gebhart/patrepeval huggingface dataset:
Toll-Like Receptor 4 Mediates Innate Immune Responses to Haemophilus influenzae Infection in Mouse Lung (2002)

Toll-like receptors (TLRs) have been implicated in the regulation of host responses to microbial Ags. This study characterizes the role of TLR4 in the innate immune response to intrapulmonary administration of Haemophilus influenzae in the mouse. Two different strains of mice efficiently cleared aerosolized H. influenzae concurrent with a brisk elaboration of IL-1beta, IL-6, TNF-alpha, macrophage-inflammatory protein (MIP)-1alpha, and MIP-2 in bronchoalveolar lavage and a corresponding mobilization of intrapulmonary neutrophils. Congenic strains of mice deficient in TLR4 demonstrated a substantial delay in clearance of H. influenzae with diminished IL-1beta, IL-6, TNF-alpha, MIP-1alpha, and MIP-2 in bronchoalveolar lavage and a notable absence of intrapulmonary neutrophils. In TLR4-expressing animals, but not TLR4-deficient animals, TNF-alpha and MIP-1alpha expression was up-regulated in epithelial cells of the conducting airway in response to H. influenzae which was preceded by an apparent activation of the NF-kappaB pathway in these cells based on the findings of decreased overall IkappaB and an increase in its phosphorylated form. This study demonstrates a critical role of TLR4 in mediating an effective innate immune response to H. influenzae in the lung. This suggests that the airway epithelia might contribute to sensing of H. influenzae infection and signaling the innate immune response.
Differential regulation of the central neural cardiorespiratory system by metabotropic neurotransmitters (2009)

Central neurons in the brainstem and spinal cord are essential for the maintenance of sympathetic tone, the integration of responses to the activation of reflexes and central commands, and the generation of an appropriate respiratory motor output. Here, we will discuss work that aims to understand the role that metabotropic neurotransmitter systems play in central cardiorespiratory mechanisms. It is well known that blockade of glutamatergic, gamma-aminobutyric acidergic and glycinergic pathways causes major or even complete disruption of cardiorespiratory systems, whereas antagonism of other neurotransmitter systems barely affects circulation or ventilation. Despite the lack of an 'all-or-none' role for metabotropic neurotransmitters, they are nevertheless significant in modulating the effects of central command and peripheral adaptive reflexes. Finally, we propose that a likely explanation for the plethora of neurotransmitters and their receptors on cardiorespiratory neurons is to enable differential regulation of outputs in response to reflex inputs, while at the same time maintaining a tonic level of sympathetic activity that supports those organs that significantly autoregulate their blood supply, such as the heart, brain, retina and kidney. Such an explanation of the data now available enables the generation of many new testable hypotheses.
[Pharmacokinetic parameters as criteria for clinical use of hydroxyethyl starch preparations]. (1991)

Pharmacokinetic Parameters as Criteria for Clinical Use of Hydroxyethyl Starch Preparations In a study with volunteers (n = 2 x 6) pharmacokinetic data of two only marginally differing starch preparations were investigated. We were able to demonstrate that there exist significant differences in raw materials used which determined the pharmacokinetic data in humans. Newly implemented analyzing methods (LALLS) were used. In addition to the degree of substitution, further differences concerning the position of hydroxyethylization at the anhydroglucose molecule could be documented. The C2/C6 positions of hydroxyethylization at the molecule seem to be most essential. To classify and to differentiate starch preparations we propose to include these data in general informations for clinicians because these differences might determine clinical usage and efficacy.
Direct effect of physiological doses of arginine vasopressin on the arterial wall in vivo (1978)

Effects of topically applied arginine vasopressin (VPA), in 100-150 muU/ml blood concentration, on external diameter (D) and on dynamic elastic modulus (E*) of surgically denervated common carotid (CC) and femoral (FA) arteries have been studied before and after hypophysectomy in anesthetized dogs. Changes in D, E*, and flow resistance (R) of the CC and FA vascular beds before and after removal of the pituitary were also determined. It was found that VPA elicited a substantial (max 21-26%) decrease in E* and a smaller (max 5.9-6.9%) reduction in D of FA independent of the presence of absence of the pituitary gland. The VPA effect developed more rapidly after hypophysectomy than before. In the CC, VPA did not significantly affect values of E*. During the 1-h period after hypophysectomy, statistically significant decreases in E*-CC, E*-FA, and D-CC were observed, but D-FA did not change, although arterial pressure as well as R-FA and R-CC were diminished. These results give further support to physiological vascular actions of VPA and a possible role in short-term circulatory control. In large arteries, the effects of VPA also seem to be regionally differentiated.
In vitro cytotoxicity of recombinant ricin A chain-antitransferrin receptor immunotoxin against human adenocarcinomas of the colon and pancreas. (1988)

