gebhart/patrepeval huggingface dataset:
[Bronchodilating effect of inhalation of aerosolized aminophylline in asthmatic patients]. (1995)

Inhalation of aerosolized aminophylline solution (Neophylline) was examined for it's bronchodilating effect. Tests were done on the patient with bronchial asthma aged from 8 to 16 years of age which were divided into two groups, i.e., 21 wheezy patients, 8 non-wheezy patients and on another 14 under normal controls. 1.2 ml. of neophylline (30 mgs. of aminophylline) was inhaled to each patient by the micronebulizer for 6 minutes. VC, FEV1, PFR, V50 and V25 were measured by a Flow-volume recorder OST 7OD just before and after inhalation. The results showed that the bronchodilating effect of inhaled neophylline was detected in the wheezy patients group but not in the non-wheezy patients group nor in the control group. Furthermore, the duration of the bronchodilating effect was examined on another 19 wheezy patients by a peak flow meter. The effect appeared to be sustained for 4 hours after inhalation. Inhalation of serosolized neophylline is considered to be useful because of the fact that the bronchodilation can be obtained without an elevation of serum concentration of theophylline.
Synthesis and anti-HIV evaluation of D4T and D4T 5'-monophosphate prodrugs (1993)

Several 5-monophosphate D4T derivatives and their analogues were synthesized as potential lipophilic prodrugs of D4T. Cholesteryl D4T phosphate diester and bis-5'-D4T phosphate inhibited HIV replication in CEM-Cl13 cells more efficiently than D4T itself as measured by the inhibition of cytopathic effect based on MTT assay or reverse transcriptase activity. The two compounds were devoid of toxicity on CEM-Cl13 cells at doses equal to 50 and 100 microM, respectively, which brought the selectivity index into the same range as AZT.
Percutaneous lumbar diskectomy using a new aspiration probe: porcine and cadaver model. (1985)

A method of percutaneous aspiration of the nucleus pulposus of lumbar disks is described as performed in four pigs and three cadavers. Through a lateral oblique percutaneous approach, 80-100% of the nucleus pulposus was removed in each of the pigs; approximately 30% of the cadaver disk was removed. A unique aspiration probe and the introducing set as well as the technique are described. The implications for clinical use in patients are discussed. We believe this technique may be an alternative to both surgical diskectomies and chymopapain injection in the treatment of herniated disk disease of the lumbar spine.
Suboptimal activation of CD8(+) T cells by melanoma-derived altered peptide ligands: role of Melan-A/MART-1 optimized analogues. (2003)

Suboptimal activation of T lymphocytes by tumor cells may contribute to the failure of the immune system to control tumor growth. We recently demonstrated that Melan-A/MART-1-reactive CTLs can be anergized by peptide analogues with partial agonist/antagonist functions, which selectively impair interleukin (IL)-2 release. Here we analyze the potential expression of partial agonist/antagonist peptides by tumor cells and their role in suboptimal T-cell activation. HLA-bound peptide fractions were eluted from HLA-A*0201/Melan-A/MART-1(+) melanoma cells and analyzed for reconstitution of the MART-1-specific T-cell epitope. Among the peptide fractions able to induce IFN-gamma release by MART-1-specific T cells, only fraction 43-44 activated IL-2 production by anti-MART-1 T cells, whereas the remaining two fractions acted as peptide antagonists by inhibiting IL-2 release in response to the native epitope. A comparable down-modulation of IL-2 release could also be induced by the MART-1-derived peptide 32-40, previously identified in one of the two anergizing fractions. A substantial deficit in IL-2 release was additionally detected in tumor-specific CD8(+) T cells infiltrating melanoma lesions. To overcome IL-2 impairment by peptide antagonists, anti-MART-1 T cells were generated by in vitro sensitization with the two optimized analogues Melan-A/MART-1(27-35) 1L (with superagonist features) and Melan-A/MART-1(26-35) 2L (with improved HLA-A*0201 binding). T cells raised with the superagonist Melan-A/MART-1(27-35) 1L showed resistance to the inhibition of IL-2 release mediated by melanoma-derived peptide fractions, whereas Melan-A/MART-1(26-35) 2L-specific T cells appeared to be as sensitive as T cells raised with the parental epitope. This resistance was associated with the enhanced ability of Melan-A/MART-1(27-35) 1L-specific T cells to release IL-2. Taken together, these data indicate that melanoma cells can process and present on their surface peptides inhibiting optimal T-cell activation against immunodominant epitopes and that the usage of optimized peptide analogues could represent a promising approach for overcoming tumor-induced immunosuppression and possibly designing more successful vaccines for cancer patients.
Effect of Host Modification and Age on Airway Epithelial Gene Transfer Mediated by a Murine Leukemia Virus-Derived Vector (1998)

