Miracle-dz/UniFAR-FTUs huggingface dataset:
Subdivisions of the turtle Pseudemys scripta hypothalamus based on the expression of regulatory genes and neuronal markers

The patterns of distribution of a set of conserved brain developmental regulatory transcription factors and neuronal markers were analyzed in the hypothalamus of the juvenile turtle, Pseudemys scripta. Combined immunohistochemical techniques were used for the identification of the main boundaries and subdivisions in the optic, paraventricular, tuberal, and mammillary hypothalamic regions. The combination of Tbr1 and Pax6 with Nkx2.1 allowed identification of the boundary between the telencephalic preoptic area, rich in Nkx2.1 expression, and the prethalamic eminence, rich in Tbr1 expression. In addition, at this level Nkx2.2 expression defined the boundary between the telencephalon and the hypothalamus. The dorsalmost hypothalamic domain was the supraoptoparaventricular region that was defined by the expression of Otp/Pax6 and the lack of Nkx2.1/Isl1. It is subdivided into rostral, rich in Otp and Nkx2.2, and caudal, only Otp‐positive, portions. Ventrally, the suprachiasmatic area was identified by its catecholaminergic groups and the lack of Otp, and could be further divided into a rostral portion, rich in Nkx2.1 and Nkx2.2, and a caudal portion, rich in Isl1 and devoid of Nkx2.1 expression. The expressions of Nkx2.1 and Isl1 defined the tuberal hypothalamus, whereas only the rostral portion expressed Otp. Its caudal boundary was evident by the lack of Isl1 in the adjacent mammillary area, which expressed Nkx2.1 and Otp. All these results provide an important set of data on the interpretation of the hypothalamic organization in a reptile, and hence make a useful contribution to the understanding of hypothalamic evolution. J. Comp. Neurol. , 2012;520:453–478. © 2011 Wiley Periodicals, Inc.
Back pain in childhood.

Case history A 9 year old girl was referred with a three month history of low back pain which was related to increased physical activity, radiating to both legs. Periodic weakness in both legs was associated with occasional paraesthesiae in both feet. There were no bladder, bowel, or other systemic symptoms. Before the onset of back pain the child had been well, with no history of any trauma. On examination, she appeared to be of short stature for age, but of normal proportion. On standing there was a hyperlordosis of the thoracolumbar spine. Percussion over the lumbar spine at the L2/L3 level elicited marked tenderness. There was a generalised reduction of all spinal movements. Straight leg raising was 40 degrees bilaterally, with limitation due to low back pain. Neurological examination of the lower limbs was normal. She was afebrile and general systemic examination was normal. Following initial radiographic examination, she
FDA Review Summary: Mozobil in Combination with Granulocyte Colony-Stimulating Factor to Mobilize Hematopoietic Stem Cells to the Peripheral Blood for Collection and Subsequent Autologous Transplantation

Purpose: On December 15, 2008, the US Food and Drug Administration approved plerixafor (Mozobil®; Genzyme Corp.), a new small-molecule inhibitor of the CXCR4 chemokine receptor, for use in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). This summary reviews the database supporting this approval. Experimental Design: The safety and efficacy of plerixafor were demonstrated by 2 multicenter, randomized, placebo-controlled studies in patients with NHL and MM who were eligible for autologous HSC transplantation. The primary efficacy end points were the collection of ≧5 × 106 CD34+ cells/kg from the peripheral blood in 4 or fewer apheresis sessions in patients with NHL or ≧6 × 106 CD34+ cells/kg from the peripheral blood in 2 or fewer apheresis sessions in patients with MM. Results: The 2 randomized studies combined enrolled 600 patients (298 with NHL and 302 with MM). Fifty-nine percent of patients with NHL who were mobilized with G-CSF and plerixafor had peripheral blood HSC collections of ≧5 × 106 CD34+ cells/kg in 4 or fewer apheresis sessions, compared with 20% of patients with NHL who were mobilized with G-CSF and placebo (p < 0.001). Seventy-two percent of patients with MM who were mobilized with Mozobil and G-CSF had peripheral blood HSC collections of ≧6 × 106 CD34+ cells/kg in 2 or fewer apheresis sessions, compared with 34% of patients with MM who were mobilized with placebo and G-CSF (p < 0.001). Common adverse reactions included diarrhea, nausea, vomiting, flatulence, injection site reactions, fatigue, arthralgia, headache, dizziness, and insomnia. Conclusions: This report describes the Food and Drug Administration review supporting the approval of plerixafor.
Human granulosa-lutein cells express functional EP1 and EP2 prostaglandin receptors.

