In particular, they insist that “official,” that is, state-sanctioned, representations of masculinity did not change. Yet, as I show, there is evidence that socialist authors, journalists, and even the politburos of the regions’ communist parties did reflect on what they perceived as the need to change the conceptions of men and fathers. They advocated men’s greater participation in housework and child care. In this article, I examine this “struggle for a socialist fatherhood” in the GDR, focusing mainly on the discussions and suggestions of sociologists, educationalists, psychologists, and sexologists active in the study of childhood and adolescence, sex education, or marriage and family. From the 1960s on, experts from these fields as well as communist politicians targeted increasingly men to implement equality in marriage and parenting. In the 1970s and 1980s, their suggestions became more and more concrete. These suggestions as well as the theoretical discussions demonstrate the enduring belief in the socialist society’s ability to overcome traditional gender stereotypes. Even in the late 1980s, they were future directed and contained a utopian element.
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Perry, Seymour. "Primary Health Care: Public Involvement, Family Medicine, Epidemiology, and Health Economics. Proceedings of a Conference Held in Ulm, Germany, 1987. Petra Bergerhoff , Dieter Lehmann , Peter Novak." Quarterly Review of Biology 67, no. 2 (June 1992): 240. http://dx.doi.org/10.1086/417636.
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Ernst, Anja, Vang Q. Le, Allan T. H�jland, Inge S. Pedersen, Tine H. S�rensen, Lise L. Bjerregaard, Troels J. B. Lyngbye, Ninna M. Gammelager, Henrik Krarup, and Michael B. Petersen. "The PHF6 Mutation c.1A>G; pM1V Causes B�rjeson-Forsman-Lehmann Syndrome in a Family with Four Affected Young Boys." Molecular Syndromology 6, no. 4 (September 29, 2015): 181–86. http://dx.doi.org/10.1159/000441047.
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Henschel, Frank. "The Embodiment of Deviance: The Biopolitics of the “Difficult Child” in Socialist Czechoslovakia." East European Politics and Societies: and Cultures 34, no. 4 (June 7, 2020): 837–57. http://dx.doi.org/10.1177/0888325419890126.
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This article belongs to the special cluster, “Family, Gender and (dis)Abled Bodies after 1953”, guest-edited by Maike Lehmann and Alexandra Oberländer. In this article, I examine the academic discourses and socio-educational practices in post-war socialist Czechoslovakia concerning children who were considered “behaviorally difficult,” and I analyze those discourses and practices as elements of biopolitics and governmentality. I concentrate on the diagnostic conceptualizations introduced into the psycho-medical discourse of the 1950s and 1960s by what was called “defectology.” Czechoslovak defectologists, who composed their approaches from Soviet, Czech, and other academic sources, explained children’s difficult behavior in terms of “defectivity,” that is, a disturbed relationship between the individual and his or her social environment. The educational aims of defectology and the communist regime converged in the ideal of the “embodiment of socialism,” according to which the difficult child should be taught to be a conforming, able-minded, and productive citizen. The preferred treatment for reaching this goal was reeducation in the expanding network of residential institutions. However, defectology had no solution to the increasing number of children diagnosed as difficult or deviant. Moreover, other disciplines, like psychology, pediatrics, and pedagogy, criticized its conceptual inadequacy, which reoriented the discourse and governmentality toward prevention. I also show how gender and ethnicity abetted the diagnosis and affected the treatment of behavioral difficulties, for defectologists and other practitioners considered “sexually depraved” girls and “Gypsy children” as the “embodiment of deviance.”
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Pamula, Natalia. "Violent Inclusion: Disability and the Nation in Polish 1950s and 1960s Young Adult Literature." East European Politics and Societies: and Cultures 34, no. 4 (June 7, 2020): 858–78. http://dx.doi.org/10.1177/0888325419897787.
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This article belongs to the special cluster, “Family, Gender and (dis)Abled Bodies after 1953”, guest-edited by Maike Lehmann and Alexandra Oberländer. My article “Violent Inclusion: Disability and the Nation in Polish 1950s and 1960s Young Adult Literature” analyzes representations of physical and sensory disability in some of the most popular young adult novels published in 1950s and 1960s Poland written by Krystyna Siesicka, Jadwiga Korczakowska, Irena Krzywicka, Jadwiga Ruth-Charlewska, and Hanna Mortkowicz-Olczakowa. It argues that the recurring trope that connects the novels—the overcoming of disability—serves as a synecdoche for the Polish nation overcoming the catastrophe of World War II. Moreover, it shows that compulsory rehabilitation functions as a way of including disabled subjects into a Polish post-war society. At the same time, participation in the “rehabilitative regime” constitutes a patriotic duty for a disabled Polish child or teenager and paves a way to a socialist citizenship. Rehabilitation is always successful and culminates with a child or teenager transforming into an able-bodied socialist citizen reminding of a successful, yet sacrificial, reconstruction process of Poland. My article focuses on the sites of the overcoming of disability showing that Polish nature, whether it is a sea or woods, is crucial to the healing of a disabled subject. This way, the writers accentuate the connection between Polish nature and land and a “healthy” body, thus reconsolidating their fantasy of “Polishness.” What the novels ultimately testify to is the emergence of an embodied socialist subjectivity constructed through the corporeal rehabilitative practices and internalization of socialist values.
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Logan, Alec. "In praise of: Richard Lehman." British Journal of General Practice 68, no. 673 (July 26, 2018): 381. http://dx.doi.org/10.3399/bjgp18x698153.
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Altman, Julia E., Carson J. Walker, Emily K. Zboril, Nicole S. Hairr, Rachel K. Myrick, David C. Boyd, Jennifer E. Koblenski, et al. "Abstract 1750: Decoding breast cancer: Unraveling subtype and model differences through multi-model single-cell RNA sequencing data integration." Cancer Research 84, no. 6_Supplement (March 22, 2024): 1750. http://dx.doi.org/10.1158/1538-7445.am2024-1750.
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Abstract Breast cancer's complex transcriptional landscape requires a deep understanding of sample and cell diversity to identify effective treatments. In this study, we amalgamate single-cell RNA sequencing data from breast cancer patient-derived xenografts (PDX), organoids, cell lines, patient tumors and reduction mammoplasties resulting in a comprehensive dataset of 117 samples with 506,719 total cells. These samples encompass hormone receptor positive (HR+), human epidermal growth factor receptor 2 enriched (HER2E), and triple-negative breast cancer (TNBC) subtypes. We aimed to delineate similarities and distinctions across model systems and patient samples while also exploring stratification of therapeutic drug efficacy based on subtype proportions within tumors. Mammary tumor PDXs, organoids, and established cell lines exhibited higher proliferation and lower heterogeneity observed via UMAP dimensionality reduction compared to most patient tumors or normal breast epithelium. TNBCs had elevated proliferative and pro-metastatic signatures compared to HR+ and HER2E samples. Interestingly, compared to matched PDX tumors, organoids from these same models were found to exhibit stark differences in gene expression, including upregulation of metabolically active aldo-keto reductase family genes, highlighting differences in the model systems with implications for pre-clinical drug testing. Single-cell tumor subtyping analyses with scSubtype and TNBCtype methods found that therapeutically treated samples had shifts in the proportions of cell-wise subtype annotations when compared to matched untreated samples. Similarly, patient lymph node metastasis when compared with matched primary tumors were significantly linked to decreases in Basal-like and HER2-enriched cell-wise annotations in untreated ER+ samples. In vitro assessment of anti-cancer compounds on PDX cells showed significant correlation of subtype proportion with cell viability following treatment with targeted therapeutic agents. This subtyping methodology offers a powerful tool to monitor the evolving gene expression landscape within samples and predict responses to therapeutic agents. We present here a dynamic approach to cell-wise sample annotation and a substantial multi-model dataset for use facilitating informed decision-making in preclinical research and therapeutic development. Citation Format: Julia E. Altman, Carson J. Walker, Emily K. Zboril, Nicole S. Hairr, Rachel K. Myrick, David C. Boyd, Jennifer E. Koblenski, Madhavi Puchalapalli, Bin Hu, Mikhail G. Dozmorov, Xi Chen, Yunshun Chen, Charles M. Perou, Brian D. Lehmann, Jane E. Visvader, Amy L. Olex, J. Chuck Harrell. Decoding breast cancer: Unraveling subtype and model differences through multi-model single-cell RNA sequencing data integration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1750.
