Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct cytochemical localization of catalytic subunits dissociated from cAMP-dependent protein kinase in Reuber H-35 hepatoma cells. I. Development and validation of fluorescinated inhibitor

A specific and sensitive procedure has been developed that reliably localizes intracellular sites of free catalytic unit (C) dissociated from cAMP-dependent protein kinase. The method is based on a FITC conjugate (F:PKI) of affinity column-purified heat-stable protein inhibitor (PKI) of free C. The fidelity of this cytochemical probe was determined using cultures of Reuber H-35 hepatoma cells that had been stimulated for 2 h with 0.1 mM DBcAMP, or with diluent, then fixed with anhydrous acetone at -30 degrees C. In these preparations the F:PKI probe complexed with free C in cytoplasm, nucleolus, and, to a minor extent, in nucleoplasm. Binding of the F:PKI molecule to free C was competitively diminished by arginine analogues, guanidinium HCI and polyarginine, each used over a 2-log dose range. When the inhibitor's arginine residues were blocked by reaction with cyclohexanedione it no longer inhibited phosphotransferase activity of free C, and when fluorescinated it failed to localize C in stimulated cells. Similarly, when F:PKI was preabsorbed with excess pure C it no longer functioned as a cytochemical stain. Affinity column-purified antibody to free C also reduced significantly the ability of F:PKI to complex with C in cell cultures stimulated with 0.1 mM DBcAMP. 1 microgram of antibody reduced by approximately 10% the binding of F:PKI to all cell compartments while 5 microgram of antibody diminished binding by greater than 50%. Together, these results indicate that the F:PKI binds specifically, perhaps exclusively, to the catalytic units of cAMP- dependent protein kinase. The cytochemical procedure, unlike its biochemical counterparts, is able to locate the dissociation of cAMP- dependent protein kinase in individual cells of functionally or histologically complex cultures. Also, it reveals variations in the time- and dose-dependent activation of the kinase amongst clonal cells stimulated with cyclic nucleotide analogues or hormones.
New view of population genetics of zooplankton: RAD‐seq analysis reveals population structure of the North Atlantic planktonic copepod Centropages typicus

Detection of population genetic structure of zooplankton at medium‐to‐small spatial scales in the absence of physical barriers has remained challenging and controversial. The large population sizes and high rates of gene flow characteristic of zooplankton have made resolution of geographical differentiation very difficult, especially when using few genetic markers and assuming equilibrium conditions. Next‐generation sequencing now allows simultaneous sampling of hundreds to thousands of genetic markers; new analytical approaches allow studies under nonequilibrium conditions and directional migration. Samples of the North Atlantic Ocean planktonic copepod, Centropages typicus, were analysed using restriction site‐associated DNA (RAD) sequencing on a PROTON platform. Although prior studies revealed no genetic differentiation of populations across the geographical range of the species, analysis of RAD tags showed significant structure across the North Atlantic Ocean. We also compared the likelihood for models of connectivity among NW Atlantic populations under various directional flow scenarios that replicate oceanographic conditions of the sampled domain. High‐density marker sampling with RAD sequencing markedly outperformed other technical and analytical approaches in detection of population genetic structure and characterization of connectivity of this high geneflow zooplankton species.
Relationship Repair After Infidelity: Looking at Other Perspectives

Prior research examining relationship repair after infidelity scenarios tends to focus primarily on heterosexual relationships, and often does not take into consideration the nuance between emotional and sexual infidelity, which, according to evolutionary psychology theories, tends to be salient to individuals based on their reproductive challenges. This research intended to rectify that dearth, hypothesizing that non-heterosexual participants would be more likely to repair a relationship where a partner has committed sexual infidelity than they would be to repair a relationship where a partner has committed an emotional infidelity. As well, based on prior research, there were expectations for sex differences in the likelihood of repairing a relationship after infidelity by a partner for participants in committed relationships, with female participants likely to repair emotional infidelity and male participants likely to repair sexual infidelity. In a survey of volunteers online, likelihood of repair for relationships after sexual or emotional infidelity was related to the sexual orientation of participants. Homosexual/other individuals were equally likely to repair their relationship after an emotional or sexual infidelity was committed by a partner and were more likely to repair a relationship after a partner committed a sexual infidelity than heterosexual individuals were. A qualitative question component obtained more information about the participants’ logic behind their reconciliation choices, and these results along with the quantitative results are discussed and interpreted using themes from earlier
p53 expression controls prostate cancer sensitivity to chemotherapy and the MDM2 inhibitor Nutlin-3

