Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of the androgen‐sensitive MDA‐kb2 cell line for assessing complex environmental mixtures

Synthetic and natural steroidal androgens and estrogens and many other non‐steroidal endocrine‐active compounds commonly occur as complex mixtures in aquatic environments. It is important to understand the potential interactive effects of these mixtures to properly assess their risk. Estrogen receptor agonists exhibit additivity in mixtures when tested in vivo and in vitro. Little is known, however, concerning possible mixture interactions of androgen receptor agonists. In these studies we used the MDA‐kb2 cell line, a human breast cancer cell line with endogenous androgen receptors and a stably transfected luciferase reporter gene construct to quantify the androgenic activity of seven natural and synthetic androgens: 17β‐trenbolone, dihydrotestosterone, methyltestosterone, testosterone, trendione, 17α‐trenbolone, and androstenedione. We tested combinations of these androgens and compared the observed activity to expected androgenic activity based on a concentration addition model. Our analyses support the hypothesis that androgen receptor agonists cause additive responses in a mixture. Binary mixtures of 17β‐trenbolone with 17β‐estradiol or triclocarban (an anti‐microbial found in the environment) were also tested. 17β‐Estradiol induced androgenic activity, but only at concentrations 600‐fold greater than those found in the environment. Triclocarban enhanced the activity of 17β‐trenbolone. Additionally, three anti‐androgens were each paired with three androgens of varying potencies. The relative potencies of the antagonists were a vinclozolin metabolite (M2) > procymidone > prochloraz regardless of the androgen used. The results of our studies demonstrate the potential utility of the androgen‐responsive MDA‐kb2 cell line for quantifying the activity of mixtures of endocrine‐active chemicals in complex wastes such as municipal effluents and feedlot discharges. Environ. Toxicol. Chem. 2010;29:1367–1376. © 2010 SETAC
The Lifestyle Behaviour Checklist: a measure of weight-related problem behaviour in obese children.

OBJECTIVE Parents are often targeted for childhood obesity interventions and parent training is regarded as an integral component of family-based treatments for obesity. However, few studies have examined what challenges parents of obese children face managing their children's behaviour, and how these challenges might be addressed in treatment. To address this gap in knowledge, we describe the development and evaluation of a new measure, the Lifestyle Behaviour Checklist (LBC). METHODS The LBC lists 26 concerns parents might have about children's eating behaviour, activity, and other weight-related behaviours; and includes a Problem scale (extent of problems) and Confidence scale (parents' confidence in dealing with these problems). This study explored the psychometric properties of the LBC in a sample of 182 parents of healthy weight, overweight, or obese 4 to 11-year-old children. A comparison is given for families with healthy weight children and families with obese children. RESULTS The new measure successfully differentiated families with and without obese children, correctly classifying 91.1% of participants. Parents of healthy weight children reported lower levels of lifestyle behaviour problems (d=2.40) and higher levels of parenting self-efficacy (d=1.96) than parents of obese children. The LBC scales had high internal consistency and moderate test-retest stability (12 weeks). CONCLUSION The lifestyle behaviour construct appears a useful way to conceptualise parenting challenges faced by parents of obese children, and the LBC a valid and reliable instrument. Routine administration of the LBC in childhood obesity research may assist in the development of more effective management approaches.
A New Type of Cytokine Receptor Antagonist Directly Targeting gp130*

The interleukin-6-type family of cytokines bind to receptor complexes that share gp130 as a common signal-transducing subunit. So far, receptor antagonists for interleukin-6-type cytokines have been constructed that still bind to the specific ligand binding subunit of the receptor complex, but have lost the ability to stimulate gp130. Such receptor antagonists compete for a specific receptor of a member of the cytokine family. Interleukin-6 only binds to gp130 when complexed with the interleukin-6 receptor that exists as a membrane bound and soluble molecule. Here we have constructed fusion proteins that consist of the soluble form of the human interleukin-6 receptor covalently linked to interleukin-6 receptor antagonists. These fusion proteins directly bind to gp130. Moreover, at concentrations of 10–50 nm they completely neutralize not only the biological activity of interleukin-6 but also of other cytokines of the interleukin-6-type family that act via gp130 homodimers or gp130/LIF-R heterodimers. Therefore, these gp130 targeting cytokine antagonists might be useful therapeutic tools in disease states that are related to cytokines of the interleukin-6 family.
Involvement of a neutral glycolipid in differential cell adhesion in the Xenopus blastula.

