Miracle-dz/UniFAR-FTUs huggingface dataset:
The neuropsychiatry of impulsivity

Purpose of review Impulsive symptoms occur across neuropsychiatric disorders, with important ramifications for everyday functioning and quality of life. This article considers recent developments in the neuropsychological assessment of impulsivity with a focus on the ability to suppress motor responses (response inhibition). Recent findings Using objective tests, response inhibition deficits were identified in several neuropsychiatric conditions associated with impulsivity, namely attention deficit hyperactivity disorder, trichotillomania, obsessive–compulsive disorder, and chronic substance abuse. Deficits were also found in unaffected first-degree relatives of attention deficit hyperactivity disorder and obsessive–compulsive disorder patients. Evidence from patients with focal brain lesions and from healthy volunteers using functional MRI and transcranial stimulation implicated the right inferior frontal gyrus in response inhibition. Pharmacological manipulations of the serotonin system had no detectable behavioural effects on response inhibition, whereas manipulations of the noradrenaline system did. Summary Neuropsychological assessment shows great promise in the investigation of impulsivity and its brain substrates. These results support a key role for response inhibition, a function linked to the right inferior frontal gyrus, in the manifestation of impulsivity. Measures of response inhibition will contribute to the search for psychiatric endophenotypes, novel treatments, and more optimal diagnostic classification systems for neuropsychiatric disorders.
Heterologous Aquaporin (AQY2–1) Expression Strongly Enhances Freeze Tolerance of Schizosaccharomyces pombe

Aquaporin membrane proteins enable the transport of water across membranes in various organisms. In yeast their expression has been shown to correlate strongly with freeze tolerance. When we analyzed the freeze tolerance of Schizosaccharomyces pombe, an organism whose genome sequence has revealed no genes encoding a bona fide water channel, we found very low intrinsic freeze tolerance compared to other yeast species with aquaporin-encoding genes. Deletion of Spac977.17, which encodes a putative glycerol facilitator, resulted in no significant differences in freeze tolerance with its corresponding wild-type strain in all growth conditions tested. However, when we expressed the Saccharomyces cerevisiae aquaporin-encoding gene AQY2–1 in S. pombe cells, we found that the relatively low freeze tolerance of S. pombe could be significantly enhanced. Therefore, (i) the absence of a bona fide water channel in S. pombe might provide in part an explanation for its overall low freeze tolerance compared to other yeast species, and (ii) aquaporin overexpression might be a tool to improve cryopreservation of many other cell types as well, as has recently been shown for mouse oocytes and fish embryos.
Cross-talk with Ca2+ Influx Does Not Underlie the Role of Extracellular Signal-regulated Kinases in Cytotoxic T Lymphocyte Lytic Granule Exocytosis*

One important mechanism cytotoxic T lymphocytes use to kill target cells is exocytosis of lytic granules that contain cytotoxic agents such as perforin and granzyme. Ca2+ influx and activation of protein kinase C have been known for many years to be key signals for granule exocytosis. Recent work has suggested that activation of extracellular signal-regulated kinases (ERK), members of the mitogen-activated protein kinase (MAP kinase) family, may be a third required signal. We surmised that the involvement of ERK in lytic granule exocytosis could be mediated through cross-talk with Ca2+ influx, rather than constituting an independent signal. We tested this idea using TALL-104 human leukemic CTLs as a model system and discovered the following. 1) ERK inhibition caused a modest decrease in the amplitude of increases in intracellular Ca2+ concentration, but this effect cannot account for the profound inhibition of granule exocytosis. 2) Ca2+ influx can activate ERK in TALL-104 cells, but this effect does not contribute to ERK activation stimulated by solid phase anti-CD3 monoclonal antibodies. We conclude that cross-talk between ERK signaling and Ca2+ does not mediate the role of ERK in CTL lytic granule exocytosis.
Gender Differences in the Choice of Major: The Importance of Female Role Models

We conducted a field experiment aimed at increasing the percentage of women majoring in economics. We exposed students enrolled in introductory classes to successful and charismatic women who majored in economics at the same university. The intervention significantly impacted female students’ enrollment in further economics classes, increasing their likelihood to major in economics by 8 percentage points. This is a large effect, given that only 9 percent of women were majoring in economics at baseline. Since the impacted women were previously planning to major in lower-earning fields, our low-cost intervention may have a positive effect on their future incomes. (JEL A22, C93, I23, I26, J16)
Characterization of the copper(II)- and nickel(II)-transport site of human serum albumin. Studies of copper(II) and nickel(II) binding to peptide 1-24 of human serum albumin by 13C and 1H NMR spectroscopy.

