gebhart/patrepeval huggingface dataset:
Assembly and Maturation of the Flavivirus Kunjin Virus Appear To Occur in the Rough Endoplasmic Reticulum and along the Secretory Pathway, Respectively (2001)

The intracellular assembly site for flaviviruses in currently not known but is presumed to be located within the lumen of the rough endoplasmic reticulum (RER). Building on previous studies involving immunofluorescence (IF) and cryoimmunoelectron microscopy of Kunjin virus (KUN)-infected cells, we sought to identify the steps involved in the assembly and maturation of KUN. Thus, using antibodies directed against envelope protein E in IF analysis, we found the accumulation of E within regions coincident with the RER and endosomal compartments. Immunogold labeling of cryosections of infected cells indicated that E and minor envelope protein prM were localized to reticulum membranes continuous with KUN-induced convoluted membranes (CM) or paracrystalline arrays (PC) and that sometimes the RER contained immunogold-labeled virus particles. Both proteins were also observed to be labeled in membranes at the periphery of the induced CM or PC structures, but the latter were very seldom labeled internally. Utilizing drugs that inhibit protein and/or membrane traffic throughout the cell, we found that the secretion of KUN particles late in infection was significantly affected in the presence of brefeldin A and that the infectivity of secreted particles was severely affected in the presence of monensin and N-nonyl-deoxynojirimycin. Nocodazole did not appear to affect maturation, suggesting that microtubules play no role in assembly or maturation processes. Subsequently, we showed that the exit of intact virions from the RER involves the transport of individual virions within individual vesicles en route to the Golgi apparatus. The results suggest that the assembly of virions occurs within the lumen of the RER and that subsequent maturation occurs via the secretory pathway.
Prevention of graft-versus-host disease in allogeneic bone marrow transplantation by pretreatment with 2'-deoxycoformycin. (1986)

Germ-free mice were used as a model for acute graft-versus-host disease (GVHD) in allogeneic bone marrow transplantation (BMT). C3H/He recipients of DBA/2 cells showed typical symptoms of acute GVHD and died within 8 days. Incubation of the cells with 10 microM 2'-deoxycoformycin (2dCF) + 100 microM deoxyadenosine (dAdo) for 1 h inhibited all T-cell functions as well as T-cell-dependent B-cell functions, but had no effect on B-cell functions that are T-cell independent, nor on the hemopoietic stem cells (CFU-S). Recipients of allogeneic cells that had been incubated with 2dCF + dAdo for 1 h prior to inoculation showed no signs, gross or histological, of acute or chronic GVHD up to 15 months after transplantation. The recovery patterns of the blood and bone marrow were not affected by the treatment, and were similar to those of recipients of treated and untreated syngeneic cells.
Protein‐based virtual screening of chemical databases. II. Are homology models of g‐protein coupled receptors suitable targets? (2002)

The aim of the current study is to investigate whether homology models of G-Protein-Coupled Receptors (GPCRs) that are based on bovine rhodopsin are reliable enough to be used for virtual screening of chemical databases. Starting from the recently described 2.8 A-resolution X-ray structure of bovine rhodopsin, homology models of an "antagonist-bound" form of three human GPCRs (dopamine D3 receptor, muscarinic M1 receptor, vasopressin V1a receptor) were constructed. The homology models were used to screen three-dimensional databases using three different docking programs (Dock, FlexX, Gold) in combination with seven scoring functions (ChemScore, Dock, FlexX, Fresno, Gold, Pmf, Score). Rhodopsin-based homology models turned out to be suitable, indeed, for virtual screening since known antagonists seeded in the test databases could be distinguished from randomly chosen molecules. However, such models are not accurate enough for retrieving known agonists. To generate receptor models better suited for agonist screening, we developed a new knowledge- and pharmacophore-based modeling procedure that might partly simulate the conformational changes occurring in the active site during receptor activation. Receptor coordinates generated by this new procedure are now suitable for agonist screening. We thus propose two alternative strategies for the virtual screening of GPCR ligands, relying on a different set of receptor coordinates (antagonist-bound and agonist-bound states).
The phase amplitude coupling to assess brain network system integration (2016)