Many different molecular species mediate cell adhesion during embryonic development. These can have either protein or carbohydrate functional groups, which can act in either a homophilic or a heterophilic manner, and often in concert. We report here that a monoclonal antibody, M4B, raised against Xenopus blastomere membranes, inhibits the calcium‐dependent adhesion of dissociated blastomeres. M4B maintains its inhibitory effect on adhesion when converted into univalent fragments, and specifically affects calcium‐dependent adhesion. The antigen is regulated in both space and time during early development. It is found on cell surfaces throughout the egg to blastula stages, but is more concentrated on cells in the animal and marginal zones of the blastula. It is dramatically downregulated during gastrulation, and becomes largely restricted to gut epithelium by the larval stages. We show also that M4B function is spatially differentiated at the blastula stage, since it inhibits the aggregation of dissociated animal cells to a greater extent than vegetal cells. This membrane antigen may therefore play a role in the differential adhesion observed between different regions of the blastula, and which we presume to underlie the segregation of the primary germ layers during gastrulation. M4B recognizes a complex of plasma membrane glycolipids. Periodate treatment destroys the ability of these glycolipids to react with the antibody, indicating that the epitope resides in the carbohydrate moiety of the glycolipids. Chemical characterization shows that it is a neutral glycolipid, and that the major component is of the glycoglycerolipid, rather than the more common glycosphingolipid class. Blocking experiments with oligosaccharides of defined structure, and antibody crossreactivity show that the M4B antibody does not recognize several known embryonic carbohydrate antigens. These results demonstrate that M4B antibody recognizes a novel group of developmentally regulated glycolipids which function in calcium‐dependent cell‐‐cell adhesion in the Xenopus blastula.
Phase II Study of Biweekly Paclitaxel Plus Infusional 5-Fluorouracil and Leucovorin as First-Line Chemotherapy in Patients With Advanced Gastric Cancer

Purpose:This study was conducted to evaluate the efficacy and safety of combination chemotherapy with biweekly paclitaxel plus infusional 5-fluorouracil (5-FU) and leucovorin as first-line treatment for patients with advanced gastric cancer. Methods:Eligible patients with histologically confirmed advanced or metastatic gastric cancer were enrolled. The chemotherapeutic regimen consisted of paclitaxel (100 mg/m2 on day 1) as a 3-hour intravenous infusion, followed sequentially by leucovorin (400 mg/m2 on day 1) as a 2-hour intravenous infusion, bolus 5-FU (400 mg/m2 on day 1), and then continuous infusion 5-FU (3000 mg/m2 on day 1) over 46 hours. Cycles were repeated every 2 weeks. Results:Sixty patients were enrolled (median age, 52.5 years old). Of these, 65% patients had Eastern Cooperative Oncology Group performance status of grade 2. A median of 8 cycles was administered (range, 4–12). Fifty-five patients were evaluable for response. Two patients achieved a complete response and 28 patients achieved a partial response, producing an overall response rate of 50% by intent-to-treat analysis. The median duration of response was 6.4 months (95% CI, 5.14–7.60 months). Median progression-free survival and median overall survival were 7.7 months (95% CI, 6.5–8.9 months) and 14.3 months (95% CI, 9.4–19.1 months), respectively. Hematologic toxicity was mild; grade 3 neutropenia was noted in only 6.7% of patients. Alopecia was the most common nonhematologic toxicity in 51 patients (71.4%). Grade 3 alopecia occurred in 11 patients (18.3%). Conclusion:Combination chemotherapy of biweekly paclitaxel followed sequentially by infusion leucovorin, bolus 5-FU, and continuous infusion 5-FU over 46 hours is effective and well tolerated in patients with advanced gastric cancer, especially in patients with poor performance status who cannot tolerate aggressive chemotherapy regimens.
Spaceflight‐induced enhancement of 2‐keto‐L‐gulonic acid production by a mixed culture of Ketogulonigenium vulgare and Bacillus thuringiensis

