Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Requirements of Transmembrane Domain 3 for Activation by the M1 Muscarinic Receptor Agonists AC-42, AC-260584, Clozapine, and N-Desmethylclozapine: Evidence for Three Distinct Modes of Receptor Activation

Transmembrane domain 3 (TM3) plays a crucial role mediating muscarinic acetylcholine receptor activation by acetylcholine, carbachol, and other muscarinic agonists. We compared the effects of point mutations throughout TM3 on the interactions of carbachol, 4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl] piperidine hydrogen chloride (AC-42), a potent structural analog of AC-42 called 4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one (AC-260584), N-desmethylclozapine, and clozapine with the M1 muscarinic receptor. The binding and activation profiles of these ligands fell into three distinct patterns; one exemplified by orthosteric compounds like carbachol, another by structural analogs of AC-42, and a third by structural analogs of N-desmethylclozapine. All mutations tested severely reduced carbachol binding and activation of M1. In contrast, the agonist actions of AC-42 and AC-260584 were greatly potentiated by the W101A mutation, slightly reduced by Y106A, and slightly increased by S109A. Clozapine and N-desmethylclozapine displayed substantially increased maximum responses at the Y106A and W101A mutants, slightly lower activity at S109A, but no substantial changes in potency. At L102A and N110A, agonist responses to AC-42, AC-260584, clozapine, and N-desmethylclozapine were all substantially reduced, but usually less than carbachol. D105A showed no functional responses to all ligands. Displacement and dissociation rate experiments demonstrated clear allosteric properties of AC-42 and AC-260584 but not for N-desmethylclozapine and clozapine, indicating that they may contact different residues than carbachol to activate M1 but occupy substantially overlapping spaces, in contrast to AC-42 and AC-260584, which occupy separable spaces. These results show that M1 receptors can be activated in at least three distinct ways and that there is no requirement for potent muscarinic agonists to mimic acetylcholine interactions with TM3.
Optic Disc Characteristics and Visual Field Progression in Normal Tension Glaucoma Patients With Tilted Optic Discs

Purpose of the Study:The purpose of the study was to evaluate the optic disc characteristics associated with visual field (VF) progression in normal tension glaucoma (NTG) eyes with tilted optic discs. Methods:Sixty-six eyes of 66 NTG patients with tilted optic disc were included in this cross-sectional study, who were examined by at least 5 Humphrey 30-2 VFs. Glaucomatous VF progression was evaluated using pointwise linear regression. Optic nerve heads were scanned with enhanced-depth imaging optical coherence tomography (EDI-OCT), and evaluated for the focal lamina cribrosa (LC) defects and LC thicknesses. Optic disc torsion degrees and tilt ratios were measured from disc photographs. Logistic regression analyses were used to identify the risk factors for VF progression and focal LC defects. Results:Multivariate analysis showed that VF progression was associated with the presence of focal LC defects and greater number of VFs. The eyes with focal LC defects were associated with greater torsion degree and tilt ratio in multivariate analysis. The VF mean deviation slopes and localized VF progression rates in eyes with focal LC defects were greater than those without defects. Conclusions:The greater optic disc tilt and torsion in NTG eyes with tilted optic disc were associated with focal LC defects, but not with VF progression. The focal LC defects were associated with VF progression. This study suggests that the focal LC defects in NTG patients with tilted optic disc may be an independent risk factor for glaucomatous VF progression, and the development of focal LC defects could be influenced by optic disc torsion or tilt.
Monotone Imitation Dynamics in Large Populations

