gebhart/patrepeval huggingface dataset:
Nodal signaling patterns the organizer (2000)

Spemann's organizer plays an essential role in patterning the vertebrate embryo. During gastrulation, organizer cells involute and form the prechordal plate anteriorly and the notochord more posteriorly. The fate mapping and gene expression analyses in zebrafish presented in this study reveal that this anteroposterior polarity is already initiated in the organizer before gastrulation. Prechordal plate progenitors reside close to the blastoderm margin and express the homeobox gene goosecoid, whereas notochord precursors are located further from the margin and express the homeobox gene floating head. The nodal-related genes cyclops and squint are expressed at the blastoderm margin and are required for prechordal plate and notochord formation. We show that differential activation of the Nodal signaling pathway is essential in establishing anteroposterior pattern in the organizer. First, overexpression of cyclops and squint at different doses leads to the induction of floating head at low doses and the induction of both goosecoid and floating head at higher doses. Second, decreasing Nodal signaling using different concentrations of the antagonist Antivin inhibits goosecoid expression at low doses and blocks expression of both goosecoid and floating head at higher doses. Third, attenuation of Nodal signaling in zygotic mutants for the EGF-CFC gene one-eyed pinhead, an essential cofactor for Nodal signaling, leads to the loss of goosecoid expression and expansion of floating head expression in the organizer. Concomitantly, cells normally fated to become prechordal plate are transformed into notochord progenitors. Finally, activation of Nodal signaling at different times suggests that prechordal plate specification requires sustained Nodal signaling, whereas transient signaling is sufficient for notochord development. Together, these results indicate that differential Nodal signaling patterns the organizer before gastrulation, with the highest level of activity required for anterior fates and lower activity essential for posterior fates.
Effects of Metal Precursors on the Stability and Observed Reactivity of Pt/γ‐Al2O3 Catalysts in Aqueous Phase Reactions (2012)

Pt precursor promotes performance: The use of H2PtCl6 as metal precursor affects the observed activity of γ-Al2O3 supported catalysts in aqueous phase conversion of cellulose to sugar alcohols. The precursor changes the point of zero charge and leads to leaching. These two phenomena shift the dissociation equilibrium of water and enhance acid-catalyzed hydrolysis of cellulose. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
An Effort Based Model of Software Usability (2009)

This paper presents a new effort based model for software usability and reports the results of a set of experiments performed to assess the validity of the model. The model is based on the notion that usability is an inverse function of effort. Physical and mental effort are obtained and inferred from logging physical activity and eye tracking. Using the new model, an objective metric of software usability that facilitates setting measurable requirements and enables the comparison of two or more implementations of the same application is developed. The experiments results show high correlation to learning theory models, strongly support the relationship of effort to usability and demonstrate that operability, learnability, and understandability of software systems can be measured using the effort based metric. 1
Abundant off-target edits from site-directed RNA editing can be reduced by nuclear localization of the editing enzyme (2017)

Site-directed RNA editing (SDRE) is a general strategy for making targeted base changes in RNA molecules. Although the approach is relatively new, several groups, including our own, have been working on its development. The basic strategy has been to couple the catalytic domain of an adenosine (A) to inosine (I) RNA editing enzyme to a guide RNA that is used for targeting. Although highly efficient on-target editing has been reported, off-target events have not been rigorously quantified. In this report we target premature termination codons (PTCs) in messages encoding both a fluorescent reporter protein and the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein transiently transfected into human epithelial cells. We demonstrate that while on-target editing is efficient, off-target editing is extensive, both within the targeted message and across the entire transcriptome of the transfected cells. By redirecting the editing enzymes from the cytoplasm to the nucleus, off-target editing is reduced without compromising the on-target editing efficiency. The addition of the E488Q mutation to the editing enzymes, a common strategy for increasing on-target editing efficiency, causes a tremendous increase in off-target editing. These results underscore the need to reduce promiscuity in current approaches to SDRE.
The changing face of urinary continence surgery in E ngland: a perspective from the H ospital E pisode S tatistics database (2014)

