Miracle-dz/UniFAR-FTUs huggingface dataset:
Recognizing the problem of delayed entry in time‐to‐event studies: Better late than never for clinical neuroscientists

One of the greatest differences I encountered in moving from being Editor‐in‐Chief of a basic science journal to the same position at Annals of Neurology was the much greater importance of meticulous review of the statistical treatment of data. In basic science, the conditions of an experiment can be set up by the investigator so that relatively simple statistical treatments can often be used with clear‐cut results. Comparing the treatment and outcomes of human studies is much messier. Humans have a history before the study started; they have lives that often cause them to deviate from the protocol; and it is much harder to measure the outcomes because our methods have to be so much less invasive than they can be in animal studies. In addition, unlike mice or rats, which are deliberately inbred in a laboratory to minimize variation between animals, we are a wild species with enormous genetic and environmental variability.
Split Calvarial Grafts in Maxillofacial Reconstruction

Experience with thirty-seven patients demonstrating the versatility of the split calvarial graft in facial reconstruction is presented. A total of sixty grafts have been used with no evidence of significant clinical reabsorption, infection, or extrusion; advantages and limitations are discussed. We conclude that the split calvarium represents a readily available and reliable source of membranous bone for grafting maxillofacial defects with minimal limitations and low morbidity.
Bag of visual words approach for image retrieval using color information

Content-based image retrieval has attracted researcher's attention due to the rapid growing of images database. Many approaches for content based image retrieval have been proposed but completely satisfactory result has not yet been obtained. In this paper a new approach for content-based image retrieval using the bag of visual words (BoW) has been proposed. In this approach, two separate visual vocabularies are produced based on the scale invariant feature transform (SIFT) and hue descriptor. Traditional SIFT BoW model do not utilize any color information in image description. We incorporate hue descriptor in our method which adds complementary information to BoW representation of images and increase the overall performance of retrieval. The quantization in BoW model is an essential step that has a great impact on the final result but it produces loss in quantization. To overcome this unfavorable effect, soft assignment is used in our proposed approach in which each feature vector can be assigned to multiple nearest visual words based on some weighting function. Experimental results on benchmark dataset showed that the proposed approach has a superior performance with respect to other methods.
Adaptive control for hypersonic vehicle based on error characteristic model

Considering that the hypersonic vehicle is fast time-varying, high nonlinear and strong coupled, which makes designing a well performed controller rather difficult, this paper proposes an attitude control method based on exact feedback linearization control and characteristic model adaptive control to ensure the stability of the control system. Firstly, a nonlinear coupled dynamic model for the hypersonic vehicle is established. Secondly, through choosing a proper attitude motion model, the original system can be decoupled and linearized and an all-state feedback linearization control law can be obtained. Then, based on the pole assignment method, an output feedback control law can be designed, simultaneously the error characteristic model is deduced, according to which an all-coefficient adaptive control law is designed to ensure the robustness of the system. Finally, the correctness and effectiveness of this controller are verified by mathematical simulations. The simulation results show that this attitude control system can track the control commands well and has strong stability and robustness.
Preparing soldiers for the stress of combat.

UNLABELLED Protracted use of stressors during military training courses does not necessarily enhance a Soldier? s ability to regulate stress on the battlefield. Extensive stress during training can be a contributing factor to suboptimal neurologic and overall long-term health. Prolonged high-stress military training programs, as well as extended duration combat deployments, should be comprehensively scrutinized for opportunities to preserve health and increase combat effectiveness. Contemporary research in neuroscience and psychology can provide insight into training techniques that can be used to control stress and optimize performance in combat. Physical fitness training programs can elevate the stress threshold. Extensive situational training can also inoculate Soldiers to specific combat stressors. Training methods such as these will enable Soldiers to achieve higher levels of performance while under enemy fire and are encouraged for units deploying to combat. KEYWORDS combat stress, military training, military deployment, physical training, post-traumatic stress disorder, sleep deprivation, stress inoculation training.
The Presynaptic Dense Projection of the Caenorhabiditis elegans Cholinergic Neuromuscular Junction Localizes Synaptic Vesicles at the Active Zone through SYD-2/Liprin and UNC-10/RIM-Dependent Interactions

