gebhart/patrepeval huggingface dataset:
Suppression of the Epithelial–Mesenchymal Transition by Grainyhead-like-2 (2012)

Grainyhead genes are involved in wound healing and developmental neural tube closure. In light of the high degree of similarity between the epithelial-mesenchymal transitions (EMT) occurring in wound-healing processes and the cancer stem cell-like compartment of tumors, including TGF-β dependence, we investigated the role of the Grainyhead gene, Grainyhead-like-2 (GRHL2) in oncogenic EMT. GRHL2 was downregulated specifically in the claudin-low subclass breast tumors and in basal-B subclass breast cancer cell lines. GRHL2 suppressed TGF-β-induced, Twist-induced or spontaneous EMT, enhanced anoikis sensitivity, and suppressed mammosphere generation in mammary epithelial cells. These effects were mediated in part by suppression of ZEB1 expression via direct repression of the ZEB1 promoter. GRHL2 also inhibited Smad-mediated transcription and it upregulated mir-200b/c as well as the TGF-β receptor antagonist, BMP2. Finally, ectopic expression of GRHL2 in MDA-MB-231 breast cancer cells triggered an MET and restored sensitivity to anoikis. Taken together, our findings define a major role for GRHL2 in the suppression of oncogenic EMT in breast cancer cells.
MARCKS-ED Peptide as a Curvature and Lipid Sensor (2012)

Membrane curvature and lipid composition regulates important biological processes within a cell. Currently, several proteins have been reported to sense and/or induce membrane curvatures, e.g., Synaptotagmin-1 and Amphiphysin. However, the large protein scaffold of these curvature sensors limits their applications in complex biological systems. Our interest focuses on identifying and designing peptides that can sense membrane curvature based on established elements observed in natural curvature-sensing proteins. Membrane curvature remodeling also depends on their lipid composition, suggesting strategies to specifically target membrane shape and lipid components simultaneously. We have successfully identified a 25-mer peptide, MARCKS-ED, based on the effector domain sequence of the intracellular membrane protein myristoylated alanine-rich C-kinase substrate that can recognize PS with preferences for highly curved vesicles in a sequence-specific manner. These studies further contribute to the understanding of how proteins and peptides sense membrane curvature, as well as provide potential probes for membrane shape and lipid composition.
Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B (2018)

The integrated stress response (ISR) is a conserved translational and transcriptional program affecting metabolism, memory, and immunity. The ISR is mediated by stress-induced phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) that attenuates the guanine nucleotide exchange factor eIF2B. A chemical inhibitor of the ISR, ISRIB, reverses the attenuation of eIF2B by phosphorylated eIF2α, protecting mice from neurodegeneration and traumatic brain injury. We describe a 4.1-angstrom-resolution cryo-electron microscopy structure of human eIF2B with an ISRIB molecule bound at the interface between the β and δ regulatory subunits. Mutagenesis of residues lining this pocket altered the hierarchical cellular response to ISRIB analogs in vivo and ISRIB binding in vitro. Our findings point to a site in eIF2B that can be exploited by ISRIB to regulate translation.
Immune responses of pigs after experimental infection with a European strain of Porcine reproductive and respiratory syndrome virus (2005)

The purpose of this experiment was to study the immune response of pigs during an experimental infection with a European strain of Porcine reproductive and respiratory syndrome virus (PRRSV). Five pigs were challenged intranasally with PRRSV strain VP21 and another five were kept as controls. Clinical course and humoral and cell-mediated responses were monitored for 70 days post-infection (p.i.). Infected pigs developed mild signs at 24 h p.i. Viraemia was detectable by nested RT-PCR until day 14 p.i. Earliest seroconversions (ELISA) were seen by day 7 p.i. (three of five animals) and, by day 14, all inoculated pigs had seroconverted (ELISA and immunoperoxidase monolayer assay). Virus-neutralizing antibodies were undetectable until day 56 p.i. and, by day 70 p.i., two inoculated pigs still were negative. Flow-cytometry assays using peripheral blood mononuclear cells (PBMC) showed an upshift in CD8(+) cells (day 7 p.i.) and a downshift of CD21(+) cells (days 7 and 28 p.i.). Regarding cell-mediated responses, development of PRRSV-specific gamma interferon-secreting cells (IFN-gamma-SC) and interleukin 4-secreting cells (IL4-SC) in PBMC was examined by ELISPOT assay. IFN-gamma-SC were not detected significantly until day 14 p.i., whereas, for IL4-SC, no differences between groups were seen. Concurrently with the onset of viraemia and the development of clinical signs, serum haptoglobin levels and interleukin 10 (IL10) in PRRSV-stimulated PBMC-culture supernatants increased significantly. These differences disappeared later on. For IL2, IL4, IL8 or transforming growth factor beta, no differences were seen among groups. These results are compatible with a model in which the immune response does not fully control the outcome of the infection.
The peripheral blood lymphocyte pattern in psoriasis preceded by an infection. (2002)

