gebhart/patrepeval huggingface dataset:
BRSK2 expression as a prognosis marker in pancreatic cancer patients (2009)

e15603 Background: The prognosis of pancreatic cancer remains dismal because of difficult early diagnosis, low resection rate and aggressive biological behavior. The research of factors related to oncogenesis, tumor infiltration and metastasis is valuable. AMPK(AMP-activated protein kinase)family is a group of regulators on the cellular energy metabolism which are sensitive to the cytoplasmic change of AMP/ATP ratio. As a member of AMPK, BRSK2 is found to be expressed in human pancreatic cell line and facilitate the tumor cell survival on glucose starving. In order to examine the expression of BRSK2 in human pancreatic cancer and explore the underline clinical implication, human pancreatic tissue was examined immunohistochemically Correlation of tumor biological behavior, prognosis and BRSK2 expression was examined. Methods: Seventy nine resected tumor specimens were collected. Immunochemical staining method was used to examine the expression pattern of BRSK2 translated protein. Semi-quantitative analysis was employed to compare the expression intensity and content of BRSK2 in tumor issues, peri-tumorous tissue and normal pancreatic tissue. Possible relationship of tumors differentiation, TNM stage, presence or absence of vessel and neural infiltration were explored with BRSK2 expression. The correlation of BRSK2 expression profile and patients survival was explored. Results: BRSK2 was weakly expressed in normal pancreatic tissues and peri-tumor tissues, including the islet and minor ducts. BRSK2 was strongly expressed in pancreatic cancer tissues, the expression intensity was correlated with extent of lymphatic metastasis, distant metastasis, TNM staging and neural invasion. Tumors with lymphatic metastasis, distant metastasis, neural invasion and later TNM stages showed stronger expression of BRSK2. The expression of BRSK2 in pancreatic cancer was closely correlated to the prognosis of patients, those with higher expression pattern showed bad prognosis. Conclusions: BRSK2 is up-regulated in pancreatic cancer; the expression of BRSK2 is correlated with tumor biological behavior and patient's prognosis. No significant financial relationships to disclose.
Circulating Hepatocellular Cells are a Bad Prognostic Factor for HCC Patients. (2015)

The presence of AFP mRNA in peripheral blood may be an indicator of CHCCs, which might predict hematogenous spreading metastasis in patients with HCC and may be as a bad prognostic factor for HCC patients.
Hetero-oligomerization between β2- and β3-Adrenergic Receptors Generates a β-Adrenergic Signaling Unit with Distinct Functional Properties (2004)

The ability of the closely related beta(2)- and beta(3)-adrenergic receptors (AR) to form hetero-oligomers was assessed by bioluminescence resonance energy transfer. Quantitative bioluminescence resonance energy transfer titration curves revealed that the beta(2)AR has identical propensity to hetero-oligomerize with the beta(3)AR than to form homo-oligomers. To determine the influence of heterooligomerization, a HEK293 cell line stably expressing an excess of beta(3)AR over beta(2)AR was generated so that all beta(2)AR are engaged in hetero-oligomerization with beta(3)AR, providing a tool to study the effect of hetero-oligomerization on beta(2)AR function in the absence of any beta(2)AR homooligomer. The hetero-oligomerization had no effect on the ligand binding properties of various beta(2)AR ligands and did not affect the potency of isoproterenol to stimulate adenylyl cyclase. Despite the unaltered ligand binding properties of the beta(2/3)AR hetero-oligomer, the stable association of the beta(2)AR with the beta(3)AR completely blocked agonist-stimulated internalization of the beta(2)AR. Given that the beta(3)AR is resistant to agonist-promoted endocytosis, the results indicate that the beta(3)AR acted as a dominant negative of the beta(2)AR endocytosis process. Consistent with this notion, the beta(2/3)AR hetero-oligomer displayed a lower propensity to recruit beta-arrestin-2 than the beta(2)AR. The hetero-oligomerization also led to a change in G protein coupling selectivity. Indeed, in contrast to beta(2)AR and beta(3)AR, which regulate adenylyl cyclase and extracellular signal-regulated kinase activity through a coupling to G(s) and G(i/o), no G(i/o) coupling was observed for the beta(2/3)AR hetero-oligomer. Together, these results demonstrate that hetero-oligomerization between beta(2)AR and beta(3)AR forms a beta-adrenergic signaling unit that possesses unique functional properties.
Effects of Urinary Trypsin Inhibitor on Myometrial Contraction in Term and Preterm Deliveries (1996)