To study retroviral gene transfer to airway epithelia, we used a transient transfection technique to generate high titers (approximately 10(9) infectious units/ml after concentration) of murine leukemia virus (MuLV)-derived vectors pseudotyped with the vesicular stomatitis virus envelope glycoprotein (VSV-G). Transformed (CFT1) and primary airway epithelial cells were efficiently transduced by a VSV-G-pseudotyped lacZ vector (HIT-LZ) in vitro. CFT1 cells and primary cystic fibrosis (CF) airway cell monolayers infected with a vector (HIT-LCFSN) containing human CF transmembrane conductance regulator (CFTR) in the absence of selection expressed CFTR, as assessed by Western blot analysis, and exhibited functional correction of CFTR-mediated Cl- secretion. In vitro studies of persistence suggested that pseudotransduction was not a significant problem with our vector preparations. In a sulfur dioxide (SO2) inhalational injury model, bromodeoxyuridine (BrdU) incorporation rates were measured and found to exceed 50% in SO2-injured murine tracheal epithelium. HIT-LZ vector (multiplicity of infection of approximately 10) instilled into the SO2-injured tracheas of anesthetized mice transduced 6.1% +/- 1.3% of superficial airway cells in tracheas of weanling mice (3 to 4 weeks old; n = 10), compared to 1.4 +/- 0.9% in mice 5 weeks of age (n = 4) and 0.2% in mice older than 6 weeks (n = 15). No evidence for gene transfer following delivery of HIT-LZ to tracheas of either weanling or older mice not injured with SO2 was detected. Because only a small fraction of BrdU-labeled airway cells were transduced, we examined the stability of the vector. No significant loss of vector infectivity over intervals (2 h) paralleling those of in vivo protocols was detected in in vitro assays using CFT1 cells. In summary, high-titer vectors permitted complementation of defective CFTR-mediated Cl- transport in CF airway cells in vitro without selection and demonstrated that the age of the animal appeared to be a major factor affecting in vivo retroviral transduction efficiency.
Invasion of collagen gels by mouse lymphoid cells. (1984)

Small mouse lymphocytes from lymph nodes rapidly invaded three-dimensional collagen gels (in the absence of any added chemical attractant). In short-term assays (2-8 hr) this property was restricted to 20-25% of the cell population. Invasion was an active process involving cell locomotion. Time-lapse cinematography revealed that movement was erratic with frequent changes in cell speed. Tracks of cell paths within collagen gels demonstrated that lymphocytes made narrow angles of turn and thus showed a 'persistent random-walk' similar to other cell types moving on plane substrata. Analysis of lymphocyte movement within aligned collagen gels demonstrated that locomotion was biased in the axis of fibre alignment, i.e. lymphocytes showed contact guidance. Separated B lymphocytes invaded collagen gels at a slower rate than unseparated lymph node cells, as also did T cells purified by filtration through nylon wool columns. This latter anomaly implied that nylon wool filtration selectively depleted cells with invasive characteristics from a heterogeneous lymphocyte population. A comparison of Peyer's patch and lymph node lymphocytes showed that both populations invaded at the same rate but the latter cell type did this in greater numbers. This difference may reflect the different proportions of B and T lymphocytes in the two tissues. Lymphocytes from oxazolone-stimulated lymph nodes showed greatly increased movement into collagen matrices compared to unstimulated control lymph node lymphocytes. This increase was demonstrated to be a property of the blast cell population by separating the cells on Percoll gradients into lymphoblast-enriched and -depleted populations.
Detection Times of Marijuana Metabolites in Urine by Immunoassay and GC-MS (1995)

