gebhart/patrepeval huggingface dataset:
Charge engineering of a protein domain to allow efficient ion-exchange recovery (2000)

We have created protein domains with extreme surface charge. These mutated domains allow for ion-exchange chromatography under conditions favourable for selective and efficient capture, using Escherichia coli as a host organism. The staphylococcal protein A-derived domain Z (Zwt) was used as a scaffold when constructing two mutants, Zbasic1 and Zbasic2, with high positive surface charge. Far-ultraviolet circular dichroism measurements showed that they have a secondary structure content comparable to the parental molecule Zwt. Although melting temperatures (Tm) of the engineered domains were lower than that of the wild-type Z domain, both mutants could be produced successfully as intracellular full-length products in E. coli and purified to homogeneity by ion-exchange chromatography. Further studies performed on Zbasic1 and Zbasic2 showed that they were able to bind to a cation exchanger even at pH values in the 9 to 11 range. A gene fusion between Zbasic2 and the acidic human serum albumin binding domain (ABD), derived from streptococcal protein G, was also constructed. The gene product Zbasic2-ABD could be purified using cation-exchange chromatography from a whole cell lysate to more than 90% purity.
Anesthesia and neurotoxicity to the developing brain: the clinical relevance (2011)

Laboratory work has confirmed that general anesthetics cause increased neuronal apoptosis and changes to the morphology of dendritic spines in the developing brains of animals. It is an effect seen with most volatile anesthetics as well as with ketamine and propofol. The effects are dose dependent and seen over particular periods of early development. There is some evidence that rodents exposed to anesthesia during infancy have delayed neurobehavioral development. There are inherent limitations in translating the preclinical data to human practice but the data cannot be ignored. Some human clinical studies have found evidence for an association between major surgery and changes in neurobehavioral outcome, although the evidence is less clear for minor surgery. These associations are certainly at least partly because of factors apart from anesthesia, such as coexisting pathology or the effect of surgery itself. Other clinical studies have found no evidence for an association between surgery and outcome. These studies are also not without limitations. Thus it remains unclear what role anesthesia exposure in infancy actually plays in determining neurobehavioral outcome. To date studies can neither confirm that anesthesia plays a role nor rule it out.
Open Multicentre Study of the P 2T Receptor Antagonist AR-C69931MX Assessing Safety, Tolerability and Activity in Patients with Acute Coronary Syndromes (2001)

Platelet aggregation is the central process in the pathophysiology of acute coronary syndromes. ADP contributes to thrombosis by activating platelets, and AR-C69931MX is a specific antagonist of this process acting at the P2T receptor. At 5 hospitals, 39 patients with unstable angina or non-Q wave myocardial infarction, who were receiving aspirin and heparin, were administered intravenous AR-C69931MX with stepped dose increments over 3 h to a plateau of either 2 microg/kg/min for 21 h (Part 1; n = 12) or up to 69 h (Part 2; n = 13) or 4 microg/kg/min for up to 69 h (Part 3: n = 14). Safety parameters, platelet aggregation (PA) induced by ADP 3 micromol/L (impedance aggregometry), bleeding time (BT) and plasma concentrations of AR-C69931XX were assessed. AR-C69931MX was well tolerated. 33 patients completed the study. There were no deaths at 30 days and no serious adverse events attributed to AR-C69931MX. Trivial bleeding (56%) was common. At 24 h, mean inhibition of PA was 96.0 +/- 8.6, 94.9 +/- 14.4 and 98.7 +/- 2.1% and BT was 9.5 +/- 8.4, 14.0 +/- 9.7 and 16.0 +/- 11.1 min for Parts 1, 2 and 3 respectively. At 1 h post-infusion, mean inhibition of PA was 36.2 +/- 39.2, 20.7 +/- 25.9 and 40.7 +/- 36.7% respectively. 90% patients had a plasma half-life for AR-C69931XX of <9 min. In conclusion, AR-C69931MX is a potent, short-acting platelet ADP receptor antagonist suitable for further studies as an antithrombotic agent.
More than fun and money. Worker motivation in crowdsourcing - a study on mechanical turk (2011)

