gebhart/patrepeval huggingface dataset:
Mechanical Ventilation and the Kidney (2009)

Acute lung injury (ALI) and acute kidney injury (AKI) are complications often encountered in the setting of critical illness. Both forms of end-organ injury commonly occur in similar settings of systemic inflammatory response syndrome, shock, and evolving multiple organ dysfunction. Recent elucidation of the pathobiology of critical illness has led to a more basic mechanistic understanding of the complex interplay between injured organs in patients with multiple organ dysfunction syndrome; this has been aptly called 'the slippery slope of critical illness' [Kidney Int Suppl 1998;66:S25-S33]. Distant organ effects of apparently isolated injuries to the lungs, gut, and kidneys have all been discovered in recent years. In this article, we will review the harmful bidirectional interaction between ALI and AKI, which appears to be a common clinical syndrome with routine clinical implications. We will review the current understanding of lung-kidney interactions from both perspectives, including the renal effects of ALI and mechanical ventilation, and the pulmonary sequelae of AKI. In this review of the emerging evidence of deleterious bidirectional organ cross talk between lung and kidney, we will focus on the role of ventilator-induced kidney injury in the pathogenesis of AKI in patients with ALI.
Remote control and robots: an Internet solution (1996)

The development of remote control is discussed with reference to the control of robots. The new opportunities for control that are offered by the Internet are evaluated and the range of potential applications are considered. The specification of remotely controlled instrumentation is investigated and the concept of autonomy and supervisory control is discussed with particular reference to the Bradford Robotic Telescope.
Clinical resistance to the kinase inhibitor STI-571 in chronic myeloid leukemia by mutation of Tyr-253 in the Abl kinase domain P-loop (2002)

The Abl tyrosine kinase inhibitor STI-571 is effective therapy for stable phase chronic myeloid leukemia (CML) patients, but the majority of CML blast-crisis patients that respond to STI-571 relapse because of reactivation of Bcr-Abl signaling. Mutations of Thr-315 in the Abl kinase domain to Ile (T315I) were previously described in STI-571-resistant patients and likely cause resistance from steric interference with drug binding. Here we identify mutations of Tyr-253 in the nucleotide-binding (P) loop of the Abl kinase domain to Phe or His in patients with advanced CML and acquired STI-571 resistance. Bcr-Abl Y253F demonstrated intermediate resistance to STI-571 in vitro and in vivo when compared with Bcr-Abl T315I. The response of Abl proteins to STI-571 was influenced by the regulatory state of the kinase and by tyrosine phosphorylation. The sensitivity of purified c-Abl to STI-571 was increased by a dysregulating mutation (P112L) in the Src homology 3 domain of Abl but decreased by phosphorylation at the regulatory Tyr-393. In contrast, the Y253F mutation dysregulated c-Abl and conferred intrinsic but not absolute resistance to STI-571 that was independent of Tyr-393 phosphorylation. The Abl P-loop is a second target for mutations that confer resistance to STI-571 in advanced CML, and the Y253F mutation may impair the induced-fit interaction of STI-571 with the Abl catalytic domain rather than sterically blocking binding of the drug. Because clinical resistance induced by the Y253F mutation might be overcome by dose escalation of STI-571, molecular genotyping of STI-571-resistant patients may provide information useful for rational therapeutic management.
Interferon gamma inhibits apoptotic cell death in B cell chronic lymphocytic leukemia. (1993)

The malignant, CD5+ B lymphocytes of B cell chronic lymphocytic leukemia (B-CLL) die by apoptosis in vitro. This is in contrast to the prolonged life span of the leukemic cells in vivo and likely reflects the lack of essential growth factors in the tissue culture medium. We found that interferon gamma (IFN-gamma) inhibits programmed cell death and promotes survival of B-CLL cells in culture. This effect may also be important in vivo: increased serum levels of IFN-gamma, ranging from 60 to > 2,200 pg/ml, were found in 7 of 10 B-CLL samples tested, whereas the sera of 10 healthy individuals did not contain detectable levels of this cytokine (< 20 pg/ml). High levels of IFN-gamma message were detected in RNA from T cell-depleted B-CLL peripheral blood samples by Northern blot analysis. Synthesis of IFN-gamma by B-CLL lymphocytes was confirmed by in situ hybridization and flow cytometry. The majority of B-CLL cells (74-82%) expressed detectable levels of IFN-gamma mRNA, and CD19+ B-CLL cells were labeled with anti-IFN-gamma monoclonal antibodies. These results show that IFN-gamma inhibits programmed cell death in B-CLL cells and suggest that the malignant cells are able to synthesize this cytokine. By delaying apoptosis, IFN-gamma may extend the life span of the malignant cells and thereby contribute to their clonal accumulation.
ICA-based Clustering of Genes from Microarray Expression Data (2003)