Prostate cancer is the second most commonly diagnosed cancer in men, and approximately one-third of those diagnosed succumb to the disease. The development of prostate cancer from small regions of hyperplasia to invasive tumors requires genetic and epigenetic alterations of critical cellular components to aid in the development of cells more adapted for aberrant growth. The p53 transcription factor is a critical element in the cell’s ability to regulate the cell cycle and its response to DNA damage. Mutations within the DNA-binding domain of p53 are common and allow the formation of tetramers; however, these alterations prevent this protein complex from associating with target gene promoters. In the present study, we examined the effects of p53 functionality in prostate cancer cells that harbored wild-type (WT) or mutant forms of the protein in response to commonly used chemotherapeutic drugs. The androgen receptor positive 22Rv-1 and LNCaP prostate cancer cell lines carry WT p53 and were demonstrated to have a decrease in chemotherapeutic drug sensitivity when transfected with a dominant-negative (DN) p53. Conversely, expression of the WT p53 in the p53-mutated and more advanced DU145 prostate cancer cell line significantly increased its overall sensitivity to anti-neoplastic drugs. Furthermore, analysis of colony formation in soft agar revealed that the functional status of p53 in each cell line altered the cell’s ability to proliferate in an anchorage-independent fashion. Prostate cancer colony growth was more prevalent when p53 transcriptional activity was decreased, whereas growth was more limited in the presence of functional p53. These results demonstrate that the functional status of the tumor suppressor p53 is important in the progression of prostate cancer and dictates the overall effectiveness a given drug would have on disease treatment.
Domain Adaptation for Machine Translation with Instance Selection

Abstract Domain adaptation for machine translation (MT) can be achieved by selecting training instances close to the test set from a larger set of instances. We consider 7 different domain adaptation strategies and answer 7 research questions, which give us a recipe for domain adaptation in MT. We perform English to German statistical MT (SMT) experiments in a setting where test and training sentences can come from different corpora and one of our goals is to learn the parameters of the sampling process. Domain adaptation with training instance selection can obtain 22% increase in target 2-gram recall and can gain up to 3:55 BLEU points compared with random selection. Domain adaptation with feature decay algorithm (FDA) not only achieves the highest target 2-gram recall and BLEU performance but also perfectly learns the test sample distribution parameter with correlation 0:99. Moses SMT systems built with FDA selected 10K training sentences is able to obtain F1 results as good as the baselines that use up to 2M sentences. Moses SMT systems built with FDA selected 50K training sentences is able to obtain F1 point better results than the baselines.
Predicting Insider Threat Risks through Linguistic Analysis of Electronic Communication

Organizations face growing risks from malicious or careless insiders. An insider threat may take many forms, including disgruntled workers, individuals under financial stress or intentional acts of espionage. Waiting for threats to manifest may leave an organization open to liability, hurt morale and in extreme cases lead to physical harm of others. However, predicting who may pose the greatest risk is challenging. Legal and economic concerns make direct psychological examinations challenging, while reliance upon supervisor or co-worker assessments may lead to unfounded accusations. This research investigates the potential for active monitoring of electronic communications as a method that may identify problems early, allowing for proactive mitigation through coaching, assistance programs and where warranted, termination. Research has found correlations between word use and behavior. This research demonstrates that subtle but measurable differences in the frequency of common words found in electronic communication may provide clues about potential insider threat risks.
Utility of pedometers for assessing physical activity: convergent validity.

Valid assessment of physical activity is important to researchers and practitioners interested in surveillance, screening, programme evaluation and intervention. The validity of an assessment instrument is commonly considered its most important attribute. Convergent validity is the extent to which an instrument's output is associated with that of other instruments intended to measure the same exposure of interest. A systematic review of the literature produced 25 articles directly relevant to the question of convergent validity of pedometers against accelerometers, observation, and self-reported measures of physical activity. Reported correlations were pooled and a median r-value was computed. Pedometers correlate strongly (median r = 0.86) with different accelerometers (specifically uniaxial accelerometers) depending on the specific instruments used, monitoring frame and conditions implemented, and the manner in which the outputs are expressed. Pedometers also correlate strongly (median r = 0.82) with time in observed activity. Time in observed inactivity correlated negatively with pedometer outputs (median r = -0.44). The relationship with observed steps taken depended upon monitoring conditions and speed of walking. The highest agreement was apparent during ambulatory activity (running, walking) or during sitting (when both observation and pedometers would register few steps taken). There was consistent evidence of reduced accuracy during slow walking. Pedometers correlate moderately with different measures of energy expenditure (median r = 0.68). The relationship between pedometer outputs and energy expenditure is complicated by the use of many different direct and indirect measures of energy expenditure and population samples. Concordance with self-reported physical activity (median r = 0.33) varied depending upon the self-report instrument used, individuals assessed, and how pedometer outputs are expressed (e.g. steps, distance travelled, energy expenditure). Pedometer output has an inverse relationship with reported time spent sitting (r = -0.38). The accumulated evidence herein provides ample support that the simple and inexpensive pedometer is a valid option for assessing physical activity in research and practice.
MicroRNA-143/-145 in Cardiovascular Diseases

