gebhart/patrepeval huggingface dataset:
Spliceosome mutations exhibit specific associations with epigenetic modifiers and proto-oncogenes mutated in myelodysplastic syndrome (2013)

The recent identification of acquired mutations in key components of the spliceosome machinery strongly implicates abnormalities of mRNA splicing in the pathogenesis of myelodysplastic syndromes. However, questions remain as to how these aberrations functionally combine with the growing list of mutations in genes involved in epigenetic modification and cell signaling/transcription regulation identified in these diseases. In this study, amplicon sequencing was used to perform a mutation screen in 154 myelodysplastic syndrome patients using a 22-gene panel, including commonly mutated spliceosome components (SF3B1, SRSF2, U2AF1, ZRSR2), and a further 18 genes known to be mutated in myeloid cancers. Sequencing of the 22-gene panel revealed that 76% (n=117) of the patients had mutations in at least one of the genes, with 38% (n=59) having splicing gene mutations and 49% (n=75) patients harboring more than one gene mutation. Interestingly, single and specific epigenetic modifier mutations tended to coexist with SF3B1 and SRSF2 mutations (P<0.03). Furthermore, mutations in SF3B1 and SRSF2 were mutually exclusive to TP53 mutations both at diagnosis and at the time of disease transformation. Moreover, mutations in FLT3, NRAS, RUNX1, CCBL and C-KIT were more likely to co-occur with splicing factor mutations generally (P<0.02), and SRSF2 mutants in particular (P<0.003) and were significantly associated with disease transformation (P<0.02). SF3B1 and TP53 mutations had varying impacts on overall survival with hazard ratios of 0.2 (P<0.03, 95% CI, 0.1-0.8) and 2.1 (P<0.04, 95% CI, 1.1-4.4), respectively. Moreover, patients with splicing factor mutations alone had a better overall survival than those with epigenetic modifier mutations, or cell signaling/transcription regulator mutations with and without coexisting mutations of splicing factor genes, with worsening prognosis (P<0.001). These findings suggest that splicing factor mutations are maintained throughout disease evolution with emerging oncogenic mutations adversely affecting patients' outcome, implicating spliceosome mutations as founder mutations in myelodysplastic syndromes.
Current advancements and potential strategies in the development of MERS-CoV vaccines (2014)

Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the in vivo efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future.
Aspects of the Application of Electrochemistry to the Extraction of Titanium and Its Applications (2017)

For over five decades the main route for the extraction of titanium has been the Kroll process. It is regarded as being expensive, labour intensive, reliant on a high quality feedstock, and environmentally unfriendly, but it has thus far not been possible to replace it. As a result the usage of titanium is still restricted to a few high end applications. During the past twenty years several new molten salt based electrochemical approaches for the reduction of titanium oxide have been introduced to meet these challenges, and these may, eventually, lead to novel extraction processes for titanium and other reactive metals. This paper summarises the many interesting concepts that underlie these electrochemical methods, of which some have already advanced to the stage of substantial pilot plants whilst others are still being developed at the laboratory level. The paper also reviews the development of new materials for use as the anode in these processes. Finally, it touches upon the development of processes for the regeneration of oxidised titanium and for the welding of titanium under cathodic protection in cases where protective gas shielding is not possible.
Radiation-induced and chemotherapy-induced pulmonary injury (2001)

