gebhart/patrepeval huggingface dataset:
Potential for Using Histidine Tags in Purification of Proteins at Large Scale (2005)

Abstract Attachment of oligo‐histidine tag (His‐tag) to the protein N‐ or C‐terminus is a good example of early and successful protein engineering to design a unique and generalized purification scheme for virtually any protein. Thus relatively strong and specific binding of His‐tagged protein is achieved on an Immobilized Metal‐Ion Affinity Chromatography (IMAC) matrix. Most popular hexa‐histidine tag and recently also deca‐histidine tag are used in combination with three chelating molecules: iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), and carboxymethyl aspartic acid (CM‐Asp), covalently attached to the chromatographic matrix. The following combinations with divalent metal ions are preferentially used: (Cu, Zn, Ni, Co)‐IDA, Ni‐NTA, and Co‐CM‐Asp. At large scale, regarding cost and product purity, a decisive step is precise and efficient cleavage of His‐tag by the cleavage enzyme. Two‐step IMAC followed by a polishing step appears to be a minimum but still realistic as an approach to generic technology also for more demanding products. Possible drawbacks in using His‐tags and IMAC, such as leaching of metal ions, inefficient cleavage, and batch‐to‐batch reproducibility must be carefully evaluated before transferred to large scale. Although a great majority of reports refer to small laboratory scale isolations for research purposes it appears there is much higher potential for more extensive use of His‐tags and IMAC at large scale than currently documented.
Conjugative plasmid transfer from Escherichia coli to Clostridium acetobutylicum (1990)

The conjugation mechanism of IncP plasmids may be employed to mobilize small non-conjugative plasmids from Escherichia coli to a wide range of different organisms. This strategy has been adapted for use with the Gram-positive anaerobe, Clostridium acetobutylicum NCIB 8052. Several shuttle vectors containing replicons from pAM beta 1 (Enterococcus faecalis), pCB101 (Clostridium butyricum) or pWV01 (Streptococcus cremoris), together with the cis-acting oriT region of RK2, have been constructed, and transferred to and established in this organism. One of the vectors apparently contains a hot spot for insertion of IS1. Conjugative mobilization of plasmids from E. coli will provide a useful alternative to electroporation for effecting gene transfer to this industrially important anaerobe.
Audit of pain management at home following tonsillectomy in children (2001)

The pain experienced at home and the burden this places on primary care resources is considerable following tonsillectomy in children. This was audited by postal questionnaire in 52 patients (36 responders). We found a significant proportion of patients experiencing moderately severe to severe pain and a high rate of consultation with general practitioners (50 per cent) for pain-related issues. These findings lead to changes in practice which included the provision of five days discharge medication (paracetamol/ibuprofen in non-asthmatics; paracetamol/dihydrocodeine in asthmatics) and improved written discharge advice. On re-auditing a year later in 100 patients (56 responders), we found reduced rates of consultation with general practitioners (27 per cent). However, the proportion of children experiencing moderately severe to severe pain was not reduced probably because most children were given the recommended analgesia during the first audit. We also found that paracetamol and ibuprofen was superior to paracetamol and dihydrocodeine for analgesia (p <0.05). Suggestions for further improvements are discussed.
Single Stage to Orbit: Politics, Space Technology, and the Quest for Reusable Rocketry (2003)

While the glories and tragedies of the space shuttle make headlines and move the nation, the story of the shuttle forms an inseparable part of a lesser-known but no less important drama-the search for a re-useable single-stage-to-orbit rocket. Here an award-winning student of space science, Andrew J. Butrica, examines the long and tangled history of this ambitious concept, from it first glimmerings in the 1920s, when technicians dismissed it as unfeasible, to its highly expensive heyday in the midst of the Cold War, when conservative-backed government programs struggled to produce an operational flight vehicle. Butrica finds a blending of far-sighted engineering and heavy-handed politics. To the first and oldest idea-that of the reusable rocket-powered single-stage- to-orbit vehicle-planners who belonged to what President Eisenhower referred to as the military-industrial complex added experimental ( X ), aircraft-like capabilities and, eventually, a faster, cheaper, smaller managerial approach. Single Stage to Orbit traces the interplay of technology, corporate interest, and politics, a combination that well served the conservative space agenda and ultimately triumphed-not in the realization of inexpensive, reliable space transport-but in a vision of space militarization and commercialization that would appear settled United States policy in the early twenty-first century. 'holy grail' of the spaceship movement has been the development of a vehicle that could accomplish single stage to orbit (SSTO) flight. This study describes the evolution of this concept from the 192'0s to the present, revealing a conservative space agenda that has not yet been the subject of historical analysis. As such, it makes an important contribution to space history literature.-Roger D. Launius, The Smithsonian Institution.
Estimates of red marrow dose by sacral scintigraphy in radioimmunotherapy patients having non-Hodgkin's lymphoma and diffuse bone marrow uptake. (1995)

