gebhart/patrepeval huggingface dataset:
New IL-17 Family Members Promote Th1 or Th2 Responses in the Lung: In Vivo Function of the Novel Cytokine IL-25 (2002)

We have biologically characterized two new members of the IL-17 cytokine family: IL-17F and IL-25. In contrast to conventional in vitro screening approaches, we have characterized the activity of these new molecules by direct in vivo analysis and have compared their function to that of other IL-17 family members. Intranasal administration of adenovirus expressing IL-17, IL-17C, or IL-17F resulted in bronchoalveolar lavage neutrophilia and inflammatory gene expression in the lung. In contrast, intranasal administration of IL-25-expressing adenovirus or IL-25 protein resulted in the production of IL-4, IL-5, IL-13, and eotaxin mRNA in the lung and marked eosinophilia in the bronchoalveolar lavage and lung tissue. Mice given intranasal IL-25 also developed epithelial cell hyperplasia, increased mucus secretion, and airway hyperreactivity. IL-25 gene expression was detected following Aspergillus and Nippostrongylus infection in the lung and gut, respectively. IL-25-induced eosinophilia required IL-5 and IL-13, but not IL-4 or T cells. Following IL-25 administration, the IL-5(+) staining cells were CD45R/B220(+), Thy-1(+/-), but were NK1.1-, Ly-6G(GR-1)-, CD4-, CD3-, and c-kit-negative. gamma-common knockout mice did not develop eosinophilia in response to IL-25, nor were IL-5(+) cells detected. These findings suggest the existence of a previously unrecognized cell population that may initiate Th2-like responses by responding to IL-25 in vivo. Further, these data demonstrate the heterogeneity of function within the IL-17 cytokine family and suggest that IL-25 may be an important mediator of allergic disease via production of IL-4, IL-5, IL-13, and eotaxin.
The Arabidopsis TT2 Gene Encodes an R2R3 MYB Domain Protein That Acts as a Key Determinant for Proanthocyanidin Accumulation in Developing Seed (2001)

In Arabidopsis, proanthocyanidins specifically accumulate in the endothelium during early seed development. At least three TRANSPARENT TESTA (TT) genes, TT2, TT8, and TTG1, are necessary for the normal expression of several flavonoid structural genes in immature seed, such as DIHYDROFLAVONOL-4-REDUCTASE and BANYULS (BAN). TT8 and TTG1 were characterized recently and found to code for a basic helix-loop-helix domain transcription factor and a WD-repeat-containing protein, respectively. Here the molecular cloning of the TT2 gene was achieved by T-DNA tagging. TT2 encoded an R2R3 MYB domain protein with high similarity to the rice OsMYB3 protein and the maize COLORLESS1 factor. A TT2-green fluorescent protein fusion protein was located mostly in the nucleus, in agreement with the regulatory function of the native TT2 protein. TT2 expression was restricted to the seed during early embryogenesis, consistent with BAN expression and the proanthocyanidin deposition profile. Finally, in gain-of-function experiments, TT2 was able to induce ectopic expression of BAN in young seedlings and roots in the presence of a functional TT8 protein. Therefore, our results strongly suggest that stringent spatial and temporal BAN expression, and thus proanthocyanidin accumulation, are determined at least partially by TT2.
Detection and Differentiation of Chlamydiae by Fluorescence In Situ Hybridization (2002)

Chlamydiae are important pathogens of humans and animals but diagnosis of chlamydial infections is still hampered by inadequate detection methods. Fluorescence in situ hybridization (FISH) using rRNA-targeted oligonucleotide probes is widely used for the investigation of uncultured bacteria in complex microbial communities and has recently also been shown to be a valuable tool for the rapid detection of various bacterial pathogens in clinical specimens. Here we report on the development and evaluation of a hierarchic probe set for the specific detection and differentiation of chlamydiae, particularly C. pneumoniae, C. trachomatis, C. psittaci, and the recently described chlamydia-like bacteria comprising the novel genera Neochlamydia and PARACHLAMYDIA: The specificity of the nine newly developed probes was successfully demonstrated by in situ hybridization of experimentally infected amoebae and HeLa 229 cells, including HeLa 229 cells coinfected with C. pneumoniae and C. trachomatis. FISH reliably stained chlamydial inclusions as early as 12 h postinfection. The sensitivity of FISH was further confirmed by combination with direct fluorescence antibody staining. In contrast to previously established detection methods for chlamydiae, FISH was not susceptible to false-positive results and allows the detection of all recognized chlamydiae in one single step.
Isolation and Characterization of the S-Carboxymethyl Heavy Chain Derivative of Human Plasmin (1971)