The management of cancer has continued to advance with the development of new chemotherapeutic agents and improved techniques of radiation therapy. Although new therapeutic approaches have improved survival in cancer patients, each form of intervention has the potential to produce adverse effects on normal host tissues. Some of these toxicities may be accentuated with combined modality therapy. The use of chemotherapy and radiation therapy, alone or combined, can be associated with clinically significant pulmonary toxicity. The pulmonary toxic effects of chemotherapy can be divided into (1) early onset, resulting in interstitial lung injury, and (2) late onset, with pulmonary fibrosis as a sequela. These toxic effects are frequently dose related but may be enhanced by radiation therapy. Similar to chemotherapy, radiation can produce acute or chronic lung injury depending on dose rate, duration, preexisting lung disease, and concomitant steroid use. Acute radiation injury typically occurs 2 weeks to 3 months after treatment and is usually limited to the irradiated field. Mild injury often resolves without treatment, whereas more serious injury results in fibrosis 6 to 12 months after treatment. Histopathologic evaluation of acute lung injury is no different from drug-induced injury, and damage to vascular endothelial cells and alveolar lining cells is seen. This article reviews and provides an update on the clinically important chemotherapy and radiation-induced pulmonary injuries, the pathologic mechanisms, where known, and the treatment advances that have occurred in this field.
Early Detection ofAspergillusInfection after Allogeneic Stem Cell Transplantation by Polymerase Chain Reaction Screening (2000)

Invasive aspergillosis (IA) has become a major cause of mortality in patients after allogeneic stem cell transplantation. To assess the potential of prospective polymerase chain reaction (PCR) screening for early diagnosis of IA, 84 recipients of an allogeneic stem cell transplant were analyzed with the investigators blinded to clinical and microbiologic data. Of 1193 blood samples analyzed, 169 (14.2%) were positive by PCR. In patients with newly diagnosed IA (n=7), PCR positivity preceded the first clinical signs by a median of 2 days (range, 1-23 days) and preceded clinical diagnosis of IA by a median of 9 days (range, 2-34 days). Pretransplantation IA (relative risk [RR], 2.37), acute graft-versus-host disease (RR, 2.75), and corticosteroid treatment (RR, 6.5) were associated with PCR positivity. The PCR assay revealed a sensitivity of 100% (95% confidence interval [CI], 48%-100%) and a specificity of 65% (95% CI, 53%-75%). None of the PCR-negative patients developed IA during the study period. Thus, prospective PCR screening allows for identification of patients at high risk for subsequent onset of IA.
Preparation of multishell ICF target plastic foam cushion materials by thermally induced phase inversion processes (1982)

Homogeneous, low‐density plastic foams for ICF targets have been prepared by thermally induced phase inversion processes. Uniform, open cell foams have been obtained by the rapid freezing of water solutions of modified cellulose polymers with densities in the range of 50–7 mg/cm3 and respective average cell sizes of 2 to 40 μm. In addition, low‐density, microcellular foams have been prepared from the hydrocarbon polymer poly(4‐methyl‐l‐pentene) via a similar phase inversion process using homogeneous solutions in organic solvents. These foams have densities from 20 to 50 mg/cm3 and average cell sizes of 20 μm.
Initiation of methyl-directed mismatch repair. (1992)

Escherichia coli MutH possesses an extremely weak d(GATC) endonuclease that responds to the state of methylation of the sequence (Welsh, K. M., Lu, A.-L., Clark, S., and Modrich, P. (1987) J. Biol. Chem. 262, 15624-15629). MutH endonuclease is activated in a reaction that requires MutS, MutL, ATP, and Mg2+ and depends upon the presence of a mismatch within the DNA. The degree of activation correlates with the efficiency with which a particular mismatch is subject to methyl-directed repair (G-T greater than G-G greater than A-C greater than C-C), and activated MutH responds to the state of DNA adenine methylation. Incision of an unmethylated strand occurs immediately 5' to a d(GATC) sequence, leaving 5' phosphate and 3' hydroxy termini (pN decreases pGpAp-TpC). Unmethylated d(GATC) sites are subject to double strand cleavage by activated MutH, an effect that may account for the killing of dam- mutants by 2-aminopurine. The mechanism of activation apparently requires ATP hydrolysis since adenosine-5'-O-(3-thiotriphosphate) not only fails to support the reaction but also inhibits activation promoted by ATP. The process has no obligate polarity as d(GATC) site incision by the activated nuclease can occur either 3' or 5' to the mismatch on an unmethylated strand. However, activation is sensitive to DNA topology. Circular heteroduplexes are better substrates than linear molecules, and activity of DNAs of the latter class depends on placement of the mismatch and d(GATC) site within the molecule. MutH activation is supported by a 6-kilobase linear heteroduplex in which the mismatch and d(GATC) site are centrally located and separated by 1 kilobase, but a related molecule, in which the two sites are located near opposite ends of the DNA, is essentially inactive as substrate. We conclude that MutH activation represents the initiation stage of methyl-directed repair and suggest that interaction of a mismatch and a d(GATC) site is provoked by MutS binding to a mispair, with subsequent ATP-dependent translocation of one or more Mut proteins along the helix leading to cleavage at a d(GATC) sequence on either side of the mismatch.
Algal production in wastewater treatment high rate algal ponds for potential biofuel use (2011)