Two bacterial strains used for industrial production of 2‐keto‐L‐gulonic acid (2‐KLG), Ketogulonigenium vulgare 2 and Bacillus thuringiensis 1514, were loaded onto the spacecraft Shenzhou VII and exposed to space conditions for 68 h in an attempt to increase their fermentation productivities of 2‐KLG. An optimal combination of mutants B. thuringiensis 320 and K. vulgare 2194 (KB2194‐320) was identified by systematically screening the pH and 2‐KLG production of 16 000 colonies. Compared with the coculture of parent strains, the conversion rate of L‐sorbose to 2‐KLG by KB2194‐320 in shake flask fermentation was increased significantly from 82·7% to 95·0%. Furthermore, a conversion rate of 94·5% and 2‐KLG productivity of 1·88 g l−1 h−1 were achieved with KB2194‐320 in industrial‐scale fermentation (260 m3 fermentor). An observed increase in cell number of K2194 (increased by 47·8%) during the exponential phase and decrease in 2‐KLG reductase activity (decreased by 46·0%) were assumed to explain the enhanced 2‐KLG production. The results suggested that the mutants KB2194‐320 could be ideal substitutes for the currently employed strains in the 2‐KLG fermentation process and demonstrated the feasibility of using spaceflight to breed high‐yielding 2‐KLG‐producing strains for vitamin C production.
Pseudorabies virus envelope glycoproteins gp50 and gII are essential for virus penetration, but only gII is involved in membrane fusion

To investigate the function of the envelope glycoproteins gp50 and gII of pseudorabies virus in the entry of the virus into cells, we used linker insertion mutagenesis to construct mutant viruses that are unable to express these proteins. In contrast to gD mutants of herpes simplex virus, gp50 mutants, isolated from complementing cells, were able to form plaques on noncomplementing cells. However, progeny virus released from these cells was noninfectious, although the virus was able to adsorb to cells. Thus, the virus requires gp50 to penetrate cells but does not require it in order to spread by cell fusion. This finding indicates that fusion of the virus envelope with the cell membrane is not identical to fusion of the cell membranes of infected and uninfected cells. In contrast to the gp50 mutants, the gII mutant was unable to produce plaques on noncomplementing cells. Examination by electron microscopy of cells infected by the gII mutant revealed that enveloped virus particles accumulated between the inner and outer nuclear membranes. Few noninfectious virus particles were released from the cell, and infected cells did not fuse with uninfected cells. These observations indicate that gII is involved in several membrane fusion events, such as (i) fusion of the viral envelope with the cell membrane during penetration, (ii) fusion of enveloped virus particles with the outer nuclear membrane during the release of nucleocapsids into the cytoplasm, and (iii) fusion of the cell membranes of infected and uninfected cells.
Challenging Historical Frameworks: Aboriginal Rights, The Trickster, and Originalism

Abstract:The Supreme Court of Canada has created a narrow framework for recognizing Aboriginal and treaty rights in Canada’s Constitution by reference to historic moments of contact, assertions of sovereignty, and negotiated agreements. This approach has placed historical inquiries that search for “original” understandings at the centre of the court’s jurisprudence. This article argues that law should not be equated with history in this way. It has severely disadvantaged Indigenous peoples. As a “living tree,” Canadian constitutional law should regard the “past” as a grab bag of possibilities for present reasoning, rather than as a constraint on present developments, because they do not have analogues in a bygone era. Résumé:La Cour suprême du Canada a créé un cadre étroit pour la reconnaissance des droits des Autochtones et des droits issus de traités dans la Constitution canadienne en s’appuyant sur les moments historiques de contact, les assertions de souveraineté et les ententes négociées. Cette façon de voir a placé les enquêtes historiques visant à trouver des accords « originels » au cœur de la jurisprudence de la Cour. Le présent article soutient que le droit ne devrait pas être assimilé à l’histoire de cette façon, car cette assimilation a gravement désavantagé les Autochtones. Le droit constitutionnel canadien est un « arbre vivant » et, à ce titre, il devrait envisager le « passé » comme un mélange hétéroclite de possibilités pouvant alimenter le raisonnement actuel, et non comme un carcan empêchant l’évolution actuelle des événements parce qu’ils n’ont pas d’équivalent dans une époque révolue.
Arm function after axillary dissection for breast cancer: A pilot study to provide parameter estimates

