Miracle-dz/UniFAR-FTUs huggingface dataset:
LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11

In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to differentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor LHX2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that LHX2 binds to the nucleosome remodeling and histone deacetylase histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin. When LHX2 is absent, active histone marks at the Fezf2 and Sox11 loci are increased. Loss of LHX2 produces an increase, and overexpression of LHX2 causes a decrease, in layer 5 Fezf2 and CTIP2-expressing neurons. Our results provide mechanistic insight into how LHX2 acts as a necessary and sufficient regulator of genes that control cortical neuronal subtype identity. SIGNIFICANCE STATEMENT The functional complexity of the cerebral cortex arises from an array of distinct neuronal subtypes with unique connectivity patterns that are produced from common progenitors. This study reveals that transcription factor LHX2 regulates the numbers of specific cortical output neuron subtypes by controlling the genes that are required to produce them. Loss or increase in LHX2 during neurogenesis is sufficient to increase or decrease, respectively, a particular subcerebrally projecting population. Mechanistically, LHX2 interacts with chromatin modifying protein complexes to edit the chromatin landscape of its targets Fezf2 and Sox11, which regulates their expression and consequently the identities of the neurons produced. Thus, LHX2 is a key component of the control network for producing neurons that will participate in cortical circuitry.
Evaluation of Transmission Line Model Structures for Silicide-to-Silicon Specific Contact Resistance Extraction

In order to measure silicide-to-silicon specific contact resistance rhoc, transmission line model (TLM) structures were proposed as attractive candidates for embedding in CMOS processes. We optimized TLM structures for nickel silicide and platinum silicide and evaluated them for various doping levels of n- and p-type Si. The measurement limitations and accuracy of the specific contact resistance extraction from the optimized TLM structures are discussed in this paper.
Real governance beyond the 'failed state': negotiating education in the Democratic Republic of the Congo

In the Democratic Republic of Congo (DRC), the state administration has retreated from much of the public domain. The specific case of the education sector - a domain traditionally reserved for the state - shows how public services continue to be provided, and how the Congolese state continues to survive and transform itself. Although no overall power governs the system - there is no overall regulatory authority - this does not mean that the education sector is ungoverned. The state survives as an administrative framework whose role in providing public services has been redefined rather than evaporated. This article describes the organization of the educational system as the direct result of an evolving negotiation process between state and non-state actors. It shows how this negotiated nature of statehood, and the power differentials between the various actors, involve constant renegotiation. Instead of producing uniform results within the education sector, this form of regulation depends on power configurations in particular localities at particular times.
Exact and Approximate Area-Proportional Circular Venn and Euler Diagrams

Scientists conducting microarray and other experiments use circular Venn and Euler diagrams to analyze and illustrate their results. As one solution to this problem, this paper introduces a statistical model for fitting area-proportional Venn and Euler diagrams to observed data. The statistical model outlined in this paper includes a statistical loss function and a minimization procedure that enables formal estimation of the Venn/Euler area-proportional model for the first time. A significance test of the null hypothesis is computed for the solution. Residuals from the model are available for inspection. As a result, this algorithm can be used for both exploration and inference on real data sets. A Java program implementing this algorithm is available under the Mozilla Public License. An R function venneuler () is available as a package in CRAN and a plugin is available in Cytoscape.
On least coherence-preserving negations

We focus on the notion of coherent L-interpretations with respect to a negation operator, as a convenient generalization to a fuzzy or multiple-valued environment of the classical notion of consistent interpretation. We show that, given an L-interpretation I, the set of negation operators n satisfying that I is coherent w.r. t. n has a structure of complete lattice; so there exists the greatest and the least negation operators satisfying such property; moreover, the expression of the least negation operator n satisfying that I is coherent w.r. t. n is presented. Finally, for the case in which the underlying set of truth-values is the real unit interval [0, 1], we describe a method to achieve a practical expression for the least coherence-preserving negation.
Deficiency of iPLA2β Primes Immune Cells for Proinflammation: Potential Involvement in Age-Related Mesenteric Lymph Node Lymphoma

