Miracle-dz/UniFAR-FTUs huggingface dataset:
Spacer length impacts the efficacy of targeted docetaxel conjugates in prostate-specific membrane antigen expressing prostate cancer

Abstract Combination of targeted delivery and controlled release is a powerful technique for cancer treatment. In this paper, we describe the design, synthesis, structure validation and biological properties of targeted and non-targeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-docetaxel conjugates. Docetaxel (DTX) was conjugated to HPMA copolymer via a tetrapeptide spacer (–GFLG-). 3-(1,3-dicarboxypropyl)-ureido]pentanedioic acid (DUPA) was used as the targeting moiety to actively deliver DTX for treatment of Prostate-Specific Membrane Antigen (PSMA) expressing prostate cancer. Short and long spacer DUPA monomers were prepared, and four HPMA copolymer – DTX conjugates (non-targeted, two targeted with short spacer of different molecular weight and targeted with long spacer) were prepared via Reversible Addition-Fragmentation Chain Transfer (RAFT) copolymerization. Following confirmation of PSMA expression on C4-2 cell line, the DTX conjugates’ in vitro cytotoxicity was tested against C4-2 tumor cells and their anticancer efficacies were assessed in nude mice bearing s.c. human prostate adenocarcinoma C4-2 xenografts. The in vivo results show that the spacer length between targeting moieties and HPMA copolymer backbone can significantly affect the treatment efficacy of DTX conjugates against C4-2 tumor bearing nu/nu mice. Moreover, histological analysis indicated that the DUPA-targeted DTX conjugate with longer spacer had no toxicity in major organs of treated mice.
Structural Results on Optimal Rate and Number of Clusters in Cluster based Cooperative MIMO Sensor Networks

We present structural results on optimal number of clusters and optimal rate with respect to long haul distance in a cluster based cooperative multiple input and multiple output (MIMO) sensor network. Using the concepts of super and sub modular functions and their associated properties it has been proved that the number of clusters to minimize the energy consumption is a decreasing function of long haul distance. From this, we conclude that as the long haul distance increases the cooperation among the nodes increases to counter the path loss due to fading in the channel. Furthermore, we also prove the rate to minimize the energy consumption is a decreasing function of long haul distance. Finally, through our numerical results we observe that optimizing node cooperation can lead to large scale energy savings.
Tools or Toys--Inventing the Need for Domestic Appliances in Postwar and Postmodern Finland

The article describes how the boundary between necessary and unnecessary consumption items was defined in Finland in the years following World War II. On the basis of extensive comparative data, it focuses on the history of two items: the washing machine and the cellular phone. The data consist of press coverage and material published by manufacturers and consumer counseling organizations. The need for household appliances was invented, shaped, normalized, and legitimized through a social interaction process in which the media were a central vehicle. The data suggest that the need for novelties is interpreted though similar types of cultural modes, no matter what the product or type of cultural text. Thus, the entry of technology into the home in the postwar years was accompanied by a discussion flavored not only by technological determinism, but also by a form of social and cultural determinism manifested in deep-grounded conceptual distinctions, such as tools versus toys. The world-record pace at which Finnish consumers took up new technology in the postwar period provides illustrative evidence and new stimuli for evaluating the potential for digitalizing the home in the twenty-first century.
Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma

Abstract We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production. Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production. The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P < 0.05). LHCGR levels were also significantly elevated in APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P < 0.05). Patients with APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n = 13) (P < 0.05). Multiple regression analysis revealed that the presence of the KCNJ5 mutation was linked to GNRHR mRNA expression (&bgr; = 0.94 and P < 0.01). HAC15 cells with KCNJ5 gene carrying T158A mutation exhibited a significantly lower GNRHR expression than that in control cells (P < 0.05). We clarified increased expression of GNRHR and LHCGR in APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation.
Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation

We have defined the molecular basis of cell adhesion to fibrillin-1, the major structural component of extracellular microfibrils that are associated with elastic fibres. Using human dermal fibroblasts, and recombinant domain swap fragments containing the Arg-Gly-Asp motif, we have demonstrated a requirement for upstream domains for integrin-α5β1-mediated cell adhesion and migration. An adjacent heparin-binding site, which supports focal adhesion formation, was mapped to the fibrillin-1 TB5 motif. Site-directed mutagenesis revealed two arginine residues that are crucial for heparin binding, and confirmed their role in focal adhesion formation. These integrin and syndecan adhesion motifs juxtaposed on fibrillin-1 are evolutionarily conserved and reminiscent of similar functional elements on fibronectin, highlighting their crucial functional importance.
The sixth international workshop on economics-driven software engineering research (EDSER-6)

