Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineered serine protease inhibitor prevents furin-catalyzed activation of the fusion glycoprotein and production of infectious measles virus

We have identified the major cellular endoprotease that activates the fusion (F) glycoprotein of measles virus (MV) and have engineered a serine protease inhibitor (serpin) to target the endoprotease and inhibit the production of infectious MV. The F-protein precursor of MV was not cleaved efficiently into the mature F protein in human colon carcinoma cells lacking functional furin, indicating that furin is the major enzyme responsible for activation of the MV F protein. A human serpin alpha 1-antitrypsin variant was engineered to specifically inhibit furin. When expressed from a recombinant vaccinia virus in primate cells infected by MV, the engineered serpin (alpha 1-PDX) specifically inhibited furin-catalyzed cleavage of the F-protein precursor without affecting synthesis of other MV proteins. We generated human glioma cells stably expressing alpha 1-PDX. MV infection in these cells did not result in syncytia. The infected cells produced all the MV proteins, but the F-protein precursor remained largely uncleaved. This did not prevent virus assembly. However, the released virions contained inactive F-protein precursor rather than mature F protein, and infectious-virus titers were reduced by 3 to 4 orders of magnitude. These results show that a mature F protein is not required for the assembly of MV but is crucial for virus infectivity. The engineered serpin may offer a novel molecular antiviral approach against MV.
Learning in real-time in repeated games using experts

Despite much progress, state-of-the-art learning algorithms for repeated games still often require thousands of moves to learn eectively { even in simple games. Our goal is to nd algorithms that learn to play eective strategies in tens of moves in many games when paired against various associates. Toward this end, we describe a new meta-algorithm designed to increase the learning speed and prociency of expert algorithms. We show that this meta-algorithm enhances four expert algorithms so that they quickly learn effective strategies in two-player repeated games.
Abnormal neutrophil phenotype and neutrophil FcRIII deficiency corrected by bone marrow transplantation

BACKGROUND: Neutrophils from a patient in first remission of acute myeloid leukemia were found to lack NA1 and NA2 alloantigens. This NA null phenotype was converted to the normal phenotype of NA1, NB2 by the transplantation of bone marrow from an HLA‐identical sibling. To investigate the inherited or acquired nature of this rare phenotype, a combination of conventional neutrophil serology and recently developed restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) assays was used.
Assessment of the need for triglyceride blank measurements.

Two methods of triglyceride blank measurement were critically investigated. For 38 samples a mean blank value of 7.2 mg/dl was obtained when the blanks were measured by replacing the saponifying reagent with 80% isopropanol. For the same samples, consistently higher blank values were obtained (mean = 18.3 mg/dl) when these were determined by the Kessler-Lederer method. It is suggested that, when true blank values are desired, the former method is to be preferred. Based on theoretical considerations, however, as well as on our experimental data on the effect of in vitro hydrolysis on triglyceride blank measurements, we recommend that in routine triglyceride measurements, blank determinations are not needed.
Vestibular Function Change in a Vasopressin-Induced Hydrops Model.

