Miracle-dz/UniFAR-FTUs huggingface dataset:
The Egg and the Nucleus: A Battle for Supremacy

POST-NOBEL PERSPECTIVE This brief introduction is followed by a published version of my Nobel Laureate lecture, re-published herein with the kind permission of the Nobel Foundation. Much has happened since my original research, for which that prize was awarded. Hence, I am pleased to offer a few thoughts about the future of my research and its possible impact on humankind. Although the original work on nuclear transfer and reprogramming was done over half a century ago, advances continue to be made. In particular the Takahashi and Yamanaka induced pluripotent stem cells (iPS) procedure has opened up the field of cell replacement to a great extent. Now, more recently, further advances make this whole field come closer to actual usefulness for humans. Recently, in the UK, the government approved the use of mitochondrial replacement therapy to avoid the problems associated with genetically defective mitochondria in certain women. Although the House of Commons (members of Parliament) and the House of Lords had to debate and discuss whether to allow this kind of human therapy, I was very pleased to find that both bodies approved this procedure. This means that a patient can choose to make use of the procedure; it does not in any way force an individual to have a procedure that they are not comfortable with. In my view, this is a great advance in respect to giving patients a choice about the treatment they receive. I am told that the UK is the first country in the world to approve mitochondrial replacement therapy. Now that the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPr) technology is being widely used and works well, one can foresee that there will be those who wish to use this technology to make genetic changes to humans. For example, if a human has a gene that makes it susceptible to infection or any other disorder, the removal of that gene might give such a person immunity from that disease. If this gene deletion is done within the germ line, the genetic change will be inherited. However, one can imagine that various people will strongly object and say that this technology should not be allowed. I would very much hope that various regulatory bodies, governments, etc. will allow the choice to remain with the individual. I can see no argument for such bodies to make a law that removes any choice whatsoever by an individual.
The Elliptic GL(n) Dynamical Quantum Group as an -Hopf Algebroid

Using the language of -Hopf algebroids which was introduced by Etingof and Varchenko, we construct a dynamical quantum group, , from the elliptic solution of the quantum dynamical Yang-Baxter equation with spectral parameter associated to the Lie algebra . We apply the generalized FRST construction and obtain an -bialgebroid . Natural analogs of the exterior algebra and their matrix elements, elliptic minors, are defined and studied. We show how to use the cobraiding to prove that the elliptic determinant is central. Localizing at this determinant and constructing an antipode we obtain the -Hopf algebroid .
Effect of Qi-protecting powder (Huqi San) on expression of c-jun, c-fos and c-myc in diethylnitrosamine-mediated hepatocarcinogenesis.

AIM To study the inhibitory effect of Huqi San (Qi-protecting powder) on rat prehepatocarcinoma induced by diethylinitrosamine (DEN) by analyzing the mutational activation of c-fos proto-oncogene and over-expression of c-jun and c-myc oncogenes. METHODS A Solt-Farber two-step test model of prehepatocarcinoma was induced in rats by DEN and 2-acetylaminofluorene (AAF) to investigate the modifying effects of Huqi San on the expression of c-jun, c-fos and c-myc in DEN-mediated hepatocarcinogenesis. Huqi San was made of eight medicinal herbs containing glycoprival granules, in which each milliliter contains 0.38 g crude drugs. gamma-glutamy-transpeptidase-isoenzyme (gamma-GTase) was determined with histochemical methods. Level of 8-hydroxydeoxyguanosine (OHdG) formed in liver and c-jun, c-fos and c-myc proto-oncogenes were detected by immunohistochemical methods. RESULTS The level of 8-OHdG, a mark of oxidative DNA damage, was significantly decreased in the liver of rats with prehepatocarcinoma induced by DEN who received 8 g/kg body weight or 4 g/kg body weight Huqi San before (1 wk) and after DEN exposure (4 wk). Huqi San-treated rats showed a significant decrease in number of gamma-GT positive foci (P < 0.001, prevention group: 4.96 +/- 0.72 vs 29.46 +/- 2.17; large dose therapeutic group: 7.53 +/- 0.88 vs 29.46 +/- 2.17). On the other hand, significant changes in expression of c-jun, c-fos and c-myc were found in Huqi San-treated rats. CONCLUSION Activation of c-jun, c-fos and c-myc plays a crucial role in the pathogenesis of liver cancer. Huqi San can inhibit the over-expression of c-jun, c-fos and c-myc oncogenes and liver preneolastic lesions induced by DEN.
X-ray computed tomography