According to the recommendations of the Dosimetry Task Group of the American Association of Physicists in Medicine, blood-derived estimates of the red marrow (RM) dose from radiolabeled monoclonal antibodies (MAbs) are valid only if the RM is devoid of any specific uptake. There is, therefore, a clear need for an alternative method for estimating the RM dose in patients receiving MAbs that target normal or abnormal (malignant) bone marrow elements. Radiolabeled LL2, an anti-B-cell murine MAb, targets normal B cells and malignant lymphoma cells in the RM. This may result in an increased radiation dose to the RM through neighboring targeted activity. We investigated whether imaging-based estimates of the RM dose, particularly using sacral scintigraphy, correlate with myelotoxicity in non-Hodgkin's lymphoma patients who received 131I-LL2. The sacrum-based RM dose (RMs) was estimated from sacral activity by assuming that 9.9% of the total adult RM is contained in the sacrum. The sacrum was not used if there was focally increased or decreased sacral uptake. Myelotoxicity was assessed based on Radiation Therapy Oncology Group criteria. Twelve of 21 non-Hodgkin's lymphoma patients treated had adequate imaging, dosimetry, and follow-up to evaluate myelotoxicity. Eight of these patients had diffusely increased RM uptake on their MAb scans. The average estimated RMs in the eight patients was 168 +/- 62 cGy (mean +/- SD) with only 50 mCi 131I-LL2. Six of these patients (75%) developed grade 3 or 4 myelotoxicity. In contrast, the average RMs in the four patients who did not have any enhanced uptake on their scans was 71 +/- 30 cGy (P < 0.02). None of these patients developed grade 3 or 4 toxicity. These results suggest that image-based estimates of the RM dose may be predictive of myelotoxicity and should be used in patients with diffuse RM uptake on their scans.
Position location technologies using signal strength in cellular systems (2002)

This paper proposes a novel algorithm to locate a mobile terminal (MS) in a cellular system. The proposed algorithm is based on signal strength measurements. It considers the fluctuation in received signal strength due to shadowing, and obtains probability density functions (PDFs) of the propagation distances. An overall PDF, obtained by combining the PDFs, is used to determine the MS location. Results obtained from computer simulations and field experiments show that the proposed algorithm is more accurate than the conventional cell-based algorithm.
Ability of the HPV16 E7 protein to bind RB and induce DNA synthesis is not sufficient for efficient transforming activity in NIH3T3 cells. (1990)

Previous studies have demonstrated that the HPV-16 E7 gene product encodes the major transforming activity of the virus in rodent cell systems. In this study we have generated a series of point mutations affecting the region of HPV-16 E7, which shows homology to adenovirus E1a conserved domain (CD)1. In conjunction with previously described mutants in the region of E7 with similarity to E1a CD2 and SV40 LT, we have investigated three known activities of the E7 protein; transformation, association with the cellular RB protein and induction of cellular DNA synthesis. The results show that RB binding correlates with the ability of E7 to induce cellular DNA synthesis and mediate cell transformation. In addition an unidentified function of E7, which is necessary for transformation of NIH3T3 cells, but does not affect RB binding or the ability to induce cellular DNA synthesis, has also been demonstrated. This study therefore identifies two separate regions of the E7 gene necessary for transformation of established cells. One of these, in the region of E7 which shows similarity to E1a CD2 and LT, is required for RB binding and DNA synthesis. The other region important for transformation, in the N-terminus of E7, is separable from the RB binding/DNA synthesis function.
Chloroquine is a potent inhibitor of SARS coronavirus infection and spread (2005)

