Miracle-dz/UniFAR-FTUs huggingface dataset:
miRNA engineering of CHO cells facilitates production of difficult‐to‐express proteins and increases success in cell line development

In recent years, coherent with growing biologics portfolios also the number of complex and thus difficult‐to‐express (DTE) therapeutic proteins has increased considerably. DTE proteins challenge bioprocess development and can include various therapeutic protein formats such as monoclonal antibodies (mAbs), multi‐specific affinity scaffolds (e.g., bispecific antibodies), cytokines, or fusion proteins. Hence, the availability of robust and versatile Chinese hamster ovary (CHO) host cell factories is fundamental for high‐yielding bioprocesses. MicroRNAs (miRNAs) have emerged as potent cell engineering tools to improve process performance of CHO manufacturing cell lines. However, there has not been any report demonstrating the impact of beneficial miRNAs on industrial cell line development (CLD) yet. To address this question, we established novel CHO host cells constitutively expressing a pro‐productive miRNA: miR‐557. Novel host cells were tested in two independent CLD campaigns using two different mAb candidates including a normal as well as a DTE antibody. Presence of miR‐557 significantly enhanced each process step during CLD in a product independent manner. Stable expression of miR‐557 increased the probability to identify high‐producing cell clones. Furthermore, production cell lines derived from miR‐557 expressing host cells exhibited significantly increased final product yields in fed‐batch cultivation processes without compromising product quality. Strikingly, cells co‐expressing miR‐557 and a DTE antibody achieved a twofold increase in product titer compared to clones co‐expressing a negative control miRNA. Thus, host cell engineering using miRNAs represents a promising tool to overcome limitations in industrial CLD especially with regard to DTE proteins. Biotechnol. Bioeng. 2017;114: 1495–1510. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
Initiation of human myoblast differentiation via dephosphorylation of Kir2.1 K+ channels at tyrosine 242

Myoblast differentiation is essential to skeletal muscle formation and repair. The earliest detectable event leading to human myoblast differentiation is an upregulation of Kir2.1 channel activity, which causes a negative shift (hyperpolarization) of the resting potential of myoblasts. After exploring various mechanisms, we found that this upregulation of Kir2.1 was due to dephosphorylation of the channel itself. Application of genistein, a tyrosine kinase inhibitor, increased Kir2.1 activity and triggered the differentiation process, whereas application of bpV(Phen), a tyrosine phosphatase inhibitor, had the opposite effects. We could show that increased Kir2.1 activity requires dephosphorylation of tyrosine 242; replacing this tyrosine in Kir2.1 by a phenylalanine abolished inhibition by bpV(Phen). Finally, we found that the level of tyrosine phosphorylation in endogenous Kir2.1 channels is considerably reduced during differentiation when compared with proliferation. We propose that Kir2.1 channels are already present at the membrane of proliferating, undifferentiated human myoblasts but in a silent state, and that Kir2.1 tyrosine 242 dephosphorylation triggers differentiation.
A Third Phytoene Synthase Is Devoted to Abiotic Stress-Induced Abscisic Acid Formation in Rice and Defines Functional Diversification of Phytoene Synthase Genes1[W]

We here report on the characterization of a novel third phytoene synthase gene (PSY) in rice (Oryza sativa), OsPSY3, and on the differences among all three PSY genes with respect to the tissue-specific expression and regulation upon various environmental stimuli. The two already known PSYs are under phytochrome control and involved in carotenoid biosynthesis in photosynthetically active tissues and exhibit different expression patterns during chloroplast development. In contrast, OsPSY3 transcript levels are not affected by light and show almost no tissue-specific differences. Rather, OsPSY3 transcripts are up-regulated during increased abscisic acid (ABA) formation upon salt treatment and drought, especially in roots. The simultaneous induction of genes encoding 9-cis-epoxycarotenoid dioxygenases (NCEDs), involved in the initial steps of ABA biosynthesis, indicate that decreased xanthophyll levels are compensated by the induction of the third PSY gene. Furthermore, OsPSY3 and the OsNCEDs investigated were also induced by the application of ABA, indicating positive feedback regulation. The regulatory differences are mirrored by cis-acting elements in the corresponding promoter regions, with light-responsive elements for OsPSY1 and OsPSY2 and an ABA-response element as well as a coupling element for OsPSY3. The investigation of the gene structures and 5′ untranslated regions revealed that OsPSY1 represents a descendant of an ancient PSY gene present in the common ancestor of monocots and dicots. Since the genomic structures of OsPSY2 and OsPSY3 are comparable, we conclude that they originated from the most recent common ancestor, OsPSY1.
Repeated Sprint Ability in Young Soccer Players at Different Game Stages