The aim of this research was to study the concentration of urinary trypsin inhibitor in amniotic fluid (AF) and its effect on myometrial contraction in term and preterm deliveries. Urinary trypsin inhibitor was measured in AF of term and preterm labor. Immunohistochemical staining of amnion and myometrium was carried out. Isometric uterine contraction was studied to elucidate the effect of AF and urinary trypsin inhibitor on the contractile activity of term and preterm myometrium. The effect of urinary trypsin inhibitor on the production of prostaglandin E2 (PGE2) from myometrial cultures stimulated by IL-8, IL-1 and LPS was verified. Urinary trypsin inhibitor was significantly increased in AF of cases of preterm delivery (p < 0.0001). Amnion and myometrium of preterm deliveries were faintly stained for urinary trypsin inhibitor compared to term delivery. Amniotic fluid and urinary trypsin inhibitor could successfully inhibit-myometrial contraction. Also, urinary trypsin inhibitor could significantly inhibit the production of PGE2 in the myometrial cell cultures stimulated by IL-1 and LPS (p < 0.001 and 0.0005). IL-8 has no significant effect on PGE2 production from myometrial cell culture. Urinary trypsin inhibitor suppresses myometrial contraction in term and preterm deliveries. It may play a role in maintaining normal pregnancy and preventing preterm delivery.
Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules (2001)

During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.
The Transcription Factors Sp1, Sp3, and AP-2 Are Required for Constitutive Matrix Metalloproteinase-2 Gene Expression in Astroglioma Cells (1999)

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that contribute to pathological conditions associated with angiogenesis and tumor invasion. MMP-2 is highly expressed in human astroglioma cells, and contributes to the invasiveness of these cells. The human MMP-2 promoter contains potential cis-acting regulatory elements including cAMP response element-binding protein, AP-1, AP-2, PEA3, C/EBP, and Sp1. Deletion and site-directed mutagenesis analysis of the MMP-2 promoter demonstrates that the Sp1 site at -91 to -84 base pairs and the AP-2 site at -61 to -53 base pairs are critical for constitutive activity of this gene in invasive astroglioma cell lines. Electrophoretic gel shift analysis demonstrates binding of specific DNA-protein complexes to the Sp1 and AP-2 sites: Sp1 and Sp3 bind to the Sp1 site, while the AP-2 transcription factor binds the AP-2 element. Co-transfection expression experiments in Drosophilia SL2 cells lacking endogenous Sp factors demonstrate that Sp1 and Sp3 function as activators of the MMP-2 promoter and synergize for enhanced MMP-2 activation. Overexpression of AP-2 in AP-2-deficient HepG2 cells enhances MMP-2 promoter activation. These findings document the functional importance of Sp1, Sp3, and AP-2 in regulating constitutive expression of MMP-2. Delineation of MMP-2 regulation may have implications for development of new therapeutic strategies to arrest glioma invasion.
Automatic construction of multiple-object three-dimensional statistical shape models: application to cardiac modeling (2002)

A novel method is introduced for the generation of landmarks for three-dimensional (3-D) shapes and the construction of the corresponding 3-D statistical shape models. Automatic landmarking of a set of manual segmentations from a class of shapes is achieved by 1) construction of an atlas of the class, 2) automatic extraction of the landmarks from the atlas, and 3) subsequent propagation of these landmarks to each example shape via a volumetric nonrigid registration technique using multiresolution B-spline deformations. This approach presents some advantages over previously published methods: it can treat multiple-part structures and requires less restrictive assumptions on the structure's topology. In this paper, we address the problem of building a 3-D statistical shape model of the left and right ventricle of the heart from 3-D magnetic resonance images. The average accuracy in landmark propagation is shown to be below 2.2 mm. This application demonstrates the robustness and accuracy of the method in the presence of large shape variability and multiple objects.
Zika Virus (2016)