Mid-urethral synthetic tapes now represent the mainstream treatment of SUI in women, but tape-related complications have led to an increase in procedures to remove these devices. The uptake of botulinum toxin A and sacral neuromodulation has led to fewer clam ileocystoplasty procedures being performed. The steady increase in insertions of AUSs in men is unsurprising and reflects the widespread uptake of radical prostatectomy in recent years. There are limitations to results sourced from the HES database, with potential inaccuracy of coding; however, these data support the trends observed by experts in this field.
Molecular and evolutionary relationships among enteric bacteria (1991)

Classification of bacterial species into genera has traditionally relied upon variation in phenotypic characteristics. However, these phenotypes often have a multifactorial genetic basis, making unambiguous taxonomic placement of new species difficult. By designing evolutionarily conserved oligonucleotide primers, it is possible to amplify homologous regions of genes in diverse taxa using the polymerase chain reaction and determine their nucleotide sequences. We have constructed a phylogeny of some enteric bacteria, including five species classified as members of the genus Escherichia, based on nucleotide sequence variation at the loci encoding glyceraldehyde-3-phosphate dehydrogenase and outer membrane protein 3A, and compared this genealogy with the relationships inferred by biotyping. The DNA sequences of these genes defined congruent and robust phylogenetic trees indicating that they are an accurate reflection of the evolutionary history of the bacterial species. The five species of Escherichia were found to be distantly related and, contrary to their placement in the same genus, do not form a monophyletic group. These data provide a framework which allows the relationships of additional species of enteric bacteria to be inferred. These procedures have general applicability for analysis of the classification, evolution, and epidemiology of bacterial taxa.
Studies of Photochemical Action Spectra on N, N, N', N'-Tetramethyl-p-phenylenediamine-Oxidase-Negative Mutants of Azotobacter vinelandii (1980)

Studies of photochemical action spectra employing a tunable dye laser as a source of intense monochromatic light were performed on phosphorylating membranes of Azotobacter vinelandii. Two classes of N, N, N′, N′-tetramethyl-p-phenylenediamine-oxidase-negative mutants were used as controls in this study. Class I mutants were found to be blocked between cytochromes c4+c5 and the oxidases, cytochromes o and a1, and class II mutants lacked the c-type cytochromes. For both classes of mutants, cytochrome oxidases o and a1 appeared to be non-functional. Photochemical action spectra of the N, N, N′, N′-tetramethyl-p-phenylenediamine-oxidase-negative mutants were identical to spectra obtained with the parent strain when physiological substrates such as NADH, malate, or succinate were used. Cytochrome d (637 nm) was the only oxidase which exhibited light relief of the carbon-monoxide-inhibited respiration. With reduced Ph(NMe2)2 as substrate, cytochrome o and cytochrome a1, but not cytochrome d exhibited light relief (parent strain only). Cytochrome d, was found to be the least sensitive to the effects of light and the laser power at which one-half maximal light relief occurred (P1/2) was about 68 mW cm−2 at 637 nm. Cytochromes o and a1 were much more sensitive to light having P1/2 values of 3.8 and 13.5 mW cm−2 at 560 and 590 nm, respectively. The P1/2 values appear to reflect differences in the affinity of carbon monoxide for terminal oxidases. This study could not demonstrate by methods using photochemical action spectra that cytochromes o and a1 oxidize physiological substrates under steady-state conditions.
Pharmacological characterisation of the spared nerve injury model of neuropathic pain (2002)

