Miracle-dz/UniFAR-FTUs huggingface dataset:
Nondepleting anti-CD4 and soluble interleukin-1 receptor prevent autoimmune destruction of syngeneic islet grafts in diabetic NOD mice1

Background. Successful islet transplantation in type 1 diabetes requires tolerance induction of both allo- and autoreactive T-cell responses. Monoclonal antibodies targeting the CD4 coreceptor on T-helper cells have been shown to be effective in this regard. In type 1 diabetes, there is some evidence to suggest that cytokines such as interleukin (IL)-1 may be involved in &bgr;-cell destruction. The high glucose levels associated with type 1 diabetes are also known to be toxic to beta cells. Method. The tempo of T-cell and macrophage infiltration into syngeneic islets transplanted into diabetic nonobese diabetic (NOD) mice was examined by immunohistochemistry. We investigated the ability of a nondepleting anti-CD4 monoclonal antibody (YTS177) to induce tolerance to syngeneic islet grafts in female spontaneous diabetic NOD mice and in an adoptive transfer model of diabetes in NOD mice. The spontaneous model was used to test the effect on graft function of perioperative insulin therapy in mice treated with YTS177. The ability of soluble interleukin (sIL)-1 receptor (R) type II (sIL-1RII) to inhibit IL-1 effects in syngeneic islet transplants was also assessed. Results. Cellular infiltration of CD3+ cells and macrophages into the islet graft coincided with loss of graft function in untreated mice. Self-tolerance to beta cells was restored with YTS177, allowing long-term graft survival in a proportion of animals. The use of perioperative insulin therapy increased the number of successful grafts in spontaneously diabetic NOD mice treated with YTS177. The combination of YTS177 with sIL-1RII significantly improved the rates of graft survival compared with graft survival in YTS177-treated spontaneously diabetic NOD mice. Conclusions. Nondepleting anti-CD4 antibodies restore self tolerance to syngeneic islet transplants in diabetic NOD mice. Insulin therapy improves graft survival in mice treated with YTS177. Preventing the action of IL-1 greatly improves graft survival induced with YTS177.
Recent advances in craniofacial morphogenesis

Craniofacial malformations are involved in three fourths of all congenital birth defects in humans, affecting the development of head, face, or neck. Tremendous progress in the study of craniofacial development has been made that places this field at the forefront of biomedical research. A concerted effort among evolutionary and developmental biologists, human geneticists, and tissue engineers has revealed important information on the molecular mechanisms that are crucial for the patterning and formation of craniofacial structures. Here, we highlight recent advances in our understanding of evo–devo as it relates to craniofacial morphogenesis, fate determination of cranial neural crest cells, and specific signaling pathways in regulating tissue–tissue interactions during patterning of craniofacial apparatus and the morphogenesis of tooth, mandible, and palate. Together, these findings will be beneficial for the understanding, treatment, and prevention of human congenital malformations and establish the foundation for craniofacial tissue regeneration. Developmental Dynamics 235:2353–2375, 2006. © 2006 Wiley‐Liss, Inc.
Probing the Relation between Students’ Integrated Knowledge and Knowledge-in-Use about Energy using Network Analysis

Modern science standards emphasize knowledge-in-use, i.e., connecting scientific practices with content. For knowledge to become usable in knowledge-in-use performances, students need well organized knowledge networks that allow them to activate and connect sets of relevant ideas across contexts, i.e. students need integrated knowledge. We conducted a longitudinal interview study with 30 students in a 7th grade energy unit and used network analysis to investigate students’ integrated knowledge, i.e., their knowledge networks. Linking these results with results from knowledge-in-use assessments, we found a strong connection between integrated knowledge and knowledge-in-use about energy. Further, we found evidence that well-connected ideas around the idea of energy transfer were particularly helpful for using energy ideas in the knowledge-in-use assessments. We present network analysis as a valuable extension of existing approaches to investigating students’ knowledge networks and the connection between them and knowledge-in-use.
Digital Objects as Passwords