We analyze a class of imitation dynamics with mutations for games with any finite number of actions, and give conditions for the selection of a unique equilibrium as the mutation rate becomes small and the population becomes large. Our results cover the multiple-action extensions of the aspiration-and-imitation process of Binmore and Samuelson [Muddling through: noisy equilibrium selection, J. Econ. Theory 74 (1997) 235-265] and the related processes proposed by BenaIÂ¨m and Weibull [Deterministic approximation of stochastic evolution in games, Econometrica 71 (2003) 873-903] and Traulsen et al. [Coevolutionary dynamics: from finite to infinite populations, Phys. Rev. Lett. 95 (2005) 238701], as well as the frequency-dependent Moran process studied by Fudenberg et al. [Evolutionary game dynamics in finite populations with strong selection and weak mutation, Theoretical Population Biol. 70 (2006) 352-363]. We illustrate our results by considering the effect of the number of periods of repetition on the selected equilibrium in repeated play of the prisoner's dilemma when players are restricted to a small set of simple strategies.
Integrating CBR-Functionality into a KM-System : The TO _ KNOW-Approach

Knowledge-Management (KM)-systems integrate multiple technologies with the purpose of supporting users who have "knowledge-related" problems. Case-Based Reasoning (CBR)-technology is well known for improving problem solutions. Combining both concepts the project "TO_KNOW" has the goal to design a CBR-component that is adaptable to typical KM-Systems. The basic idea is to take into account user-queries as (intermediate) problem-solutions for getting the needed information from the KM-System's discovery services. This paper describes an architecture to integrate CBR-functionality into a KM-system. We list different scenarios, their potential for synergetic effects, and a set of interfaces and functionalities reflecting the different possibilities of integration.
Failure rates of short (≤ 10 mm) dental implants and factors influencing their failure: a systematic review.

PURPOSE The aim of this study was to evaluate the long-term failure rates of short dental implants (≤ 10 mm) and to analyze the influence of various factors on implant failure. MATERIALS AND METHODS The PubMed and Cochrane Library databases were consulted for follow-up studies published between the years 1980 and 2009. For those studies that met the inclusion and exclusion criteria, data concerning the number of implants (≤ 10 mm) placed and lost and any related risk factors were gathered in tables and subjected to analysis. Univariate and multivariate analyses were performed. RESULTS The heterogeneity and low quality of the included studies made meta-analysis impossible. A total of 35 human studies fulfilled the criteria. The studies included 14,722 implants, of which 659 failed. The total failure rate was 4.5%. The failure rates of implants with lengths of 6, 7, 7.5, 8, 8.5, 9, and 10 mm were 4.1%, 5.9%, 0%, 2.5%, 3.2%, 0.6%, and 6.5%, respectively. A majority (57.9%) of failures occurred before prosthesis connection. There was no statistically significant difference between the failure rates of short dental implants and standard implants or between those placed in a single stage and those placed in two stages (multivariate analysis). There was a tendency toward higher failure rates for the maxilla and for dental implants with a machined surface compared with the mandible and dental implants with a rough surface, respectively. CONCLUSIONS Among the risk factors examined, most failures of short implants can be attributed to poor bone quality in the maxilla and a machined surface. Although short implants in atrophied jaws can achieve similar long-term prognoses as standard dental implants with a reasonable prosthetic design according to this review, stronger evidence is essential to confirm this finding.
Materialism and Morality

That human beings autonomously attempt to decide whether their actions are good or evil appears to be a late historical phenomenon. A highly-developed European individual can bring into the light of clear consciousness and morally evaluate not just important decisions, but also those primarily instinctual and habitual reactions of which his life for the most part consists. However, human actions appear more compulsive as their subjects belong to earlier historical formations. The capacity to subject instinctual reactions to moral criticism and to change them on the basis of individual considerations could only develop with the growing differentiation of society.
Dental status of Portuguese HIV+ patients and related variables: a multivariate analysis.