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Siva, Kavitha, Pekka Jaako, Kenichi Miharada, Emma Rörby, Mats Ehinger, Göran Karlsson, and Stefan Karlsson. "Sparc Is Dispensable for Murine Hematopoiesis, Despite Its Suspected Role in 5q- Myelodysplastic Syndrome." Blood 118, no. 21 (November 18, 2011): 4822. http://dx.doi.org/10.1182/blood.v118.21.4822.4822.
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Abstract Abstract 4822 Hematopoiesis is a complex process where a limited number of stem cells give rise to all mature blood cells. It involves interplay of several factors, many of which are yet to be identified. In a search for novel regulators of hematopoiesis, we chose to study SPARC (Secreted Protein Acidic and Rich in Cysteine, also known as Osteonection and BM40) because it is downregulated upon hematopoietic differentiation (Bruno et al., Mol Cell Biol, 2004) and might therefore play a role in the regulation of hematopoietic stem cells (HSC). SPARC is a matricellular protein that forms a major component of bone and is ubiquitously expressed in a variety of tissues. It is the founding member of a family of SPARC-like proteins. Several publications have indicated an important role for SPARC in hematopoiesis. In particular – knockdown of SPARC in zebrafish embryos resulted in an altered number of circulating blood cells, and a knockout mouse model showed thrombocytopenia and reduced erythroid colony formation. We carried out an in depth phenotypic and functional analysis of the hematopoietic system of SPARC knockout mice; using it as a model to gain insight into the role of SPARC in hematopoiesis. These mice are viable and fertile but show severe osteopenia and age-onset cataract at about six months of age. They also show an altered response to tumour growth and wound healing. We used mice (129SVJ background) (Gilmour et al. EMBO, 1998) that were less than six months old. These mice had normal peripheral blood counts and the bone marrow and spleen showed no alterations in morphology or cellularity. A detailed phenotypic analysis of precursors within the bone marrow showed no significant differences in myelo-erythroid precursors as compared to wild types (n=6). Though in vitro, the precursors showed lower ability to form BFU-E (n=5, p=0.048). In transplantations of lethally irradiated recipient mice, SPARC knockout cells gave rise to multi-lineage long-term reconstitution. Also, when competed with wild type cells, they provided reconstitution as well as their wild type counterparts. When SPARC knockout mice (n=8) were transplanted with wild type cells, there was normal reconstitution, indicating that a SPARC deficient niche can fully support normal hematopoiesis. We also tested if SPARC deficient mice respond differently to hematopoietic stress. We subjected mice (n=7) to sub lethal dose of irradiation and to experimentally induced anemia (n=7) and followed recovery by analyzing peripheral blood counts. In both SPARC knockouts and wild type mice, the blood counts recovered in a similar fashion. In conclusion, we find that SPARC is dispensable for murine hematopoiesis. It is possible that there are compensatory mechanisms involving other members of the SPARC family that ultimately lead to normal hematopoiesis in the murine model. In humans, SPARC maps to the deleted region in 5q MDS and has been reported to be 71 % down regulated in patient samples (Lehmann et al. Leukemia, 2007). It is the most prominent gene that is up regulated in response to lenalidomide, a drug that inhibits the malignant clone (Pellagatti et al. PNAS, 2007). SPARC is thus increasingly speculated to be involved in the pathophysiology of this hematopoetic disease. We analysed the expression levels of SPARC mRNA in the hematopoietic stem/progenitor cell compartment and found high expression levels in the CD34+ fraction of human cord blood cells. In contrast, there is very low level of SPARC expression in all compartments of murine HSCs. Therefore SPARC function may play a more important role in human hematopoiesis than in murine blood cell regulation. Disclosures: No relevant conflicts of interest to declare.
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Xu, Lixiang, Yuanyan Tang, Bin Luo, Lixin Cui, Xiu Chen, and Jin Xiao. "A combined Weisfeiler–Lehman graph kernel for structured data." International Journal of Wavelets, Multiresolution and Information Processing 16, no. 05 (September 2018): 1850039. http://dx.doi.org/10.1142/s021969131850039x.
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Different graph kernels may correspond to using different notions of similarity or may be using information coming from multiple sources. In this paper, we develop a common method to construct combined graph kernel (CGK) which is based on a family of graph kernels. We define three kinds of CGK. The first one is called the weighted combined graph kernel and is a parametric CGK. The second one is called the accuracy ratio weighted combined graph kernel and is a non-parametric CGK. The third one is called the product combined graph kernel and also belongs to non-parametric CGK. The three kinds of definition of CGK can be applied for constructing CGK based on a family of graph kernels. This family of kernels is demonstrated based on the Weisfeiler–Lehman (WL) sequence of graphs in this paper, including a highly efficient subtree kernel, edge kernel, and shortest path kernel. Experiments demonstrate that our CGK based on WL graph kernels outperforms the corresponding single WL graph kernel on several classification benchmark data sets.
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Munch, Janet Butler. "20th-century Bronx Childhood: Recalling the Faces and Voices." Collections: A Journal for Museum and Archives Professionals 13, no. 2 (June 2017): 91–102. http://dx.doi.org/10.1177/155019061701300204.
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A popular photographic exhibit on childhood, originally featured in the Lehman College Art Gallery in the Bronx, New York, was brought to life two decades later through a library digitization grant. The website Childhood in the Bronx ( http://www.lehman.edu/library/childhood-bronx/home.htm ) features 61 photographs of boys and girls with family or friends, at play, on streets, and in parks, schools, shelters, hospitals, and other locales. Oral history sound excerpts about their childhood, not heard in the original exhibit, complement the 18 vintage photographs shown. The combination of images with the spoken word enhances the user's sensory experience with deeper meaning and enjoyment. This article discusses how the project was accomplished and what can be learned from the Lehman digitization team's experience.
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Schulz, Till, Pascal Welke, and Stefan Wrobel. "Graph Filtration Kernels." Proceedings of the AAAI Conference on Artificial Intelligence 36, no. 8 (June 28, 2022): 8196–203. http://dx.doi.org/10.1609/aaai.v36i8.20793.
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The majority of popular graph kernels is based on the concept of Haussler's R-convolution kernel and defines graph similarities in terms of mutual substructures. In this work, we enrich these similarity measures by considering graph filtrations: Using meaningful orders on the set of edges, which allow to construct a sequence of nested graphs, we can consider a graph at multiple granularities. A key concept of our approach is to track graph features over the course of such graph resolutions. Rather than to simply compare frequencies of features in graphs, this allows for their comparison in terms of when and for how long they exist in the sequences. In this work, we propose a family of graph kernels that incorporate these existence intervals of features. While our approach can be applied to arbitrary graph features, we particularly highlight Weisfeiler-Lehman vertex labels, leading to efficient kernels. We show that using Weisfeiler-Lehman labels over certain filtrations strictly increases the expressive power over the ordinary Weisfeiler-Lehman procedure in terms of deciding graph isomorphism. In fact, this result directly yields more powerful graph kernels based on such features and has implications to graph neural networks due to their close relationship to the Weisfeiler-Lehman method. We empirically validate the expressive power of our graph kernels and show significant improvements over state-of-the-art graph kernels in terms of predictive performance on various real-world benchmark datasets.
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dos Reis Teixeira, Liliana, John Humphreys, Haixia He, Radha Akella, and Elizabeth Goldsmith. "Abstract LB031: WNK are drug targets for triple negative breast cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): LB031. http://dx.doi.org/10.1158/1538-7445.am2022-lb031.