Wastewater treatment High Rate Algal Ponds with CO2 addition could provide cost-effective and efficient tertiary-level wastewater treatment with the co-benefit of algal biomass production for biofuel use. Wastewater grown algal biomass can have a lipid content of 10-30% of dry weight, which could be used to make biodiesel. This research investigated algal biomass and total lipid production by two pilot-scale wastewater treatment HRAP(S) (4-day HRT) with and without CO2 addition under New Zealand mid summer (Nov-Jan) conditions. The influence of CO2 addition on wastewater treatment performance was also determined. CO2 was added to one of the HRAPs (the HRAP(E)) by maintaining the maximum pH of the pond below 8. Measurements of HRAP influent and effluent water qualities, total lipid content and algal biomass production were made twice a week over the experimental period. Both HRAP(S) achieved high levels of organic compound and nutrient removal, with >85% SBOD5, >92 NH4(+)-N and >70% DRP removal. Algal/bacterial biomass production in the HRAP(E) (15.2 g/m2/d) was improved by CO2 addition by approximately 30% compared with that of the control HRAP(W) (10.6 g/m2/d). Total lipid content of the biomass grown on both HRAP(S) was slightly reduced (from 25% to 20%) with CO2 addition and the maximum total lipid content of approximately 40% was observed in the HRAP(W) when low NH4(+)-N concentration (<0.5 mg/L) and high maximum pH (>10.0) occurred. Total lipid content of the biomass increased by approximately 15% under nitrogen limiting conditions, however, overall algal/bacterial biomass production was reduced by half during the period of nitrogen limitation. More research is required to maintain algal production under near nitrogen-limiting conditions.
Tunable, continuous-wave Terahertz photomixer sources and applications (2011)

This review is focused on the latest developments in continuous-wave (CW) photomixing for Terahertz (THz) generation. The first part of the paper explains the limiting factors for operation at high frequencies ∼ 1 THz, namely transit time or lifetime roll-off, antenna (R)-device (C) RC roll-off, current screening and blocking, and heat dissipation. We will present various realizations of both photoconductive and p-i-n diode–based photomixers to overcome these limitations, including perspectives on novel materials for high-power photomixers operating at telecom wavelengths (1550 nm). In addition to the classical approach of feeding current originating from a small semiconductor photomixer device to an antenna (antenna-based emitter, AE), an antennaless approach in which the active area itself radiates (large area emitter, LAE) is discussed in detail. Although we focus on CW photomixing, we briefly discuss recent results for LAEs under pulsed conditions. Record power levels of 1.5 mW average power and conversion efficiencies as high as 2 × 10−3 have been reached, about 2 orders of magnitude higher than those obtained with CW antenna-based emitters. The second part of the paper is devoted to applications for CW photomixers. We begin with a discussion of the development of novel THz optics. Special attention is paid to experiments exploiting the long coherence length of CW photomixers for coherent emission and detection of THz arrays. The long coherence length comes with an unprecedented narrow linewidth. This is of particular interest for spectroscopic applications, the field in which THz research has perhaps the highest impact. We point out that CW spectroscopy systems may potentially be more compact, cheaper, and more accurate than conventional pulsed systems. These features are attributed to telecom-wavelength compatibility, to excellent frequency resolution, and to their huge spectral density. The paper concludes with prototype experiments of THz wireless LAN applications. For future telecommunication systems, the limited bandwidth of photodiodes is inadequate for further upshifting carrier frequencies. This, however, will soon be required for increased data throughput. The implementation of telecom-wavelength compatible photomixing diodes for down-conversion of an optical carrier signal to a (sub-)THz RF signal will be required.
Natural history of atopic dermatitis and its relationship to serum total immunoglobulin E in a population‐based birth cohort study (2004)

