Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular interactions of the physiological anti-hypertensive peptide catestatin with the neuronal nicotinic acetylcholine receptor

Catestatin (CST), a chromogranin-A-derived peptide, is a potent endogenous inhibitor of the neuronal nicotinic acetylcholine receptor (nAChR). It exerts an anti-hypertensive effect by acting as a ‘physiological brake’ on transmitter release into the circulation. However, the mechanism of interaction of CST with nAChR is only partially understood. To unravel molecular interactions of the wild-type human CST (CST-WT) as well as its naturally occurring variants (CST-364S and CST-370L, which have Gly→Ser and Pro→Leu substitutions, respectively) with the human α3β4 nAChR, we generated a homology-modeled human α3β4 nAChR structure and solution structures of CST peptides. Docking and molecular dynamics simulations showed that ~90% of interacting residues were within 15 N-terminal residues of CST peptides. The rank order of binding affinity of these peptides with nAChR was: CST-370L>CST-WT>CST-364S; the extent of occlusion of the receptor pore by these peptides was also in the same order. In corroboration with computational predictions, circular dichroism analysis revealed significant differences in global structures of CST peptides (e.g. the order of α-helical content was: CST-370L>CST-WT>CST-364S). Consistently, CST peptides blocked various stages of nAChR signal transduction, such as nicotine- or acetylcholine-evoked inward current, rise in intracellular Ca2+ and catecholamine secretion in or from neuron-differentiated PC12 cells, in the same rank order. Taken together, this study shows molecular interactions between human CST peptides and human α3β4 nAChR, and demonstrates that alterations in the CST secondary structure lead to the gain of potency for CST-370L and loss of potency for CST-364S. These findings have implications for understanding the nicotinic cholinergic signaling in humans.
Muscleblind, BSF and TBPH are mislocalized in the muscle sarcomere of a Drosophila myotonic dystrophy model

SUMMARY Myotonic dystrophy type 1 (DM1) is a genetic disease caused by the pathological expansion of a CTG trinucleotide repeat in the 3′ UTR of the DMPK gene. In the DMPK transcripts, the CUG expansions sequester RNA-binding proteins into nuclear foci, including transcription factors and alternative splicing regulators such as MBNL1. MBNL1 sequestration has been associated with key features of DM1. However, the basis behind a number of molecular and histological alterations in DM1 remain unclear. To help identify new pathogenic components of the disease, we carried out a genetic screen using a Drosophila model of DM1 that expresses 480 interrupted CTG repeats, i(CTG)480, and a collection of 1215 transgenic RNA interference (RNAi) fly lines. Of the 34 modifiers identified, two RNA-binding proteins, TBPH (homolog of human TAR DNA-binding protein 43 or TDP-43) and BSF (Bicoid stability factor; homolog of human LRPPRC), were of particular interest. These factors modified i(CTG)480 phenotypes in the fly eye and wing, and TBPH silencing also suppressed CTG-induced defects in the flight muscles. In Drosophila flight muscle, TBPH, BSF and the fly ortholog of MBNL1, Muscleblind (Mbl), were detected in sarcomeric bands. Expression of i(CTG)480 resulted in changes in the sarcomeric patterns of these proteins, which could be restored by coexpression with human MBNL1. Epistasis studies showed that Mbl silencing was sufficient to induce a subcellular redistribution of TBPH and BSF proteins in the muscle, which mimicked the effect of i(CTG)480 expression. These results provide the first description of TBPH and BSF as targets of Mbl-mediated CTG toxicity, and they suggest an important role of these proteins in DM1 muscle pathology.
Practical clinical tool to monitor dementia symptoms: the HABC-Monitor