We propose an unsupervised methodology using independent component analysis (ICA) to cluster genes from DNA microarray data. Based on an ICA mixture model of genomic expression patterns, linear and nonlinear ICA finds components that are specific to certain biological processes. Genes that exhibit significant up-regulation or down-regulation within each component are grouped into clusters. We test the statistical significance of enrichment of gene annotations within each cluster. ICA-based clustering outperformed other leading methods in constructing functionally coherent clusters on various datasets. This result supports our model of genomic expression data as composite effect of independent biological processes. Comparison of clustering performance among various ICA algorithms including a kernel-based nonlinear ICA algorithm shows that nonlinear ICA performed the best for small datasets and natural-gradient maximization-likelihood worked well for all the datasets.
Differentiation of Naive CTL to Effector and Memory CTL: Correlation of Effector Function with Phenotype and Cell Division (1998)

Phenotypically and functionally, the early steps of T cell differentiation are not well characterized. In addition, the effector T cell stage shares several phenotypic characteristics with memory T cells, which has made the analysis of T cell memory difficult. In this study, we have investigated in vitro and in vivo the differentiation of naive CTL into effector and memory CTL as a function of cell division using lymphocytic choriomeningitis virus-specific TCR-transgenic spleen cells labeled with the vital dye carboxyfluorescein diacetate, succinimidyl ester. The following major points emerged. 1) During the first nine cell divisions, the investigated cell surface markers were strongly modulated. 2) The TCR was stepwise down-regulated during viral infection. 3) Cytotoxic effector function was acquired within one cell division and was retained during the next four to five divisions. 4) In vitro, CTL reached a CD44highCD62L+ memory phenotype after 6-10 cell divisions and required restimulation to exert effector function. 5) Lymphocytic choriomeningitis virus memory mice contained two distinct memory populations: a CD44highCD62L- population, predominately located in the spleen and exerting rapid effector function, and a CD44highCD62L+ population found in the spleen and the lymph nodes, which had lost immediate effector function. This finding suggests that two types of memory CTL exist. The correlation between CD62L expression, effector function, and Ag persistence is discussed.
Impact of Circulating Free Tumor Cells in the Peripheral Blood of Colorectal Cancer Patients during Laparoscopic Surgery (2004)

Despite widespread use of laparoscopic surgery for colorectal operations, its application for curative resection of colorectal cancer is still controversial. One of the major concerns is the impact of the laparoscopic procedure on dissemination of tumor cells. The main purpose of this study was to investigate the impact of laparoscopic surgery on circulating tumor cells in colorectal cancer patients. Quantitation of circulating free tumor cells (FTCs) was performed preoperatively, during the operation, and 14 days later by means of real-time quantitative reverse transcriptasepolymerase chain reaction (RT-PCR) targeting guanylyl cyclase C (GCC) mRNA in 42 colorectal cancer patients undergoing laparoscopic resections. Despite an increasing trend of FTC detection in patients with advancing stage, there is no significant difference in the preoperative FTC level by disease stage. No elevation in FTC level was found during the laparoscopic procedure in most patients compared with their preoperative FTC value. Patients with a persistently high FTC load [per nucleated blood cells (NBCs)] (> 10(2) FTCs/10(6) NBCs) 2 weeks postoperatively portends a poor prognosis regarding disease recurrence and tumor-related mortality when compared to those with an undetectable or low FTC load (< or = 10(2) FTCs/10(6) NBCs). We concluded that the laparoscopic procedure itself had no significantly deleterious effect on circulating FTCs and that the detection of FTCs by real-time qRT-PCR might be of clinical importance during the postoperative follow-up for colorectal cancer patients.
GM-CSF and IL-4 Derived Fusion Cytokine Reprograms Leukemic B-Cells to Anti-CLL Effectors (2012)

