Miracle-dz/UniFAR-FTUs huggingface dataset:
PINK1 and Parkin to control mitochondria remodeling

Parkinson's disease (PD), one of the most common neurodegenerative diseases, is characterized by movement disorders and a loss of dopaminergic (DA) neurons. PD mainly occurs sporadically, but may also result from genetic mutations in several PD-linked genes. Recently, genetic studies with Drosophila mutants, parkin and PINK1, two common PD-associated genes, demonstrated that Parkin acts downstream of PINK1 in maintaining mitochondrial function and integrity. Further studies revealed that PINK1 translocates Parkin to mitochondria and regulates critical mitochondrial remodeling processes. These findings, which suggest that mitochondrial dysfunction is a prominent cause of PD pathogenesis, provide valuable insights which may aid in the development of effective treatments for PD.
Development and Characterization of a Tissue-engineered Human Oral Mucosa Equivalent Produced in a Serum-free Culture System

A problem maxillofacial surgeons face is a lack of sufficient autogenous oral mucosa for reconstruction of the oral cavity. Split-thickness or oral mucosa grafts require more than one surgical procedure and can result in donor site morbidity. Skin has disadvantages of adnexal structures and a different keratinization pattern than oral mucosa. In this study, we successfully assembled, ex vivo, a human oral mucosa equivalent, consisting of epidermal and dermal components, in a defined, essential-fatty-acid-deficient, serum-free culture medium without a feeder layer, that could be used for intra-oral grafting in humans. Autogenous oral keratinocytes were seeded onto a cadaveric dermis, AlloDerm™. The oral mucosa equivalent was cultured at an air-liquid interface for 2 wks. The resulting equivalent had a well-stratified parakeratinized epithelial layer similar to native oral keratinized mucosa. Expression of differentiation markers, filaggrin and cytokeratin 10/13, suggested a premature keratinized state. The presence of proliferation markers, proliferating cell nuclear antigen (PCNA) and Ki-67, suggested a state of hyperproliferation. Fatty acid composition of the equivalent was similar to that of in vitro cultured oral keratinocytes but differed from the that of in vivo native tissue, showing a lower content of 18:2 and 20:4, and a higher content of 16:1 and 18:1 fatty acids, respectively. The keratinocytes of the equivalent appeared to be in a more active and proliferative state than native keratinized mucosa. The dynamic nature of the cell population on the oral mucosa equivalent may be beneficial for intra-oral grafting procedures and for transfection of the keratinocytes.
Identification of Combined Genetic Determinants of Liver Stiffness within the SREBP1c-PNPLA3 Pathway

The common PNPLA3 (adiponutrin) variant, p.I148M, was identified as a genetic determinant of liver fibrosis. Since the expression of PNPLA3 is induced by sterol regulatory element binding protein 1c (SREBP1c), we investigate two common SREBP1c variants (rs2297508 and rs11868035) for their association with liver stiffness. In 899 individuals (aged 17–83 years, 547 males) with chronic liver diseases, hepatic fibrosis was non-invasively phenotyped by transient elastography (TE). The SREBP1c single nucleotide polymorphisms (SNPs) were genotyped using PCR-based assays with 5′-nuclease and fluorescence detection. The SREBP1c rs11868035 variant affected liver fibrosis significantly (p = 0.029): median TE levels were 7.2, 6.6 and 6.0 kPa in carriers of (TT) (n = 421), (CT) (n = 384) and (CC) (n = 87) genotypes, respectively. Overall, the SREBP1c SNP was associated with low TE levels (5.0–8.0 kPa). Carriers of both PNPLA3 and SREBP1c risk genotypes displayed significantly (p = 0.005) higher median liver stiffness, as compared to patients carrying none of these variants. The common SREBP1c variant may affect early stages of liver fibrosis. Our study supports a role of the SREBP1c-PNPLA3 pathway as a “disease module” that promotes hepatic fibrogenesis.
The New, Longer Road to Adulthood: Schooling, Work, and Idleness among Rural Youth. Number 9.