Brain Dynamics seems to be the most actual approach to the brain responses to external stimuli. Even if Event Related Potentials can be detected, the EEG band power perturbation and the Phase Amplitude Coupling (PAC) seems to be the most appropriate way to assess such a brain dynamics. In this study 13 borderline subject with a child maltreatment history were studied in respect to 11 controls without any psychopathologic history. Both group were exposed to the Odd Ball Paradigm and related EEG activities were recorded from 256 electrodes on the scalp. The maltreated people resulted in higher levels of dystimia and worst behavioral performances as well as with a higher emotional dysregulation. Electro-physiological correlates were assessed with a different brain dynamics detected in maltreated group when target stimuli were presented. The results confirm the importance of the PAC and of the assessment of Cross Frequency Modulation (CfM). The results support the role of such a method for clinical diagnostics and suggest an explanation for the use of brain entrainment effect for therapeutic interventions. More over the presence of these oscillatory phenomena and this kind of brain dynamics suggest the compatibility of such results with scale free structures in the brain network architectures, where a small number of hubs, with high connection degrees, are embedded within a large assembly of neurons with low connection degrees.
The nuclear receptor hepatocyte nuclear factor 4α acts as a morphogen to induce the formation of microvilli (2006)

Microvilli are actin-based organelles found on apical plasma membranes that are involved in nutrient uptake and signal transduction. Numerous components, including ezrin/radixin/moesin (ERM) proteins, have been identified that link filamentous actins to transmembrane proteins, but the signals driving microvillus biogenesis are not known. In this study, we show that the conditional and/or ectopic expression of a nuclear receptor, hepatocyte nuclear factor 4alpha (HNF4alpha), triggers microvillus morphogenesis. We also demonstrate that HNF4alpha expression induces ERM-binding phosphoprotein 50 (EBP50) expression and that attenuation of EBP50 using RNA interference inhibits microvillus development. We conclude that HNF4alpha acts as a morphogen to trigger microvillus formation.
Juvenile psoriasis (1998)

Psoriasis is a lifelong disease with genetic, systemic, and environmental roots and an unpredictable course. In more than one third of patients, onset is in the first two decades of life. Primary care physicians are in a unique position to help these young patients by providing early treatment and education.
Automatic reconstruction of stationary 3-D objects from multiple uncalibrated camera views (2000)

A system for the automatic reconstruction of real-world objects from multiple uncalibrated camera views is presented. The camera position and orientation for all views, the 3-D shape of the rigid object, as well as the associated color information, are recovered from the image sequence. The system proceeds in four steps. First, the internal camera parameters describing the imaging geometry are calibrated using a reference object. Second, an initial 3-D description of the object is computed from two views. This model information is then used in a third step to estimate the camera positions for all available views using a novel linear 3-D motion and shape estimation algorithm. The main feature of this third step is the simultaneous estimation of 3-D camera-motion parameters and object shape refinement with respect to the initial 3-D model. The initial 3-D shape model exhibits only a few degrees of freedom and the object shape refinement is defined as flexible deformation of the initial shape model. Our formulation of the shape deformation allows the object texture to slide on the surface, which differs from traditional flexible body modeling. This novel combined shape and motion estimation using sliding texture considerably improves the calibration data of the individual views in comparison to fixed-shape model based camera-motion estimation. Since the shape model used for model based camera-motion estimation is only approximate, a volumetric 3-D reconstruction process is initiated in the fourth step that combines the information from ail views simultaneously. The recovered object consists of a set of voxels with associated color information that describes even fine structures and details of the object. New views of the object can be rendered from the recovered 3-D model, which has potential applications in virtual reality or multimedia systems and the emerging field of video coding using 3-D scene models.
Chromosome condensation activity (CCA) in bisected C57BL/6JxCBA mouse oocytes (1995)

