gebhart/patrepeval huggingface dataset:
Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America (2011)

This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving. What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens. Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care-associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.
Oxidative burst and anticancer activities of rat neutrophils (2005)

It is assumed that oxidative damage caused by reactive oxygen species (ROS) from activated neutrophil granulocytes may contribute to pathology of tumors. ROS are crucial in neutrophil-mediated tumor cell lysis. The present study is focused on the oxidative burst and antitumorous activities of neutrophils when challenged with Walker carcinoma W256. Survival and tumor growth dynamics were monitored in vivo, while tumor cell proliferation when mixed with neutrophils was studied in vitro together with the generation/release of neutrophil respiratory burst products, primarily 1O2. Neutrophils were collected upon Sephadex injection. The survival of Sephadex injected animals was slightly improved, while their tumors grew less than in controls. The presence of tumor cells in vitro activated neutrophils to produce singlet oxygen similar to phorbol ester. Neutrophils from Sephadex-bearing animals diminished tumor cell proliferation in vitro (measured by 3H-TdR incorporation), while neutrophils from Sephadex and the tumor-bearing animals did not show such activity in vitro. Our results confirm that in the case of rapidly growing tumors such as murine W256 carcinoma neutrophils have antitumorous effects in the early phase of tumor development.
Fermentation and Sulfur Reduction in the Mat-Building Cyanobacterium Microcoleus chthonoplastes (1996)

The mat-building cyanobacterium Microcoleus chthonoplastes carried out a mixed-acid fermentation when incubated under anoxic conditions in the dark. Endogenous storage carbohydrate was fermented to acetate, ethanol, formate, lactate, H(inf2), and CO(inf2). Cells with a low glycogen content (about 0.3 (mu)mol of glucose per mg of protein) produced acetate and ethanol in equimolar amounts. In addition to glycogen, part of the osmoprotectant, glucosyl-glycerol, was degraded. The glucose component of glucosyl-glycerol was fermented, whereas glycerol was released into the medium. Cells with a high content of glycogen (about 2 (mu)mol of glucose per mg of protein) did not utilize glucosyl-glycerol. These cells produced more acetate than ethanol. M. chthonoplastes was also capable of using elemental sulfur as the electron acceptor during fermentation, resulting in the production of sulfide. With sulfur present, acetate production increased whereas ethanol production decreased. Also, less formate was produced and the evolution of hydrogen ceased completely. In general, the carbon recoveries were satisfactory but the oxidation-reduction balances were too high. The latter could be explained by assuming the reduction of ferric iron, which is associated with the cells, mediated by the oxidation of formate. The switch from photoautotrophic to fermentative metabolism did not require de novo protein synthesis, and fermentation started immediately upon transfer to dark anoxic conditions. From the molar ratios of the fermentation products and from measurement of enzyme activities in cell extracts, we concluded that glucose derived from glycogen and glucosyl-glycerol is degraded via the Embden-Meyerhof-Parnas pathway.
On channel capacity of OFDM with SLM method for PAPR reduction (2006)

One major drawback of OFDM is the large Peak to Average Power Ratio (PAPR). OFDM is a linear modulation, therefore large PAPR requires large linear dynamic range of the transmitter (TX) as well as the receiver (RX) paths. The weak point in the TX-RX chain is the Power Amplifier (PA). As known, a linear PA which is able to amplify signals with large PAPR has to have a large dynamic range that results with low power efficiency, thus by reducing PAPR one may improve the efficiency of PA. A PAPR reducing method in OFDM, based on SeLective Mapping (SLM) is considered. As known, SLM requires transmitting a Side Information (SI). Increasing the SLM order reduces the PAPR but increases the size of SI. In order to transmit the SI some power and bandwidth are needed, those are taken from the total power and bandwidth budget and thus lowering the capacity. On the other hand the reduced PAPR improves the PA efficiency, thus increases the channel capacity. Accordingly maximal value of channel capacity is expected as well as an optimal SLM order.
Development and validation of an audit instrument: the Prostate Outcomes Questionnaire (1998)

The POQ is a practical and scientifically sound patient-based measure of outcome after treatment for BPH which can be used for routine audit. It takes < 5 min to complete, is feasible for routine monitoring of large numbers of patients by postal survey, and is accompanied by a Users' Manual which provides practical help in conducting a local patient survey, and a computer program for scoring data. Most importantly, the POQ has been shown scientifically to perform well, having met standard psychometric criteria for reliability and validity.
T cell stemness and dysfunction in tumors are triggered by a common mechanism (2019)