This Article is brought to you for free and open access by the Research Institutes, Centers and Programs at University of New Hampshire Scholars'Repository. It has been accepted for inclusion in The Carsey Institute at the Scholars' Repository by an authorized administrator of University of NewHampshire Scholars' Repository. For more information, please contactmeredith.ricker@unh.edu.
Budget Error-Correcting under EarthMover Distance

We study the following budget error-correcting problem: Alice has a point set x and Bob has a point set y in the d-dimensional grid. Alice wants to send a short message to Bob so that Bob can use this information to adjust his point set y towards x to minimize the Earth-Mover Distance between the two point sets. A more intuitive way to understand this problem is: Alice tries to help Bob to recall Eve’s face by sending him a short message. Of course Bob will fail to recall if he does not know Eve, but if he knows something about Eve, the message could help a lot. Naturally, there is a trade-off between the message size and the quality of such an adjustment. Now given a quality constraint, we want to minimize the message size. This problem is well motivated by applications including image exchange/synchronization and video compression. In this paper, we give almost matching upper and lower bounds for this problem.
Anaphylaxis During the Perioperative Period

Anesthesiologists use a myriad of drugs during the provision of an anesthetic. Many of these drugs have side effects that are dose related, and some lead to severe immune-mediated adverse reactions. Anaphylaxis is the most severe immune-mediated reaction; it generally occurs on reexposure to a specific antigen and requires the release of proinflammatory mediators. Anaphylactoid reactions occur through a direct non-immunoglobulin E-mediated release of mediators from mast cells or from complement activation. Muscle relaxants and latex account for most cases of anaphylaxis during the perioperative period. Symptoms may include all organ systems and present with bronchospasm and cardiovascular collapse in the most severe cases. Management of anaphylaxis includes discontinuation of the presumptive drug (or latex) and anesthetic, aggressive pulmonary and cardiovascular support, and epinephrine. Although a serum tryptase confirms the diagnosis of an anaphylactic reaction, the offending drug can be identified by skinprick, intradermal testing, or serologic testing. Prevention of recurrences is critical to avoid mortality and morbidity.
Developmental insights into the pathology of and therapeutic strategies for DM1: Back to the basics

Myotonic Dystrophy type 1 (DM1), the most prevalent adult onset muscular dystrophy, is a trinucleotide repeat expansion disease caused by CTG expansion in the 3′‐UTR of DMPK gene. This expansion results in the expression of toxic gain‐of‐function RNA that forms ribonuclear foci and disrupts normal activities of RNA‐binding proteins belonging to the MBNL and CELF families. Changes in alternative splicing, translation, localization, and mRNA stability due to sequestration of MBNL proteins and up‐regulation of CELF1 are key to DM1 pathology. However, recent discoveries indicate that pathogenic mechanisms of DM1 involves many other factors as well, including repeat associated translation, activation of PKC‐dependent signaling pathway, aberrant polyadenylation, and microRNA deregulation. Expression of the toxic repeat RNA culminates in the developmental remodeling of the transcriptome, which produces fetal isoforms of proteins that are unable to fulfill the physiological requirements of adult tissues. This review will describe advances in the understanding of DM1 pathogenesis as well as current therapeutic developments for DM1. Developmental Dynamics 244:377–390, 2015. © 2014 Wiley Periodicals, Inc.
The effects of high-fat diet on implant osseointegration: an experimental study

Objectives In this study, we investigated whether a high-fat diet (HFD) affected the bone implant connection (BIC) in peri-implant bone. Materials and Methods Four male rabbits were used in this study. Dental implant surgery was introduced into each tibia, and four implants were integrated into each animal. In both the normal diet (ND) group (n=2) and HFD group (n=2), 8 implants were integrated, for a total of 16 integrated implants. The animals continued with their respective diets for 12 weeks post-surgery. Afterward, the rabbits were sacrificed, and the BIC was assessed histomorphometrically. Results Histologic and histomorphometric analyses demonstrated that BIC was not impaired in the HFD group compared to the ND group. Conclusion Within the limitations of this study, we found that HFD did not decrease the BIC in rabbit tibias.
National innovation surveys in latin America: empirical evidence and policy implications