The active zone (AZ) of chemical synapses is a specialized area of the presynaptic bouton in which vesicles fuse with the plasma membrane and release neurotransmitters. Efficient signaling requires synaptic vesicles (SVs) to be recruited, primed, and retained at the AZ, in close proximity to voltage-dependent calcium channels that are activated during presynaptic depolarization. The electron-dense specializations at the AZ might provide a molecular platform for the spatial coordination of these different processes. To investigate this hypothesis, we examined high-resolution three-dimensional models of Caenorhabditis elegans cholinergic neuromuscular junctions generated by electron tomography. First, we found that SVs are interconnected within the bouton by filaments similar to those described in vertebrates. Second, we resolved the three-dimensional structure of the dense projection centered in the AZ. The dense projection is a more complex structure than previously anticipated, with filaments radiating from a core structure that directly contact SVs in the interior of the bouton as well as SVs docked at the plasma membrane. Third, we investigated the functional correlate of these contacts by analyzing mutants disrupting two key AZ proteins: UNC-10/RIM and SYD-2/liprin. In both mutants, the number of contacts between SVs and the dense projection was significantly reduced. Similar to unc-10 mutants, the dependence of SV fusion on extracellular calcium concentration was exacerbated in syd-2 mutants when compared with the wild type. Hence, we propose that the dense projection ensures proper coupling of primed vesicles with calcium signaling by retaining them at the AZ via UNC-10/RIM and SYD-2/liprin-dependent mechanisms.
A Similarity-Based Hierarchical Clustering Method for Manufacturing Process Models

As the adoption of information technologies increases in the manufacturing industry, manufacturing companies should efficiently manage their data and manufacturing processes in order to enhance their manufacturing competency. Because smart factories acquire processing data from connected machines, the business process management (BPM) approach can enrich the capability of manufacturing operations management. Manufacturing companies could benefit from the well-defined methodologies and process-centric engineering practices of this BPM approach for optimizing their manufacturing processes. Based on the approach, this paper proposes a similarity-based hierarchical clustering method for manufacturing processes. To this end, first we describe process modeling based on the BPM-compliant standard so that the manufacturing processes can be controlled by BPM systems. Second, we present similarity measures for manufacturing process models that serve as a criterion for the hierarchical clustering. Then, we formulate the hierarchical clustering problem and describe an agglomerative clustering algorithm using the measured similarities. Our contribution is considered on the assumption that a manufacturing company adopts the BPM approach and it operates various manufacturing processes. We expect that our method enables manufacturing companies to design and manage a vast amount of manufacturing processes at a coarser level, and it also can be applied to various process (re)engineering problems.
Csk suppression of Src involves movement of Csk to sites of Src activity

Csk phosphorylates Src family members at a key regulatory tyrosine in the C-terminal tail and suppresses their activities. It is not known whether Csk activity is regulated. To examine the features of Csk required for Src suppression, we expressed Csk mutants in a cell line with a disrupted csk gene. Expression of wild-type Csk suppressed Src, but Csk with mutations in the SH2, SH3, and catalytic domains did not suppress Src. An SH3 deletion mutant of Csk was fully active against in vitro substrates, but two SH2 domain mutants were essentially inactive. Whereas Src repressed by Csk was predominantly perinuclear, the activated Src in cells lacking Csk was localized to structures resembling podosomes. Activated mutant Src was also in podosomes, even in the presence of Csk. When Src was not active, Csk was diffusely located in the cytosol, but when Src was active, Csk colocalized with activated Src to podosomes. Csk also localizes to podosomes of cells transformed by an activated Src that lacks the major tyrosine autophosphorylation site, suggesting that the relocalization of Csk is not a consequence of the binding of the Csk SH2 domain to phosphorylated Src. A catalytically inactive Csk mutant also localized with Src to podosomes, but SH3 and SH2 domain mutants did not, suggesting that the SH3 and SH2 domains are both necessary to target Csk to places where Src is active. The failure of the catalytically active SH3 mutant of Csk to regulate Src may be due to its inability to colocalize with active Src.
Immunosuppressive TOR kinase inhibitor everolimus (RAD) suppresses growth of cells derived from posttransplant lymphoproliferative disorder at allograft-protecting doses