As a basis for understanding the role of albumin in the transport of metal ions, detailed investigations have been carried out to elucidate the structure of Ni(II)- and Cu(II)-binding site of the peptide residue corresponding to the NH2-terminal peptide fragment 1-24 of human serum albumin by 1H and 13C NMR spectroscopy. These studies have been conducted in aqueous medium at different pH values and at different ligand/metal ratios. The results show the following: (i) Diamagnetic Ni(II) complex and paramagnetic Cu(II) complex are in slow exchange NMR time scale. (ii) Titration results of Ni(II)-bound form of peptide 1-24 show the presence of a 1:1 complex in the wide pH range (6.0-11.0), and the same stoichiometry is proposed for Cu(II) as well. (iii) Analysis of the spectra suggests that both Ni(II) and Cu(II) have one specific binding site at the NH2-terminal tripeptide segment (Asp-Ala-His.) involving the Asp alpha-NH2, His N(1) imidazole, two deprotonated peptide nitrogens (Ala NH and His NH), and the Asp COO- group. (iv) Complexation of Ni(II) and Cu(II) causes conformational change near the metal-binding site of the polypeptide chain, but there is no other binding group involved besides those in the first three residues.
Switching from serotonin reuptake inhibitors to duloxetine in patients with resistant obsessive compulsive disorder: a case series

Obsessive compulsive disorder (OCD) is a chronic disorder, currently recognized as one of the most common psychiatric disorder as well as one of the most disabling of all medical disorders. OCD is characterized by high rates of partial and/or absent response to standard, recommended treatments (serotonin reuptake inhibitors and psychotherapy). Recent investigation showed that Venlafaxine, a dual serotonin and norepinephrine reuptake inhibitor (SNRI), may be a valid alternative for some treatment-refractory patients. We present the cases of four OCD patients with comorbid mood or anxiety disorders, who were treated with serotonin reuptake inhibitors (SRIs) at adequate doses for at least 12 weeks, showing partial/no response. Patients were then switched to Duloxetine up to 120 mg/day and followed up for 12 weeks. Three out of four patients showed a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score reduction ≥35%. Duloxetine may be helpful in patients with treatment-resistant OCD, although larger and controlled studies are warranted to confirm this preliminary observation.
Escherichia coli replicative helicase PriA protein-single-stranded DNA complex. Stoichiometries, free energy of binding, and cooperativities.

Analyses of interactions of the Escherichia coli replicative helicase, PriA protein, with a single-stranded (ss) DNA have been performed, using the quantitative fluorescence titration technique. The stoichiometry of the PriA helicase.ssDNA complex has been examined in binding experiments with a series of ssDNA oligomers. The total site-size of the PriA.ssDNA complex, i.e. the maximum number of nucleotide residues occluded by the PriA helicase in the complex, is 20 +/- 3 residues per protein monomer. However, the protein can efficiently form a complex with a minimum of 8 nucleotides. Thus, the enzyme has a strong ssDNA-binding site that engages in direct interactions with a significantly smaller number of nucleotides than the total site-size. The ssDNA-binding site is located in the center of the enzyme molecule, with the protein matrix protruding over a distance of approximately 6 nucleotides on both sides of the binding site. The analysis of the binding of two PriA molecules to long oligomers was performed using statistical thermodynamic models that take into account the overlap of potential binding sites, cooperative interactions, and the protein.ssDNA complexes with different stoichiometries. The intrinsic affinity depends little upon the length of the ssDNA. Moreover, the binding is accompanied by weak cooperative interactions.
Selective Mutism: The Fraternal Twin of Childhood Social Phobia

