gebhart/patrepeval huggingface dataset:
Effects of Intrafollicular Injections of Prostaglandins in Non-Pregnant and Pregnant Ewes (1975)

Responses to three doses of prostaglandin (PG)F2α (100, 150 and 200 jug) and a single dose (200 µg) of PGF1α, PGE2 and arachidonic acid or buffer injected on day 9 into the largest follicle on the ovary with the corpus luteum were compared in groups of six non-pregnant unilaterally-ovulating ewes. Jugular venous plasma was collected at 0 time and .5, 1, 4 and 24 hr post-injection. Only ewes treated with PGF2α returned to estrus within 72 hr after injection (200 µg, 4 of 6; 150 µg, 3 of 6; 100 µg, 1 of 6). Progesterone concentrations in ewes treated with PGF2α did not differ among doses or from controls at 0 and 4 hr, while at 1 hr all ewes treated with PGF2α had values lower than control ewes. At 24 hr, ewes treated with 150 µg PGF2α had lower progesterone than control ewes or ewes receiving 100 µg PGF2α:- Progesterone concentrations in ewes treated with PGF1α or arachidonic acid did not differ from those in control ewes. Ewes treated with PGE2 had higher progesterone than control ewes at 4 hr and exceeded ewes in all other groups at 24 hours. Estrone and estradiol-17β did not vary with treatment or time in ewes receiving buffer, 200 µg PGF2α or 200 µg PGF1α. A single large follicle in each ovary bearing corpora lutea in each of 17 mated and 14 non-mated ewes was injected with 200 µg PGF2α on day 12. Jugular venous blood was collected at 0 time and 1, 4 and 24 hr post-injection. Mated ewes were sacrificed to check for embryos in the uterus as they returned to estrus or on days 17 to 22. Progesterone declined similarly in non-mated ewes (14), mated ewes with no embryos (9) and mated ewes with embryos (8), except that some apparent recovery was seen by 24 hr in pregnant ewes. In non-mated ewes and mated ewes without embryos, 11/14 and 8/9 returned to estrus early and mean intervals from treatment to estrus were 2.9 and 2.4 days, respectively. Five of eight ewes with embryos did not return to estrus, and two of the three returning to estrus had small embryos believed to have stopped developing before injection of PGF2α It is suggested that a factor from the conceptus overcomes the luteolytic effect of PGF2α in sheep.
CD154/CD40 and CD70/CD27 interactions have different and sequential functions in T cell-dependent B cell responses: enhancement of plasma cell differentiation by CD27 signaling (1997)

CD40, a TNF receptor family member, plays a central role in T cell-mediated B cell activation. We have recently demonstrated that CD27, another TNF receptor family member, was also involved in B cell regulation and enhanced Ig production. In this report we compare CD27 and CD40 signals in B cell function. We selectively mimicked the effect of T cell help by addition to peripheral blood B cells activated with Staphylococcus aureus Cowan I strain and IL-2 of irradiated 300-19 cells transfected with either the CD70 (CD27 ligand) gene or the CD154 (CD40 ligand) gene, the vector alone, or both CD70 and CD154 genes. CD27 ligation induced only a slight increase in B cell proliferation compared with the dramatic enhancement induced by CD40 ligation; double ligation proved to be less efficient than CD40 ligation alone. In contrast, IgG production was increased only by CD27 ligation alone. Moreover, the CD27 signal was more efficient when it was given on day 2 of the culture rather than on day 0. Phenotypic analysis of the activated cells showed that CD27 ligation increased the percentage of cells showing a plasma cell profile (CD19-, CD38+), whereas upon CD40 ligation most of the cells still had a germinal center-like phenotype (CD19+, CD38+). Our results suggest that the CD27 and CD40 signals are not synergistic but, rather, are complementary and involve distinct steps of T cell-dependent B cell activation. CD27 may be more important in the induction of plasma cell differentiation at a time when the expansion phase has already occurred.
Imaging the nanoscale organization of peptidoglycan in living Lactococcus lactis cells (2010)