Chromosome condensation activity (CCA) has been analysed in C57BL/6Jx CBA mouse oocytes bisected (i) shortly after germinal vesicle breakdown (GVBD), (ii) in metaphase I (MI) and (iii) in metaphase II (MII) into two equal halves (nucleated, enucleated) which were thereafter fused to S- or G2-phase 4-cell-stage mouse blastomeres. In nucleated halves, premature chromosome condensation (PCC) in transplanted nuclei was always induced irrespective of the cell cycle stage of the blastomere, whereas in enucleated halves only G2 nuclei underwent PCC after transplantation. Premature chromosome condensation in S-phase nuclei was induced only in enucleated halves produced shortly after GVBD. Although S-phase nuclei transplanted to MI or MII enucleated halves remained intact, their capacity to synthesize DNA was invariably suppressed. When spindles were destroyed by preincubation of the oocytes in colcemid before bisection, both nucleated and enucleated halves produced at MI or MII induced PCC of both G2- or S-phase nuclei. These results demonstrate that chromosome condensation activity in mammalian oocytes is compartmentalized rather than uniformly distributed across the cell, and that the enucleation of mammalian oocytes before nuclear transplantation may, under some conditions, influence the levels of CCA and subsequent response of introduced nuclei to cytoplasmic factors.
Passive hemagglutination technique for serotyping Campylobacter fetus subsp. jejuni on the basis of soluble heat-stable antigens (1980)

Antigenic materials were extracted from Campylobacter fetus subsp. jejuni strains by heating bacterial suspensions in saline at 100 degrees C and by exposure to ethylenediaminetetraacetic acid. The antigens were heat stable at 100 degrees C, capable of sensitizing sheep erythrocytes for agglutination in antisera, and able to elicit production of specific antibody in rabbits; they occurred with different immunological specificities in 23 strains. Antisera against the 23 strains could be used for discriminating among isolates of the species when the passive hemagglutination technique was used for serotyping. Three serotypes were more common than others among a collection of human isolates.
On the design of door-less access passages to shielded enclosures (2017)

RF shielded enclosures have been common features in laboratories and manufacturing areas for over 70 years. They provide a quiet environment where RF measurements can be performed without interference from outdoor sources and are used to keep potentially classified frequencies and modulations from leaking out. In general, these shielded rooms have shielded doors to maintain the shielding integrity of the enclosure until they are opened. In some cases, to maintain the shielding integrity as personnel moves from the inside to the outside of the room and vice-versa, dual shielded doors with a small vestibule between them are used. However, the presence of multiple doors increases the time to access the enclosure. To solve this, some enclosures are designed featuring access passages to maintain the shielding integrity over a broad frequency without the use of doors. Although this type of access has been around for over 40 years, its design has never been discussed in the literature. In this paper, a door-less access is analyzed and some design rules are presented. The limitations of these accesses are also presented. While clearly they do not have the shielding performance of a shielded door, they are ideal for certain applications.
Expression of a retinoic acid receptor gene in myeloid leukemia cells. (1989)

Retinoic acid (RA) has been shown to increase differentiation in some leukemia cell lines (HL-60 and KG-1) but not others (K562). Similarly, RA has been reported to have variable effects on fresh blast cells. Recently, molecular clones have been obtained for the nuclear receptor for retinoic acid. The experiments described in this paper were designed to compare expression of the receptor to biological activity in myeloblastic leukemia cells. In four continuous AML cell lines, a positive correlation was found between retinoic acid receptor (RAR) expression by Northern analysis or RNA dot blot and the ability of RA to inhibit colony formation. Kinetic studies of the most sensitive cell line showed that inhibition of colony formation was associated with reduced blast cell self-renewal and differentiation-like events. RAR was detected in freshly obtained blast cells from 23 AML patients. Patient-to-patient variation was observed; however, a correlation was not found between RAR expression and response of the freshly obtained blast cells to RA.
Substantial Susceptibility of Chronic Lymphocytic Leukemia to BCL2 Inhibition: Results of a Phase I Study of Navitoclax in Patients With Relapsed or Refractory Disease (2011)

BCL2 is a valid therapeutic target in CLL, and its inhibition by navitoclax warrants further evaluation as monotherapy and in combination in this disease.
Streptomyces polyantibioticus sp. nov., isolated from the banks of a river (2009)