Security proponents heavily emphasize the importance of choosing a strong password (one with high entropy). Unfortunately, by design, most humans are apparently incapable of generating such passwords, or memorizing a random-looking, machine-generated one for long-term use. Infrequently used passwords pose even bigger security and usability problems. We exploit the fact that many users now own or have access to a large quantity of digitized personal or personally meaningful content in designing an object-based password scheme called ObPwd. ObPwd enables users to select a password generating object from their local collection or from the web, and then converts the password object (e.g. an image, a particular piece of music, excerpt from a book) to a (potentially) high-entropy text password that can be used for regular or secondary web authentication, or in local applications (e.g. encryption). Instead of requiring users to memorize an exact password, ObPwd only requires one to remember a hint or pointer to the password object used. We believe that choosing digital objects as passwords is an interesting alternative to explore, and may enable users to create and maintain high quality passwords. We have implemented a prototype, and solicit feed-back from the research community in regard to using digital objects as passwords.
miRNAMap 2.0: genomic maps of microRNAs in metazoan genomes

MicroRNAs (miRNAs) are small non-coding RNA molecules that can negatively regulate gene expression and thus control numerous cellular mechanisms. This work develops a resource, miRNAMap 2.0, for collecting experimentally verified microRNAs and experimentally verified miRNA target genes in human, mouse, rat and other metazoan genomes. Three computational tools, miRanda, RNAhybrid and TargetScan, were employed to identify miRNA targets in 3′-UTR of genes as well as the known miRNA targets. Various criteria for filtering the putative miRNA targets are applied to reduce the false positive prediction rate of miRNA target sites. Additionally, miRNA expression profiles can provide valuable clues on the characteristics of miRNAs, including tissue specificity and differential expression in cancer/normal cell. Therefore, quantitative polymerase chain reaction experiments were performed to monitor the expression profiles of 224 human miRNAs in 18 major normal tissues in human. The negative correlation between the miRNA expression profile and the expression profiles of its target genes typically helps to elucidate the regulatory functions of the miRNA. The interface is also redesigned and enhanced. The miRNAMap 2.0 is now available at http://miRNAMap.mbc. nctu.edu. tw/.
The Determination of Soil Boron Fractions, Their Relationships to Soil Properties and the Availability to Olive (Olea europea L.) Trees

ABSTRACT This study was conducted to investigate the various boron fractions in olive tree grown soils. The correlations between boron fractions in leaves, fruits and soil properties were examined. For this purpose cv “Gemlik” olive (Olea europaea L.) orchards were visited. Soil samples from 0–30 cm and 30–60 cm deep, the leaf and fruit samples were collected. The greatest proportion of total soil boron is present in residual form (85–88%). It is followed by organically bound B (2.84–4.50%), specifically adsorbed on soil colloid surfaces (0.93–1.31%), oxides (manganese oxyhydroxides, amorphous Fe and Al oxides, crystalline Fe and Al oxides) bound B (7.27–8.31%). The smallest one readily soluble (extracting plant available) boron values were composed of only 0.40–0.50% of total boron ranging. To determine readily soluble boron five different extraction solutions were in the order Hot water ˃ 0.01 M CaCl2 ˃ 1 M NH4OAc ˃ 0.1 M KCl ˃ 0.005 M DTPA. Fruit boron concentration and soil boron fractions showed close correlations than leaf boron concentration.
Two-degree-of-freedom proportional integral control of inverse response second-order processes

The aim of this paper is to present a robust tuning method for two-degree-of-freedom (2DoF) proportional integral (PI) controllers for inverse response controlled processes modeled by a second-order plus a right-half plane zero (SOPRHPZ) transfer function. This is based on the use of a servo and regulatory control closed-loop model reference optimization procedure. The robustness of the control system is analyzed for model right-half plane zero relative positions in the range from 0.1 to 4.0. It is found that the non-minimum phase zero position affects the achievable control system robustness level. Controller tuning equations that guarantee the design robustness level are provided for inverse response second-order models with right-half plane zero relative positions in ranges that depend of the target robustness level. The designer is allowed to deal with the performance/robustness trade-off of the closed-loop control system by specifying the desired robustness level through selecting the desired maximum sensitivity in the range from 1.4 to 2.0. In addition, a smooth servo/regulatory performance combination is obtained by forcing both closed-loop transfer functions to perform as closely as possible to non-oscillatory dynamic targets. Comparative examples show the effectiveness of the proposed robust tuning method and its exact achievement of the control system robustness target for the inverse response controlled process models considered.
Off‐target immune cell toxicity caused by AG‐012986, a pan‐CDK inhibitor, is associated with inhibition of p38 MAPK phosphorylation

