Development Of Wiskott-Aldrich Syndrome Knock Out Protocol For Drug Substance Assay Development

Wiskott-Aldrich Syndrome (WAS) is a rare X-linked primary immunodeficiency affecting approximately 1 in 100,000 live XY births in North America and is caused by a mutation to the WAS gene which is expressed across hematopoietic lineages. The WAS protein (WASp) plays a role in regulating actin polymerization. On a cellular level, there are a variety of effects of a lack of WASp or expression of a dysfunctional WASp protein for patients including issues with migration, adhesion, chemotactic response, phagocytosis, activation, and proliferation across different cell types in addition to reduced platelet size and output. This can lead to several systematic effects for the patients however because mutations to the WAS gene are not limited to one location or type there is a great amount of variability between patient symptoms making it challenging to diagnose. Major symptoms include frequent and recurrent infections, uncontrolled bleeding episodes, issues associated with autoimmunity, and malignancy, the most common form being lymphoma. Without treatment, the life expectancy of an individual diagnosed with WAS is 14 years of age, and the only curative treatment strategy available is hematopoietic stem and progenitor cell transfer (HSPCT). If not performed with an HLA-identical donor, which is available to less than 10% of patients, and within the first two years of life, the risk of graft versus host disease (GvHD) increases drastically for the patient. A gene therapy using autologous and genetically corrected CD34+ cells would be advantageous to the patients due to a reduction in preparative conditioning, immunosuppressive aftercare, and the risk of GvHD. CSL Behring is currently in the development of a lentiviral gene therapy to fulfill this gap in care, however, to develop the assays required to assess and characterize the drug substance usually an uncorrected patient sample is compared with a gene-edited sample. The limitation here is that due to the risk of infection and bleeding patient sample is very limited and therefore the development of a mock patient sample is necessary for early development. The goal of the project is to develop a WAS-KO protocol utilizing CRISPR/Cas9 and its characterization

Diffusion and bulk flow in phloem loading - a theoretical analysis of the polymer trap mechanism in plants

Plants create sugar in the mesophyll cells of their leaves by photosynthesis. This sugar, mostly sucrose, has to be loaded via the bundle sheath into the phloem vascular system (the sieve elements), where it is distributed to growing parts of the plant. We analyze the feasibility of a particular loading mechanism, active symplasmic loading, also called the polymer trap mechanism, where sucrose is transformed into heavier sugars, such as raffinose and stachyose, in the intermediary-type companion cells bordering the sieve elements in the minor veins of the phloem. Keeping the heavier sugars from diffusing back requires that the plasmodesmata connecting the bundle sheath with the intermediary cell act as extremely precise filters, which are able to distinguish between molecules that differ by less than 20% in size. In our modeling, we take into account the coupled water and sugar movement across the relevant interfaces, without explicitly considering the chemical reactions transforming the sucrose into the heavier sugars. Based on the available data for plasmodesmata geometry, sugar concentrations and flux rates, we conclude that this mechanism can in principle function. We find that the water flow through the plasmodesmata, which has not been quantified before, contributes only 10-20% to the sucrose flux into the intermediary cells, while the main part is transported by diffusion. On the other hand, the subsequent sugar translocation into the sieve elements would very likely be carried predominantly by bulk water flow through the plasmodesmata. Thus, in contrast to apoplasmic loaders, all the necessary water for phloem translocation would be supplied in this way with no need for additional water uptake across the plasma membranes of the phloem.Comment: 29 pages with 5 figure

Investment Behavior of Ugandan Smallholder Farmers: An Experimental Analysis

In this study, we experimentally analyze the investment behavior of smallholder farmers in Uganda. We consider a problem of optimal stopping, stylizing an option to invest in a project. We ascertain whether, and to what extent, the real options approach and the classical investment theory can predict farmers’ investment behaviors. We also examine differences in the investment behavior with respect to the presence of a price floor, which is often used to stimulate investments. Furthermore, we look at learning effects. Our results show that both theories do not exactly explain the observed investment behavior. However, our results suggest that real options models better predict the decision behavior of farmers than the classical investment theory. The presence of a price floor and learning from personal experience during the experiment do not significantly affect the investment behavior. However, we find that specific socio-demographic and socio-economic characteristics affect the investment behavior of farmers