Computed tomography (CT) is a non-destructive X-ray imaging method, which allows to visualize three-dimensional X-ray absorption properties of an object. In this lab course you will learn the basics about X-ray imaging and computed tomography using a simple CT setup. Next to theoretical and experimental basics of X-ray imaging and radiography, you will get an idea how CT reconstruction using filtered backprojection (FBP) works and how typical reconstruction artifacts look like. You may also bring along your own sample to be scanned (max. 4 cm in diameter and max. 3 cm in height, nonmetallic). You do not need to print this manual since a printout is available at the experimental setup.
Multidrug Resistance Protein MRP2 Contributes to Blood-Brain Barrier Function and Restricts Antiepileptic Drug Activity

The blood-brain barrier (BBB) is a physical and metabolic barrier between the brain and the systemic circulation, which functions to protect the brain from circulating drugs, toxins, and xenobiotics. ATP-dependent multidrug transporters such as P-glycoprotein (Pgp; ABCB1), which are found in the apical (luminal) membranes of brain capillary endothelial cells, are thought to play an important role in BBB function by limiting drug penetration into the brain. More recently, the multidrug resistance protein MRP2 (ABCC2) has been found in the luminal surface of brain capillary endothelium of different species, including humans. In endothelial cells from patients with drug-resistant epilepsy, MRP2 was shown to be overexpressed, indicating that it may be critically involved in multidrug resistance of such patients. However, the role of MRP2 in drug disposition into the brain is defined poorly. Herein, we used different strategies to study the contribution of MRP2 to BBB function. First, the MRP inhibitor probenecid was shown to increase extracellular brain levels of the major antiepileptic drug phenytoin in rats, indicating that phenytoin is a substrate of MRP2 in the BBB. This was substantiated by using MRP2-deficient TR– rats, in which extracellular brain levels of phenytoin were significantly higher compared with the normal background strain. In the kindling model of epilepsy, coadministration of probenecid significantly increased the anticonvulsant activity of phenytoin. In kindled MRP2-deficient rats, phenytoin exerted a markedly higher anticonvulsant activity than in normal rats. These data indicate that MRP2 substantially contributes to BBB function.
Terra MODIS band 27 electronic crosstalk: cause, impact, and mitigation

MODIS-Terra is one of the key sensors in the suite of remote sensing instruments in the Earth Observing System (EOS). MODIS on the Terra platform was launched into orbit in December of 1999 and has successfully completed eleven plus years of operation. MODIS has 36 spectral channels with wavelengths varying from 0.4 μm to 14.4 μm. The native spatial resolutions for the reflective channels are 2 bands at 0.25 km, 5 bands at 0.5 km and 29 bands at 1km. However, the MODIS L1B product allows the high spatial resolution bands to be aggregated into 1km resolution. All the thermal channels in MODIS (i.e. 3.75μm - 14.24μm) have a native spatial resolution of 1 km. Over the eleven plus years of mission lifetime, the sensor degradation has been carefully monitored using various On-Board Calibrators (OBC). In particular, the thermal channels are monitored using the on-board Black-Body (BB) which is traceable to NIST standards. MODIS also has a unique feature for calibration reference in terms of lunar irradiance. The lunar observations are scheduled for MODIS periodically (at least 9 observations in a calendar year). Based on the lunar observations, it was found that there was a possible signal leak for band 27 from its neighboring bands located on the Long-Wave Infrared (LWIR) focal plane. Further investigations revealed a possible leak from bands 28, 29 and 30. The magnitude of the leak was trended and correction coefficients were derived. In this paper, we demonstrate the across-band signal leak in MODIS band 27, its potential impact on the retrieved Brightness temperature (B.T.). Also, the paper explores a correction methodology to relieve the artifacts due to the across-band signal leak. Finally, the improvement in the band 27 image quality is quantified.
The Origins, Evolution, and Future of Preference Assessments in Applied Behavior Analysis