AG‐012986 is a pan‐CDK (cyclin‐dependent kinase) inhibitor that has in vitro and in vivo antitumor properties but was stopped in development due in part to rapid bone‐marrow‐independent white blood cell toxicity in preclinical studies and the potential for acute and delayed immunosuppression in humans. Because peripheral lymphocytes are largely nonproliferating, it was hypothesized the toxicity of AG‐012986 was due to an off‐target mechanism and not driven by the intended pharmacology. We show the toxicity mechanism in primary human immune cells is caspase driven. T‐cells treated with AG‐012986 and acutely stimulated through the T‐cell receptor exhibited decreased toxicity while still maintaining cell division inhibition. This indicated that the pharmacology of AG‐012986 functioned as expected but the toxicity had now been decoupled through activation. Induced phosphorylation of p38 and IL‐2 production was impaired with AG‐012986. Thus, AG‐012986 could cause apoptosis of T‐cells by targeting upstream kinases in the p38 Mitogen‐activated protein kinase (MAPK) pathway and impairing cellular survival. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:101–108 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20415
Somatoform disorders in general practice

Background General practitioners play a pivotal part in the recognition and treatment of psychiatric disorders. Identifying somatoform disorders is important for the choice of treatment. Aims To quantify the prevalence of, and functional impairment associated with, somatoform disorders, and their comorbidity with anxiety/depressive disorders. Method Two-stage prevalence study: a set of questionnaires was completed by 1046 consecutive patients of general practitioners (aged 25–80 years), followed by a standardised diagnostic interview (SCAN 2.1). Results The prevalence of somatoform disorders was 16.1% (95% CI 12.8-19.4). When disorders with only mild impairment were included, the prevalence increased to 21.9%. Comorbidity of somatoform disorders and anxiety/depressive disorders was 3.3 times more likely than expected by chance. In patients with comorbid disorders, physical symptoms, depressive symptoms and functional limitations were additive. Conclusions Our findings underline the importance of a comprehensive diagnostic approach to psychiatric disorders in general practice.
Placental Cytokines and the Pathogenesis of Preeclampsia

The authors explore the hypothesis that tumor necrosis factor‐α (TNF‐α) and possibly other inflammatory cytokines are overproduced by the placenta in response to local ischemia/hypoxia contributing to increased plasma levels, and subsequent endothelial activation and dysfunction in the pregnancy disorder, preeclampsia. It is widely held that inadequate trophoblast invasion and physiologic remodeling of spiral arteries initiate placental ischemia/hypoxia in preeclampsia. Furthermore, focal areas of placental hypoxia have been implicated in the production of “toxic” factor(s) by the placenta, which circulate and cause maternal disease. Placental trophoblast cells and fetoplacental macrophages normally produce TNF‐α and in‐terleukin‐1 (IL‐1), which are capable of producing endothelial cell activation and dysfunction. Hypoxia has recently been reported to increase TNF‐α and IL‐1 production by term villous explants from the human placenta. Placental cells also express erythropoietin (EPO), which is the prototype molecule for transcriptional regulation by hypoxia in mammals. Interestingly, TNF‐α and IL‐1 have DNA sequences homologous or nearly homologous to the hypoxia‐responsive enhancer element of the EPO gene, thus providing a potential, but as of yet, untested molecular link between placental hypoxia and stimulation of cytokine production. Inflammatory cytokines overproduced by the placenta in response to hypoxia may then lead to increased plasma levels and endothelial activation and dysfunction in preeclampsia. The purpose of this short review is to critically evaluate the hypothesis that placental cytokines contribute to the pathogenesis of preeclampsia. Of note, the etiology of the disease presumably related to deficient trophoblast invasion is beyond the scope of this work.
The impact of season, parity and breed on selected reproductive performance parameters of sows