In this paper we study the determinants of technical cooperation agreements in a less developed country. By estimating biprobit and poisson models and correcting for selection bias we confirm previous evidence that larger firms tend to innovate more. However, technical cooperation is inversely related with firm size suggesting that larger firms tend to vertically integrate their R&D activities. Results show, however, that public support enhances technical cooperation among firms. This is especially relevant when results also show that radical innovations are, among other things, heavily dependent on the existence of technical cooperation contracts.
Comparative Pharmacokinetics Study of Icariin and Icariside II in Rats

To explore the pharmacokinetic properties of icariin (ICA) and icariside II (ICA II) following intragastric and intravenous administration in rats, a rapid and sensitive method by using ultra-performance liquid chromatography–tandem mass spectroscopy (UPLC-MS/MS) was developed and validated for the simultaneous quantification of ICA and ICA II in rat plasma. The quantification was performed by using multiple reaction monitoring of the transitions m/z 677.1/531.1 for ICA, 515.1/369.1 for ICA II and 463.1/301.1 for diosmetin-7-O-β-d-glucopyranoside (IS). The assay showed linearity over the concentration range of 1.03–1032 ng/mL, with correlation coefficients of 0.9983 and 0.9977. Intra- and inter-day precision and accuracy were within 15%. The lower limit of quantification for both ICA and ICA II was 1.03 ng/mL, respectively. The recovery of ICA and ICA II was more than 86.2%. The LC-MS/MS method has been successfully used in the pharmacokinetic studies of ICA and ICA II in rats. The results indicated that 91.2% of ICA was transformed into ICA II after oral administration by rats, whereas only 0.4% of ICA was transformed into ICA II after intravenous administration. A comparison of the pharmacokinetics of ICA and ICA II after oral administration revealed that the Cmax and AUC0–t of ICA II were 3.8 and 13.0 times higher, respectively, than those of ICA. However, after intravenous administration, the Cmax and AUC0–t of ICA II were about only 12.1% and 4.2% of those of ICA. These results suggest that ICA and ICA II have distinct pharmacokinetic properties, and the insights obtained facilitate future pharmacological action studies.
Deep Brain Stimulation in Anorexia Nervosa: Hope for the Hopeless or Exploitation of the Vulnerable? The Oxford Neuroethics Gold Standard Framework

Neurosurgical interventions for psychiatric disorders have a long and troubled history (1, 2) but have become much more refined in the last few decades due to the rapid development of neuroimaging and robotic technologies (2). These advances have enabled the design of less invasive techniques, which are more focused, such as deep brain stimulation (DBS) (3). DBS involves electrode insertion into specific neural targets implicated in pathological behavior, which are then repeatedly stimulated at adjustable frequencies. DBS has been used for Parkinson’s disease and movement disorders since the 1960s (4–6) and over the last decade has been applied to treatment-refractory psychiatric disorders, with some evidence of benefit in obsessive–compulsive disorder (OCD), major depressive disorder, and addictions (7). Recent consensus guidelines on best practice in psychiatric neurosurgery (8) stress, however, that DBS for psychiatric disorders remains at an experimental and exploratory stage. The ethics of DBS—in particular for psychiatric conditions—is debated (1, 8–10). Much of this discourse surrounds the philosophical implications of competence, authenticity, personality, or identity change following neurosurgical interventions, but there is a paucity of applied guidance on neuroethical best practice in psychiatric DBS, and health-care professionals have expressed that they require more (11). This paper aims to redress this balance by providing a practical, applied neuroethical gold standard framework to guide research ethics committees, researchers, and institutional sponsors. We will describe this as applied to our protocol for a particular research trial of DBS in severe and enduring anorexia nervosa (SE-AN) (https://clinicaltrials.gov/ct2/show/NCT01924598, unique identifier NCT01924598), but believe it may have wider application to DBS in other psychiatric disorders.
Nonindependent Domestication of the Two Rice Subspecies, Oryza sativa ssp. indica and ssp. japonica, Demonstrated by Multilocus Microsatellites