Proinflammation can predispose the body to autoimmunity and cancer. We have reported that iPLA2β−/− mice are susceptible to autoimmune hepatitis and colitis. Here we determined whether cytokine release by immune cells could be affected by iPLA2β deficiency alone or combined with CD95/FasL-antibody treatment in vivo. We also determined whether cancer risk could be increased in aged mutant mice. Immune cells were isolated from 3-month old male WT and iPLA2β−/− mice, and some were injected with anti-CD95/FasL antibody for 6 h. Kupffer cells (KC) or splenocytes and liver lymphocytes were stimulated in vitro by lipopolysaccharide or concanavalinA, respectively. Whole-body iPLA2β deficiency caused increased apoptosis in liver, spleen, and mesenteric lymph node (MLN). KC from mutant mice showed suppressed release of TNFα and IL-6, while their splenocytes secreted increased levels of IFNγ and IL-17a. Upon CD95/FasL activation, the mutant KC in turn showed exaggerated cytokine release, this was accompanied by an increased release of IFNγ and IL-17a by liver lymphocytes. Aged iPLA2β−/− mice did not show follicular MLN lymphoma commonly seen in aged C57/BL6 mice. Thus, iPLA2β deficiency renders M1- and Th1/Th17-proinflammation potentially leading to a reduction in age-related MLN lymphoma during aging.
Worry in adolescents with visual impairment

We assessed worries of 162 German adolescents with visual impairment. Most adolescents reported low levels of worry. Nonetheless, about 25% showed moderate to high levels of worry related to a further decline of vision and not finding the right romantic partner. While adolescents with visual impairment reported lower levels of worry than an age- and gender-matched sample of sighted adolescents, adolescents with stronger visual impairment worried more than those with lower levels of visual impairment. In addition, higher levels of worry were associated with more depressive symptoms and, in part, with less optimism, negative changes of vision in recent years, higher age, and worse grades at school. Possible reasons for the inconsistent associations of visual impairment with levels of worry are discussed.
‘Bad Mothers’ and ‘Delinquent Children’: Unravelling anti-begging rhetoric in the Ecuadorian Andes

In this paper I examine the rhetorics that circulate surrounding the lives of young indigenous women and children who beg on the streets of Quito, Ecuador. I focus particularly on rhetorics being produced and reproduced by urban planners, social workers, religious leaders and the media. Drawing on in-depth interviews, I reveal how these groups regularly imagine indigenous women and children in terms of child exploitation/child delinquency, false manipulation of public sympathies, ignorance, laziness and filth. Indigenous women and children are further understood as being fundamentally ‘out of place’ in the city. I unravel these rhetorics in order to draw attention to how begging is differentiated according to gender, race and age and to reveal how these rhetorics become inserted into exclusionary policies and practices. Moreover, and as a counterpoint to such rhetorics, I provide an alternative understanding of women's and children's involvement in begging by drawing upon the perspectives of indigenous women and children themselves. I argue that far from being passive victims, indigenous women and children work with and around oppressive conditions and mobilise them to their own advantage.
Adaptive Algebraic Multigrid

Efficient numerical simulation of physical processes is constrained by our ability to solve the resulting linear systems, prompting substantial research into the development of multiscale iterative methods capable of solving these linear systems with an optimal amount of effort. Overcoming the limitations of geometric multigrid methods to simple geometries and differential equations, algebraic multigrid methods construct the multigrid hierarchy based only on the given matrix. While this allows for efficient black-box solution of the linear systems associated with discretizations of many elliptic differential equations, it also results in a lack of robustness due to unsatisfied assumptions made on the near null spaces of these matrices. This paper introduces an extension to algebraic multigrid methods that removes the need to make such assumptions by utilizing an adaptive process. Emphasis is on the principles that guide the adaptivity and their application to algebraic multigrid solution of certain symmetric positive-definite linear systems.
The Governance of Nonprofit Organizations