The sensitivity of three human colon adenocarcinoma cell lines (LoVo, LS174T, and SW1116) and a human pancreatic adenocarcinoma cell line (Hs766T) to a recombinant ricin A chain-antitransferrin receptor immunotoxin was studied. In addition, the carboxylic ionophore monensin was used in conjunction with the immunotoxin to determine the possibility of increased cytotoxicity without loss of specificity. The immunotoxin, 454A12-rRTA, is composed of the monoclonal antibody 454A12 directed against transferrin receptor and of ricin A chain, which was produced by recombinant DNA techniques. In 18 h dose-response cytotoxicity assays, the median inhibitory dose (ID50) against LoVo, LS174T, and SW1116 was found to be 3 X 10(-10), 3.6 X 10(-11), and 3.6 X 10(-10) M, respectively; in the same assay, the ID50 for Hs766T was found to be 4 X 10(-10) M. In the presence of monensin, the ID50 for the adenocarcinoma cell lines was reduced 9-fold, 28-fold, and 5-fold, respectively. In cytotoxic kinetic assays, 50% of control protein inhibition was reached in immunotoxin-treated LS174T cells 12-fold faster in the presence of monensin than in its absence. Immunotoxin-treated LoVo cells reached 50% inhibition of control protein synthesis fivefold faster in the presence of monensin than in its absence. Furthermore, no toxicity of immunotoxin or potentiation by monensin was observed in either a control cell line (Swiss albino mouse 3T6) treated with specific immunotoxin or with a control immunotoxin assay. These results show the in vitro specificity and selectivity of 454A12-rRTA immunotoxin for human gastrointestinal and pancreatic cancer cell lines.
Human pancreatic adenocarcinomas express Fas and Fas ligand yet are resistant to Fas-mediated apoptosis. (1998)

The Fas system, comprising the Fas receptor (Fas, CD95, APO-1) and its ligand, Fas ligand (FasL), is a central mediator of programmed cell death in various physiological and pathological processes. Recent evidence indicated that tumor cells can exploit this system to their benefit in the dialogue with the host immune system. We have shown that all human pancreatic adenocarcinoma cell lines tested by fluorescence-activated cell sorting analysis (6 of 6) and immunocytochemistry (12 of 12) were positive for Fas expression, as were normal and malignant duct cells in pancreatic tissue sections. However, despite Fas expression, pancreatic tumor cells have become largely resistant toward recombinant FasL- or anti-APO-1 agonistic antibody-induced apoptosis. This resistance correlated with high levels in pancreatic tumor cells of mRNA for FAP-1, a Fas-associated phosphatase that can block the apoptotic function of Fas. Using a variety of methodological approaches, we also present evidence for the production of FasL by pancreatic tumor cells because 6 of 6 pancreatic tumor cell lines were found to contain FasL mRNA as well as the Mr 40,000 and Mr 26,000 forms of the FasL protein. Likewise, pancreatic tissue revealed FasL-specific immunostaining in pancreatic tumor cells but not in the surrounding stroma. In coculture experiments, pancreatic tumor cells displayed a cytotoxic effect toward the Fas-sensitive Jurkat T-cell line, which could be inhibited by a FasL-specific neutralizing antibody. Together, these results support the recently proposed "counterattack model" for local deletion of tumor-reactive T-cells by tumor cell-derived FasL.
Responsiveness in instant messaging (2006)

For the majority of us, inter-personal communication is an essential part of our daily lives. Instant Messaging, or IM, has been growing in popularity for personal and work-related communication. The low cost of sending a message, combined with the limited awareness provided by current IM systems result in messages often arriving at inconvenient or disruptive times. In a step towards solving this problem, we created statistical models that successfully predict responsiveness to incoming instant messages -- simply put: whether the receiver is likely to respond to a message within a certain time period. These models were constructed using a large corpus of real IM interaction collected from 16 participants, including over 90,000 messages. The models we present can predict, with accuracy as high as 90.1%, whether a message sent to begin a new session of communication would get a response within 30 seconds, 1, 2, 5, and 10 minutes. This type of prediction can be used, for example, to drive online-status indicators, or in services aimed at finding potential communicators.
Dexamethasone disrupts intercellular junction formation and cytoskeleton organization in human trabecular meshwork cells. (2010)

