gebhart/patrepeval huggingface dataset:
The Uncoating and Infectivity of the Flavivirus West Nile on Interaction with Cells: Effects of pH and Ammonium Chloride (1986)

Infectivity of the West Nile virus (WNV; Flaviviridae) was inactivated on exposure for brief periods (90 s) to pH 6.6 and below. This inactivation was not due to decreased interaction between cells and acid-treated virus. The RNA of [3H]uridine-labelled virus particles prebound to the cell surface before acidic pH treatment underwent rapid uncoating within 1 min at 37 degrees C at the same pH values that inactivated virus particles. The uncoating of [3H]uridine-labelled virus particles was also studied over longer time periods after synchronized internalization by P388D1 cells. At pH 7.6 uncoating occurred rapidly after a reproducible time lag of 1 min on warming to 37 degrees C and was essentially complete by 15 to 30 min after the start of internalization, leaving uncoated RNA in an infectious form. In contrast, at pH 6.2 viral uncoating occurred rapidly without any time lag and the uncoated RNA appeared to be far less infectious than that uncoated at pH 7.6. Ammonium chloride could almost totally inhibit both the infectivity and uncoating of virus particles on synchronized internalization into P388D1 cells, with a pH optimum of 8.0. These results suggest that the uncoating of virus particles is dependent on an acidic pH, although the location of uncoating (prelysosomal endosome or plasma membrane) decides whether the uncoated RNA will be infectious or not. Essentially the same results were obtained when infections were carried out in the presence of enhancing antibody.
Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication (2005)

About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.
Molecular Biology of Adenosine Triphosphate-Sensitive Potassium Channels* (1999)

KATP channels are a newly defined class of potassium channels based on the physical association of an ABC protein, the sulfonylurea receptor, and a K+ inward rectifier subunit. The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry. The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4. The two subunits form a tightly integrated whole. KIR6.2 can be expressed in the plasma membrane either by deletion of an ER retention signal at its C-terminal end or by high-level expression to overwhelm the retention mechanism. The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane. Coexpression with SUR restores the normal channel properties. The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity. KATP channels set the resting membrane potential of beta-cells, and their loss results in a constitutive depolarization that allows voltage-gated Ca2+ channels to open spontaneously, increasing the cytosolic Ca2+ levels enough to trigger continuous release of insulin. The loss of KATP channels, in effect, uncouples the electrical activity of beta-cells from their metabolic activity. PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides. The results indicate that SUR1 is important in sensing nucleotide changes, as implied by its sequence similarity to other ABC proteins, in addition to being the drug sensor. An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1. A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP. The result implies that ATP tonically inhibits KATP channels, but that the ADP level in a fasting beta-cell antagonizes this inhibition. Decreases in the ADP level as glucose is metabolized result in KATP channel closure. Although KATP channels are the target for sulfonylureas used in the treatment of NIDDM, the available data suggest that the identified KATP channel mutations do not play a major role in diabetes. Understanding how KATP channels fit into the overall scheme of glucose homeostasis, on the other hand, promises insight into diabetes and other disorders of glucose metabolism, while understanding the structure and regulation of these channels offers potential for development of novel compounds to regulate cellular electrical activity.
Surface‐expressed invariant chain (CD74) is required for internalization of human leucocyte antigen‐DR molecules to early endosomal compartments (1999)

Transport of major histocompatibility complex (MHC) class II molecules to the endocytic route is directed by the associated invariant chain (Ii). In the endocytic pathway, Ii is proteolytically cleaved and, upon removal of residual Ii fragments, class II alpha beta dimers are charged with antigenic peptide and recognized by CD4+ T cells. Although distinct peptide-loading compartments such as MIIC (MHC class II loading compartment) and CIIV (MHC class II vesicles) have been characterized in different cells, there is growing evidence of a multitude of subcellular compartments in which antigenic peptide loading takes place. We employed a physiological cellular system in which surface Ii (CD74) and surface human leucocyte antigen (HLA)-DR were induced either alone or in combination. This was achieved by transient exposure of HT-29 cells to recombinant interferon-gamma (rIFN-gamma). Using distinct cellular variants, we showed that: (i) the majority of Ii molecules physically associate on the cell membrane with class II dimers to form DR alpha beta:Ii complexes; (ii) the presence of surface Ii is a prerequisite for the rapid uptake of HLA-DR-specific monoclonal antibodies into early endosomes because only the surface DR+/Ii+ phenotype, and not the DR+/Ii- variant, efficiently internalizes; and (iii) the HLA-DR:Ii complexes are targeted to early endosomes, as indicated by co-localization with the GTPase, Rab5, and endocytosed bovine serum albumin. Internalization of HLA-DR:Ii complexes, accommodation of peptides by DR alphabeta heterodimers in early endosomes and recycling to the cell surface may be a mechanism used to increase the peptide repertoire that antigen-presenting cells display to MHC class II-restricted T cells.
Characterization of angiotensin-converting enzymes 1 and 2 in the soleus and plantaris muscles of rats (2010)

