Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of human miRNAs using tissue-selective motifs in 3′ UTRs

MicroRNAs (miRNAs) play an important role in posttranscriptional regulation of genes. We developed a method to predict human miRNAs without requiring cross-species conservation. We first identified lowly/moderately expressed tissue-selective genes using EST data and then identified overrepresented motifs of seven nucleotides in the 3′ UTRs of these genes. Using these motifs as potential target sites of miRNAs, we recovered more than two-thirds of the known human miRNAs. We then used those motifs that did not match any known human miRNA seed region to infer novel miRNAs. We predicted 36 new human miRNA genes with 44 mature forms and 4 novel alternative mature forms of 2 known miRNA genes when a stringent criterion was used and many more novel miRNAs when a less stringent criterion was used. We tested the expression of 11 predicted miRNAs in three human cell lines and found 5 of them expressed in all three cell lines and 1 expressed in one cell line. We selected 2 of them, P-2 and P-27–5p, to do functional validation, using their mimics and inhibitors and using both luciferase assay and Western blotting. These experiments provided strong evidence that both P-2 and P-27–5p are novel miRNAs and that CREB3L3, which encodes cAMP-responsive element binding protein 3-like 3, is a target gene of P-2, whereas LAMB3, which encodes laminin β3, is a target gene of P-27–5p.
Morbid obesity is not an independent predictor of graft failure or patient mortality after kidney transplantation.

OBJECTIVE Obesity is often an absolute contraindication to kidney transplant, but an internal analysis of our center's recipients suggests that not all obese populations exhibit poor outcomes. We used national data to compare outcomes in select groups of morbidly obese and normal-weight recipients after kidney transplant. DESIGN This study was a retrospective analysis of the Organ Procurement and Transplant Network/United Network for Organ Sharing database. SUBJECTS The study sample consisted of 30,132 morbidly obese (body mass index [BMI] 35-40 kg/m(2)) and normal-weight (BMI 18.5-24.9 kg/m(2)) patients who underwent primary kidney-only transplantation between 2001 and 2006. MAIN OUTCOME MEASURE Crude 3-year graft and patient survival rates of morbidly obese and normal-weight subgroups were evaluated. Logistic regression modeling compared 3-year graft failure and patient mortality in morbidly obese and normal-weight subgroups with opposite characteristics. Kaplan-Meier survival curves were created for 3-year graft and patient survival. Cox proportional hazard regression modeling was used to determine hazards for patient and graft mortality. RESULTS No differences in crude graft and patient survival rates were seen between normal weight and morbidly obese recipients who were African American, diabetic, and 50 to 80 years of age. Morbidly obese recipients who were nondialysis dependent, nondiabetic, had good functional status, and received living-donor transplants had significantly lower 3-year graft failure and patient mortality risk compared with normal-weight recipients who were dialysis dependent, diabetic, had poor functional status, and received a deceased-donor transplant, respectively (P < .01). Morbidly obese recipients have significantly lower graft and patient survival curves compared with normal-weight recipients; however, multivariate regression analysis reveals that morbid obesity is not an independent predictor of graft failure or patient mortality. CONCLUSIONS Morbid obesity is not independently associated with graft failure or patient mortality; therefore, it should not be used as a contraindication to kidney transplantation.
‘She was there if I needed to talk or to try and get my point across’: specialist advocacy for parents with intellectual disability in the Australian child protection system

ABSTRACT Parents with intellectual disability are overrepresented in child protection matters due to a combination of socioeconomic disadvantage and assumptions of parenting incapacity by child welfare workers and courts. Inability to understand the investigation process or instruct a solicitor can deny these parents equal access to justice. Specialist support can ensure parents exercise their legal capacity to participate in proceedings and have their views heard. Semi-structured interviews were undertaken with parents with intellectual disability (n = 10) who accessed a specialist advocacy programme in New South Wales, Australia. Thematic analysis was used to identify the influence of advocacy on parents’ experiences. Parents felt powerlessness as they navigated a bewildering child protection and court system that had prejudged them unfit to parent. This compounded the grief and loss of child removal. The advocate played a critical role in creating a bridge between parents and professionals. This helped to build parents’ skills and confidence and improve the disability awareness of professionals. Specialist advocacy for all parents with intellectual disability in care proceedings is consistent with Australia’s obligations under the Convention on the Rights of Persons with Disabilities.
Games of Two Halves: Non- Experimental Evidence on Cooperation, Defection and the Prisoner's Dilemma