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Abstract Triple negative breast cancer (TNBC) accounts for 10-20% of breast cancer cases, and is associated with poor diagnosis and prognostics. Due to the lack of therapeutics available, it is urgent to identify biomolecular targets to develop more efficient treatments [1]. Depletion and inhibition of the protein kinase With No Lysine (WNK) reduces migration of breast cancer cells, slowing down TNBC metastasis [2][3]. For this reason, WNKs are promising cancer drug targets. Other works suggest WNKs are also targets for the treatment of hypertension and stroke. The main focus of this work is to understand the molecular mechanisms of this family of proteins, which will help to develop more efficient drugs. WNKs are serine-threonine kinases important in ion transport regulation [4]. WNKs are critical intracellular osmosensors, with their function related to an equilibrium between an inactive dimer and an autophosphorylation-competent monomer. The dimer conformation covers phosphorylation sites [5], while simultaneously trapping water molecules [6]. The water trapping feature is hypothesized to be linked to ion pairs and clusters of charges between the Activation loop and the Catalytic loop. To access the role of these ion pairs, we expressed and purified seven mutants of key amino acids, analyzed their activity, phosphorylation state and sensitivity to ions and pressure. Some of these mutants are more monomeric, active and autophosphorylation competent than the wild-type, elucidating the role of these amino acids in the function of WNKs. Interestingly, some mutants are more sensitive to potassium, which confirms the WNK inhibition site for this ion [7]. [1]B. D. Lehmann et al., “Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies,” J. Clin. Invest., vol. 121, no. 7, pp. 2750–67, 2011.[2]S. Shyamasundar, et al., “miR-93 inhibits the invasive potential of triple-negative breast cancer cells in vitro via protein kinase WNK1,” Int. J. Oncol., vol. 49, no. 6, pp. 2629–36, 2016.[3]A. B. Jaykumas et al., “WNK1 Enhances Migration and Invasion in Breast Cancer Models,” Mol. Cancer Ther., vol. 20, no. 10, pp. 1800–08, 2021.[4]D. R. Alessi, et al., “The WNK-SPAK/OSR1 pathway: master regulator of cation-chloride cotransporters,” Sci. Signal., vol. 7, p. 334, 2014.[5]X. Min, et al., “Crystal structure of the kinase domain of WNK1, a kinase that causes a hereditary form of hypertension,” Structure, vol. 12, no. 7, pp. 1303-11, 2004.[6]R. Akella et al., “Osmosensing by WNK Kinases,” Mol. Biol. Cell, vol. 32, no. 18, pp. 1614–23, 2021.[7]J. M. Pleinis et al., “WNKs are potassium-sensitive kinases,” Am. J. Physiol Cell Physiol, vol. 320, no. 5, pp. C703-21, 2021. Citation Format: Liliana dos Reis Teixeira, John Humphreys, Haixia He, Radha Akella, Elizabeth Goldsmith. WNK are drug targets for triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB031.
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Yakovlev, Roman V., Ramon Hulsbosch, and Vadim V. Zolotuhin. "Revision of the family Metarbelidae (Lepidoptera) of the Oriental Region. XI. Genus Psychidarbela Roepke, 1938." Ecologica Montenegrina 65 (September 6, 2023): 51–59. http://dx.doi.org/10.37828/em.2023.65.7.
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The article presents an illustrated catalog of the genus Psychidarbela Roepke, 1938 (Lepidoptera: Cossoidea, Metarbelidae), which includes four species. New synonymy and combination is established: Psychidarbela Roepke, 1938 = Laonagoda Nonaka, 2021 syn. n. and Psychidarbela pellucida (Nonaka, 2021) comb. n. Two new species are described: Psychidarbela lehmanni Yakovlev & Hulsbosch, sp. n. (Type locality: Indonesia, West Timor, env. Buraen, 60 km SE Kupang) and Psychidarbela blancoi Yakovlev & Hulsbosch, sp. n. (Type locality: Philippinen, Mindanao, Prov. Simangani, Cotabato, Mt. Busa, near Kainba). The female of Psychidarbela pellucida (Nonaka, 2021) is described. The distributional maps for all the species of the genus are provided.
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Frech, Miriam, Kathleen Stabla, Andrea Nist, Marco Mernberger, Heidi Altmann, Uwe Platzbecker, Christian Thiede, et al. "The Genes for Tissue Factor F3 and Nuclear Receptor 4A Are Down-Regulated in Early Death Acute Promyelocytic Leukemia Patients." Blood 132, Supplement 1 (November 29, 2018): 3902. http://dx.doi.org/10.1182/blood-2018-99-112978.
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Abstract Introduction: Acute promyelocytic leukemia (APL) patients are successfully treated via differentiation therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Attempts to apply ATRA-based differentiation therapy to non-APL acute myeloid leukemia (AML) patients have not been effective so far (Johnson & Redner, 2015). Furthermore, 10-30% of the APL patients suffer an early death (ED) within 30 days, due to hemorrhages, infections, differentiation syndrome and thrombosis. Different risk factors have been identified, but the underlying mechanisms and successful treatment of ED in APL patients still have not been established (Kwaan et al., 2014, Lehmann et al., 2017). Hence, it is highly important to identify novel risk factors to understand the mechanistic processes in APL ED patients. Methods: To identify target genes, 50 bp single-read RNA sequencing (RNAseq) of 6 ED and 9 APL controls (cohort #1; n=15) and 4 ED and 5 APL controls (cohort #2; n=9) was executed. Samples were taken from patients with confirmed diagnosis of APL before beginning of treatment. Cohort #1 consisted of 15 patients: median age 60 years (range 37-73 years), 10 high-risk patients and 5 low/intermediate-risk patients according to Sanz score. Patients of cohort #1 were treated according to the AIDA2000 protocol of the Study Alliance Leukemia (SAL) study group. Cohort #2 consisted of 9 patients: median age 55 years (range 36-79 years), 4 high-risk patients and 5 low/intermediate-risk patients. Most patients of cohort 2 were treated according to the AIDA2000 (SAL) or APL0406 protocol. Gene validation was performed via RT-qPCR. PML-RARα variants were determined by Mentype AMLplexQS (Biotype). Survival and RT-qPCR analyses were performed with 64 non-APL AML patients´ samples treated within the clinical trial of the AMLSG HD98B study (Schlenk et al., 2004). In this trial, all patients received ICE (idarubicin, cytarabine, etoposide) chemotherapy. The patients were randomly assigned to ATRA or no ATRA. In our cohort, 26 patients had received ICE-ATRA, whereas 38 only ICE. Amaxa nucleofector technology was used for overexpression of PML-RARα bcr1 or bcr3 variant in U937 cells. NB4 or AML cells treated with 1 µM ATRA up to 72 h or 1-2 µM ATO up to 48 h were analyzed via flow cytometry, CellTiter-Glo viability assay, RT-qPCR or Western blot. Results: RNAseq of cohorts 1 and 2 showed F3 (Tissue Factor) and members of nuclear receptor 4A family, NR4A1/2/3, significantly downregulated in ED compared to control APL cases. GSEA analysis further identified a gene family including F3 and members of nuclear receptor 4A family, NR4A1/2/3, co-regulated upon leukotriene and thrombin treatment. Downregulation of F3 was further validated by RT-qPCR. Analysis of PML-RARα variants in APL control and ED cases (n=38, Chi-square p < 0.041) showed a significant enrichment of the short variant bcr3 in ED APL. Artificial overexpression of the short bcr3 and long bcr1 PML/RARα variant in U937 further revealed a correlation between bcr3 and downregulation of NR4A2/3. Moreover, treatment of the APL NB4 cell line with ATRA or ATO induced further downregulation of F3 but upregulation of NR4A2/3 transcripts. ATRA treatment induced the same effects on F3 and NR4A3 protein levels, while ATO led not only to a decrease of F3 but also NR4A3 protein levels. We next sought to address the role of F3 and NR4A in non-APL AML. In 5 non-APL AML cell lines high F3 transcript and protein levels were positively correlated with a better response to ATRA treatment in vitro. Consistently, analyzing samples taken from the AMLSG HD98B trial, AML patients with high F3 but also NR4A3 transcript levels treated with ICE chemotherapy showed a significantly prolonged overall survival upon additional ATRA treatment in vivo (Log-rank p < 0.008). Conclusions: Expression of F3 and NR4A1/2/3 is downregulated in APL ED and decreased expression of NR4A2/3 is associated with short PML-RARα variant bcr3, which is significantly enriched in ED APL. Since NR4A members are associated with coagulation and inflammation, they may be important F3-related factors, contributing to the bcr3 ED APL phenotype. As ATRA and ATO treatment is known to further inhibit F3 expression, alternative therapies not inhibiting F3 expression could be worthwhile in APL ED patients. Moreover, F3 and NR4A3 expression levels seem to be highly relevant as marker for the prediction of ATRA response in non-APL AML patients. Figure. Figure. Disclosures Platzbecker: Celgene: Research Funding. Thiede:Novartis: Honoraria, Research Funding; AgenDix: Other: Ownership. Schlenk:Pfizer: Research Funding, Speakers Bureau.