Abstract Meckel, Y, Einy, A, Gottlieb, R, and Eliakim, A. Repeated sprint ability in young soccer players at different game stages. J Strength Cond Res 28(9): 2578–2584, 2014—The purpose of this study was to determine the repeated sprint ability (RSA) of young (16.9 ± 0.5 years) soccer players at different game stages. Players performed repeated sprint test (RST) (12 × 20 m) after warm-up before a game, at half-time, and after a full soccer game, each on a different day, in a random order. The ideal (fastest) sprint time (IS) and total (accumulative) sprint time (TS) were significantly slower at the end of the game compared with those after the warm-up before the game (p < 0.01 for each). Differences between IS and TS after the warm-up before the game and at half-time, and between half-time and end of the game, were not statistically significant. There was no significant difference in the performance decrement during the RST after warm-up before the game, at half-time, or the end of the game. Significant negative correlation was found between predicted V[Combining Dot Above]O2 and the difference between TS after the warm-up before the game and the end of the game (r = −0.52), but not between predicted V[Combining Dot Above]O2 and the difference in any of the RST performance indices between warm-up before the game and half-time, or between half-time and the end of the game. The findings indicate a significant RSA reduction only at the end but not at the half-time of a soccer game. The results also suggest that the contribution of the aerobic system to soccer intensity maintenance is crucial, mainly during the final stages of the game.
Dynamic RCS Estimation of Chaff Clouds

We analytically investigated electromagnetic wave propagation through chaff clouds. The chaff fibers are assumed to be long and thin cylinders. The trajectory tracking algorithm was developed based on a combination of the six degree-of-freedom (6 DOF) equations of motion and the aerodynamic forces and moment acting on the chaff fibers. For the low Reynolds number flows around the chaff fibers, the normal force was obtained from a curve-fit formula offered by Sucker and Brauer, while an analytic solution offered by Curle is used to obtain the tangential force. The position and orientation of the chaff fibers as a function of time are thereupon obtained. As inputs of a generalized equivalent conductivity (GEC) method, this information is used to calculate the radar cross section (RCS) of the chaff cloud. The GEC method can estimate the RCS of a chaff cloud with an arbitrary orientation distribution for reducing computation time. The proposed chaff cloud model (CCM) can be applied to predict accurately the steady state response as well as the transient response before the RCS of the chaff cloud reaches the steady state.
Identification and characterization of cis‐ and trans‐acting elements involved in prophage induction in Streptococcus thermophilus J34

The genetic switch region of temperate Streptococcus thermophilus phage TP‐J34 contains two divergently oriented promoters and several predicted operator sites. It separates lytic cycle‐promoting genes from those promoting lysogeny. A polycistronic transcript comprises the genes coding for repressor Crh, metalloproteinase‐motif protein Rir and superinfection exclusion lipoprotein Ltp. Weak promoters effecting monocistronic transcripts were localized for ltp and int (encoding integrase) by Northern blot and 5′‐RACE‐PCR. These transcripts appeared in lysogenic as well as lytic state. A polycistronic transcript comprising genes coh (encoding Cro homolog), ant (encoding putative antirepressor), orf7, orf8 and orf9 was only detected in the lytic state. Four operator sites, of which three were located in the intergenic regions between crh and coh, and one between coh and ant, were identified by competition electromobility shift assays. Cooperative binding of Crh to two operator sites immediately upstream of coh could be demonstrated. Coh was shown to bind to the operator closest to crh only. Oligomerization was proven by cross‐linking Crh by glutaraldehyde. Knock‐out of rir revealed a key role in prophage induction. Rir and Crh were shown to form a complex in solution and Rir prevented binding of Crh to its operator sites.
A two-beam slotted leaky waveguide array for mobile reception of dual polarization DBS

Mobile reception of direct broadcast satellites (DBS) has been very popular and the number of vehicles with DBS receiving systems is also rapidly increasing in Japan. Low-profile, mass-produceable, beam-tilting and high-efficiency receiving antennas had been desired to this end. We developed a single-layer slotted leaky waveguide array antenna for the single-polarized DBS in Japan which satisfies all these requirements. A novel single layer feed structure is applied to the antenna, which consists of cascades of /spl pi/-junctions and radiating waveguides as shown. The cross slots are densely arranged on the broad wall of the radiating waveguides. The leaky wave radiates a circular polarized beam in a large tilting angle of about 45 degrees from the zenith. It is advantageous for mobile DBS reception since the antenna can be installed horizontally on the roof of vehicles. A mechanical system steers the antenna to track the satellite only in the azimuthal plane. Tracking is not necessary in the elevation plane, since the beam width of the antenna with a short radiating waveguide is broad.
Nursing management of fever in children: a systematic review.