Abstract Abstract 4606 Fusion cytokines derived from GM-CSF and common γ-chain interleukins have potent gain-of-function properties to alter host immune response. Considering leukemic B cells from chronic lymphocytic leukemia (CLL) patients broadly express the IL-4 receptor, we generated a human GM-CSF and IL-4 derived fusokine GIFT4 to test its immune function on CLL-B cells. Unexpectedly, GIFT4 protein reprograms leukemic B cells into anti-CLL effectors with T-helper features. We show that GIFT4 recombinant protein led to IL4R-dependent hyper-phosphorylation of STAT5 in primary human CLL cells. GIFT4 treated CLL B-cells also up-regulated the expression of co-stimulatory molecules CD40, CD80 and CD86. These cells also secreted IL-1b, IL-6, ICAM1 and substantial IL-2. GIFT4-CLL B cells further propelled the expansion of IFN-g-producing CD314+ autologous cytotoxic NK and T cells in vitro. Administration of GIFT4 protein in NSG immune deficient mice decreased the survival of primary CLL cells from patients in murine circulation. Altogether, our data demonstrate that GIFT4 has potent anti-CLL immune function by reprograming leukemic B cells into anti-CLL helper cells. We propose that the newly bio-engineered fusokine GIFT4 could serve as a potential immunotherapeutic for CLL treatment. Disclosures: Flowers: Genentech: Membership on an entity's Board of Directors or advisory committees.
Characterization of the 17 strains of regulatory T cell-inducing human-derived Clostridia (2014)

The gut microbiota plays important roles in the development of the host immune system. We have previously shown that a combination of 46 strains of commensal Clostridia isolated from conventionally reared mice can induce the accumulation of CD4(+)Foxp3(+) regulatory T (Treg) cells in the mouse colonic lamina propria. Subsequently, we succeeded in isolating and selecting 17 strains of Clostridia from a healthy human fecal sample that can significantly increase the number and function of colonic Treg cells in colonized rodents, thereby attenuating symptoms of experimental allergic diarrhea and colitis. Here we characterize each of the 17 strains of human-derived Clostridia in terms of sensitivity to antibiotics and ability to produce short chain fatty acids and other metabolites, and discuss their potential as biotherapeutics to correct dysbiosis and treat immune-inflammatory diseases.
Antibiotics for treating bacterial vaginosis in pregnancy (2007)

Antibiotic treatment can eradicate bacterial vaginosis in pregnancy. This review provides little evidence that screening and treating all pregnant women with asymptomatic bacterial vaginosis will prevent PTB and its consequences. However, there is some suggestion that treatment before 20 weeks' gestation may reduce the risk of PTB. This needs to be further verified by future trials.
Automated Aircraft Trajectory Prediction Based on Formal Intent-Related Language Processing (2013)

This paper proposes a new paradigm for the formulation of aircraft trajectory computation and prediction processes. Under this paradigm, an aircraft trajectory can be expressed at different levels of detail using a set of novel intent-related formal languages. These languages can be used for describing different aspects of aircraft motion or the resulting predicted trajectory, ranging from high-level restrictions imposed on the trajectory to details on how the aircraft will be operated at any specific instant. After defining the complete hierarchy of these formal languages, the concept of trajectory language processing engine is introduced. Every engine can perform automated modifications over a trajectory specified at different levels or at the same level considering the language hierarchy. Finally, several engine examples are described, and a complete trajectory computation process is built as an engine composed through the smart interconnection of several engines. Examples of executions of these automated processes are also included.
The Pretreatment Effect of Chemical Skin Penetration Enhancers in Transdermal Drug Delivery Using Iontophoresis (1999)