For nearly thirty years, preference assessments have been utilized in determining items of interest for individuals afflicted with developmental disabilities. Originally, preference assessments were conducted on individuals with severe and profound disabilities, however over time, preference assessments have been adapted to suit individuals with various levels of functioning, as well as those with physical disabilities. Five primary methodologies have become widely accepted for conducting such assessments, and as new techniques have emerged, researchers have conducted a wide range of comparative studies, in hopes of sorting out each respective assessment's strengths and weaknesses, as well as identify which specific populations for which each is best-suited. To this point, the strengths and weaknesses of each assessment have largely been isolated, however the picture is somewhat more cloudy when attempting to match the ideal assessment to a particular subpopulation. Future research may continue to work to clarify this issue, and in addition may utilize new innovations in technology to determine preference in populations previously inaccessible to traditional methods.
Targeted sequencing identifies associations between IL7R-JAK mutations and epigenetic modulators in T-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia is caused by the accumulation of multiple oncogenic lesions, including chromosomal rearrangements and mutations. To determine the frequency and co-occurrence of mutations in T-cell acute lymphoblastic leukemia, we performed targeted re-sequencing of 115 genes across 155 diagnostic samples (44 adult and 111 childhood cases). NOTCH1 and CDKN2A/B were mutated/deleted in more than half of the cases, while an additional 37 genes were mutated/deleted in 4% to 20% of cases. We found that IL7R-JAK pathway genes were mutated in 27.7% of cases, with JAK3 mutations being the most frequent event in this group. Copy number variations were also detected, including deletions of CREBBP or CTCF and duplication of MYB. FLT3 mutations were rare, but a novel extracellular mutation in FLT3 was detected and confirmed to be transforming. Furthermore, we identified complex patterns of pairwise associations, including a significant association between mutations in IL7R-JAK genes and epigenetic regulators (WT1, PRC2, PHF6). Our analyses showed that IL7R-JAK genetic lesions did not confer adverse prognosis in T-cell acute lymphoblastic leukemia cases enrolled in the UK ALL2003 trial. Overall, these results identify interconnections between the T-cell acute lymphoblastic leukemia genome and disease biology, and suggest a potential clinical application for JAK inhibitors in a significant proportion of patients with T-cell acute lymphoblastic leukemia.
The Rab3A-22A Chimera Prevents Sperm Exocytosis by Stabilizing Open Fusion Pores*

At the final stage of exocytotis, a fusion pore opens between the plasma and a secretory vesicle membranes; typically, when the pore dilates the vesicle releases its cargo. Sperm contain a large dense-core secretory granule (the acrosome) whose contents are secreted by regulated exocytosis at fertilization. Minutes after the arrival of the triggering signal, the acrosomal and plasma membranes dock at multiple sites and fusion pores open at the contact points. It is believed that immediately afterward, fusion pores dilate spontaneously. Rab3A is an essential component of human sperm exocytotic machinery. Yet, recombinant, persistently active Rab3A halts calcium-triggered secretion when introduced after docking into streptolysin O-permeabilized cells; so does a Rab3A-22A chimera. Here, we applied functional assays, electron and confocal microscopy to show that the secretion blockage is due to the stabilization of open fusion pores. Other novel findings are that sperm SNAREs engage in α-SNAP/NSF-sensitive complexes at a post-fusion stage. Complexes are disentangled by these chaperons to achieve vesiculation and acrosomal contents release. Thus, post-fusion regulation of the pores determines their expansion and the success of the acrosome reaction.
IS ADULT DEFINITION OF ANEMIA APPLICABLE TO A GERIATRIC POPULATION? STUDY OF ERYTHROCYTE PARAMETERS IN INDIAN GERIATRIC INPATIENTS