The origins of the Asian cultivated rice Oryza sativa from its wild ancestor O. rufipogon have been debated for decades. The question mainly concerns whether it originated monophyletically or polyphyletically. To shed light on the origins and demographic history of rice domestication, we genotyped a total of 92 individual plants from the two O. sativa subspecies and O. rufipogon for 60 microsatellites. An approximate Bayesian method was applied to estimate demographic parameters for O. rufipogon vs. O. sativa ssp. indica and O. rufipogon vs. O. sativa ssp. japonica. We showed that the japonica subspecies suffered a more severe bottleneck than the indica subspecies and thus a greater loss of genetic variation during its domestication. Across microsatellite loci there is a significant positive correlation in the reduction of genetic diversity between the two subspecies. The results suggest that completely independent domestication of indica and japonica subspecies may not explain our data and that there is at least partial sharing of their ancestral populations and/or recent gene flow between them.
Acoustic communication in territorial butterflyfish: test of the sound production hypothesis

SUMMARY Butterflyfishes are conspicuous members of coral reefs and well known for their visual displays during social interactions. Members of the genus Chaetodon have a unique peripheral arrangement of the anterior swim bladder that connects with the lateral line (the laterophysic connection) and in many species projects towards the inner ear. This morphology has lead to the proposal that the laterophysic connection and swim bladder system may be a specialized structure for the detection of sound. However, the relevant stimuli, receiver mechanisms and functions for these putative hearing structures were unknown because butterflyfishes were previously not recognized to produce sounds during natural behavior. We performed field experiments to test the hypothesis that Chaetodon produces sounds in natural social contexts. Acoustic and motor behaviors of the monogamous multiband butterflyfish, C. multicinctus, were evoked and recorded by placement of bottled fish into feeding territories of conspecific pairs. We demonstrate that territory defense includes the production of agonistic sounds and hydrodynamic stimuli that are associated with tail slap, jump, pelvic fin flick and dorsal-anal fin erection behaviors. In addition, grunt pulse trains were produced by bottled intruders and are tentatively interpreted to function as an alert call among pair mates. Acoustic behaviors include low frequency hydrodynamic pulses <100 Hz, sounds with peak energy from 100 Hz to 500 Hz, and a broadband high frequency click (peak frequency=3.6 kHz), which is produced only during the tail slap behavior. These results provide a biological framework for future studies to interpret the proximate function of the acoustico-lateralis sensory system, the evolution of the laterophysic mechanism and their relevance to butterflyfish social behavior.
Warrant for terror : fatwas of radical Islam and the duty of jihad

Chapter 1 Preface Chapter 2 Introduction Chapter 3 1. 'Ulama and Fatwas in Islam Chapter 4 2. The Mechanism of the Jihad Fatwa Chapter 5 3. The House of Islam vs. the House of War Chapter 6 4. The Doctrine of Jihad Chapter 7 5. The Defensive Jihad, an Individual Duty Chapter 8 6. Rules of Engagement Chapter 9 7. Apostates and Apostate Rulers Chapter 10 8. Palestine, Afghanistan, and Iraq Chapter 11 9. The War of the Fatwas Chapter 12 Conclusion
Creating a Large Benchmark for Open Information Extraction

Open information extraction (Open IE) was presented as an unrestricted variant of traditional information extraction. It has been gaining substantial attention, manifested by a large number of automatic Open IE extractors and downstream applications. In spite of this broad attention, the Open IE task deﬁnition has been lacking – there are no formal guidelines and no large scale gold standard annotation. Subsequently, the various implementations of Open IE resorted to small scale post-hoc evaluations, inhibiting an objective and re-producible cross-system comparison. In this work, we develop a methodology that leverages the recent QA-SRL annotation to create a ﬁrst independent and large scale Open IE annotation, 1 and use it to automatically compare the most prominent Open IE systems.
Frontal Hemodynamic Responses to High Frequency Yoga Breathing in Schizophrenia: A Functional Near-Infrared Spectroscopy Study