We investigated the natural history of atopic dermatitis (AD) in a population-based birth cohort and assessed whether children at risk of visible eczema at 5 years of age can be identified from total immunoglobulin E (IgE) levels measured at 8, 12 and 18 months. AD data collected included a whole body examination for visible eczema at 49 months (4 years) and 61 months (5 years) of age and parent completed questionnaire data throughout their early lives. Children were divided into four groups based on their natural history of early AD: persistent (AD at 1, 6, 18, 30 and 42 months, n = 34), intermittent early onset (before 18 months of age, n = 495), intermittent late onset (18-42 months of age, n = 273) and unaffected (n = 429). Visible eczema at 5 years of age was present in 12.2% (117/957) (95% confidence interval [CI] 10.1-14.3%) of the children. Levels of total IgE at 8, 12 and 18 months of age were associated with early onset of AD, but not with AD of later onset. For all four natural history groups, the geometric mean total IgE at 12 months was higher in those who subsequently had visible eczema than those who did not. However, the degree of overlap was such that total IgE at 12 months of age was a poor predictor of eczema at age five. A cutoff point of 78 kU/l had the highest positive predictive value for visible eczema at 5 years of age of 28.6%, with a sensitivity of 12% and specificity of 95%.
Practical Gammatone-Like Filters for Auditory Processing (2007)

This paper deals with continuous-time filter transfer functions that resemble tuning curves at particular set of places on the basilar membrane of the biological cochlea and that are suitable for practical VLSI implementations. The resulting filters can be used in a filterbank architecture to realize cochlea implants or auditory processors of increased biorealism. To put the reader into context, the paper starts with a short review on the gammatone filter and then exposes two of its variants, namely, the differentiated all-pole gammatone filter (DAPGF) and one-zero gammatone filter (OZGF), filter responses that provide a robust foundation for modeling cochlea transfer functions. The DAPGF and OZGF responses are attractive because they exhibit certain characteristics suitable for modeling a variety of auditory data: level-dependent gain, linear tail for frequencies well below the center frequency, asymmetry, and so forth. In addition, their form suggests their implementation by means of cascades of N identical two-pole systems which render them as excellent candidates for efficient analog or digital VLSI realizations. We provide results that shed light on their characteristics and attributes and which can also serve as Ã¢Â€Âœdesign curvesÃ¢Â€Â for fitting these responses to frequency-domain physiological data. The DAPGF and OZGF responses are essentially a Ã¢Â€Âœmissing linkÃ¢Â€Â between physiological, electrical, and mechanical models for auditory filtering.
Functional analysis of the cysteine residues of activin A. (1994)

Site-directed mutagenesis and mammalian cell expression was used to analyze the function of each of the 13 cysteine residues in the human activin A beta-subunit precursor. Substitution of the four cysteine residues in the proregion with alanine residues did not affect the function of the proregion in facilitating the dimerization and secretion of activin A homodimers. A series of activin mutants were constructed in which the nine cysteine residues (amino acids 4, 11, 12, 40, 44, 80, 81, 113, and 115) in the mature 116-amino acid beta-subunit were individually altered to alanine residues. Alanine substitution at either cysteine residues 4 or 12 did not interfere with homodimer formation, but the mutant activin A molecules had reduced biological and receptor binding activity (2- to 3-fold). Activin A monomers were produced when cysteine mutants 44, 80, and 113 were expressed in tissue culture cells. Monomers of cys mutants 44 and 80 had approximately 2% of the biological and receptor binding activity of wild type activin A. Cys 113 monomers had undetectable levels of biological activity. No detectable activin monomers or dimers were secreted from cells transfected with plasmids containing cys mutants 11, 40, 81, and 115. The data presented here suggest that a low level of noncovalent dimer formation of cysteine mutant monomers 44 and 80 may explain their low level of biological activity. Therefore, dimer formation is suggested to be an essential prerequisite for high affinity receptor binding and biological potency.(ABSTRACT TRUNCATED AT 250 WORDS)
Synchrotron Radiation SAXS/WAXS Study of Polymorph-Dependent Phase Behavior of Binary Mixtures of Saturated Monoacid Triacylglycerols (2003)