OBJECTIVES The aim of the present review was to determine whether the best available evidence supports the types and timing of the various nursing interventions that are commonly used to reduce fever in non-critically-ill children, and to what extent the outcomes are influenced by these nursing actions. METHODS Studies included were randomised or quasi-randomised controlled trials that involved non-critically-ill children with a fever aged between 3 months and 16 years. The search strategy sought to identify both published and unpublished research reports in the English language and covered all major databases up to 1998. The methodological quality of each study was assessed by two independent reviewers using a piloted critical appraisal checklist. Despite all studies being randomised, heterogeneity precluded conduction of a meta-analysis; therefore, evidence was synthesised using narrative summaries. RESULTS Ten studies were assessed as being of sufficient quality to be included in the review. These studies addressed two of the intervention categories identified in the protocol: (i) administration of antipyretics (paracetamol); and (ii) direct cooling measures on the outcome measure (reduction of or prevention of increase in fever). The review found little benefit from sponging in temperate climates and usually at the expense of the child's comfort. There may be situations in high environmental temperatures and high humidity, or where there is a need for immediate temperature reduction, in which sponging may be warranted. Risks were identified when paracetamol was administered on a sustained basis over even a short period of time and above a relatively low total daily dosage. There was a lack of evidence to support the administration of antipyretics to reduce the incidence of febrile convulsions. There is a need for parental education that focuses on knowledge of the body's protective physiological responses and how to support these responses. CONCLUSION The primary purpose for intervening when a child has a fever is to increase the child's comfort. This consideration should be weighed against any harm that might result from intervening. There was a lack of evidence to support the routine use of sponging. The administration of paracetamol should be used selectively and with caution. In summary, care needs to be individualised, based on current knowledge of the effectiveness and risks of interventions.
A two-stage cluster-based resource management scheme in ultra-dense networks

As the demand for mobile data services skyrockets and the scarcity of spectrum increasing, femtocell networks overlaying with macrocell networks becomes a promising solution. However, the dense and random deployment of femto-cells and their uncoordinated operations cause severe inter-cell interference. This paper studies cluster-based wireless resource management issues in ultra-dense networks (UDN). Firstly, a modified K-means algorithm is performed in the clustering process. A reasonable number of clusters is derived instead of the predefined value as the input parameter. The wireless resource management is investigated to maximize the sum-throughput in UDN. Specifically, this paper propose a two-stage resource management scheme to solve this problem. In the first stage, primary resource allocation is performed by using a greedy search algorithm in each cluster. In the second stage, a supplementary allocation algorithm (SAA) is presented to assign the remainder subchannels. Finally, numerical results show that the proposed scheme achieves a satisfying performance in terms of average SINR, the system throughput, and the spatial spectrum efficiency, which provides guidelines for the practical dense deployment of femtocells.
Welfare reform and the perinatal health and health care use of Latino women in California, New York City, and Texas.

OBJECTIVES This study analyzed changes in the financing of prenatal care and delivery, the use of prenatal care, and birth outcomes among foreign-born vs US-born Latino women following enactment of the Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA) in August 1996. METHODS We used a pre-post design with a comparison group. The sample consisted of resident Latinas in California, New York City, and Texas who delivered a live infant in 1995 or 1998. RESULTS The proportion of births to Latinas that initiated prenatal care in the first 4 months of pregnancy increased for all foreign-born Latinas in California, New York City, and Texas between 1995 and 1998 (P <.05). Except for non-Dominicans in New York City, there was no increase in the proportion of low- or very-low-birthweight births among foreign-born vs US-born Latinas in the 3 localities between 1995 and 1996. CONCLUSIONS There is little evidence from vital statistics in California, New York City, and Texas that PRWORA had any substantive impact on the perinatal health and health care utilization of foreign-born relative to US-born Latinas.
Standardizing assessment and reporting of adverse effects in rheumatology clinical trials II: the Rheumatology Common Toxicity Criteria v.2.0.

OBJECTIVE The OMERACT Drug Safety Working Group focuses on standardization of assessment and reporting of adverse events in clinical trials and longitudinal and observational studies in rheumatology. This group developed the Rheumatology Common Toxicity Criteria (RCTC) in 1999, building on the Oncology Common Toxicity Criteria. At OMERACT 8, a workshop group reviewed the use of the RCTC and other instruments in rheumatology clinical trials to date, to revise and to stimulate its implementation. METHODS The Working Group drafted a revision of the RCTC after an iterative examination of its contents, terms, and definitions. The RCTC were compared with the Oncology Common Toxicity Criteria (CTC v.2.0), and the Common Terminology Criteria for Adverse Events (CTCAE v.3.0). In addition a pharmaceutical company focus group met to clarify the challenges of application of RCTC terms and definitions, relative to the standard in pharmaceutical clinical trials, i.e., verbatim recording of adverse events followed by mapping to Medical Dictionary of Drug Regulatory Activities (MedDRA) terms. The workshop focused on the proposed revision of RCTC to version 2.0 and on the research agenda, including a validation of the RCTC in future trials. RESULTS At OMERACT 8, breakout groups amended the contents of the 4 current and 2 new categories of adverse event terms within the draft RCTC v.2.0. Participants recognized the need to standardize the definitions for disease flares, infection, malignancy, and certain syndromes such as drug hypersensitivity and infusion reactions. Moderate consensus (62%) was reached in the final plenary session that the amended RCTC v.2.0 should be promulgated and tested in available trials of anti-tumor necrosis factor agents. CONCLUSION The RCTC has face validity and construct validity. However, documentation of discrimination and feasibility (the other elements of the OMERACT filter) is needed. Collaboration with drug safety working groups in rheumatology professional organizations is necessary to enable this project.
Chronic pancreatitis.