Sixty‐three women participated in a study in Calgary, Alberta to assess the rate of arm recovery and factors affecting it up to one year after axillary node dissection for breast cancer. Outcomes included objective measures of swelling, mobility, and strength, and subjective assessments of pain (at rest and with movement) and stiffness. Approximately 42% of women had residual impairment of at least one type one year after surgery, the most common problems being pain (16%) and reduced grip strength (16%). Except for lymphedema, measurements one year after surgery showed little change from measurements at 6 months, suggesting that the shorter follow‐up may be appropriate for assessing the long term effects of axillary dissection. Lymphedema was the only sequela which increased over time. The results provide parameter estimates for designing studies to evaluate the role of physiotherapy after axillary dissection. © 1992 Wiley‐Liss, inc.
Nandrolone abuse decreases anxiety and impairs memory in rats via central androgenic receptors.

Anabolic androgenic steroids (AASs) affect areas of the central nervous system, which are involved in emotional and cognitive responses such as sexuality, anxiety, and memory. In the present study we imitated the abuse of AASs by administering high doses of the AAS nandrolone decanoate (ND) to rats. Thereafter rats were exposed to an elevated plus-maze and an olfactory social memory test to evaluate their anxiety-like and cognitive behaviour. To reveal whether these emotional and cognitive changes evoked by ND were caused via direct activation of androgenic receptors (ARs) in the brain, the AR antagonist flutamide (FL) was administered intracerebroventricularly (i.c.v.). Male rats were randomly divided in four groups, one group received 15 mg/kg ND subcutaneously, once daily for 6 wk (ND group). In the second group, in addition to ND, a daily dose of 5 microg FL was injected i.c. v. also for 6 wk (ND+FL group). The third group of rats received only FL and in the control group the vehicle was injected. The ND group clearly spent more time investigating the open arms in the maze test and recognizing the juvenile during the olfactory social memory test in comparison to the control group. In the ND+FL group rats showed similar emotional behaviour and cognitive ability to that of the control group. Injection of FL alone did not affect either anxiety or memory. These results indicate that repeated, high-dose administration of ND decreases anxiety and impairs memory in rats via direct activation of central ARs.
The America Invents Act: A New Patent System for the 21st Century

Abstract From its first patent statute, the United States awarded patents to the first person to invent. The rest of the world eventually adopted “first to file” regimes, in which the first person to file a patent application was awarded the patent. In 2013, the United States moved closer to harmonizing with the rest of the world. The America Invents Act created a “first inventor to file” system, representing the most dramatic change in US patent law in over fifty years. This chapter explores the new provisions by offering a basic operation of how they operate. It then discusses the myriad of new administrative procedures at the United States Patent and Trademark Office that were created in the America Invents Act. These procedures have the potential to challenge patents more cheaply than in litigation. The chapter discusses the various requirements and limitations of these provisions.
Identification and functional analysis of the Rz/Rz1‐like accessory lysis genes in the membrane‐containing bacteriophage PRD1

Bacteriophage PRD1 is a tailless membrane‐containing double‐stranded (ds) DNA virus infecting a variety of Gram‐negative bacteria. In order to affect cell lysis, like most dsDNA phages, PRD1 uses the holin‐endolysin system. In this study, we identified two accessory lysis genes, XXXVI and XXXVII, coding for proteins P36 and P37, respectively. Using genetic complementation assays, we show that protein pair P36/P37 is a functional and interchangeable analogue of the Rz/Rz1 of bacteriophage λ. Utilizing molecular biology, electrochemical as well as various microscopic techniques, we characterized the lysis phenotypes of PRD1 host cells infected with mutant viruses. Our results indicate that proteins P36 and P37 confer a competitive advantage to the phage by securing the efficient disruption of the infected cell and consequent release of the phage progeny under less favourable growth conditions. In concordance with prior data and the results obtained in this study, we propose a model explaining the role of Rz/Rz1‐like proteins in the lysis process: Rz/Rz1 complexes transform the mechanical stress caused by the holin lesion at the CM to the OM leading to its disintegration. Finally, identification of the Rz/Rz1‐like genes in PRD1 suggests that tailless icosahedral phages are involved in genetic trade with tailed bacteriophages.
Digital Screen Time Limits and Young Children's Psychological Well-Being: Evidence From a Population-Based Study.