The payment in paid crowdsourcing markets like Amazon Mechanical Turk is&#13;\nvery low, and still collected demographic data shows that the participants&#13;\nare a very diverse group including highly skilled full time workers. Many&#13;\nexisting studies on their motivation are rudimental and not grounded on&#13;\nestablished motivation theory. Therefore, we adapt different models from&#13;\nclassic motivation theory, work motivation theory and Open Source Software&#13;\nDevelopment to crowdsourcing markets. The model is tested with a survey of&#13;\n431 workers on Mechanical Turk. We find that the extrinsic motivational&#13;\ncategories (imme-diate payoffs, delayed payoffs, social motivation) have a&#13;\nstrong effect on the time spent on the platform. For many workers, however,&#13;\nintrinsic motivation aspects are more important, especially the different&#13;\nfacets of enjoyment based motivation like “task autonomy” and “skill&#13;\nvariety”. Our contribution is a preliminary model based on established&#13;\ntheory intended for the comparison of different crowdsourcing platforms.
Polypeptide Delivery Across The Blood-Brain Barrier (2004)

The blood-brain barrier (BBB) used to be considered impermeable to polypeptides. However, this view has evolved rapidly over the past two decades. Not only do polypeptides have the potential to serve as carriers for selective therapeutic agents, but they themselves may directly cross the BBB after delivery into the bloodstream to become potential treatments for a variety of CNS disorders, including neurodegeneration, autoimmune diseases, stroke, depression, and obesity. The interactions of polypeptides with the BBB can take many forms, such as simple diffusion, saturable transport, or facilitation of entry of another peptide or protein. In some instances, interactions in the blood compartment (outside the BBB) or within the endothelial cells (at the BBB level) can significantly impede the passage of polypeptides across the BBB. We shall review the different aspects of interactions between peptides / proteins and the BBB that affect their delivery as potential drugs in their natural form, and discuss recent advances in the cell biology of polypeptide transport across the BBB. Better understanding of the BBB will provide insight and direction for future research in the treatment of CNS disorders.
TheN-Ethyl-N-Nitrosourea-InducedGoldenticketMouse Mutant Reveals an Essential Function ofStingin theIn VivoInterferon Response toListeria monocytogenesand Cyclic Dinucleotides (2010)

Type I interferons (IFNs) are central regulators of the innate and adaptive immune responses to viral and bacterial infections. Type I IFNs are induced upon cytosolic detection of microbial nucleic acids, including DNA, RNA, and the bacterial second messenger cyclic-di-GMP (c-di-GMP). In addition, a recent study demonstrated that the intracellular bacterial pathogen Listeria monocytogenes stimulates a type I IFN response due to cytosolic detection of bacterially secreted c-di-AMP. The transmembrane signaling adaptor Sting (Tmem173, Mita, Mpys, Eris) has recently been implicated in the induction of type I IFNs in response to cytosolic DNA and/or RNA. However, the role of Sting in response to purified cyclic dinucleotides or during in vivo L. monocytogenes infection has not been addressed. In order to identify genes important in the innate immune response, we have been conducting a forward genetic mutagenesis screen in C57BL/6 mice using the mutagen N-ethyl-N-nitrosourea (ENU). Here we describe a novel mutant mouse strain, Goldenticket (Gt), that fails to produce type I IFNs upon L. monocytogenes infection. By genetic mapping and complementation experiments, we found that Gt mice harbor a single nucleotide variant (T596A) of Sting that functions as a null allele and fails to produce detectable protein. Analysis of macrophages isolated from Gt mice revealed that Sting is absolutely required for the type I interferon response to both c-di-GMP and c-di-AMP. Additionally, Sting is required for the response to c-di-GMP and L. monocytogenes in vivo. Our results provide new functions for Sting in the innate interferon response to pathogens.
Peptides derived from two separate domains of the matrix protein thrombospondin-1 have anti-angiogenic activity (1993)