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the genus Flavivirus and the family Flaviviridae. ZIKV was first isolated from a nonhuman primate in 1947 and from mosquitoes in 1948 in Africa, and ZIKV infections in humans were sporadic for half a century before emerging in the Pacific and the Americas. ZIKV is usually transmitted by the bite of infected mosquitoes. The clinical presentation of Zika fever is nonspecific and can be misdiagnosed as other infectious diseases, especially those due to arboviruses such as dengue and chikungunya. ZIKV infection was associated with only mild illness prior to the large French Polynesian outbreak in 2013 and 2014, when severe neurological complications were reported, and the emergence in Brazil of a dramatic increase in severe congenital malformations (microcephaly) suspected to be associated with ZIKV. Laboratory diagnosis of Zika fever relies on virus isolation or detection of ZIKV-specific RNA. Serological diagnosis is complicated by cross-reactivity among members of the Flavivirus genus. The adaptation of ZIKV to an urban cycle involving humans and domestic mosquito vectors in tropical areas where dengue is endemic suggests that the incidence of ZIKV infections may be underestimated. There is a high potential for ZIKV emergence in urban centers in the tropics that are infested with competent mosquito vectors such as Aedes aegypti and Aedes albopictus.
Analysis of a peptide hormone–receptor interaction in the yeast two-hybrid system (1997)

Interaction between a peptide hormone and extracellular domains of its receptor is a crucial step for initiation of hormone action. We have developed a modification of the yeast two-hybrid system to study this interaction and have used it to characterize the interaction of insulin-like growth factor 1 (IGF-1) with its receptor by using GAL4 transcriptional regulation with a beta-galactosidase assay as readout. In this system, IGF-1 and proIGF-1 bound to the cysteine-rich domain, extracellular domain, or entire IGF-1 proreceptor. This interaction was specific. Thus, proinsulin showed no significant interaction with the IGF-1 receptor, while a chimeric proinsulin containing the C-peptide of IGF-1 had an intermediate interaction, consistent with its affinity for the IGF-1 receptor. Over 2000 IGF-1 mutants were generated by PCR and screened for interaction with the color assay. About 40% showed a strong interaction, 20% showed an intermediate interaction, and 40% give little or no signal. Of 50 mutants that were sequenced, several (Leu-5 --> His, Glu-9 --> Val, Arg-37 --> Gly, and Met-59 --> Leu) appeared to enhance receptor association, others resulted in weaker receptor interaction (Tyr-31 --> Phe and Ile-43 --> Phe), and two gave no detectable signal (Leu-14 --> Arg and Glu-46 --> Ala). Using PCR-based mutagenesis with proinsulin, we also identified a gain of function mutant (proinsulin Leu-17 --> Pro) that allowed for a strong IGF-1-receptor interaction. These data demonstrate that the specificity of the interaction between a hormone and its receptor can be characterized with high efficiency in the two-hybrid system and that novel hormone analogues may be found by this method.
Characterization of a high coherence, Brillouin microcavity laser on silicon (2012)

Recently, a high efficiency, narrow-linewidth, chip-based stimulated Brillouin laser (SBL) was demonstrated using an ultra-high-Q, silica-on-silicon resonator. In this work, this novel laser is more fully characterized. The Schawlow Townes linewidth formula for Brillouin laser operation is derived and compared to linewidth data, and the fitting is used to measure the mechanical thermal quanta contribution to the Brillouin laser linewidth. A study of laser mode pulling by the Brillouin optical gain spectrum is also presented, and high-order, cascaded operation of the SBL is demonstrated. Potential application of these devices to microwave sources and phase-coherent communication is discussed.
Pulse-periodic laser etching of diamond-like carbon coatings (1991)

The rates of etching of α-C:H films by excimer laser radiation were determined in air and in vacuum. Two ablation mechanisms—chemical and physical—dominated in different energy density ranges. An analysis was made of the processes influencing the occurrence of chemical etching and limiting its rate. A comparison was made of the energy losses in the treatment of α-C:H films by cw and pulse-periodic laser radiation.
Nanoscale Resistive Switching in Amorphous Perovskite Oxide (a‐SrTiO3) Memristors (2014)