The spatial organization of peptidoglycan, the major constituent of bacterial cell-walls, is an important, yet still unsolved issue in microbiology. In this paper, we show that the combined use of atomic force microscopy and cell wall mutants is a powerful platform for probing the nanoscale architecture of cell wall peptidoglycan in living Gram-positive bacteria. Using topographic imaging, we found that Lactococcus lactis wild-type cells display a smooth, featureless surface morphology, whereas mutant strains lacking cell wall exopolysaccharides feature 25-nm-wide periodic bands running parallel to the short axis of the cell. In addition, we used single-molecule recognition imaging to show that parallel bands are made of peptidoglycan. Our data, obtained for the first time on living ovococci, argue for an architectural feature of the cell wall in the plane perpendicular to the long axis of the cell. The non-invasive live cell experiments presented here open new avenues for understanding the architecture and assembly of peptidoglycan in Gram-positive bacteria.
Text-learning and related intelligent agents: a survey (1999)

In surveying current research in the development of text-learning intelligent agents, the author focuses on three key criteria: what representation the particular application uses for documents, how it selects features, and what learning algorithm it uses. She then describes Personal WebWatcher, a content-based intelligent agent that uses text-learning for user-customized Web browsing.
Acoustic microscopy-a summary (1992)

Acoustic microscopy enables one to image the interaction of acoustic waves with the elastic properties of a specimen with microscopic resolution. A lens with good focusing properties on the axis can be used for both transmitting and receiving the signal, and an image is formed by scanning the lens mechanically over the specimen. In pressurised superfluid helium with nonlinear coupling to harmonics a resolution of 15 nm has been achieved, but for routine use 2 GHz is the highest practical frequency, which offers a resolution of about 0.7 mu m. The information is contained in the way that the acoustic wave is reflected from the specimen. For subsurface imaging, especially in polymer based materials such as composites and electronic packaging, the enhanced depth resolution of a confocal imaging system can be exploited to give good contrast from the plane of interest even when the specimen contains many scatters. In higher stiffness specimens, including most metals, semiconductors and ceramics, a dominant role in the contrast can be played by Rayleigh waves in the surface. If the specimen has a surface layer, then the propagation of the Rayleigh waves is sensitive to the perturbing action of the layer. If the specimen is anisotropic, then there will be a dependence on the orientation of the surface and the direction of propagation in it. If there are surface cracks or boundaries, then there will be strong contrast when they scatter the Rayleigh waves. Detailed theory is available to relate the elastic properties of the surface to the contrast, and these enable informed interpretation of the acoustic images to be made, and also provide a foundation for more quantitative acoustic microscopy.
Endogenous GLP-1 modulates hippocampal activity in β-amyloid protein-treated rats (1999)

We examined the relationship between the histochemical distribution of endogenous GLP-1 (7-36) amide in the hippocampus and memory impairment assessed by a step-through type passive avoidance task in rats continuously infused with beta-amyloid protein (1-40) into the lateral cerebroventricle using a mini-osmotic pump. Our results demonstrated that endogenous GLP-1 (7-36) amide appears in the hippocampus accompanied by progression of memory impairment. Electrophysiological studies also indicated that endogenous GLP-1 inhibits hippocampal neuronal activity in beta-amyloid protein-treated rats.
Gap junctions in isolated rat aorta: evidence for contractile responses that exhibit a differential dependence on intercellular communication (2000)

Connexin43 (Cx43) is a major gap junction protein present in the Fischer-344 rat aorta. Previous studies have identified conditions under which selective disruption of intercellular communication with heptanol caused a significant, readily reversible and time-dependent diminution in the magnitude of alpha1-adrenergic contractions in isolated rat aorta. These observations have indentified a significant role for gap junctions in modulating vascular smooth muscle tone. The goal of these steady-state studies was to utilize isolated rat aortic rings to further evaluate the contribution of intercellular junctions to contractions elicited by cellular activation in response to several other vascular spasmogens. The effects of heptanol were examined (0.2-2.0 mM) on equivalent submaximal ( approximately 75% of the phenylephrine maximum) aortic contractions elicited by 5-hydroxytryptamine (5-HT; 1-2 microM), prostaglandin F2alpha (PGF2alpha; 1 microM) and endothelin-1 (ET-1; 20 nM). Statistical analysis revealed that 200 microM and 500 microM heptanol diminished the maximal amplitude of the steady-state contractile responses for 5-HT from a control response of 75 +/- 6% (N = 26 rings) to 57 +/- 7% (N = 26 rings) and 34.9 +/- 6% (N = 13 rings), respectively (P<0.05), and for PGF2alpha from a control response of 75 +/- 10% (N = 16 rings) to 52 +/- 8% (N = 19 rings) and 25.9 +/- 6% (N = 18 rings), respectively (P<0.05). In contrast, 200 microM and 500 microM heptanol had no detectable effect on the magnitude of ET-1-induced contractile responses, which were 76 +/- 5. 0% for the control response (N = 38 rings), 59 +/- 6.0% in the presence of 200 microM heptanol (N = 17 rings), and 70 +/- 6.0% in the presence of 500 microM heptanol (N = 23 rings) (P<0.13). Increasing the heptanol concentration to 1 mM was associated with a significant decrease in the magnitude of the steady-state ET-1-induced contractile response to 32 +/- 5% (21 rings; P<0.01); further increasing the heptanol concentration to 2 mM had no additional effect. In rat aorta then, junctional modulation of tissue contractility appears to be agonist-dependent.
Avelumab (MSB0010718C; anti-PD-L1) in patients with metastatic Merkel cell carcinoma previously treated with chemotherapy: Results of the phase 2 JAVELIN Merkel 200 trial. (2016)