Polymorphic influences on the phase behavior of three types of binary mixtures of saturated monoacid triacylglycerols (TAGs), trilaurin/trimyristin (LLL/MMM), trilaurin/tripalmitin (LLL/PPP), and trilaurin/tristearin (LLL/SSS), were examined by small- and wide-angle X-ray scattering (SAXS/WAXS) using synchrotron radiation. The carbon numbers (Cn) for the fatty acid chains of the three TAGs are 12 (LLL), 14 (MMM), 16 (PPP), and 18 (SSS). In the LLL/MMM system, miscible phase behavior occurred in metastable α and β‘ forms, whereas the most stable β form exhibited a eutectic phase. On the other hand, LLL/PPP and LLL/SSS mixtures showed immiscible phases for α, β‘, and β forms. Therefore, the TAG binary mixtures were miscible in metastable polymorphs of α and β‘ forms when Cn differed by 2, whereas the immiscible mixtures were constructed in all polymorphic forms when Cn differed by 4 and 6.
Spatial Heterodyne Spectroscopy: An Emerging Technology for Interference Spectroscopy (2003)

Spatial Heterodyne Spectroscopy (SHS) stands poised to play a significant role in astrophysics from space and ground-based platforms. Compared with conventional instruments of similar resolving power and sensitivity, the field-widened spatial heterodyne spectrometer is highly compact and robust, has a throughput roughly 10⁴ times higher, and is very forgiving of optical flatness defects. This paper will briefly describe the technique, its advantages, and applications in progress.
The Orientation of Semifluorinated Alkanes Attached to Polymers at the Surface of Polymer Films (2000)

The surface molecular orientation of a liquid crystalline (LC) layer made up of semifluorinated (SF) single side groups [−CO−(CH2)x-1−(CF2)yF] (single SF groups) attached to polyisoprene homopolymer or the isoprene block of a styrene−isoprene diblock copolymer was determined by analyzing the partial electron yield C-edge NEXAFS signal. The results show that the surfaces of thin SF polymer films are covered with a uniform layer, consisting of the SF−LC groups whose average −CF2− tilt angle with the surface normal lies in the range 29−46°. This is in direct contrast to the bulk, where the directors of the SF−LC mesogens are aligned parallel to the polystyrene/SF−polyisoprene interface of the block copolymers. This average tilt angle increases with increasing the length of the −(CH2)x-1− group (x increases) but decreases with increasing the length of the −(CF2)y− part of the molecule (y increases) at constant x.
Patterns of cytokine production in psoriatic synovium. (1998)

The cytokine profile in PsA is characterized by the presence of Th1 cytokines and the monokines TNF-alpha and IL-1beta and very elevated levels of IL-10. The higher levels of these cytokines in PsA compared to RA suggest the presence of different underlying mechanisms.
Architectural flexibility in lambda site‐specific recombination: three alternate conformations channel the attL site into three distinct pathways (1996)

The recombination pathway described in this work apparently uses a unique attL architecture, one which requires bending by IHF and is inhibited by Int bound at the P'1 site. In addition to demonstrating the architectural flexibility of the lambda system, this pathway should be a valuable resource for separating the basic requirements of strand exchange chemistry from the features which impart directionality.