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Reid, Sonya, Run Fan, Lindsay Venton, Anne Weidner, Ann Tezak, Mya Roberson, Susan Vadaparampil, et al. "Abstract PO2-09-08: Biological and non-biological predictors of breast cancer disease-free survival among young Black females." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO2–09–08—PO2–09–08. http://dx.doi.org/10.1158/1538-7445.sabcs23-po2-09-08.
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Abstract Introduction: Young Black females bear a disproportionate burden of breast cancer (BC) deaths compared to White females yet remain underrepresented in clinical studies. We sought to discover predictors of disease-free survival (DFS) in a cohort of young Black females with BC. Methods: Black females diagnosed with invasive BC ≤ age 50 from 2005 to 2016 were recruited through the Florida and Tennessee state cancer registries. Participants were asked to complete a questionnaire, medical records release, and tissue/tumor release. Saliva was also requested for germline DNA extraction. For the primary outcome of BC DFS, univariate analyses were conducted using the following variables: proportion of West African ancestry, RNA expression based on PAM50 analyses, body mass index (BMI), social determinants of health (i.e., employment and insurance), immunohistochemistry (IHC) subtype, treatment category (i.e., chemotherapy, radiation, and surgery), and BC family history. Multivariate analyses were conducted using backward selection among these variables to analyze in the reduced model. Results: Of 701 consented, 687 participants with early-stage disease were included in the analysis; 14 participants with stage 4 disease at diagnosis were excluded. Among the 687 participants, the median age at diagnosis was 44, 28% had triple-negative breast cancer (TNBC), 13% were deceased, and 5% had recurrent disease. Clinically, participants with TNBC and lymph node involvement had worse BC DFS (p=0.001 and p=0.0002, respectively). Socio-economically, full-time employement was associated with higher BC DFS (p=0.0003). Among those for whom global ancestry data were available (n=551), multivariate analysis showed an association between increased percent of West African ancestry and worse BC DFS with HRIQR=1.23*, which approached significance (p=0.085). Additional subgroup analyses among those with hormone receptor-positive (HR+) (estrogen and/or progesterone receptor positive) BC (n=431) showed that participants with private insurance had better BC DFS (HR=0.45; p=0.05), while those with lymph node involvement had worse BC DFS (HR=2.07; p=0.001). Among HR+ participants with available ancestry data (n=349), worse BC DFS was associated with increased West African ancestry (p=0.05) and lymph node involvement (p=0.08). When ancestry was included in the model, private insurance was no longer associated with BC DFS in this HR+ subgroup (p=0.31). Other predictors analyzed did not reach statistical significance. Conclusion: Our findings confirm prior established adverse predictors of BC DFS, such as TNBC with lymph node involvement and the protective effect of full-time employment. We also found a novel association with West African ancestry among patients with HR+ breast cancer. Although further large-scale studies are needed, results from this cohort of young Black females with BC and highlight the critical need to support research to understand biological and non-biological factors contributing to BC DFS and develop targeted strategies to improve survival outcomes. * HRIQR is the ratio of hazard rates corresponding to upper and lower quartiles of percent West African (interquartile range (IQR): 70.0%-80.8%). Citation Format: Sonya Reid, Run Fan, Lindsay Venton, Anne Weidner, Ann Tezak, Mya Roberson, Susan Vadaparampil, Xuefeng Wang, Sean Yoder, Marilin Rosa, Jibril Hirbo, Jennifer Whisenant, Jennifer Pietenpol, Sheila Rajagopal, Brian Lehmann, Fei Ye, Tuya Pal. Biological and non-biological predictors of breast cancer disease-free survival among young Black females [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-09-08.
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Романюк, Людмила. "Interrelationships of Personal Values: A Moderated Mediation Analysis Based on Gender and Age." East European Journal of Psycholinguistics 4, no. 2 (December 28, 2017): 84–94. http://dx.doi.org/10.29038/eejpl.2017.4.2.rom.
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The present study describes ten personal values expressed by men and women from two countries, and it explores the relationships between two opposing values, Achievement and Benevolence, specifying Stimulation as a mediator between them. It is further explored whether such a mediation model could be further qualified by age and Gender as moderators. The 40-item Portraits Values Questionnaire (PVQ), measuring ten basic values, was administered to 1,000 young adults from two countries. Hierarchical regression methods were applied to examine mediation and moderation mechanisms.Minor gender and country differences emerged for some of the ten basic values. An indirect relationship among the three selected values was identified. Stimulation was found to operate as a mediator between achievement and benevolence. A conditional process model was established with Gender moderating the Achievement – Stimulation path (men had a steeper slope than women), whereas age moderated the Stimulation – Benevolence path (younger individuals had a steeper slope than older ones). Gender also moderated the Achievement – Benevolence path (men had a steeper slope than women). For men, the association between achievement and stimulation was stronger than for women. For the younger persons, the association between stimulation and benevolence was stronger than for older ones. For women, the level of benevolence was independent of their achievement level. The present analyses shed new light on indirect and differential associations among personal values, adding a novel perspective to research on cognitive mechanisms involved in the ten basic values’ becoming.
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Sergeev, Philipp, Sadiksha Adhikari, Juho J. Miettinen, Maiju-Emilia Huppunen, Minna Suvela, Ana Slipicevic, Nina N. Nupponen, Fredrik Lehmann, and Caroline A. Heckman. "Single Cell RNA Sequencing Identifies Potential Molecular Indicators of Response to Melflufen in Multiple Myeloma." Blood 138, Supplement 1 (November 5, 2021): 1194. http://dx.doi.org/10.1182/blood-2021-147191.