9508 Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer associated with Merkel cell polyomavirus. Therapeutic options are limited for metastatic MCC that has progressed after 1st-line chemotherapy. PD-L1 is frequently expressed in the MCC tumor microenvironment on tumor and immune cells. Avelumab* is a fully human anti-PD-L1 IgG1 mAb showing efficacy and an acceptable safety profile in multiple cancers. Avelumab received FDA breakthrough therapy and fast-track as well as FDA and EMA orphan drug designations in MCC. Methods: This phase 2 trial (NCT02155647) reports on single-agent avelumab in patients (pts) with metastatic MCC who had progressed on chemotherapy. Pts received avelumab 10 mg/kg IV Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 wks (RECIST 1.1 by independent review). Objective response rate (ORR; primary endpoint), duration of response, and PFS were evaluated. PD-L1 expression was assessed by IHC. Results: As of Nov 20, 2015, 88 pts with metastatic MCC were treated with avelumab. Median age was 72.5 y (range 33-88) and ECOG PS was 0 (55.7%) or 1 (44.3%). 65.9% of pts had received 1 prior therapy for metastatic disease; 34.1% had >1. For the subgroup followed ≥24 wks (61 pts), confirmed ORR was 29.5% (18/61 pts; 95% CI: 18.5, 42.6). Six pts (9.8%) had complete responses, 12 (19.7%) had partial responses, and 7 (11.5%) had stable disease. 15/18 (83.3%) responses were ongoing. Response duration was 2.8-14.6+ mos (median not reached). 14/18 responses occurred by week 7. Median PFS was 2.6 mos (95% CI: 1.4, 4.2) and PFS rate at 6 mos was 36% (95% CI: 23, 49). Treatment-related (TR) AEs occurred in 59 pts (67.0%); those occurring ≥10% were fatigue (21.6%) and infusion-related reaction (13.6%). Grade 3 TRAEs were reported in 3 pts (3.4%); there were no grade 4 TRAEs or treatment-related deaths. Conclusions: Avelumab showed a manageable safety profile with durable responses in pts with metastatic MCC who had progressed on chemotherapy. Additional clinical evaluation is warranted. *Proposed INN. Clinical trial information: NCT02155647.
Pathogenesis of giant-cell arteritis: how targeted therapies are influencing our understanding of the mechanisms involved (2017)

GCA is a chronic granulomatous vasculitis that affects large- and medium-sized vessels. Both the innate and the adaptive immune system are thought to play an important role in the initial events of the pathogenesis of GCA. Amplification cascades are involved in the subsequent development and progression of the disease, resulting in vascular inflammation, remodelling and occlusion. The development of large-vessel vasculitis in genetically modified mice has provided some evidence regarding potential mechanisms that lead to vascular inflammation. However, the participation of specific mechanistic pathways in GCA has not been fully established because of the paucity and limitations of functional models. Treatment of GCA is evolving, and novel therapies are being incorporated into the GCA treatment landscape. In addition, to improve the management of GCA, targeted therapies are providing functional proof of concept of the relevance of particular pathogenic mechanisms in the development of GCA and in sustaining vascular inflammation.
One Hundred Seventy-Fold Increase in Excretion of an FV Fragment-Tumor Necrosis Factor Alpha Fusion Protein (sFV/TNF-α) from Escherichia coli Caused by the Synergistic Effects of Glycine and Triton X-100 (1998)

