gebhart/patrepeval huggingface dataset:
Persistent Experimental Salmonella dublin Intramammary Infection in Dairy Cows (1991)

Experimental intramammary infections were induced in five post-parturient Holstein cows by inoculation of low numbers (5000 colony forming units) of virulent Salmonella dublin via the teat canal of mammary gland quarters. Rectal temperature, pulse and respiratory rates, milk yield, and milk quality as assessed by the California Mastitis Test (CMT) and somatic cell counts (SCC) were recorded every 12 hours at milking. Bacteriologic cultures of foremilk quarter samples and feces were obtained daily, as were complete blood counts. ELISA titers for IgG and IgM recognizing S. dublin lipopolysaccharide (LPS) were obtained weekly on serum and quarter milk samples. All cows excreted S. dublin intermittently from infected quarters, but no changes were detected in rectal temperature, appearance of the mammary gland or secretions, CBC, milk yield, and pulse and respiratory rates. Somatic cell counts were modestly increased in infected quarters as compared with uninfected quarters (P = .015, paired t test); however, CMT scores after infection remained low, and were not significantly different from pre-infection scores (P greater than .10, sign test). After infection, administration of dexamethasone resulted in signs of clinical mastitis and increased excretion of S. dublin from mammary quarters (P = .0004, paired t test). One cow had necrotizing mastitis and S. dublin septicemia and was euthanatized. In the four surviving cows, clinical improvement was observed after systemic gentamicin therapy and intramammary infusion with polymyxin B, but all cows continued to excrete S. dublin intermittently from one or more quarters and occasionally from feces for the remaining period of observation. All infected cows demonstrated a rise in IgG and IgM ELISA titers recognizing S. dublin LPS in serum and milk. At necropsy (13-25 weeks postinfection), S. dublin was recovered only from the mammary tissue or supramammary lymph nodes in three of four cows. In one cow, mammary gland and lymph-node samples were negative for S. dublin despite positive milk cultures. In all cows, histopathologic examination revealed multifocal areas of chronic active mastitis. These lesions were similar to histopathologic findings from mammary gland carriers with naturally acquired S. dublin infection.
Cell-Mediated Immunity to Human Tumors (1973)

The reactivity of peripheral blood leukocytes from patients with carcinoma of the gastrointestinal tract and malignant melanoma was assessed by the leukocyte migration technique to membrane fractions of histologically similar and unrelated tumors. Inhibition of migration was observed when the tumor membranes were derived from histologically similar tumors but not with those from unrelated tumors. Normal volunteers' leukocytes failed to inhibit with either type of tumor membrane antigen. Inhibition of migration was noted when the leukocytes were cultured in serum-free medium. Autologous serum produced complete abrogation of the response, but decreased inhibition of migration was also noted when allogeneic serum was added to the culture medium. Seven patients with disseminated melanoma were treated with BCG therapy administered repeatedly by the oral route. This type of treatment effected a regression in three of seven patients and had prevented tumor progression in an additional two patients. No alteration in the reactivity of these patients' leukocytes to tumor membrane antigens was noted during the course of the therapy.
Plasmonic properties of silver-based alloy thin films (2015)