We develop a stylized two-period game-theoretic model of the strategic choices made by soccer teams when selecting between defensive and attacking team formations, and between non-violent and violent styles of play. Cooperative behaviour during the early stages of matches is typically superseded by non-cooperation during the latter stages. The propensity for violent play to take place in the latter stages of soccer matches is interpreted as novel non-experimental evidence that players typically resort to mutually detrimental non-cooperative forms of behaviour when the payoffs assume a prisoner’s dilemma structure.
Pieter Cullis’ quest for a lipid-based, fusogenic delivery system for nucleic acid therapeutics: success with siRNA so what about mRNA?

Abstract For the best part of 40 years, lipids and membrane fusion have been at the center of Pieter’s research. Projects range from the purely academic quest of understanding the roles of lipids in biological membranes, to the translation of this knowledge into the most advanced lipid nanoparticle (LNP) drug delivery systems in clinical trials to-date. Pieter’s pioneering work in lipid polymorphism and characterizing the unique properties of unsaturated phospatidyethanolamines (PE), together with the introduction of ionizable, dialkylamino lipids to trigger membrane fusion at acidic pH, provided the foundation on which a new generation of highly potent, well-tolerated LNPs for intravenous delivery of nucleic acid therapeutics has been built. In this contribution to the special edition honoring Pieter’s achievements we highlight key research conducted in Pieter’s laboratory and at several biotechnology companies, some spun out of his research group, which resulted in the development of a fusogenic delivery system for siRNA therapeutics. Patisiran®, an LNP encapsulating siRNA for hepatic gene silencing, is currently in Phase III clinical trials for treatment of Transthyretin amyloidosis as are several other siRNA products employing this delivery technology. Finally, we describe more recent work in which the platform shows real promise in the rapidly growing new field of mRNA therapeutics.
IL-6 Increases Primed Cell Expansion and Survival

Cytochrome c-specific CD4 T cells from transgenic donors transferred to syngeneic B10.A mice expand more vigorously upon immunization if exogenous IL-6 is provided during the initial phase of immunization. The resultant increase in the frequency and number of Ag-specific cells is observed in the blood, lymph nodes, spleen, liver, and lung and persists for at least 3 mo. Treatment of immunized recipients with anti-IL-6 or use of IL-6 knockout recipients reduced the frequency of Ag-specific CD4 T cells during a comparable period, indicating that IL-6 is physiologically involved in the expansion of memory and/or effector cells and thus in the persistence of memory. IL-6 did not alter the duration of Ag-presenting activity. Both CFSE dilution studies and labeling with BrdU indicated that IL-6 does not effect proliferative rates of responding CD4 T cells. By contrast, annexin V staining was diminished in responding cells from the IL-6-treated animals, particularly among those cells that had undergone five or more divisions. These results indicate that IL-6 reduces the level of apoptosis among Ag-stimulated cells; thus, it plays a central role in determining numbers of memory and/or effector CD4 T cells in response to immunization over extended periods.
Ascites syndrome in broilers: physiological and nutritional perspectives