Reports of prolonged drug excretion have provided the basis for the common assumption that cannabinoid metabolites may he detected in urine for a week or longer. The accuracy, sensitivity, and specificity of immunoassays for the detection of cannabinoids and metabolites are unique for a specific assay and may change overtime. it is important that individuals who select assays and those who interpret test results be aware of qualitative and quantitative changes that occur. In the present study, detection times of cannabinoids in urine were determined using cannabinoid immunoassays with 20-, 50-, and 100-ng/mL cutoffs and using gas chromatography-mass spectrometry (GC-MS). Six subjects each smoked a single marijuana cigarette (placebo, 1.75, or 3.55% delta9-tetrahydrocannabinol [THC]) each week while residing on the clinical ward of the Addiction Research Center. Each urine specimen was analyzed under blind conditions by immunoassay according to the manufacturer's instructions. The following cannabinoid reagents were evaluated: EMIT d.a.u. 100, EMIT d.a.u. 50, EMIT d.a.u. 20, EMIT II 100, EMIT II 50, Abuscreen OnLine, and Abuscreen RIA, DRI, and ADx. All urine specimens were also analyzed for 11-nor-9-carboxy-delta9-THC by GC-MS using a 15-ng/mL cutoff. Urinary cannabinoid detection times varied substantially across assays, subjects, doses, and cutoff concentrations. Detection times were shorter than previously assumed. Mean detection times increased from a maximum of 0.5 days after the low dose to 1.5 days after the high dose using the 100-ng/mL cutoff. Mean detection times were less than 1 day following the low dose and less than 2 days following high-dose exposure using the 50-ng/mL cutoff. Mean detection times ranged from 1 to 5 days after the low dose and from 3 to 6 days after the high dose using the 20-ng/mL cutoff immunoassay. GC-MS detection times were approximately twice as long as mean detection times using an immunoassay with a cutoff of 50 ng/mL. Differences in sensitivity and specificity between the available immunoassay products affected the efficiency of detection of marijuana use. These results indicate that recent reductions in cannabinoid cutoffs by military and federally mandated programs will increase detection times and improve sensitivity, as expected. However, monitoring acute marijuana usage with a commercial cannabinoid immunoassay that has a 50-ng/mL cutoff concentration provides only a narrow window of detection of 1-2 days.
Structural insights into the processivity of endopolygalacturonase I from Aspergillus niger (2003)

Endopolygalacturonase I is a processive enzyme, while the 60% sequence identical endopolygalacturonase II is not. The 1.70 A resolution crystal structure of endopolygalacturonase I reveals a narrowed substrate binding cleft. In addition, Arg96, a residue in this cleft previously shown to be critical for processivity, interacts with the substrate mimics glycerol and sulfate in several well-defined conformations in the six molecules in the asymmetric unit. From this we conclude that both Arg96 and the narrowed substrate binding cleft contribute to retaining the substrate while it moves through the active site after a cleavage event has occurred.
Deacylation and deformylation of pyrroles (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDeacylation and deformylation of pyrrolesKevin M. Smith, Michiko Miura, and Hani D. TabbaCite this: J. Org. Chem. 1983, 48, 24, 4779–4781Publication Date (Print):December 1, 1983Publication History Published online1 May 2002Published inissue 1 December 1983https://doi.org/10.1021/jo00172a067RIGHTS & PERMISSIONSArticle Views752Altmetric-Citations20LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (417 KB) Get e-Alerts Get e-Alerts
Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve (2011)

There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABA(B1b) mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABA(Aα2) mRNA expression in the prefrontal cortex and amygdala, but increased GABA(Aα2) in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut-brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression.
CRISPR-engineered T cells in patients with refractory cancer (2020)

