gebhart/patrepeval huggingface dataset:
Reasons for instability of bacterial vaccines. (1996)

Stability problems in relation to bacterial vaccines vary widely between different types of product. Killed whole cell bacterial vaccines including pertussis, cholera and typhoid vaccines generally show a high degree of stability of potency. Reversion to toxicity may occur in incompletely inactivated pertussis vaccines. Live attenuated vaccines such as BCG and Ty21a typhoid vaccines lose potency through loss of viability when exposed to adverse conditions. Both vaccines are susceptible to ultra violet radiation but Ty21a also has low thermal stability. Its fragility is probably a consequence of multiple mutations affecting structural and metabolic factors. Diphtheria and tetanus toxoids generally show high stability of potency. Reversion to toxicity may occur if the toxoiding process is inadequate. Decline in potency may result from exposure to adverse conditions, such as freezing, that affect the interaction with the adjuvant. Similar problems may be encountered with purified subunit vaccines such as acellular pertussis preparations. Some components, in particular pertussis toxin and filamentous haemagglutinin, show inherent low stability and degrade on storage at refrigerator temperatures unless stabilized by a protein cross-linking agent. Bacterial proteases carried over from the cell cultures may also be responsible for degradation of purified components. Purified bacterial polysaccharides usually show high stability if freeze-dried under appropriate conditions. Catalytic degradation may occur however, if the stabilizers are of inadequate purity. Polysaccharide-protein conjugates such as Haemophilus influenzae b (Hib) polyribosylribityl phosphate-protein conjugates show high thermal stability if freeze dried. In the liquid state, such conjugates tend to degrade by hydrolysis of the polysaccharide chains. Combined vaccines may present special stability problems because of the interaction of the various components in the liquid state. It can be difficult to freeze-dry some components of such vaccines, particularly aluminium hydroxide-adsorbed diphtheria-tetanus-pertussis (DTP) components. Slow release vaccines based on polyglycolide-factolide microspheres may show suboptimal stability of encapsulated antigen under both in vitro conditions as a result of gradual acidification through polymer hydrolysis. Vaccines based on the use of live recombinant strains to express heterologous protective antigens may present special stability problems. Apart from the carrier strains, heterologous genes carried on plasmids may be subject to spontaneous deletion under adverse conditions. These issues have received relatively little attention hitherto but are likely to achieve greater prominence as development of such preparations proceeds.
Sticky DNA, a Self-associated Complex Formed at Long GAA·TTC Repeats in Intron 1 of the Frataxin Gene, Inhibits Transcription (2001)

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by the expansion of GAA.TTC repeats in the first intron of the frataxin (X25) gene. FRDA patients carrying two expanded GAA.TTC repeats show very low levels of mature frataxin mRNA and protein. A novel type of unusual DNA structure, sticky DNA, was previously found in the expanded GAA.TTC repeats from FRDA patients. To evaluate the effect of sticky DNA on transcription, in vitro transcription studies of (GAA.TTC)(n) repeats (where n = 9-150) were carried out using T7 or SP6 RNA polymerase. When a gel-isolated sticky DNA template was transcribed, the amount of full-length RNA synthesized was significantly reduced compared with the transcription of the linear template. Surprisingly, transcriptional inhibition was observed not only for the sticky DNA template but also another DNA molecule used as an internal control in an orientation-independent manner. The molecular mechanism of transcriptional inhibition by sticky DNA was a sequestration of the RNA polymerases by direct binding to the complex DNA structure. Moreover, plasmids containing the (GAAGGA.TCCTTC)(65) repeat, which does not form sticky DNA, did not inhibit in vitro transcription, as expected. These results suggest that the role of sticky DNA in FRDA may be the sequestration of transcription factors.
Advancing Cancer Therapy with Present and Emerging Immuno-Oncology Approaches (2017)

