Miracle-dz/UniFAR-FTUs huggingface dataset:
Challenges in the development of new therapies for bronchiectasis

Introduction: Bronchiectasis is a neglected condition for which there are no licensed therapies. Increasing recognition of the disease has led to a surge in interest over recent years, with a number of active drug development programmes. Areas covered: Disappointing results with therapies successful in cystic fibrosis (CF) have forced a re-evaluation of how we develop new treatments for bronchiectasis. Bronchiectasis presents a unique array of challenges. These include a heterogeneous and poorly characterized patient population, a lack of agreed standards of care and a lack of understanding of the natural history. Pre-clinical development is limited by the lack of an adequate animal model of disease, and by our limited understanding of pathogenesis. There is no agreement on how to define key clinical trials end points including exacerbations and quality of life. The difficulty in translating positive Phase II data into successful Phase III trials suggests the need for better early phase trial end points. Expert opinion: Extrapolating from CF and chronic obstructive pulmonary disease has been a necessity but now risks holding back development if we do not recognize the unique challenges in bronchiectasis. This article comprehensively reviews the barriers to new drug development for bronchiectasis.
Lte-advanced and 4g Wireless Communications Lte-advanced: an Operator Perspective an Overview of Release 10 Carrier Aggregation Potential Use Cases of Release 10 Carrier Aggregation

INTRODUCTION The thirst for greater data rates exhibited by users of mobile wireless services has been on an exponential trajectory. Long Term Evolution (LTE)-Advanced seeks to improve voice quality and expand broadband data services, to deliver high-definition video and audio and other on-demand and real-time contentin an " anything-anywhere-anytime " manner. In addition, LTE-Advanced continues to advance means to lower latency and round-trip delays, reduce intercell interference, and support coexistence between the various flavors of cells — macrocells, micocells, femtocells, and so on. Relays are being designed to provide greater coverage, while using in-band backhaul via the existing radio interface. In this article, operators representing a cross-section of the globe have come together to provide a perspective on expectations for LTE-Advanced from the operator point of view. Obviously, LTE-Advanced, as with all leading edge topics, has a multitude of aspects we would like to have covered; however, the following key topics are dealt with herein: • Carrier aggregation — Pingping Zong and Jin Yang, Verizon (United States) • Advanced DL MIMO techniques — Satoshi Nagata, NTT DOCOMO (Japan) • Advanced UL MIMO techniques — Aspects touched on but not limited to include: motivations for LTE-Advanced, primary use cases, scenarios, expectations, competitive pressures, device and infrastructure challenges, and deployment and operational costs. CARRIER AGGREGATION MOTIVATION Wireless customers are increasingly using mobile devices as their main tool to surf the Internet, play games, stay connected with friends and family , and watch real-time news, favorite TV programs , or the latest blockbuster movie. Offering high-speed data over wireless networks to meet and encourage such ever-increasing service demands is of significant interest to the wireless operators around the world. The wireless industry has evolved from using second-generation (2G) technologies to today's Third Generation Partnership Project (3GPP) LTE Release 8, with increasing spectrum efficiency more than 100 times. With the limitation of available contiguous spectrum being allocated and licensed to the wireless operators, carrier aggregation is needed to meet the International Telecommunication Union — Radiocommunication Sector's (ITU-R's) 1 Gb/s peak rate requirement for IMT-ABSTRACT LTE-Advanced extends the capabilities originally developed in LTE within the 3GPP. Carrier aggregationis the most significant, albeit complex, improvement provided by LTE-Advanced. Band-widths from various portions of the spectrum are logically concatenated resulting in a virtual block of a much larger band, enabling increased data throughput. Additionally, enhancements to MIMO antenna techniques in the uplink and downlink further increase the …
Spiritual Formation in an Australian Baptist Theological College: A Survey-based Case Study1

Abstract This article reports on preliminary research into spiritual formation at a Baptist theological college in Queensland, Australia. In response to a growing awareness of the need to quantify spiritual formation (as defined by Queensland Baptists) a 55 item inventory was developed and made available to all 250 college students with a response rate of nearly 50 per cent (122 students). The survey enabled the comparison of students in different demographic segments and at different stages in their theological education. The research suggests that in the areas where the College has been intentionally allocating resources and emphasis (as driven by its aspirational Graduate Attributes Statement) it has largely been effective in spiritual formation. However the research also suggests that development in some areas has resulted in retardation in other areas.
The nature of staphylococcal beta hemolysin. I. Mode of action.