Abstract. The aim of the study was to identify the detailed impact of the season, parity and breed on reproductive performance of sows. The experimental material consisted of 2100 sows, in 3 breed variants: 700 PL, 700 PLW, 700 crossbreeds PL × PLW. Sows were observed until parity 5. In the context of the breed, depending on the order of parity groups of 140 sows were isolated. Then, sows were divided in terms of farrowing season into subgroups numbering 35 sows. At the age of 8 months gilts were allocated for reproduction performance. The highest seasonal impact was noted for piglet birth weight (P≤0.01). Parity had less effect only on the number of piglets weaned (P≤0.05). Breed influenced to a lesser extent the number of piglets born live and weaned (P≤0.05), while birth and weaning weight had greater importance for piglets (P≤0.01). The interaction between the studied factors was also observed. The impact of season, parity and breed interdependence on the number of piglets born live were confirmed statistically (P≤0.05). The analysis of piglet birth weight allowed the stronger interaction effect of parity × breed on this parameter to be noted (P≤0.01). The analysis of variance for piglet weaning weight confirmed strong relations between all tested factors (P≤0.01). Our study has shown that reproductive parameters can be strongly affected by season and parity. In addition, it must be emphasized that the impact of these factors was different for the studied breeds of sows.
HER2/neu, Topoisomerase 2a, Estrogen and Progesterone Receptors: Discordance between Primary Breast Cancer and Metastatic Axillary Lymph Node in Expression and Amplification Characteristics

Molecular classification of breast cancer (BC) and the evaluation of new biological markers such as estrogen receptor (ER), progesterone receptor (PR), ErbB2 (HER2) and topoisomerase 2a (Topo2a) status are claimed to be important parameters in the management of BC therapy. In case of heterogeneity between primary BC and metastatic site, this implies profound limitations of efficient systemic therapy. Therefore, it is essential to analyze whether biological markers of BC relate to identical expression profiles of metastatic lymph nodes (mLNs). We used paraffin-embedded tumor tissue from 119 patients with at least 1 mLN. Immunohistochemistry (IHC) was used to analyze ER, PR, HER2 and Topo2a. In addition, HER2 and Topo2a amplification was evaluated by fluorescence/chromogenic in situ hybridization (FISH/CISH) in all samples with a HER2 score of 2+/3+ by IHC. Overall, the percentage of discordant marker status in the BC and its mLN was 2.6% for ER, 3.5% for PR, 3.4% for HER2, and 3.4% for Topo2a. With FISH/CISH, the amplification rate for Topo2a and HER2 was concordant in all cases. Because there are no prospective studies, it remains unclear whether these discrepancies have an effect on patient survival.
Pharmacological Aspects and Potential New Clinical Applications of Ketamine: Reevaluation of an Old Drug

Ketamine, the phencyclidine derivative described in 1965, is an intravenous anesthetic with a variety of applications. The enthusiasm following its initial release subsided due to side effects from the central nervous system. New anesthetics limited the role of ketamine in anesthetic practice. However, its hemodynamically stable profile, along with its beneficial respiratory properties and analgesic potency, rendered the drug invaluable in battlefield medicine, sedation of the uncooperative child, analgesia, and sedation in burn units. Reevaluation, though, of analgesic properties of ketamine resulted in new interest regarding its use in perioperative and chronic pain management. Moreover, recent studies in the effects of the substance on intracranial pressure and cerebral blood flow led to revising the recommendation against its use in brain injury. Furthermore, the bronchodilating effects of the substance led to increasing interest for potential use in asthma treatment. In addition, separation of the 2 enantiomers and subsequent separate studies indicated beneficial results of the S(+) one. Thus, new controlled multicentered clinical trials are to be conducted to justify approval for new uses of ketamine and take advantage of its unique range of applications.
Metformin and The United Kingdom