Immuno-oncology (I-O) is a young and growing field on the frontier of cancer therapy. Contrary to cancer therapies that directly target malignant cells, I-O therapies stimulate the body's immune system to target and attack the tumor, which is otherwise invisible to, or inhibiting the immune response. To this end, several methods have been developed: First, passive therapies that enable T-cells to fight the tumor without direct manipulation, typically through binding and modifying the intracellular signaling of surface receptors. Checkpoint inhibitors, perhaps the most well known of I-O therapies; are an example of such. These are monoclonal antibodies that block binding of the tumor cell at receptors that inactivate the T-cell. A variety of small molecules can achieve the same effect by affecting metabolic or signaling pathways to boost the immune response or prevent its attenuation. Drugs originally formulated for unrelated disease states are now being used to treat cancer under the I-O approach. Second, active therapies which often involve direct manipulations that occur <i>in vitro</i> and once introduced to the patient will directly attack the tumor. Adoptive cell transfer is the oldest of these methods. It involves the removal of T-cells from the body, which are then expanded and genetically modified for specificity toward tumor-associated antigens (TAAs), and then reintroduced to the patient. A similar approach is taken with cancer vaccines, where TAAs are identified and reintroduced with adjuvants to stimulate an immune response, sometimes in the context of antigen-presenting cells or viral vectors. Oncolytic viruses are genetically modified natural viruses for selectivity toward tumor cells. The resulting cytotoxicity has the potential to elicit an immune response that furthers tumor cell killing. A final active approach is bi-specific T-cell engagers. These modified antibodies act to link a T-cell and tumor cell through surface receptors and thereby forcibly generate immune recognition. The therapies in each of these subfields are all still very new and ongoing clinical trials could provide even further additions. The full therapeutic potential of the aforementioned therapies, alone or in combination, has yet to be realized, but holds great promise for the future of cancer treatment.
[Pulmonary hypertension and obesity]. (2002)

Obesity is a morbid condition with hemodynamic consequences affecting the systemic and pulmonary circulations leading to a risk of pulmonary hypertension. Data in the literature do not argue in favor of a direct relationship between pulmonary hypertension and obesity. These two conditions appear to be two distinct entities, the different co-morbidities observed in obesity favoring pulmonary hypertension. Certain co-morbidities, for instance use of anorexic agents, exhibit a clear relationship with pulmonary hypertension. There is also a possible relationship with left ventricular failure, hypoxemia, and other respiratory disorders (including obstructive sleep apnea), hypothyroidism, and thomboembolism.
High-Performance, Low-Voltage, and Easy-Operable Bending Actuator Based on Aligned Carbon Nanotube/Polymer Composites (2011)

In this work, we show that embedding super-aligned carbon nanotube sheets into a polymer matrix (polydimethylsiloxane) can remarkably reduce the coefficient of thermal expansion of the polymer matrix by two orders of magnitude. Based on this unique phenomenon, we fabricated a new kind of bending actuator through a two-step method. The actuator is easily operable and can generate an exceptionally large bending actuation with controllable motion at very low driving DC voltages (<700 V/m). Furthermore, the actuator can be operated without electrolytes in the air, which is superior to conventional carbon nanotube actuators. Proposed electrothermal mechanism was discussed and confirmed by our experimental results. The exceptional bending actuation performance together with easy fabrication, low-voltage, and controllable motion demonstrates the potential ability of using this kind of actuator in various applicable areas, such as artificial muscles, microrobotics, microsensors, microtransducers, micromanipulation, microcantilever for medical applications, and so on.
Advanced line current differential protection with reduced channel requirements (2010)

Line current differential protection creates challenges for relay design and application. From a design perspective, the distributed nature of the line current differential system imposes limits on the amount of data that can be exchanged between the system terminals and calls for data alignment schemes to enable the differential protection principle. From the application perspective, line current differential schemes are concerned with current transformer (CT) saturation, particularly in dual-breaker applications; in-zone reactors and line-charging current; in-line and tapped transformers; security on channel impairments; application to multiterminal lines; and so on. This paper reviews technical solutions to the line current differential design and application, addressing the common design constraints and application needs. (5 pages)
Cytokines in Chronic Inflammatory Synovitis (1988)