To the Editor: Although Kamal-Bahl et al. demonstrated that elderly patients commonly use propoxyphene, the authors stated that the use of propoxyphene is inappropriate for this population. Unfortunately, such statements are typical of long-standing misconceptions about propoxyphene. First, although the authors effectively employ 1998 Medicare Current Beneficiary Survey data, they neither provide epidemiological evidence of widespread detrimental effects associated with the proper use of propoxyphene nor cite references solidly demonstrating such purported effects. Second, the authors base their assumption on the works of Beers et al., consensus publications that have significant methodological flaws, designed to fault only propoxyphene for adverse effects attributable to the entire class of opioids. The Kamal-Bahl et al. study is but the most recent study among many that systematically exhibits these flaws. A likely reason that some practitioners have considered propoxyphene inappropriate for elderly patients may be because it is believed to increase the probability of falls. Yet, in a recent survey of more than 8,000 community-dwelling women aged 65 and older, multivariate analyses show that opioids are not associated with an increased likelihood of falls. As a rheumatologist with 25 years of clinical experience, I have treated many thousands of patients, approximately 60% of whom are aged 65 and older. I have used propoxyphene in many of these patients, achieving acceptable analgesic efficacy with only rare adverse experiences. By and large, except for occasional dose modifications for the extremely elderly, frail, or chronically ill, my patients tolerate full therapeutic doses. Propoxyphene, especially in combination with acetaminophen, is a safe, effective analgesicFa proven, established agent in the physician’s armamentarium against pain. Few analgesics have demonstrated 40-plus-year histories of safety and efficacy in elderly patients. Terms such as ‘‘inappropriate prescribing’’ need to be based on results of controlled clinical studies or outcomes research in which risks outweigh benefits. Dr. Morton serves on the advisory board of aaiPharma, Inc. (Wilmington, NC), which markets propoxyphene.
Foam Cells : New Target for Antioxidant Therapy? -acetyl-cysteine Decreases the Matrix-degrading Capacity of Macrophage-derived N N-acetyl-cysteine Decreases the Matrix-degrading Capacity of Macrophage-derived Foam Cells New Target for Antioxidant Therapy?

Background—Atherosclerotic plaque destabilization triggers clinical cardiovascular disease and thus represents an attractive therapeutic target. Weakening of tissue through the action of matrix-degrading enzymes, called matrix metalloproteinases (MMPs), released by resident macrophages was previously implicated in unstable vascular syndromes. Methods and Results—We used a hypercholesterolemic rabbit model of atherosclerosis to investigate the gelatinolytic activity associated with macrophage-derived foam cells (FCs). Gelatinolytic activity and expression of MMP-9 but not of MMP-2 cosegregated with macrophage FCs in aortic lesions. Macrophage-derived gelatinases were further investigated in vitro. MMP-9 was identified as the main macrophage-derived gelatinase in cells isolated from aortic lesions and from granuloma induced in the same rabbits to increase cell yield. Importantly, detection of activated MMP-9 in the FC culture medium supports the notion that these cells can independently initiate processing of secreted MMP zymogens to active enzymes. We further examined whether FC gelatinolytic activity is dependent on the presence of reactive oxygen species (ROS). We found that treatment (1 to 5 days) with 1 to 10 mmol/L N-acetyl-L-cysteine (NAC), an ROS scavenger, decreased not only gelatinolytic activity but also gelatinase expression by FCs. Similarly, NAC treatment of explanted lesions abolished in situ gelatinolytic activity and MMP-9 expression. Conclusions—Macrophage FCs are an abundant source of gelatinolytic activity that can be inhibited in vitro and in situ by NAC. This newly described action of antioxidant therapy might prove useful to inhibit matrix degradation and to improve vascular stability.
Global production networks and the analysis of economic development

This article outlines a framework for the analysis of economic integration and its relation to the asymmetries of economic and social development. Consciously breaking with state-centric forms of social science, it argues for a research agenda that is more adequate to the exigencies and consequences of globalization than has traditionally been the case in 'development studies'. Drawing on earlier attempts to analyse the cross-border activities of firms, their spatial configurations and developmental consequences, the article moves beyond these by proposing the framework of the 'global production network' (GPN). It explores the conceptual elements involved in this framework in some detail and then turns to sketch a stylized example of a GPN. The article concludes with a brief indication of the benefits that could be delivered by research informed by GPN analysis.
Racial Gaps in Labor Market Outcomes in the Last Four Decades and Over the Business Cycle