To target tumor necrosis factor alpha (TNF-alpha) to tumor cells, recombinant DNA techniques were used to construct and express the fused gene VKLVH-TNF-alpha, which encodes the secreted form of single-chain fusion protein sFV/TNF-alpha in Escherichia coli. sFV/TNF-alpha was secreted into the culture medium and purified by affinity chromatography. The production of the fusion protein in the culture medium under the optimal conditions of 30 degrees C and 37 micromol of isopropyl-beta-D-thiogalactopyranoside (IPTG) per liter was 16- and 5-fold higher than that under the standard conditions of 37 degrees C and 1 mmol of IPTG per liter. Fusion protein excretion into culture medium with 2% glycine, 1% Triton X-100, or both of these two chemicals was either 14-, 38-, or 170-fold higher, respectively than that without the two chemicals. The final yield of sFV/TNF-alpha was estimated to be 50 mg/liter. The loss of integrity of the cellular membrane may be a potential mechanism for enhancement of fusion protein production and excretion by treatment with glycine and Triton X-100. This study thus provides a practical, large-scale method for more efficient production of the heterologous fusion protein sFV/TNF-alpha in E. coli by using glycine and Triton X-100.
Space-time coded OFDM for high data-rate wireless communication over wideband channels (2002)

There has been an increasing interest in providing high data-rate services such as video-conferencing, multimedia Internet access and wide area network over wideband wireless channels. Wideband wireless channels available in the PCS band (2 GHz) have been envisioned to be used by mobile (high Doppler) and stationary (low Doppler) units in a variety of delay spread profiles. This is a challenging task, given the limited link budget and severity of wireless environment, and calls for the development of novel robust bandwidth efficient techniques which work reliably at low SNRs. To this end, we design a space-time coded orthogonal frequency division multiplexing (OFDM) modulated physical layer. This combines coding and modulation. Space-time codes were previously proposed for narrowband wireless channels. These codes have high spectral efficiency and operate at very low SNR (within 2-3 dB of the capacity). On the other hand, OFDM has matured as a modulation scheme for wideband channels. We combine these two in a natural manner and propose a system achieving data rates of 1.5-3 Mbps over a 1 MHz bandwidth channel. This system requires 18-23 dB (resp. 9-14 dB) receive SNR at a frame error probability of 10/sup -2/ with two transmit and one receive antennas (resp. two transmit and two receive antennas). As space-time coding does not require any form of interleaving, the proposed system is attractive for delay-sensitive applications.
Friction Stir Processing: A New Grain Refinement Technique to Achieve High Strain Rate Superplasticity in Commercial Alloys (2001)

Friction stir processing is a new thermo-mechanical processing technique that leads to a microstructure amenable for high strain rate superplasticity in commercial aluminum alloys. Friction stirring produces a combination of very fine grain size and high grain boundary misorientation angles. Preliminary results on a 7075 Al demonstrate high strain rate superplasticity in the temperature range of 430-510 °C. For example, an elongation of >1000 % was observed at 490 °C and 1 × 10 -2 s -1 . This demonstrates a new possibility to economically obtain a superplastic microstructure in commercial aluminum alloys. Based on these results, a three-step manufacturing process to fabricate complex shaped components can be envisaged: cast sheet or hot-pressed powder metallurgy sheet + friction stir processing + superplastic forging or forming.
The immunohistochemical localization of drug‐metabolizing enzymes in prostate cancer (1995)

The major groups of enzymes involved in activating and detoxifying therapeutic drugs, not least several anti-cancer drugs, include the cytochromes P450 (P450s), epoxide hydrolase, and glutathione S-transferases (GSTs). The expression of these enzymes in malignant tumours is one possible mechanism of anti-cancer drug resistance. This study has investigated the presence, cellular localization, and distribution of drug-metabolizing enzymes in prostate cancer. The P450 subfamilies CYP1A, CYP2C, and CYP3A were present in 63, 25, and 61 per cent of tumours, respectively. Epoxide hydrolase was identified in 96 per cent of tumours. GST-alpha and GST-mu were expressed in 29 and 41 per cent of tumours, respectively, while there was no immunoreactivity for the pi form of GST. The absence of GST-pi in prostate cancer contrasts with the frequent expression of GST-pi observed in other types of malignant tumour. In non-neoplastic prostatic epithelium, there was expression of CYP1A, CYP2C, epoxide hydrolase, and the different forms of GST, while there was no apparent immunoreactivity for CYP3A.
Cytoplasmic transport and nuclear import of plasmid DNA (2017)