Angiotensin-converting enzymes 1 (ACE1) and 2 (ACE2) are key enzymes of the renin-angiotensin system, which act antagonistically to regulate the levels of angiotensin II (Ang II) and Ang-(1-7). Considerable data show that ACE1 acts on normal skeletal muscle functions and architecture. However, little is known about ACE1 levels in muscles with different fiber compositions. Furthermore, ACE2 levels in skeletal muscle are not known. Therefore, the purpose of this study was to characterize protein expression and ACE1 and ACE2 activities in the soleus and plantaris muscles. Eight-week-old female Wistar rats (N = 8) were killed by decapitation and the muscle tissues harvested for biochemical and molecular analyses. ACE1 and ACE2 activities were investigated by a fluorometric method using Abz-FRK(Dnp)P-OH and Mca-YVADAPK(Dnp)-OH fluorogenic substrates, respectively. ACE1 and ACE2 protein expression was analyzed by Western blot. ACE2 was expressed in the skeletal muscle of rats. There was no difference between the soleus (type I) and plantaris (type II) muscles in terms of ACE2 activity (17.35 ± 1.7 vs 15.09 ± 0.8 uF·min(-1)·mg(-1), respectively) and protein expression. ACE1 activity was higher in the plantaris muscle than in the soleus (71.5 ± 3.9 vs 57.9 ± 1.1 uF·min(-1)·mg(-1), respectively). Moreover, a comparative dose-response curve of protein expression was established in the soleus and plantaris muscles, which indicated higher ACE1 levels in the plantaris muscle. The present findings showed similar ACE2 levels in the soleus and plantaris muscles that might result in a similar Ang II response; however, lower ACE1 levels could attenuate Ang II production and reduce bradykinin degradation in the soleus muscle compared to the plantaris. These effects should enhance the aerobic capacity necessary for oxidative muscle activity.
Targeting EGFR and HER-2 receptor tyrosine kinases for cancer drug discovery and development (2006)

Conventional anticancer therapy using cytotoxic drugs lacks selectivity and is prone to toxicity and drug resistance. Anticancer therapies targeting aberrant growth factor receptor signaling are gaining interest. The erbB receptor family belongs to the type I, the receptor tyrosine kinases class, and comprises EGFR, HER-2, HER-3, and HER-4. It has been targeted for solid tumor therapy, including breast, ovarian, colon, head-and-neck, and non-small-cell lung cancers. This review summarizes structural aspects of this class of growth factor receptors, their oncogenic expression, and various pharmacological interventions including biological products and small molecules that inhibit these enzymes. We have also discussed various mutations that occur in EGFR and their consequences on anticancer therapy.
Synthesis and properties of 7-azaxanthopterin (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and properties of 7-azaxanthopterinEdward C. Taylor and Anthony J. CocuzzaCite this: J. Org. Chem. 1979, 44, 7, 1125–1128Publication Date (Print):March 1, 1979Publication History Published online1 May 2002Published inissue 1 March 1979https://pubs.acs.org/doi/10.1021/jo01321a020https://doi.org/10.1021/jo01321a020research-articleACS PublicationsRequest reuse permissionsArticle Views86Altmetric-Citations10LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Role of αIIbβ3 integrin in prostate cancer metastasis (1998)

BACKGROUND Integrins participate in cell-cell and cell-matrix interactions. In this study we determined whether αIIbβ3 integrin is involved in metastasis of human prostate adenocarcinoma cells. METHODS Prostate adenocarcinoma PC-3 and DU-145 cell lines express αIIbβ3. Northern blotting, 5′-RACE, and immunofluorescent localization confirmed expression of αIIb integrin in prostate adenocarcinoma cells. We used orthotopic/ectopic site of implantation and lung colonization assays in SCID mice to determine whether αIIbβ3 participates in metastatasis of tumor cells. RESULTS Immunofluorescent localization of αIIb integrin in fibronectin-adherent DU-145 and PC-3 cells is remarkably different. In DU-145 cells the integrin localizes to focal contact sites, whereas it is predominantly intracellular in PC-3 cells. Both tumor cell lines are tumorigenic when implanted subcutaneously or intraprostatically in SCID mice, but only DU-145 cells injected intraprostatically metastasize. Flow cytometry with a mAb directed to αIIbβ3 revealed higher expression of αIIbβ3 in DU-145 tumor cell suspensions isolated from the prostate when compared to DU-145 tumor cells from the subcutis. Function-blocking mAbs to αIIbβ3 inhibit lung colonization of tail vein-injected DU-145 cells. CONCLUSIONS Altogether, the data suggest that αIIbβ3 integrin participates in the metastatic progression of prostatic adenocarcinoma. Prostate 35:185–192, 1998. © 1998 Wiley-Liss, Inc.
A negative V/sub th/ cell architecture for highly scalable, excellently noise-immune, and highly reliable NAND flash memories (1999)