MicroRNAs (miRNAs) play an essential role in the onset and development of many cardiovascular diseases. Increasing evidence shows that miRNAs can be used as potential diagnostic biomarkers for cardiovascular diseases, and miRNA-based therapy may be a promising therapy for the treatment of cardiovascular diseases. The microRNA-143/-145 (miR-143/-145) cluster is essential for differentiation of vascular smooth muscle cells (VSMCs) and determines VSMC phenotypic switching. In this review, we summarize the recent progress in knowledge concerning the function of miR-143/-145 in the cardiovascular system and their role in cardiovascular diseases. We discuss the potential role of miR-143/-145 as valuable biomarkers for cardiovascular diseases and explore the potential strategy of targeting miR-143 and miR-145.
Characterization of midazolam metabolism in locusts: the role of a CYP3A4-like enzyme in the formation of 1′-OH and 4-OH midazolam

Abstract 1. The metabolism of midazolam was investigated in vivo in locusts in order to evaluate the presence of an enzyme with functionality similar to human CYP3A4/5. 2. Hydroxylated metabolites of midazolam identical to human metabolites were detected in locusts and the apparent affinities (Km values) were in the same range as reported in humans (in locusts: 7–23 and 33–85 µM for the formation of the 1′-OH and 4-OH metabolites, respectively). 3. The formation of hydroxylated metabolites could successfully be inhibited by co-administration of ketoconazole, a known CYP3A4/5 inhibitor. 4. Besides phase I metabolites, a number of conjugated metabolites were detected using high-resolution mass spectrometry. The most abundant metabolites detected were structurally identified by 1H NMR as two N-glucosides. NMR analysis strongly suggested that the glycosylation occurred at the two nitrogens (either one in each case) of the imidazole ring. 5. Distribution of midazolam and the glucose conjugates were successfully measured using desorption electrospray mass spectrometry imaging revealing time-dependent changes in distribution over time. 6. In conclusion, it appears that an enzyme with functionality similar to human CYP3A4/5 is present in locusts. However, it appears that conjugation with glucose is the main detoxification pathway of midazolam in locusts.
Spatial accessibility to basic public health services in South Sudan

At independence in 2011, South Sudan’s health sector was almost non-existent. The first national health strategic plan aimed to achieve an integrated health facility network that would mean that 70% of the population were within 5 km of a health service provider. Publically available data on functioning and closed health facilities, population distribution, road networks, land use and elevation were used to compute the fraction of the population within 1 hour walking distance of the nearest public health facility offering curative services. This metric was summarised for each of the 78 counties in South Sudan and compared with simpler metrics of the proportion of the population within 5 km of a health facility. In 2016, it is estimated that there were 1747 public health facilities, out of which 294 were non-functional in part due to the on-going civil conflict. Access to a service provider was poor with only 25.7% of the population living within one-hour walking time to a facility and 28.6% of the population within 5 km. These metrics, when applied sub-nationally, identified the same high priority, most vulnerable counties. Simple metrics based upon population distribution and location of facilities might be as valuable as more complex models of health access, where attribute data on travel routes are imperfect or incomplete and sparse. Disparities exist in South Sudan among counties and those with the poorest health access should be targeted for priority expansion of clinical services.
Similarities and Differences in RANTES- and (AOP)-RANTES–triggered Signals: Implications for Chemotaxis

Chemokines are a family of proinflammatory cytokines that attract and activate specific types of leukocytes. Chemokines mediate their effects via interaction with seven transmembrane G protein–coupled receptors (GPCR). Using CCR5-transfected HEK-293 cells, we show that both the CCR5 ligand, RANTES, as well as its derivative, aminooxypentane (AOP)- RANTES, trigger immediate responses such as Ca2+ influx, receptor dimerization, tyrosine phosphorylation, and Gαi as well as JAK/STAT association to the receptor. In contrast to RANTES, (AOP)-RANTES is unable to trigger late responses, as measured by the association of focal adhesion kinase (FAK) to the chemokine receptor complex, impaired cell polarization required for migration, or chemotaxis. The results are discussed in the context of the dissociation of the late signals, provoked by the chemokines required for cell migration, from early signals.
Implementation of an Ebola virus disease vaccine clinical trial during the Ebola epidemic in Liberia: Design, procedures, and challenges