The spared nerve injury (SNI) model involves a lesion of two of the three terminal branches of the sciatic nerve (tibial and common peroneal nerves) leaving the sural nerve intact. The changes in pain-like sensation of the injured animals appear to correlate with a number of symptoms presented in human patients with neuropathic pain syndromes. In order to characterise the SNI model pharmacologically, reflex nociceptive responses to mechanical and cold stimulation were measured after systemic administration of morphine, mexiletine, gabapentin and the glutamate receptor antagonists, MK-801 and NS1209. We observed that injection of morphine (6 mg/kg, s.c.) in non-sedative doses significantly attenuated mechanical hypersensitivity in response to von Frey hair and pin prick stimulation and cold hypersensitivity in response to ethyl chloride. The sodium-channel blocker, mexiletine (37.5 mg/kg, i.p.), relieved both cold allodynia and mechanical hyperalgesia, but the most distinct and prolonged effect was observed on mechanical allodynia. Gabapentin (100 mg/kg, i.p.) significantly alleviated mechanical allodynia for at least 3h, while no significant effects were observed for either mechanical hyperalgesia or cold allodynia. In contrast, the NMDA receptor antagonist MK-801 (0.1 mg/kg, i.p.) and the AMPA receptor antagonist NS1209 (6 mg/kg, i.p.) did not relieve any of the pain-like behaviours of the SNI animals. The present study has shown that a variety of drugs with proven analgesic potency in other models of chronic pain, have differing analgesic profiles in the SNI model of neuropathic pain.
Peripheral infection with adenovirus causes unexpected long-term brain inflammation in animals injected intracranially with first-generation, but not with high-capacity, adenovirus vectors: Toward realistic long-term neurological gene therapy for chronic diseases (2000)

Although adenoviral vectors provide prolonged gene expression in the brain by comparison to peripheral organs, expression is eliminated by a severe inflammatory infiltration (i.e., activated macrophages/microglia and T-lymphocytes) after peripheral infection with adenovirus. Here, we demonstrate that high-capacity adenoviral (HC-Ad) vectors succeed in maintaining long-term transgene expression in the brain, even in the presence of an active peripheral immunization with adenovirus that completely eliminates expression from first-generation vectors within 60 days. Importantly, even 60 days after the peripheral infection, brains injected with first-generation vectors exhibited evidence of a chronic infiltration of CD8(+) cells, macrophage/microglial activation, and up-regulation of brain MHC-I expression. No inflammation was observed in the brains injected with the HC-Ad vector. Thus, these results demonstrate that HC-Ad vectors will allow safe, stable, and long-term transgene expression in the brain, even in the presence of peripheral infection with adenovirus. This markedly improves the prospects for the use of adenoviral vectors for long-term gene therapy of neurological disorders.
AlGaAs Window Stripe Buried Multiquantum Well Lasers (1985)

Transverse mode controlled high power AlGaAs lasers with a window stripe buried multiquantum well structure have been developed using the simple and reliable Zn-diffusion-induced disordering process. The maximum pulsed light output of the laser is 240 mW. The lasers operate in a fundamental transverse mode up to 100 mW. The threshold current and external differential quantum efficiency depend on the total window region length, because of large free carrier absorption in the Zn diffused window region. By controlling the diffusion depth and window region length, the lasers with low threshold current and high external differential quantum efficiency are realized.
It's a Non-book World (2007)

Looking for a selection of non-book products to add value to your book sales and attract new customers? Jo Case spoke to several booksellers, publishers and product suppliers to find out what's on the market - and how to work it in your bookstore.
Anomaly detection in multiple scale for insider threat analysis (2011)

Insiders now pose the greatest risk to organizations' information infrastructure when they have the incentive, opportunity, rationalization and the capability to circumvent rules. Cost estimates approach $1000 B/year from modification of data, security mechanisms, unauthorized network connections, covert channels, and physical damage and destruction including information extrusion/exfiltration.
Serial Changes in Cerebral Blood Flow and Flow—Metabolism Uncoupling in Primates with Acute Thromboembolic Stroke (2001)