OBJECTIVE The aim of this cross-sectional study was to evaluate the dental status of 101 Portuguese HIV+ subjects aged 22-71 years (mean = 39) and its association with clinical, socioeconomic, and behavioral variables. MATERIALS AND METHODS A calibrated dentist performed clinical examination and collected data on dental caries, periodontal status, dental plaque levels, prosthetic conditions, and need. The volunteers completed questionnaires on socioeconomic and behavioral variables as well as the Oral Health Impact Profile (OHIP-14) questionnaire. Univariate and multiple logistic regression (MLR) analyses were performed. RESULTS The mean number of decayed, missing or filled teeth index (DMFT index) was 16.44, standard deviation (s.d.) = 8.42. MLR demonstrated that salaried employee and those with OHIP-14 <or=4.22, or any/no dental plaque were less prone to have DMFT > median (=17). As regards prosthetic status, 28.8% of the examined individuals used dental prosthesis. MLR demonstrated that HIV+ with DMFT >17 or those who knew they were HIV-positive for longer than 5 years were more prone to need dental prostheses. The mean OHIP-14 index was 5.83 (s.d. = 7.79). CONCLUSIONS The dental health status of HIV-infected Portuguese patients was unsatisfactory and related to clinical, socioeconomic, and behavioral variables.
Gender discourse about an ethic of care: nursery schoolteachers' perspectives

In this paper we will show some of the results of research which took place in the Principality of Asturias (Spain). Its purpose was finding out the gender discourses used by nursery teachers. Although we will not provide an exhaustive list of all the conclusions reached so far, we will put forward one of the aspects which has been developed throughout the investigation; that is, we will discuss some of our observations and hypotheses on the differences observed by the teachers in boys and girls' caring and supporting behaviours. In order to do so, we focus on the type of discourse related to the ethic of care. We consider it a tool which allows teachers to build a type of narrative in which boys and girls are presented as opposites, relational and different from one another.
Stability and change in personality disorders.

Stability is thought to be one of the major distinguishing features between personality disorders (PDs) and other forms of psychopathology. The development of more reliable PD assessments and the implementation of four major longitudinal studies on PD stability have provided critical data with which to evaluate the stability of PD features. Results from these and other studies reveal significant complexity in the interpretation of PD stability because of several issues that can impact stability estimates. Such estimates will vary as a function of the type of constructs being assessed, the type of stability being considered, the modality and reliability of the assessments being used, and the impacts of sampling. In this article, longitudinal research on PD stability is reviewed in the context of these issues. It is concluded that no single answer can be given to the question, "How stable are PDs? " and that future research and classification need to consider carefully and account for the complexity of this question.
Determinants of Sexual Network Structure and Their Impact on Cumulative Network Measures

There are four major quantities that are measured in sexual behavior surveys that are thought to be especially relevant for the performance of sexual network models in terms of disease transmission. These are (i) the cumulative distribution of lifetime number of partners, (ii) the distribution of partnership durations, (iii) the distribution of gap lengths between partnerships, and (iv) the number of recent partners. Fitting a network model to these quantities as measured in sexual behavior surveys is expected to result in a good description of Chlamydia trachomatis transmission in terms of the heterogeneity of the distribution of infection in the population. Here we present a simulation model of a sexual contact network, in which we explored the role of behavioral heterogeneity of simulated individuals on the ability of the model to reproduce population-level sexual survey data from the Netherlands and UK. We find that a high level of heterogeneity in the ability of individuals to acquire and maintain (additional) partners strongly facilitates the ability of the model to accurately simulate the powerlaw-like distribution of the lifetime number of partners, and the age at which these partnerships were accumulated, as surveyed in actual sexual contact networks. Other sexual network features, such as the gap length between partnerships and the partnership duration, could–at the current level of detail of sexual survey data against which they were compared–be accurately modeled by a constant value (for transitional concurrency) and by exponential distributions (for partnership duration). Furthermore, we observe that epidemiological measures on disease prevalence in survey data can be used as a powerful tool for building accurate sexual contact networks, as these measures provide information on the level of mixing between individuals of different levels of sexual activity in the population, a parameter that is hard to acquire through surveying individuals.
Correlation Between Glycolytic Phenotype and Tumor Grade in Soft-Tissue Sarcomas by 18F-FDG PET

