gebhart/patrepeval huggingface dataset:
Exploring the sequence space for tetracycline-dependent transcriptional activators: Novel mutations yield expanded range and sensitivity (2000)

Regulatory elements that control tetracycline resistance in Escherichia coli were previously converted into highly specific transcription regulation systems that function in a wide variety of eukaryotic cells. One tetracycline repressor (TetR) mutant gave rise to rtTA, a tetracycline-controlled transactivator that requires doxycycline (Dox) for binding to tet operators and thus for the activation of P(tet) promoters. Despite the intriguing properties of rtTA, its use was limited, particularly in transgenic animals, because of its relatively inefficient inducibility by doxycycline in some organs, its instability, and its residual affinity to tetO in absence of Dox, leading to elevated background activities of the target promoter. To remove these limitations, we have mutagenized tTA DNA and selected in Saccharomyces cerevisiae for rtTA mutants with reduced basal activity and increased Dox sensitivity. Five new rtTAs were identified, of which two have greatly improved properties. The most promising new transactivator, rtTA2(S)-M2, functions at a 10-fold lower Dox concentration than rtTA, is more stable in eukaryotic cells, and causes no background expression in the absence of Dox. The coding sequences of the new reverse TetR mutants fused to minimal activation domains were optimized for expression in human cells and synthesized. The resulting transactivators allow stringent regulation of target genes over a range of 4 to 5 orders of magnitude in stably transfected HeLa cells. These rtTA versions combine tightness of expression control with a broad regulatory range, as previously shown for the widely applied tTA.
Nicotinamide (vitamin B3) increases the polyploidisation and proplatelet formation of cultured primary human megakaryocytes (2006)

Megakaryocytic (Mk) cell maturation involves polyploidisation, and the number of platelets produced increases with Mk DNA content. Ploidy levels in cultured human MK cells are much lower than those observed in vivo. This study demonstrated that adding the water-soluble vitamin nicotinamide (NIC) to mobilised peripheral blood CD34+ cells cultured with thrombopoietin (Tpo) more than doubled the percentage of high-ploidy (> or = 8N) MK cells. This was observed regardless of donor-dependent differences in Mk differentiation. Furthermore, MK cells in cultures with NIC were larger, had more highly lobated nuclei, reached a maximum DNA content of 64N (vs. 16N with Tpo alone), and exhibited more frequent and more elaborate cytoplasmic extensions. NIC also increased the ploidy of cultured primary murine MK cells and a cell line model (CHRF-288) of Mk differentiation. However, NIC did not alter Mk commitment, apoptosis, or the time at which endomitosis was initiated. Despite the dramatic phenotypic differences observed with NIC addition, gene expression microarray analysis revealed similar overall transcriptional patterns in primary human Mk cultures with or without NIC, indicating that NIC did not disrupt the normal Mk transcriptional program. Elucidating the mechanisms by which NIC increases Mk maturation could lead to advances in the treatment of Mk and platelet disorders.
The AltaVista tunnel: using the Internet to extend corporate networks (1997)

The public Internet has become a low-cost connection medium for joining remote employees or offices to a private intranet and for permitting impromptu high-speed connections between business partners. This connectivity is offset by a significant loss in security. The AltaVista Tunnel, a DIGITAL product, offers secure network-level routing over Internet connections by combining two well-known networking technologies: tunneling and secure channels. This paper discusses the design and implementation of the AltaVista Tunnel and describes our experience in deploying the product within DIGITAL. The public Internet is fast becoming a ubiquitous and
Vasculature segmentation of CT liver images using graph cuts and graph-based analysis (2008)

Extracting hepatic vasculature from 3D imagery is important for diagnosis of liver disease and planning liver surgery. In this paper we propose to segment vessels from liver CT images using a 3D graph-cuts based method that utilizes probabilistic intensity information and surface smoothness as constraints. A semi-automatic graph-based technique is then employed to efficiently separate the hepatic vessel systems. The complete vascular analysis method has been evaluated on 6 liver CT datasets using manual segmentation as the reference and showing that the method is reasonable robust to parameter choice and gives results of similar accuracy to previous methods in a time-efficient manner.
The impact of high-κ gate dielectrics and metal gate electrodes on sub-100 nm MOSFETs (1999)