HYPOTHESIS A vasopressin-induced endoymphatic hydrops model can represent an acute vertiginous attack in Menière's disease (MD). BACKGROUND Previous animal models are not appropriate to evaluate the efficacy of new treatments for hydrops because they cannot represent an acute attack of MD. Recently, a new dynamic model was introduced for acute hydrops exacerbation using the vasopressin type 2 receptor agonist, desmopressin (1-deamino-8-D-Arginine vasopressin, VP); however, resulting changes in vestibular function have not been investigated. METHODS A total of 37 guinea pigs were used. Two to 4 weeks after surgical ablation of endolymphatic sacs in 33 guinea pigs, acute exacerbation of hydrops was induced by a single VP injection in 18 animals (group A). Next, two VP injections at 1 hour interval were administered to investigate the effect of multiple VP doses on vestibular function in the other 15 animals (group B). In the remaining four animals, VP was injected without surgery for the control group (control). Bidirectional sinusoidal harmonic acceleration (SHA) tests of vestibular function were performed. "Type I response" was defined as when the maximum slow-phase velocity (SPV) during left rotation (toward the operated ear) was lower than that during right rotation (toward the normal ear). In contrast, "Type II response" was defined as when maximum SPV at the left rotation was higher than that at the right rotation. Vestibular symmetry scores were analyzed at baseline and after each of two VP injections given 1 hour apart. RESULTS Vestibular symmetry scores increased at 1 hour after VP injection in all 18 animals in group A (p < 0.001). Two hours after VP injection, symmetry score decreased to the initial score. Two different types of vestibular response were observed after VP. However, the symmetry scores between type I and II responses were not significantly different (p = 0.173). In all 15 animals of Group B, vestibular asymmetry was sustained over 3 hours when two VP injections were given 1 hour apart. In three of Group B, the type of vestibular response changed from type II response to type I response after the 2nd VP injection; however, no animal demonstrated a shift from type I to type II response. CONCLUSION VP can transiently induce an acute exacerbation of hydrops and asymmetric vestibular dysfunction in guinea pigs. This model could help in studying new treatments for acute hydrops and in explaining the mechanism of bidirectional nystagmus in MD.
Defragmentation of flexible dense wavelength division multiplexing (FDWDM) networks using wavelength tunability criterion

Flexible spectrum ROADMs facilitate networks to support channels operating at heterogeneous line rates by allocating spectral resources in a dynamic and flexible manner leading to better Spectral Efficiency. In a realistic network, traffic scenario is very dynamic in nature leading to continuous tear down of existing demands and set up of new demands. This dynamic tear down and set up process leads to fragmentation of the network, in terms of spectral resources, called “Spectral fragmentation” resulting in the blocking of new demands. Therefore, an optimization mechanism handling spectrum fragmentation, called “Spectrum Defragmentation”, is of vital importance in flexgrid optical networks. Defragmentation of the spectral resources can be obtained by either changing wavelength of the demand or route of the demand or both. This paper discusses a novel defragmentation algorithm considering only the wavelength tunability criterion and performs defragmentation by moving as minimal existing traffic demands as possible in order to support the new demand.
Variability and predictability in sleep patterns of chronic insomniacs

Sleep of chronic insomniacs is often characterized by extensive night‐to‐night variability. To date, no study has examined this variability with long series of daily sleep data. The present study examined night‐to‐night variability with a sample of 106 participants meeting DSM‐IV diagnostic criteria for persistent primary insomnia. Participants completed daily sleep diaries for an average of 31 days (range: 18–56). Sleep efficiency, sleep onset latency and wake after sleep onset were derived from this measure. Despite evidence of extensive night variability, results showed that sleep patterns could be classified in three clusters. The first one was characterized by a high probability of having poor sleep, the second one by a low and decreasing probability, and the third one by a constant median probability of having a poor sleep, which is an unpredictable sleep pattern. In the first cluster, poor sleep was expected each night for patients with a predominance mixed insomnia including the three insomnia subtypes. In the second cluster, patients presented moderate insomnia, sleep‐onset latency below the threshold level and a predominance of sleep‐maintenance insomnia. In the third pattern, poor nights seemed unpredictable for patients with moderate to severe insomnia associated with the lowest proportion of sleep‐maintenance insomnia. Overall, sleep was predictable for about two‐thirds of individuals, whereas it was unpredictable for about one‐third. These findings confirm the presence of extensive variability in the sleep of chronic insomniacs and that poor sleep may be predictable for some of them. Additional research is needed to characterize those sleep patterns in terms of clinical features and temporal course.
Batch vs. Sequential Displays: Effects on Human Problem Solving1