Thrombospondin-1 (TSP1) is a large modular matrix protein containing three identical disulfide-linked 180-kD chains that inhibits neovascularization in vivo (Good et al., 1990). To determine which of the structural motifs present in the 180-kD TSP1 polypeptide mediate the anti-angiogenic activity, a series of protease-generated fragments were tested using several in vitro and in vivo assays that reflect angiogenic activity. The majority of the anti-angiogenic activity of TSP1 resides in the central 70-kD stalk region which alone could block neovascularization induced by bFGF in the rat cornea in vivo and inhibit both migration in a modified Boyden chamber and [3H]thymidine incorporation stimulated by bFGF in cultured capillary endothelial cells. Although TSP1 has been shown to bind active TGF beta 1, this cytokine could not account for the inhibitory effects of the stalk region of TSP1 on cultured endothelial cells. Peptides and truncated molecules were used to further localize inhibitory activity to two domains of the central stalk, the procollagen homology region and the properdin-like type 1 repeats. Trimeric recombinant TSP1 containing NH2-terminal sequences truncated after the procollagen-like module inhibited endothelial cell migration in vitro and corneal neovascularization in vivo whereas trimeric molecules truncated before this domain were inactive as was the NH2-terminal heparin-binding domain that is present in both recombinant molecules. A series of peptides from the procollagen-like region, the smallest of which consisted of residues 303-309 of TSP1, inhibited angiogenesis in vivo in the rat cornea and the migration of endothelial cells in vitro. A 19-residue peptide containing these sequences blocked vessel formation in the granulation tissue invading a polyvinyl sponge implanted into the mouse. Nineteen residue peptides derived from two of the three type 1 repeats present in the intact TSP1 molecule blocked neovascularization in vivo in the rat cornea and inhibited the migration of cultured endothelial cells with ED50's of 0.6-7 microM. One of these peptides, containing residues 481-499 of TSP1, also inhibited vessel formation in granulation tissue invading sponges in vivo. These results suggest that the large TSP1 molecule employs at least two different structural domains and perhaps two different mechanisms to accomplish a single physiological function, the inhibition of neovascularization. The definition of short peptides from each of these domains that are able to block the angiogenic process may be of use in designing targeted inhibitors of the pathological neovascularization that underlies many diseases.
Single Ion Channel Sensitivity in Suspended Bilayers on Micromachined Supports (2001)

This paper describes the formation of bilayer lipid membranes on a micromachined support, consisting of a 128 μm (diameter) aperture on a gold/SU8 surface suspended over a small aqueous reservoir (∼25 nL). The bilayers are highly impermeable to ion transport with specific resistance values up to 107 Ω cm2. Single-channel activities of gramicidin and alamethicin were observed in these systems. This work demonstrates that micromachined supports for bilayers are promising for the development of a biosensor with single-channel sensitivity.
A low-power adaptive bandwidth PLL and clock buffer with supply-noise compensation (2003)

This paper describes a fully integrated low-jitter CMOS phase-locked loop and clock buffer for low-power digital systems with a wide range of operating frequencies. The design uses static CMOS inverters as a building block of the voltage-controlled oscillator and clock buffering. To reduce supply-induced jitter, programmable circuits with opposite sensitivity compensate for the delay variations. Both elements have supply-induced delay sensitivity of /spl les/0.1%-delay/1%-V/sub DD/. The design is fabricated in 0.25-μm CMOS technology and consumes 10mW from a 2.5-V supply. The experimental results verify that the proposed methods significantly improve the jitter.
The effect of an inhaled steroid on the hypothalamic‐pituitary‐adrenal axis‐which tests should be used? (1990)