As part of an antibiotic-screening programme, an actinomycete, designated strain SPR(T), was isolated from soil collected from the banks of the Umgeni River, KwaZulu-Natal Province, South Africa. The isolate produced branching vegetative mycelia with sporangiophores bearing sporangia developing at a late stage of growth. The sporangia contained smooth, almond-shaped, non-motile spores. Strain SPR(T) exhibited antibiosis against various Gram-positive and Gram-negative bacteria, including Enterococcus faecium VanA (a vancomycin-resistant strain), Mycobacterium aurum A+ and Escherichia coli ATCC 25922. The chemotaxonomic characteristics of the strain, with the exception of the phospholipid pattern, corresponded with those of the members of the family Streptomycetaceae Waksman and Henrici 1943. Furthermore, phylogenetic analysis based on 16S rRNA genes showed that the strain was closely related to members of the genus Streptomyces, which supports its classification in the family Streptomycetaceae. Thus strain SPR(T) represents a novel species of the genus Streptomyces, for which the name Streptomyces polyantibioticus sp. nov. is proposed. The type strain is SPR(T) (=DSM 44925(T)=NRRL B-24448(T)).
MRP9, an unusual truncated member of the ABC transporter superfamily, is highly expressed in breast cancer (2002)

Combining a computer-based screening strategy and functional genomics, we previously identified MRP9 (ABCC12), a member of the ATP-binding cassette (ABC) superfamily. We now show that the gene has two major transcripts of 4.5 and 1.3 kb. In breast cancer, normal breast, and testis, the MRP9 gene transcript is 4.5 kb in size and encodes a 100-kDa protein. The protein is predicted to have 8 instead of 12 membrane-spanning regions. When compared with closely related ABC family members, it lacks transmembrane domains 3, 4, 11, and 12 and the second nucleotide-binding domain. In other tissues including brain, skeletal muscle, and ovary, the transcript size is 1.3 kb. This smaller transcript encodes a nucleotide-binding protein of approximately 25 kDa in size. An in situ hybridization study shows that the 4.5-kb transcript is expressed in the epithelial cells of breast cancer. An antipeptide antibody designed to react with the amino terminus of the protein detects a 100-kDa protein in testis and the membrane fraction of a breast cancer cell line. Because the 4.5-kb RNA is highly expressed in breast cancer and not expressed at detectable levels in essential normal tissues, MRP9 could be a useful target for the immunotherapy of breast cancer. Because of the unusual topology of the two variants of MRP9, we speculate that they may have a different function from other family members.
Expression and RNA Splicing of the Maize Glutathione S-Transferase Bronze2 Gene Is Regulated by Cadmium and Other Stresses (1997)

The Bronze2 (Bz2) gene in maize (Zea mays) encodes a glutathione S-transferase that performs the last genetically defined step in anthocyanin biosynthesis--tagging anthocyanin precursors with glutathione, allowing for recognition and entry of anthocyanins into the vacuole. Here we show that Bz2 gene expression is highly induced by heavy metals such as cadmium. Treatment of maize seedlings with cadmium results in a 20-fold increase in Bz2 message accumulation and a 50-fold increase in the presence of the unspliced, intron-containing transcript. The increase in message levels during cadmium stress appears to result, at least in part, from activation of an alternative mRNA start site approximately 200 nucleotides upstream of the normal start site; this site is not used in unstressed or heat-stressed tissues. The effect of cadmium on the RNA splicing of Bz2 seems to be specific: splicing of other intron-containing maize genes, including a maize actin gene under the control of the cadmium-inducible Bz2 promoter, is unaffected by cadmium stress. Conversely, Bz2 intron splicing is not affected by other stress conditions that induce Bz2 gene expression, such as abscisic acid, auxin, or cold stress. Surprisingly, the increase in Bz2 mRNA during cadmium stress does not result in an increase in Bz2 glutathione S-transferase activity. We propose that an alternative protein may be encoded by Bz2 that has a role during responses to heavy metals.
Augmentation Versus Inhibition: Effects of Conjunctional OX-40 Receptor Monoclonal Antibody and IL-2 Treatment on Adoptive Immunotherapy of Advanced Tumor (2001)