This study was concerned with problem solving under two display conditions. In one condition (“Sequential”), only those response alternatives permissable at any given time were displayed at that time. Under the other condition (“Batch”), all response alternatives, permissable at the moment or not, were presented at all times. Significantly greater time was found to be required to learn solutions using the “Batch” display. This requirement was attributed to the significantly greater display search-time which was found to be required in that condition. No significant difference in number of trials to reach the criterion of learning solutions was found, indicating that the additional material displayed in the “Batch” condition carries no significant amount of useful information. It is concluded that displaying data which has only potential relevance is not only ineffective but actually degrades performance.
Comparison of the cost and cost‐effectiveness of insecticide‐treated bednets and residual house‐spraying in KwaZulu‐Natal, South Africa

Residual house‐spraying (RHS) has been the mainstay of South African malaria prevention for more than 50 years, but it has been argued that insecticide‐treated bednets (ITBN) could be a more effective and appropriate method of control. To provide a rational basis for choosing between the interventions, a trial was conducted during 1998 and 1999 in northern KwaZulu‐Natal to collect comparable data on the effectiveness, acceptability and cost of the two interventions. The current practice of house‐spraying once a year was compared with ITBN, distributed free to households and retreated annually at several specific centres. The base case results show ITBN to be significantly more effective in preventing malaria cases than RHS (overall adjusted rate ratio of 0.69), and also more costly, with an incremental economic cost per person of ITBN compared with RHS of R8.68 (US$1.42) per year, giving a gross incremental cost per case averted of R111 ($18) (1999 prices). Estimating the number of deaths averted, based on the average case fatality rate, gave a gross incremental cost per death averted of R11 718 ($1915). The additional cases averted were estimated to lead to drug cost savings of around R1 ($0.16) per capita per year, giving a net cost per case averted of R98 ($16), and net cost per death averted of R10 377 ($1696). Although the finding that the economic costs of ITBN were higher than those for RHS was relatively robust to parameter variations, the extent of the cost margin was sensitive to changes in the price and useful life of the net, and the price of the insecticide. Moreover, a switch to ITBN could lead to net financial savings if the price per net fell below $3.57 (R21.85), or if a change in policy allowed a significant reduction in the number of permanent full‐time malaria control staff. In view of the greater effectiveness of ITBN, policy makers may view ITBN as a cost‐effective use of resources, even if the economic costs are higher. If ITBN are implemented, close monitoring will be required of use, retreatment and useful life of nets, and resistance to insecticides, to assess any change over time in relative cost‐effectiveness, and any threat to the role of the programme as a barrier to the spread of malaria transmission to other areas.
POSH acts as a scaffold for a multiprotein complex that mediates JNK activation in apoptosis

We report that the multidomain protein POSH (plenty of SH3s) acts as a scaffold for the JNK pathway of neuronal death. This pathway consists of a sequential cascade involving activated Rac1/Cdc42, mixed‐lineage kinases (MLKs), MAP kinase kinases (MKKs) 4 and 7, c‐Jun N‐terminal kinases (JNKs) and c‐Jun, and is required for neuronal death induced by various means including nerve growth factor (NGF) deprivation. In addition to binding GTP‐Rac1 as described previously, we find that POSH binds MLKs both in vivo and in vitro, and complexes with MKKs 4 and 7 and with JNKs. POSH overexpression promotes apoptotic neuronal death and this is suppressed by dominant‐negative forms of MLKs, MKK4/7 and c‐Jun, and by an MLK inhibitor. Moreover, a POSH antisense oligonucleotide and a POSH small interfering RNA (siRNA) suppress c‐Jun phosphorylation and neuronal apoptosis induced by NGF withdrawal. Thus, POSH appears to function as a scaffold in a multiprotein complex that links activated Rac1 and downstream elements of the JNK apoptotic cascade.
Prevention of breast cancer growth, invasion, and metastasis by antiestrogen tamoxifen alone or in combination with urokinase inhibitor B-428.