Inhaled corticosteroids may produce systemic effects which include decreased hypothalamic-pituitary-adrenal (HPA) axis activity. Four tests of HPA axis function were assessed in 12 healthy volunteers, during inhalation of two actuations of beclomethasone dipropionate (250 micrograms) aerosol four times daily for 15 days, to determine the most appropriate test for this effect of inhaled corticosteroids. Measurement of basal adrenal activity showed that both 24-hr urinary free cortisol and 0900 hr plasma cortisol were decreased by the fourth day of steroid treatment. All 12 subjects had decreases in basal adrenal activity. Overall the 24-hr urinary free cortisol showed the greater change, with mean pre-steroid baseline values of 497 and 515 nmol/24 hr reduced to 167 nmol/24 hr on the ninth day of treatment (P less than 0.001). The single-dose metyrapone test showed marked changes in each of the six subjects tested. The mean 11-deoxycortisol response was 96 nmol/l on the eleventh day of treatment, compared to baseline and eight-day post-treatment values of 439 and 407 nmol/l respectively (P less than 0.001). In contrast, no consistent treatment-related changes were observed with the short tetracosactrin test. Only two out of six subjects had an abnormal short tetracosactrin test, although all showed a decrease in basal adrenal activity. From these results, the 24-hr urinary free cortisol and single-dose metyrapone test at 0600 hr are recommended to assess the effect of inhaled glucocorticoids on the HPA axis.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of E2F through ubiquitin–proteasome-dependent degradation: Stabilization by the pRB tumor suppressor protein (1997)

The E2F family of transcription factors plays a key role in regulating cell-cycle progression. Accordingly, E2F is itself tightly controlled by a series of transcriptional and posttranscriptional events. Here we provide evidence that E2F1 protein levels are regulated by the ubiquitin–proteasome-dependent degradation pathway. An analysis of E2F1 mutants identified a conserved carboxyl-terminal region, which is required for eliciting ubiquitination and protein turnover. Fusion of this E2F1 carboxyl-terminal sequence to a heterologous protein, GAL4, resulted in destabilization of GAL4. Previous studies identified an overlapping region of E2F1 that facilitates complex formation with retinoblastoma tumor suppressor protein, pRB, and we found that pRB blocks ubiquitination and stabilizes E2F1. These results suggest a new mechanism for controlling the cell-cycle regulatory activity of E2F1.
Growth and Optical Properties of Highly Uniform and Periodic InGaN Nanostructures (2007)

10.1002/adma.200602110
Behavioral performance of rats following transient forebrain ischemia. (1984)

Rats subjected to transient forebrain ischemic injury by the method of four vessel occlusion (4-VO) develop irreversible injury to select populations of vulnerable neurons which include pyramidal cells in the CA-1 region of the hippocampus. This brain area is thought to be crucial for learning and memory. Rats subjected to 30 minutes of 4-VO, and then cerebral reperfusion were tested on a radial 8-arm maze task after they had recovered. The data shows that both 4-VO and control animals improve their performance over trials, but that 4-VO rats are impaired on "working" and "reference" tasks. The data suggest that 4-VO rats' impaired "working" performance is permanent, compared to their transient "reference" impairment. Alterations in sensorimotor activity could not account for these performance deficits since control and 4-VO rats demonstrated equivalent choice time per maze arm. Performance deficits in rats following forebrain ischemic injury may be similar to some of the cognitive deficits found in humans survivors of cerebral hypoxia-ischemia.
Supercontinuum generation in air–silica microstructured fibers with nanosecond and femtosecond pulse pumping (2002)

We study the generation of supercontinua in air–silica microstructured fibers by both nanosecond and femtosecond pulse excitation. In the nanosecond experiments, a 300-nm broadband visible continuum was generated in a 1.8-m length of fiber pumped at 532 nm by 0.8-ns pulses from a frequency-doubled passively Q-switched Nd:YAG microchip laser. At this wavelength, the dominant mode excited under the conditions of continuum generation is the LP11 mode, and, with nanosecond pumping, self-phase modulation is negligible and the continuum generation is dominated by the interplay of Raman and parametric effects. The spectral extent of the continuum is well explained by calculations of the parametric gain curves for four-wave mixing about the zero-dispersion wavelength of the LP11 mode. In the femtosecond experiments, an 800-nm broadband visible and near-infrared continuum has been generated in a 1-m length of fiber pumped at 780 nm by 100-fs pulses from a Kerr-lens model-locked Ti:sapphire laser. At this wavelength, excitation and continuum generation occur in the LP01 mode, and the spectral width of the observed continuum is shown to be consistent with the phase-matching bandwidth for parametric processes calculated for this fiber mode. In addition, numerical simulations based on an extended nonlinear Schrödinger equation were used to model supercontinuum generation in the femtosecond regime, with the simulation results reproducing the major features of the experimentally observed spectrum.
Structure and evolution of mammalian ribosomal proteins (1995)