Productive transfection and gene transfer require not simply the entry of DNA into cells and subsequent transcription from an appropriate promoter, but also a number of intracellular events that allow the DNA to move from the extracellular surface of the cell into and through the cytoplasm, and ultimately across the nuclear envelope and into the nucleus before any transcription can initiate. Immediately upon entry into the cytoplasm, naked DNA, either delivered through physical techniques or after disassembly of DNA-carrier complexes, associates with a large number of cellular proteins that mediate subsequent interactions with the microtubule network for movement toward the microtubule organizing center and the nuclear envelope. Plasmids then enter the nucleus either upon the mitotic disassembly of the nuclear envelope or through nuclear pore complexes in the absence of cell division, using a different set of proteins. This review will discuss our current understanding of these pathways used by naked DNA during the transfection process. While much has been elucidated on these processes, much remains to be discerned, but with the development of a number of model systems and approaches, great progress is being made.
<title>Study of Fourier descriptors statistical features</title> (1993)

In this paper we present a new approach to reduce the computations involved in recognition applications. Fourier descriptors are treated as a occurrence of a complex random variable. Statistical function measures are then used to characterize the behavior of the complex variable. A study of pattern regeneration based on these statistical features was carried out. Some of these statistical measures were found to comprehend most of the object global features. Thus, they could be used for classification and recognition purposes.
Genetic deficiency in tissue kallikrein activity in mouse and man: effect on arteries, heart and kidney (2008)

Tissue kallikrein (KLK1) is a kinin-forming serine protease synthesized in many organs including arteries and kidney. Study of the physiological role of KLK1 has benefited from the availability of mouse and human genetic models of KLK1 deficiency, through engineering of KLK1 mouse mutants and discovery of a major polymorphism in the human KLK1 gene that induces a loss of enzyme activity. Studies in KLK1-deficient mice and human subjects partially deficient in KLK1 have documented its critical role in arterial function in both species. KLK1 is also involved in the control of ionic transport in the renal tubule, an action that may not be kinin-mediated. Studies of experimental diseases in KLK1-deficient mice have revealed cardio- and nephro-protective effects of KLK1 and kinins in acute cardiac ischemia, post-ischemic heart failure, and diabetes. Potential clinical and therapeutic developments are discussed.
The Missing ApoE Allele (2007)

The human apoE gene (APOE, GenBank accession AF261279) shows a common polymorphism, with the three epsilon2, epsilon3 and epsilon4 alleles resulting from the haplotypes of two C-->T SNPs. However, whereas the three common T-T, T-C and C-C haplotypes corresponding to the epsilon2, epsilon3 and epsilon4 alleles are well known, the last C-T haplotype (GenBank accession AY077451), encoding a fourth apoE allele, has rarely been reported. We detected this fourth allele in a Caucasian patient with motor neuron disease (MND). According to the literature we refer to this allele as epsilon3r. Although several explanations may be proposed for its formation, the existence of this fourth allele is consistent with the evolutionary hypothesis generally accepted for the apoE alleles. The rarity and physiological role of epsilon3r remains to be explained, and requires further investigation.
Motor and somatosensory evoked potentials in hereditary spastic paraplegia. (1991)

Motor evoked potentials (MEPs) from the arms and legs to transcranial stimulation of the motor cortex and somatosensory evoked potentials (SSEPs) from stimulation of the nerves of the arms and legs, were recorded in 11 patients with hereditary spastic paraplegia. Electrophysiological abnormalities were found to be distributed differently among the systems examined; the longer the pathway, the higher the incidence and severity of impairment. MEPs from the leg were either absent or clearly reduced or prolonged in all patients. Eight patients showed abnormal cortical SSEPs on stimulation of the leg (absent or reduced responses in four, slowed central conduction velocity in seven), but only two of these patients had abnormal MEPs from the arm (absent responses). Cortical SSEPs on stimulation of the median nerve were reduced in two patients. Mean values of amplitude and central conduction velocity for MEPs and SSEPs from the leg were significantly different between patients and controls. Such differences were not found for either MEPs or SSEPs from the arm. This distribution of abnormalities, which suggests a differential involvement of the spinal pathways, parallels the reported pathological pattern in which degeneration of axons is more common and severe in the motor and sensory fibres supplying the leg.