The mode of action of highly punned beta hemolysin derived from the R-1 strain of Staphylococcus aureus has been investigated. Sphingomyelin was absent from lipid extracts of sheep erythrocytes treated with beta hemolysin when compared to normal cells. A correlation was also established between the sphingomyelin content of other erythrocyte species and their sensitivity to beta hemolysin. Further investigations revealed that sphingomyelin is hydrolyzed to yield phosphorylcholine and N-acyl sphingosine. Thus, the mode of action of the beta hemolysin is like that of phospholipase C. Various phosphate compounds other than sphingomyelin, including RNA, glycerophosphate, phenyl-phosphate, phosphatidylethanolamine, and phosphatidylcholine were tested as substrates, but virtually no hydrolysis was observed. In contrast with the results of other workers, R-1 beta hemolysin did not release detectable amounts of carbohydrate from staphylococcal cell walls.
Effectiveness of Thoracoscopic Talc Pleurodesis in the Management of Complicated Spontaneous Pneumothorax

Background:Complicated (recurring or persistent) spontaneous pneumothorax requires intervention either by surgical or nonsurgical pleurodesis or other interventions. As for high-risk patients, aggressive interventions may be associated with morbidity, the safety and effectiveness of less aggressive alternative interventions like thoracoscopic talc pleurodesis (TTP) should be evaluated. Methods:Data were extracted on patients who had undergone TTP for complicated spontaneous pneumothorax at Interventional Clinic, University Hospital, Brussels, Belgium. The complications, length of hospital stay, and success rate over a 24-month period were studied. Results:A total of 41 TTP procedures were performed for 25 (61%) cases of primary spontaneous pneumothorax and for 16 (39%) cases of secondary spontaneous pneumothorax. Twenty-four cases were first episodes, whereas it was a recurrence in 17. Of 4 patients with blebs/bullae, 2 had recurrence after TTP.No patient had acute respiratory distress syndrome or any other serious complication after TTP. Recurrence rates after TTP in primary and secondary spontaneous pneumothorax were 9.5% and 25% at 24 months, respectively. The mean length of hospital stay after TTP was 3±3.2 days. Conclusions:TTP is a safe and effective intervention in complicated spontaneous pneumothorax.
Learning Hierarchical Task Networks from Plan Traces

We present HTN-MAKER, an offline and incremental algorithm for learning the structural relations between tasks in a Hierarchical Task Network (HTN). HTN-MAKER receives as input a STRIPS domain model, a collection of STRIPS plans, and a collection of task definitions, and produces an HTN domain model. HTN-MAKER is capable of learning an HTN domain model that reflects the provided task definitions. In particular, if the tasks have different levels of abstraction, these will be reflected in the HTN. We have conducted an empirical evaluation of HTN-MAKER on the logisticstransportation domain. These experiments demonstrate that HTN-MAKER quickly learns an HTN domain model that may be used to solve nearly all problems in the domain. Challenges and future work are discussed.
The Interplay between E-Government Service Adoption Preferences and E-Government Service Delivery in Germany