Our findings not only provide molecular insights to the pathogenesis of GC-induced glaucoma but also suggest that junctional proteins ZO-1 and Cx43 as well as F-actin are targets for developing new modalities in glaucoma therapy.
Human CD34 + Cells in Experimental Myocardial Infarction (2010)

Angiogenesis and/or paracrine effect, but not myogenesis, is responsible for functional improvement following CD34(+) cells therapy.
Chemoselective Modification of Turnip Yellow Mosaic Virus by Cu(I) Catalyzed Azide−Alkyne 1,3-Dipolar Cycloaddition Reaction and Its Application in Cell Binding (2010)

Turnip yellow mosaic virus (TYMV) is an icosahedral plant virus with a diameter of 28-30 nm that can be isolated in gram quantities from turnip or Chinese cabbage inexpensively. In this study, TYMV combined with spatially addressable surface chemistries was selected as a prototype bionanoparticle for modulating patterns of cell adhesion, morphology, and proliferation. We exploited the chemical reactivity of TYMV using the mild conditions of Cu(I) catalyzed azide-alkyne cycloaddition (CuAAC) reaction, the best example of "click" chemistry. Oligo-ethylene glycol (OEG) short chain, coumarintriazole, and RGD-containing peptide were grafted on the surface of TYMV via carbodiimide activation and CuAAC reaction. The bioconjugation to intact viral particles was confirmed by MS, TEM, FPLC, and SDS-PAGE with fluorescence visualization analysis. Therefore, this method is a generally useful means of incorporating various types of functionalities onto the TYMV surface. Further studies were done to learn the behavior of NIH-3T3 fibroblast cells on the modified or unmodified TYMV surfaces. OEG-modified TYMV surfaces retarded cell attachment and growth, while cell adhesion, spreading, and proliferation were dramatically enhanced on RGD-modified TYMV surfaces. Compared with RGD immobilized 3-aminopropyltriethoxysilane-coated glass surface, the cells are more ready to spread fully and proliferate on TYMV-RGD coated surface, which thus provides a more cell-friendly environment with nanometer-scale surface features. This illustrates the potential application of plant virus based materials in tissue engineering, drug delivery, and biosensing.
Characterization of the Role of the Divalent Metal Ion-Dependent Transcriptional Repressor MntR in the Virulence of Staphylococcus aureus (2003)

DtxR-type metal ion-dependent repressors, present in many bacterial pathogens, may regulate expression of virulence genes such as that encoding diphtheria toxin. SirR, a DtxR homologue initially identified in Staphylococcus epidermidis, governs the expression of the adjacent sitABC operon encoding a putative metal ion ABC transporter system. We identified a sirR homologue, mntR, in Staphylococcus aureus and demonstrated by gel shift assay that the corynebacterial repressor DtxR binds to the S. aureus mntABC operator in the presence of Fe(2+) or Mn(2+). Since a mutant DtxR, DtxR(E175K), functions as an iron-independent hyperrepressor in certain settings, we constructed a heterodiploid S. aureus strain expressing dtxR(E175K) from the native mntR promoter. Transcription of the S. aureus mntABC operon was repressed in the presence of Fe(2+) or Mn(2+) in wild-type and heterodiploid S. aureus strains. Under metal ion-limiting conditions, mntABC transcription was reduced but not abolished in S. aureus isolates expressing dtxR(E175K) compared with an isogenic control, suggesting that DtxR(E175K) binds the S. aureus MntR box in vivo. Under all conditions tested, mntABC transcription in the dtxR(E175K)-expressing strain was reduced relative to the isogenic control, indicating that DtxR(E175K) function was constitutively active. In the mouse skin abscess model, dtxR(E175K)-expressing S. aureus recombinants showed significantly reduced CFU levels compared with the isogenic wild-type control. We conclude that the S. aureus MntR box is recognized by corynebacterial DtxR proteins and thus belongs to the DtxR family of metal-dependent operator sites. Moreover, constitutive repression by DtxR(E175K) reduces the virulence of S. aureus in the mouse skin abscess model.
Site-Specific Conjugation to Interleukin 4 Containing Mutated Cysteine Residues Produces Interleukin 4-Toxin Conjugates with Improved Binding and Activity (1994)