Traditionally, the study of software engineering has been primarily a technical endeavor with minimal attention given to its economic context. Design and implementation methods are proposed based on technical merits without making adequate links to economic considerations. Engineering seeks to create value relative to resources invested in a given context, whether commercial or not. Software development essentially is an irreversible capital investment and software should add value to the organization just as any other capital expenditure that creates a net benefit.
Colonialism and the Construction of National Identities: The Case of Eritrea

Abstract In spite of the common agreement on the relevance of Italian rule on the political and social shaping of Eritrea, little investigation has been carried out to analyse the political, juridical and economical, nature of the colonial system in Eritrea and its impact on Eritrean society. This article focuses on the structure and strategies of the colonial state in Eritrea. Special attention is given to the development of an alternative juridical and institutional system for colonial subjects, which is described as both a key aspect of the development and consolidation of colonial powers and a crucial factor in moulding new identities. The final section of the article discusses relations between the colonial state and local elites. It is a common assumption that one of the main negative consequences of the harsh policies adopted by Italian colonialism in order to frustrate Eritrean aspiration and access to education was the suppression of a local elite. It is argued that, while true in a general sense.
Session 4: CVD, diabetes and cancer Diet, insulin resistance and diabetes: the right (pro)portions

Excess energy intake and positive energy balance are associated with the development of obesity and insulin resistance, which is a key feature underlying the pathophysiology of type 2 diabetes. It is possible that dietary macronutrient intake may also be important, in particular increased levels of sugar and fat. High-fat energy-dense diets contribute to energy excess and obesity. Fat type is also a factor, with evidence suggesting that saturated fat intake is linked to insulin resistance. However, controversy exists about the role of carbohydrate in the development of diabetes. Epidemiological studies suggest that the risk of diabetes is unrelated to the total amount of carbohydrate, but that fibre intake and glycaemic load are important. Common dietary advice for the prevention of diabetes often advocates complex carbohydrates and restriction of simple carbohydrates; however, sugars may not be the main contributor to glycaemic load. Evidence continues to emerge in relation to the influence of dietary sugars intake on insulin resistance. In broader dietary terms fruit and vegetable intake may influence insulin resistance, possibly related to increased intake of fibre and micronutrients or displacement of other food types. There is also considerable debate about the most effective diet and appropriate macronutrient composition to facilitate weight loss. Recent evidence suggests comparable effects of diets with varying macronutrient profiles on weight loss, which is predominantly related to energy restriction. However, based on the results of diabetes prevention trials focusing on lifestyle measures, evidence favours low-fat diets as the preferred approach for weight loss and diabetes prevention.
Analysis of FHMA performance on block cipher based frequency-hopping sequences

Based on the triple Data Encryption Standard (DES) block cipher frequency-hopping (FH) sequences, a kind of packet protocol for frequency-hopping multiple-access (FHMA) network is suggested in this paper. In theory, the performances of both the packet error and the throughput are derived, which shows that the ratio of the packet length M to the frequency slots number q is most key parameter to determine the FHMA system performance under the condition of large user number. Computer simulation results of 3-DES FH sequences compared with those of the chaotic FH sequences are also included to support our developments.
Oxidation of Endogenous N-Arachidonoylserotonin by Human Cytochrome P450 2U1*

Background: Cytochrome P450 (P450, CYP) 2U1 is an “orphan” enzyme, only reported to catalyze some fatty acid oxidations. Results: Metabolomic screening led to the identification of N-arachidonoylserotonin as a substrate. Conclusion: P450 2U1 catalyzes oxygenation at C-2 of the indole ring. Significance: The localization of P450 2U1 and its metabolism of an inhibitor of fatty acid amide hydrolase may indicate a function in brain. Cytochrome P450 (P450) 2U1 has been shown to be expressed, at the mRNA level, in human thymus, brain, and several other tissues. Recombinant P450 2U1 was purified and used as a reagent in a metabolomic search for substrates in bovine brain. In addition to fatty acid oxidation reactions, an oxidation of endogenous N-arachidonoylserotonin was characterized. Subsequent NMR and mass spectrometry and chemical synthesis showed that the main product was the result of C-2 oxidation of the indole ring, in contrast to other human P450s that generated different products. N-Arachidonoylserotonin, first synthesized chemically and described as an inhibitor of fatty acid amide hydrolase, had previously been found in porcine and mouse intestine; we demonstrated its presence in bovine and human brain samples. The product (2-oxo) was 4-fold less active than N-arachidonoylserotonin in inhibiting fatty acid amide hydrolase. The rate of oxidation of N-arachidonoylserotonin was similar to that of arachidonic acid, one of the previously identified fatty acid substrates of P450 2U1. The demonstration of the oxidation of N-arachidonoylserotonin by P450 2U1 suggests a possible role in human brain and possibly other sites.
The impact of paternity leave and paternal involvement in child care on maternal postpartum depression

