Miracle-dz/UniFAR-FTUs huggingface dataset:
AF64A: An Active Site Directed Irreversible Inhibitor of Choline Acetyltransferase

Abstract: Ethylcholine mustard aziridinium ion (AF64A, MEChMAz) has been proposed as a cholinergic neuronspecific neurotoxin. We report that in further studies on its mechanism of action incubation of the cholinergic neuroblastoma × glioma cell line, NG‐108‐15, with 100 μM AF64A resulted in a rapid decrease in cellular choline acetyltransferase (ChAT) activity which preceded cytotoxicity. Thus, a 60–85% decrease in ChAT activity was measured within 5 h of AF64A exposure, whereas cell lysis (measured as the release of the cytosolic enzyme lactate dehydrogenase into the medium) did not become apparent until 18 h of AF64A exposure. This led us to examine the effects of AF64A on partially purified ChAT. We report a concentration‐ and time‐dependent inhibition of partially purified ChAT by AF64A that could not be reversed by dialysis but could be prevented by coincubation of the enzyme and AF64A with choline but not with acetyl‐coenzyme A. We present kinetic evidence that choline and AF64A compete for the same site on the enzyme. In addition, thiosulfate, which inactivates the aziridinium ion, eliminated AF64A's capacity to inhibit the enzyme. AF64A also irreversibly inhibited partially purified choline kinase and acetylcholinesterase but not lactate dehydrogenase, alcohol dehydrogenase, carboxypeptidase A, or chymotrypsinogen, enzymes that do not use choline as a substrate or product. Thus, the data suggest that AF64A acts as an irreversible active site directed inhibitor of ChAT and possibly other enzymes recognizing choline.
Mitotic Regulators Govern Progress through Steps in the Centrosome Duplication Cycle

Centrosome duplication is marked by discrete changes in centriole structure that occur in lockstep with cell cycle transitions. We show that mitotic regulators govern steps in centriole replication in Drosophila embryos. Cdc25string, the expression of which initiates mitosis, is required for completion of daughter centriole assembly. Cdc20fizzy, which is required for the metaphase-anaphase transition, is required for timely disengagement of mother and daughter centrioles. Stabilization of mitotic cyclins, which prevents exit from mitosis, blocks assembly of new daughter centrioles. Common regulation of the nuclear and centrosome cycles by mitotic regulators may ensure precise duplication of the centrosome.
Model-based segmentation and recognition from range data

This paper aims at developing a model-based system for the object recognition of three-dimensional objects with curved surfaces using range images. The model data is represented using a CAD-model, providing a mathematical precise and reliable description of arbitrary shapes. The proposed method is based on model-based range image segmentation, using curvature as invariant features. By integrating model information into the segmentation stage, the segmentation process is guided to provide a partitioning corresponding to that of the CAD-model. The work provides a way to detect objects in arbitrary positions and derive the transformation onto a CAD-model. Thereby it contributes to the development of automated systems in the areas of inspection, manufacturing and robotics.
A Remote Parallel Computation System for Biomedical Data Visualization on the Grid

In this paper, a collaborative system for visualizing biomedical dataset on a Grid environment was proposed. Globus Toolkit was used for the integration of computational resources in the Grid environment, and the Visualization Toolkit (VTK) is used as the tool for processing the biomedical dataset. The results can be viewed by the users who are located at different places and connected together via internet. To allow the users to discuss the results cooperatively, Access Grid (AG) is used as the basic operation platform. Several shared applications were designed to allow users at remote sites to share user interface and visualizations. The system allows for the manipulating of the viewing objects by rotation, translation, and scaling.
Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement

Significance The first retinal gene therapy in human blindness from RPE65 mutations has focused on safety and efficacy, as defined by improved vision. The disease component not studied, however, has been the fate of photoreceptors in this progressive retinal degeneration. We show that gene therapy improves vision for at least 3 y, but photoreceptor degeneration progresses unabated in humans. In the canine model, the same result occurs when treatment is at the disease stage equivalent to humans. The study shows the need for combinatorial therapy to improve vision in the short term but also slow retinal degeneration in the long term. Leber congenital amaurosis (LCA) associated with retinal pigment epithelium-specific protein 65 kDa (RPE65) mutations is a severe hereditary blindness resulting from both dysfunction and degeneration of photoreceptors. Clinical trials with gene augmentation therapy have shown partial reversal of the dysfunction, but the effects on the degeneration are not known. We evaluated the consequences of gene therapy on retinal degeneration in patients with RPE65-LCA and its canine model. In untreated RPE65-LCA patients, there was dysfunction and degeneration of photoreceptors, even at the earliest ages. Examined serially over years, the outer photoreceptor nuclear layer showed progressive thinning. Treated RPE65-LCA showed substantial visual improvement in the short term and no detectable decline from this new level over the long term. However, retinal degeneration continued to progress unabated. In RPE65-mutant dogs, the first one-quarter of their lifespan showed only dysfunction, and there was normal outer photoreceptor nuclear layer thickness retina-wide. Dogs treated during the earlier dysfunction-only stage showed improved visual function and dramatic protection of treated photoreceptors from degeneration when measured 5–11 y later. Dogs treated later during the combined dysfunction and degeneration stage also showed visual function improvement, but photoreceptor loss continued unabated, the same as in human RPE65-LCA. The results suggest that, in RPE65 disease treatment, protection from visual function deterioration cannot be assumed to imply protection from degeneration. The effects of gene augmentation therapy are complex and suggest a need for a combinatorial strategy in RPE65-LCA to not only improve function in the short term but also slow retinal degeneration in the long term.
Cycles of Control: Worker Participation in Sociological and Historical Perspective

This paper argues that worker participation has not evolved out of the humanization of capitalism, as is usually suggested, but has appeared cyclically. These cycles are traced over more than a century and are shown to correspond to periods when management authority is felt to be facing challenge. Participation is thus best understood as a means of attempting to secure labour's compliance. However, the framework of common interests upon which participation is premised is untenable, and in practice the efficiency of such schemes in Britain has been for the most part severely attenuated by the realities of structural conflict.
Student nurses' conceptions of internationalisation in general and as an essential part of Swedish nurses' education

The aim of this study was to describe student nurses’ conceptions of internationalisation. Firstly this is done in terms of what they themselves conceive as important and related to internationalisation. Secondly, student nurses’ conceptions of internationalisation are described in terms of how they experience internationalisation in their current nursing education programme, based on their teachers’ interpretation of the curriculum objectives on internationalisation. This empirical study was conducted using a phenomenographic approach to analyse and interpret data from interviews with 24 student nurses. Analyses of the data reveal that student nurses’ conceptions of internationalisation differ significantly, in terms of perspective, focus and relation to educational content. The findings are described in three categories of conceptions of internationalisation. Some crucial aspects of internationalisation identified by the students do not correspond to any actual educational content, that is, are not experienced by students as being part of the present educational content. Instead, the students’ awareness of these aspects of internationalisation is related to their informal, unique and cultural background. From a pedagogical point of view the findings indicate a need to increase the attention given to internationalisation in nurses’ education. The description of variations in students’ awareness of aspects of internationalisation provides the students (and teachers) with the opportunity to compare various ways of conceptualising internationalisation. Knowledge of these variations can broaden and deepen understanding of internationalisation.
New Organizational Forms: Towards a Generative Dialogue

The concept of `new organizational forms' has been with us for over 20 years, but little attention has been given to the diverse assumptions underlying various researchers' use of this term. We identify five areas where different assumptions are in use, underpinned by a variety of theoretical perspectives. We urge scholars to engage in a generative dialogue about new organizational forms across theoretical perspectives. The aim of a generative dialogue is to identify where areas of agreement about new organizational forms can be achieved and where differences can be accepted and respected.
Verapamil and tiapamil in prevention of ventricular fibrillation in pigs with coronary ligation. Comparative effects on left ventricular function.