The potential impact of high-/spl kappa/ gate dielectrics on device short-channel performance is studied over a wide range of dielectric permittivities using a two-dimensional (2-D) simulator implemented with quantum mechanical models. It is found that the short-channel performance degradation is caused by the fringing fields from the gate to the source/drain regions. These fringing fields in the source/drain regions further induce electric fields from the source/drain to channel which weakens the gate control. The gate dielectric thickness-to-length aspect ratio is a proper parameter to quantify the percentage of the fringing field and thus the short channel performance degradation. In addition, the gate stack architecture plays an important role in the determination of the device short-channel performance degradation. Using double-layer gate stack structures and low-/spl kappa/ dielectric as spacer materials can well confine the electric fields within the channel thereby minimizing short-channel performance degradation. The introduction of a metal gate not only eliminates the poly gate depletion effect, but also improves short-channel performance. Several approaches have been proposed to adjust the proper threshold voltage when midgap materials or metal gates are used.
Oxidants and human disease: some new concepts 1 (1987)

Oxidant species such as superoxide radical (O.2-), hydrogen peroxide (H2O2), hydroxyl radical (HO.), and lipid peroxides (LOOH) are becoming increasingly implicated in human disease. However, the question of whether such oxidants are a major cause of tissue injury in human disease or are merely produced during such injury has been difficult to answer because of inadequate experimental techniques, and possibly because of an overemphasis on lipid peroxidation as a mechanism of oxidant injury. Recent developments in methodology, in our understanding of the primary mechanism of oxidant toxicity to cells, and in concepts of antioxidant protection are reviewed. Good evidence now exists for some role of oxidant damage to tissues in the pathology of several human diseases, including rheumatoid arthritis, reperfusion injury, immune injury to lung and kidney, and cerebral trauma or ischemia. These have led to promising suggestions for new therapeutic approaches.
Hematopoietic Stem Cells Are Uniquely Selective in Their Migratory Response to Chemokines (2002)

Although hematopoietic stem cell (HSC) migration into and out of sites of active hematopoiesis is poorly understood, it is a critical process that underlies modern clinical stem cell transplantation and may be important for normal hematopoietic homeostasis. Given the established roles of chemotactic cytokine (chemokine)-directed migration of other leukocyte subsets, the migration of murine HSC to a large panel of CC and CXC chemokines was investigated. HSC migrated only in response to stromal derived factor-1alpha, the ligand for the CXC chemokine receptor 4 (CXCR4). CXCR4 expression by HSC was confirmed by reverse transcription polymerase chain reaction analysis. Surprisingly, HSC also expressed mRNA for CCR3 and CCR9, although they failed to migrate to the ligands for these receptors. The sharply restricted chemotactic responsiveness of HSC is unique among leukocytes and may be necessary for the specific homing of circulating HSC to bone marrow, as well as for the maintenance of HSC in hematopoietic microenvironments.
Genetic analysis of the BRCA1 region in a large breast/ovarian family: refinement of the minimal region containing BRCA1 (1993)

We have analyzed a single multi-affected breast/ovarian cancer pedigree (BOV3) and have shown consistent inheritance of markers on chromosome 17q with the disease confirming that this family is due to the BRCA1 gene. Analysis of 17q haplotypes shows a recombination event in a bilateral breast cancer case which suggests that the BRCA1 gene lies distal to D17S857; D17S857 is thus the new proximal boundary for the region containing BRCA1. Combining this information with previously published mapping information suggests that BRCA1 is contained in a region estimated at 1-1.5 Mb in length. All seven breast tumour/blood pairs examined from this family show loss of heterozygosity in the tumours. The allel retained in each tumour was from the disease-bearing chromosome implicating BRCA1 as a tumour suppressor gene. We have sequenced the 17 beta-oestradiol dehydrogenase genes (EDH17B1 and EDH17B2) which have been suggested as candidate genes for BRCA1 in four members of this family. No germline mutations were detected.
Molecular cloning, sequence, and tissue distribution of the human ubiquitin-activating enzyme E1. (1991)