Objectives: The aim of the study was to explore the impact of paternity leave and paternal involvement and notably paternal participation in infant care on the development of symptoms of maternal postpartum depression. Method: At 2–5 days postpartum, a sample of 119 couples completed the Edinburgh Postnatal Depression Scale (EPDS), assessing postpartum depression. Mothers also completed the Multidimensional Scale of Perceived Social Support (MSPSS). At 2 months postpartum, 4 questionnaires were completed: the EPDS, the MSPSS, the Maternal Attitude Questionnaire (MAQ), measuring cognitions relating to role change and expectations of motherhood, as well as a questionnaire assessing paternal involvement in infant care. Fathers also completed the EPDS and a questionnaire assessing paternal involvement in infant care. Results: Paternity leave was not highlighted as a significant protective factor against postpartum depression. However, the lack of paternal involvement in infant care was significantly associated with maternal depression intensity. Discussion: Our findings highlight the importance of encouraging and taking into account paternal involvement in infant care as early as possible.
Self-compassion training for binge eating disorder: a pilot randomized controlled trial.

OBJECTIVES The present pilot study sought to compare a compassion-focused therapy (CFT)-based self-help intervention for binge eating disorder (BED) to a behaviourally based intervention. DESIGN Forty-one individuals with BED were randomly assigned to 3 weeks of food planning plus self-compassion exercises; food planning plus behavioural strategies; or a wait-list control condition. METHODS Participants completed weekly measures of binge eating and self-compassion; pre- and post-intervention measures of eating disorder pathology and depressive symptoms; and a baseline measure assessing fear of self-compassion. RESULTS Results showed that: (1) perceived credibility, expectancy, and compliance did not differ between the two interventions; (2) both interventions reduced weekly binge days more than the control condition; (3) the self-compassion intervention reduced global eating disorder pathology, eating concerns, and weight concerns more than the other conditions; (4) the self-compassion intervention increased self-compassion more than the other conditions; and (5) participants low in fear of self-compassion derived significantly more benefits from the self-compassion intervention than those high in fear of self-compassion. CONCLUSIONS Findings offer preliminary support for the usefulness of CFT-based interventions for BED sufferers. Results also suggest that for individuals to benefit from self-compassion training, assessing and lowering fear of self-compassion will be crucial. PRACTITIONER POINTS Individuals with BED perceive self-compassion training self-help interventions, derived from CFT, to be as credible and as likely to help as behaviourally based interventions. The cultivation of self-compassion may be an effective approach for reducing binge eating, and eating, and weight concerns in individuals with BED. Teaching individuals with BED CFT-based self-help exercises may increase their self-compassion levels over a short period of time. It may be important for clinicians to assess and target clients' fear of self-compassion for clients to benefit from self-compassion training interventions.
The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor

There are over 120 types of brain tumor and approximately 45% of primary brain tumors are gliomas, of which glioblastoma multiforme (GBM) is the most common and aggressive with a median survival rate of 14 months. Despite progress in our knowledge, current therapies are unable to effectively combat primary brain tumors and patient survival remains poor. Tumor metabolism is important to consider in therapeutic approaches and is the focus of numerous research investigations. Lactate dehydrogenase A (LDHA) is a cytosolic enzyme, predominantly involved in anaerobic and aerobic glycolysis (the Warburg effect); however, it has multiple additional functions in non‐neoplastic and neoplastic tissues, which are not commonly known or discussed. This review summarizes what is currently known about the function of LDHA and identifies areas that would benefit from further exploration. The current knowledge of the role of LDHA in the brain and its potential as a therapeutic target for brain tumors will also be highlighted. The Warburg effect appears to be universal in tumors, including primary brain tumors, and LDHA (because of its involvement with this process) has been identified as a potential therapeutic target. Currently, there are, however, no suitable LDHA inhibitors available for tumor therapies in the clinic.
Insecurity and shiftwork as characteristics of negative work environment: psychosocial and behavioural mediators.