Chloroquine is effective in preventing the spread of SARS CoV in cell culture. Favorable inhibition of virus spread was observed when the cells were either treated with chloroquine prior to or after SARS CoV infection. In addition, the indirect immunofluorescence assay described herein represents a simple and rapid method for screening SARS-CoV antiviral compounds.
NMR imaging in the earth's magnetic field (1990)

The most important and very expensive part of a magnetic resonance imaging set-up is the magnet, which is capable of generating a constant and highly homogeneous magnetic field. Here a new MR imaging technique without the magnet is introduced. This technique uses the earth's magnetic field instead of a magnetic field created by a magnet. This new method has not yet reached the stage of medical application, but the first images obtained by MRIE (magnetic resonance imaging in the earth's field) show that the resolution is close to that expected based on sensitivity estimations.
Pathogenesis of lupus nephritis: a review. (1998)

Systemic lupus erythematosus (SLE) is a non-organ specific autoimmune disease in which the primary autoantigen has been a subject of debate despite detection of antibodies to several nuclear antigens. Contrary to previously held belief that SLE and, by extension, lupus nephritis is an immune complex disease mediated by DNA-AntiDNA complexes, it is becoming increasingly clear that nucleosomes and possibly complement factor Clq are the major players in the pathogenesis of these entities. This review article looks at the structure, source and possible pathogenetic role of nucleosomes and anti-nucleosome specific antibodies in lupus nephritis. Additionally, the possible role of Clq and anti-Clq antibodies in the pathogenesis of lupus nephritis is considered.
Wireless tomography, Part III: Compressed sensing for ultra-wideband signals (2010)

This is Part III of the wireless tomography three-paper series. Wireless tomography is related to wireless communications in that it requires the channel recovery between different waveforms at transmit and receive, as well as multiple-input-multiple-output (MIMO) communication system. According to the pulse propagation mechanisms of reflection and diffraction, ultra-wideband (UWB) waveforms suffer pulse distortion. Distorted pulses will overlap and therefore increases the sampling rate for accurate UWB channel recovery. Thanks to the recent progresses in sampling theory and radio propagation theory, we are able to propose a compressed sensing (CS) based UWB channel recovery method considering pulse distortion. The concept has been demonstrated through simulations. The sampling rate is as low as 2 Gsps, compared with the Nyquist rate of 50 Gsps. A CS based 2×2 MIMO communication system is also proposed and simulated. The communication problem is modeled as CS problem, and further reduce sampling rate required at the receiver.
Theoretical study of the electronic and magnetic structures of the Heusler alloysCo2Cr1−xFexAl (2005)

The electronic structure, x-ray absorption (XAS), x-ray magnetic circular dichroism (XMCD), and magneto-optical spectra of the doped Heusler alloys ${\mathrm{Co}}_{2}{\mathrm{Cr}}_{1\ensuremath{-}x}{\mathrm{Fe}}_{x}\mathrm{Al}$ ($x=0$, 0.125, 0.25, 0.375, 0.5, 0.625, 0.75, and 1) were investigated theoretically from first principles, using the fully relativistic Dirac linear-muffin-tin-orbital band structure method. It was shown that the concentration and arrangement of Fe atoms in the lattice play the leading role in the formation of the magnetic properties of the compounds, determining to a considerable extent the magnetic states of Co and Cr atoms. The spin polarization of electron states at the Fermi energy is quite high (about 95%) for the compositions between $x=0$ and $x=0.4$, owing to the presence of high peaks of majority-spin Cr and Co $d$ density of states at the Fermi energy. Further increasing of Fe content leads to the abrupt decreasing of the spin polarization of carriers. The band structure calculations in the LSDA approximation reproduce quite well the shape of the XAS and XMCD spectra at the Co, Fe, and Cr ${L}_{2,3}$ edges. The energy dependence of the matrix elements affects strongly the values of both the spin and the orbital magnetic moments derived from the calculated XAS and XMCD spectra using the sum rules. Our calculations show that the magneto-optical measurements are sensitive to changes in the structure of compounds (doping, disorder, etc.) accompanied by changes of the magnetic states of atoms.
Ytterbium-doped fiber amplifiers (1997)