Abstract The S-carboxymethyl heavy chain derivative of human plasmin was prepared in a highly purified form by precipitating out the contaminating S-carboxymethyl light chain derivative in 1 m trichloracetic acid-8 m urea. The S-carboxymethyl heavy chain derivative was shown to be homogeneous by ultracentrifugal, carboxyl-terminal amino acid, and cellulose acetate electrophoretic analyses. Its weight average molecular weight was determined to be 48,800 ± 3,000 and its sedimentation coefficient was determined to be 2.8 S. Arginine was verified to be its carboxyl-terminal amino acid. The heavy chain derivative consists of approximately 410 amino acid residues.
The Growing Burden of Tuberculosis (2003)

The HIV pandemic presents a massive challenge to global TB control. The prevention of HIV and TB, the extension of WHO DOTS programs, and a focused effort to control HIV-related TB in areas of high HIV prevalence are matters of great urgency.
Screening of agrochemicals in foodstuffs using low-temperature plasma (LTP) ambient ionization mass spectrometry (2010)

Low-temperature plasma (LTP) permits direct ambient ionization and mass analysis of samples in their native environment with minimal or no prior preparation. LTP utilizes dielectric barrier discharges (DBDs) to create a low power plasma which is guided by gas flow onto the sample from which analytes are desorbed and ionized. In this study, the potential of LTP-MS for the detection of pesticide residues in food is demonstrated. Thirteen multi-class agricultural chemicals were studied (ametryn, amitraz, atrazine, buprofezin, DEET, diphenylamine, ethoxyquin, imazalil, isofenphos-methyl, isoproturon, malathion, parathion-ethyl and terbuthylazine). To evaluate the potential of the proposed approach, LTP-MS experiments were performed directly on fruit peels as well as on fruit/vegetable extracts. Most of the agrochemicals examined displayed remarkable sensitivity in the positive ion mode, giving limits of detection (LOD) for the direct measurement in the low picogram range. Tandem mass spectrometry (MS/MS) was used to confirm identification of selected pesticides by using for these experiments spiked fruit/vegetable extracts (QuEChERS, a standard sample treatment protocol) at levels as low as 1 pg, absolute, for some of the analytes. Comparisons of the data obtained by direct LTP-MS were made with the slower but more accurate conventional LC-MS/MS procedure. Herbicides spiked in aqueous solutions were detectable at LODs as low as 0.5 microg L(-1) without the need for any sample preparation. The results demonstrate that ambient LTP-MS can be applied for the detection and confirmation of traces of agrochemicals in actual market-purchased produce and in natural water samples. Quantitative analysis was also performed in a few selected cases and displayed a relatively high degree of linearity over four orders of magnitude.
Vehicle-to-Infrastructure and Vehicle-to-Vehicle Information System in Work Zones (2012)

This paper describes the architecture, functionality, and field demonstration results of a newly developed dedicated short-range communication–based vehicle-to-infrastructure work zone traffic information system with vehicle-to-vehicle assistance. The new system is portable and can automatically acquire important work zone travel information such as the travel time and the starting location of congestion and then relay this information to drivers approaching the congestion site. Such information can help drivers make informed decisions on route choice, prepare for upcoming congestion, or both. The authors had designed a similar system earlier; that system had limited congestion coverage and message broadcast ranges, but the new system can achieve a much longer broadcast range (up to a few tens of kilometers) and can handle much longer congestion coverage (up to a few kilometers) by incorporating vehicle-to-infrastructure communication assisted by vehicle-to-vehicle communication. The system requires only a single roadside unit to acquire traffic data by engaging the vehicles traveling on the road whether within or outside of its direct wireless access range. From the traffic data, the system estimates important traffic parameters such as travel time and starting location of congestion and periodically broadcasts this information back to the vehicles approaching the congestion well before they enter the congested area. The results from the field demonstration show that the new system can adapt to a dynamically changing work zone traffic environment and can handle much longer congestion lengths as compared with the previous system, which used only vehicle-to-infrastructure communication without vehicle-to-vehicle assistance.
Positive selection of V beta 8+ CD4-8- thymocytes by class I molecules expressed by hematopoietic cells. (1993)