The United Kingdom Prospective Diabetes Study (UKPDS) was the largest and longest trial ever conducted into diabetes mellitus. This landmark study was set up in 1977, recruited 5,012 patients with type 2 diabetes mellitus (DM) from 23 centres in the UK, and finished at the end of 1997, with the initial final results published in two papers in the Lancet and in a further three papers in the British Medical Journal in September 1998 (1-5), at the same time as the results were first presented publically at the European Association for the Study of Diabetes (EASD) meeting in Barcelona. The study was co-ordinated by the late Professor Robert Turner and his colleagues in Oxford, UK.
Numerically robust least-squares lattice-ladder algorithms with direct updating of the reflection coefficients

New time-recursive equations are derived for the reflection coefficients and the ladder gains in the a priori and a posteriori forms of the exact least-squares (LS) lattice-ladder filtering algorithms. The numerical accuracy of the LS lattice-ladder algorithms obtained by use of these new direct time update equations is analyzed and compared to the accuracy resulting from the conventional LS lattice-ladder algorithms. The analysis and a number of simulation results which are presented lead us to conclude that the new a priori and a posteriori forms of the LS lattice-ladder algorithms yield superior performance.
Discovery of Swine as a Host for the Reston ebolavirus

Not Reston at All Reston ebolavirus is named, mistakenly perhaps, for Reston, Virginia, where it was discovered in the 1970s in imported macaques. After some alarm it was found not to be virulent in humans, uniquely among the ebola viruses, which are characteristically fatal causing a horrific spectrum of symptoms. Using a panviral detection assay, Reston ebolavirus has been rediscovered by Barrette et al. (p. 204) in domesticated pigs in the Philippines in association with other viruses that cause respiratory illness. The strains involved are closely related to the original macaque strain and, given how little variance there is among the viruses, it appears that it is freely circulating between these species possibly, like several other zoonotic viruses, having a reservoir in bats. Serological assays indicated that farm workers have become infected, although no obvious symptoms of human disease have been reported. Respiratory infections in pigs in the Philippines are associated with a cocktail of viruses, including a monkeys filovirus. Since the discovery of the Marburg and Ebola species of filovirus, seemingly random, sporadic fatal outbreaks of disease in humans and nonhuman primates have given impetus to identification of host tropisms and potential reservoirs. Domestic swine in the Philippines, experiencing unusually severe outbreaks of porcine reproductive and respiratory disease syndrome, have now been discovered to host Reston ebolavirus (REBOV). Although REBOV is the only member of Filoviridae that has not been associated with disease in humans, its emergence in the human food chain is of concern. REBOV isolates were found to be more divergent from each other than from the original virus isolated in 1989, indicating polyphyletic origins and that REBOV has been circulating since, and possibly before, the initial discovery of REBOV in monkeys.
Resolving the role of jellyfish in marine food webs

Jellyfish populations in the Irish Sea have been increasing. This has caused a variety of economic problems, such as the destruction of aquaculture installations, and new opportunities, such as the establishment of a jellyfish fishery. However, interactions between jellyfish and other biota in the ecosystem is poorly characterised and ecological consequences of an increasing jellyfish population remains unknown. Molecular gut content analysis methodologies were developed to address this data gap. Cnidarian specific primers were developed and showed using more than 2500 stomachs that, during February and March, moon and mauve-stinger jellyfish were consumed by common fish species including herring, whiting, and lesser-spotted dogfish. Revisiting the ecosystem in October with 375 additional samples, the primers indicated jellyfish predation varied temporally: small jellyfish were still targeted by mackerel, however moon jellyfish adults were not preyed upon. To understand the context in which jellyfish consumption occurred a high throughput sequencing (HTS) approach using two universal primers was developed. A meta-analysis of HTS studies suggested results contained a quantitative signal, and the methodology could be used to move beyond a presence/absence approach. Using 188 samples from nine fish species, it was shown that jellyfish were consumed as part of a generalised diet during summer months. Finally, the approaches used to model jellyfish in the ecosystem model Ecopath with Ecosim (EwE) were reviewed. Jellyfish were included more frequently over time, however approaches remained relatively crude in the absence of high quality data in many ecosystems. Together, these approaches have gone some way towards addressing the data gap: jellyfish interactions with other biota have been recorded, and new approaches for studying these interactions have been developed. This has established a baseline for novel research opportunities such as mechanistic modelling of jellyfish, exploration of quantitative HTS approaches, and the generation of dietary time-series data to be conducted.