The ytterbium-doped fiber amplifier offers a number of attractive features, including a broad-gain bandwidth and a high efficiency, due in large part to its freedom from various competing processes seen in other rare-earth dopants. Here we discuss the main features that influence design and possible applications of ytterbium-doped fiber amplifiers.
CAR-dependent and CAR-independent pathways of adenovirus vector–mediated gene transfer and expression in human fibroblasts (1999)

Primary fibroblasts are not efficiently transduced by subgroup C adenovirus (Ad) vectors because they express low levels of the high-affinity Coxsackie virus and adenovirus receptor (CAR). In the present study, we have used primary human dermal fibroblasts as a model to explore strategies by which Ad vectors can be designed to enter cells deficient in CAR. Using an Ad vector expressing the human CAR cDNA (AdCAR) at high multiplicity of infection, primary fibroblasts were converted from being CAR deficient to CAR sufficient. Efficiency of subsequent gene transfer by standard Ad5-based vectors and Ad5-based vectors with alterations in penton and fiber was evaluated. Marked enhancement of binding and transgene expression by standard Ad5 vectors was achieved in CAR-sufficient fibroblasts. Expression by AdDeltaRGDbetagal, an Ad5-based vector lacking the arginine-glycine-aspartate (RGD) alphaV integrin recognition site from its penton base, was achieved in CAR-sufficient, but not CAR-deficient, cells. Fiber-altered Ad5-based vectors, including (a) AdF(pK7)betagal (bearing seven lysines on the end of fiber) (b) AdF(RGD)betagal (bearing a high-affinity RGD sequence on the end of fiber), and (c) AdF9sK betagal (bearing a short fiber and Ad9 knob), demonstrated enhanced gene transfer in CAR-deficient fibroblasts, with no further enhancement in CAR-sufficient fibroblasts. Together, these observations demonstrate that CAR deficiency on Ad targets can be circumvented either by supplying CAR or by modifying the Ad fiber to bind to other cell-surface receptors.
Resonant interband tunnel diodes (1989)

Novel device structures are proposed, incorporating quantum wells and a pn diode structure. Such a device combines the structure and behavior of both resonant tunneling diodes and conventional tunnel diodes, leading to high speed and low excess current. There is interband tunneling between the conduction band and the valence band, as is in the case for a tunnel diode, but carriers are confined within quantum wells. Under small forward bias the diodes are expected to behave in a manner very similar to that of a tunnel diode formed of bulk material. Under large forward bias, however, the devices act much like resonant tunneling diodes, and display additional negative resistance regions.
Discovery of a Potent, Peripherally Selective trans-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonist for the Treatment of Gastrointestinal Motility Disorders (1994)

Structure-activity relationship studies were pursued within N-substituted-trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines in an effort to discover a peripherally selective opioid antagonist with high activity following systemic administration. Altering the size and the polarity of the N-substituent led to the discovery of 3 (LY246736). Compound 3 has high affinity for opioid receptors (Ki = 0.77, 40, and 4.4 nM for mu, kappa, and delta receptors, respectively). It is a potent mu receptor antagonist following parenteral and oral administration and distributes selectively (> 200-fold selectivity) to peripheral receptors. Thus, 3 has properties suitable for the clinical investigation of mu opioid receptor involvement in GI motility disorders.
Context-Aware Visual Policy Network for Sequence-Level Image Captioning (2018)

Many vision-language tasks can be reduced to the problem of sequence prediction for natural language output. In particular, recent advances in image captioning use deep reinforcement learning (RL) to alleviate the "exposure bias'' during training: ground-truth subsequence is exposed in every step prediction, which introduces bias in test when only predicted subsequence is seen. However, existing RL-based image captioning methods only focus on the language policy while not the visual policy (eg, visual attention), and thus fail to capture the visual context that are crucial for compositional reasoning such as visual relationships (\eg, "man riding horse'') and comparisons (eg. "smaller cat"). To fill the gap, we propose a Context-Aware Visual Policy network (CAVP) for sequence-level image captioning. At every time step, CAVP explicitly accounts for the previous visual attentions as the context, and then decides whether the context is helpful for the current word generation given the current visual attention. Compared against traditional visual attention that only fixes a single image region at every step, CAVP can attend to complex visual compositions over time. The whole image captioning model --- CAVP and its subsequent language policy network --- can be efficiently optimized end-to-end by using an actor-critic policy gradient method with respect to any caption evaluation metric. We demonstrate the effectiveness of CAVP by state-of-the-art performances on MS-COCO offline split and online server, using various metrics and sensible visualizations of qualitative visual context. The code is available at \urlhttps://github.com/daqingliu/CAVP
Harnessing T cells to fight cancer with BiTE® antibody constructs – past developments and future directions (2016)