Urokinase (urokinase plasminogen activator, uPA) and its cell surface receptor (uPA receptor, uPAR) play an important role in a variety of physiological and pathological processes requiring cell migration and tissue remodeling. Using our syngeneic model of uPAR overexpression by the rat breast cancer cell line Mat B-III, we have examined the ability of the nonsteroidal antiestrogen, tamoxifen (TAM), and of a selective synthetic inhibitor of uPA, 4-iodo benzo[b]thiophene-2-carboxamidine (B-428), to inhibit expression of uPA and uPAR as well as cell growth, invasion, and metastasis of wild-type Mat B-III cells and of cells overexpressing uPAR (Mat B-III-uPAR). Both TAM and B-428 inhibited uPAR gene transcription, mRNA expression, protein production and also decreased the proliferative and invasive capacity of Mat B-III and Mat B-III-uPAR. The effects of TAM and B-428 were more pronounced when these agents were tested in combination. Both control and experimental cells (1 x 10(6) cells) were inoculated orthotopically into the mammary fat pad of syngeneic female Fisher rats, and animals were infused i.p. with either TAM and B-428 alone or in combination for 2 weeks. Control animals receiving vehicle alone developed large tumors and macroscopic metastases to lungs, liver, and lymph nodes. In contrast to this, experimental animals receiving TAM and B-428 showed a significant decrease in primary tumor volume and metastases. Combination therapy had especially marked effects in blocking progression of the primary tumor in experimental animals inoculated with highly aggressive Mat B-III-uPAR cells. These results underscore the utility of anti-proteolytic agents (B-428) in addition to standard hormone therapy (TAM) in advanced breast cancer patients where the uPA/uPAR system plays a key role in tumor progression.
Analysis of Mental Health Substance Abuse–Related Emergency Department Visits from 2002 to 2008

Background Mental health substance abuse (MHSA)-related visits in the emergency department (ED) are a growing concern. Methods This study analyzed MHSA ED visits by age, gender, ethnicity, region, season, and duration of stay between 2002 and 2008 using the National Hospital Ambulatory Care Survey (NHAMCS). The authors used descriptive statistics and examined ED length of stay using a generalized linear model with a log link, and compared length of stay for these visits. Results Mental health–related visits increased from 6.4% of visits in 2002 to 7.0% in 2008 (P = .002). Substance abuse–related visits increased from 1.8% to 2.1% (P = .004). Substance abuse-related visits accounted for a 49% increase (CI = 0.051–0.23%) in the total mental health visits to the ED. Male visits increased whereas female visits remained unchanged, with non-Latino white males showing the highest increase. The southern United States had the highest increase in MHSA visits. MHSA visits (5.6 hours) were on average 1.2 hours longer than other non–MHSA-related visits (4.4 hours). MHSA-related visits had a higher percentage of all visits on weekends (2.3%) than on weekdays (2.0%; P < .00005). Conclusions Concentrated programmatic efforts to decrease the burden of MHSA visits to the ED may reduce the burden of disease.
Planar Superconducting Resonators with Internal Quality Factors above One Million

We describe the fabrication and measurement of microwave coplanar waveguide resonators with internal quality factors above 10 million at high microwave powers and over 1 million at low powers, with the best low power results approaching 2 million, corresponding to ~1 photon in the resonator. These quality factors are achieved by controllably producing very smooth and clean interfaces between the resonators' aluminum metallization and the underlying single crystal sapphire substrate. Additionally, we describe a method for analyzing the resonator microwave response, with which we can directly determine the internal quality factor and frequency of a resonator embedded in an imperfect measurement circuit.
The Matilda Effect in Science Communication

An experiment with 243 young communication scholars tested hypotheses derived from role congruity theory regarding impacts of author gender and gender typing of research topics on perceived quality of scientific publications and collaboration interest. Participants rated conference abstracts ostensibly authored by females or males, with author associations rotated. The abstracts fell into research areas perceived as gender-typed or gender-neutral to ascertain impacts from gender typing of topics. Publications from male authors were associated with greater scientific quality, in particular if the topic was male-typed. Collaboration interest was highest for male authors working on male-typed topics. Respondent sex did not influence these patterns.
Un modelo de equilibrio general regional para Antioquia