Background Dementia care providers need a clinical assessment tool similar to the blood pressure cuff (sphygmomanometer) used by clinicians and patients for managing hypertension. A “blood pressure cuff ” for dementia would be an inexpensive, simple, user-friendly, easily standardized, sensitive to change, and widely available multidomain instrument for providers and informal caregivers to measure severity of dementia symptoms. The purpose of this study was to assess the reliability and validity of the Healthy Aging Brain Care Monitor (HABC-Monitor) for measuring and monitoring the severity of dementia symptoms through caregiver reports. Methods The first prototype of the HABC-Monitor was developed in collaboration with the Indianapolis Discovery Network for Dementia, which includes 200 members representing 20 disciplines from 20 local organizations, and an expert panel of 22 experts in dementia care and research. The HABC-Monitor has three patient symptom domains (cognitive, functional, behavioral/psychological) and a caregiver quality of life domain. Patients (n = 171) and their informal caregivers (n = 171) were consecutively approached and consented during, or by phone shortly following, a patient’s routine visit to their memory care provider. Results The HABC-Monitor demonstrated good internal consistency (0.73–0.92); construct validity indicated by correlations with the caregiver-reported Neuropsychiatric Inventory (NPI) total score and NPI caregiver distress score; sensitivity to three-month change compared with NPI “reliable change” groups; and known-groups validity, indicated by significant separation of Mini-Mental Status Examination severity groups and clinical diagnostic groups. Although not designed as a screening study, there was evidence for good operating characteristics, according to area under the receiver-operator curve with respect to gold standard clinical diagnoses, relative to Mini-Mental Status Examination or NPI. Conclusion The HABC-Monitor demonstrates good reliability and validity as a clinically practical multidimensional tool for monitoring symptoms of dementia through the informal caregiver.
Frame of Reference Rater Training Issues: Recall, Time and Behavior Observation Training

This study investigated three controversial issues regarding frame of reference training (FOR), a type of rater training: (1) Does it improve behavioral recall, (2) Can it be improved by incorporating behavior observation training (BOT), and (3) Can its effects persist over time? Results suggested that even though FOR training increases the number of behaviors recalled, it does not necessarily improve the quality of the recalled behaviors, but a combined FOR BOT program does improve recall quality. Lastly, results suggested that FOR training can improve rating accuracy, even after a two-week delay between rater training and the rating task.
High Level of Gastrointestinal Nosocomial Infections in the German Surveillance System, 2002–2008

Objective. Surveillance of nosocomial infections (NIs) is well established in many countries but often does not include gastrointestinal infections. We sought to determine the proportion of NIs among all hospitalized cases for the 4 most prevalent types of gastrointestinal infections in Germany. Methods. We analyzed all notifications of laboratory-confirmed or epidemiologically linked gastrointestinal infections due to norovirus, rotavirus, Salmonella species, and Campylobacter species reported to the Robert Koch Institute in Berlin, Germany, from 2002 through 2008. Infections were considered nosocomial if disease onset was more than 2 days after hospitalization for norovirus, rotavirus, and Salmonella infection and more than 5 days after hospitalization for Campylobacter infection. Results. During the study period, 710,725 norovirus, 394,500 rotavirus, 395,736 Salmonella, and 405,234 Campylobacter gastrointestinal infections were reported. Excluding cases for which nosocomial status could not be determined, we identified 39,424 (49%) of 80,650 norovirus, 11,592 (14%) of 83,451 rotavirus, 3,432 (8%) of 43,348 Salmonella, and 645 (2%) of 33,503 Campylobacter gastrointestinal infections as definite nosocomial cases. Multivariate analysis confirmed higher risk of gastrointestinal NIs for patients aged more than 70 years (relative risk [RR], 7.0 [95% confidence interval {CI}, 6.7–7.2]; P < .001) and residents of western states (RR, 1.3 [95% CI, 1.2–1.3]; P < .001) and lower risk for female patients (RR, 0.9 [95% CI, 0.9–0.9; P < .001). Yearly NI proportions remained stable except for norovirus. Conclusions. The investigated gastrointestinal NIs in Germany do not show a clear trend, but they are at high level, revealing potential for public health action and improvement of hospital infection control mainly among older patients. National prevalence studies on gastrointestinal NIs would be of additional value to give more insight on how and where to improve hospital infection control.
Administrative Promotion: The Power of Gender.