A new, negative V/sub th/ cell architecture is proposed where both the erased and the programmed state have negative V/sub th/. This architecture realizes highly scalable, excellently noise-immune, and highly reliable NAND flash memories. The program disturbance that limits the scaling of a local oxidation of silicon (LOCOS) width in a conventional NAND-type cell is drastically reduced. As a result, the scaling limit of the LOCOS width decreases from 0.56 to 0.45 /spl mu/m, which leads to 20% isolation width reduction. The proposed cell is essential for the future scaled shallow trench isolated cells because improved program disturb characteristics can be obtained irrespective of the process technology or feature size. New circuit techniques, such as a PMOS drive column latch and a V/sub cc/-bit-line shield sensing method are also utilized to realize the proposed cell operation. By using these novel circuit technologies, array noise, such as a source-line noise and an inter bit line capacitive coupling noise, are eliminated. Consequently, the V/sub th/ fluctuation due to array noise is reduced from 0.7 to 0.1 V, and the V/sub th/ distribution width decreases from 1.2 to 0.6 V. In addition to the smaller cell size and the high noise immunity, the proposed cell improves device reliability. The read disturb time increases by more than three orders of magnitude, and a highly reliable operation can be realized.
Long-term growth hormone-releasing factor administration on growth hormone, insulin-like growth factor-I concentrations, and bone healing in the Beagle. (1996)

Twelve 11 month old male Beagles were assigned to two treatment groups: a control group (saline) and a group receiving human growth hormone (GH)-releasing factor (hGRF) [1-29]NH2 (25 micrograms/kg, SC, TID). Treatment was started 6 days prior to surgery (day 1) and continued until necropsy (3 dogs per group/day) on d 29 or 58. Two porous polyethylene rods were surgically implanted on the lateral diaphysis of the femoral shaft and a 3 mm hole was drilled through the cortex between the two implants of each dog on day 1. Blood and urine were collected on d -6, 27 and 56. Human GRF injections produced a significant (P < 0.05) increase in GH release following each injection. An increase in GH response was also observed (P < 0.05) over time. The concentration of insulin-like growth factor-1 (IGF-1) increased for 5 weeks and then reached a plateau. None of the hematologic or urine measured parameters was affected by the treatment (P > 0.05). Albumin, calcium, and protein concentrations were higher (P < 0.05) on d 27 and 56 in GRF-treated animals. Histological sections of the onlay sites showed that bony ingrowth tended to be greater into the porous polyethylene material in GRF-treated animals than the controls at d 28 and 57, while no difference was observed in the degree of periosteal bone formation around the implants at either time period (P > 0.05). Bone formation into the cortical defect was greater in the GRF-treated dogs when compared to controls at day 57 only. In conclusion, chronic hGRF [1-29]NH2 treatment in Beagle dogs produced an increased GH response over time and increased IGF-1 concentrations. It also appeared to promote bony ingrowth into a porous polyethylene onlay and into a bony deficit.
Numerical modeling, calibration, and validation of an ultrasonic separator (2013)

Our overall goal is to apply acoustic separation technology for the recovery of valuable particulate matter from wastewater in industry. Such large-scale separator systems require detailed design and evaluation to optimize the system performance at the earliest stage possible. Numerical models can facilitate and accelerate the design of this application; therefore, a finite element (FE) model of an ultrasonic particle separator is a prerequisite. In our application, the particle separator consists of a glass resonator chamber with a piezoelectric transducer attached to the glass by means of epoxy adhesive. Separation occurs most efficiently when the system is operated at its main eigenfrequency. The goal of the paper is to calibrate and validate a model of a demonstrator ultrasonic separator, preserving known physical parameters and estimating the remaining unknown or less-certain parameters to allow extrapolation of the model beyond the measured system. A two-step approach was applied to obtain a validated model of the separator. The first step involved the calibration of the piezoelectric transducer. The second step, the subject of this paper, involves the calibration and validation of the entire separator using nonlinear optimization techniques. The results show that the approach lead to a fully calibrated 2-D model of the empty separator, which was validated with experiments on a filled separator chamber. The large sensitivity of the separator to small variations indicated that such a system should either be made and operated within tight specifications to obtain the required performance or the operation of the system should be adaptable to cope with a slightly off-spec system, requiring a feedback controller.
A Planar Monopole Antenna Design With Band-Notched Characteristic (2006)