Our research demonstrated changes in the percentage and expression of certain subpopulations of T lymphocytes in peripheral blood in the course of psoriasis preceded by a bacterial infection, which suggests not only local, but also systemic activation of the immune system.
Binding of cytochalasin B to human erythrocyte glucose transporter (1980)

Cytochalasin B, a potent inhibitor of D-glucose transport systems, binds to the glucose transporter purified from human erythrocytes as described previously [Kasahara, M., & Hinkle, P. C. (1977) J. Biol. Chem. 252, 7384]. The transporter binds 9.2 +/- 1.3 nmol of cytochalasin B/mg of protein with a dissociation constant of 0.18 microM. The binding is competitively inhibited by D-glucose (Ki = 43 mM). Phloretin, diethylstilbestrol, maltose, 6-O-propyl-D-galactose, propyl beta-D-glucopyranoside, and dithiothreitol were also linear competitive inhibitors of cytochalasin B binding. The propyl sugars have been shown to inhibit transport from either the plasma or cytoplasma side of the membrane, respectively. The binding of cytochalasin B to the isolated transporter was inhibited by both propyl sugars.
Oxygen Sensors Based on Luminescence Quenching: Interactions of Metal Complexes with the Polymer Supports (1994)

Oxygen quenching of [Ru(Ph2phen)3]Cl2 (Ph2phen = 4,7-diphenyl-1,10-phenanthroline) has been studied in a diverse series of polymers, most with a common poly-(dimethylsiloxane) (PDMS) component. Systematic variations in the polymer properties have been made in order to delineate the structural features important for satisfactory use of supports for oxygen sensors. Most measurements were made using homo- or copolymers containing a PDMS region, although some measurements were made on small ring siloxane polymers. In particular, quenching behavior was examined as a function of polymer structure as well as the type of and amount of polar copolymer cross-linkers. Cross-linkers were added to enhance the solubility of oxygen probes in an otherwise nonpolar polymer. In addition, hydrophobic silica was added to alter quenching properties. Domain models are used to explain the variations in oxygen quenching properties as a function of additives and cross-linkers. These considerations have led to the most sensitive ruthenium-based sensor reported to date. The relative affinity of the different domains for the complex and the efficacy of the domains for oxygen quenching control the overall behavior of the sensing response. Guidelines for design of suitable polymer supports for oxygen sensors are proposed.
Effect of channel estimation error on M-QAM BER performance in Rayleigh fading (1999)

We determine the bit-error rate (BER) of multilevel quadrature amplitude modulation (M-QAM) in flat Rayleigh fading with imperfect channel estimates, Despite its high spectral efficiency, M-QAM is not commonly used over fading channels because of the channel amplitude and phase variation. Since the decision regions of the demodulator depend on the channel fading, estimation error of the channel variation can severely degrade the demodulator performance. Among the various fading estimation techniques, pilot symbol assisted modulation (PSAM) proves to be an effective choice. We first characterize the distribution of the amplitude and phase estimates using PSAM. We then use this distribution to obtain the BER of M-QAM as a function of the PSAM and channel parameters. By using a change of variables, our exact BER expression has a particularly simple form that involves just a few finite-range integrals. This approach can be used to compute the BER for any value of M. We compute the BER for 16-QAM and 64-QAM numerically and verify our analytical results by computer simulation. We show that for these modulations, amplitude estimation error leads to a 1-dB degradation in average signal-to-noise ratio and combined amplitude-phase estimation error leads to 2.5-dB degradation for the parameters we consider.
[Immunology in clinical practice. VII. Psoriasis]. (1997)