Tumor glycolytic phenotyping can be accomplished with 18F-FDG PET. Tumor 18F-FDG uptake correlates with tumor grade in several cancers. However, the role of 18F-FDG PET for the grading of soft-tissue sarcomas (STSs) warrants further research. Methods: One hundred two patients (48 men and 54 women; mean age ± SD, 50 ± 17 y) with 12 STS subtypes underwent 18F-FDG PET/CT before treatment. Tumor 18F-FDG uptake, expressed as maximum standardized uptake value (SUVmax), was compared among subtypes and correlated with histopathologic grade. Two frequently used sarcoma grading systems—the 3-tier system of the French Federation of Cancer Centers Sarcoma Group (Fédération Nationale des Centres de Lutte Contre le Cancer [FNCLCC]) and a 2-tier system (low grade vs. high grade)—were used. Results: More than 90% of STSs (93/102) exhibited a strong glycolytic phenotype (SUVmax, 2.7–52.2 g/mL). Tumor SUVmax differed significantly among tumor grades (P < 0.001 for the 3- and 2-tier grading systems). The FNCLCC and 2-tier grading systems predicted tumor grade with similar accuracy (area under the curve, 0.83 and 0.85, respectively; P = 0.35). SUVmax differed significantly among histologic subtypes (P = 0.03) in the entire population but not when high-grade STSs were analyzed separately (P = 0.31). Conclusion: The tumor glycolytic phenotype correlated significantly with histologic grade as determined by both the FNCLCC and 2-tier (high vs. low) grading systems. 18F-FDG PET cannot be used to reliably distinguish among grade 2 and 3 STSs (by FNCLCC) and the various subtypes.
Late Quaternary intensified monsoon phases control landscape evolution in the northwest Himalaya

The intensity of the Asian summer-monsoon circulation varies over decadal to millennial time scales and is reflected in changes in surface processes, terrestrial environments, and marine sedi- ment records. However, the mechanisms of long-lived (2-5 k.y.) intensified monsoon phases, the related changes in precipitation distribution, and their effect on landscape evolution and sedimen- tation rates are not yet well understood. The arid high-elevation sectors of the orogen correspond to a climatically sensitive zone that currently receives rain only during abnormal (i.e., strength- ened) monsoon seasons. Analogous to present-day rainfall anom- alies, enhanced precipitation during an intensified monsoon phase is expected to have penetrated far into these geomorphic threshold regions where hillslopes are close to the angle of failure. We as- sociate landslide triggering during intensified monsoon phases with enhanced precipitation, discharge, and sediment flux leading to an increase in pore-water pressure, lateral scouring of rivers, and ov- ersteepening of hillslopes, eventually resulting in failure of slopes and exceptionally large mass movements. Here we use lacustrine deposits related to spatially and temporally clustered large land- slides (.0.5 km 3 ) in the Sutlej Valley region of the northwest Him- alaya to calculate sedimentation rates and to infer rainfall patterns during late Pleistocene (29-24 ka) and Holocene (10-4 ka) inten- sified monsoon phases. Compared to present-day sediment-flux measurements, a fivefold increase in sediment-transport rates re- corded by sediments in landslide-dammed lakes characterized these episodes of high climatic variability. These changes thus em- phasize the pronounced imprint of millennial-scale climate change on surface processes and landscape evolution.
CRISPR-Cas9 Human Genome Editing: Challenges, Ethical Concerns and Implications

Genome editing technologies may in the future have therapeutic potential for various incurable diseases: cancer, genetic disorders, HIV/AIDS to mention the most obvious. Genome editing of somatic cells, which is at it various clinical stages, is a promising area of therapeutic development. This year, a group of Chinese researchers led by Junjiu Huang - a gene-function researcher at Sun Yat-sen University in Guangzhou, used complex enzyme-editing tool CRISPR-Cas9 as a therapeutic agent to eradicate the human β-globulin (HBB) gene from the germline of the human embryo. The mutations in HBB gene cause β-thalassaemia (a deadly blood disorder). The research was, however, not completely successful, and had to be abandoned at its preliminary stage. This research was published in the journal Protein and Cell after it was rejected by the journal Nature and Science on ethical grounds. Caution flags have been raised about the use of CRISPR-Cas9 on human germline editing. This research has generated the debate among the world-renowned scientists about the ethical concerns and implications of CRISPR-Cas9 human germline editing. While some members of the scientific community have argued that a moratorium should be called on human germline editing, others have argued that it is unethical to withhold a technology that would eliminate devastating genetic diseases. This paper critically evaluates the challenges, ethical concerns and implications of CRISPR-Cas9 human germ line editing.
Motion-guided mechanical toy modeling