Due to the rapid developments in information technologies, e-government has gained increasing attention lately, both by practitioners and researchers. However, research so far widely neglects the interplay of e-government service adoption preferences and government's delivery. Moreover, research on e-service delivery channels has just started. To address these gaps, we investigated two research questions using Germany as an example. (1) To what extent does the current level of e-services delivered match citizens' preferences? (2) To what extent do current e-service delivery channels match citizens' preferences? Following an exploratory research approach, we surveyed 956 citizens in six German cities. Furthermore we reviewed these cities' e-service deliveries. Our findings indicate no significant correlation between e-service adoption and delivery. Rather, we observed a large gap between citizens' level of digital preferences and cities' level of digitalization. In respect to delivery channels, cities' supply matches citizens' preferences for classic online channels but not for multi-channel.
Cloning of an Avian Adeno-Associated Virus (AAAV) and Generation of Recombinant AAAV Particles

ABSTRACT Recent studies have proposed that adeno-associated viruses (AAVs) are not evolutionarily linked to other mammalian autonomous parvoviruses but are more closely linked to the autonomous parvoviruses of birds. To better understand the relationship between primate and avian AAVs (AAAVs), we cloned and sequenced the genome of an AAAV (ATCC VR-865) and generated recombinant AAAV particles. The genome of AAAV is 4,694 nucleotides in length and has organization similar to that of other AAVs. The entire genome of AAAV displays 56 to 65% identity at the nucleotide level with the other known AAVs. The AAAV genome has inverted terminal repeats of 142 nucleotides, with the first 122 forming the characteristic T-shaped palindromic structure. The putative Rep-binding element consists of a tandem (GAGY)4 repeat, and the putative terminal resolution site (trs), CCGGT/CG, contains a single nucleotide substitution relative to the AAV2trs. The Rep open reading frame of AAAV displays 50 to 54% identity at the amino acid level with the other AAVs, with most of the diversity clustered at the carboxyl and amino termini. Comparison of the capsid proteins of AAAV and the primate dependoviruses indicate that divergent regions are localized to surface-exposed loops. Despite these sequence differences, we were able to produce recombinant AAAV particles carrying a lacZ reporter gene by cotransfection in 293T cells and were able to examine transduction efficiency in both chicken primary cells and several cell lines. Our findings indicate that AAAV is the most divergent AAV described to date but maintains all the characteristics unique to the genera of dependovirus.
Variance, Genetic Control, and Spatial Phenotypic Plasticity of Morphological and Phenological Traits in Prunus spinosa and Its Large Fruited Forms (P. x fruticans)

Prunus spinosa is a highly esteemed shrub in forest and landscape plantings. Shrubs with larger organs occur often and are considered either as large fruited forms of P. spinosa or as P. x fruticans, involving a hybridization process with the ancient cultivated P. insititia (crop-to-wild gene flow). As climate change may augment hybridization processes in the future, a hybrid origin is important to detect. In addition, studying crop-to-wild gene flow can give insights in putative consequences for the wild populations. We studied the P. spinosa–P. x fruticans group, focusing on morphology and phenology in three experimental plantations. Two plantings harbored cuttings of P. spinosa (clone plantations). A third plantation comprised of a half-sib offspring from a population with both P. spinosa and P. x fruticans (family plantation). Several results point to a hybridization process as the origin of P. x fruticans. The clone plantation revealed endocarp traits to be more genetically controlled than fruit size, while this was the opposite in the family plantation, suggesting the control of fruit size being derived from the putative P. insititia parent. Bud burst, flower opening, and leaf fall were genetically controlled in the clone plantation, whereas in the family plantation intrafamily variability was remarkably large for the bud burst and leaf fall, but not for the flower opening. This suggests there is a reduced genetic control for the first two phenophases, possibly caused by historic hybridization events. Pubescence on the long shoot leaves in the family plantation deviated from the short shoot leaves on the same plants and from long and short shoot leaves in the clone plantation, suggesting again a P. insititia origin. Finally, we quantified spatial phenotypic plasticity, indicating how P. spinosa may react in a changing environment. In contrast to the bud burst and leaf fall, flower opening did not demonstrate plasticity. The fruit size was diminished at the growth site with the shortest growing season while interestingly, the leaf width was enlarged. Leaf size traits appeared more plastic on the long shoots compared to the short shoots, although partitioning of variance did not display a lesser genetic control.
Adversity and Regulatory Processes in Preschool Children: Impact on Psychosocial Adjustment