Background: Selective mutism (SM) is an anxiety disorder with a close link to childhood social phobia (SP). Our studies compare behavioral problem profiles in children and adolescents with SM and SP and control groups and assess the comorbidity patterns of SM and SP. Methods: Participants aged 3-18 years with SM (n = 95), SP (n = 74) and internalizing disorders (INT, n = 46) and a typically developing control group (CG, n = 119) were assessed with the Child Behavior Checklist (CBCL); adolescents were additionally assessed with the Youth Self-Report (YSR). Comorbidity was assessed in SM and SP participants with a diagnostic interview. Results: SP was detected in 94% of children with SM. SM participants showed different behavioral and psychiatric symptoms than SP: they were more frequently affected by lifetime separation anxiety disorder (SM: 45%, SP: 26%) and oppositional defiant disorder (SM: 22%, SP: 5%), and less by generalized anxiety disorder (SM: 6%, SP: 20%) and major depression (SM: 12%, SP: 26%). Adolescents with SM showed high rates of agoraphobia (SM 27%; SP 10%) and more social problems (YSR), and were more withdrawn (CBCL, YSR) than those with SP alone. Specific behavioral problems of SM and SP compared to INT and CG were observed. Conclusion: SM and SP represent separate but closely related disorders, distinct from other INT and CG, with specific patterns of lifetime comorbidities.
Strategic planning in the public sector : the case of the Turkish Ministry of Interior

This thesis investigates the difficulties and challenges experienced in the first strategic planning process of the Turkish Ministry of Interior (MoI) between the years 2007 and 2013 through case study method. Specifically, it documents how and why top-down, mandatory and formal strategic planning in a one-size-fits-all fashion can be poorly implemented through an authoritative and bureaucratic ministry located in the Turkish central government, within the context of a highly centralised and dynamic policymaking environment. Triangulating data from multiple sources, the research applies the theories of rational planning and incrementalism to the case through a pattern-matching approach along with a rival explanation logic in order to explain the structures and mechanisms that lead to ineffective practice in strategic planning in the MoI. The research proposes a variety of underlying mechanisms for ineffective strategic planning that originate from; the formal-legal strategic planning framework, environmental and institutional contingencies, socio-political factors, cultural tendencies, practitioners’ actual practice, culture of democracy, public service and domain characteristics, organisational memory, leadership, values, external powers and tendencies. The research argues that no single theory fully explains the strategic planning process and practice of the MoI, although incrementalism fits better than rational planning. It proposes a rule-based decision-making mental model as a generative mechanism that leads, in interaction with other mechanisms, to incremental analysis. It demonstrates that incremental decision-making may still continue in a public organisational setting while formal strategic planning is in force and legally binding. The research concludes that the application of strategic planning does not produce automatic results, at least in the short-run, and effective strategic planning requires transformation of mental models from rule-based to goal-based, which can be made possible by the effective intellectual preparation of strategy practitioners. Thereby, the research calls for increased attention on strategy practitioners and their actual practice in strategic planning processes.
BOTH MALE AND FEMALE NOVEL TRAITS PROMOTE THE CORRELATED EVOLUTION OF GENITALIA BETWEEN THE SEXES IN AN ARTHROPOD

The correlated evolution of genitalia between sexes has been demonstrated in many taxa. However, it remains unclear whether female rather than male genitalia can play a key role in the correlated evolution of male and female genitalia. We conducted an extensive cross‐population analysis of the divergence patterns of genital structures, weights of whole genital organs, and the bodies of both sexes, and male genital length in a group of xystodesmid millipedes showing diverse genital morphologies. We demonstrate that the correlated evolution of male and female genitalia toward exaggerated states has occurred in the millipedes, which have evolved novel traits in both males (forceps‐like gonopods) and females (retractable bellows). Enlargement and elongation of forceps‐like gonopods may be advantageous in sperm competition, whereas enlargement and elongation of the bellows may facilitate acceptance/rejection of insemination for ensuring the female's fitness. These male and female genital parts have affected the correlated evolution in the opposite sex, resulting in diversification and exaggeration of genital morphology. Our study suggests that evolutionary novel traits in not only males but also in females could play an important role in the correlated evolution of genitalia between the sexes.
Impairment of the ubiquitin‐proteasome system causes dopaminergic cell death and inclusion body formation in ventral mesencephalic cultures