Do Changing Probabilities or Payoffs in Lottery-Choice Experiments Matter? Evidence from Rural Uganda

This study compares risk attitudes of smallholder farmers elicited from two different lottery designs (i) with fixed payoffs and changing probabilities and (ii) with fixed probabilities and changing payoffs. We utilize a combination of experimental and household survey data collected from 332 randomly selected smallholder coffee farmers in Uganda. Both methods reveal high proportions of farmers who are classified as risk averse. However, comparing the different risk categories shows that the two elicitation methods yield significantly different results. Furthermore, we relatively find low inconsistency rates in the response behavior for the two methods compared to other studies in the past. Specific socio-demographic and socioeconomic characteristics also affect farmers’ risk attitudes

Expressed Emotion in the Family: A Meta-Analytic Review of Expressed Emotion as a Mechanism of the Transgenerational Transmission of Mental Disorders

Background High Expressed Emotion (HEE) has been identified as a risk factor for the exacerbation and course of mental illness. EE has been investigated as a caregiver's response to an offspring's problem behavior and pathology. The present meta-analysis regards EE from a transgenerational perspective and as one mechanism that might explain the transgenerational transmission of mental disorders. Method We identified a total of 13 studies relying on 16 independent samples of parent-child dyads of parents with a mental illness and healthy controls; these were included in our analysis. Results were synthesized into one effect size per sample; meta-regression on additional effects of parental diagnostic category, child mental illness, and child age were also applied. Results Parents with a mental illness are classified as HEE significantly more often. Effects were established for high criticism, albeit of small size (OR = 1.45), although they become stronger whenever offspring exhibit mental illness themselves (OR = 2.82). Conclusion The current study highlights the dearth of studies on EE in families in which a parent has a mental illness and its effects on their children. Our findings highlight EE as a potential mechanism for attributing the transgenerational transmission of mental disorders, especially for the EE-variable criticism, indicating dysfunctional parent-child interactions. Systematic Review Registration http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019117609, identifier: CRD42019117609.Peer Reviewe

ANALISIS LATAR – PELATARAN DAN DAMPAKNYA TERHADAP TOKOH DAN PENOKOHAN NOVEL HIKAYAT PUTRI PENELOPE KARYA IDRUS SERTA KESESUAIANNYA DENGAN BAHAN AJAR TUNTUTAN KURIKULUM 2013 DI SMA

Pembelajaran sastra di sekolah merupakan salah satu pembelajaran yang sangat penting, guna menumbuhkan rasa peduli dan perkembangan sosial terhadap peserta didik. Salah satu pembelajaran sastra di SMA ialah novel. Novel merupakan salah satu bentuk prosa fiksi. Di dalam karya sastra seperti novel, biasanya terdapat struktur. Salah satu struktur novel yaitu latar dan pelataran cerita. Namun, masih banyak yang menganggap bahwa latar – pelataran hanya sebatas keterangan tempat dan waktu dalam cerita, sehingga esensi cerita tersebut kurang yang mengakibatkan banyak peserta didik kesulitan dalam menganalisis latar – pelataran pada novel, serta bahan ajar novel kurang inovasi. Dengan demikian, pada penelitian ini penulis memiliki tujuan untuk menganalisis unsur latar – pelataran dan dampaknya terhadap tokoh dan penokohan dalam novel Hikayat Putri Penelope Karya Idrus, yaitu sebagai berikut: (1) untuk mengetahui dampak unsur latar – pelataran terhadap tokoh pada novel Hikayat Putri Penelope karya Idrus; (2) untuk mengetahui kesesuaian hasil analisis mengenai unsur latar – pelataran terhadap tokoh dan penokohan novel Hikayat Putri Penelope karya Idrus serta pemanfaatan sebagai bahan ajar Bahasa Indonesia sesuai tuntutan kurikulum 2013. Pada penelitian ini, penulis menggunakan metode kualitatif dengan jenis deskriptif dan sumber data primer berupa novel Hikayat Putri Penelope karya Idrus. Berdasarkan analisis penelitian yang telah dilakukan, didapatkan data bahwa novel Hikayat Putri Penelope karya Idrus yang telah dianalisis, memuat secara lengkap unsur latar – pelataran. Di antaranya yaitu latar tempat, latar waktu, dan latar sosial serta dampak latar – pelataran terhadap tokoh dan penokohan novel. Novel Hikayat Putri Penelope karya Idrus dapat dimanfaatkan sebagai alternatif pemilihan bahan ajar pada peserta didik tingkat Sekolah Menengah Atas (SMA). Kata Kunci: analisis, latar dan pelataran, tokoh dan penokohan, novel, kurikulum 201