The plasmonic properties of silver-based alloy thin films were studied. Silver-ytterbium (Ag-Yb) and silver-magnesium (Ag-Mg) prepared by thermal co-evaporation were investigated extensively for various thin film properties. The optical properties were intensively analyzed and discussed because the dielectric response of a material is particularly significant in terms of its plasmonic properties. The study of silver-based alloy thin films has been mostly about Ag alloying with other transition metals, but the results of Ag-Yb and Ag-Mg in this work showed that the intensity of plasma resonance is tunable, in which the idea may also apply to other silver-rich binary alloy thin films regardless of the kind of second metal components. In our research, the Ag plasma resonance was weakened with respect to the concentration of Yb and Mg in the alloy thin films. The change in the optical characteristics around Ag plasma resonance frequency was attributed to an increase in “resonance damping. This is confirmed from modeling using classical free-electron theory. The increase in the damping was experimentally corroborated by the concentration dependence of electrical conductivity and estimated average crystallite size of Ag-Yb and Ag-Mg thin films. The reduction in electrical conductivity was not only caused by introducing less conductive Yb or Mg but also through disturbing the Ag lattice structure to promote additional electron scattering at grain boundaries. The Ag-Yb and Ag-Mg alloys carried intermediate properties between their pure components despite the presence of Yb or Mg oxides. Besides optical and electrical properties, changes in the electronic work function were also assessed since it is also important in applications. Plasmonic nanostructures and transparent organic light-emitting diodes (OLEDs) were fabricated to demonstrate their potential applications. Two-dimensional disc-arrays nanostructures composed of pure Ag and Ag-Yb were implemented to evaluate the plasmonic properties. The damping loss in Ag-Yb caused weakened coupling of incident photons and surface plasmons when compared to pure Ag without altering the coupling wavelengths, suggesting potential plasmonic materials for tuning the coupling strength of surface plasmons by controlling the concentration of Yb which may also apply to Ag-Mg. Ultrathin Ag-Yb and Ag-Mg films were used as cathodes in transparent OLEDs for demonstration, which was beneficial by virtue of overall device transmittance though sacrificing electrical conduction leading to poor light emission unless inserting additional ultrathin lithium fluoride to modify the ultrathin cathodes.
High-Efficiency Gene Transfer into Normal and Adenosine Deaminase-Deficient T Lymphocytes Is Mediated by Transduction on Recombinant Fibronectin Fragments (1998)

Primary human T lymphocytes are powerful targets for genetic modification, although the use of these targets in human gene therapy protocols has been hampered by low levels of transduction. We have shown previously that significant increases in the transduction of hematopoietic stem and progenitor cells with retroviral vectors can be obtained by the colocalization of the retrovirus and target cells on specific fibronectin (FN) adhesion domains (H. Hanenberg, X. L. Xiao, D. Dilloo, K. Hashino, I. Kato, and D. A. Williams, Nat. Med. 2:876-882, 1996). We studied the transfer of genes into primary T lymphocytes by using FN-assisted retroviral gene transfer. Activated T lymphocytes were infected for three consecutive days on the recombinant FN fragment CH-296 with a retroviral vector encoding the murine B7-1 protein. Transduced lymphocytes were analyzed for murine B7-1 expression, and it was found that under optimal conditions, 80 to 89% of the CD3+ lymphocytes were transduced. Gene transfer was predominantly augmented by the interaction between VLA-4 on the T lymphocytes and the FN adhesion site CS-1. Adenosine deaminase (ADA)-deficient primary T lymphocytes transduced on CH-296 with a retrovirus encoding murine ADA (mADA) exhibited levels of mADA activity severalfold higher than the levels of the endogenous human ADA protein observed in normal human T lymphocytes. Strikingly, the long-term expression of the transgene was dependent on the activation status of the lymphocytes. This approach will have important applications in human gene therapy protocols targeting primary T lymphocytes.
Lack of Pain Associated with Microfabricated Microneedles (2001)

Implications Microscopic needles previously shown capable of transdermal delivery of drugs and proteins are demonstrated to be painless when pressed into the skin of human subjects.
Lanthanide-induced peptide folding: variations in lanthanide affinity and induced peptide conformation (1983)

The present work has demonstrated the utility of the diamagnetic lanthanides lutetium and lanthanum as metal binding probes for a synthetic 13-residue fragment representing calcium binding site 3 of rabbit skeletal troponin C (residues 103-115). The peptide conformation induced by these metals was monitored by the proton magnetic resonance at 270 MHz. The peptide affinity for these rare earths is 50-400 times higher than that for calcium (KLu3+, 1.3 X 10(4) M-1; KLa3+, 1.1 X 10(5) M-1; KCa2+, 3 X 10(2) M-1) which is related to the change in cation charge from 2+ to 3+. The peptide conformation induced by the presence of La3+ generates a different 1H NMR spectrum than the one observed for the lutetium-saturated peptide. Thus, it appears that these metals do not fold the peptide into exactly the same conformation. The resonance shifts observed during the Lu3+ titration are much smaller than those seen in the case of La3+ addition. The fact that lutetium binds less tightly than lanthanum to the peptide may be linked directly or indirectly to the difference in ionic radius between these metals (Lu3+, 0.86 A; La3+, 1.03 A). This may in turn indicate that the peptide primary sequence encodes for some aspects of metal ion specificity. The 1H NMR results also demonstrate that glycine-108 adopts a restricted geometry in the absence of metal such that its two alpha-carbon protons are in different environments which are further affected by the addition of either metal. These observations support the concept that geometric constraints arising from the particular peptide folding pattern near this residue correlate with the highly conserved nature of this site of the EF hand. This position remains occupied by glycine in most EF hand domains with the exception of known distorted calcium binding sites present in intestine calcium binding proteins and S-100.
Activated monocytes and platelet-monocyte aggregates in patients with sickle cell disease* (2002)

Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) increase endothelial surface receptors that mediate the adherence of sickle erythrocytes to the endothelium. Increased circulating levels of these cytokines have been found in patients with sickle cell disease (SCD). Monocytes are a source of both of these inflammatory mediators; we therefore determined whether circulating monocytes were activated in SCD, as defined by intracellular expression of these cytokines. Blood was also assayed for the presence of platelet-monocyte aggregates (PMAs), as platelet adherence is one possible mechanism for monocyte activation. The median percentages of monocytes expressing intracellular TNF-alpha and IL-1beta in SCD patients were 6.8 (2.8-17.3) [median (range)] and 14.1 (1.3-44.8), respectively. In African-American controls the corresponding percentages were 0.3 (0.1-0.5) and 0.4 (0.1-3.0), and in Caucasians 0.2 (0.1-0.5) and 0.8 (0.8-1.9) (P < 0.001, Kruskal-Wallis). The mean percentage (+/- SD) of PMA was 14.0 +/- 8.3 for Caucasian controls, 25.7 +/- 7.3 for African-American controls, and 45.7 +/- 21.6 for patients with SCD (P < 0.001, RM ANOVA; P < 0.05, Newman-Keuls posthoc test). We conclude that there are increased circulating PMAs and monocyte activation in patients with SCD.
The t(4;14) is associated with poor prognosis in myeloma patients undergoing autologous stem cell transplant (2004)

The frequency and prognostic relevance of translocations t(11;14) and t(4;14), the most common translocations involving the immunoglobulin heavy chain (IgH) gene in multiple myeloma (MM), were investigated in 128 patients treated with intensive chemotherapy and autologous stem cell transplant. Myeloma cells were identified by cytoplasmic light chain immunofluorescence combined with fluorescence in situ hybridization (cIg-FISH) for detection of translocations t(11;14) and t(4;14). Overall, t(11;14) was detected in 16 of 125 (12.8%) and t(4;14) in 15 of 120 (12.5%) patients. Progression-free and overall survivals were similar for patients with or without t(11;14). However, patients with t(4;14) had significantly shorter progression-free (median 9.9 months vs. 25.8 months; P = 0.0003) and overall survivals (median 18.3 months vs. 48.1 months; P < 0.0001) than patients without t(4;14). The t(4;14) was associated with IgA and t(11;14) with light chain MM. There was no association between the t(11;14) or t(4;14) and other biological parameters including age, gender, haemoglobin, beta-2 microglobulin, C-reactive protein, calcium, creatinine, albumin, or the percentage of bone marrow plasma cells. Multivariate analysis identified t(4;14) as the only adverse prognostic factor for both progression-free survival and overall survival. Our results indicate that the t(4;14) detected by cIg-FISH is associated with a poor prognosis in MM patients receiving intensive chemotherapy and autotransplant.
Low frequency of pathogenic mutations in the ubiquitin carboxyterminal hydrolase gene in familial Parkinsonʼs disease (1999)

A coding substitution (I93M) in the ubiquitin carboxy-terminal L1 (UCH-L1) gene has recently been identified in a German family with Parkinson's disease. We have sequenced the entire coding region of the gene in 11 families who have a pattern of disease consistent with autosomal dominant inheritance. We found a polymorphism (S18Y) in exon 3, two polymorphisms in the 5' non-coding region, upstream of the transcription start, and an insertion/deletion polymorphism in intron 4. The S18Y allele is present on approximately 20% of chromosomes in a Caucasian population. These changes are, therefore, unlikely to be pathogenic. We conclude that the I93M variant must either be a rare cause of disease or a harmless substitution whose occurrence in the family reflects a chance co-occurrence.
First-Trimester or Second-Trimester Screening, or Both, for Down's Syndrome (2005)