A paradox of tumor immunology is that tumor-infiltrating lymphocytes are dysfunctional in situ, yet are capable of stem cell-like behavior including self-renewal, expansion, and multipotency, resulting in the eradication of large metastatic tumors. We find that the overabundance of potassium in the tumor microenvironment underlies this dichotomy, triggering suppression of T cell effector function while preserving stemness. High levels of extracellular potassium constrain T cell effector programs by limiting nutrient uptake, thereby inducing autophagy and reduction of histone acetylation at effector and exhaustion loci, which in turn produces CD8<sup>+</sup> T cells with improved in vivo persistence, multipotency, and tumor clearance. This mechanistic knowledge advances our understanding of T cell dysfunction and may lead to novel approaches that enable the development of enhanced T cell strategies for cancer immunotherapy.
The fate of phenothiazine-based redox shuttles in lithium-ion batteries (2015)

The stability and reactivity of the multiple oxidation states of aromatic compounds are critical to the performance of these species as additives and electrolytes in energy-storage applications. Both for the overcharge mitigation in ion-intercalation batteries and as electroactive species in redox flow batteries, neutral, radical-cation, and radical-anion species may be present during charging and discharging processes. Despite the wide range of compounds evaluated for both applications, the progress identifying stable materials has been slow, limited perhaps by the overall lack of analysis of the failure mechanism when a material is utilized in an energy-storage device. In this study, we examined the reactivity of phenothiazine derivatives, which have found interest as redox shuttles in lithium-ion battery applications. We explored the products of the reactions of neutral compounds in battery electrolytes and the products of radical cation formation using bulk electrolysis and coin cell cycling. Following the failure of each cell, the electrolytes were characterized to identify redox shuttle decomposition products. Based on these results, a set of decomposition mechanisms is proposed and further explored using experimental and theoretical approaches. The results highlight the necessity to fully characterize and understand the chemical degradation mechanisms of the redox species in order to develop new generations of electroactive materials.
Discovery of 2-Phenylamino-imidazo[4,5-h]isoquinolin-9-ones:  A New Class of Inhibitors of Lck Kinase (2002)

An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to understand how 1 binds to a related kinase, hck. These results suggested that removing the gem-dimethyl group and flattening the ring would enhance activity. This was realized by converting 1 to the imidazo[4,5-h]isoquinolin-9-one (20), resulting in an 18-fold improvement in potency against lck and a 50-fold increase in potency in a cellular assay.
Nerve Growth Factor Activates Mast Cells Through the Collaborative Interaction with Lysophosphatidylserine Expressed on the Membrane Surface of Activated Platelets (2002)

Effect of nerve growth factor (NGF) on platelet-associated mast cell activation was investigated. Although neither NGF alone nor platelets alone induced significant 5-hydroxytriptamine (5-HT) release from rat peritoneal mast cells, marked 5-HT release was detected when costimulated with NGF and calcium ionophore-activated platelets. This response reached maximal levels as early as 5 min after the initiation of the coincubation and was completely blocked by anti-NGF Ab or by an inhibitor for a tyrosine kinase of the trkA NGF receptor. Paraformaldehyde-fixed platelets activated with either calcium ionophore or thrombin exhibited the collaborative ability, suggesting the possible involvement of some membrane molecules expressed on activated platelets in mast cell activation. Because activation of platelets induced expression of phosphatidylserine (PS) and/or lysoPS on membrane surface, and since lysoPS, unlike PS, initiated the NGF-induced 5-HT release, lysoPS expressed on activated platelets may be involved in the mast cell activation. Moreover, intradermal injection of NGF and activated platelets into the rat skin increased local vascular permeability. These findings suggested that NGF collaboratively worked with membrane lysoPS of activated platelets to induce mast cell activation. Thus, NGF released in response to inflammatory stimuli may contribute to mast cell activation in collaboration with locally activated platelets in the process of inflammations and tissue repair.
Architectural Requirements for the Effective Support of Adaptive Mobile Applications (2000)