Prostaglandin E(2) (PGE(2)) exerts mainly luteotrophic effects in the corpus luteum. In other tissues, PGE(2) acts via specific PGE(2) receptor subtypes including EP1, which modulates intracellular calcium ([Ca(2+)](i)) and EP2, which is coupled to cyclic AMP (cAMP) generation. We have therefore investigated the presence of functional EP1 and EP2 receptors using human granulosa-lutein (GL) cells. Reverse-transcription PCR revealed that GL cells expressed mRNA transcripts encoding both EP1 and EP2 receptors. When GL cells were challenged with ligands that can bind to both receptor subtypes (PGE(2) and 16,16 dimethyl PGE(2)) or exclusively to EP2 (butaprost), both cAMP formation and progesterone synthesis were stimulated. Furthermore, the cAMP response to these agonists could be significantly blocked by an EP1/2 antagonist AH6809 but not by an EP1-selective antagonist SC19220. Exposure of GL cells to 16,16-dm PGE(2) transiently raised [Ca(2+)](i) levels, which could be prevented by both AH6809 and SC19220. We therefore conclude that human GL cells express functional EP1 and EP2 receptors.
The Changing Landscape of Language Teachers’ Usage of ICT in Classrooms in SMK Bandaraya Kota Kinabalu, Sabah, Malaysia

The Malaysian Smart School is a learning institution that has been systemically reinvented in terms of teaching and learning practices in schools and school management processes in order to prepare students cope with the information age. It aims to produce proactive, efficient and competent students in information literacy so that they will be self-regulated learners who practise self-accessed and self-directed learning, at their own learning pace. In addition the Ministry of Education, Malaysia has also stated clearly in the National Education Blueprint (2013 – 2025) under Shift 7: Leverage ICT to scale up quality learning across Malaysia. Using models from Fullan’s Change Theory and Rogers’ Diffusion of Innovation Theory, a study was carried out on language teachers’ changing mindset in integrating ICT in their classroom teaching in the school, SMK Bandaraya Kota Kinabalu. The study was carried out using observation techniques supported by the results obtained from the SSQS survey questions and a language teacher’s feedback form to determine language teachers’ progressive usage of ICT in their teaching process. Special focus is given to the changing attitudes of the language teachers in using ICT in their classrooms. Some issues that arise in the school’s context and smart solutions taken to overcome these issues are also discussed. In conclusion, the writer proposes ways to further enhance and to upgrade the school’s achievement in using ICT in the teaching and learning process.
Monetary Policy and Long-Run Risk-Taking

Since the outbreak of the global financial crisis, prolonged periods of accommodative monetary policy that lead to an increase in financial risk in the medium and long term have been labeled as the risk-taking channel of monetary policy. In this paper, we analyze the presence of this channel in the Eurozone using long-term causality measures. Considering various auxiliary variables, we find a significant long-term effect of monetary policy on risk, but no short-term effect. Reverse causality is rejected. Finally, we conclude that the risk-taking channel is difficult to separate from the traditional credit channel.
Generalization Bounds of SGLD for Non-convex Learning: Two Theoretical Viewpoints

Algorithm-dependent generalization error bounds are central to statistical learning theory. A learning algorithm may use a large hypothesis space, but the limited number of iterations controls its model capacity and generalization error. The impacts of stochastic gradient methods on generalization error for non-convex learning problems not only have important theoretical consequences, but are also critical to generalization errors of deep learning. In this paper, we study the generalization errors of Stochastic Gradient Langevin Dynamics (SGLD) with non-convex objectives. Two theories are proposed with non-asymptotic discrete-time analysis, using Stability and PAC-Bayesian results respectively. The stability-based theory obtains a bound of $O\left(\frac{1}{n}L\sqrt{\beta T_k}\right)$, where $L$ is uniform Lipschitz parameter, $\beta$ is inverse temperature, and $T_k$ is aggregated step sizes. For PAC-Bayesian theory, though the bound has a slower $O(1/\sqrt{n})$ rate, the contribution of each step is shown with an exponentially decaying factor by imposing $\ell^2$ regularization, and the uniform Lipschitz constant is also replaced by actual norms of gradients along trajectory. Our bounds have no implicit dependence on dimensions, norms or other capacity measures of parameter, which elegantly characterizes the phenomenon of "Fast Training Guarantees Generalization" in non-convex settings. This is the first algorithm-dependent result with reasonable dependence on aggregated step sizes for non-convex learning, and has important implications to statistical learning aspects of stochastic gradient methods in complicated models such as deep learning.
Faculty attitudes and opinions about problem‐based learning