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Abstract Introduction Melphalan flufenamide (melflufen), is a novel peptide-drug conjugate that targets aminopeptidases and selectively delivers alkylating agents in tumors. Melflufen was recently FDA approved for the treatment of relapsed/refractory multiple myeloma (MM) patients. Considering the challenges in treating this group of patients, and the availability of several new drugs for MM, information that can support treatment selection is urgently needed. To identify potential indicators of response and mechanism of resistance to melflufen, we applied a multiparametric drug sensitivity assay to MM patient samples ex vivo and analyzed the samples by single cell RNA sequencing (scRNAseq). Ex vivo drug testing identified MM samples that were distinctly sensitive or resistant to melflufen, while differential gene expression analysis revealed pathways associated with response. Methods Bone marrow (BM) aspirates from 24 MM patients were obtained after written informed consent following approved protocols in compliance with the Declaration of Helsinki. BM mononuclear cells from 12 newly diagnosed (ND) and 12 relapsed/refractory (RR) patients were used for multi-parametric flow cytometry-based drug sensitivity and resistance testing (DSRT) evaluation to melflufen and melphalan, and for scRNAseq. Based on the results from the DSRT tests and drug sensitivity scores (DSS), we divided the samples into three groups - high sensitivity (HS, DSS > 40 (melflufen) or DSS > 16 (melphalan)), intermediate sensitivity (IS, 31 ≤ DSS ≤ 40 (melflufen) or 10 ≤ DSS ≤ 16 (melphalan)), and low sensitivity (LS, DSS < 31 (melflufen) or DSS < 10 (melphalan)). To identify genes, responsible for the general sensitivity to melphalan-based drugs we conducted differential gene expression (DGE) analyses separately for melphalan and melflufen focusing on the plasma cell populations, comparing gene expression between HS and LS samples for both drugs ("HS vs. LS melphalan" and "HS vs. LS for melflufen", respectively). In addition, to explain the increased sensitivity of RR samples, we conducted the DGE analysis for ND vs. RR samples and searched for similarities between these three datasets. Results DSRT data indicated that samples from RRMM patients were significantly more sensitive to melflufen compared to samples from NDMM (Fig. 1A). In addition, we observed that samples with a gain of 1q (+1q) were more sensitive to melflufen while those with deletion of 13q (del13q) appeared to be less sensitive, although these results lacked significance (Fig. 1A). After separating the samples into different drug sensitivity groups (HS, IS, LS), DGE analysis showed significant downregulation of the drug efflux and multidrug resistance protein family member ABCB9 in the melflufen HS group opposed to the LS group (2.2-fold, p < 0.001). A similar pattern was detected for the melphalan HS vs. LS comparison suggesting that this alteration might be a common indicator of sensitivity to melphalan-based drugs. Furthermore, in the melflufen HS group we observed downregulation of the matrix metallopeptidase inhibitors TIMP1 and TIMP2 (3-fold and 1.6-fold, p < 0.001, respectively), and cathepsin inhibitors CST3 and CSTB (3.2-fold and 1.3-fold, p < 0.001, respectively) (Fig. 1B). This effect was observed in both "ND vs. RR" and "HS vs. LS for melflufen" comparisons, but not for melphalan, suggesting that these changes are associated with disease progression and specific indicators of sensitivity to melflufen. Moreover, gene set enrichment analysis (GSEA) showed activation of pathways related to protein synthesis, as well as amino acid starvation for malignant and normal cell populations in the HS group. Conclusion In summary, our results indicate that melflufen is more active in RRMM compared to NDMM. In addition, samples from MM patients with +1q, which is considered an indicator of high-risk disease, tended to be more sensitive to melflufen. Based on differential GSEA and pathway enrichment, several synergizing mechanisms could potentially explain the higher sensitivity to melflufen, such as decreased drug efflux and increased drug uptake. Although these results indicate potential indicators of response and mechanisms of drug efficacy, further validation of these findings is required using data from melflufen treated patients. Figure 1 Figure 1. Disclosures Slipicevic: Oncopeptides AB: Current Employment. Nupponen: Oncopeptides AB: Consultancy. Lehmann: Oncopeptides AB: Current Employment. Heckman: Orion Pharma: Research Funding; Oncopeptides: Consultancy, Research Funding; Novartis: Research Funding; Celgene/BMS: Research Funding; Kronos Bio, Inc.: Research Funding.
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Dienes, Brittney, Bartlomiej P. Przychodzen, Michael Clemente, Wenyi Shen, Chantana Polprasert, Naoko Hosono, Satoru Miyano, et al. "Impact and Function of Somatic PHF6 Mutations in Myeloid Neoplasms." Blood 124, no. 21 (December 6, 2014): 3581. http://dx.doi.org/10.1182/blood.v124.21.3581.3581.
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Abstract Borjeson−Forssman−Lehmann syndrome (BFLS), a hereditary X-linked disorder characterized by mental retardation, truncal obesity, gynecomastia, hypogonadism and other dysmorphic features, is known to be caused by germline (GL) mutations of plant homeo domain finger protein 6 (PHF6). PHF6 is a highly conserved 41kDa protein showing ubiquitous expression in a variety of tissues, including bone marrow, CD34+ cells and blood leukocytes. Human PHF6 is located on chrXq26.2. Recently, rare somatic nonsense mutations and deletions have been detected in patients with T-ALL and AML and found in some T-ALL cell lines. Patients with BFLS with PHF6 mutations have been reported to develop leukemia, suggesting PHF6 mutations may predispose cancer. Although the actual function and molecular pathogenesis is unknown, PHF6 has been suggested to be a tumor suppressor gene involved in the control of myeloid development. In an index case of a young adult female patient with proliferative CMML with dysmorphic features, we have identified remarkable GL mosaicism for PHF6 mutation (p.K44fs), confirmed by deep sequencing of marrow, CD3+ cells and skin tissue. Subsequently, we screened patients with myeloid neoplasms by targeted multi-amplicon sequencing to determine the prevalence and distribution of PHF6 gene alterations. Sequencing results from 1072 cases were analyzed (728 by targeted deep sequencing and 344 by whole exome sequencing). In total, we identified 21 cases with PHF6 mutations, 13 of which were frameshift or nonsense mutations. Previously, PHF6 have been included in screening panels by Haferlach et al., (Leukemia 2014) and Papaemmanuil et al., (Blood 2013) and somatic mutations were found in 24/944 and 21/738 cases of MDS, respectively. These results along with ours suggest that PHF6 mutations are common driver events. The somatic nature of these defects was confirmed by analysis of non-clonal CD3+ lymphocytes, thus, PHF6 mutations occur at a frequency of 2.0% and are most frequently observed among patients with secondary AML (33%, P=.0021). Gender distribution showed a strong male predominance (76%), likely due to the location of PHF6 on chrX and indicating that retention of a single copy of PHF6 may be protective. SNP-array karyotyping showed that deletions of Xq, involving the PHF6 locus (Xq26), were present in about 1.2% of myeloid neoplasms and affect only female patients. As a family, plant homeo domain (PHD) finger genes are affected by mutations associated with various cancers. JARID1A, PHF23, NSD1 and NSD3 were described to serve as fusion partners with the NUP98 in a subset of AML cases. The most frequent chromosomal aberration observed in conjunction with PHF6 mutations was trisomy-8 (P=.08). The most commonly associated somatic mutations were in RUNX1 (N=7; P=.001), U2AF1 (N=5), ASXL1 (N=5), IDH1 (N=4), and DNMT3A (N=4). Interestingly, 6/7 cases with concomitant PHF6 and RUNX1 mutations showed a poor prognosis AML. Subsequent analysis of clonal architecture using variant allelic frequency calculations and serial samples for these cases suggested that PHF6 may function as a founder driver gene while RUNX1 mutations are acquired as secondary events. Recent studies proposed that PHF6 deficiency leads to impaired cell proliferation, cell cycle arrest at G2/M phase and an increase of DNA damage. To examine DNA damage and quantify double stranded breaks (DSBs) in primary cells from PHF6-mutants, those with wild-type (WT) PHF6 and normal bone marrow we used a flow cytometric anti-γH2AX assay, following induction of DNA damage with Camptothecin. As judged by greater percentages of anti-γH2AX labeled cells, DSBs were more common in mutant cases consistent with more DNA damage present in PHF6 mutant compared to WT MDS and normal bone marrow cells. In conclusion, our results indicate that PHF6 mutations are generally present in more aggressive types of myeloid neoplasms, frequently associated with RUNX1 mutations. Our functional in vitro studies along with recently published reports suggest an association of PHF6 deficiency with genomic instability and thereby provide a basis for a mutator phenotype conveyed by ancestral lesions, consistent with its role as a tumor suppressor gene. Disclosures Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen Corp: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim Corp: Membership on an entity's Board of Directors or advisory committees.
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Przychodzen, Bartlomiej P., Xiaorong Gu, Dewen You, Cassandra M. Hirsch, Michael J. Clemente, Mikkael A. Sekeres, Aziz Nazha, Hideki Makishima, and Jaroslaw P. Maciejewski. "PHF6 Somatic Mutations and Their Functional Role in the Pathophysiology of Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)." Blood 128, no. 22 (December 2, 2016): 2736. http://dx.doi.org/10.1182/blood.v128.22.2736.2736.