The transdermal drug delivery (TDD) system has largely been divided into physical, biochemical and chemical methods. Recently, combinations of these methods were introduced for more effective delivery with less side effects. We performed this study to identify the effectiveness and mechanism of TDD using the physical method, 'iontophoresis', plus the chemical method, 'pretreatment with chemical enhancer'. The action sites of chemical enhancers in the stratum corneum (SC) were observed by electron microscope. We also studied whether this combined method synergistically impaired the skin barrier. To confirm the synergistic effect on skin penetration by this combined method, we measured the blood glucose level after insulin iontophoresis following a chemical enhancer pretreatment in rabbits. The results were that (1) dilatation of the intercellular lipid layers of the SC and lacunae was prominent in pretreatment with chemical enhancers inducing high transepidermal water loss (TEWL); (2) the skin barrier impairment, with repeated treatments showing an increased TEWL and also epidermal proliferation, was increased with the chemical enhancers that showed a high TEWL immediately after treatment; (3) the combination of chemical enhancer pretreatment and iontophoresis showed no synergistic impairment of the skin barrier, and (4) the chemical enhancer pretreatment with greater impairment of the skin barrier could increase the delivery of insulin by iontophoresis. The results showed that a combination of chemical enhancer pretreatment and iontophoresis could deliver drugs more effectively than iontophoresis alone. Our proposed theory is that iontophoretic drug delivery may be easier through the dilated intercellular spaces of the SC which have a lower electrical impedance following the chemical enhancer pretreatment. Because the effect and the side effects in the combination are decided by the chemical enhancer rather than iontophoresis, the development of proper chemical enhancers is important in future plans.
Internet Traffic: Visualising and Analysing Congestion in a Global Network (2007)

Global Internet traffic can be modelled by a set of equations describing the periodicity of the time-based distributions of congestion. Congestion can be generated, firstly, by peak traffic from different time zones or secondly, by inadequacies within the regional network. The model is a dynamic form of spatial interaction modelling and can investigate the time delay of pings and packet loss at routers. The model is tested using data generated from a global network compiled by the Stanford Linear Accelerator Centre (SLAC) from 1998 to 2004. Examples are used from the US and Australia to show the problems that this country has experienced in the past from either the 'tyranny of distance', an 'island effect' or inadequate investment in capacity. Sites can be classified relative to a regression line standardised relative to the rotation of the Earth. There is also a limit to transferring information by the Internet and this is expressed as an inequality underpinned by the speed of light. Despite a significant rise in demand, the capacity of the Internet had increased, particularly within 1000km of the monitoring sites, from large scale regional investment in infrastructure. This investment has seen a considerable improvement in performance for the Internet from 2000 to 2004.
Characterization of Streptococcus thermophilus Host Range Phage Mutants (2006)

To investigate phage-host interactions in Streptococcus thermophilus, a phage-resistant derivative (SMQ-301R) was obtained by challenging a Tn917 library of phage-sensitive strain S. thermophilus SMQ-301 with virulent phage DT1. Mutants of phages DT1 and MD2 capable of infecting SMQ-301 and SMQ-301R were isolated at a frequency of 10(-6). Four host range phage mutants were analyzed further and compared to the two wild-type phages. Altogether, three genes (orf15, orf17, and orf18) contained point mutations leading to amino acid substitutions and were responsible for the expanded host range. These three proteins were also identified in both phages by N-terminal sequencing and/or matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. The results suggest that at least three phage structural proteins may be involved in phage-host interactions in S. thermophilus.
Hematopoietic Progenitor Kinase 1 Is a Component of Transforming Growth Factor β-induced c-Jun N-terminal Kinase Signaling Cascade (1999)

The c-Jun N-terminal kinase (JNK) signaling pathway is involved in transforming growth factor beta (TGF-beta) signaling in a variety of cell systems. We report here that hematopoietic progenitor kinase 1 (HPK1), a novel Ste20-like protein serine/threonine kinase, serves as an upstream mediator for the TGF-beta-activated JNK1 cascade in 293T cells. TGF-beta treatment resulted in a time-dependent activation of HPK1, which was accompanied by similar kinetics of JNK1 activation. The activation of JNK1 by TGF-beta was abrogated by a kinase-defective HPK1 mutant but not by a kinase-defective mutant of kinase homologous to Ste20/Sps1. This result indicates that HPK1 is specifically required for TGF-beta-induced activation of JNK1. We also found that TGF-beta-induced JNK1 activation was blocked by a kinase-defective mutant of TGF-beta-activated kinase 1 (TAK1). In addition, interaction between HPK1 and TAK1 was observed in transient transfection assays, and this interaction was enhanced by TGF-beta treatment. Both stress-activated protein kinase/extracellular signal-regulated kinase kinase (SEK) and mitogen-activated protein kinase kinase 7 (MKK7) are immediate upstream activators of JNK1. Although SEK and MKK7 acted downstream of TAK1, only a kinase-defective SEK mutant blocked TGF-beta-induced activation of JNK1, indicating that the TGF-beta signal is relayed solely through SEK, but not MKK7, in vivo. Furthermore, TGF-beta-induced activating protein 1 activation was blocked by a HPK1 mutant, as well as by TAK1 and SEK mutants. Taken together, these studies establish a potential cascade of TGF-beta-activated interacting kinases beginning with HPK1, a Ste20 homolog, and ending in JNK1 activation: HPK1 --> TAK1 --> SEK --> JNK1.
High‐affinity immunoglobulin E receptor (FcεRI)‐bearing eosinophils, mast cells, macrophages and Langerhans’ cells in allergen‐induced late‐phase cutaneous reactions in atopic subjects (1998)