Memristive devices are the precursors to high density nanoscale memories and the building blocks for neuromorphic computing. In this work, a unique room temperature synthesized perovskite oxide (amorphous SrTiO 3 : a‐ STO) thin film platform with engineered oxygen deficiencies is shown to realize high performance and scalable metal‐oxide‐metal (MIM) memristive arrays demonstrating excellent uniformity of the key resistive switching parameters. a‐ STO memristors exhibit nonvolatile bipolar resistive switching with significantly high (10 3 –10 4 ) switching ratios, good endurance (&gt;10 6 I–V sweep cycles), and retention with less than 1% change in resistance over repeated 10 5 s long READ cycles. Nano‐contact studies utilizing in situ electrical nanoindentation technique reveal nanoionics driven switching processes that rely on isolatedly controllable nano‐switches uniformly distributed over the device area. Furthermore, in situ electrical nanoindentation studies on ultrathin a‐ STO/metal stacks highlight the impact of mechanical stress on the modulation of non‐linear ionic transport mechanisms in perovskite oxides while confirming the ultimate scalability of these devices. These results highlight the promise of amorphous perovskite memristors for high performance CMOS/CMOL compatible memristive systems.
Efficient high-temperature CW operation of oxide-confined long-wavelength InAs quantum dot lasers (2000)

Summary form only given. Intensive research has been conducted in improving the performance of quantum dot (QD) lasers. We describe the achievement of efficient CW lasing at /spl lambda//spl ap/1.28 /spl mu/m by narrow-stripe, laterally-oxide-confined QD lasers containing two InAs quantum dot-in-well (DWELL) layers, with very low threshold current density (24 A/cm/sup 2/), high differential efficiency (55%), and a wide temperature range for CW operation (T/sub max/>100/spl deg/C). The QD laser was grown by solid-source MBE and has an oxide-confined device structure. The active region consists of two InAs DWELL layers separated by a 30 nm GaAs barrier layer, which is situated in the middle of a 220 nm thick GaAs waveguide bounded by AlGaAs cladding layers.
Effect of hydrogen peroxide exposure on normal human erythrocyte deformability, morphology, surface characteristics, and spectrin-hemoglobin cross-linking. (1985)

To further define the conditions for forming spectrin-hemoglobin cross-linking in human erythrocyte membranes and to examine its possible effects on membrane function, we incubated normal human erythrocytes for up to 3 h in concentrations of H2O2, varying from 45 to 180 microM, in an azide phosphate buffer, pH 7.4. The chemical changes observed indicated that methemoglobin formation occurred early and at a low concentration (45 microM). Morphologic changes characterized by increased echinocyte formation occurred in a dose-dependent fashion. In addition, decreased cell deformability commensurate with increased membrane rigidity was found. Finally, an increase in cell recognition as determined by monocyte phagocytosis and adherence in vitro, as well as decreased phosphatidylcholine accessibility to bee venom phospholipase A2, was found in H2O2-treated erythrocytes compared with controls. Both of these latter changes were closely correlated with the extent of spectrin-hemoglobin cross-linking. In addition to these protein-mediated interactions, lipid peroxidation also occurred after H2O2 exposure, as shown by generation of fluorescent amino propene derivatives. The addition of the antioxidant, butylated hydroxytoluene, decreased the fluorescent derivatives, but did not prevent the effects on membrane function. This suggests that lipid peroxidation, though present, was not necessary for the membrane changes found. In contrast, spectrin-hemoglobin aggregation and the alterations in membrane function were completely prevented by prior exposure of the erythrocytes to carbon monoxide.
Ornatins: potent glycoprotein IIb‐IIIa antagonists and platelet aggregation inhibitors from the leech Placobdella ornata (1991)