This paper proposes a novel type of ultrawide-band (UWB) antenna, which has a low voltage standing wave ratio (VSWR) while excepting from interference with existing wireless system with band notched characteristics. The bandwidth and central frequency of the notched band can be adjusted with ease by proper selection of antenna parameters. Simulation results well justify the design methods presented in the paper. As an important example, a band-notched antenna that yields an impedance bandwidth of 3.1-10.6 GHz with VSWR<2, except the bandwidth of 5.15-5.825 GHz for IEEE802.11, is proposed and evaluated.
Multivitamin prophylaxis in prevention of post-gastric bypass vitamin and mineral deficiencies. (1991)

One hundred forty patients were followed for a mean 24.2 months after gastric bypass. Postop multivitamin (MV) prophylaxis was recommended for all patients and 90 of 140 patients (64 percent) were regularly compliant. Deficiencies in iron, vitamin B-12 or folate were recognized in 88 of 140 patients (63 percent). Thirty of 45 patients (67 percent) with iron deficiency developed anemia. Forty-three of the 52 patients who did not have deficiencies were regularly taking MV vs 47 of 88 patients who developed deficiencies (P less than 0.001). MV prophylaxis was successful in preventing folate (P less than or equal to 0.05) and vitamin B-12 deficiencies (P less than or equal to 0.02) but did not prevent development of iron deficiency or subsequent anemia. There was no correlation between taking prescribed supplements and resolution of either iron deficiency of anemia. B-12 and folate supplements corrected deficiencies in 73 percent of cases. We conclude that oral MV prophylaxis is useful in preventing folate and B-12 deficiency after gastric bypass. Additional prophylactic iron supplements should be provided for women to prevent iron deficiency and associated anemia.
Ala-->Gly mutation in the putative catalytic loop confers temperature sensitivity on Ros, insulin receptor, and insulin-like growth factor I receptor protein-tyrosine kinases. (1994)

Temperature-sensitive mutations in the avian sarcoma virus UR2 oncogene ros, encoding a receptor protein-tyrosine kinase (PTK), were identified. The Ala385-->Gly change mapping within the highly conserved RDLAARN motif in the Ros kinase domain was responsible for the temperature-sensitive phenotype. Based on the sequence homology of all known protein kinases and the crystalline structure of the cAMP-dependent protein kinase, this conserved region probably represents the PTK catalytic loop. The same mutation when introduced into the human insulin and insulin-like growth factor I receptors made these PTKs temperature sensitive in both biological function and kinase activity. Our results support the presumed catalytic role of this highly conserved sequence in PTKs. Due to its highly conserved nature, we predict that the same mutation would probably confer temperature sensitivity on other PTKs.
A Multiplex Assay to Measure RNA Transcripts of Prostate Cancer in Urine (2012)

The serum prostate-specific antigen (PSA) test has a high false positive rate. As a single marker, PSA provides limited diagnostic information. A multi-marker test capable of detecting not only tumors but also the potentially lethal ones provides an unmet clinical need. Using the nanoString nCounter gene expression system, a 20-gene multiplex test was developed based on digital gene counting of RNA transcripts in urine as a means to detect prostate cancer. In this test, voided urine is centrifuged to pellet cells and the purified RNA is amplified for hybridization to preselected probesets. Amplification of test cell line RNA appeared not to introduce significant bias, and the counts matched well with gene abundance levels as measured by DNA microarrays. For data analysis, the individual counts were compared to that of β2 microglobulin, a housekeeping gene. Urine samples of 5 pre-operative cases and 2 non-cancer were analyzed. Pathology information was then retrieved. Signals for a majority of the genes were low for non-cancer and low Gleason scores, and 6/6 known prostate cancer markers were positive in the cases. One case of Gleason 4+5 showed, in contrast, strong signals for all cancer-associated markers, including CD24. One non-cancer also showed signals for all 6 cancer markers, and this man might harbor an undiagnosed cancer. This multiplex test assaying a natural waste product can potentially be used for screening, early cancer detection and patient stratification. Diagnostic information is gained from the RNA signatures that are associated with cell types of prostate tumors.
Fast Lithium Ion Conduction in Garnet‐Type Li7La3Zr2O12 (2007)

Low activation energy and fast lithium ion conduction have been observed for the new compound Li7La3Zr2O12. Relative to previously reported lithium garnets, the solid electrolyte shows a larger cubic lattice constant, higher lithium ion concentration, lower degree of chemical interaction between the Li+ ions and the other lattice constituents, and higher densification.