Therapeutic efficacy of adoptive immunotherapy of malignancies is proportional to the number of effector T cells transferred. Traditionally, exogenous IL-2 treatment has been used to promote the survival and function of transferred cells. Recently, we described the therapeutic effects of in vivo ligation of the costimulatory receptor, OX-40R, on activated T cells during early tumor growth. In this study, we examined the effects of IL-2 and OX-40R mAb on adoptive immunotherapy of advanced tumors. For treatment of 10-day 3-methylcholanthrene 205 pulmonary metastases, systemic transfer of 50 x 10(6) activated tumor-draining lymph node T cells resulted in >99% reduction of metastatic nodules. With either IL-2 or OX-40R mAb conjunctional treatment, only 20 x 10(6) cells were required. Advanced 10-day 3-methylcholanthrene 205 intracranial tumors could be cured by the transfer of 15 x 10(6) L-selectin(low) T cells derived from draining lymph nodes. In this situation, IL-2 administration inhibited therapeutic effects of the transferred cells. By contrast, 5 x 10(6) T cells were sufficient to cure all mice if OX-40R mAb was administrated. Studies on trafficking of systemically transferred T cells revealed that IL-2, but not OX-40R mAb, impeded tumor infiltration by T cells. Tumor regression required participation of both CD4 and CD8 T cells. Because only CD4 T cells expressed OX-40R at cell transfer, direct CD4 T cell activation is possible. Alternatively, OX-40R might be up-regulated on transferred T cells at the tumor site, rendering them reactive to the mAb. Our study suggests OX-40R mAb to be a reagent of choice to augment T cell adoptive immunotherapy in clinical trials.
The Effects of Oral Dehydroepiandrosterone on Endocrine-Metabolic Parameters in Postmenopausal Women* (1990)

To discern the pharmacological effects of dehydroepiandrosterone (DHEA) in older women with low endogenous DHEA and DHEA sulfate (DS), 1600 mg/day (in four divided doses) were administered orally to six postmenopausal women for 28 days in a double blind placebo-controlled cross-over study. Serum concentrations of androgens after the first 400-mg dose of DHEA increased rapidly and reached a maximum at 180-240 min, resulting in increases over baseline of 6-fold for DHEA (5.8 +/- 2.1 to 28.8 +/- 5.5 nmol/L), 12-fold for DS (3.0 +/- 1.6 to 28.2 +/- 4.6 mumol/L) and androstenedione (1.4 +/- 0.3 to 19.5 +/- 9.8 nmol/L), 2.5-fold for testosterone (0.7 +/- 0.1 to 2.2 +/- 0.6 nmol/L), and 15-fold for dihydrotestosterone (0.2 +/- 0.06 to 2.73 +/- 1.0 nmol/L), but estrone, estradiol, and sex hormone-binding globulin (SHBG) were unchanged. Assessment at weekly intervals revealed a further increase in all androgens which was maximal at 2 weeks and remained markedly elevated, although it declined somewhat by 4 weeks. The increments observed after 2 weeks of DHEA administration reached 15-fold for DHEA (71.9 +/- 14.2 nmol/L), 9-fold for testosterone (6.5 +/- 1.7 nmol/L), and 20-fold for DS (65.1 +/- 14.9 nmol/L), androstenedione (30.5 +/- 11.5 nmol/L), and dihyrotestosterone (3.8 +/- 1.5 nmol/L). Both estrone and estradiol showed a progressive increase to 2-fold the basal value at 4 weeks. Integrated SHBG and thyroid binding globulin levels decreased (P less than 0.05) during DHEA treatment. However, LH, FSH, body weight, and percent body fat, as measured by underwater weighing, were unaltered during the 4-week experiment. A marked decline of 11.3% (P less than 0.05) in serum cholesterol and 20.0% (P less than 0.05) in high density lipoprotein noted within the first week of DHEA administration persisted for the 28-day period and was accompanied by a nonsignificant downward trend in low density lipoprotein, very low density lipoprotein, and triglycerides. Peak insulin levels during the 3-h oral glucose tolerance test were significantly higher (P less than 0.05) after the 28 days of DHEA (1126 +/- 165 vs. 746 +/- 165 pmol/L) and were accompanied by a 50% increase in the integrated insulin response (P less than 0.01) without a significant change in fasting glucose insulin or glucose-6-phosphate dehydrogenase values.(ABSTRACT TRUNCATED AT 400 WORDS)
128 Mb/s multiport CMOS binary active-pixel image sensor (2002)

A 128/spl times/128 photo-diode active pixel sensor (APS) with an on-chip array sequencing controller and 1b thresholding circuitry processes 8,192-frames/s at a 128 Mb data rate onto a 8 b wide parallel-digital output port. In addition, the on-chip controller can be commanded to output data through either a serial digital port for lower bandwidth requirements or through a serial analog port for higher-resolution off-chip analog-to-digital conversion.