The purification and characterization of six isoforms of ornatin, potent glycoprotein IIb-IIIa (GP IIb-IIIa) antagonists and platelet aggregation inhibitors are described. These isoforms were purified from whole leech homogenates of the leech Placobdella ornata, a North American leech commonly known as the turtle leech, by trichloroacetic acid precipitation, Sephadex G-50 size exclusion chromatography, GP IIb-IIIa affinity chromatography, and C18 reverse-phase HPLC. Each of the five completely sequenced isoforms, which range from 41 to 52 residues in length, contains the Arg-Gly-Asp (RGD) sequence, a common recognition sequence in adhesion proteins, as well as 6 cysteine residues; the positions of both of these features are conserved in the primary sequences. The amino acid sequences of ornatin isoforms B, C, D, and E are highly conserved, whereas ornatin A2 and A3 are less similar and lack 9 residues at the N-terminus. The ornatins are approximately 40% identical with decorsin, a GP IIb-IIIa antagonist isolated from the leech Macrobdella decora [Seymour, J. L., Henzel, W. J., Nevins, B., Stults, J. T. & Lazarus, R. A. (1990) J. Biol. Chem. 265, 10143-10147]; furthermore, the RGD sequence and 5 out of 6 cysteine residues are maintained in the same relative positions in both decorsin and ornatin. The ornatin isoforms do not exhibit significant similarity to any members of the snake-venom-derived family of GP IIb-IIIa antagonists [Dennis, M. S., Henzel, W. J., Pitti, R. M., Lipari, M. T., Napier, M. A., Deisher, T. A., Bunting, S. & Lazarus, R. A. (1990) Proc. Natl Acad. Sci. USA 87, 2471-2475] except in the RGD region of these proteins. The ornatin isoforms inhibit the binding of GP IIb-IIIa to immobilized fibrinogen with IC50 values ranging over 2.9-5.3 nM; ornatin isoforms A2, C, and E inhibit ADP-induced human platelet aggregation with IC50 values of about 130, 280, and 440 nM, respectively.
Obtention and Engineering of Non-Human Primate (NHP) Antibodies for Therapeutics (2009)

Recombinant antibodies are therapeutic molecules of choice regarding their efficacy, pharmacokinetics and tolerance - all the more if they are human. The efficacy of antibodies generally depends on their affinity for their antigens. The most straightforward approach to isolate human antibodies with high affinities is the construction and screening of human immune libraries, but Humans cannot be immunized with all antigens of interest, for ethical and practical reasons. We circumvented that difficulty by utilizing non-human primates (NHP) instead of Humans and, in the course of our different studies, we have obtained several antibody fragments with high or very high affinities (from 3 nM to 50 pM) and neutralizing properties. The framework regions (FR) - the regions most implicated in tolerance - of these NHP antibody fragments were shown to be very similar to FR encoded by human germline genes. In one case, in a process called "germline humanization" (or "super-humanization"), we have increased that level of similarity and managed to go even beyond the level observed for human antibodies, without any loss of affinity. Here, the methodological peculiarities of our approach, in comparison with immune libraries built from immunised Humans, and the rationales behind these peculiarities, will be reviewed. The isolation of NHP antibody fragments from immune libraries, followed by the "super-humanization" process, opens a new and highly efficient approach for the production of high-quality recombinant antibodies for therapeutic uses.
Gene induction in response to unfolded protein in the endoplasmic reticulum is mediated through Ire1p kinase interaction with a transcriptional coactivator complex containing Ada5p (1997)

In eukaryotic cells, accumulation of unfolded protein in the endoplasmic reticulum induces transcription of a family of genes encoding endoplasmic reticulum protein chaperones through a conserved unfolded protein response element. In Saccharomyces cerevisiae, activation of a transmembrane receptor kinase, Ire1p (Ern1p), initiates signaling, although the mediators immediately downstream of Ire1 kinase are unknown. Here we demonstrate interaction of Ire1p with the transcriptional coactivator, Gcn5p (for general control nonrepressed; also known as Ada4p). Gcn5p associates with other Ada (for alteration/deficiency in activation) gene products in a heteromeric complex and has histone acetyltransferase activity. We show that the Gcn5/Ada complex is selectively required for the unfolded protein response but not for the heat shock response. A novel mechanism is proposed in which activation of a receptor kinase recruits a transcription coactivator complex to a specific chromosomal locus to mediate localized histone acetylation, thus making specific gene sequences accessible for transcription.