A new hypothesis of the pathogenesis of psoriasis holds that psoriasis is an epidermal hyperproliferative disorder resulting from abnormal interaction between T cells and basal layer stem cell keratinocytes. New therapies aimed at reducing T cell activity are most successful, as exemplified by the efficacy of systemic cyclosporine in severe cases of psoriasis. New developments in immunogenetics and immunodermatology are anticipated and it is expected that they will fully explain the chain of pathological events.
Poxvirus multiprotein entry–fusion complex (2005)

Poxviruses have evolved elaborate mechanisms for cell entry, assembly, and exocytosis. Recently, four vaccinia virus membrane proteins, namely A21, A28, H2 and L5, were reported to be necessary for cell entry and virus-induced cell-cell fusion but not for virion morphogenesis or attachment of virus particles to cells. Using immunoaffinity purification followed by mass spectrometry, we now show that these four proteins as well as four additional previously uncharacterized putative membrane proteins (A16, G3, G9, and J5) form a stable complex. These proteins fall into two groups: A21, A28, G3, H2, and L5 have an N-terminal transmembrane domain, 0-2 intramolecular disulfide bonds, and no sequence similarity, whereas A16, G9, and J5 have a C-terminal transmembrane domain and 4-10 predicted disulfide bonds and are homologous. Studies with conditional-lethal null mutants indicated that the viral membrane was crucial for assembly of the complex and that the absence of individual polypeptide components profoundly decreased complex formation or stability, suggesting a complicated interaction network. Analysis of purified virions, however, demonstrated that the polypeptides of the complex trafficked independently to the viral membrane even under conditions in which the complex itself could not be isolated. All eight proteins comprising the entry-fusion complex are conserved in all poxviruses, suggesting that they have nonredundant functions and that the basic entry mechanism evolved before the division between vertebrate and invertebrate poxvirus species.
Prognostic Value of Nocturnal Cheyne-Stokes Respiration in Chronic Heart Failure (1999)

The AHI is a powerful independent predictor of poor prognosis in clinically stable patients with CHF. The presence of an AHI >/=30/h adds prognostic information compared with other clinical, echocardiographic, and autonomic data and identifies patients at very high risk for subsequent cardiac death.
Hyaluronidase in Clinical Isolates ofPropionibacterium acnes (2015)

Objectives. We sought to describe the prevalence of a hyaluronidase gene and hyaluronidase production in 197 clinical isolates of P. acnes; we assessed kinetics of hyaluronidase production in a subset of three isolates. Methods. The hyaluronidase gene was detected using polymerase chain reaction. Hyaluronidase production was detected by growing isolates on BHI agar containing 400 μg/mL hyaluronic acid and 1% albumin and flooding plates with 2 N glacial acetic acid to precipitate unbound hyaluronic acid, with a zone of clearing representing a positive phenotype. Hyaluronidase production kinetics were measured as a function of hyaluronic acid digestion over time in a liquid medium. Results. A hyaluronidase gene and hyaluronidase production were detected in 100 and 97% of P. acnes isolates, respectively. Hyaluronidase production in liquid medium was detectable after 96 hours of growth. Conclusions. Hyaluronidase production is nearly universal among P. acnes isolates. Three days appear to be required for significant hyaluronidase production in a liquid medium. Detection of hyaluronidase in tissue specimens may be a strategy to differentiate P. acnes infection from colonization when P. acnes is isolated from a clinical specimen.
Sildenafil for Treatment of Erectile Dysfunction in Men With Diabetes (1999)

Oral sildenafil is an effective and well-tolerated treatment for erectile dysfunction in men with diabetes.
Pharmacological IKK2 inhibition blocks liver steatosis and initiation of non-alcoholic steatohepatitis (2008)

The data demonstrate that AS602868-mediated IKK2 inhibition represents a new therapeutic approach to prevent dietary-induced NASH progression.
Subunit Vaccine against the Seven Serotypes of Botulism (2007)