Broiler chickens are intensively selected for productive traits. The management of these highly productive animals must be optimal to allow their full genetic potential to be expressed. If this is not done, inefficient production and several metabolic diseases such as ascites become apparent. The causes of the ascites are multifactorial but diet and, particularly, interactions between diet, other environmental and genetic factors play an important role. The relatively high heritability estimates for ascites-related traits and the significance of maternal genetic effects for most of the traits indicate that direct and maternal genetic effects play an important role in development of the ascites syndrome. An imbalance between oxygen supply and the oxygen required to sustain rapid growth rates and high food efficiencies causes ascites in broiler chickens. Because of the relationship to oxygen demand, ascites is affected and/or precipitated by factors such as growth rate, altitude (hypoxia) and environmental temperature. As the high metabolic rate (fast growth) is a major factor contributing to the susceptibility of broilers to ascites, early-age feed or nutrient restriction (qualitative or quantitative) or light restriction in order to slow down the growth rate seem practically viable methods, since final body weight is not compromised. Manipulation of the diet composition and/or feed allocation system can have a major effect on the incidence of ascites. Optimization of the house temperature and ventilation in cold weather seem helpful practices to decrease ascites incidence.
Volatility Aversion in the Options Market Based on News Sentiment

The perennial question of efficient markets is whether investors respond rationally to new information. If they “overreact” or “underreact” to a news release, is it a simple error or systematic bias? A major problem in testing this is the need to be clear on what “news” is and when investors learn it. This is especially hard because evaluating new information is inherently subjective and may have its largest impact on what is typically called investor sentiment. In this article, the author focuses on news about the macroeconomy, using textual analysis on news items carried by Thomson Reuters to explore the impact of positive and negative news on implied volatilities (IVs) from SPX options. What should move the market is a change in sentiment, which the author measures by the change in the incidence of positive and negative words in relevant news items. Coefficient estimates across moneyness and maturity are uniformly negative for positive sentiment (good news makes IVs go down) and positive for negative sentiment. Differences show up between puts and calls and across moneyness. Interestingly, the impact is significant in most cases for positive but not negative news. Short maturity out-of-the-money put IVs are particularly sensitive to positive macro information, while negative news affects both calls and puts at the money.
THE POLITENESS OF ASSERTIVE SPEECH ACTS: SYNERGIZING THE LINGUISTIC POLITENESS DEVICES IN CONFLICT RESOLUTION COMMUNICATION

This article studies the realisastion of politeness assertive speech act on the scholarly dialogue called Religious Freedom Project (RFP) at the Georgetown University, US. The primary data in this article is in the form of written data (document), which is the transcription of the RFP dialogues conversation. In addition to the supplementary data is the video record of the dialogues retrieved from Youtube. The assertive SA in this study refer to the utterances that bind S to the truth of something he/she expresses. The result shows that there were found the use of six types of assertive speech acts that go hand in hand to reflect the Leech's Politeness Principles, among others the acts of admitting, informing, assuring, arguing, affirming, and reporting. Based on the basis of finding data from 137 speech acts of assertive type, it is concluded that in RFP dialogue, the politeness markers were classified into eight types referring House & Kasper’s, i.e.; hedging, understaters, downtowners, committers (both enhancers and reducers of S’s self commitment), agent-avoiders, intensifiers, overstaters, and politeness markers. Politeness devices or markers reflect a great deal and effect on the production of utterances force in the RFP, all of which were directed toward criticism.
Temperature‐dependent localization of GPI‐anchored intestinal alkaline phosphatase in model rafts

In plasma membranes, most of glycosylphosphatidylinositol (GPI)‐anchored proteins would be associated with rafts, a category of ordered microdomains enriched in sphingolipids and cholesterol (Ch). They would be also concentrated in the detergent resistant membranes (DRMs), a plasma membrane fraction extracted at low temperature. Preferential localization of GPI‐anchored proteins in these membrane domains is essentially governed by their high lipid order, as compared to their environment. Changes in the temperature are expected to modify the membrane lipid order, suggesting that they could affect the distribution of GPI‐anchored proteins between membrane domains. Validity of this hypothesis was examined by investigating the temperature‐dependent localization of the GPI‐anchored bovine intestinal alkaline phophatase (BIAP) into model raft made of palmitoyloleoylphosphatidylcholine/sphingomyelin/cholesterol (POPC/SM/Chl) supported membranes. Atomic force microscopy (AFM) shows that the inserted BIAP is localized in the SM/Chl enriched ordered domains at low temperature. Above 30°C, BIAP redistributes and is present in both the ‘fluid’ POPC enriched and the ordered SM/Chl domains. These data strongly suggest that in cells the composition of plasma membrane domains at low temperature differs from that at physiological temperature. Copyright © 2007 John Wiley & Sons, Ltd.
The Association Between Fetal Sex and Preterm Birth in Twin Pregnancies