Cytokines likely play a role in the pathogenesis of rheumatoid arthritis and other chronic inflammatory arthritidies. Recent studies on the cytokine profile of inflammatory synovitis have provided insight into the mechanisms of cellular activation in the inflamed joint. Although gamma interferon has been proposed as a major macrophage activating factor and inducer of class II major histocompatibility antigens in the joint, studies using sensitive and specific immunoassays have shown that the concentration of this lymphokine in synovial fluid is probably not sufficient to account for the high level of HLA-DR expression on Type A synoviocytes and macrophages in the joint. In contrast, GM-CSF has recently been identified in synovial effusions of patients with rheumatoid arthritis and is produced by synovial tissue cells in vitro. Like gamma interferon, GM-CSF is a known macrophage activating factor and induces HLA-DR on cells of macrophage lineage. Furthermore, supernatants of cultured synovial tissue cells contain an HLA-DR inducing factor that is neutralized by specific antibodies to GM-CSF but not by antibodies to gamma interferon. These data suggest that GM-CSF plays a significant role in macrophage activation in the synovium.
Sexually-acquired reactive arthritis (2001)

Reactive arthritis is the most frequent cause of acute peripheral arthritis in young men. The aetiopathogenesis of reactive arthritis is reviewed, together with the varied clinical features. Finally the treatment and prognosis of this challenging condition are discussed.
Symptoms and signs caused by neural plasticity (2001)

Plastic changes in the central nervous system are associated with hyperactivity, hypersensitivity, and spread of activity including activation of brain regions that are not typically involved. Symptoms and signs such as neuropathic pain and tinnitus and hyperactive disorders such as muscle spasm and synkinesis may result from such changes in function. Plastic changes that cause symptoms of diseases can be initiated by novel stimulations, overstimulation, or deprivation of input and the induced changes in the function of central nervous system structures may persist and aggravate after these events have ceased if the condition is not reversed. Disorders that are caused by neural plasticity are potentially reversible with treatment. However, the absence of morphologic abnormalities makes diagnosis of these conditions difficult and their treatment has been hampered by lack of understanding of their pathophysiology. Here the role of neural plasticity in the pathophysiology of several disorders is reviewed.
Multi-Task Learning for Voice Trigger Detection (2020)

We describe the design of a voice trigger detection system for smart speakers. In this study, we address two major challenges. The first is that the detectors are deployed in complex acoustic environments with external noise and loud playback by the device itself. Secondly, collecting training examples for a specific keyword or trigger phrase is challenging resulting in a scarcity of trigger phrase specific training data. We describe a two-stage cascaded architecture where a low-power detector is always running and listening for the trigger phrase. If a detection is made at this stage, the candidate audio segment is re-scored by larger, more complex models to verify that the segment contains the trigger phrase. In this study, we focus our attention on the architecture and design of these second-pass detectors. We start by training a general acoustic model that produces phonetic transcriptions given a large labelled training dataset. Next, we collect a much smaller dataset of examples that are challenging for the baseline system. We then use multi-task learning to train a model to simultaneously produce accurate phonetic transcriptions on the larger dataset and discriminate between true and easily confusable examples using the smaller dataset. Our results demonstrate that the proposed model reduces errors by half compared to the baseline in a range of challenging test conditions without requiring extra parameters.
Chapter 2. Thermochemistry (1982)

M. N. Jones and H. A. Skinner, Annu. Rep. Prog. Chem., Sect. C: Phys. Chem., 1982, 79, 3 DOI: 10.1039/PC9827900003
Highly Regioselective Synthesis of Amino-Functionalized Dendritic Polyglycerols by a One-Pot Hydroformylation/Reductive Amination Sequence (2005)