Fusion of a ligand to another protein frequently impairs the binding of the ligand. Recombinant toxins composed of mutants of Pseudomonas exotoxin (PE) fused to the C-terminus of human interleukin 4 (IL4) are cytotoxic to IL4 receptor- (IL4R-) bearing tumor cells but bind to the IL4R with only 1% the affinity of IL4. We have developed a method to connect a toxin to a ligand which allows the junction to be moved to a location on the ligand which would minimize the binding impairment. We designed mutants of IL4 in which residue 28, 38, 68, 70, 97, or 105 was substituted with cysteine. All purified mutants bound to the IL4R with 60-100% the affinity of IL4, indicating that the IL4 structure was essentially unchanged. The IL4 mutants were then each conjugated through a disulfide bond to PE35, a truncated form of PE which contains a single cysteine. IL4 conjugated to PE35 at residue 28, 38, or 105 of IL4 bound with 10-fold improved affinity and was 10-fold more cytotoxic than the recombinant IL4-toxin in which PE is fused to position 129 at the C-terminus of IL4. IL4 containing PE35 conjugated at position 68, 70, or 97 had lower binding affinity and cytotoxic activity. These results indicate that the location of the ligand-protein junction can be selectively moved to enhance conjugate effectiveness, and implications could be made regarding which regions of IL4 are important for binding.
LEAFY COTYLEDON1Is a Key Regulator of Fatty Acid Biosynthesis in Arabidopsis (2008)

In plants, fatty acids are de novo synthesized predominantly in plastids from acetyl-coenzyme A. Although fatty acid biosynthesis has been biochemically well studied, little is known about the regulatory mechanisms of the pathway. Here, we show that overexpression of the Arabidopsis (Arabidopsis thaliana) LEAFY COTYLEDON1 (LEC1) gene causes globally increased expression of fatty acid biosynthetic genes, which are involved in key reactions of condensation, chain elongation, and desaturation of fatty acid biosynthesis. In the plastidial fatty acid synthetic pathway, over 58% of known enzyme-coding genes are up-regulated in LEC1-overexpressing transgenic plants, including those encoding three subunits of acetyl-coenzyme A carboxylase, a key enzyme controlling the fatty acid biosynthesis flux. Moreover, genes involved in glycolysis and lipid accumulation are also up-regulated. Consistent with these results, levels of major fatty acid species and lipids were substantially increased in the transgenic plants. Genetic analysis indicates that the LEC1 function is partially dependent on ABSCISIC ACID INSENSITIVE3, FUSCA3, and WRINKLED1 in the regulation of fatty acid biosynthesis. Moreover, a similar phenotype was observed in transgenic Arabidopsis plants overexpressing two LEC1-like genes of Brassica napus. These results suggest that LEC1 and LEC1-like genes act as key regulators to coordinate the expression of fatty acid biosynthetic genes, thereby representing promising targets for genetic improvement of oil production plants.
Lysine residues 165 and 166 are essential for the cofactor function of tissue factor. (1991)

Tissue factor, a 45-kilodalton membrane glycoprotein, is an essential cofactor for the plasma serine protease factor VII which activates factor X in the first step of the extrinsic coagulation cascade. Two adjacent lysine residues (numbers 165 and 166) were identified in the extracytoplasmic domain of tissue factor that are crucial for function. Site-directed mutagenesis of both lysines to alanines results in complete loss of activity. Mutation of either lysine alone results in a molecule which is much more sensitive to the phospholipid composition of the activating surface than the wild-type molecule. It is postulated that interactions between the extracytoplasmic domain of tissue factor and the membrane surface are necessary for bound factor VII or VIIa to assume a conformation capable of efficient catalysis.
Intrinsic human glomerular mesangial cells can express receptors for IgG complexes (hFc gamma RIII-A) and the associated Fc epsilon RI gamma-chain. (1994)