The ubiquitin-activating enzyme E1 catalyzes the first step in ubiquitin conjugation. We have cloned and sequenced the cDNA for human E1. This clone predicts a protein of 110,450 Da. Cys-194 lies within a region of identity to active-site Cys-88 of the ubiquitin carrier protein E2, suggesting a potential role for this region in enzymatic function of this protein. In addition, Cys-454 lies within a region of identity to the thiol ester consensus sequence of several proteins involved in thioester formation. Tissue distribution reveals a single 3.5-kilobase E1 message ubiquitous among tissues and cell lines.
Quantum-well-base heterojunction bipolar light-emitting transistor (2004)

This letter reports the enhanced radiative recombination realized by incorporating InGaAs quantum wells in the base layer of light-emitting InGaP/GaAs heterojunction bipolar transistors (LETs) operating in the common-emitter configuration. Two 50 Å In1−xGaxAs (x=85%) quantum wells (QWs) acting, in effect, as electron capture centers (“traps”) are imbedded in the 300 Å GaAs base layer, thus improving (as a “collector” and recombination center) the light emission intensity compared to a similar LET structure without QWs in the base. Gigahertz operation of the QW LET with simultaneously amplified electrical output and an optical output with signal modulation is demonstrated.
Coexpression of heparanase activity, cathepsin L, tissue factor, tissue factor pathway inhibitor, and MMP-9 in proliferative diabetic retinopathy. (2016)

The coexpression of these angiogenesis regulatory factors suggests cross-talk between these factors and pathogenesis of PDR angiogenesis.
Infusion of red blood cell-loaded asparaginase in monkey. Immunologic, metabolic, and toxicologic consequences. (1983)

In order to evaluate enzyme loading of RBCs as a drug delivery system, the antitumor agent asparaginase was loaded into the erythrocytes of nine monkeys at three different doses and autologously injected back into these animals. Nine control monkeys were also once injected intravenously at the same doses of enzyme, but the enzyme was free in solution rather than entrapped in RBCs. The RBCs and asparaginase were labeled with 51Cr and 125I, respectively. The circulating half-life of the enzyme-loaded, resealed RBCs was 7 days, as compared to 9 days in the control RBCs. Beginning at 5 days, circulating enzyme activity was several orders of magnitude higher in the monkeys injected with RBC-loaded asparaginase than in controls. Targeting of drug-loaded RBCs into the spleen and liver was apparent. Suppression of the serum substrate level of asparaginase in the monkeys treated with the single intravenous injection of RBCs loaded with asparaginase was 20 days, which was twice as long as the suppression in the control monkeys. Production of anti-asparaginase antibody was shown to reach a higher level and persist longer in the monkeys with RBC-entrapped asparaginase. Evidence was also obtained showing that entrapping asparaginase in RBCs protects against anaphylaxis in the guinea pig. Thus this drug delivery system is also proposed as a strategy to avoid life-threatening allergic reactions. Advantages and limitations of RBC loading as a drug delivery system are discussed.
Sodium channel mutations in paramyotonia congenita exhibit similar biophysical phenotypes in vitro. (1994)