We examine racial disparities in key labor market outcomes for men and women over the past four decades, with a special emphasis on their evolution over the business cycle. Blacks have substantially higher and more cyclical unemployment rates than whites, and observable characteristics can explain very little of this differential, which is importantly driven by a comparatively higher risk of job loss. In contrast, the Hispanic-white unemployment rate gap is comparatively small and is largely explained by lower educational attainment of (mostly foreign-born) Hispanics. Regarding labor force participation, the remarkably low participation rate of black men is largely unexplained by observables, is mostly driven by high labor force exit rates from employment, and has shown little improvement over the last 40 years. Furthermore, even among those who work, blacks and Hispanics are more likely than whites to work part-time schedules despite wanting to work additional hour s, and the racial gaps in this involuntary part-time employment are large even after controlling for observable characteristics. Our findings also suggest that the robust recovery of the labor market in the last few years has contributed significantly to reducing the gaps that had widened dramatically as a result of the Great Recession; however, the disparities remain substantial.
Evaluation of a Computer-Based Training Program for Enhancing Arithmetic Skills and Spatial Number Representation in Primary School Children

Calcularis is a computer-based training program which focuses on basic numerical skills, spatial representation of numbers and arithmetic operations. The program includes a user model allowing flexible adaptation to the child's individual knowledge and learning profile. The study design to evaluate the training comprises three conditions (Calcularis group, waiting control group, spelling training group). One hundred and thirty-eight children from second to fifth grade participated in the study. Training duration comprised a minimum of 24 training sessions of 20 min within a time period of 6–8 weeks. Compared to the group without training (waiting control group) and the group with an alternative training (spelling training group), the children of the Calcularis group demonstrated a higher benefit in subtraction and number line estimation with medium to large effect sizes. Therefore, Calcularis can be used effectively to support children in arithmetic performance and spatial number representation.
Detection of Chlamydia pneumoniae-Specific Antibodies Binding to the VD2 and VD3 Regions of the Major Outer Membrane Protein

ABSTRACT Although Chlamydia pneumoniae is an important human pathogen, the antigens eliciting a specific humoral immune response remain elusive. We scrutinized several recombinant chlamydial surface proteins for species-specific recognition by a panel of human sera previously tested for the presence of anti-C. pneumoniae and anti-C. trachomatis antibodies by microimmunofluorescence and enzyme-linked immunosorbent assay. The 15-kDa cysteine-rich protein (CrpA), porin-b (PorB), 9-kDa outer membrane protein (OMP3), 60-kDa outer membrane protein (OMP2), and four fragments of the major outer membrane protein (MOMP) representing each variable domain (VD) were overexpressed in Escherichia coli, affinity purified, and employed for Western blot analysis. None of the sera tested contained antibodies recognizing PorB and OMP3 of C. pneumoniae. Sera from C. pneumoniae-immune patients cross-reacted with OMP2 of C. trachomatis, and sera from C. trachomatis-immune patients cross-reacted with CrpA of C. pneumoniae, indicating that some of chlamydial surface molecules share antigenic epitopes. In contrast, the VD2, as well as the VD3, regions of the MOMP of C. pneumoniae were only recognized by C. pneumoniae-positive sera, suggesting the existence of species-specific epitopes. The identification of such epitopes of cell surface molecules provides new insights into C. pneumoniae-specific immune responses and may be of value for the improvement of C. pneumoniae-specific diagnostic assay systems based on defined recombinant antigens.
Parametric effects of word frequency in memory for mixed frequency lists.

[Correction Notice: An Erratum for this article was reported in Vol 39(6) of Journal of Experimental Psychology: Learning, Memory, and Cognition (see record 2013-27860-001). In the article there were omissions in Figure 1. All versions of this article have been corrected. ] The word frequency paradox refers to the finding that low frequency words are better recognized than high frequency words yet high frequency words are better recalled than low frequency words. Rather than comparing separate groups of low and high frequency words, we sought to quantify the functional relation between word frequency and memory performance across the broad range of frequencies typically used in episodic memory experiments. Here we report that both low frequency and high frequency words are better recalled than midfrequency words. In contrast, we only observe a low frequency advantage when participants were given a subsequent item recognition test. The U-shaped relation between word frequency and recall probability may help to explain inconsistent results in studies using mixed lists with separate groups of high and low frequency words.