Background. Posttransplant lymphoproliferative disorders (PTLDs) represent a life-threatening complication of standard immunosuppressive therapy. The impact of novel, rapamycin-related immunosuppressive drugs on the pathogenesis of PTLDs remains undefined. Methods. We tested the effect of everolimus (RAD, Novartis Pharma AG, Basel, Switzerland) on human PTLD-derived cells using in vitro assays and an in vivo severe combined immunodeficiency disease mouse xenotransplant model. Results. Everolimus profoundly inhibited the proliferation, cell-cycle progression, and survival of the PTLD-1 cell line established from a pulmonary PTLD. Equally profound inhibition of PTLD-1 growth was achieved in vivo at well-tolerated everolimus doses of 0.5 to 5 mg/kg per day. Five mg/kg per day of everolimus, given once per day, inhibited PTLD-1 tumor volume gain by more than 10-fold in treated mice compared with untreated mice. Because the subsequent pharmacokinetic analysis indicated rapid everolimus absorption, distribution, and clearance in mice (with a half-life of 3 to 6 hr and maximum drug blood concentration reached after 0.5 to 1 hr), treatment was changed to a twice-daily regimen. Everolimus given twice daily at 0.5 mg/kg per dose inhibited tumor-volume gain by more than 60-fold and at 0.25 mg/kg per dose by more than 10-fold. Similar everolimus doses were required to prevent graft rejection in a mouse heart allotransplantation model; the highest dose tested (1.5 mg/kg twice daily) resulted in long-term graft survival in all mice that underwent transplantation. Conclusions. Everolimus displays a potent inhibitory effect on PTLD-derived cells in vitro and in vivo in a dose range leading to prevention of allograft rejection and may prove effective in both the prevention and treatment of PTLDs in transplant patients.
Perceived influence of relationship communication on insurance service quality and customer satisfaction

Extant literature in marketing and communications has long recognized the importance of effective communication as the essential link for sustainable relationship between organizations and their customers. In spite of its importance, many studies have revealed that practices of communication in relationship marketing in some service firms are fraught with problems, which influence the perceptions of customers about the commitment of those organizations to service quality and customer value. This exploratory study was undertaken to analyze how insurance customers perceive their relationships with insurers through received messages. The study also sought to identify the inherent differences in the perception of relational messages received from insurers by the customers based on gender. A simple random sample of 145 insurance customers were drawn for the study from three insurance agencies. Useful responses were received from 120 automobile insurance policyholders, which represented 82.76% of the sample. Four hypotheses were tested with Pearson Correlation, one-way analysis of variance (ANOVA), and multiple regression analysis. The results of the study suggested significant relationship between relational messages, service quality, and customer satisfaction. In terms of differences in the perceptions of male and female respondents, the study indicated significant differences in the perception of personal values and perceived quality through received messages. Similarly, significant differences were recorded in the perception of message credibility by the female participants as compared with those of the males. The study also revealed the need for insurance companies to fully imbibe relationship communication with their customers, through assessment of the internal and external situations which surround the information needs of individual customers.
Clinical Treatment of Radiotherapy Tissue Damage by Lipoaspirate Transplant: A Healing Process Mediated by Adipose-Derived Adult Stem Cells