The purpose of this investigation was to examine the development of self-regulation across preschool and early childhood, with an emphasis on identifying basic developmental processes, implications for adjustment, and contextual influences. Study 1 utilized a path analytic framework to assess longitudinal transactional relations between emotion and behavior regulation. Study 2 utilized a latent change analytic framework to assess the development of self-regulation and the influence of context. The use of these two complementary paradigms sought to clarify individual patterns of growth and stability, and to elucidate the mechanism behind potential cross domain effects.Data were drawn from a diverse sample of 250 children who completed annual observational assessments of regulation during laboratory tasks at ages four, five, and six. Additional measures included parent report of adversity exposure, teacher report of social competence, internalizing problems, and externalizing problems, and laboratory-measured academic achievement. Study 1 found modest stability of regulation across early childhood, and bidirectional prospective relations between emotion and behavior regulation. Better behavior regulation at age four predicted better emotion regulation at age six, while better emotion regulation at age five predicted better behavior regulation at age six. Each cross-domain longitudinal relation controlled for the stability of prior within-domain regulation and concurrent cross-domain relations. Behavior regulation evidenced direct relations with adjustment in multiple domains, with indirect effects of emotion regulation emerging through its effect on behavior regulation. Study 2 found that emotion and behavior regulation evidenced different patterns of growth. Emotion regulation improved from age four to five, and remained relatively constant from age five to six. Furthermore, higher levels of cumulative adversity predicted a decrease in the slope of emotion regulation trajectories, such that children who experienced more adversity improved less in emotion regulation over time. There was no significant effect of adversity on initial levels of regulation. Although behavior regulation appeared to increase in a linear fashion, a latent change model could not be fit successfully, which precluded assessing the effect of adversity on behavior regulation, or interrelations between regulatory trajectories. Implications are for the development of context-sensitive interventions and increased specification of key domains of self-regulation in investigations.
Orphan Receptor DAX-1 Is a Shuttling RNA Binding Protein Associated with Polyribosomes via mRNA

ABSTRACT The DAX-1 (NR0B1) gene encodes an unusual member of the nuclear hormone receptor superfamily which acts as a transcriptional repressor. Mutations in the human DAX-1 gene cause X-linked adrenal hypoplasia congenita (AHC) associated with hypogonadotropic hypogonadism (HHG). We have studied the intracellular localization of the DAX-1 protein in human adrenal cortex and mouse Leydig tumor cells and found it to be both nuclear and cytoplasmic. A significant proportion of DAX-1 is associated with polyribosomes and is found complexed with polyadenylated RNA. DAX-1 directly binds to RNA, two domains within the protein being responsible for cooperative binding activity and specificity. Mutations in DAX-1 found in AHC-HHG patients significantly impair RNA binding. These findings reveal that DAX-1 plays multiple regulatory roles at the transcriptional and posttranscriptional levels.
The Effect of New Links on Google Pagerank

PageRank is one of the principle criteria according to which Google ranks Web pages. PageRank can be interpreted as the frequency that a random surfer visits a Web page, and thus it reflects the popularity of a Web page. We study the effect of newly created links on Google PageRank. We discuss to what extent a page can control its PageRank. Using asymptotic analysis we provide simple conditions that show whether or not new links result in increased PageRank for a Web page and its neighbors. Furthermore, we show that there exists an optimal (although impractical) linking strategy. We conclude that a Web page benefits from links inside its Web community and on the other hand irrelevant links penalize the Web pages and their Web communities.
E-Cosmic: A Business Process Model Based Functional Size Estimation Approach