Antiarrhythmic and hemodynamic effects of the calcium channel antagonist verapamil were compared with those of tiapamil, a congener, in open-chest pigs with anterior descending coronary artery ligation. Tiapamil (6 mg/kg i.v.) decreased the incidence of ventricular fibrillation to 4 of 10 versus 22 of 25 in controls (p less than 0.05) and maintained left ventricular dP/dtmax after ligation (predrug value: 2,312 +/- 112 mm Hg/sec; 20 minutes after ligation: 2,139 +/- 229 mm Hg/sec). Tiapamil increased blood flow in the peripheral ischemic zone (24 +/- 3.2% vs. 16.9 +/- 1.6% of preligation value in controls, p less than 0.05) as well as in the peri-ischemic and nonischemic zones (153.9 +/- 12.7% and 186.3 +/- 17.1%, respectively; both p less than 0.0001 vs. 97.9 +/- 5% and 91.3 +/- 4.7% in controls). Verapamil (0.6 mg/kg i.v.) decreased the incidence of ventricular fibrillation to 0 of 7 versus 22 of 25 in controls (p less than 0.005); left ventricular dP/dtmax decreased from 2,062 +/- 144 to 1,060 +/- 168 mm Hg/sec (p less than 0.0001). Verapamil did not change blood flow in the peripheral, peri-ischemic, or nonischemic zones. Thus, tiapamil, and not verapamil, decreased ischemic ventricular fibrillation while maintaining left ventricular mechanical function. Verapamil congeners warrant further evaluation as antiarrhythmic agents in acute myocardial ischemia.
Sebastian Scholz : Derivatives and Default Risk

Upstream producers that possess market power, sell forwards with a lengthy duration to regional electricity companies (REC). As part of the liberalization of the electricity market, RECs have been privatized and exposed to a possible bankruptcy threat if spot prices have fallen below their expected value. The downstream firms’ expected profit is larger, when it is less likely to be bailed out, the effect on upstream profits is ambiguous while consumers loose. Options are less welfare increasing than forwards, but the difference is minimal. In the presence of bankruptcy, options are the preferred welfare maximizing market instrument.
Childhood Risky Family Environments and Romantic Relationship Functioning Among Young Adult Dating Couples

This study evaluated associations between dating partners’ risky family backgrounds in childhood and current romantic relationship functioning. One hundred young adult dating couples (N = 200) self-reported childhood risky family environments (e.g., conflict, nonnurturing behavior, neglect) and current relationship satisfaction. Partners also engaged in laboratory-based conflict, which was subsequently coded for positive and negative interaction qualities. Results revealed a positive linkage between males’ and females’ risky family backgrounds. Actor–Partner Interdependence Modeling, which accommodated dyadic data and controlled for neuroticism levels, indicated that males’ riskier family backgrounds were associated with their female partners’ greater observed negative interaction qualities (e.g., conflict) and with their partners’ lower observed positive interaction (e.g., support, communication skills). Experiencing interparental divorce during childhood moderated the results, with riskier family backgrounds holding more negative implications for subsequent young adult romantic relationships when the parents remained together during childhood compared to when the parents divorced.
Story-retelling as a measure of expressive language in school-aged children a normative study

In this study, the expressive language abilities of 100 5-to 9-year-old normally developing Cantonese-speaking children in five age groups were examined through a story re-telling task. Developmentally sensitive grammatical structures and lexical items were embedded in the story written for this task. The use of these target structures and items in each child's story was summarized as the Grammatical score and the Lexical score respectively. On both measures, children received higher scores with age. The Grammatical score discriminated the five age groups better than the Lexical score. Differences on the Grammatical score between consecutive age groups were all significant except between the 8and 9-year olds. The Mean Length of C-units (MLCU) showed a moderate positive correlation with age, indicating potential as a developmental index of language development in school-aged children, A moderate positive correlation was also found between MLCU and the Grammatical score, and between MLCU and the Lexical score. These results confirm the developmental sensitivity of these two scores. In sum, findings from this study indicated that measures of children's use of specific grammatical structures and lexical items through story re-retelling do show potentials for further development into a screening tool for identifying children with language impairment.
[Effect of Electroacupuncture Intervention on Expression of Pain Sensory and Affective Proce- ssing-related µ-opioid Receptor, etc. in the Amygdala in Chronic Neuropathy Pain Rats].