A small subset of T cells of mature phenotype express the alpha/beta T cell receptor, but not CD4 and CD8 coreceptors (alpha/beta double-negative [DN] cells). The repertoire of V beta usage of alpha/beta DN cells is strongly biased towards V beta 8 expression, suggesting that the formation of the population is subject to selection. We now report that deficiency of class I expression leads to a strongly depressed frequency of V beta 8+ DN cells, but has little effect on V beta 8- DN cells. Studies of hematopoietic chimeras between class I+ and class I- mice demonstrated that expression of class I molecules by hematopoietic cells is necessary and sufficient for selection of most V beta 8 DN cells. The lack of a role for class I expression by thymic epithelial cells suggests that the mechanism of selection of these cells by class I differs significantly from the mechanism of selection of conventional T cells. Models to explain the selection of these cells as well as their possible function in vivo are discussed.
Anti-cancer activity of 9-nitrocamptothecin liposome aerosol in mice. (2000)

We have found that 9-nitrocamptothecin (9-NC) administered in a liposome formulation by small-particle aerosol is remarkably effective in the treatment of cancer in mice in doses that are several-fold lower than is required by other routes of administration. This favorable response was noted when used against human cancer xenografts implanted subcutaneously (1) and against human osteosarcoma cells given intravenously to produce experimental pulmonary metastases, all in the nude mouse model. B-16 murine melanoma cells given intravenously to produce pulmonary metastases also responded to the treatment. Pharmacokinetic (2) and toxicology studies (unpublished) were performed in mice and dogs. These studies suggested that the methodology might have application in treatment of cancer in humans. A report of these studies follows.
Mechanisms of functional recovery and regeneration after spinal cord transection in larval sea lamprey. (1978)

1. Large sea lamprey larvae, close to metamorphosis, regained swimming coordination after several weeks following complete spinal cord transection. Recovery was much faster when animals were kept at 23 than at 12 degrees C. 2. The behavioural recovery involved a regenerative mechanism in the spinal cord, since stimulation of the head resulted in tail curling, even when all tissue other than spinal cord and notocord was stripped away for several cm above and below the transection. 3. Following complete behavioural recovery, stimulation of the rostral cord evoked electrical signals recorded from the cord dorsum for only 10 mm below the transection. 4. Dorsal cells and giant interneurones, which normally project to the brain, could not be antidromically activated across the transection zone. However, giant interneurones could be activated polysynaptically by descending volleys. 5. Twelve of eighteen large reticulospinal axons followed in serial sections regenerated across the glial-ependymal scar, but branched abnormally and migrated away from their customary locations. They became smaller, and were finally lost within 4 mm of the centre of the transection zone. 6. These data suggest that behavioural recovery does not involve long axon tract regeneration. An alternate hypothesis, that short distance sprouting of axons across the transection zone may result in synapse formation with propriospinal interneurones which relay the necessary information, is discussed.
Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 1: High-Throughput Screening and Preliminary Exploration (2017)

Lysine specific demethylase 1 KDM1A (LSD1) regulates histone methylation and it is increasingly recognized as a potential therapeutic target in oncology. We report on a high-throughput screening campaign performed on KDM1A/CoREST, using a time-resolved fluorescence resonance energy transfer (TR-FRET) technology, to identify reversible inhibitors. The screening led to 115 hits for which we determined biochemical IC<sub>50</sub>, thus identifying four chemical series. After data analysis, we have prioritized the chemical series of N-phenyl-4H-thieno[3, 2-b]pyrrole-5-carboxamide for which we obtained X-ray structures of the most potent hit (compound 19, IC<sub>50</sub> = 2.9 μM) in complex with the enzyme. Initial expansion of this chemical class, both modifying core structure and decorating benzamide moiety, was directed toward the definition of the moieties responsible for the interaction with the enzyme. Preliminary optimization led to compound 90, which inhibited the enzyme with a submicromolar IC<sub>50</sub> (0.162 μM), capable of inhibiting the target in cells.
GeneBuilder: interactive in silico prediction of gene structure. (1999)