The purpose of this article is to provide a more comprehensive principal–agent theory of nonprofit organizations by combining agency theory with aspects of stakeholder theory, stewardship theory, and empirical literature on the governance and management of nonprofit organizations. First, the use of a stakeholder perspective allows us to identify the principals of a nonprofit organization and to divide nonprofit principal–agent relationships into different categories. Next, we discuss the assumptions and prescriptions of agency theory and stewardship theory and suggest that a complementary use of these theories can contribute to the research of principal–agent relationships. By discussing empirical literature from a stewardship–agency perspective, we are able to address issues of nonprofit accountability. We conclude by giving suggestions for further research and by stressing the importance of a recruitment policy to avoid internal agency problems.
The role of molybdenum in suppressing cold dwell fatigue in titanium alloys

We test a hypothesis to explain why Ti-6242 is susceptible to cold dwell fatigue (CDF), whereas Ti-6246 is not. The hypothesis is that, in Ti-6246, substitutional Mo-atoms in α-Ti grains trap vacancies, thereby limiting creep relaxation. In Ti-6242, this creep relaxation enhances the loading of grains unfavourably oriented for slip and they subsequently fracture. Using density functional theory to calculate formation and binding energies between Mo-atoms and vacancies, we find no support for the hypothesis. In the light of this result, and experimental observations of the microstructures in these alloys, we agree with the recent suggestion (Qiu et al. 2014 Metall. Mater. Trans. A 45, 6075–6087. (doi:10.1007/s11661-014-2541-5)) that Ti-6246 has a much smaller susceptibility to CDF because it has a smaller grain size and a more homogeneous distribution of grain orientations. We propose that the reduction of the susceptibility to CDF of Ti-6242 at temperatures above about 200°C is due to the activation of 〈c+a〉 slip in ‘hard’ grains, which reduces the loading of grain boundaries.
Intrathecal Narcotics for Labor Revisited: The Combination of Fentanyl and Morphine Intrathecally Provides Rapid Onset of Profound, Prolonged Analgesia

Many anesthesiologists are frustrated by the limitations of currently available techniques for labor analgesia (1). Parenteral medications, commonly used for labor analgesia, can depress both mother and baby without providing adequate pain relief (1,2). Lumbar epidural analgesia, although very effective at relieving the pain of labor, is actually received by only 16% of laboring patients in the United States (1). Reasons cited for the underutilization of this technique include the amount of time required and the poor reimbursement offered (1). Intrathecal morphine (1-2 mg) can be rapidly administered and provides good analgesia for the first stage of labor; however, the associated long latency, high incidence of side effects, and lack of perineal anesthesia severely limit its usefulness (3-6). We hypothesized that the intrathecal administration of a combination of fentanyl, a narcotic with a short latency and a brief duration of action, and a lower dose of morphine might provide satisfactory labor analgesia with a shorter latency and a lower incidence of side effects. Here, we report the results of administering intrathecal fentanyl 25 pg and morphine 0.25 mg to 15 laboring patients.
Canoe Pedagogy and Colonial History: Exploring Contested Spaces of Outdoor Environmental Education

In this paper, I explore how histories of colonialism are integral to the Euro-Western idea of wilderness at the heart of much outdoor environmental education. In the context of canoe tripping, I speculate about why the politics of land rarely enters into teaching on the land. Finally, because learning from difficult knowledge often troubles the learner, I consider the pedagogical value of emotional responses to curricula that address colonial implication.
Use of School-Based Health Centres for Mental Health Support in Cape Breton, Nova Scotia