BACKGROUND: Systematic research on faculty attitudes toward problem-based learning (PBL) has focused exclusively on the opinions of tutors. The purpose of the present study was to examine the attitudes of faculty at a single medical school who either (1) did not participate in the first year of a new PBL curriculum or (2) participated in ways other than as PBL tutors. METHOD: In 1993-94, at the end of the first year of a new PBL curriculum, a questionnaire used in an earlier, larger study of PBL tutors was sent to all 494 faculty at the University of Missouri-Columbia School of Medicine. RESULTS: The response rate was better for participants (76%, 115 of 151) than for non-participants (28%, 96 of 343). Overall, nonparticipants judged the new curriculum to be approximately equal to the “old” curriculum that preceded it. In contrast, participants were significantly more positive and judged the new PBL curriculum to be superior in most respects. For both groups the new curriculum received its highest ratings in the areas of student interest, clinical preparation, and medical reasoning and its lowest ratings in the teaching of factual knowledge in the basic sciences and efficiency of learning. The attitudes of participating faculty varied with their teaching roles in the new curriculum. Those whose primary roles were as PBL tutors or as leaders of other small discussion groups were more favorable to the new curriculum than those who primarily served as lecturers. Faculty who served in several different roles were more positive than faculty who served in only one role. There were also plausible qualitative differences among the teaching-role groups in what they liked and disliked about the new curriculum. CONCLUSION: In general, the attitudes and opinions of the faculty varied with the degrees and types of participation in the new curriculum. The attitudes and opinions of faculty with different teaching roles were plausibly related to differences in these roles. The opinions of the faculty about the strengths and weaknesses of PBL that emerged in this survey are much like those found in prior research. In addition, student performances on Step 1 of the United States Medical Licensing Examination suggest that the faculty may have underestimated the value of the new PBL curriculum for helping students acquire factual knowledge in the basic sciences.
VEGF Family Members Regulate Myocardial Tubulogenesis and Coronary Artery Formation in the Embryo

This study tested the hypothesis that coronary tubulogenesis and coronary artery formation require VEGF family members. Quail embryos were injected with soluble vascular endothelial growth factor (VEGF) receptors R1 (Flt-1), R2 (Flk-1), R3 (Flt-4), VEGF-Trap (a chimera of R1 and R2), or neutralizing antibodies to VEGF-A, VEGF-B, or fibroblast growth factor (FGF)-2. Our data document that tubulogenesis is temporally dependent on multiple VEGF family members, because the early stage of tubulogenesis was markedly inhibited by VEGF-Trap and to a lesser extent by soluble VEGFR-1. Some inhibition of tubulogenesis was documented when anti-FGF-2, but not anti-VEGF-A, antibodies were injected at embryonic day 6 (E6). Most importantly, we found that VEGF-Trap injected at either E6 or E7 prevented the formation of coronary arteries. Soluble VEGFR-1 and soluble VEGFR-2 modified the formation of coronary arteries, whereas soluble VEGFR-3 was without effect. Antibodies to VEGF-B, but not VEGF-A, had a strong inhibitory effect on coronary artery development. The absence of coronary artery stems, and thus a functional coronary circulation, in the embryos injected with VEGF-Trap caused an accumulation of erythrocytes in the subepicardium and muscular interventricular septum. Using retroviral cell tagging, we showed that some of the erythrocytes in blood islands and small vascular tubes were progeny of the proepicardium. Thus, another salient finding of this study is the first definitive documentation of proepicardially derived hemangioblasts, which can differentiate into erythrocytes.
Whole-Body PET/MR Imaging: Quantitative Evaluation of a Novel Model-Based MR Attenuation Correction Method Including Bone