Dramatic increases in the number of administrative and professional staff members employed in higher education during the past twenty years have resulted in increased attention to the composition of this burgeoning group. 1 At large public research universities, the number of administrative staff members has increased substantially [14, 19], and in at least one major land-grant university, the numbers nearly doubled in a seven-year period [53]. In a survey of 1 15 institutions in 1968, Blau reported a ratio of one administrator to four faculty members [ 12]. In a survey of college and university personnel in 1980-82, 42 percent of the public institutions and 88 percent of the private institutions reported a ratio of three administrators to two faculty members [15]. During this period of growth, equal opportunity and affirmative action legislation prompted efforts to examine and improve the numbers
Comparing DNS resolvers in the wild

The Domain Name System (DNS) is a fundamental building block of the Internet. Today, the performance of more and more applications depend not only on the responsiveness of DNS, but also the exact answer returned by the queried DNS resolver, e.g., for Content Distribution Networks (CDN). In this paper, we compare local DNS resolvers against GoogleDNS and OpenDNS for a large set of vantage points. Our end-host measurements inside 50 commercial ISPs reveal that two aspects have a significant impact on responsiveness: (1) the latency to the DNS resolver, (2) the content of the DNS cache when the query is issued. We also observe significant diversity, even at the AS-level, among the answers provided by the studied DNS resolvers. We attribute this diversity to the location-awareness of CDNs as well as to the location of DNS resolvers that breaks the assumption made by CDNs about the vicinity of the end-user and its DNS resolver. Our findings pinpoint limitations within the DNS deployment of some ISPs, as well as the way third-party DNS resolvers bias DNS replies.
Enhancing the Alternative and Augmentative Communication Use of a Child with Autism through a Parent‐implemented Naturalistic Intervention

The effects of a parent‐implemented naturalistic intervention on the communication skills of a 4‐year‐old boy with autism using an alternative and augmentative communication (AAC) system were investigated. The child’s mother was taught to use 4 naturalistic teaching strategies that incorporated a picture communication system during 2 typical home routines. Generalisation probes to assess the caregiver’s use of the intervention techniques and generalisation of the child’s communication outcomes were conducted in 2 similar interactions. A multiple baseline design was used to evaluate the effects of the intervention. Data indicated an increase in the use of 2 caregiver–teaching strategies across two routines following treatment. No consistent changes were observed in the use of the other caregiver strategies across the routines. An increase in the child’s frequency of initiations and responses and the use of the communication system also were observed.
Machiavellianism in parents and their children.

The role of the family in the development of Machiavellianism was examined in this study. Highand low-Machiavellian sixth graders played a bluffing game. Their parents completed Machiavellian belief measures. The Machiavellianism of fathers and mothers was positively related to their children's success at deceiving others but not at seeing through others' attempts at deception. In addition, fathers' Machiavellianism was positively related to their children's Machiavellian beliefs. These data support a modeling hypothesis for the development of Machiavellianism. Unexpectedly, the children's own behaviors and beliefs were unrelated. This pattern of results suggests that a child's manipulative behaviors and beliefs are learned separately and only become consistent over time.
Histone H3 (lys-9) Deacetylation is Associated with Transcriptional Silencing of E-cadherin in Colorectal Cancer Cell Lines

Epigenetic parameters linked to E-cadherin gene were investigated in 5 human colorectal cancer cell lines. Treatment with trichostatin A led to enhanced acetylation of histone H3-K9 with concurrent induction of E-cadherin mRNA in 3 E-cadherin low/negative cell lines that are not DNA methylated. Co-treatment with 5-aza-2′-deoxycytidine and trichostatin A resulted in additive/synergic induction of E-cadherin mRNA in all 5 cell lines with concomitant enhancement of histone H3-K9 acetylation in 4 E-cadherin low/negative cell lines. Our results suggest that histone H3-K9 deacetylation appears to play a crucial role in transcriptional repression of E-cadherin in colorectal cancers.
A VH12 Transgenic Mouse Exhibits Defects in Pre-B Cell Development and Is Unable to Make IgM+ B Cells1