OBJECTIVE: To assess the association between the fetal sex and preterm birth. METHODS: We performed a retrospective population-based cohort study using the 1995–1997 registration twin data in the United States (148,234 live-birth twin pairs). The twin pairs were divided into 3 groups: male-male (male-male), female-female, and opposite sex. We used 3 different cutoff values of preterm birth: less than 28, 32, and 36 gestational weeks. The preterm birth rates among the 3 study groups were compared, and the adjusted risk ratios (relative risk) were estimated by multiple logistic regression. RESULTS: The male-male twin pairs had the highest preterm birth rate (less than 28 weeks: 4.9%; less than 32 weeks: 12.4%; less than 36 weeks: 40.2%), the female-female twin pairs were intermediate (less than 28 weeks: 4.1%; less than 32 weeks: 10.6%; less than 36 weeks: 37.8%), and the opposite-sex twin pairs had the lowest rate (less than 28 weeks: 4.1%; less than 32 weeks: 10.1%; less than 36 weeks: 36.8%). Adjustment for important confounding factors or excluding twin pairs born to mothers who had an induction of labor or a cesarean delivery with medical complications did not change the results. The adjusted relative risks (95% confidence intervals) were 1.19 (1.11, 1.27), 1.21 (1.16, 1.26), and 1.09 (1.07, 1.11), respectively, for male-male twins compared with the opposite-sex twins under the 3 different cutoff values of preterm births. CONCLUSION: Male sex is associated with increased risk of preterm births in twin pregnancy. LEVEL OF EVIDENCE: II-2
Monetary Policy Under Uncertainty: Practice Versus Theory

For central banks, conducting policy in an environment of uncertainty is a daily fact of life. This uncertainty can take many forms, ranging from incomplete knowledge of the correct economic model and data to future economic and geopolitical events whose precise magnitudes and effects cannot be known with certainty. The objective of this paper is to summarize and compare the main results that have emerged in the literature on optimal monetary policy under uncertainty with actual central bank behaviour. To this end, three examples are studied in which uncertainty played a significant role in the Bank of Canada’s policy decision, to see how closely they align with the predictions from the literature. Three principles emerge from this analysis. First, some circumstances—such as when the policy rate is at risk of being constrained by the effective lower bound—should lead the central bank to be more pre-emptive in moving interest rates, whereas others can rationalize more of a wait-and-see approach. In the latter case, the key challenge is finding the right balance between waiting for additional information and not falling behind the curve. Second, the starting-point level of inflation can matter for how accommodative or restrictive policy is relative to the same situation without uncertainty, if there are thresholds in the central bank’s preferences associated with specific ranges for the target variable, such as the risk of inflation falling outside of the inflation control range. Third, policy decisions should be disciplined, where possible, by formal modelling and simulation exercises in order to support robustness and consistency in decision making over time. The paper concludes with a set of suggested areas for future research.
Studies of Host‐Plasmid Interactions in Recombinant Microorganisms a