Mobile applications are required to operate in environments that change. Specifically, the availability of resources and services may change significantly during typical system operation. As a consequence, mobile applications need to be capable of adapting to these changes to ensure they offer the best possible level of service to the user. Our experiences of developing adaptive applications have led us to believe that existing middleware fails to provide the necessary support for such applications. Moreover, we believe that current research in this area is also failing to address the core requirements of adaptive mobile systems. In this paper we present a set of requirements for future mobile middleware which have been derived by considering the shortcomings of existing approaches and the needs of application developers. Key among these requirements is the need to support coordinated action between application and system components and the resolution of conflicts caused by the need to adapt to multiple contextual triggers. The paper concludes with the presentation of an architectural framework within which middleware researchers can deploy solutions to the problems identified.
Role of platelet-derived growth factors in mouse development (1995)

The current understanding of platelet-derived growth factor (PDGF) physiological functions in vivo is discussed in the context of mouse development. In particular, the review focuses on recent experiments in which genetic approaches have been applied in order to mutate the PDGF and PDGF receptor genes in the mouse. Thus, the PDGF-B and PDGF beta receptor (PDGFRb) genes were recently inactivated by homologous recombination in embryonic stem cells. Their phenotypes are highly similar, displaying cardiovascular, hematological and renal defects. The latter is particularly interesting since it consists of a specific cellular defect: the complete loss of kidnety glomerular mesangial cells. As such, the phenotype not only sheds light on the developmental importance of PDGF-B-PDGFRb interactions, but also reveals information about the function of mesangial cells. Based on detailed morphological studies of mutant glomeruli and the absence of urine collection in the urinary bladder, I propose that the mesangial cells function as interior "filter holders", the "filter" consisting of the glomerular basement membrane and associated cell types. The filter holder model would predict that glomerular filtration is critically dependent on an interior structural support of the filter, which is normally provided by the mesangial cells and the mesangial matrix. In addition to the mutants generated by gene targeting, the mouse patch mutation is discussed. This deletion encompasses the PDGFRa locus. The last part of the review focuses on the problems encountered when interpreting gene knockout phenotypes in the physiological functions of gene products.
The rationale for intensity-modulated proton therapy in geometrically challenging cases (2013)

Intensity-modulated proton therapy (IMPT) delivered with beam scanning is currently available at a limited number of proton centers. However, a simplified form of IMPT, the technique of field 'patching', has long been a standard practice in proton therapy centers. In field patching, different parts of the target volume are treated from different directions, i.e., a part of the tumor gets either full dose from a radiation field, or almost no dose. Thus, patching represents a form of binary intensity modulation. This study explores the limitations of the standard binary field patching technique, and evaluates possible dosimetric advantages of continuous dose modulations in IMPT. Specifics of the beam delivery technology, i.e., pencil beam scanning versus passive scattering and modulation, are not investigated. We have identified two geometries of target volumes and organs at risk (OAR) in which the use of field patching is severely challenged. We focused our investigations on two patient cases that exhibit these geometries: a paraspinal tumor case and a skull-base case. For those cases we performed treatment planning comparisons of three-dimensional conformal proton therapy (3DCPT) with field patching versus IMPT, using commercial and in-house software, respectively. We also analyzed the robustness of the resulting plans with respect to systematic setup errors of ±1 mm and range errors of ±2.5 mm. IMPT is able to better spare OAR while providing superior dose coverage for the challenging cases identified above. Both 3DCPT and IMPT are sensitive to setup errors and range uncertainties, with IMPT showing the largest effect. Nevertheless, when delivery uncertainties are taken into account IMPT plans remain superior regarding target coverage and OAR sparing. On the other hand, some clinical goals, such as the maximum dose to OAR, are more likely to be unmet with IMPT under large range errors. IMPT can potentially improve target coverage and OAR sparing in challenging cases, even when compared with the relatively complicated and time consuming field patching technique. While IMPT plans tend to be more sensitive to delivery uncertainties, their dosimetric advantage generally holds. Robust treatment planning techniques may further reduce the sensitivity of IMPT plans.
Time-resolved fluorescence and photon migration studies in biomedical and model random media (1997)