[reaction: see text] Dendritic architectures with neutral core structures and amines groups in the shell are a synthetic challenge, and there is a need for an efficient access. In this paper, highly selective Rh-catalysts are used for sequential hydroformylation/reductive amination of dendritic perallylated polyglycerols 1 with various amines in a one-pot procedure to give dendritic polyamines 3a-e in high yields (73-99%). In all cases, complete conversion of the allyl ether and aldehyde intermediate has been observed. Furthermore, the use of protected amines provides reactive core-shell-type architectures after deprotection. These soluble but membrane filterable multifunctional dendritic polyamines are of high interest as reagents in synthesis or as supports in homogeneous catalysis as well as nonviral vectors for DNA-transfection.
AUTOMATED MALARIA DETECTION (1999)

We agree with most of the points raised by Drs Hänscheid and Valadas. Regarding the reference methods, details of standard procedures were omitted in the interest of brevity, as the main substance of the paper dealt with the white cell pigment method (1). To answer the question, thick films were examined in their entirety before being designated negative. The ability of Para-sight F to detect convalescent malaria is, of course, well known. We find the comments on gametocytes and schizonts useful as we were unable on our data to exclude these as possible contributors towards abnormal white cell distribution profiles encountered in malaria. On the low sensitivity in white patients, we stated in the paper that ‘previous exposure or varied patterns of presentation could account for some of the differences found’. We are thus in agreement with Drs Hänscheid and Valadas on this point as well. With regard to the distribution of automated FBC counters in Africa we agree that in most holo- and hyper-endemic areas such technology is scarce. In these areas, however, malaria is not likely to be overlooked as a possible cause of symptoms. In contrast, in other areas, where the index of suspicion is lower, the availability of automated counters is much higher. In South Africa, for example, there are hundreds of laboratories equipped with automated counters. Finally, we of course agree that the instrument detects convalescent as well as active malaria. Both the Materials and Methods and the Results sections of our paper spelt this out explicitly. It may well also be that some or all of the five cases assigned to the false positive category could have been undiagnosed or convalescent malaria patients, but we were unable to document this. With regard to the specificity and sensitivity figures, whether the truth is defined as acute malaria or combined acute and convalescent malaria, it is clear that the method cannot be regarded as an alternative to existing methods of malaria diagnosis or monitoring, and once again this point was explicitly stressed, this time in the Discussion. It was and remains our conclusion that the main utility of our study was that it drew attention to the potential to make an unexpected diagnosis of active malaria as part of a screening FBC, in some cases. We are of the opinion that in such cases the exercise could well be life-saving, especially as white cell pigment has been associated with adverse prognosis. If the price to be paid for this unexpected bonus is that some practitioners are alerted by the laboratory to a convalescent state of which they are already aware, we do not believe this price to be excessive.
Superaligned Carbon Nanotube Grid for High Resolution Transmission Electron Microscopy of Nanomaterials (2008)

Nano is one of the hottest topics in current science and technology. Characterizations of nanomaterials by high resolution transmission electron microscopy (TEM) are becoming indispensable today. To gain better performance of TEM, people are expecting a novel TEM grid of which the supporting film should be highly conductive, ultrathin but robust, and preferably nanoholey. Here we report a method of mass producing such a kind of carbon nanotube TEM grids. The supporting films are made by cross stacking ultrathin superaligned carbon nanotube films, resulting in a large number of nanosized holes and numerous effective edges. Together with the robustness, good conductivity, and strong adsorbability inherited from carbon nanotubes, these TEM grids show much better performance than conventional amorphous carbon grids.
Vascular endothelial growth factor in coronary sinus: Evidence for its association with coronary collaterals (2005)

The association between local, endogenous secretion of VEGF and coronary collateral formation is compatible with a paracrine role for this growth factor in pathophysiologic collateral formation.
Cathepsin B-related proteases in the insulin secretory granule. (1984)