Software size is the key input for cost and effort estimation models. The effort and cost estimations as well as software size is needed at as early a phase of the project as possible. Conventional Early Functional Size Estimation methods enable predicting size at early phases but frequently variation of the results are high due to manual calculations and requirements of high degree of interpretation in situations where there is a lack of structured artifacts. On the other hand, automated Functional Size Measurement calculation approaches require constructs which are available in considerably late software development phases. In this study, an approach called e-Cosmic to overcome the reliability and subjectivity problems of early size estimation models is developed. As part of the approach a mapping between functional size measurement components of COSMIC FSM Method and common business process model constructs, was developed. The proposed method (e-Cosmic) is validated by three case studies. The result of the case studies has consistently showed less than 10% deviation with respect to the COSMIC FSM results. In addition, the automation of the estimation procedure eliminated measurer dependency and effort in conventional early functional size estimation methods.
Auxiliary Subunit GSG1L Acts to Suppress Calcium-Permeable AMPA Receptor Function

AMPA-type glutamate receptors are ligand-gated cation channels responsible for a majority of the fast excitatory synaptic transmission in the brain. Their behavior and calcium permeability depends critically on their subunit composition and the identity of associated auxiliary proteins. Calcium-permeable AMPA receptors (CP-AMPARs) contribute to various forms of synaptic plasticity, and their dysfunction underlies a number of serious neurological conditions. For CP-AMPARs, the prototypical transmembrane AMPAR regulatory protein stargazin, which acts as an auxiliary subunit, enhances receptor function by increasing single-channel conductance, slowing channel gating, increasing calcium permeability, and relieving the voltage-dependent block by endogenous intracellular polyamines. We find that, in contrast, GSG1L, a transmembrane auxiliary protein identified recently as being part of the AMPAR proteome, acts to reduce the weighted mean single-channel conductance and calcium permeability of recombinant CP-AMPARs, while increasing polyamine-dependent rectification. To examine the effects of GSG1L on native AMPARs, we manipulated its expression in cerebellar and hippocampal neurons. Transfection of GSG1L into mouse cultured cerebellar stellate cells that lack this protein increased the inward rectification of mEPSCs. Conversely, shRNA-mediated knockdown of endogenous GSG1L in rat cultured hippocampal pyramidal neurons led to an increase in mEPSC amplitude and in the underlying weighted mean single-channel conductance, revealing that GSG1L acts to suppress current flow through native CP-AMPARs. Thus, our data suggest that GSG1L extends the functional repertoire of AMPAR auxiliary subunits, which can act not only to enhance but also diminish current flow through their associated AMPARs. SIGNIFICANCE STATEMENT Calcium-permeable AMPA receptors (CP-AMPARs) are an important group of receptors for the neurotransmitter glutamate. These receptors contribute to various forms of synaptic plasticity, and alterations in their expression or regulation are also seen in a number of serious neurological conditions, including stroke, motor neuron disease, and cocaine addiction. Several groups of auxiliary transmembrane proteins have been described that enhance the function and cell-surface expression of AMPARs. We now report that the recently identified auxiliary protein GSG1L decreases weighted mean channel conductance and calcium permeability of CP-AMPARs while increasing polyamine-dependent rectification by diminishing outward current. Our experiments reveal that GSG1L is an auxiliary subunit that can markedly suppress CP-AMPAR function, in both recombinant systems and central neurons.
Protein abnormality in denervated skeletal muscles from patients with brachial injury

A proteomic analysis was performed to compare protein expression between normal sternocleidomastoid muscle and denervated muscle. Two‐dimensional electrophoresis (2‐DE) of muscle proteins showed that 26 proteins among about 800 spots in 2‐DE gel displayed a decrease and 6 proteins an increase in expression in muscles with denervation atrophy compared to normal controls; the identified proteins that were abnormally expressed could be generally grouped together as metabolic proteins, chaperone proteins, and contractile‐apparatus proteins. The significance of these altered proteins is discussed. In particular, the decrease in hD54 may reduce the activity of transmembrane signaling in atrophied muscle, while the disregulation of DnaJC 1 showed a possible role of molecular chaperones in the functional recovery of atrophied muscles. © 2005 Wiley‐Liss, Inc. Microsurgery 25:316–321, 2005.