This review highlights time-resolved fluorescence kinetics and photon transport in tissues and other biomedical media with a special emphasis on ultrafast measurements of key optical parameters. Measurements of fluorescence decay lifetimes from human breast and atherosclerotic artery tissues in the uv and visible region are described after a brief description of fundamentals of fluorescence kinetics. A time-dependent diffusion model for photon migration and various ultrafast methods for time-resolved light scattering measurements to obtain key optical parameters of tissues and other model turbid media are presented. The usefulness of optical parameters as markers in optical diagnostics and imaging is considered. Time-gated measurements of ballistic and snake photons to obtain shadowgrams and an inverse numerical reconstruction of the interior map of a turbid medium from time-resolved data in the context of optical tomography are presented.
DaiMoN: A Decentralized Artificial Intelligence Model Network (2019)

We introduce DaiMoN, a decentralized artificial intelligence model network, which incentivizes peer collaboration in improving the accuracy of machine learning models for a given classification problem. It is an autonomous network where peers may submit models with improved accuracy and other peers may verify the accuracy improvement. The system maintains an append-only decentralized ledger to keep the log of critical information, including who has trained the model and improved its accuracy, when it has been improved, by how much it has improved, and where to find the newly updated model. DaiMoN rewards these contributing peers with cryptographic tokens. A main feature of DaiMoN is that it allows peers to verify the accuracy improvement of submitted models without knowing the test labels. This is an essential component in order to mitigate intentional model overfitting by model-improving peers. To enable this model accuracy evaluation with hidden test labels, DaiMoN uses a novel learnable Distance Embedding for Labels (DEL) function proposed in this paper. Specific to each test dataset, DEL scrambles the test label vector by embedding it in a low-dimension space while approximately preserving the distance between the dataset's test label vector and a label vector inferred by the classifier. It therefore allows proof-of-improvement (PoI) by peers without providing them access to true test labels. We provide analysis and empirical evidence that under DEL, peers can accurately assess model accuracy. We also argue that it is hard to invert the embedding function and thus, DEL is resilient against attacks aiming to recover test labels in order to cheat. Our prototype implementation of DaiMoN is available at https://github.com/steerapi/daimon.
Expanding and understanding the CRISPR toolbox for Bacillus subtilis with MAD7 and dMAD7 (2020)

The CRISPR-Cas9 system has become increasingly popular for genome engineering across all fields of biological research, including in the Gram-positive model organism Bacillus subtilis. A major drawback for the commercial use of Cas9 is the IP landscape requiring a license for its use, as well as reach-through royalties on the final product. Recently an alternative CRISPR nuclease, free to use for industrial R&D, MAD7 was released by Inscripta (CO). Here we report the first use of MAD7 for gene editing in B. subtilis, in which editing rates of 93% and 100% were established. Additionally, we engineer the first reported catalytically inactive MAD7 (dMAD7) variant (D877A, E962A, and D1213A) and demonstrate its utility for CRISPR interference (CRISPRi) at up to 71.3% reduction of expression at single and multiplexed target sites within B. subtilis. We also confirm the CRISPR-based editing mode of action in B. subtilis providing evidence that the nuclease-mediated DNA double-strand break acts as a counterselection mechanism after homologous recombination of the donor DNA.
Chronic Exposure to a TLR Ligand Injures Hematopoietic Stem Cells (2011)

Hematopoietic stem cells (HSC) can be harmed by disease, chemotherapy, radiation, and normal aging. We show in this study that damage also occurs in mice repeatedly treated with very low doses of LPS. Overall health of the animals was good, and there were relatively minor changes in marrow hematopoietic progenitors. However, HSC were unable to maintain quiescence, and transplantation revealed them to be myeloid skewed. Moreover, HSC from treated mice were not sustained in serial transplants and produced lymphoid progenitors with low levels of the E47 transcription factor. This phenomenon was previously seen in normal aging. Screening identified mAbs that resolve HSC subsets, and relative proportions of these HSC changed with age and/or chronic LPS treatment. For example, minor CD150(Hi)CD48(-) populations lacking CD86 or CD18 expanded. Simultaneous loss of CD150(Lo/-)CD48(-) HSC and gain of the normally rare subsets, in parallel with diminished transplantation potential, would be consistent with age- or TLR-related injury. In contrast, HSC in old mice differed from those in LPS-treated animals with respect to VCAM-1 or CD41 expression and lacked proliferation abnormalities. HSC can be exposed to endogenous and pathogen-derived TLR ligands during persistent low-grade infections. This stimulation might contribute in part to HSC senescence and ultimately compromise immunity.
ChemInform Abstract: Diphenylpropionic Acids as New AT1 Selective Angiotensin II Antagonists. (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.