The authors recently developed a primate thromboembolic stroke model. To characterize the primate model, the authors determined serial changes in cerebral blood flow (CBF) and the relation between CBF and cerebral metabolic rate of glucose (CMRglc) using high-resolution positron emission tomography. Thromboembolic stroke was produced in male cynomolgus monkeys (n = 4). Acute obstruction of the left middle cerebral artery was achieved by injecting an autologous blood clot into the left internal carotid artery. Cerebral blood flow was measured with [15O]H2O before and 1, 2, 4, 6, and 24 hours after embolization. CMRglc was measured with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) 24 hours after embolization. Lesion size and location 24 hours after embolization was determined by the 2,3,5-triphenyltetrazolium chloride (TTC) staining method. The results are summarized as follows: (1) 1 hour after embolization, CBF in the temporal cortex and the basal ganglia decreased to < 40% of the contralateral values. In these regions, regarded as an ischemic core, CBF decreased further with time and CMRglc at 24 hours also decreased. Infarcted lesions as indicated by being unstained with TTC were consistently observed in these regions. (2) In the parietal cortex and several regions surrounding the ischemic core, CBF was > 40% of the contralateral values 1 hour after embolization and recovered gradually with time (ischemic penumbra). In these regions, CMRglc at 24 hours increased compared with that in the contralateral regions, indicating an uncoupling of CBF and CMRglc. No obvious TTC-unstained lesions were detected in these regions. The authors demonstrated a gradual recovery of reduced CBF, an elevated CMRglc and a CBF-CMRglc uncoupling in the penumbra regions of the primate model. Positron emission tomography investigations using this model will provide better understanding of the pathophysiology of thromboembolic stroke in humans.
Use of Antidiabetic Drugs in the U.S., 2003–2012 (2014)

The antidiabetic drug market is characterized by steady increases in volume, and newly approved drugs experienced substantial uptake, especially DPP-4 inhibitors. The use of rosiglitazone has been negligible since restrictions were put in place in 2011. Further study is needed to understand why one-third to one-half of other noninsulin antidiabetic drug use was not concomitant with metformin use despite guidelines recommending that metformin be continued when other agents are added to treatment.
Effective management of obesity. (2003)

Successful treatment of obesity usually requires multiple interventions. The choice of therapies should be guided by the initial assessment of a patient's degree of obesity and comorbid conditions, if present. A variety of interventions can achieve short-term weight loss, but rebound weight gain is common when therapy is stopped. Thus, programs for weight maintenance are critical to ultimate success.
Immunolocalization of protease‐activated receptor‐2 in skin: receptor activation stimulates interleukin‐8 secretion by keratinocytes in vitro (1998)

The protease-activated receptor-2 (PAR-2) is a seven transmembrane domain receptor related to the thrombin receptor, which is activated in vitro by cleavage by trypsin. Affinity-purified rabbit IgG raised against a peptide corresponding to the trypsin cleavage site of PAR-2 was used for an immunohistochemical study of skin. The expression of PAR-2 in epidermis was striking, with keratinocytes showing abundant intercellular and cytoplasmic staining. Basal cells showed the strongest staining intensity and the stratum corneum was negative. Staining with control IgG used at the same concentration was consistently negative. The functional expression of PAR-2 by the simian virus transformed human skin keratinocyte cell line SVK14 was demonstrated by Northern blot analysis, flow cytometric analysis and the measurement of intracellular calcium. Treatment of SVK14 with trypsin or a receptor agonist peptide (SLIGKV-NH2) caused a dose-dependent increase in the secretion of the chemokine interleukin-8 (IL-8) in vitro. The effect of the peptide was specific, since control acetylated peptide was without activity. We conclude that PAR-2 is highly expressed by epidermal keratinocytes and receptor activation in vitro leads to increased IL-8 secretion by keratinocytes. These data raise the possibility that PAR-2 may play a role in epidermal homeostasis and inflammatory conditions.
Bisperoxovanadium, a phospho‐tyrosine phosphatase inhibitor, reprograms myogenic cells to acquire a pluripotent, circulating phenotype (2007)