Mutations in α‐synuclein, parkin and ubiquitin C‐terminal hydrolase L1, and defects in 26/20S proteasomes, cause or are associated with the development of familial and sporadic Parkinson's disease (PD). This suggests that failure of the ubiquitin–proteasome system (UPS) to degrade abnormal proteins may underlie nigral degeneration and Lewy body formation that occur in PD. To explore this concept, we studied the effects of lactacystin‐mediated inhibition of 26/20S proteasomal function and ubiquitin aldehyde (UbA)‐induced impairment of ubiquitin C‐terminal hydrolase (UCH) activity in fetal rat ventral mesencephalic cultures. We demonstrate that both lactacystin and UbA caused concentration‐dependent and preferential degeneration of dopaminergic neurons. Inhibition of 26/20S proteasomal function was accompanied by the accumulation of α‐synuclein and ubiquitin, and the formation of inclusions that were immunoreactive for these proteins, in the cytoplasm of VM neurons. Inhibition of UCH was associated with a loss of ubiquitin immunoreactivity in the cytoplasm of VM neurons, but there was a marked and localized increase in α‐synuclein staining which may represent the formation of inclusions bodies in VM neurons. These findings provide direct evidence that impaired protein clearance can induce dopaminergic cell death and the formation of proteinaceous inclusion bodies in VM neurons. This study supports the concept that defects in the UPS may underlie nigral pathology in familial and sporadic forms of PD.
AHITS-UPT: A High Quality Academic Resources Recommendation Method

Personalized recommendation technology provides the possibility for users to obtain academic resources quickly and accurately. However, the existing recommendation methods based on user's historical behaviors and paper contents are limited in terms of expanding user perspectives. The existing methods that evaluate the authority and quality of academic resources based on academic network ignore paper information or consider some unreasonable information, leading to various quality levels of recommendation results. In order to recommend high quality academic resources to users and expand the horizons of users, we propose an Advanced Hyperlink Induced Topic Search (AHITS) algorithm to evaluate the quality and authority of academic resources, propose a user research interest model based on constructing a tripartite graph, namely User-Paper-Topic (UPT), and propose an academic resource recommendation method based on AHITS and UPT. Experimental results show that the methods presented in this paper can effectively remedy the problem that content based recommendation method is not conducive to expand the horizons of users, recommend authoritative authors and high quality papers to users, improve the accuracy of the recommendation results, and effectively reduce the time complexity of algorithm.
Macro- and microscale variables regulate stent haemodynamics, fibrin deposition and thrombomodulin expression

Drug eluting stents are associated with late stent thrombosis (LST), delayed healing and prolonged exposure of stent struts to blood flow. Using macroscale disturbed and undisturbed fluid flow waveforms, we numerically and experimentally determined the effects of microscale model strut geometries upon the generation of prothrombotic conditions that are mediated by flow perturbations. Rectangular cross-sectional stent strut geometries of varying heights and corresponding streamlined versions were studied in the presence of disturbed and undisturbed bulk fluid flow. Numerical simulations and particle flow visualization experiments demonstrated that the interaction of bulk fluid flow and stent struts regulated the generation, size and dynamics of the peristrut flow recirculation zones. In the absence of endothelial cells, deposition of thrombin-generated fibrin occurred primarily in the recirculation zones. When endothelium was present, peristrut expression of anticoagulant thrombomodulin (TM) was dependent on strut height and geometry. Thinner and streamlined strut geometries reduced peristrut flow recirculation zones decreasing prothrombotic fibrin deposition and increasing endothelial anticoagulant TM expression. The studies define physical and functional consequences of macro- and microscale variables that relate to thrombogenicity associated with the most current stent designs, and particularly to LST.
Phase IIIb safety results from an expanded-access protocol of talimogene laherparepvec for patients with unresected, stage IIIB–IVM1c melanoma