There is little empirical understanding of how young children's screen engagement links to their well-being. Data from 19,957 telephone interviews with parents of 2- to 5-year-olds assessed their children's digital screen use and psychological well-being in terms of caregiver attachment, resilience, curiosity, and positive affect in the past month. Evidence did not support implementing limits (< 1 or < 2 hr/day) as recommended by the American Academy of Pediatrics, once variability in child ethnicity, age, gender, household income, and caregiver educational attainment were considered. Yet, small parabolic functions linked screen time to attachment and positive affect. Results suggest a critical cost-benefit analysis is needed to determine whether setting firm limits constitutes a judicious use of caregiver and professional resources.
Assessing Cognitive Distraction in the Automobile

Objective: The objective was to establish a systematic framework for measuring and understanding cognitive distraction in the automobile. Background: Driver distraction from secondary in-vehicle activities is increasingly recognized as a significant source of injuries and fatalities on the roadway. Method: Across three studies, participants completed eight in-vehicle tasks commonly performed by the driver of an automobile. Primary, secondary, subjective, and physiological measures were collected and integrated into a cognitive distraction scale. Results: In-vehicle activities, such as listening to the radio or an audio book, were associated with a low level of cognitive workload; the conversation activities of talking to a passenger in the vehicle or conversing with a friend on a handheld or hands-free cell phone were associated with a moderate level of cognitive workload; and using a speech-to-text interfaced e-mail system involved a high level of cognitive workload. Conclusion: The research established that there are significant impairments to driving that stem from the diversion of attention from the task of operating a motor vehicle and that the impairments to driving are directly related to the cognitive workload of these in-vehicle activities. Moreover, the adoption of voice-based systems in the vehicle may have unintended consequences that adversely affect traffic safety. Application: These findings can be used to help inform scientifically based policies on driver distraction, particularly as they relate to cognitive distraction stemming from the diversion of attention to other concurrent activities in the vehicle.
CoCloud: Enabling efficient cross-cloud file collaboration based on inefficient web APIs

Cloud storage services such as Dropbox have been widely used for file collaboration among multiple users. However, this desirable functionality is yet restricted to the “walled-garden” of each service. At present, the only effective approach to cross-cloud file collaboration seems to be using web APIs, whose performance is known to be highly unstable and unpredictable. Now that using inefficient web APIs is inevitable, in this paper we attempt to achieve sound user-perceived performance for cross-cloud file collaboration. This attempt is enabled by two key observations from real-world measurements. First, for each cloud, we are always able to deploy one or several nearby (client) proxies which can efficiently access the web APIs. Second, during file collaboration, significant similarity exists among different versions of a file. This can be exploited to substantially reduce inter-proxy traffic and thus shorten the data sync time. Guided by the observations, we design and implement an open-source prototype system called CoCloud. Currently, it supports file collaboration among four popular cloud storage services in the US and China. Its performance is well acceptable to users under representative workloads, even approaching or exceeding intra-cloud performance in many cases.
Robust performance iterative learning control : Analysis, synthesis and experimental validation

This paper addresses robust performance analysis and synthesis of lifted system iterative learning control (ILC). By applying the full block S-procedure, sufficient conditions for the robust performance of ILC with both unstructured and structured uncertainty are derived. In the synthesis problem, we consider the design of the learning filter Q for model-inversion based ILC. The problem is reformulated as a convex optimization problem such that the converged tracking error is minimized subject to the monotonic convergence condition. This synthesis approach enables full automation of the ILC design since neither an uncertainty model has to be identified nor a robustness filter has to be chosen. The advantages of this novel robust performance ILC technique are demonstrated on an experimental linear motor test setup.