We introduce a new method to synthesize mechanical toys solely from the motion of their features. The designer specifies the geometry and a time-varying rotation and translation of each rigid feature component. Our algorithm automatically generates a mechanism assembly located in a box below the feature base that produces the specified motion. Parts in the assembly are selected from a parameterized set including belt-pulleys, gears, crank-sliders, quick-returns, and various cams (snail, ellipse, and double-ellipse). Positions and parameters for these parts are optimized to generate the specified motion, minimize a simple measure of complexity, and yield a well-distributed layout of parts over the driving axes. Our solution uses a special initialization procedure followed by simulated annealing to efficiently search the complex configuration space for an optimal assembly.
Learning to Grasp Objects : A Novel Approach for Localizing Objects Using Depth Based Segmentation

We consider the problem of grasping novel objects with a robotic arm. A recent successful technique applies machine learning to identify a point in an image corresponding to the most likely location at which to grasp an object. Another approach extends their method to accomodate grasps with multiple contact points. This paper proposes a novel approach that tries to find graspable points in an object after localizing it. We present a depth based segmentation scheme for object localization and discuss how depth information can be combined with visual imagery to improve the performance of both segmentation and object localization.
Implementing Student-Led IEPs: Student Participation and Student and Teacher Reactions

Greater student involvement in the Individual Education Program (IEP) and transition process has been advocated by many; however, teachers are unaware of the materials that can assist them in preparing students for this involvement, and many students continue to be left out of their own planning meetings. In this study, researchers implemented student-led IEPs with 43 high school students in a culturally diverse high school in a mid-Atlantic state. Interviews held with 35 (81%) of these students confirmed that they were able to describe the purpose and benefits of an IEP, their disabilities, and their rights. Observation of student participation in IEP meetings for five (12%) students verified that all of them participated throughout their IEP meetings. Observations indicated that the five students participated for 49 (98%) of 50 opportunities for involvement. Interviews with 10 general and special education teachers at that school further documented the value of this student involvement, particularly in increasing student self-confidence and self-advocacy.
Naughty Firms, Noisy Disclosure Effects of Cartel Enforcement on Corporate Disclosure∗

We empirically study how collusion in the product markets affects firms’ financial disclosure strategies. By exploiting exogenous variations to the costs of illegal pricefixing, we find that U.S. firms start sharing more detailed information in their financial disclosure about their customers, contracts, and products, potentially benefiting peers and helping to tacitly coordinate actions in product markets. At the same time, the disclosure on firms’ competitive environment, which might benefit antitrust regulators, becomes more murky. Our findings suggest that transparency in financial statements can come at the expense of consumer welfare.
The Effects of Parental Mediation of Sexual Content on the Sexual Knowledge, Attitudes, and Behaviors of Adolescents in the US

This study explored the effects of parental mediation of sexual television content on adolescents' sexual knowledge, attitudes, and behaviors. Undergraduate students enrolled in an introductory communication class (N = 180) recalled the mediation behaviors their parents used when they were in high school as well as reported their past and current sexual behaviors, attitudes, and knowledge. The results revealed that coviewing of sexual content serves as an endorsement of the material for adolescents, restrictive mediation is best in moderate amounts, and that active mediation is most effective when it is paired with an open, conversational delivery style. Overall this study highlights the importance of the role of context, style, and nuance when studying the effects of parental mediation on adolescents' outcomes. The implications of this work for encouraging positive parent–child relationships and comfortable, healthy exchanges about sex are discussed.