OBJECTIVE To observe the effect of electroacupuncture (EA) on expression of pain sensory and affective processing-related µ-opioid receptor (MOR), glutamatergic AMPA receptor subunit GIuA 1, extracellular signal-regulated kinase (ERK 1/2), cAMP response element binding protein(CREB) in the amygdala in chronic constrictive injury (CC) + negative affection(NA) rats, so as to reveal its mechanism underlying pain relief. METHODS A total of 32 male Wistar rats were randomized into normal control, model, EA, and anesthesia+ EA (AEA) groups (n = 8 in each group). The neuropathic pain NA model was established by ligation of the left sciatic nerve and repeated electrical stimulation of the paw-bottom in the pain-paired compartment. EA was applied to bilateral "Zusanli" (ST 36) and "Yanglingquan" (GB 34) for 30 min, once daily for 7 days. Thermal pain threshold (paw withdrawl latency, PWL) of the bilateral paws was measured by using a Tail-Flick Unit. The expression levels of MOR and p-CREB in the central amygdala (CeA) and those of MOR, GluA 1, p-ERK 1/2 and p-CREB in the right amygdala area were determined using immunofluorescence and Western blot, respectively. RESULTS in comparison with the normal group, PWL difference (PWLD) values of the model group were significantly increased (P < 0.001), and the time spent in the CPA-paired. compartment was considerably decreased (P < 0.001). After EA, the PWLD levels of both EA and AEA groups were apparently decreased (P < 0.05), showing a pain relief; and the time spent in the CPA-paired compartment was apparently increased in the EA group (P < 0.05) , rather than in the AEA group (P > 0.05). Additionally , compared to the normal group, the expression level of MOR protein in the amygdala was remarkably increased (P < 0.05) and those of GIuA 1, p-ERK 2 and p-CREB proteins were apparently decreased (P < 0.05). After EA intervention for 7 days, the expression levels of these four proteins in the EA group, and those of MOR, p-ERK 2 and p-CREB in the AEA group were significantly up-regulated (P < 0.001, P < 0.01, P < 0.05). The expression level of GIuA 1 was significantly higher in the EA group than in the AEA group (P < 0.05). CONCLUSION Repeated EA stimulation of ST 36-GB 34 has a definite effect in relieving both sensation and affection dimensions of pain in NA rats, which may be related to its effect in up-regulating the expression of GIuA 1 in the amygdala, but the effects of MOR, p-ERK 2 and p-CREB need being researched further.
Range Verification Methods in Particle Therapy: Underlying Physics and Monte Carlo Modeling

Hadron therapy allows for highly conformal dose distributions and better sparing of organs-at-risk, thanks to the characteristic dose deposition as function of depth. However, the quality of hadron therapy treatments is closely connected with the ability to predict and achieve a given beam range in the patient. Currently, uncertainties in particle range lead to the employment of safety margins, at the expense of treatment quality. Much research in particle therapy is therefore aimed at developing methods to verify the particle range in patients. Non-invasive in vivo monitoring of the particle range can be performed by detecting secondary radiation, emitted from the patient as a result of nuclear interactions of charged hadrons with tissue, including β+ emitters, prompt photons, and charged fragments. The correctness of the dose delivery can be verified by comparing measured and pre-calculated distributions of the secondary particles. The reliability of Monte Carlo (MC) predictions is a key issue. Correctly modeling the production of secondaries is a non-trivial task, because it involves nuclear physics interactions at energies, where no rigorous theories exist to describe them. The goal of this review is to provide a comprehensive overview of various aspects in modeling the physics processes for range verification with secondary particles produced in proton, carbon, and heavier ion irradiation. We discuss electromagnetic and nuclear interactions of charged hadrons in matter, which is followed by a summary of some widely used MC codes in hadron therapy. Then, we describe selected examples of how these codes have been validated and used in three range verification techniques: PET, prompt gamma, and charged particle detection. We include research studies and clinically applied methods. For each of the techniques, we point out advantages and disadvantages, as well as clinical challenges still to be addressed, focusing on MC simulation aspects.
The Role of Career and Technical Education in Iowa Community Colleges