Objective: To determine whether students with self-reported needs for mental health support used school-based health centres (SBHCs) for this purpose. Method: A secondary analysis was conducted on self-reported data collected from 1629 high school students from Cape Breton, Nova Scotia. Descriptive statistics and logistic regression analyses were employed to determine the influence of sex, grade, sexual orientation, socioeconomic status (SES), school performance, social involvement, and health risk-taking behaviours on need for mental health support and use of SBHC for that purpose. Results: One-half of surveyed students reported needs for mental health support. Risk for depression was the most commonly reported indicator of need. Only 13% of students visited a SBHC nurse for mental health support, and 4 times as many females than males used the SBHC for this purpose (20.4%, compared with 5.3%, P < 0.001). There was a significantly increased likelihood of use of SBHC for mental health support, given the presence of a greater number of need factors. Multivariate logistic regression determined that female sex (OR 5.57, 95% CI 3.07 to 10.09), lower SES factor (OR 1.19, 95% CI 1.11 to 1.28), sexual health risk-taking behaviours (OR 1.72, 95% CI 1.28 to 2.31), and suicidal behaviour (OR 1.83, 95% CI 1.48 to 2.27) were significantly associated with the use of SBHCs for mental health support. Conclusions: Substantial need for mental health support and significant unmet need were observed. In particular, male students underused the services relative to their self-reported need. Implications for SBHCs and directions for future research are discussed.
Building Upon the Theoretical Debate: A Critical Review of the Empirical Studies of Mezirow's Transformative Learning Theory

This critical literature review is an attempt to build upon the theoretical debate of Mezirow's transformative learning theory by investigating what the empirical studies have to say about a perspective transformation. The review finds much support for Mezirow's theory, but at the same time suggests a need to reconceptualize the process of a perspective transformation. The review discloses a learning process that needs to recognize to a greater degree the significant influence of context, the varying nature of the catalyst of the process, the minimization of the role of critical reflection and increased role of other ways of knowing and relationships, and an overall broadening of the definitional outcome of a perspective transformation. Research needs to continue, particularly in the areas of cultural diversity, the fostering of transformative learning in the classroom, and the nature of and relationship between critical reflection and other ways of knowing. Designs of research including other methods beyond interviews, such as observations and content analysis in an ongoing educational context, would also be valuable.
HYDROLYSIS OF IRINOTECAN AND ITS OXIDATIVE METABOLITES ,

Carboxylesterases metabolize ester, thioester, carbamate, and amide compounds to more soluble acid, alcohol, and amine products. They belong to a multigene family with about 50% sequence identity between classes. CES1A1 and CES2 are the most studied human isoenzymes from class 1 and 2, respectively. In this study, we report the cloning and expression of a new human isoenzyme, CES3, that belongs to class 3. The purified recombinant CES3 protein has carboxylesterase activity. Carboxylesterases metabolize the carbamate prodrug 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11; irinotecan) to its active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38), a potent topoisomerase I inhibitor. CYP3A4 oxidizes CPT-11 to two major oxidative metabolites, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1piperidino] carbonyloxycamptothecin (APC) and 7-ethyl-10-[4-(1piperidino)-1-amino]-carbonyloxycamptothecin (NPC). In this study, we investigate whether these oxidative metabolites, NPC and APC, can be metabolized to SN-38 by purified human carboxylesterases, CES1A1, CES2, and CES3. We find that CPT-11, APC, and NPC can all be metabolized by carboxylesterases to SN-38. CES2 has the highest catalytic activity of 0.012 min 1 M 1 among the three carboxylesterases studied for hydrolysis of CPT-11. NPC was an equally good substrate of CES2 in comparison to CPT-11, with a catalytic efficiency of 0.005 min 1 M . APC was a very poor substrate for all three isoenzymes, exhibiting a catalytic activity of 0.015 10 3 min 1 M 1 for CES2. Catalytic efficiency of CES3 for CPT-11 hydrolysis was 20to 2000-fold less than that of CES1A1 and CES2. The relative activity of the three isoenzymes was CES2 > CES1A1 CES3, for all three substrates. CPT-11 is a water-soluble carbamate prodrug of camptothecin and is activated in vivo to SN-38, a potent topoisomerase I inhibitor (Kunimoto et al., 1987). CPT-11 either alone or in combination with other chemotherapeutic agents has shown promising clinical activity against several solid tumors (Rothenberg, 2001). Currently, CPT-11 in combination with 5-fluorouracil and leucovorin is approved by the U.S. Food and Drug Administration as first-line therapy in the treatment of metastatic carcinoma of colon or rectum [Camptosar (irinotecan hydrochloride) package insert, Pharmacia & Upjohn Co., 2002
Downlink Non-Orthogonal Multiple Access (NOMA) in Poisson Networks