First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection of Down's syndrome, with low false positive rates.
Thermal Denaturation of Human γ-Interferon. A Calorimetric and Spectroscopic Study (1999)

The thermal denaturation of a recombinant human gamma-interferon has been studied as a function of pH in the range from 2 to 10 and buffer concentration in the range from 5 to 100 mM by differential scanning calorimetry, circular dichroism, fluorescence, 1H NMR, and biological activity measurements. The thermal transitions are irreversible at high buffer concentrations at all pH values studied, although they are reversible between pH 3.5 and 5.4 at low buffer concentrations. The denaturation enthalpy, DeltaH(Tm), at denaturation temperature Tm was a function of both Tm and the buffer concentration, and this resulted in heat capacity changes decreasing with buffer concentration. When the denaturation enthalpies were corrected for Tm dependence, they did not appear to change versus pH. The denaturation entropies, however, appeared to decrease with pH, leading to a small but appreciable increase in the stability of the protein with pH. The difference between the number of moles of protons stoichiometrically bound to a mole of protein in the native and thermally denatured state, was calculated from the variation of Tm versus pH at each buffer concentration. The values obtained appear to depend on pH alone rather than upon temperature or buffer concentration, a result which agrees with the invariance of the denaturation enthalpies with pH. This dependence was fitted to the titration curve of a group with a pK of 5.4.
Medipix3 CT for material sciences (2013)

Innovative detector systems for non-destructive material analysis and for medical diagnosis are an important development to improve the performance and the quality of examination methods. For a number of years now photon-counting X-ray detectors are being developed to process incoming X-ray photons as single events. These detectors facilitate a higher signal-to-noise ratio (SNR) than conventional, non-photon-counting, scintillator based detector systems, which detect X-ray photons indirectly through conversion into visible light. The Medipix is a pixelated photon counting semiconductor detector which features adjustable energy thresholds allowing energy selective, multispectral X-ray imaging. The Medipix chip is under continued development by the ``Medipix2 Collaboration'' and ``Medipix3 Collaboration'' at CERN [1]. The Medipix electronic offers 256 × 256 pixels with a pixel pitch of 55 × 55 μm2 and can be hybridized with different sensor materials like Si, CdTe or GaAs. The newest member of the Medipix family is the Medipix3 (ASIC in 0.13 μm CMOS technology) providing up to eight separate 12-bit counters per pixel. It offers a couple of different working modes [2], which are useful for X-ray imaging applications. A Medipix3 CT X-ray measuring station was built up for small animal X-ray imaging and non-destructive material analysis [3]. The combination of the low energy threshold ( ∼ 4 keV) of the Medipix3 with its multispectral capability enables tomographic investigations on objects with low absorption contrast. The advantage of photon counting, multispectral detectors like Medipix3 for material sciences will be presented here as well as a comparison with a scintillator based CT.
RtsA and RtsB Coordinately Regulate Expression of the Invasion and Flagellar Genes inSalmonella entericaSerovar Typhimurium (2003)

Salmonella enterica serovar Typhimurium encounters numerous host environments and defense mechanisms during the infection process. The bacterium responds by tightly regulating the expression of virulence genes. We identified two regulatory proteins, termed RtsA and RtsB, which are encoded in an operon located on an island integrated at tRNA(PheU) in S. enterica serovar Typhimurium. RtsA belongs to the AraC/XylS family of regulators, and RtsB is a helix-turn-helix DNA binding protein. In a random screen, we identified five RtsA-regulated fusions, all belonging to the Salmonella pathogenicity island 1 (SPI1) regulon, which encodes a type III secretion system (TTSS) required for invasion of epithelial cells. We show that RtsA increases expression of the invasion genes by inducing hilA expression. RtsA also induces expression of hilD, hilC, and the invF operon. However, induction of hilA is independent of HilC and HilD and is mediated by direct binding of RtsA to the hilA promoter. The phenotype of an rtsA null mutation is similar to the phenotype of a hilC mutation, both of which decrease expression of SPI1 genes approximately twofold. We also show that RtsA can induce expression of a SPI1 TTSS effector, slrP, independent of any SPI1 regulatory protein. RtsB represses expression of the flagellar genes by binding to the flhDC promoter region. Repression of the positive activators flhDC decreases expression of the entire flagellar regulon. We propose that RtsA and RtsB coordinate induction of invasion and repression of motility in the small intestine.
Properties of Human IgG1s Engineered for Enhanced Binding to the Neonatal Fc Receptor (FcRn) (2006)