Background: There is evidence that stem cells contribute to the restoration of tissue vascularization and organ function. The objective of this study was to assess the presence of adipose-derived adult stem cells left in their natural scaffold in the purified lipoaspirate and to assess the clinical effectiveness of lipoaspirate transplantation in the treatment of radiation side effects. Methods: This study was designed beginning with surgical procedures in 2002 and envisaging a continuous patient follow-up to 31 months. Twenty consecutive patients undergoing therapy for side effects of radiation treatment with severe symptoms or irreversible function damage (LENT-SOMA scale grade 3 and 4) were enrolled. Purified autologous lipoaspirates (60 to 120 cc) taken from a healthy donor site were administered by repeated low-invasive computer-assisted injection. Therapy outcomes were assessed by symptoms classification according to the LENT-SOMA scale, cytofluorimetric characterization, and ultrastructural evaluation of targeted tissue. Results: In the isolated stromal vascular fraction of 2 cc of human lipoaspirate, cells with mesenchymal stem cell physical properties and immunophenotype were in average 1.07 ± 0.5 percent (n = 4), with a clonogenic fraction of 0.139 percent. At least 1.02 × 103 colony-forming units–fibroblast were present in each lipoaspirate. Ultrastructure of target tissue systematically exhibited progressive regeneration, including neovessel formation and improved hydration. Clinical outcomes led to a systematic improvement or remission of symptoms in all evaluated patients, including otherwise untreatable patients exhibiting initial irreversible functional damage. Conclusions: This surgical procedure is a low-invasive therapeutic approach for resolving the late side effects of radiotherapy. According to the proposed hypothesis of the ischemic nature of radiolesions, treatment with lipoaspirate transplantation is potentially extended to other forms of microangiopathies.
Isolation and Characterization of Two Novel Phosphodiesterase PDE11A Variants Showing Unique Structure and Tissue-specific Expression*

cDNAs encoding a novel phosphodiesterase, phosphodiesterase 11A (PDE11A), were isolated by a combination of reverse transcriptase-polymerase chain reaction using degenerate oligonucleotide primers and rapid amplification of cDNA ends. Their catalytic domain was identical to that of PDE11A1 (490 amino acids) reported during the course of this study. However, the cDNAs we isolated had N termini distinct from PDE11A1, indicating two novel N-terminal variants of PDE11A. PDE11A3 cDNA encoded a 684-amino acid protein including one complete and one incomplete GAF domain in the N-terminal region. PDE11A4 was composed of 934 amino acids including two complete GAF domains and shared 630 C-terminal amino acids with PDE11A3 but had a distinct N terminus containing the putative phosphorylation sites for cAMP- and cGMP-dependent protein kinases. PDE11A3 transcripts were specifically expressed in testis, whereas PDE11A4 transcripts were particularly abundant in prostate. Recombinant PDE11A4 expressed in COS-7 cells hydrolyzed cAMP and cGMP with K m values of 3.0 and 1.4 μm, respectively, and the V maxvalue with cAMP was almost twice that with cGMP. Although PDE11A3 showed the same K m values as PDE11A4, the relativeV max values of PDE11A3 were approximately one-sixth of those of PDE11A4. PDE11A4, but not PDE11A3, was phosphorylated by both cAMP- and cGMP-dependent protein kinases in vitro. Thus, the PDE11A gene undergoes tissue-specific alternative splicing that generates structurally and functionally distinct gene products.
Functional dissection of the glucose signaling pathways that regulate the yeast glucose transporter gene (HXT) repressor Rgt1