Plasmid genes redirect some components of cellular metabolism into synthesis of plasmid gene products and additional plasmids. The stoichiometric and kinetic implications of these host-plasmid interactions have been investigated theoretically and experimentally. Using known pathway energetics, maximum theoretical yield factors based on ATP, glucose, and O2 have been estimated for recombinant Escherichia coli and compared with corresponding estimates for host cells alone, indicating major changes in carbon and energetic stoichiometry in recombinant cells in cases of high cloned gene expression. The influence of the number of plasmids in recombinant E. coli has been experimentally characterized using a series of pMB1 derivatives stably propagated at copy numbers from 12 to 408. Recombinant cell growth rate declines monotonically as plasmid content increases as does efficiency of plasmid gene expression. A detailed metabolically structured single-cell model for E. coli has successfully simulated these trends. Interrelationships among number of plasmids per cell, induction of expression of a plasmid gene, and recombinant population growth rate have been experimentally delineated for Saccharomyces cerevisiae containing plasmid pLGSD5 and derivatives in which the 2-micron origin of replication has been replaced by a cloned ARS1 sequence or its deletion fragments. The CEN4 centromere sequence has been included in some of these plasmids to provide more regular segregation. Specific growth rate of these recombinant yeasts exhibits a maximum as a function of plasmid content, an effect attributed to the interplay between beneficial effects of the plasmid in selective medium and parasitic effects on metabolism at larger plasmid content or with more plasmid gene expression activity. The yeast strains investigated exhibit substantial segregational instability that was characterized using a rapid-flow cytometry measurement based upon single-cell deletion of E. coli beta-galactosidase activity in recombinant cells.
Until the last breath: exploring the concept of hope for parents and health care professionals during a child's serious illness.

OBJECTIVE To investigate the concept of hope for families and pediatric health care professionals during a child's serious illness. DESIGN Eight focus groups. SETTING Academic pediatric medical center. PARTICIPANTS Bereaved parents, pediatricians, pediatric residents, and nurses (N = 39). Intervention Participants were asked standardized questions related to their definition of hope, its role in medical decisions, and the benefits and detriments of hope in focus group sessions. MAIN OUTCOME MEASURES We identified attributes of participants' concepts of hope using qualitative analysis of audio-taped sessions. RESULTS While all participants identified common elements in their definition of hope, parents identified their role as bearers of hope; it was a cornerstone of decision making. Health care professionals tended to view hope as related to a positive outcome. Some physicians reported difficulty in maintaining hope in the face of prognostic data; others acknowledged the importance of the family's hope. Nurses identified particular challenges around parents' decisions to continue treatment when it prolonged the child's suffering. All participants noted the changing nature of hope and its implications for care. CONCLUSIONS The tension between maintaining hope and accepting the reality of the prognosis may lessen when acknowledging that parents see their role as bearers of hope. Supporting families around the changing nature of hope may allow health care professionals to partner with parents while maintaining honest communication.
Novel Algorithms for Efficient Design and Operation of Multi-SIM UE in 5G and Beyond

Multi Subscriber Identity Modules (SIMs) in user equipment (UE) is designed using System on Chip (SoC) and Radio Frequency Integrated Circuit (RFIC) with more than one Receive (Rx) and Transmit (Tx) paths to communicate with the multiple network operators at the same time by a UE. Generally, Rx and Tx paths in a UE is less than number of SIMs to reduce the area of SoC, cost, and power consumption. Hence, SIMs connected to different operators share Rx or Tx paths to receive or transmit data. The above sharing of Rx or Tx paths between SIMs leads to wastage of Physical Channel Resource (PCR) allocated by Operator-l to SIM-l, due to tune away of Rx or Tx path to SIM-2 of Operator-2. The PCR wastage degrades the performance of the network as well as of the UE. Thus, the choice of the number of Rx and Tx paths becomes a complex design challenge for meeting the power, performance, area, and cost (PP AC), not solved optimally in the available literature. We present a novel algorithm (DesignAlgo) for the optimal choice of the number of Rx and Tx paths for a multi-SIM UE in the 5G network. In addition to above, we also propose a new algorithm (OperateAlgo) for scenario-specific dynamic power optimization by selectively enabling required Rx and Tx paths. Through extensive simulations derived from mathematical modeling, the results reveal that the proposed algorithms can save up to 22 % area/cost in the SoC and RFIC component and over 33% in dynamic power consumption, over available literature, while meeting the performance targets for the PCR wastage.