The GeneBuilder system is implemented as a part of the WebGene a the URL: http://www.itba.mi. cnr.it/webgene and TRADAT (TRAncription Database and Analysis Tools) launcher URL: http://www.itba.mi.cnr.it/tradat.
Carbon dioxide laser polishing of fused silica surfaces for increased laser-damage resistance at 1064 nm (1982)

Mechanically polished fused silica surfaces were heated with continuous-wave CO(2) laser radiation. Laser-damage thresholds of the surfaces were measured with 1064-nm 9-nsec pulses focused to small spots and with large-spot, 1064-nm, 1-nsec irradiation. A sharp transition from laser-damage-prone to highly laser-damage-resistant took place over a small range in CO(2) laser power. The transition to high damage resistance occurred at a silica surface temperature where material softening began to take place as evidenced by the onset of residual strain in the CO(2) laser-processed part. The small-spot damage measurements show that some CO(2) laser-treated surfaces have a local damage threshold as high as the bulk damage threshold of SiO(2). On some CO(2) laser-treated surfaces, large-spot damage thresholds were increased by a factor of 3-4 over thresholds of the original mechanically polished surface. These treated parts show no obvious change in surface appearance as seen in bright-field, Nomarski, or total internal reflection microscopy. They also show little change in transmissive figure. Further, antireflection films deposited on CO(2) laser-treated surfaces have thresholds greater than the thresholds of antireflection films on mechanically polished surfaces.
Ceramic packaging in neural implants (2020)

The lifetime of neural implants is strongly dependent on packaging due to the aqueous and biochemically aggressive nature of the body. Over the last decade, there has been a drive towards neuromodulatory implants which are wireless and approaching millimeter-scales with increasing electrode count. A so-far unrealized goal for these new types of devices is an in-vivo lifetime comparable to a sizable fraction of a healthy patient's lifetime (>10-20 years). Existing, approved medical implants commonly encapsulate components in metal enclosures (e.g. titanium) with brazed ceramic inserts for electrode feedthrough. It is unclear how amenable the traditional approach is to the simultaneous goals of miniaturization, increased channel count, and wireless communication. Ceramic materials have also played a significant role in traditional medical implants due to their dielectric properties, corrosion resistance, biocompatibility, and high strength, but are not as commonly used for housing materials due to their brittleness and the difficulty they present in creating complex housing geometries. However, thin-film technology has opened new opportunities for ceramics processing. Thin films derived largely from the semiconductor industry can be deposited and patterned in new ways, have conductivities which can be altered during manufacturing to provide conductors as well as insulators, and can be used to fabricate flexible substrates. In this review, we give an overview of packaging for neural implants, with an emphasis on how ceramic materials have been utilized in medical device packaging, as well as how ceramic thin-film micromachining and processing may be further developed to create truly reliable, miniaturized, neural implants.
Astroglial Inhibition of NF-κB Does Not Ameliorate Disease Onset and Progression in a Mouse Model for Amyotrophic Lateral Sclerosis (ALS) (2011)

Motor neuron death in amyotrophic lateral sclerosis (ALS) is considered a "non-cell autonomous" process, with astrocytes playing a critical role in disease progression. Glial cells are activated early in transgenic mice expressing mutant SOD1, suggesting that neuroinflammation has a relevant role in the cascade of events that trigger the death of motor neurons. An inflammatory cascade including COX2 expression, secretion of cytokines and release of NO from astrocytes may descend from activation of a NF-κB-mediated pathway observed in astrocytes from ALS patients and in experimental models. We have attempted rescue of transgenic mutant SOD1 mice through the inhibition of the NF-κB pathway selectively in astrocytes. Here we show that despite efficient inhibition of this major pathway, double transgenic mice expressing the mutant SOD1(G93A) ubiquitously and the dominant negative form of IκBα (IκBαAA) in astrocytes under control of the GFAP promoter show no benefit in terms of onset and progression of disease. Our data indicate that motor neuron death in ALS cannot be prevented by inhibition of a single inflammatory pathway because alternative pathways are activated in the presence of a persistent toxic stimulus.
Rate of 59Fe Uptake into Brain and Cerebrospinal Fluid and the Influence Thereon of Antibodies Against the Transferrin Receptor (1993)