A network model is considered, where Poisson distributed base stations transmit to <inline-formula> <tex-math notation="LaTeX">$N$ </tex-math></inline-formula> power-domain non-orthogonal multiple access (NOMA) users (UEs) each that employ successive interference cancellation (SIC) for decoding. We propose three models for the clustering of NOMA UEs and consider two different ordering techniques for the NOMA UEs: mean signal power-based and instantaneous signal-to-intercell-interference-and-noise-ratio-based. For each technique, we present a signal-to-interference-and-noise ratio analysis for the coverage of the typical UE. We plot the rate region for the two-user case and show that neither ordering technique is consistently superior to the other. We propose two efficient algorithms for finding a feasible resource allocation that maximize the cell sum rate <inline-formula> <tex-math notation="LaTeX">$\mathcal {R}_{\mathrm{ tot}}$ </tex-math></inline-formula>, for general <inline-formula> <tex-math notation="LaTeX">$N$ </tex-math></inline-formula>, constrained to: 1) a minimum throughput <inline-formula> <tex-math notation="LaTeX">$\mathcal {T}$ </tex-math></inline-formula> for each UE, 2) identical throughput for all UEs. We show the existence of: 1) an optimum <inline-formula> <tex-math notation="LaTeX">$N$ </tex-math></inline-formula> that maximizes the constrained <inline-formula> <tex-math notation="LaTeX">$\mathcal {R}_{\mathrm{ tot}}$ </tex-math></inline-formula> given a set of network parameters and 2) a critical SIC level necessary for NOMA to outperform orthogonal multiple access. The results highlight the importance in choosing the network parameters <inline-formula> <tex-math notation="LaTeX">$N$ </tex-math></inline-formula>, the constraints, and the ordering technique to balance the <inline-formula> <tex-math notation="LaTeX">$\mathcal {R}_{\mathrm{ tot}}$ </tex-math></inline-formula> and fairness requirements. We also show that interference-aware UE clustering can significantly improve performance.
Conditioning in identical twins with ataxia-telangiectasia

Abstract Evidence has accumulated to indicate an essential role for the cerebellum in eyeblink classical conditioning, with normal acquisition impaired by lesions in the cerebellar cortex. For this reason, eyeblink conditioning was studied in a pair of 16-year-old identical twin females with ataxia-telangiectasia (AT), a disorder with onset in early childhood characterized by diffuse, almost selective, degeneration of the cerebellar cortex with extensive loss of Purkinje cells. We also tested a pair of 16-year-old identical twin female normal control subjects. Twins with AT produced significantly fewer conditioned responses (CRs). The mean percentages of CRs over 144 trials for each eye were 23.0% (left eye) and 10.2% (right eye) in patients with AT, and 45.9% (left eye) and 45.3% (right eye) in normal control subjects. The magnitude of the eyeblink reflex, assessed as unconditioned response amplitude, was not different between patients with AT and control subjects. The results indicate that patients with.
The Implications of Dying Cancer Patients' Talk on Cardiopulmonary Resuscitation and Do-Not-Resuscitate Orders

Current medical emphasis on autonomy requires that patients be primary in authorizing do-not-resuscitate (DNR) orders, countermanding provision of cardiopulmonary resuscitation (CPR) on terminally ill patients. The assumptions that patients make regarding CPR and DNR orders will influence their choices about them. Using discursive analysis, the authors examined the speech of 28 patients dying of cancer regarding the appropriateness of refraining from CPR or of instituting DNR orders. Most participants identified CPR as inappropriate in their circumstances, favoring institution of DNR orders. However, a minority drew on dominant construals of DNR orders and CPR to locate themselves outside the category of suitable candidates for DNR orders, thus justifying a preference for CPR—even though some had current DNR orders. Doctors' and patients' assessments of eligibility for DNR orders might not coincide, and when patient autonomy is presumed by patients to be determinant, discrepancies between patient expectations and instituted medical practice are inevitable.