Mutations in the skeletal muscle voltage-gated Na+ channel alpha-subunit have been found in patients with two distinct hereditary disorders of sarcolemmal excitation: hyperkalemic periodic paralysis (HYPP) and paramyotonia congenita (PC). Six of these mutations have been functionally expressed in a heterologous cell line (tsA201 cells) using the recombinant human skeletal muscle Na+ channel alpha-subunit cDNA hSkM1. PC mutants from diverse locations in this subunit (T1313M, L1433R, R1448H, R1448C, A1156T) all exhibit a similar disturbance in channel inactivation characterized by reduced macroscopic rate, accelerated recovery, and altered voltage dependence. PC mutants had no significant abnormality in activation. In contrast, one HYPP mutation studied (T704M) has a normal inactivation rate but exhibits shifts in the midpoints of steady-state activation and inactivation along the voltage axis. These findings help to explain the phenotypic differences between HYPP and PC at the molecular and biophysical level and contribute to our understanding of Na+ channel structure and function.
Colour Mapping: A Review of Recent Methods, Extensions and Applications (2015)

Abstract The objective of colour mapping or colour transfer methods is to recolour a given image or video by deriving a mapping between that image and another image serving as a reference. These methods have received considerable attention in recent years, both in academic literature and industrial applications. Methods for recolouring images have often appeared under the labels of colour correction, colour transfer or colour balancing, to name a few, but their goal is always the same: mapping the colours of one image to another. In this paper, we present a comprehensive overview of these methods and offer a classification of current solutions depending not only on their algorithmic formulation but also their range of applications. We also provide a new dataset and a novel evaluation technique called ‘evaluation by colour mapping roundtrip’. We discuss the relative merit of each class of techniques through examples and show how colour mapping solutions can have been applied to a diverse range of problems.
Bridges Between Silos: A Microsoft Research Project (2005)

Enterprise data is locked away in silos. As a result people spend too much time looking for information – or they spend too little and make decisions based on incomplete information. The simplest remedy is to pull all the silos into a common full-text search index, but doing so realizes only part of the opportunity. The rest lies in automatically finding and representing the relationships among the objects in the index. Relationships take many forms, ranging from schematized references to allusions in text. All these relationships can be recorded in the index, thus combining structured, semi-structured, and unstructured relationships together in a normalized representation, forming bridges between data silos. The result is a graph, which makes it possible to make queries like “find all x’s related to y.” For example the graph could be used to find all the people or discussions related to a particular method. The graph is stored in a SQL-based search index that also has a rich notion of time and history. The index is exposed to the user in three ways: a search portal, an implicit query sidebar, and object-based search commands in client applications. The index improves search in several ways, allowing for richer filtering, scoring, and search results presentation. These ideas can turn siloed data into working knowledge, making the enterprise work more efficiently.
Robust statistical methods for reducing sferics noise contaminating transient electromagnetic measurements (1996)

Abstract The transient electromagnetic (TEM) method is used extensively for mineral exploration and other applications such as geothermal soundings, oil exploration, groundwater pollution, soil salinity and geological mapping. Sferics pulses produced by lightning strokes propagating in the ionosphere-earth waveguide cavity induce noise in a bandwidth of a few Hz to tens of kHz. The usual method of stacking and calculating the mean of a given stack cannot effectively reduce the spike-like noise induced by high-amplitude sferics pulses. To reduce this type of noise, a number of different ways of stacking data were investigated and compared. Noise data were stacked by using robust estimators such as the median, trimmed mean, and a range of M-estimators. Since storage of all the samples of a given stack can take up a prohibitively large amount of microprocessor memory, recursive algorithms for the M-estimators and their standard error were developed for the real-time reduction of sferics pulses. The recursive algorithms have been demonstrated to work effectively on windowed data, and thus the memory normally required to obtain the mean is sufficient for calculation of the M-estimate. In the recursive calculation of the robust estimate of the transient response, the spread of the background noise distribution (known as the scale of the data) needs to be known or calculated. In the algorithm that has been developed, the scale of the data is derived from a noise run carried out before pulsing the transmitter loop with current. It has been assumed that the presence of a signal does not change the scale of the data. This value of the scale of the data has been used to obtain a robust estimate of the transient response itself. To allow for possible changes in the background noise level during a given survey, the estimate of the scale of the data is updated throughout the survey. Many tests of the performance of the recursive algorithms have been carried out with both simulated noise data and sferics data that have been recorded previously on magnetic tape. The results show that for sferics activity as high as that observed in northern latitudes of Australia in summer, a noise reduction by a factor of about 5 (when compared with simple stacking) should be obtained. In areas where sferics noise predominates over geological background signal, such a reduction should lead to an increase in target detection depth by approximately 50%.
The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling (2014)