Este trabajo consiste en desarrollar un modelo de equilibrio general teorico para la economia regional de Antioquia. La idea basica es que hay un proceso productivo que demanda insumos intermedios y factores que agregan valor, cuyos precios estan determinados por la interaccion entre la demanda y la cantidad disponible de ellos. En terminos contables, la produccion es la suma de una serie de actividades primarias (produccion primaria) y una produccion secundaria de otras actividades o ramas. Ademas, se considera que existen margenes de comercio y transporte e impuestos al valor agregado, que aumentan el precio final (de adquisicion) de las mercancias, ademas de importaciones del resto del pais y del mundo que aumentan la oferta total por mercancia. El marco basico de analisis es la competencia perfecta, donde los mercados se aclaran a los precios de equilibrio, existe informacion perfecta y los agentes son tomadores de precios. A pesar de las criticas que ha tenido el modelo de equilibrio general computable, puede resultar en una herramienta util para la comprension de las relaciones intersectoriales y los efectos de cambios en los precios relativos sobre el funcionamiento de la economia, en este caso, regional.
Stability of Robot Manipulators Under Saturated PID Compensation

The joint position regulation problem for robot manipulators under a standard saturated proportional-integral differential (PID) compensator is studied in this brief. The main result states the existence of PID control gains yielding semiglobal asymptotic stability if the control torque bounds are larger than gravitational torques. Energy shaping plus damping injection methods, as well as singular perturbation analysis, are used to establish stability conditions to achieve regulation at any desired position. Some experiments are carried out to illustrate the stability results.
A Theory of Expert Leadership

How much knowledge should leaders have of their organization's core business? This is an important question but not one that has been addressed in the management literature. In a new 'theory of expert leadership' (TEL), this paper blends conceptual work with recent empirical evidence. It suggests that organizations perform more effectively when led by individuals who have a deep understanding of the core business of their organization. Being a capable general manager is not sufficient. Expert leaders are those with (1) inherent knowledge, acquired through technical expertise combined with high ability in the core-business activity; (2) industry experience, which stems from time and practice within the core-business industry; and (3) leadership capabilities, which include management skills and a leader's innate characteristics. This paper criticizes the rise of the professional manager and generalist CEO. It argues that expert leaders improve organizational performance through knowledge-based strategy, by acting as a standard bearer, by creating the right environment for core workers, and, finally, by adopting the long view. The paper concludes by identifying the potential boundaries of TEL.
Calcium-dependent protein kinase/NADPH oxidase activation circuit is required for rapid defense signal propagation

In animals and plants, pathogen recognition triggers the local activation of intracellular signaling that is prerequisite for mounting systemic defenses in the whole organism. We identified that Arabidopsis thaliana isoform CPK5 of the plant calcium-dependent protein kinase family becomes rapidly biochemically activated in response to pathogen-associated molecular pattern (PAMP) stimulation. CPK5 signaling resulted in enhanced salicylic acid–mediated resistance to the bacterial pathogen Pst DC3000, differential plant defense gene expression, and synthesis of reactive oxygen species (ROS). Using selected reaction monitoring MS, we identified the plant NADPH oxidase, respiratory burst oxidase homolog D (RBOHD), as an in vivo phosphorylation target of CPK5. Remarkably, CPK5-dependent in vivo phosphorylation of RBOHD occurs on both PAMP- and ROS stimulation. Furthermore, rapid CPK5-dependent biochemical and transcriptional activation of defense reactions at distal sites is compromised in cpk5 and rbohd mutants. Our data not only identify CPK5 as a key regulator of innate immune responses in plants but also support a model of ROS-mediated cell-to-cell communication, where a self-propagating mutual activation circuit consisting of the protein kinase, CPK5, and the NADPH oxidase RBOHD facilitates rapid signal propagation as a prerequisite for defense response activation at distal sites within the plant.