Frontal hemodynamic responses to high frequency yoga breathing technique, Kapalabhati (KB), were compared between patients of schizophrenia (n = 18; 14 males, 4 females) and age, gender, and education matched healthy subjects (n = 18; 14 males, 4 females) using functional near-infrared spectroscopy. The diagnosis was confirmed by a psychiatrist using DSM-IV. All patients except one received atypical antipsychotics (one was on typical). They had obtained a stabilized state as evidenced by a steady unchanged medication from their psychiatrist for the past 3 months or longer. They learned KB, among other yoga procedures, in a yoga retreat. KB was practiced at the rate of 120 times/min for 1 min. Healthy subjects who were freshly learning yoga too were taught KB. Both the groups had no previous exposure to KB practice and the training was carried out over 2 weeks. A chest pressure transducer was used to monitor the frequency and intensity of the practice objectively. The frontal hemodynamic response in terms of the oxygenated hemoglobin (oxyHb), deoxygenated hemoglobin (deoxyHb), and total hemoglobin (totalHb) or blood volume concentration was tapped for 5 min before, 1 min during, and for 5 min after KB. This was obtained in a quiet room using a 16-channel functional near-infrared system (FNIR100-ACK-W, BIOPAC Systems, Inc., USA). The average of the eight channels for each side (right and left frontals) was obtained for the three sessions. The changes in the levels of oxyHb, deoxyHb, and blood volume for the three sessions were compared between the two groups using independent samples t-test. Within group comparison showed that the increase in bilateral oxyHb and totalHb from the baseline was highly significant in healthy controls during KB (right oxyHb, p = 0.00; left oxyHb, p = 0.00 and right totalHb, p = 0.01; left totalHb, p = 0.00), whereas schizophrenia patients did not show any significant changes in the same on both the sides. On the other hand, schizophrenia patients showed significant reduction in deoxyHb in the right pre-frontal cortex (right deoxyHb, p = 0.00). Comparison between the groups showed that schizophrenia patients have reduced bilateral pre-frontal activation (right oxyHb, p = 0.01; left oxyHb, p = 0.03 and right total Hb, p = 0.03; left total Hb, p = 0.04) during KB as compared to healthy controls. This hypo-frontality of schizophrenia patients in response to KB may be used clinically to support the diagnosis of schizophrenia in future.
Enlarged Memory T-Cell Pool and Enhanced Th1-Type Responses in Chronic Myeloid Leukemia Patients Who Have Successfully Discontinued IFN-α Monotherapy

A small proportion of chronic myeloid leukemia patients treated with interferon-α (IFN-α) monotherapy are able to discontinue the treatment without disease relapse although residual leukemia cells are present. Recently, we showed that these patients have increased amount of NK-cells and a distinct blood cytokine profile. We now aimed to study the function of NK- and T-cells in order to understand the role of the immune system in maintaining the treatment response after IFN-α discontinuation. The study included 13 patients: 5 patients were still treated with IFN-α monotherapy (IFN-ON, median treatment time 163 months) and 8 had stopped the treatment successfully (IFN-OFF, median time without therapy 42 months). Detailed immunophenotype and cytokine production of NK- and T-cells was analyzed with flow cytometry. In addition, the cytotoxicity of NK-cells was studied using K562 as target cells and both the degranulation and direct killing was measured. Compared to healthy controls, IFN-OFF patients had increased proportion of CD4+ effector memory (CCR7−CD45RA−; median 23% vs. healthy 16%, p = 0.009) and CD8+ central memory T-cells (CCR7+CD45RA−; median 26% vs. healthy 14%, p = 0.004). Further, upon stimulation the IFN-γ/TNF-α cytokine secretion by CD4+ T-cells was significantly enhanced in IFN-OFF patients (median 13.7% vs. healthy 7.8%, p = 0.01), and CD4+ effector and central memory cells were the main cytokine producers. No similar increase was observed in IFN-ON group (6.5%). In addition, the proportion of NK-cells was significantly increased in IFN-OFF patients (median IFN-OFF 24%, healthy 13%, p = 0.04), but their direct killing of K562 cells was impaired. The cytotoxicity of NK-cells was also diminished in IFN-ON patients. To conclude, in addition to elevated NK-cell count, IFN-OFF patients have increased amount of memory T-cells, which are able to induce strong cytokine response upon stimulation. This activity may contribute to the maintenance of prolonged remission after successful IFN-α discontinuation.