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Abstract Recurrent somatic nonsense PHF6 mutations have been reported in patients with T-acute lymphocytic leukemia, AML and chronic myeloid leukemia in blast crisis. Germ line (GL) PHF6 mutations are responsible for Borjeson−Forssman−Lehmann syndrome (BFLS), a hereditary X-linked disorder characterized by mental retardation and dysmorphic features. PHF6 is a highly conserved 41kDa protein with ubiquitous expression in hematopoietic cells, including CD34+ cells. We screened patients (N=1166) with myeloid neoplasms by targeted multi-amplicon deep NGS targeting all ORFs of PHF6 to determine the prevalence and distribution and molecular context of PHF6 gene alterations. In total, we identified and verified 52 cases with somatic PHF6 mutations, 32 of which were frameshift or nonsense mutations and with a strong male predominance (76%). Mutations were distributed almost equally between 2 DNA binding domains. Previously, PHF6 has been included in other screening panels (Haferlach et al. 2014 and Papaemmanuil 2013) with somatic mutations found in 24/944 and 21/738 MDS cases, respectively. SNP-array karyotyping showed that microdeletions involving the PHF6 locus were present in about 1.2% of myeloid neoplasms, but affected only female patients. The most frequent chromosomal aberration observed in conjunction with PHF6 mutations was trisomy-8 (P=.018). The most commonly associated somatic mutations included RUNX1 (P=.001) and IDH1 (P=.008) but not IDH2 (P>.1). There was no impact on overall survival with respect to PHF6 mutant status in total or within individual risk groups (low risk (RA,RARS) vs. high-risk (RAEB1/2). Concomitant PHF6 and RUNX1 mutations were associated with particularly poor prognosis. RUNX1 mutational status correlated with PHF6 expression levels and PHF6 expression inversely correlated with RUNX1 mRNA levels. Subsequent analysis of clonal architecture using VAF calculations and serial samples for these cases suggested that PHF6 may function as a founder driver gene in 18% of cases. PHF6 variant allelic frequency (VAF) varied between disease subtypes, with the highest clonal burden found in AML patients (P<.01). Within MDS patients we also found lower expression of PHF6 mRNA in CD34+ cells in MDS overall vs. controls (P<.01), as well as lower expression of PHF6 in advanced myeloid neoplasms (P<.05). Lower expression (defined as mean+1SD of controls) was found in 12% and 23% of patients with lower- or higher- risk MDS, respectively. Recent studies have proposed that PHF6 deficiency leads to impaired cell proliferation, cell cycle arrest at G2/M phase and DNA damage. Following shRNA knockdown, hematopoietic cell lines showed only moderately accelerated growth and increased response to growth factors, while EPO-dependent UT7, did not result in growth factor autonomy. To delineate the possible pathophysiological pathway involving PHF6, we compared transcriptional expression profiles of 5 different cell lines with shPHF6 to WT counterparts. We then studied the consequences of PHF6 knockdown on transcriptional profiles. We have found 1020 transcripts differentially expressed (with at least 1.5x change up/down) in the context of shPHF6 knock down. Concordant results among all 5 cell lines resulted in 354 genes that were upregulated and 766 that were down-regulated. Analyses with primary patient data derived from low PHF6 expressors and mutant cases found a concordance of 71 upregulated genes and 80 genes that were downregulated. The most significant functional group of transcripts that was found to be modulated was a family belonging to ribosomal biogenesis pathway (pFDR<1x10-6). Mass spec fingerprinting found protein-protein interaction partners that were found to be dysregulated on a transcriptional level. This finding of protein interaction/transcriptional dependence might suggest feedback mechanisms on a transcriptional level. In conclusion, our results indicate that PHF6 mutations are generally present in more aggressive types of myeloid neoplasms, frequently associated with RUNX1/IDH1 mutations. Our functional in vitro studies along with recently published reports suggest an association of PHF6 deficiency with transcriptional regulation and thereby provide a basis for a phenotype conveyed by ancestral lesions, consistent with its role as a tumor suppressor gene. Disclosures Sekeres: Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Makishima:The Yasuda Medical Foundation: Research Funding.
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Boom, Donna C. Vanden, and Daniel C. Lustig. "The Relationship Between Employment Status and Quality of Life For Individuals with Severe and Persistent Mental Illness." Journal of Applied Rehabilitation Counseling 28, no. 4 (December 1, 1997): 4–8. http://dx.doi.org/10.1891/0047-2220.28.4.4.
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The relationship between quality of life and employment status for individuals with severe and persistent mental illness was investigated. Forty individuals in the Program for Assertive Community Treatment (PACT) participated in the study. PACT is a community-based program for persons with severe and persistent mental illness which emphasizes the importance of employment in rehabilitation. Participants were interviewed using Lehman's Quality of Life Interview. A large effect size for difference between individuals who were employed and those who were unemployed was found for assessment of global quality of life. Medium and small effect sizes were found for satisfaction with family, financial situation, health and social relations, safety, and daily activities. Minimal effect size was found for satisfaction with living situation.
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MOLOSHNIKOV, Sergey. "FINDS OF THE DUNKLEOSTEID PLACODERMS (PISCES, PLACODERMI) IN THE EUROPEAN PART OF RUSSIA (CENTRAL DEVONIAN FIELD)." LIFE OF THE EARTH 43, no. 1 (February 17, 2021): 67–76. http://dx.doi.org/10.29003/m1995.0514-7468.2020_43_1/67-76.
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The Dunkleosteidae Stensiö family includes large predatory Paleozoic armour fishes. Their remains are rare in the Devonian deposits of the European part of Russia (Central Devonian field). The finds of both Eastmanosteus Obruchev and Dunkleosteus Lehman genus representatives and indefinte dunkleosteids were detected in the area. currently there is a collection of some dunkleosteid remains at the Earth Sciences Museum of Moscow State University. The materials were collected in two localities in 2007-2008 years by the author. Plates of the head and trunk shields, preliminarily determined as Eastmanosteus aff. E. pustulosus (Eastman), were found in the sandy clay deposits of the Ardatovka Horizon (Givetian, Middle Devonian) in the Pavlovsk Quarry, Voronezh Region. An incomplete anterior ventro-lateral plate of Dunkleosteidae gen. et sp. indet., similar to the same plates of the Dunkleosteus-species, was discovered in the sandy deposits of the Zadonsk Horizon (Lower Famennian, Upper Devonian) in the Lime Factory Quarry not far from Livny Town, Orel Region. The brief description of the new findings supplementing the data on the Middle-Late Devonian dunkleosteids of the Central Devonian field is given.
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Krčmar, Stjepan. "Diversity of flesh flies (Sarcophagidae, Sarcophaginae) of pond habitats in rural areas in the Croatian part of Baranja." ZooKeys 1159 (April 24, 2023): 17–36. http://dx.doi.org/10.3897/zookeys.1159.100878.
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The diversity of grey flesh flies (Sarcophagidae: Sarcophaginae) from the Croatian part of Baranja was studied during 2019 to 2021, resulting in 37 species, of which the following are new for the area: Ravinia pernix (Harris, 1780); Sarcophaga (Het.) depressifrons Zetterstedt, 1845; S. (Het.) filia Rondani, 1860; S. (Het.) haemorrhoides Böttcher, 1913; S. (Het.) pumila Meigen, 1826; S. (Het.) vagans Meigen, 1826; S. (Lis.) dux Thomson, 1869; S. (Lis.) tuberosa Pandellé, 1896; S. (Meh.) sexpunctata (Fabricius, 1805); S. (Pan.) protuberans Pandellé, 1896; S. (Sar.) carnaria (Linnaeus, 1758); S. (Sar.) variegata (Scopoli, 1763), and S. (Pse.) spinosa Villeneuve, 1912. New locality records are provided for 25 species. Sarcophaga (Sar.) croatica Baranov, 1941 was the most abundant with 37%, followed by S. (Sar.) lehmanni Müller, 1922 (21%), and S. (Pas.) albiceps Meigen, 1826 (5%), making up 63% of all collected specimens. Most species (35) were collected in locality of Zmajevac, while the fewest (3) were collected in Bilje locality. During this study, S. (Pse.) spinosa was recorded in Croatia for the first time. Combined with previous records, 42 species of flesh flies have been recorded from Croatian Baranja, which comprise 27% of the flesh flies known to occur in Croatia. The total number of species of the family Sarcophagidae currently known in Croatia has increased to 156.