Immune complexes localize to the glomerular mesangium in many forms of human glomerulonephritis. In this investigation, we determined whether primary cultured human glomerular mesangial cells (HMC) express mRNA and functional protein of FcR for IgG. Performing reverse transcription-PCR with subsequent control Southern blots, we showed that in contrast to human monocytes or granulocytes, mRNA for Fc gamma RI and Fc gamma RII is not detectable in either growth-arrested (48 h serum free) or unstimulated proliferating (medium with 10% FCS) HMC. However, IFN-gamma in combination with LPSE.coli (LPS), but not LPS alone elicited a significant transcription of hFc gamma RIII mRNA in resting HMC, whereas cytokines, such as IL-1 beta or TGF-beta, failed to induce any of the three Fc gamma Rs in resting HMC. Proliferating HMC showed a basal transcription of Fc gamma RIII mRNA, which was enhanced by IFN-gamma in combination with LPS. Slot-blot analysis indicated that only the Fc gamma RIII-A gene encoding the transmembrane isoform of Fc gamma RIII was expressed by HMC. For the first time, transcripts for the gamma-chain of Fc epsilon RI were found in HMC. Fc gamma RIII protein expression was detected after LPS/IFN-gamma stimulation both by specific staining of paraformaldehyde-fixed HMC and immunoprecipitation of Fc gamma RIII protein from HMC membranes. Fc gamma RIII-A receptors are functionally active, as HMC IL-6 mRNA synthesis was stimulated by heat-aggregated IgG or F(ab')2 fragments of CLBGran1 mAb only after induction of Fc gamma RIII-A. These in vitro data suggest that HMC that are basically negative for Fc gamma RIII can be stimulated to express low affinity Fc gamma Rs, and thus may participate actively in human glomerulonephritis involving immune complexes.
Resource overbooking and application profiling in a shared Internet hosting platform (2009)

In this article, we present techniques for provisioning CPU and network resources in shared Internet hosting platforms running potentially antagonistic third-party applications. The primary contribution of our work is to demonstrate the feasibility and benefits of overbooking resources in shared Internet platforms. Since an accurate estimate of an application's resource needs is necessary when overbooking resources, we present techniques to profile applications on dedicated nodes, possibly while in service, and use these profiles to guide the placement of application components onto shared nodes. We then propose techniques to overbook cluster resources in a controlled fashion. We outline an empirical appraoch to determine the degree of overbooking that allows a platform to achieve improvements in revenue while providing performance guarantees to Internet applications. We show how our techniques can be combined with commonly used QoS resource allocation mechanisms to provide application isolation and performance guarantees at run-time. We implement our techniques in a Linux cluster and evaluate them using common server applications. We find that the efficiency (and consequently revenue) benefits from controlled overbooking of resources can be dramatic. Specifically, we find that overbooking resources by as little as 1% we can increase the utilization of the cluster by a factor of two, and a 5% overbooking yields a 300--500% improvement, while still providing useful resource guarantees to applications.
National Hospital Discharge Survey: 2001 annual summary with detailed diagnosis and procedure data. (2004)

An estimated 32.7 million inpatients were discharged from non-Federal short-stay hospitals in 2001. They used 159.4 million days of care and had an average length of stay of 4.9 days. Common first-listed discharge diagnoses included delivery, psychoses, pneumonia, malignant neoplasm, and coronary atherosclerosis. Males had higher rates for procedures such as cardiac catheterization and coronary artery bypass graft, and females had higher rates for procedures such as cholecystectomy and total knee replacement. The rates of all cesarean deliveries, primary and repeat, rose from 1995 to 2001; the rate of vaginal birth after cesarean delivery dropped 37 percent during this period.
Crowdsourced radiomap for room-level place recognition in urban environment (2010)

The proliferation of WLAN infrastructures has facilitated numerous indoor localization techniques using WLAN fingerprints. In particular, identifying a room or a place in urban environments could be usefully utilized in many application domains such as ubiquitous health. However, it is not straightforward how to bootstrap such a localization system because WLAN fingerprints of all places must be available in advance. In this paper, we propose a crowdsourcing approach for indoor place recognition. The key idea is to build an open participatory system through which users can contribute fingerprints. As the database size increases, it can provide place recognition service. We conducted an extensive experimental study at a university campus to demonstrate the performance of the proposed method in terms of recognition accuracy. We also studied key factors that could undermine the crowdsourcing approach such as fingerprint density, incorrect contribution, uneven contribution, and device heterogeneity.
Principles of Thermodynamics (1979)

This book makes a good attempt to bridge the gap between thermodynamics as taught to physics students and engineering students. The units and methods involved must necessarily be a compromise because the market for the book includes North America and Europe.