We describe here the functional implications of an increase in IgG binding to the neonatal Fc receptor. We have defined in a systematic fashion the relationship between enhanced FcRn binding of a humanized anti-respiratory syncytial virus (RSV) monoclonal antibody (MEDI-524) and the corresponding biological consequences in cynomolgus monkeys. The triple mutation M252Y/S254T/T256E (YTE) was introduced into the Fc portion of MEDI-524. Whereas these substitutions did not affect the ability of MEDI-524 to bind to its cognate antigen and inhibit RSV replication, they resulted in a 10-fold increase in its binding to both cynomolgus monkey and human FcRn at pH 6.0. MEDI-524-YTE was efficiently released from FcRn at pH 7.4 in both cases. We show that MEDI-524-YTE consistently exhibited a nearly 4-fold increase in serum half-life in cynomolgus monkeys when compared with MEDI-524. This constituted the largest half-life improvement described to date for an IgG in a primate. For the first time, we demonstrate that these sustained serum levels resulted in an up to 4-fold increase in lung bioavailability. Importantly, we also establish that our non-human primate model is relevant to human. Finally, we report that the YTE triple substitution provided a means to modulate the antibody-dependent cell-mediated cytotoxicity (ADCC) activity of a humanized IgG1 directed against the human integrin alpha(v)beta3. Therefore, the YTE substitutions allow the simultaneous modulation of serum half-life, tissue distribution and activity of a given human IgG1.
Molecular basis of beta-galactosidase alpha-complementation. (1975)

In previous studies, a cyanogen bromide peptide derived from amino-acid residues 3-92 of beta-galactosidase (EC 3.2.1.23; beta-D-galactoside galactohydrolase) was shown to have alpha-donor activity in intracistronic alpha-complementation. We have now isolated the defective beta-galactosidase alpha-acceptor protein from the deletion mutant strain M15 of Escherichia coli and find that it lacks residues 11-41 of betal-galactosidase. This is demonstrated by the isolation and sequence determination of a cyanogen bromide peptide from the M15 protein, which is identical to the corresponding peptide from beta-galactosidase except for the missing amino acids. We conclude that the alpha-donor peptide restores the region missing in the M15 protein.
Peptide-mediated transdermal delivery of botulinum neurotoxin type A reduces neurogenic inflammation in the skin (2010)

Release of inflammatory pain mediators from peripheral sensory afferent endings contributes to the development of a positive feedback cycle resulting in chronic inflammation and pain. Botulinum neurotoxin type A (BoNT-A) blocks exocytosis of neurotransmitters and may therefore block the release of pain modulators in the periphery. Subcutaneous administration of BoNT-A (2.5, 5 and 10U) reduced plasma extravasation (PE) caused by electrical stimulation of the saphenous nerve or capsaicin in the rat hindpaw skin (ANOVA, Post hoc Tukey, p<0.05, n=6). Subcutaneous BoNT-A also reduced blood flow changes evoked by saphenous nerve stimulation (ANOVA, Post hoc Tukey, p<0.05, n=6). Subcutaneous BoNT-A had no effect on PE induced by local injection of substance P (SP) or vasodilation induced by local CGRP injection. Although BoNT-A is an effective treatment for a wide range of painful conditions, the toxin's large size necessitates that it be injected at numerous sites. We found that a short synthetic peptide (TD-1) can facilitate effective transdermal delivery of BoNT-A through intact skin. Coadministration of TD-1 and BoNT-A to the hindpaw skin resulted in a significant reduction in PE evoked by electrical stimulation. The findings show that BoNT-A can be administered subcutaneously or topically with a novel transdermal delivery peptide to reduce inflammation produced by activating nociceptors in the skin. Peptide-mediated delivery of BoNT-A is an easy and non-invasive way of administering the toxin that may prove to be useful in clinical practice.