AIM This paper is a report of an investigation into whether insecure work contract and shiftwork are associated with reduced wellbeing indicators, such as psychological distress, low job involvement and low work ability. BACKGROUND Insecure work contracts and shiftwork have repeatedly been found to contribute to the development and continuation of negative outcomes among healthcare professionals. In particular, nurses are generally considered as being at high risk of work-related stress and reduced wellbeing. METHODS Cross-sectional survey data from the Finnish Health Care Professional Study collected in 2006 were used. The random sample of Finnish Registered Nurses comprised 2100 women and men aged 22-65 years. Information on the work contract and shiftwork were self-reported. The wellbeing indicators used were psychological distress (GHQ-12), work ability and job involvement. Psychosocial work characteristics were measured using the Job Content Questionnaire and an organizational justice scale. RESULTS Variance and linear regression analyses showed that insecure work contract was associated with lower work ability and job involvement. Shiftwork was related to psychological distress, low job involvement and low work ability. Support for a mediating role of job demands and job control and a moderating role of relational justice was obtained. CONCLUSION To reduce the negative effects of environmental stressors, such as insecure work contract and shiftwork, it may be better to focus on improving psychosocial work characteristics than on nurses' health-related behaviour.
Risk factors for Epstein-Barr virus-related post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation is a successful treatment for hematologic malignancies and a variety of genetic and metabolic disorders. In the period following stem cell transplantation, the immune-compromised milieu allows opportunistic pathogens to thrive. Epstein-Barr virus-associated post-transplant lymphoproliferative disease can be a life-threatening complication for transplanted patients because of suppressed T-cell-mediated immunity. We analyzed possible risk factors associated with post-transplant lymphoproliferative disease in a cohort of over 1,000 patients. The incidence of post-transplant lymphoproliferative disease was 4%. Significant risk factors identified by multivariate analysis were: human leukocyte antigen-mismatch (P<0.001), serological Epstein-Barr virus mismatch recipient−/donor+ (P<0.001), use of reduced intensity conditioning (P=0.002), acute graft-versus-host disease grade II to IV (P=0.006), pre-transplant splenectomy (P=0.008) and infusion of mesenchymal stromal cells (P=0.015). The risk of post-transplant lymphoproliferative disease has increased in more recent years, from less than 2% before 1998 to more than 6% after 2011. Additionally, we show that long-term survival of patients with post-transplant lymphoproliferative disease is poor despite initial successful treatment. The 3-year survival rate among the 40 patients with post-transplant lymphoproliferative disease was 20% as opposed to 62% among patients without post-transplant lymphoproliferative disease (P<0.001). The study identifies patients at risk of post-transplant lymphoproliferative disease after transplantation in need of pre-emptive measures.
Effect of Repeated Listenings on Structural Discrimination and Affective Response

Knowledge of musical form and of the structural elements that make up that form is basic to musical understanding and, eventually, musical enjoyment.1 Nevertheless, the relationship between liking a specific piece of music and understanding its composition is not always apparent. Establishing such a relationship is important, for the more that is known about creating positive reactions to music, especially art music, the more likely will better teaching methods be developed to achieve these kinds of reactions. Certain educators have indicated that more effective ways of teaching discriminative listening are necessary to achieve greater sensitivity to the formal structural elements of music.2 Listening to music may occur with relatively little awareness of what is happening within the musical performance. However, listening discriminatively necessarily involves some degree of recognition, perception, or identification of musical stimuli by a process of distinguishing and sifting out certain stimulus characteristics. It is not always possible to make fine discriminations of music in one hearing.
Conceptualizing and Exemplifying Science Teachers' Assessment Expertise

Although research in science education has led to new assessment forms and functions, the reality is that little work has been done to unpack and capture what it means for a teacher to develop expertise at assessing science. The purpose of this paper is two-fold. First, I suggest a conceptualization of assessment expertise that is organized around three dimensions: (a) designing aligned and theoretically cohesive assessment (Design), (b) using assessment to support students' science learning (Use), and (c) equitably assessing language minorities (Equity). The second purpose is to suggest and exemplify various levels of teaching expertise across the three conceptual dimensions using written assessment plans gathered from a study on secondary science pre-service teachers' assessment growth. The contribution of this paper lies in its further conceptual development of assessment expertise, instantiated in a rubric, which can spark discussion about how to capture the range of assessment practices that might be found in science classrooms as well as move toward a potential learning progression of assessment expertise.
Organization of chicken DNA sequences homologous to the transforming gene of avian myeloblastosis virus. I. Restriction enzyme analysis of total DNA from normal and leukemic cells

Hybridization probes consisting of cloned DNA recombinants which represent different regions of the leukemogenic sequence (amv) from avian myeloblastosis virus were used to carry out a more detailed restriction endonuclease analysis of the homologous sequences (proto-amv) present in normal and leukemic chicken DNA. The results show that four large introns interrupt the normal cellular proto-amv sequences and that there is no major rearrangement of these sequences in leukemic myeloblasts.