Bispecific T-cell engager (BiTE(®)) antibody constructs represent a novel immunotherapy that bridges cytotoxic T cells to tumor cells, thereby inducing target cell-dependent polyclonal T-cell activation and proliferation, and leading to apoptosis of bound tumor cells. Anti-CD19 BiTE(®) blinatumomab has demonstrated clinical activity in Philadelphia chromosome (Ph)-negative relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) eventually resulting in conditional approval by the U.S. Food and Drug Administration in 2014. This drug is currently further developed in pediatric and Ph(+) r/r, as well as in minimal residual disease-positive ALL, and might also offer clinical benefit for patients with non-Hodgkin's lymphoma, especially for those with aggressive forms like diffuse large B-cell lymphoma. Another BiTE(®) antibody construct in hemato-oncology designated AMG 330 targets CD33 on acute myeloid leukemia blast cells. After showing promising ex vivo activity, this drug candidate has recently entered phase 1 clinical development, and has further indicated potential for combination with checkpoint inhibitors. In solid tumor indications, three BiTE(®) antibody constructs have been tested in phase 1 studies so far: anti-EpCAM BiTE(®) AMG 110, anti-CEA BiTE(®) MEDI-565/AMG 211, and anti-PSMA BiTE(®) BAY2010112/AMG 212. Pertinent questions comprise how to maximize BiTE(®) penetration and T-cell infiltration of the tumor while simultaneously minimizing any adverse events, which is currently explored by a continuous intravenous infusion approach. Thus, BiTE(®) antibody constructs will hopefully provide new treatment options for patients in several indications with high unmet medical need.
Myogenic cell formation in regenerating rat skeletal muscle injured by mincing II. An autoradiographic study (1977)

Abstract Myonuclei and satellite cell nuclei were differentially labelled with 3 H‐thymidine in uninjured skeletal muscle of young rats and then traced autoradiographically at intervals after mincing the radioactive hindlimb muscles to determine the source of regenerating presumptive myoblasts. Labelled nuclei were detected by light microscopic examination of 1‐m̈ thick autoradiographs and identified by electron microscopic examination of an adjacent section. Repeated injections of 3 H‐thymidine during fetal and neonatal development, followed by a 4‐ to 5‐week maturation period, resulted in labelling of 20% of the myonuclei. Satellite cells were not observed to be labelled in this series. Eight to sixteen hours after mincing, 20% of the pyknotic myonuclei were labelled, whereas none of the regenerating presumptive myoblasts appeared labelled. A single injection of 3 H‐thymidine administered to 18‐day‐old rats, followed by sacrifice within ten hours, resulted in labelling of 23% of the satellite cell nuclei. Myonuclei were not observed to be labelled in this series. Eight to sixteen hours after mincing, silver grains were detected over both pyknotic and regenerating cell nuclei. These experiments indicate that many satellite cells survive muscle injury and transplantation to become regenerating myogenic cells at a time when most, if not all, myonuclei are undergoing pyknosis.
Impact of bowel cancer screening on the management of colorectal cancer (2014)

The NBCSP has had a positive impact on elective and emergency surgery for CRC in the West Midlands.
Interface band gap engineering in InAsSb photodiodes (2005)

The optimization of an InAs0.91Sb0.09 based infrared detector has been performed. The importance of the interfaces between the active region and the contacts in generation recombination phenomena is demonstrated. The two sides of the active region are optimized independently through heterostructure band gap engineering. The use of an Al0.15In0.85As0.91Sb0.09 quaternary makes it possible reach a detectivity of 4.4×109cm√Hz∕W at 290 K and 1.4×1010cm√Hz∕W at 250 K at 3.39μm, offering the perspective of a noncryogenic infrared imaging in the 3–5μm band with quantum detectors.