The distribution of proteases potentially reactive with peptide sequences containing pairs of basic amino acids or single basic amino acids was studied in subcellular fractions of a transplantable rat insulinoma using the affinity probes 125I-Tyr-Ala-Lys- ArgCH2Cl and 125I-Tyr-Ala-norleucine- ArgCH2Cl . Both probes labeled predominantly proteins of Mr = 39,000, 31,500, and 25,000. The Mr = 25,000 component appeared to be of lysosomal origin, while the Mr = 39,000 and 31,500 proteins were present in both the lysosomes and insulin granules. The Mr = 39,000 and 31,500 proteins were identified as precursor/product forms of the cysteine protease cathepsin B, while assays performed with fluorigenic peptide substrates suggested that the Mr = 25,000 protein was probably cathepsin L and/or H. The greater reactivity of the Mr = 39,000 form with the dibasic probe suggests that the relative proportions of the Mr = 39,000 and 31,500 forms of cathepsin B in different organelles may determine the extent to which the enzyme expresses activity as a specific (prohormone processing) endopeptidase or a more general (degradative) peptidase.
ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice (2017)

The Middle East respiratory syndrome coronavirus (MERS-CoV) has infected more than 1900 humans, since 2012. The syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. The virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. Therefore, dromedary camels are considered the only animal source of infection. Neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. Here, we developed four vaccine candidates against MERS-CoV based on ChAdOx1 and MVA viral vectors, two candidates per vector. All vaccines contained the full-length spike gene of MERS-CoV; ChAdOx1 MERS vaccines were produced with or without the leader sequence of the human tissue plasminogen activator gene (tPA) where MVA MERS vaccines were produced with tPA, but either the mH5 or F11 promoter driving expression of the spike gene. All vaccine candidates were evaluated in a mouse model in prime only or prime-boost regimens. ChAdOx1 MERS with tPA induced higher neutralising antibodies than ChAdOx1 MERS without tPA. A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. The humoral immunogenicity of a single dose of ChAdOx1 MERS with tPA was equivalent to two doses of MVA MERS (also with tPA). MVA MERS with mH5 or F11 promoter induced similar antibody levels; however, F11 promoter enhanced the cellular immunogenicity of MVA MERS to significantly higher magnitudes. In conclusion, our study showed that MERS-CoV vaccine candidates could be optimized by utilising different viral vectors, various genetic designs of the vectors, or different regimens to increase immunogenicity. ChAdOx1 and MVA vectored vaccines have been safely evaluated in camels and humans and these MERS vaccine candidates should now be tested in camels and in clinical trials.
Cold- and light-induced changes in the transcriptome of wheat leading to phase transition from vegetative to reproductive growth (2009)

Phase transition in wheat is more complex than previously reported, and there is evidence that day-length has an influence on genes that were once thought to respond exclusively to an extended period of cold.
Multiscale studies of the three-dimensional dayside X-line (2012)

We review recent experience from the Cluster, Double Star, and THEMIS missions for lessons that apply to the upcoming Magnetospheric Multiscale Mission (MMS) being developed for launch in 2014. On global scales, simulation and statistical studies lead to mean configurations of dayside reconnection, implying specific relative alignments of the inflow magnetic fields and X-line, with implications for MMS operations designed to maximize the number of close encounters with the diffusion region. At intermediate MHD-to-ion scales, reconstruction of features created by one or two X-lines have developed to the point where data from a cluster of spacecraft can determine their temporal trends and the approximate three-dimensional X-line structure. Recent petascale particle-in-cell (PIC) simulations of reconnection encompass three spatial dimensions with excellent resolution, and make striking predictions of electron scale physics that creates complex interacting flux ropes under component reconnection. High time resolution measurements from MMS will determine the detailed electron scale kinetics embedded within the global and MHD–ion scale contexts. These developments will lead to the refinement of our three-dimensional multiscale picture of reconnection, yielding improved understanding of the global, MHD, and local physics controlling the onset or quenching, variability, and mean rate of reconnection. This in turn will enable improved predictability of the structural features created by transient reconnection, and their space weather consequences.