How should libraries respond to new forms of publication? Some reflections on the expectations of users and providers and what could be realized at the present state of technical development

"The paper focuses on the possibilities and problems created for the humanities by the usage of Digital Libraries. The exchange of information, forms of discussion and the process of publication in the scientific communities have changed over the recent years. On the other hand the user group of digital libraries is heterogeneous and difficult to define. We discuss the organization structure and the working process of two communities, which have quickly adapted their communication process to the use of web-technologies: the Open Source community and the scientific research community. We have to distinguish the communication technique, the applications of the World Wide Web (WWW), including search engines, and the barely started developments to realize new Web Services for DL-oriented applications, to support the library services and finally to obtain a new concept, which we call long-term access to digital structured resources by contract. A DL user views a Web Service as a 'black box' and the service has an interface. The user has only to know the preconditions so that the postconditions will support his/her requirements. We conclude by stating that we should accept that publishing and distributing structural digital resources/information is a new way of (scientific) publication based on collaborative structures. Libraries should respond to this development by providing dynamic metadata in a decentralized network of libraries." (author's abstract

How do Children Rate Their Health? : An Investigation of Considered Health Dimensions, Health Factors, and Assessment Strategies

In large-scale surveys of both children and adults, self-rated health (SRH) based on questions such as “In general, how would you rate your health?” is a widely used measurement to assess individuals’ health status. However, while a large number of studies have investigated the health aspects people consider for their responses, and some studies show deeper insights into the assessment strategies in answering this question for adults, it is largely unknown how children assess their health based on those questions. Therefore, this study examines how children rate their health according to this question in a sample of 54 9- to 12-year-olds. By using techniques of cognitive interviewing and qualitative and quantitative content analysis, we investigate the health dimensions, health factors as well as different assessment strategies that children refer to in their self-assessment of general health. Our results indicate that children in this age group mostly refer to their physical health and daily functioning or consider health more non-specifically. They also show that children take into account a wide range of specific health aspects, with some minor differences between subgroups, especially by gender. Additionally, our study highlights that children use several assessment strategies. Finally, our results indicate that the majority of children assess their health only using one health dimension, but a substantial share of children reflect on several health factors and combine different assessment strategies. We conclude that children refer to comparable health dimensions and health factors, but use somewhat different assessment strategies compared with studies focusing on adults

Children's disclosures of sexual abuse in a population-based sample

Most previous studies on disclosing child sexual abuse (CSA) have either been retrospective or focused on children who already have disclosed. The present study aimed to explore the overall CSA disclosure rate and factors associated with disclosing to adults in a large population-based sample. A representative sample of 11,364 sixth and ninth graders participated in the Finnish Child Victim Survey conceming experiences of violence, including CSA. CSA was defined as having sexual experiences with a person at least five years older at the time of the experience. Within this sample, the CSA prevalence was 2.4%. Children reporting CSA experiences also answered questions regarding disclosure, the disclosure recipient, and potential reasons for not disclosing. The results indicate that most of the children (80%) had disclosed to someone, usually a friend (48%). However, only 26% had disclosed to adults, and even fewer had reported their experiences to authorities (12%). The most common reason for non-disclosing was that the experience was not considered serious enough for reporting (41%), and half of the children having CSA experiences did not self-label their experiences as sexual abuse. Relatively few children reported lacking the courage to disclose (14%). Logistic regression analyses showed that the perpetrator's age, the age of the victim at the time of abuse, and having no experiences of emotional abuse by the mother were associated with disclosing to an adult. The results contribute to understanding the factors underlying children's disclosure patterns in a population-based sample and highlight the need for age-appropriate safety education for children and adolescents.Peer reviewe