VH12 B cells undergo stringent selection at multiple checkpoints to favor development of B-1 cells that bind phosphatidylcholine. Selection begins with the VH third complementarity-determining region (CDR3) at the pre-B cell stage, in which most VH12 pre-B cells are selectively eliminated, enriching for those with VHCDR3s of 10 aa and a fourth position Gly (designated 10/G4). To understand this selection, we compared B cell differentiation in mice of two VH12 transgenic lines, one with the favored 10/G4 VHCDR3 and one with a non-10/G4 VHCDR3 of 8 aa and no Gly (8/G0). Both H chains drive B cell differentiation to the small pre-BII cell stage, and induce allelic exclusion and L chain gene rearrangement. However, unlike 10/G4 pre-B cells, 8/G0 pre-B cells are deficient in cell division and unable to differentiate to B cells. We suggest that this is due to poor 8/G0 pre-B cell receptor expression and to an inability to form an 8/G0 B cell receptor. Our findings also suggest that VH12 H chains have evolved such that association with surrogate and conventional L chains is most efficient with a 10/G4 CDR3. Thus, selection for phosphatidylcholine-binding B-1 cells is most likely the underlying evolutionary basis for the loss of non-10/G4 pre-B cells.
Psychological Characteristics of Heroin-Dependent and Non-Opioid-Substance-Dependent Adolescents in Community Drug Treatment Services

By examining measures of psychological distress in heroin-dependent (HD) and non-opioid-substance-dependent (NOSD) adolescents, this study attempts to ascertain whether mental health symptoms differ according to drug use predilection or gender. The Beck Youth Inventory scores of 52 HD young people and 68 NOSD youths were retrospectively reviewed. HD adolescents demonstrated poorer self-concept as well as greater anxiety, depression, and disruptive behavior than the NOSD group. Female HD adolescents reported more mental health problems related to self-concept and disruptive behaviors than male HD adolescents. While causation cannot be stipulated, this study points to the complexity of mental health needs in adolescent drug users.
Partitioning United States' feed consumption among livestock categories for improved environmental cost assessments

SUMMARY The high environmental costs of raising livestock are now widely appreciated, yet consumption of animal-based food items continues and is expanding throughout the world. Consumers' ability to distinguish among, and rank, various interchangeable animal-based items is crucial to reducing environmental costs of diets. However, the individual environmental burdens exerted by the five dominant livestock categories – beef, dairy, poultry, pork and eggs – are not fully known. Quantifying those burdens requires splitting livestock‘s relatively well-known total environmental costs (e.g. land and fertilizer use for feed production) into partial categorical costs. Because such partitioning quantifies the relative environmental desirability of various animal-based food items, it is essential for environmental impact minimization efforts to be made. Yet to date, no such partitioning method exists. The present paper presents such a partitioning method for feed production-related environmental burdens. This approach treated each of the main feed classes individually – concentrates (grain, soy, by-products; supporting production of all livestock), processed roughage (mostly hay and silage) and pasture – which is key given these classes' widely disparate environmental costs. It was found that for the current US food system and national diet, concentrates are partitioned as follows: beef 0·21±0·112, poultry 0·27±0·046, dairy 0·24±0·041, pork 0·23±0·093 and eggs 0·04±0·018. Pasture and processed roughage, consumed only by cattle, are 0·92±0·034 and 0·87±0·031 due to beef, with the remainder due to dairy. In a follow-up paper, the devised methodology will be employed to partition total land, irrigated water, greenhouse gases and reactive nitrogen burdens incurred by feed production among the five edible livestock categories.
Table of Contents, Editor's Choice, Highlights

AMIRHOSSEIN BAHREYNI, SEYED S. SAMANI, ELNAZ GHORBANI, FARZAD RAHMANI, REZA KHAYAMI, YOUNES TOROGHIAN, REIHANE BEHNAM-RASSOULI, MAJID KHAZAEI, MIKHAIL RYZHIKOV, MOHAMMAD R. PARIZADEH, MALIHE HASANZADEH, AMIR AVAN, AND SEYED M. HASSANIAN 2715 Adenosine: An Endogenous Mediator in the Pathogenesis of Gynecological Cancer Accepted manuscript online in Wiley Online Library, 8 September 2017 V O L . 2 3 3 A P R I L 2 0 1 8 N O . 4
2-Amino-N-(2-hydroxy-3-methoxybenzylidene)aniline

The reaction of o-vanillin 1 with o-phenylenediamine 2PD, in dichloromethane at low conditions produced novel amino benzeneamine: 2-amino-N-(2-hydroxy-3-methoxybenzylidene) aniline 2. Intermediate 2 is isolated and obtained as single crystals and the structure was determined and studied by x-ray crystallography. The complete assignments of 2 were made using FTIR, HRMS, 1D and 2D NMR including APT, COSY, HMQC and HMBC in CDCl3 and will be discussed.
Strategic adoption in a two-sided market : a study of college applications in Brazil