INTRODUCTION Chronic pancreatitis affects 3-9 people in 100,000; 70% of cases are alcohol-induced. METHODS AND OUTCOMES We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of lifestyle interventions in people with chronic pancreatitis? What are the effects of dietary supplements in people with chronic pancreatitis? What are the effects of drug interventions in people with chronic pancreatitis? What are the effects of nerve blocks for pain relief in people with chronic pancreatitis? What are the effects of different invasive treatments for specific complications of chronic pancreatitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS In this systematic review we present information relating to the effectiveness and safety of the following interventions: avoiding alcohol consumption, biliary decompression, calcium supplements, ductal decompression (endoscopic or surgical), low-fat diet, nerve blocks, opioid analgesics, pancreatic enzyme supplements, pseudocyst decompression (endoscopic or surgical), resection using distal pancreatectomy, resection using pancreaticoduodenectomy (Kausch-Whipple or pylorus-preserving), and vitamin/antioxidant supplements.
ADAPTATION TO A STEEP ENVIRONMENTAL GRADIENT AND AN ASSOCIATED BARRIER TO GENE EXCHANGE IN LITTORINA SAXATILIS

Abstract Steep environmental gradients offer important opportunities to study the interaction between natural selection and gene flow. Allele frequency clines are expected to form at loci under selection, but unlinked neutral alleles may pass easily across these clines unless a generalized barrier evolves. Here we consider the distribution of forms of the intertidal gastropod Littorina saxatilis, analyzing shell shape and amplified fragment length polymorphism (AFLP) loci on two rocky shores in Britain. On the basis of previous work, the AFLP loci were divided into differentiated and undifferentiated groups. On both shores, we have shown a sharp cline in allele frequencies between the two morphs for differentiated AFLP loci. This is coincident with a habitat transition on the shore where the two habitats (cliff and boulder field) are immediately contiguous. The allele frequency clines coincide with a cline in shell morphology. In the middle of the cline, linkage disequilibrium for the differentiated loci rises in accordance with expectation. The clines are extremely narrow relative to dispersal, probably as a result of both strong selection and habitat choice. An increase in FST for undifferentiated AFLPs between morphs, relative to within-morph comparisons, is consistent with there being a general barrier to gene flow across the contact zone. These features are consistent either with an episode of allopatric divergence followed by secondary contact or with primary, nonallopatric divergence. Further data will be needed to distinguish between these alternatives.
High Current Drive in Ultra-Short Impact Ionization MOS (I-MOS) Devices

This papers presents new results on silicon I-MOS devices, (where the source and the drain are doped of opposite type) obtained by an adaptation of a conventional CMOS process. Fabricated devices are fully functional down to 55nm of gate length, but the influence of the gate becomes strongly reduced for shorter devices due to technological limitations. Nevertheless, the smallest device, with a 17nm gate length and with an avalanche threshold of 5.3V, is reported. The corresponding output current-voltage features an equivalent resistance as low as 66 Omegamiddotmum. For all devices, the maximum current is only limited by the contacts destruction, positioning the measured value of 4700 muA/mum among the highest ever reported for a MOS device. In addition, it is shown that the extrapolated Ion/Ioff figure of merit is close to complying with the specifications imposed to the HP flavor of the ITRS'05 roadmap
Métodos de búsqueda de variables relevantes en análisis de segmentación: aportaciones desde una perspectiva multivariante

El analisis de segmentacion clasico, basado en el algoritmo CHAID propuesto por KASS en 1980, esta basado en contrastes de asociacion en tablas marginales, pero no lleva implicito ningun paso que garantice que tiene sentido la colapsabilidad sobre la que se basa, En este trabajo se caracterizan las situaciones en las que se verifican las condiciones de colapsabilidad grafica de Asmussen y Edwards (1983), requeridas para que el algoritmo CHAID pueda ser aplicado. Se proponen algoritmos de segmentacion alternativos basados en criterios de entropia, los cuales se aplican a un analisis de marketing electoral.