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Deeren, Dries, Johan A. Maertens, Tara L. Lin, Yves Beguin, Erik Alcantar-Orozco, Marie-Sophie Dheur, Eytan Breman, et al. "Co-Expression of an shRNA Targeting MICA/Micb Improves the Clinical Activity of a NKG2D-Based CAR T in Patients with Relapsed / Refractory AML/MDS." Blood 138, Supplement 1 (November 5, 2021): 408. http://dx.doi.org/10.1182/blood-2021-152413.
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Abstract While CAR T cell therapy has delivered impressive clinical efficacy in B cell malignancies, similar levels of clinical activity have not been demonstrated in acute myeloid leukemia (AML). One underlying reason for this lack of translation is the relative paucity of validated CAR T targets. Major Histocompatibility Complex Class 1 related proteins MICA and MICB along with the UL16 binding proteins 1-6 (ULBP1-6) are frequently over-expressed on AML and myelodysplastic syndrome (MDS) blasts. The Natural Killer Group 2D (NKG2D) is a single receptor able to bind MICA, MICB and ULBP1-6, thus providing a potentially powerful approach that could be exploited to target this family of targets thereby providing a novel CAR T approach for AML/MDS. Expressing the NKG2D receptor fused to the human CD3z cytoplasmic domain generates a CAR that, when expressed in primary T cells, generates a CAR T product (termed CYAD-01) that showed good anti-tumor activity in preclinical models. In clinical trials, CYAD-01 showed a good tolerability profile but with a disappointing level of clinical activity when combined with cyclophosphamide / fludarabine preconditioning (DEPLETHINK trial, NCT03466320). We hypothesised that the transient expression of MICA/MICB on the CAR T itself may inhibit the activity of the NKG2D CAR through self-targeting and consequent fratricide. We developed a single shRNA able to knockdown both MICA and MICB. Co-expression of this shRNA with the NKG2D CAR generated a second generation CAR T product termed CYAD-02 which was examined in a highly similar AML/MDS patient population and preconditioning regimen as employed in the DEPLETHINK trial. CYAD-02 was evaluated in the the first-in-human CYCLE-1 trial (NCT04167696) in patients with r/r AML/MDS. The dose-escalation phase evaluated three dose-levels (DL) (1x10 8, 3x10 8 and 1x10 9 total cells per infusion), administered as a single infusion after standard preconditioning chemotherapy (cyclophosphamide 300 mg/m²/day and fludarabine 30 mg/m²/day, daily for 3 days) according to a classic 3+3 design. As of July 2021, 11 patients have been treated with CYAD-02 at the different dose-levels (3 at each DL1 and 2 and 5 at DL3). In terms of safety and tolerability, there was no evidence of a differential safety profile of CYAD-02 within the CYCLE-1 trial as compared to that observed in the CYAD-01 clinical trial. Of note, five patients enrolled in all 3 DLs experienced Grade ≥ 3 adverse events (AE) at least possibly related to CYAD-02 (cytokine release syndrome, febrile neutropenia, white blood cell count decreased, infusion related reaction). With respect to clinical activity, seven patients in total achieved stable disease (2 at DL1, 3 at DL2 and 2 at DL3) with 4 demonstrating evidence of transient blast reduction or anti-leukemic activity (decrease of at least 50% of the bone marrow blasts). In addition, two MDS patients at DL3 achieved a marrow complete response. Overall, this suggests dose dependent response to CYAD-02. Furthermore, patients receiving CYAD-02 cells seem to display a greater duration of response and stronger blast reduction as compared to patients who received CYAD-01 in DEPLETHINK. Interestingly, peak engraftment levels were higher for CYAD-02 compared to CYAD-01 at the same dose (DEPLETHINK trial). At DL3, CYAD-02 cells could be readily detected in peripheral blood of 4/5 patients through month 2. In addition, and unlike what is reported in B cell CAR T-cells trials, there was very limited evidence of elevated homeostatic cytokines (IL-7/IL-15) following CyFlu administration with IL-15 not detected in any of the patients and IL-7 showing only a minor increase in 2 patients. The knockdown of MICA/MICB appears to have a positive contribution to the initial clinical activity of CYAD-02 as compared to that achieved with the first generation CYAD-01 CAR T, together with good safety and tolerability. The lack of homeostatic cytokines after preconditioning, likely limiting the engraftment and activity of CAR T cells, may be related to the biology of myeloid malignancies. One approach to further drive the potency of NKG2D-based CAR T cells would likely be armoring the CAR T through using the T cell as a vehicle to secrete cytokines alongside the CAR. Overall, shRNA knockdown technology provides a means to modify CAR T function and here shows that single shRNA can target two independent genes to enhance the phenotype of the CAR Ts. Disclosures Deeren: Alexion: Consultancy; BMS: Consultancy; Incyte: Consultancy; Novartis: Consultancy; Sanofi: Consultancy, Research Funding; Sobi: Consultancy; Takeda: Consultancy. Lin: AbbVie, Aptevo Therapeutics, Astellas Pharma, Bio-Path Holdings, Celgene, Celyad, Genentech-Roche, Gilead Sciences, Incyte, Jazz Pharmaceuticals, Novartis, Ono Pharmaceutical, Pfizer, Prescient Therapeutics, Seattle Genetics, Tolero, Trovagene: Research Funding. Alcantar-Orozco: Celyad Oncology: Current Employment. Dheur: Celyad Oncology: Current Employment. Breman: Celyad Oncology: Current Employment. Braun: Celyad Oncology: Current Employment. Lonez: Celyad Oncology: Current Employment. Gilham: Celyad Oncology: Current Employment. Flament: Celyad Oncology: Current Employment. Lehmann: Celyad Oncology: Current Employment.
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Kumar, Pawan, Sudha Singh, and Shamim Ahmed. "CHEMICAL CONSTITUENTS AND PHARMACOLOGICAL PROPERTIES OF BOUGAINVILLEA LEAVES: A REVIEW." International Journal of Pharmaceutical Sciences and Medicine 9, no. 4 (April 30, 2024): 26–37. http://dx.doi.org/10.47760/ijpsm.2024.v09i04.003.
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The genus Bougainvillea is a very widespread group throughout the world. It belongs to the family Nyctaginaceae and contains approximately 18 species i.e., B. berberidifolia, B. buttiana, B. campanulata, B. glabra, B. herzogiana, B. infesta, B. lehmanniana, B. lehmannii, B. malmeana, B. modesta, B. pachyphylla, B. peruviana, B. pomacea, B. praecox, B. spectabilis, B. spinosa, B. stipitata, and B. trollii. The genus Bougainvillea is endemic to South America and was firstly reported in Brazil in 1778 before being introduced to Europe, by French military commander Louis Antoine de Bougainville. They are bushes spread in vines or small trees. They also possess stems with internodes and with straight or slightly curved thorns. The leaves are petiolate, elliptical, or wider towards the base. The bracts and flowers are presented in different colours, depending on the species, cultivars, or hybrid. It is a rich source of Aliphatic Hydrocarbons, Fatty Acids and Fatty Alcohols, volatile compounds, phenolic compound, Peltogynoids and Flavonoids, Phytosterols, Terpenes, and Carbohydrates, Betalains etc. In conclusion, the leaves of Bougainvillea glabra are reported to have anti- inflammatory activities, anti-hyperglycaemic activity, insecticidal activity, anti hyperglycemic activity anti-ulcer, antimicrobial and anti-diarrheal activity and its antiviral proteins.
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Locke, Larry G., Ethan Mitra, and Virginia Locke. "Harnessing Whales: The Role Of Shadow Price Disclosure In Money Market Mutual Fund Reform." Journal of Business & Economics Research (JBER) 11, no. 4 (March 28, 2013): 187. http://dx.doi.org/10.19030/jber.v11i4.7747.