Satellite cells are the main source of myogenic progenitors in postnatal skeletal muscle, but their use in cell therapy for muscle disorders is limited because these cells cannot be delivered through circulation and they are rapidly exhausted in severe myopathies. The search for alternative donor cells is ongoing, but none of the candidates so far show all the features required for successful colonization and repair of diseased muscle. In this study, we show that bisperoxovanadium, a phospho-tyrosine phosphatase inhibitor, induces myogenic cells to acquire a gene expression profile and a differentiation potential consistent with the phenotype of a circulating precursors, while maintaining their myogenic potential. These effects are mediated, at least in part, by NF-kappaB activation through the Tyr42-IkappaB-alpha phosphorylation, as shown by the expression of the dominant negative mutant form of the p50 NF-kappaB subunit. Moreover, when bisperoxovanadium-treated cells are injected into the femoral artery of alpha-sarcoglican null dystrophic mice, they are able to circulate and to reach muscle tissue; importantly, they contribute to muscle regeneration, as shown by the expression of alpha-sarcoglican in some fibers. Our observations indicate that bisperoxovanadium, or similar compounds, may prove very valuable to obtain and to expand, from committed cells, multipotent cell populations suitable for gene-cell therapy applications and may help to understand the molecular basis of genome reprogramming and "stem-ness."
Isolation and Functional Analysis of a cDNA for Human Jagged2, a Gene Encoding a Ligand for the Notch1 Receptor (1997)

Signaling through Notch receptors has been implicated in the control of cellular differentiation in animals ranging from nematodes to humans. Starting from a human expressed sequence tag-containing sequence resembling that of Serrate, the gene for a ligand of Drosophila melanogaster Notch, we assembled a full-length cDNA, now called human Jagged2, from overlapping cDNA clones. The full-length cDNA encodes a polypeptide having extensive sequence homology to Serrate (40.6% identity and 58.7% similarity) and even greater homology to several putative mammalian Notch ligands that have subsequently been described. When in situ hybridization was performed, expression of the murine Jagged2 homolog was found to be highest in fetal thymus, epidermis, foregut, dorsal root ganglia, and inner ear. In Northern blot analysis of RNA from tissues of 2-week-old mice, the 5.0-kb Jagged2 transcript was most abundant in heart, lung, thymus, skeletal muscle, brain, and testis. Immunohistochemistry revealed coexpression of Jagged2 and Notch1 within thymus and other fetal murine tissues, consistent with interaction of the two proteins in vivo. Coculture of fibroblasts expressing human Jagged2 with murine C2C12 myoblasts inhibited myogenic differentiation, accompanied by increased Notch1 and the appearance of a novel 115-kDa Notch1 fragment. Exposure of C2C12 cells to Jagged2 led to increased amounts of Notch mRNA as well as mRNAs for a second Notch receptor, Notch3, and a second Notch ligand, Jagged1. Constitutively active forms of Notchl in C2C12 cells also induced increased levels of the same set of mRNAs, suggesting positive feedback control of these genes initiated by binding of Jagged2 to Notch1. This feedback control may function in vivo to coordinate differentiation across certain groups of progenitor cells adopting identical cell fates.
The Unfolded Protein Response Is Involved in the Pathology of Alzheimer's Disease (2002)

The endoplasmic reticulum (ER) performs the synthesis, posttranslational modification, and proper folding of proteins. A variety of conditions can be ER stress, causing the accumulation of unfolding or misfolding proteins in the ER. Eukaryotic cells have three different mechanisms for dealing with an accumulation of unfolded proteins in the ER known as the unfolded protein response (UPR): transcriptional induction, translational attenuation, and degradation. This paper focuses on the relationship between UPR and the pathogenesis of AD. Our results indicate a new mechanism by which PS1 mutations may affect the sensing of ER stress. Experimental manipulation of IRE1, PERK, or eIF2alpha phosphorylation or GRP78 expression might allow the development of therapeutic strategies for FAD.
Interim analysis: The alpha spending function approach (1994)

Interim analysis of accumulating data in a clinical trial is now an established practice for ethical and scientific reasons. Repeatedly testing interim data can inflate false positive error rates if not handled appropriately. Group sequential methods are a commonly used frequentist approach to control this error rate. Motivated by experience of clinical trials, the alpha spending function is one way to implement group sequential boundaries that control the type I error rate while allowing flexibility in how many interim analyses are to be conducted and at what times. In this paper, we review the alpha spending function approach, and detail its applicability to a variety of commonly used statistical procedures, including survival and longitudinal methods.