Talimogene laherparepvec is a genetically modified herpes simplex virus-1-based oncolytic immunotherapy for the local treatment of unresectable cutaneous, subcutaneous, and nodal tumors in patients with melanoma recurrence following surgery. We aim to describe the safety of talimogene laherparepvec. Intralesional talimogene laherparepvec was administered at less than or equal to 4 ml×106 PFU/ml at protocol day 1, then less than or equal to 4 ml×108 PFU/ml 21 days later, and then every 14 days. Treatment continued until complete response, absence of injectable tumors, progressive disease, intolerance, or US Food and Drug Administration approval. Adverse events were graded during and 30 days after the end of treatment. Lesions suspected to have herpetic origin were tested for talimogene laherparepvec DNA by quantitative PCR (qPCR). Between September 2014 and October 2015, 41 patients were enrolled with stage IIIB (22%), IIIC (37%), IVM1a (34%), IVM1b (5%), and IVM1c (2%) melanoma. The median age was 72 (range: 32–96) years and 54% of the patients were men. Patients had an ECOG performance status of 0 (68%) or 1 (32%). The median treatment duration was 13.1 (3.0–41.1) weeks. Treatment-related adverse events of greater than or equal to grade 3 were reported in three (7.3%) patients and included vomiting, upper abdominal pain, chills, hyperhidrosis, nausea, pyrexia, and wound infection. Suspected herpetic lesions were swabbed in five (12%) patients. One of the five tested positive for talimogene laherparepvec DNA by qPCR, but this lesion had been injected previously with talimogene laherparepvec. During the study, five patients completed treatment because of complete response per investigators. In the clinical practice setting, talimogene laherparepvec has a safety profile comparable to that observed in previous clinical trials. Talimogene laherparepvec (IMLYGIC) is now approved in the US, European Union, and Australia.
On the theory and measurement of the determinants of mortality

This article develops a model of mortality that shows how biological, demographic, and environmental factors interact to affect an individual’s probability of dying. To illustrate the usefulness of the model, we derive from it (as special cases) the Brass system of model life tables and the proportional-hazard mortality model and apply a logit version of the model to analyze the determinants of child mortality in Sri Lanka.
R.E.N.A.L. Nephrometry scoring: how well correlated are urologist, radiologist, and collaborator scores?

PURPOSE R.E. N.A. L. Nephrometry Score (NS) is an imaging-based (CT/MRI) scoring system commonly used by urologists to standardize the reporting of renal masses by enabling quantification of anatomical characteristics. We sought to examine the inter-rater correlation of NS between urologists, radiologists, and tumor-board collaborators. METHODS We identified adult patients undergoing partial or radical nephrectomy over 10 years (n=2450). Patients with autosomal dominant polycystic kidney disease (ADPKD), metastatic disease, masses >10 cm, and studies in which the study urologists or radiologists partook in patient care were excluded. Preoperative imaging was evaluated and patients with multiphasic CT available were included. Scans were provided to the reviewers to evaluate with a R.E. N.A. L. nephrometry questionnaire. Results were analyzed using kappa correlation coefficients. RESULTS One hundred twenty patients met inclusion criteria with mean age of 59.5 years. The majority of cases were partial nephrectomies (72%). Eighty-five percent of the tumors were malignant, with 26% having high-grade histology. The mean (standard deviation) overall NS was 6.8 (1.9) with fair correlation among reviewers (κ=0.222). Collaborators had the highest inter-rater correlation, ranging from 0.41 to 0.84 for NS component scores, compared with 0.42-0.85 for radiologists and 0.36-0.86 for urologists. "R" scores were best correlated (κ>0.8). NS correlation ranged between 0.16 and 0.31 for the groups while the NS complexity category correlation ranged between 0.50 and 0.61. CONCLUSIONS Despite being naive to NS, inter-radiologist scoring patterns were better correlated than inter-urologist. The urologist and radiologist collaborating in tumor board showed the highest agreement, suggesting that a multidisciplinary approach in the characterization of renal masses may provide benefit to patient management.