Mammalian (rat) ribosomes have 80 proteins; the sequence of amino acids in 75 have been determined. What has been learned of the structure of the rat ribosomal proteins is reviewed with particular attention to their evolution and to amino acid sequence motifs. The latter include: clusters of basic or acidic residues; sequence repeats or shared sequences; zinc finger domains; bZIP elements; and nuclear localization signals. The occurrence and the possible significance of phosphorylated residues and of ubiquitin extensions is noted. The characteristics of the mRNAs that encode the proteins are summarized. The relationship of the rat ribosomal proteins to the proteins in ribosomes from humans, yeast, archaebacteria, and Escherichia coli is collated.
Alternating PSM mask performance: a study of multiple fabrication technique results (2001)

In this paper we will discuss the results obtained from five alternating aperture phase-shifting masks (altPSM), each with an identical layout but manufactured using a different technique. We will show the results obtained for mask CD performance measured on a SEM for a number of dimensions and duty cycles. We will show how the results obtained from conventional mask metrology compare with results from advanced analysis including mask topography information obtained using an automated atomic force microscope (AFM). Comparison will be made showing how the metrology structures on the mask compare to the actual structures in the patterning area. A comparison of the results achieved from each mask manufacturing technique will also be made.
Visuomotor Impairment in Early-Stage Alzheimer's Disease: Changes in Relative Timing of Eye and Hand Movements (2012)

Although memory complaints are one of the first clinical symptoms in patients with Alzheimer's disease (AD), damage to the parietal lobe, a key structure in the visuomotor coordination network, was recently identified in early-stage AD. The aim of this study was to quantify visuomotor coordination in patients with probable AD and to compare their visuomotor performance with controls using five eye-hand coordination tasks of variable complexity. Eye and hand movements were measured in 16 AD patients and 18 controls. The measurement setup consisted of a touch screen, an eye-tracking device, and a motion capturing system. We investigated eye-hand coordination by quantifying absolute and relative latencies of eye and hand movements and by analyzing eye and hand kinematics. We found that AD patients need significantly more time to initiate and execute goal-directed hand movements. AD patients are also unable to suppress reflexive eye and, to a lesser extent, hand movements. Furthermore, AD patients use a stepwise approach of eye and hand movements to touch a sequence of stimuli, whereas controls more often show an anticipatory approach. The impairments in reflex suppression of eye and hand movements, and changes in relative timing of eye-hand coordination, in AD patients support the notion that cortical networks involving the posterior parietal cortex are affected at an early disease-stage. It also suggests that the problems of AD patients to perform daily activities that require eye-hand coordination are not only caused by cognitive decline, but also by degeneration of neural networks involved in visuomotor coordination.
Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet (2009)

In 2003, an international working group last reported on recommendations for diagnosis, response assessment, and treatment outcomes in acute myeloid leukemia (AML). Since that time, considerable progress has been made in elucidating the molecular pathogenesis of the disease that has resulted in the identification of new diagnostic and prognostic markers. Furthermore, therapies are now being developed that target disease-associated molecular defects. Recent developments prompted an international expert panel to provide updated evidence- and expert opinion-based recommendations for the diagnosis and management of AML, that contain both minimal requirements for general practice as well as standards for clinical trials. A new standardized reporting system for correlation of cytogenetic and molecular genetic data with clinical data is proposed.
Depth map coding with distortion estimation of rendered view (2009)

New data formats that include both video and the corresponding depth maps, such as multiview plus depth (MVD), enable new video applications in which intermediate video views (virtual views) can be generated using the transmitted/stored video views (reference views) and the corresponding depth maps as inputs. We propose a depth map coding method based on a new distortion measurement by deriving relationships between distortions in coded depth map and rendered view. In our experiments we use a codec based on H.264/AVC tools, where the rate-distortion (RD) optimization for depth encoding makes use of the new distortion metric. Our experimental results show the efficiency of the proposed method, with coding gains of up to 1.6 dB in interpolated frame quality as compared to encoding the depth maps using the same coding tools but applying RD optimization based on conventional distortion metrics.