The yeast Rgt1 repressor is a bifunctional protein that acts as a transcriptional repressor and activator. Under glucose‐limited conditions, Rgt1 induces transcriptional repression by forming a repressive complex with its corepressors Mth1 and Std1. Here, we show that Rgt1 is converted from a transcriptional repressor into an activator under high glucose conditions and this occurs through two independent but consecutive events mediated by two glucose signaling pathways: (1) disruption of the repressive complex by the Rgt2/Snf3 pathway; (2) phosphorylation of Rgt1 by the cAMP‐dependent protein kinase (cAMP‐PKA) pathway. Rgt1 is phosphorylated by PKA at four serine residues within its amino‐terminal region, but this does not occur until the repressive complex is disrupted. While phosphorylation of any one of these sites is sufficient to enable Rgt1 to induce transcriptional activation, phosphorylation of all the sites results in the release of Rgt1 from DNA. We discuss how the bifunctional properties of Rgt1 are regulated through differential phosphorylation. J. Cell. Biochem. 112: 3268–3275, 2011. © 2011 Wiley Periodicals, Inc.
Glucuronate, the precursor of vitamin C, is directly formed from UDP‐glucuronate in liver

The conversion of UDP‐glucuronate to glucuronate, usually thought to proceed by way of glucuronate 1‐phosphate, is a site for short‐term regulation of vitamin C synthesis by metyrapone and other xenobiotics in isolated rat hepatocytes [Linster CL & Van Schaftingen E (2003) J Biol Chem278, 36328–36333]. Our purpose was to explore the mechanism of this effect in cell‐free systems. Metyrapone and other xenobiotics stimulated, by approximately threefold, the formation of glucuronate from UDP‐glucuronate in liver extracts enriched with ATP‐Mg, but did not affect the formation of glucuronate 1‐phosphate from UDP‐glucuronate or the conversion of glucuronate 1‐phosphate to glucuronate. This and other data indicated that glucuronate 1‐phosphate is not an intermediate in glucuronate formation from UDP‐glucuronate, suggesting that this reaction is catalysed by a ‘UDP‐glucuronidase’. UDP‐glucuronidase was present mainly in the microsomal fraction, where its activity was stimulated by UDP‐N‐acetylglucosamine, known to stimulate UDP‐glucuronosyltransferases by enhancing the transport of UDP‐glucuronate across the endoplasmic reticulum membrane. UDP‐glucuronidase and UDP‐glucuronosyltransferases displayed similar sensitivities to various detergents, which stimulated at low concentrations and generally inhibited at higher concentrations. Substrates of glucuronidation inhibited UDP‐glucuronidase activity, suggesting that the latter is contributed by UDP‐glucuronosyltransferase(s). Inhibitors of β‐glucuronidase and esterases did not affect the formation of glucuronate, arguing against the involvement of a glucuronidation–deglucuronidation cycle. The sensitivity of UDP‐glucuronidase to metyrapone and other stimulatory xenobiotics was lost in washed microsomes, even in the presence of ATP‐Mg, but it could be restored by adding a heated liver high‐speed supernatant or CoASH. In conclusion, glucuronate formation in liver is catalysed by a UDP‐glucuronidase which is closely related to UDP‐glucuronosyltransferases. Metyrapone and other xenobiotics stimulate UDP‐glucuronidase by antagonizing the inhibition exerted, presumably indirectly, by a combination of ATP‐Mg and CoASH.
Election cycles and mining-sector governance in post-conflict Kosovo

ABSTRACT Political business cycles are typically linked to the manipulation of fiscal or monetary policy instruments. In a recent article, Imami, Lami and Uberti (ILU) argue that opportunistic politicians may also choose to manipulate non-fiscal/non-monetary policy instruments. Here, we extend ILU’s study using time-series data on mining-sector licensing from post-conflict Kosovo (2001–2018). We find robust evidence that is consistent with electoral opportunism in the allocation of mining permits, despite the checks-and-balance mechanisms introduced by Kosovo’s international administrators in an attempt to reduce the politicisation of licensing. That said, the cycle effect is only observed prior to scheduled, as opposed to early, elections. Disaggregating the data by licence type, in addition, we find that the observed election cycle is driven primarily by the manipulation of licences for the mining of construction materials. We argue that, in the context of post-conflict Kosovo, this is the category of licences whose strategic manipulation offers the greatest pay-off to the incumbent. The results raise some questions about the feasibility of fighting political opportunism (and, relatedly, corruption) by establishing formal check-and-balance mechanisms.