Uptake of 59Fe from blood into brains of anaesthetized rats and mice has been studied by intravenous infusion of [59Fe]ferrous ascorbate or of 59Fe-transferrin, the results not being significantly different. Uptakes in the rat were linear with time, but increased at longer times in the mouse. Transfer constants, K(in) (in ml/g/h x 10(3)), for cerebral hemispheres were 5.2 in the adult rat and 5.6 in the mouse. These K(in) values corresponded to 59Fe influxes of 145 and 322 pmol/g/h, respectively. 59Fe uptake into the mouse brain occurred in the following order: cerebellum > brainstem > frontal cerebral cortex > parietal cortex > occipital cortex > hippocampus > caudate nucleus. In genetically hypotransferrinaemic mice, 59Fe uptake into brain was 80-95 times greater than in To strain mice. Pretreatment of young rats and mice with monoclonal antibodies to transferrin receptors, i.e., the anti-rat immunoglobulin G OX 26 and the anti-mouse immunoglobulin M RI7 208, inhibited 59Fe uptake into spleen by 94% and 98%, respectively, indicating saturation of receptors. The antibodies reduced 59Fe uptake into rat brain by 35-60% and that into mouse brain by 65-85%. Although a major portion of iron transport across the blood-brain barrier is normally transferrin-mediated, non-transferrin-bound iron readily crosses it at low serum transferrin levels.
Potent Inhibition of Thyroid Cancer Cells by the MEK Inhibitor PD0325901 and Its Potentiation by Suppression of the PI3K and NF-κB Pathways (2008)

The MEK inhibitor PD0325901 has a wide range of potent inhibitory effects on thyroid cancer cells, some of which seemed to be genotype-selective, consistent with the results previously observed with an early-generation MEK inhibitor, CI-1040. The data provide further evidence that targeted inhibition of MEK may be therapeutically effective for thyroid cancer, particularly if the PI3K and NF-kappaB pathways are concurrently inhibited.
Noise-induced hypertension and magnesium in rats: relationship to microcirculation and calcium (1992)

It has been demonstrated that audiogenic stress (AS) can induce elevation of arterial blood pressure (ABP) in animals and humans and that noise-induced hearing loss may be associated with alterations in Mg metabolism. Experiments were designed to determine whether 1) there is a causal relationship among environmental noise stress, serum and vascular tissue (aortas and portal veins) Mg contents, and development of hypertension and 2) such noise-induced hypertension has a microcirculatory basis and what the mechanism may be. Rats maintained on normal Mg-containing diets for 12 wk (plasma [Mg] = 0.96 +/- 0.02 mM) and subjected to AS (85 dB(A), 12 h/day for 8 wk; 95 dB(A), 16 h/day for 4 wk) demonstrated significant elevation in systolic and diastolic ABP; plasma [Mg] showed a 15% deficit, whereas aortic and portal vein muscle exhibited slight reductions in Mg content and elevation in Ca. Moderate and more severely Mg-deficient animals not subjected to AS also exhibited significant elevations in systolic and diastolic ABP; vascular tissue Mg content decreased, whereas Ca content rose. Animals subjected to combined Mg deficiency and AS for 12 wk exhibited the greatest deficits in plasma and vascular muscle Mg and the greatest elevations in systolic and diastolic ABP; vascular tissue Ca contents also showed the greatest increases. In situ measurements of mesenteric arterioles, venules, and precapillary sphincters in the various subgroups revealed that the lower the plasma [Mg], the more constricted the microvessels, and the higher the ABP, the lower the plasma [Mg]. Capillary blood flow velocities were decreased in relation to the degree of plasma Mg deficit.(ABSTRACT TRUNCATED AT 250 WORDS)