In routine whole-body PET/MR hybrid imaging, attenuation correction (AC) is usually performed by segmentation methods based on a Dixon MR sequence providing up to 4 different tissue classes. Because of the lack of bone information with the Dixon-based MR sequence, bone is currently considered as soft tissue. Thus, the aim of this study was to evaluate a novel model-based AC method that considers bone in whole-body PET/MR imaging. Methods: The new method (“Model”) is based on a regular 4-compartment segmentation from a Dixon sequence (“Dixon”). Bone information is added using a model-based bone segmentation algorithm, which includes a set of prealigned MR image and bone mask pairs for each major body bone individually. Model was quantitatively evaluated on 20 patients who underwent whole-body PET/MR imaging. As a standard of reference, CT-based μ-maps were generated for each patient individually by nonrigid registration to the MR images based on PET/CT data. This step allowed for a quantitative comparison of all μ-maps based on a single PET emission raw dataset of the PET/MR system. Volumes of interest were drawn on normal tissue, soft-tissue lesions, and bone lesions; standardized uptake values were quantitatively compared. Results: In soft-tissue regions with background uptake, the average bias of SUVs in background volumes of interest was 2.4% ± 2.5% and 2.7% ± 2.7% for Dixon and Model, respectively, compared with CT-based AC. For bony tissue, the −25.5% ± 7.9% underestimation observed with Dixon was reduced to −4.9% ± 6.7% with Model. In bone lesions, the average underestimation was −7.4% ± 5.3% and −2.9% ± 5.8% for Dixon and Model, respectively. For soft-tissue lesions, the biases were 5.1% ± 5.1% for Dixon and 5.2% ± 5.2% for Model. Conclusion: The novel MR-based AC method for whole-body PET/MR imaging, combining Dixon-based soft-tissue segmentation and model-based bone estimation, improves PET quantification in whole-body hybrid PET/MR imaging, especially in bony tissue and nearby soft tissue.
The Power and Politicized Expansion of the International Criminal Court

Abstract This dissertation contributes to an understanding of why national leaders voluntarily accept the jurisdiction of the International Criminal Court (ICC), granting it the authority to prosecute them. It theorizes that leaders trade off the risk of unwanted prosecutions against the deterrent threat that prosecutions pose to political rivals and patrons of domestic enemies, who may conspire to violently oust leaders. The risk of unwanted prosecutions and the ICC's deterrent threat both arise because the court's prosecutions credibly communicate guilt for atrocities and may trigger leader-specific sanctions by wealthy donor states that prefer to keep politicians who commit atrocities out of office. Three qualities explain the ICC's credibility: a legitimacy quality, an investment quality, and a reputational quality. Empirical analysis of panel data on leaders and all modern international criminal courts supports the theory. National leaders accept the ICC's jurisdiction when it can deter their rivals from anti-regime violence – when the state depends heavily on development capital disbursed by wealthy democracies – and when the leaders can limit their own exposure to prosecution. The protection leaders obtain under the ICC's jurisdiction gives them longer and more peaceful terms in office. If an international criminal court – including, but not limited to, the ICC – indicts them, however, their chance of losing office increases greatly. If they insist on remaining in power, both the state's receipt of development capital and its domestic production tumble. These courts' indictments prove to be more consequential than other public reports about prosecutable human-rights abuses ostensibly committed by the leader's administration. The ICC's power is real, but it has gaps, politicizing the expansion of its jurisdiction.
Temperature-Sensitive Transient Receptor Potential Channels in Corneal Tissue Layers and Cells

We here provide a brief summary of the characteristics of transient receptor potential channels (TRPs) identified in corneal tissue layers and cells. In general, TRPs are nonselective cation channels which are Ca2+ permeable. Most TRPs serve as thermosensitive molecular sensors (thermo-TRPs). Based on their functional importance, the possibilities are described for drug-targeting TRP activity in a clinical setting. TRPs are expressed in various tissues of the eye including both human corneal epithelial and endothelial layers as well as stromal fibroblasts and stromal nerve fibers. TRP vanilloid type 1 (TRPV1) heat receptor, also known as capsaicin receptor, along with TRP melastatin type 8 (TRPM8) cold receptor, which is also known as menthol receptor, are prototypes of the thermo-TRP family. The TRPV1 functional channel is the most investigated TRP channel in these tissues, owing to its contribution to maintaining tissue homeostasis as well as eliciting wound healing responses to injury. Other thermo-TRP family members identified in these tissues are TRPV2, 3 and 4. Finally, there is the TRP ankyrin type 1 (TRPA1) cold receptor. All of these thermo-TRPs can be activated within specific temperature ranges and transduce such inputs into chemical and electrical signals. Although several recent studies have begun to unravel complex roles for thermo-TRPs such as TRPV1 in corneal layers and resident cells, additional studies are needed to further elucidate their roles in health and disease.
A Hierarchical Game Approach for Multi-Operator Spectrum Sharing in LTE Unlicensed