We have used in situ hybridization (ISH) and immunohistochemistry (IHC) to investigate the kinetics of the expression for Fc epsilon RI mRNA (alpha-, beta- and gamma-chains), the alpha-chain protein product, as well as the phenotype of the mRNA- or protein-positive cells in allergen-induced late-phase skin reactions in atopic subjects. Compared with diluent controls, there were significant increases in the total number of mRNA+ cells for the alpha-, beta- and gamma-chains for Fc epsilon RI at all time-points (6, 24 and 48 hr) after allergen challenge (P < 0.01). By double IHC/ISH significant increases in alpha-, beta- and gamma-chain mRNA+ macrophages, eosinophils, mast cells and CD1a+ cells were also observed after allergen challenge (P < 0.05). The distribution of Fc epsilon RI subunit (alpha-, beta-, or gamma-chain) mRNA+ co-localization was CD68+ macrophages (42-47%), EG2+ eosinophils (33-39%), tryptase+ mast cells (5-11%) and CD1a+ Langerhans' cells (2-4%). Using single IHC, significant increases in the total number of Fc epsilon RI protein+ cells (P < 0.01) were observed 24 and 48 hr after allergen challenge. Double IHC showed that the distribution of Fc epsilon RI+ cells was tryptase+ mast cells (33%), CD68+ macrophages (36%), EG2+ eosinophils (20%), CD1a+ Langerhans' cells (4%) and unidentified cells (7%), at the 24-hr allergen-challenged sites. These observations suggest that the cutaneous late-phase reaction in man is associated with up-regulation of Fc epsilon RI on eosinophils, macrophages, mast cells and Langerhans' cells.
From Theory to Practice: Sub-Nyquist Sampling of Sparse Wideband Analog Signals (2010)

Conventional sub-Nyquist sampling methods for analog signals exploit prior information about the spectral support. In this paper, we consider the challenging problem of blind sub-Nyquist sampling of multiband signals, whose unknown frequency support occupies only a small portion of a wide spectrum. Our primary design goals are efficient hardware implementation and low computational load on the supporting digital processing. We propose a system, named the modulated wideband converter, which first multiplies the analog signal by a bank of periodic waveforms. The product is then low-pass filtered and sampled uniformly at a low rate, which is orders of magnitude smaller than Nyquist. Perfect recovery from the proposed samples is achieved under certain necessary and sufficient conditions. We also develop a digital architecture, which allows either reconstruction of the analog input, or processing of any band of interest at a low rate, that is, without interpolating to the high Nyquist rate. Numerical simulations demonstrate many engineering aspects: robustness to noise and mismodeling, potential hardware simplifications, real-time performance for signals with time-varying support and stability to quantization effects. We compare our system with two previous approaches: periodic nonuniform sampling, which is bandwidth limited by existing hardware devices, and the random demodulator, which is restricted to discrete multitone signals and has a high computational load. In the broader context of Nyquist sampling, our scheme has the potential to break through the bandwidth barrier of state-of-the-art analog conversion technologies such as interleaved converters.
An evaluation of object-based programming with Visual Basic (2002)

Two popular trends in the software industry today are object-oriented programming and programming with Microsoft Visual Basic, which is not considered to be an object-oriented programming language. This paper suggests that a full-featured object-oriented programming language is not needed to take advantage of many object-oriented concepts. To explore this supposition, one of the authors developed an application in Visual Basic using as many object-oriented concepts as possible. This paper describes that project and the observed capabilities and limitations of Visual Basic with respect to object-oriented programming. Included are a set of 22 programming guidelines for object-oriented programming with Visual Basic.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>