ABSTRACT This scholarly paper describes and analyzes the role of career and technical education (CTE) in Iowa community colleges. Iowa's community colleges are doing a good job of responding to the changing workforce needs of the state and providing smooth career pathways. However, changes in the population and economy of the state will call for further changes in CTE programs. The distinctive characteristics of CTE in Iowa community colleges, the impact of community college CTE programs on the state's economy, the role of accountability, and the future implications for CTE in the state are discussed. Recommendations based on the results of the study include improving articulation agreements, increasing retention among at-risk students, and increasing collaboration among Iowa's 15 community colleges.
Optimal Dynamic Mechanism Design and the Virtual Pivot Mechanism

We consider the problem of designing optimal mechanisms for settings where agents have dynamic private information. We present the virtual-pivot mechanism, which is optimal in a large class of environments that satisfy a separability condition. The mechanism satisfies a rather strong equilibrium notion (it is periodic ex post incentive compatible and individually rational). We provide both necessary and sufficient conditions for immediate incentive compatibility for mechanisms that satisfy periodic ex post incentive compatibility in future periods. The result also yields a strikingly simple mechanism for selling a sequence of items to a single buyer. We also show that the allocation rule of the virtual-pivot mechanism has a very simple structure (a virtual index) in multiarmed bandit settings. Finally, we show through examples that the relaxation technique we use does not produce optimal dynamic mechanisms in general nonseparable environments.
Does the mode of candidate selection affect the representativeness of parties?

In this article, we analyse the impact of intra-party procedures of candidate selection for national elections on the representativeness of parties towards their voters. With regard to candidate selection we distinguish between two dimensions: inclusion and centralization. While the first identifies the type of selectorate for candidate nominations (members, delegates or committees), the second captures the territorial unit in which the nomination is decided (local, regional or national). Based on data for 53 parties in 9 Western European countries for the period 1970 to 1990, the analysis points to the relevance of the inclusion dimension. Parties in which party elites decide the nomination of candidates show slightly higher degrees of representation than parties with more inclusive selectorates. We conduct our analysis separately for two frequently used but theoretically different concepts of representation: cross-sectional representation (at one point in time) and dynamic representation (over time). Our analysis shows that candidate-selection procedures only matter for the first concept. The empirically inconsistent results between the two concepts are due to deficiencies in the way dynamic representation is currently operationalized.
Applying Hofstede’s National Culture Measures in Tourism Research: Illuminating Issues of Divergence and Convergence

Given the emerging evidence that national culture influences visitor behavior and that Hofstede’s concept (1980, 2001) has become the most accepted means to quantify dominant national cultural values, the focus of this study was to test the underlying assumptions of how these measures are applied in research. Drawing from a sample of tourists from eight countries who completed Hofstede’s original instruments, the results reveal little differences between Hofstede’s 2001 national cultural measures with the current study’s data. This finding provides strong support for Hofstede’s dimensions as a measure of central tendencies of visitors from different nations. Second, graphically contrasting respondents’ values along the five cultural dimensions reveals that the between-nation differences are relatively small when compared to the within-nation variability, indicating that subcultures do exist. This analysis also identifies international regions that cluster closely together, demonstrating that national cultural differences do not end at national borders.