CRISPR-Cas9 gene editing provides a powerful tool to enhance the natural ability of human T cells to fight cancer. We report a first-in-human phase 1 clinical trial to test the safety and feasibility of multiplex CRISPR-Cas9 editing to engineer T cells in three patients with refractory cancer. Two genes encoding the endogenous T cell receptor (TCR) chains, TCRα (<i>TRAC</i>) and TCRβ (<i>TRBC</i>), were deleted in T cells to reduce TCR mispairing and to enhance the expression of a synthetic, cancer-specific TCR transgene (NY-ESO-1). Removal of a third gene encoding programmed cell death protein 1 (PD-1; <i>PDCD1</i>), was performed to improve antitumor immunity. Adoptive transfer of engineered T cells into patients resulted in durable engraftment with edits at all three genomic loci. Although chromosomal translocations were detected, the frequency decreased over time. Modified T cells persisted for up to 9 months, suggesting that immunogenicity is minimal under these conditions and demonstrating the feasibility of CRISPR gene editing for cancer immunotherapy.
Novel Driver Authentication System using Electrocardiogram (2013)

In order to develop a driver recognition system for personally tailored services, the authors focused on personal authentication techniques using electrocardiogram (ECG) signals. These techniques typically utilized intervals and heights of the ECG waveform as parameters. Fast authentication is required for usability. However, since there is considerable variation in ECG parameters within individuals, accurate authentication is a challenging task, and it takes time, even when the person is in a relatively relaxed state. This paper reports on a study that the authors carried out to improve the accuracy of authentication under varying parameter settings. They explored the relevant parameter space by testing various sets of ECG parameters and calculating the resulting authentication accuracy. Based on these results we then selected a set of parameters that were optimal for the sample used. Parameters were selected based on their ability to discriminate between individuals using the ratio of between to within person variation.
Vascular Endothelial Growth Factor Induces Branching Morphogenesis/Tubulogenesis in Renal Epithelial Cells in a Neuropilin-Dependent Fashion (2005)

Vascular endothelial growth factor (VEGF) is well characterized for its role in endothelial cell differentiation and vascular tube formation. Alternate splicing of the VEGF gene in mice results in various VEGF-A isoforms, including VEGF-121 and VEGF-165. VEGF-165 is the most abundant isoform in the kidney and has been implicated in glomerulogenesis. However, its role in the tubular epithelium is not known. We demonstrate that VEGF-165 but not VEGF-121 induces single-cell branching morphogenesis and multicellular tubulogenesis in mouse renal tubular epithelial cells and that these morphogenic effects require activation of the phosphatidylinositol 3-kinase (PI 3-K) and, to a lesser degree, the extracellular signal-regulated kinase and protein kinase C signaling pathways. Further, VEGF-165-stimulated sheet migration is dependent only on PI 3-K signaling. These morphogenic effects of VEGF-165 require activation of both VEGF receptor 2 (VEGFR-2) and neuropilin-1 (Nrp-1), since neutralizing antibodies to either of these receptors or the addition of semaphorin 3A (which blocks VEGF-165 binding to Nrp-1) prevents the morphogenic response and the phosphorylation of VEGFR-2 along with the downstream signaling. We thus conclude that in addition to endothelial vasculogenesis, VEGF can induce renal epithelial cell morphogenesis in a Nrp-1-dependent fashion.
Identification of an alternative ligand-binding pocket in the nuclear vitamin D receptor and its functional importance in 1α,25(OH) 2 -vitamin D 3 signaling (2004)