The index case of the Ebola virus disease epidemic in West Africa is believed to have originated in Guinea. By June 2014, Guinea, Liberia, and Sierra Leone were in the midst of a full-blown and complex global health emergency. The devastating effects of this Ebola epidemic in West Africa put the global health response in acute focus for urgent international interventions. Accordingly, in October 2014, a World Health Organization high-level meeting endorsed the concept of a phase 2/3 clinical trial in Liberia to study Ebola vaccines. As a follow-up to the global response, in November 2014, the Government of Liberia and the US Government signed an agreement to form a research partnership to investigate Ebola and to assess intervention strategies for treating, controlling, and preventing the disease in Liberia. This agreement led to the establishment of the Joint Liberia–US Partnership for Research on Ebola Virus in Liberia as the beginning of a long-term collaborative partnership in clinical research between the two countries. In this article, we discuss the methodology and related challenges associated with the implementation of the Ebola vaccines clinical trial, based on a double-blinded randomized controlled trial, in Liberia.
Frequency of the thiopurine S‐methyltransferase alleles in the ancient genetic population isolate of Sardinia

Background: Thiopurine S‐methyltransferase (TPMT) is an enzyme involved in the normal metabolic inactivation of thiopurine drugs. Patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs and it was shown that inter‐individual differences in response to these drugs is largely determined by genetic variation at the TPMT locus.
Subtotal Resection of a Thalamic Glioblastoma Multiforme through Transsylvian Approach

Glioblastoma multiforme (GBM) is a malignant brain tumor with an ominous prognosis. The standard treatment includes maximal safe resection plus adjuvant therapy. Thalamic GBMs, however, are unfavorable for microsurgical removal because of deep location and proximity to critical structures. We present a patient presenting with progressive hemiparesis and decreased consciousness with a large thalamic GBM who underwent subtotal resection through a transsylvian approach. His clinical and neurologic condition improved after surgery and he survived nine months after surgery. This may propose that in selected cases, more aggressive microsurgery for debulking of tumors might have some impact in the final outcome.
Pandemic influenza A (H1N1) in Saudi Arabia: description of the first one hundred cases

Background and Objectives : In April 2009, the World Health Organization (WHO) declared pandemic influenza A (H1N1) "public health emergency of international concern". On June 11, 2009, WHO raised the pandemic alert level to phase 6, indicating a global pandemic. By December 2009, more than 208 countries and territories had reported swine flu cases. The descriptive epidemiology of the first reported 100 cases of this virus in Saudi Arabia are summarized in this report. Methods : Data were collected from 1 June to 3 July, 2009 using a predesigned questionnaire. Questionnaires were filled by Field Epidemiology Training Program residents. Data for the first 100 complete cases of confirmed pandemic influenza A (H1N1) were compiled and analyzed. Results : The age of reported cases was in the range of 1 to 56 years. The highest percentage of cases was in the age group of 20 to 30 years followed by the age group of 1 to 10 years. Females represented 55% of the cases; imported cases represented 47%, 58% of whom had come via the King Khaled Airport. The most common nationalities most were from Saudi Arabia and the Philippines. The main symptoms were fever (56%), cough (54%), and sore throat and the number of cases was seen to peak from the 27 to 29 June. Conclusion : Pandemic influenza A (H1N1) is still a threat to Saudi Arabia. Thus, comprehensive and effective measures for surveillance and prevention of the disease are needed to control its spread.
An Automatic Metric for Machine Translation Evaluation Based on Maximum Similarity

This paper describes our participation in the NIST 2008 MetricsMATR Challenge, using our recently proposed automatic machine translation evaluation metric M AX SIM . The metric calculates a similarity score between a pair of English system-reference sentences by comparing information items such as ngrams across the sentence pair. Unlike most metrics, MAX SIM computes a similarity score between items, then find a maximum weight matching between the items such that each item in one sentence is mapped to at most one item in the other sentence. Evaluation on the WMT07, WMT08, and MT06 datasets show that MAX SIM achieves good correlations with human judgment.
Chk1 inhibition activates p53 through p38 MAPK in tetraploid cancer cells

We have previously shown that tetraploid cancer cells succumb through a p53-dependent apoptotic pathway when checkpoint kinase 1 (Chk1) is depleted by small interfering RNAs (siRNAs) or inhibited with 7-hydroxystaurosporine (UCN-01). Here, we demonstrate that the Chk1 inhibition results in the activating phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). Depletion of p38 MAPK by transfection with a siRNA targeting the α isoform of p38 MAPK (p38α MAPK) abolishes the phosphorylation of p53 on serines 15 and 46 that is induced by Chk1 knockdown. The siRNA-mediated downregulation and pharmacological inhibition of p38α MAPK (with SB 203580) also reduces cell death induced by Chk1 knockdown or UCN-01. These results underscore the role of p38 MAPK as a pro-apoptotic kinase in the p53-dependant pathway for the therapeutic elimination of polyploidy cells.