Botulinum neurotoxins (BoNTs) are the most toxic proteins for humans and are classified as category A toxins. There are seven serotypes of BoNTs defined by the lack of cross-serotype toxin neutralization. Thus, an effective vaccine must neutralize each BoNT serotype. BoNTs are organized as dichain A-B toxins, where the N-terminal domain (light chain) is a zinc metalloprotease targeting soluble NSF attachment receptor proteins that is linked to the C-terminal domain (heavy chain [HC]) by a disulfide bond. The HC comprises a translocation domain and a C-terminal receptor binding domain (HCR). HCRs of the seven serotypes of BoNTs (hepta-HCR) were engineered for expression in Escherichia coli, and each HCR was purified from E. coli lysates. Immunization of mice with the E. coli-derived hepta-serotype HCR vaccine elicited an antibody response to each of the seven BoNT HCRs and neutralized challenge by 10,000 50% lethal doses of each of the seven BoNT serotypes. A solid-phase assay showed that the anti-hepta-serotype HCR sera inhibited the binding of HCR serotypes A and B to the ganglioside GT1b, the first step in BoNT intoxication of neurons. This is the first E. coli-derived vaccine that effectively neutralizes each of the seven BoNT serotypes.
A self‐learning control of atm service quality using neural network (1990)

Abstract Studies of ATM network are conducted aiming at the integrated processing of multimedia. One of the important problems is to find a control method for the ATM network which can meet various types of requirements for the service quality arising from the diversity of sources connected to the network. For such a problem, the traditional approach by exhaustive analysis and simulation that has been used in the circuit switching network has a problem in that a large number of parameters to be considered in the ATM network complicates the control and it is difficult to deal flexibly with the diversity of sources and the change of traffic characteristics due to the new service. The leaky pattern table method is proposed which can realize a highly accurate control by learning from the data with small generation rate. As an example of application of the proposed method, the call admission control in the ATM node is considered. The detailed construction of the control system is discussed, and the proposed system is evaluated by computer simulation using a basic model. From such a viewpoint, this paper applies the neural network which can realize a high‐speed learning of the multiinput/multi‐output nonlinear function by back propagation to obtain the relation between the load in the ATM network and the communication quality by training. This network is used also to effect the learning control to deal flexibly with the change of the environment.
Crystal structure of the swine-origin A (H1N1)-2009 influenza A virus hemagglutinin (HA) reveals similar antigenicity to that of the 1918 pandemic virus (2010)

Influenza virus is the causative agent of the seasonal and occasional pandemic flu. The current H1N1 influenza pandemic, announced by the WHO in June 2009, is highly contagious and responsible for global economic losses and fatalities. Although the H1N1 gene segments have three origins in terms of host species, the virus has been named swine-origin influenza virus (S-OIV) due to a predominant swine origin. 2009 S-OIV has been shown to highly resemble the 1918 pandemic virus in many aspects. Hemagglutinin is responsible for the host range and receptor binding of the virus and is therefore a primary indicator for the potential of infection. Primary sequence analysis of the 2009 S-OIV hemagglutinin (HA) reveals its closest relationship to that of the 1918 pandemic influenza virus, however, analysis at the structural level is necessary to critically assess the functional significance. In this report, we report the crystal structure of soluble hemagglutinin H1 (09H1) at 2.9 Å, illustrating that the 09H1 is very similar to the 1918 pandemic HA (18H1) in overall structure and the structural modules, including the five defined antiboby (Ab)-binding epitopes. Our results provide an explanation as to why sera from the survivors of the 1918 pandemics can neutralize the 2009 S-OIV, and people born around the 1918 are resistant to the current pandemic, yet younger generations are more susceptible to the 2009 pandemic.
Influence of Microvascular Architecture on Oxygen Exchange in Skeletal Muscle (1995)