Despite an enormous interest in the role of extracellular vesicles, including exosomes, in cancer and their use as biomarkers for diagnosis, prognosis, drug response and recurrence, there is no consensus on dependable isolation protocols. We provide a comparative evaluation of 4 exosome isolation protocols for their usability, yield and purity, and their impact on downstream omics approaches for biomarker discovery. OptiPrep density gradient centrifugation outperforms ultracentrifugation and ExoQuick and Total Exosome Isolation precipitation in terms of purity, as illustrated by the highest number of CD63-positive nanovesicles, the highest enrichment in exosomal marker proteins and a lack of contaminating proteins such as extracellular Argonaute-2 complexes. The purest exosome fractions reveal a unique mRNA profile enriched for translation, ribosome, mitochondrion and nuclear lumen function. Our results demonstrate that implementation of high purification techniques is a prerequisite to obtain reliable omics data and identify exosome-specific functions and biomarkers.
IMS cloud computing architecture for high-quality multimedia applications (2011)

A novel IP Multimedia Subsystem (IMS) framework with cloud computing architecture is proposed for use in high-quality multimedia applications. The IMS supports heterogeneous networking with Quality-of-Service (QoS) policy. MapReduce analysis is also used to enhance cloud computing capability. This architecture enables users to access high-quality multimedia applications via Android-based appliances. In this study, the IMS QoS policies of three wireless access technologies, 3G, WiFi and WiMAX, are integrated in a cloud computing environment to provide different services such as VoIP services and video streaming services. Experimental results indicate that the proposed mechanism improves system performance by allocating resources according to service priority. The proposed architecture also significantly improves system capacity to accommodate numerous users.
Polyethylene wear in total hip and knee arthroplasties (1997)

The role that ultrahigh molecular weight polyethylene (UHMWPE) wear at bearing surfaces in total hip and knee arthroplasties plays in the clinical life of these implants cannot be overemphasized. This subject has therefore been attracting enormous research attention on both fundamental and technological levels. Given this, it is important to detail the main features of the knowledge base and describe research directions that may culminate in the production of new and/or improved varieties of UHMWPE material and components. These aspects are the subject of the present review.
A Pilot trial evaluating meta050, a proprietary combination of reduced iso-alpha acids, rosemary extract and oleanolic acid in patients with arthritis and fibromyalgia (2005)

The aim of this open-label, 8-week observational trial was to investigate the efficacy of Meta050 (a proprietary, standardized combination of reduced iso-alpha-acids from hops, rosemary extract and oleanolic acid) on pain in patients with rheumatic disease. Osteoarthritis, rheumatoid arthritis and fibromyalgia patients were given 440 mg Meta050 three times a day for 4 weeks, which was changed to 880 mg twice a day for the subsequent 4 weeks in the majority of patients. Pain and condition-specific symptoms were assessed using a standard visual analog scale (VAS), an abridged arthritis impact measurement scale (AIMS2) and the fibromyalgia impact questionnaire. Fifty-four subjects with rheumatic disease completed the trial. Following treatment, a statistically significant decrease in pain of 50% and 40% was observed in arthritis subjects using the VAS (p < 0.0001; Wilcoxon-ranked sums) and AIMS2 (p < 0.0001), respectively. Fibromyalgia subject scores did not significantly improve. A decreasing trend of C-reactive protein, a marker for inflammation, was also observed in those subjects who presented with elevated C-reactive protein. No serious side effects were observed. These observations suggest that Meta050 at a dosage of 440 mg three times a day has a beneficial effect on pain in arthritis subjects.