Allowing cellular operators to offload data traffic to unlicensed spectrum has the potential to significantly increase the capacity of the cellular network systems. This paper considers the spectrum sharing among multiple cellular operators in the unlicensed spectrum. One of the main challenges for this system is how to control the interference between the cellular users and the unlicensed users in other networks, e.g., Wi-Fi, and the interference among cellular users of different operators. As such, we develop a hierarchical game where there is a Kalai- Smorodinsky bargaining game among leaders and a Stackelberg game between operators and mobile users (MU). Accordingly, multiple operators can negotiate with each other for the revenue obtained from the unlicensed spectrum and use a pricing mechanism to control the interference caused by each MU to other operators and users in other unlicensed networks. Simulation results show that our proposed strategy significantly increases the revenue and utility for both operators and MUs.
Intraocular safety and pharmacokinetics of hexadecyloxypropyl-cidofovir (HDP-CDV) as a long-lasting intravitreal antiviral drug.

PURPOSE To evaluate the intraocular safety and pharmacokinetics of hexadecyloxypropyl-cidofovir (HDP-CDV), the hydrolysis product of HDP-cyclic-CDV, a long-lasting intravitreal cidofovir prodrug for cytomegalovirus (CMV) retinitis. METHODS HDP-cyclic-CDV was suspended in phosphate-buffered saline (PBS) at 37°C and formation of HDP-CDV was monitored by high-performance liquid chromatography (HPLC) analysis for 30 weeks. The safety and pharmacokinetics of HDP-CDV intravitreal injections were studied using New Zealand Red rabbits and (14)C labeled HDP-CDV. Ocular tissues from five time points (1, 3, 7, 14, and 35 days) were analyzed by scintillation counting and HPLC to characterize the pharmacokinetics. RESULTS During the hydrolysis study, approximately 35% of the HDP-cyclic-CDV was converted to HDP-CDV. Evaluation of safety found no toxicity after intravitreal injection of HDP-CDV up to 28 μg/eye. Intravitreal pharmacokinetics of HDP-CDV in the retina, choroid, and vitreous followed a two-phase elimination process and elimination half-lives of 8.4 days (retina), 6.9 days (choroid), and 6.2 days (vitreous). In the retina, cidofovir and an unknown metabolite were detected in the first 2 weeks, and the maximum metabolite concentrations were present 48 hours after the maximum HDP-CDV concentration. CONCLUSIONS HDP-cyclic CDV, under simulated physiologic conditions, slowly converts to HDP-CDV, another potent anti-CMV prodrug that may be taken up by retinal cells and metabolized further to the active antiviral metabolite, cidofovir diphosphate. Taken together, these observations help to explain the ability of a single intravitreal dose of HDP-cyclic-CDV to prevent viral retinitis for up to 68 days in a rabbit model.
Human Rad52-mediated homology search and annealing occurs by continuous interactions between overlapping nucleoprotein complexes

The Rad52 protein has critical functions in distinct pathways of the homology-directed DNA repair, one of which is to promote the annealing of complementary strands of DNA. Both yeast and human Rad52 proteins organize into ring-shaped oligomers with the predominant form being a heptamer. Despite the wealth of information obtained in previous investigations, how Rad52 mediates homology search and annealing remains unclear. Here, we developed single-molecule fluorescence resonance energy transfer approaches to probe hRad52-mediated DNA annealing events in real time. We found that annealing proceeds in successive steps involving rearrangements of the ssDNA–hRad52 complex. Moreover, after initial pairing, further search for extended homology occurs without dissociation. This search process is driven by an interaction between 2 overlapping nucleoprotein complexes. In light of these observations we propose a model for hRad52-mediated DNA annealing where ssDNA release and dsDNA zippering are coordinated through successive rearrangement of overlapping nucleoprotein complexes.