The normal function of skeletal muscle requires that a continuous supply of oxygen be provided by the cardiovascular system. This article reviews the development of our understanding of the role of microvascular architecture on the oxygen transport system, with emphasis on direct microcirculatory observations and mathematical modeling dating from the work of August Krogh to present studies. The contributions of the various elements of the vascular network (i.e., arterioles, capillaries, and venules) and microvascular hemodynamics to oxygen exchange are discussed. Oxygen moves through the microvascular network by convection, almost all of it being reversibly bound to the hemoglobin within red blood cells. Thus, the flow properties and distribution of the red cells within the network can play a significant role in oxygen transport. Because the walls of all the vessels in the microcirculation appear to be permeable to oxygen, it continuously diffuses between the blood and the interstitium, the direction depending on the oxygen partial pressure difference. Because of the high permeability of the vascular wall to oxygen, the complex spatial relationships among the various microvessels lead to correspondingly complex diffusive interactions among them. The proximity of capillaries, arterioles, and venules, along with the anastomotic connections and tortuosity of capillaries, provides the "complex spatial relationships" that lead to diffusive interactions between neighboring capillaries, between capillaries and nearby arterioles and venules, and between paired arterioles and venules. Although there are a number of outstanding problems regarding our understanding of oxygen transport at the microcirculatory level, the most interesting and significant of these has to do with the adjustments that are made in the transition from the resting state to that of sustained aerobic exercise.
Immunolocalization of mineralocorticoid receptor in human kidney, pancreas, salivary, mammary and sweat glands: a light and electron microscopic immunohistochemical study (1992)

Using a polyclonal antibody against a synthetic fusion protein corresponding to 167 amino acids of the N-terminal region of the human renal mineralocorticoid receptor (MR), an immunohistochemical study was performed to investigate the intraglandular and intracellular localization of the receptor in human kidney, salivary gland, pancreas, mammary gland and sweat gland both at the light and electron microscopic levels. In the kidney, immunoreactivity was observed in distal convoluted tubules, branches of Henle's loop, and collecting tubules in the renal cortex, and papillary and Henle's loops' ducts in the renal medulla. No significant differences in the distribution of immunoreactivity were observed using different fixatives (10% neutral formalin, 100% methanol, 4% paraformaldehyde, PLP (periodate-lysine-2% paraformaldehyde) solution and Zamboni solution) and processing methods (paraffin embedding and frozen sectioning). Immunoreactivity in the kidney was observed in both the cytoplasm and nucleus, with cytoplasmic staining predominant, regardless of the methods of tissue preparation. Immunoelectron microscopy, employing a pre-embedding method, demonstrated the presence of immunoreaction precipitates in nuclei, endoplasmic reticulum, perinuclear cisternae, free cytoplasm and cell membranes. In nuclei, immunoreactivity was observed in euchromatin but not in heterochromatin, which is consistent with an association of MR with specific DNA regulatory elements located in transcriptionally active euchromatin. In other organs, MR was expressed in cells of the excretory ductal system where mineralocorticoids are known to play a role in electrolyte homeostasis.
Directions-of-Arrival Estimation Through Bayesian Compressive Sensing Strategies (2013)

The estimation of the directions of arrival (DoAs) of narrow-band signals impinging on a linear antenna array is addressed within the Bayesian compressive sensing (BCS) framework. Unlike several state-of-the-art approaches, the voltages at the output of the receiving sensors are directly used to determine the DoAs of the signals thus avoiding the computation of the correlation matrix. Towards this end, the estimation problem is properly formulated to enforce the sparsity of the solution in the linear relationships between output voltages (i.e., the problem data) and the unknown DoAs. Customized implementations exploiting the measurements collected at a unique time instant (single-snapshot) and multiple time instants (multiple-snapshots) are presented and discussed. The effectiveness of the proposed approaches is assessed through an extensive numerical analysis addressing different scenarios, signal configurations, and noise conditions. Comparisons with state-of-the-art methods are reported, as well.
In vivo chondrogenesis in collagen sponge sandwiched by perichondrium (1996)

In order to increase the cartilage synthesis of the perichondrium, we combined auricular perichondrium with a collagen sponge as a template (perichondrium-sandwiched collagen sponge) and implanted the assembly as an autograft into the back of rabbits. Microscopic examination revealed that cartilaginous tissue was produced in the collagen sponge and chondrosynthesis was accelerated in the collagen sponge implants in comparison with that in materials containing perichondrium alone.