Structural and molecular studies have shown that the vitamin D receptor (VDR) mediates 1alpha,25(OH)2-vitamin D3 gene transactivation. Recent evidence indicates that both VDR and the estrogen receptor are localized to plasma membrane caveolae and are required for initiation of nongenomic (NG) responses. Computer docking of the NG-specific 1alpha,25(OH)2-lumisterol to the VDR resulted in identification of an alternative ligand-binding pocket that partially overlaps the genomic pocket described in the experimentally determined x-ray structure. Data obtained from docking five different vitamin D sterols in the genomic and alternative pockets were used to generate a receptor conformational ensemble model, providing an explanation for how VDR and possibly the estrogen receptor can have genomic and NG functionality. The VDR model is compatible with the following: (i) NG chloride channel agonism and antagonism; (ii) variable ligand-stabilized trypsin digest banding patterns; and (iii) differential transcriptional activity, employing different VDR point mutants and 1alpha,25(OH)2-vitamin D3 analogs.
Network security via reverse engineering of TCP code: vulnerability analysis and proposed solutions (2002)

The transmission control protocol/Internet protocol (TCP/IP) suite is widely used to interconnect computing facilities in modern network environments. However, there exist several security vulnerabilities in the TCP specification and additional weaknesses in a number of its implementations. These vulnerabilities may enable an intruder to "attack" TCP-based systems, allowing him/her to "hijack" a TCP connection or cause denial of service to legitimate users. We analyze TCP code via a "reverse engineering" technique called "slicing" to identify several of these vulnerabilities, especially those that are related to the TCP state-transition diagram. We discuss many of the flaws present in the TCP implementation of many widely used operating systems, such as SUNOS 4.1.3, SVR4, and ULTRIX 4.3. We describe the corresponding TCP attack "signatures" (including the well-known 1994 Christmas Day Mitnick Attack) and provide recommendations to improve the security state of a TCP-based system, e.g., incorporation of a "timer escape route" from every TCP state.
Explanation of the Brightness and Color of the Sky, Particularly the Twilight Sky (1953)

By use of the Rayleigh scattering theory for pure air, primary scattering and known upper air densities from rockets, the brightness of the zenith twilight sky was calculated and values were obtained two to four times greater than those observed at Sacramento Peak, New Mexico ( J. Opt. Soc. Am.42, 353 ( 1952). The attenuation of the atmosphere there was observed to be twenty percent above that of the Rayleigh theory, and the ozone thickness was measured to be about 2.2 mm. When the absorption of the Chappuis band of ozone in the visible spectrum was added to the Rayleigh theory, the calculated sky brightness came into agreement with observation for solar depression angles below the horizon from about 0° to 6°. For the sun below 7° the calculated zenith sky brightness fell rapidly below the observed brightness, showing that primary scattering in the atmosphere above about 60 km does not contribute appreciably to the brightness, as has long been known ( J. Opt. Soc. Am.28, 227, 1938).Calculation showed that during the day the clear sky is blue according to Rayleigh, and that ozone has little effect on the color of the daylight sky. But near sunset and throughout twilight ozone affects the sky color profoundly. For example, in the absence of ozone the zenith sky would be a grayish green-blue at sunset becoming yellowish in twilight, but with ozone the zenith sky is blue at sunset and throughout twilight (as is observed), the blue at sunset being due about 13 to Rayleigh and 23 to ozone, and during twilight wholly to ozone.
Serum IL-1β, IL-6, IL-8, and TNF-α Levels in Early Diagnosis and Management of Neonatal Sepsis (2007)

Aim. To determine serum IL-1, IL-6, IL-8, and TNF- levels in neonatal sepsis at the time of diagnosis and after therapy, and to show the meaningful on the follow up. Methods. This prospective study was performed on newborns who were hospitalized for neonatal sepsis and who were classified as culture-proven sepsis (n = 12), as culture-negative sepsis (n = 21), and as healthy newborns (n = 17). Results. At the time of diagnosis, serum IL-1, IL-6, IL-8, and TNF- levels of culture-proven sepsis were significantly higher than those of the control groups (P < .05). At the time of diagnosis, IL-1, IL-6, IL-8, and TNF- levels of culture-proven sepsis and culture-negative sepsis were significantly higher than levels at the seventh day after antibiotic treatment. Conclusion. Serum IL-1, IL-6, IL-8, and TNF- are mediators of inflammation and can be used at the diagnosis and at the evaluation of the therapeutic efficiency in neonatal sepsis.