This paper measures the importance of indirect network effects in the adoption by colleges and students of ENEM, a standardized exam for high-school students in Brazil that can be used in college application processes. We estimate network effects and find that they are economically significant. Students are more likely to take ENEM the larger the number of colleges adopting it. Similarly, colleges are more likely to adopt it the larger the number of students taking the exam. Moreover, we find evidence that colleges play strategically and that heterogeneity determines their decisions. A college is less likely to adopt ENEM the larger the number of competitors adopting it. Colleges’ characteristics such as ownership and organization affect adoption decisions. In a counterfactual exercise we compare colleges’ adoption decisions under competition and under joint colleges’ payoffs maximization. Adoption rates are significantly reduced when colleges internalize the competitive effect, i.e., the effect of their decisions on other colleges’ payoffs. On the other hand, they increase when indirect network effects the effect of students’ response to their decisions on other colleges’ payoffs are also internalized. Competitive adoption rates are found to exceed joint optimum rates by a small difference. These results suggest that, without considering students’ welfare, adoption rates are excessive, but close to the joint optimum. ∗I thank Ali Hortacsu and Chad Syverson for guidance and support. I also thank Ricardo Avelino, Pradeep Chintagunta, Jean-Pierre Dube, Austan Goolsbee, Gunter Hitsch, Priscilla Medeiros, Amil Petrin, Jose Resende, Maria Salgado, and working group participants at the University of Chicago for contributions. Financial support from Capes and the Claudio Haddad Fund Dissertation Fellowship is gratefully acknowledged. †University of Chicago, Department of Economics, 1126 E. 59th Street, Chicago, IL 60637. e-mail: mrezende@uchicago.edu.
The tension between marketisation and academisation in higher education

Contemporary changes in higher education in Sweden are characterised by two educational discourses: marketisation and academisation. Demands to meet market requirements, as well as to make education more scientific, have created tensions between and within institutional cultures. Using interviews with 16 heads of departments, the authors investigate how tensions between marketisation and academisation were handled in discipline-oriented and professional-oriented departments. The heads of discipline-oriented departments experienced marketisation as a threat to the university trademark, because it was seen to challenge academic autonomy. On the other hand, heads of professional-oriented departments felt that academisation was the main issue to be dealt with, as it shifted focus from practical skills towards academic meritocracy. Consequently, it is not possible to discuss these changes without considering that conditions differ substantially across the university. Responses to these changes can be countered by culturally sensitive strategies, rather than by adopting a ‘one size fits all’ approach.
Exploring Novice Approaches to Smartphone-based Thermographic Energy Auditing: A Field Study

The recent integration of thermal cameras with commodity smartphones presents an opportunity to engage the public in evaluating energy-efficiency issues in the built environment. However, it is unclear how novice users without professional experience or training approach thermographic energy auditing activities. In this paper, we recruited 10 participants for a four-week field study of end-user behavior exploring novice approaches to semi-structured thermographic energy auditing tasks. We analyze thermographic imagery captured by participants as well as weekly surveys and post-study debrief interviews. Our findings suggest that while novice users perceived thermal cameras as useful in identifying energy-efficiency issues in buildings, they struggled with interpretation and confidence. We characterize how novices perform thermographic-based energy auditing, synthesize key challenges, and discuss implications for design.
A Theory of Global Strategy and Firm Efficiencies: Considering the Effects of Cultural Diversity

The concept of “relatedness,” though common in the product diversification literature, has not yet been widely applied to theories of internationalization. Expanding internationally requires managerial adaptation due to differences between national cultures, but these dynamics have not been used to represent the cultural diversity that may hinder efforts to integrate and coordinate efforts as required by global strategies. Tempering popular perspectives that extol the benefits of diversity, the present theory posits that cultural diversity among international divisions of a global firm may actually impede efforts to merge activities and expertise between those units. Specifically, direct (market, production, technology) and indirect (knowledge-based) benefits are more difficult to exploit when cultural diversity makes activity sharing and expertise transfer less efficient. Parallel to established product relatedness theory, this thinking postulates that culturally related international firms will enjoy greater efficiencies than culturally diverse multinationals.