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<span style="font-family: Times New Roman; font-size: small;"> </span><p style="margin: 0in 0.5in 0pt; text-align: justify; line-height: normal; mso-pagination: none;" class="MsoNormal"><span style="color: black; font-family: "Times New Roman","serif"; font-size: 10pt; mso-themecolor: text1;">The money market mutual fund industry is experiencing a sea change.<span style="mso-spacerun: yes;"> </span>Thanks, in large part, to their role in the 2008 market break, U.S. securities regulators have targeted money market funds for a structural overhaul.<span style="mso-spacerun: yes;"> </span>Runs on money market funds by institutional investors in the wake of the Lehman Brothers bankruptcy weakened the short-term credit market to the point of collapse.<span style="mso-spacerun: yes;"> </span>The resulting intervention of the Federal Reserve and the Treasury may have saved the economy from further damage but came at such a perceived cost that legislation now forbids it.<span style="mso-spacerun: yes;"> </span>Both the Securities and Exchange Commission (SEC) and the Financial Stability Oversight Council (FSOC) believe restructuring is necessary.<span style="mso-spacerun: yes;"> </span>Their only question appears to be exactly what form the product will take.</span></p><span style="font-family: Times New Roman; font-size: small;"> </span><p style="margin: 0in 0.5in 0pt; text-align: justify; line-height: normal; mso-pagination: none;" class="MsoNormal"><span style="color: black; font-family: "Times New Roman","serif"; font-size: 10pt; mso-themecolor: text1;"> </span></p><span style="font-family: Times New Roman; font-size: small;"> </span><p style="margin: 0in 0.5in 0pt; text-align: justify; line-height: normal; mso-pagination: none;" class="MsoNormal"><span style="color: black; font-family: "Times New Roman","serif"; font-size: 10pt; mso-themecolor: text1;">One of the elements being considered in the reform effort will be increased disclosure of money market fund shadow prices.<span style="mso-spacerun: yes;"> </span>The regulators have posited that more frequent and more available disclosure of fund shadow prices will lead to more discipline being exerted on the fund industry, especially by the institutional market.<span style="mso-spacerun: yes;"> </span>A revamped disclosure regime, however, has been in effect since monthly shadow price disclosures were imposed by the SEC in December 2010.</span></p><span style="font-family: Times New Roman; font-size: small;"> </span><p style="margin: 0in 0.5in 0pt; text-align: justify; line-height: normal; mso-pagination: none;" class="MsoNormal"><span style="color: black; font-family: "Times New Roman","serif"; font-size: 10pt; mso-themecolor: text1;"> </span></p><span style="font-family: Times New Roman; font-size: small;"> </span><p style="margin: 0in 0.5in 0pt; text-align: justify; line-height: normal; mso-pagination: none;" class="MsoNormal"><span style="color: black; font-family: "Times New Roman","serif"; font-size: 10pt; mso-themecolor: text1;">This study looks at the impact of those 2010 disclosure regulations on different sectors of the market.<span style="mso-spacerun: yes;"> </span>It seeks to identify a correlation between shadow prices and changes in assets for both retail and institutional funds.<span style="mso-spacerun: yes;"> </span>The authors assess the findings of the study and discuss the implications of those findings for the impending regulatory restructuring.<span style="mso-spacerun: yes;"> </span></span></p><span style="font-family: Times New Roman; font-size: small;"> </span>
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Karazi-Presler, Tair, Moti Gigi, Luis Roniger, Yossi Harpaz, Oded Adomi Leshem, Meir Elran, Dany Bahar, and Yuval Benziman. "Book Reviews." Israel Studies Review 33, no. 3 (December 1, 2018): 152–80. http://dx.doi.org/10.3167/isr.2018.330310.
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Edna Lomsky-Feder and Orna Sasson-Levy, Women Soldiers and Citizenship in Israel: Gendered Encounters with the State (New York: Routledge, 2017), 178 pp. Hardback, $149.95.Aviva Halamish, Kibbutz: Utopia and Politics. The Life and Times of Meir Yaari, 1897–1987 (Brighton, MA: Academic Studies Press, 2017), 496 pp. Hardback, $119. Paperback, $45.Eliezer Ben-Rafael, Julius H. Schoeps, Yitzhak Sternberg, and Olaf Glöckner, eds., Handbook of Israel: Major Debates (Berlin: De Gruyter Oldenbourg, 2016), 1,304 pp. Hardback, $165.00. Paperback, $81.00.Uri Ram, Israeli Sociology: Text in Context (Basingstoke: Palgrave Macmillan, 2017), 174 pp. e-Book: $54.99.Herbert C. Kelman, Transforming the Israeli-Palestinian Conflict: From Mutual Negation to Reconciliation (London: Routledge, 2018), 248 pp. Hardback, $112.00. eBook, $27.48.Charles D. Freilich, Israeli National Security: A New Strategy for an Era of Change (New York: Oxford University Press, 2018), 496 pp. Hardback, $39.95. Kindle, $14.57.David Rosenberg, Israel’s Technology Economy: Origins and Impact (New York: Palgrave Macmillan, 2018), 275 pp. Hardback, $84.95. eBook, $64.95.Lee Perlman, But Abu Ibrahim, We’re Family! (Tel Aviv: Tami Steinmetz Center for Peace Research, 2017), 198 pp. Paperback, $20.00. Shapiro Prize WinnersThis new feature of ISR will present the report of the committee choosing the recipient of the Yonathan Shapiro Prize for the best book in Israel Studies, to be awarded at the annual meeting of the Association for Israel Studies. In 2018, there was a tie, and two books received the prize. The committee members were Raphael Cohen-Almagor, Mikhal Dekel, Tamar Hermann, Sam Lehman-Wilzig, and Ruvi Ziegler.Alona Nitzan-Shiftan, Seizing Jerusalem: The Architecture of Unilateral Unification (Minneapolis: University of Minnesota Press, 2017), 376 pp. Hardback, $160.00. Paperback, $39.95.Kimmy Caplan, Amram Blau [in Hebrew] (Jerusalem: Yad Ben Zvi and the Ben-Gurion Institute, 2017), 588 pp. Paperback, NIS116.
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Hung, Jason. "Psychosocial Wellbeing Among Rural Migrant Workers in China: Did the 2008 Financial Crisis Worsen Their Vulnerability?" Asian Social Science 16, no. 1 (December 31, 2019): 54. http://dx.doi.org/10.5539/ass.v16n1p54.
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Background. Since 1980, China has been experiencing the largest migration in human history to urban areas. Rural migrant workers are exposed to disproportionate stress, a sense of marginality, language barriers and low social positions. Stress plays a significant role in the development of psychosocial challenges, including anxiety, hostility and depressive symptoms, as well as diagnosable conditions, including compulsive and post-traumatic stress disorders. This project questions whether rural migrant workers were particularly vulnerable in terms of psychosocial wellbeing after the collapse of Lehman Brothers, one of the major incidents marking the worst turmoil of the 2008 financial crisis.
Methods. Data from the Rural Urban Migration in China (RUMiC) 2007-08 and 2008-09 datasets were used for analyses. General Health Questionnaire (GHQ) -12 scores, categorised as the presence of common mental disorders (CMDs) vs. the absence of CMDs, were chosen as the dependent variable. Socioeconomic status was measured as per hukou status, job nature and working hours, each treated as an independent variable. City, gender, age, ethnicity and educational level were taken into account as confounders. Cross-tabulations and binary logistic regression analyses were run. The software package STATA 14.2 was used for secondary data analysis.
Results. The more educational qualifications rural migrant worker samples received, the more likely they were to be free from CMDs. However, tertiarily-educated rural migrant worker samples enjoyed similar levels of mental wellbeing as their counterparts who had completed elementary school or below. Additionally, there was no statistical evidence to suggest that rural migrant worker samples were more likely to experience CMDs based on their job nature (non-manual vs. manual vs. self-employed vs. family business) or working hours (< 60 hours per week vs. 60-119 hours per week vs. >= 120 hours per week).
Conclusions. The optimal rural migrant workers’ educational level, in terms of maximising their mental wellbeing, was between senior secondary school and post-secondary school level. However, socioeconomic factors, namely, job nature and working hours, were insignificant determinants of mental wellbeing of rural migrant workers. Moreover, there was no evidence suggesting rural migrant workers suffered from a distinct mental wellbeing between 2008 and 2009.