gebhart/patrepeval huggingface dataset:
The Sodium Potassium ATPase, Caveolin 1 and their Interaction as Potential Anti-Breast Cancer Therapeutic Targets (2013)

Breast cancer pathogenesis is modulated by complex signalling pathways centred on cholesterol-enriched membrane domains termed lipid rafts. Caveolae, a subtype of rafts, express the protein caveolin-1, which has been suggested as both as a tumour suppressor and promoter. One protein that interacts with caveolin-1 is the sodium potassium ATPase (Na+ K+ ATPase) ion channel. Na+ K+ ATPase has recently been implicated in cell signalling via interaction with its natural inhibitors, cardiac glycosides (CGs). Although predominantly used for heart failure indications, CGs reportedly have anti-proliferative properties in tumour cells. Given the importance of caveolin-1 in malignant behaviours, we hypothesized that CGs exert anti-breast cancer effects by modulating functional associations between Na+ K+ ATPase and caveolae. We first demonstrated concentration- and time-dependent anti-proliferative responses to the CGs digoxin, ouabain and oleandrin in breast cell lines and primary cultures. These effects were most pronounced in primary cell cultures, and least in ER/PR/HER2 triple-negative cells. We next showed concentration-dependent reductions in cell migration in response to CGs, particularly in ER-positive cells. CGs arrested the cell cycle at both G1 and S phase in ER-positive cells, with partial arrest at G1 in ER-negative cells. This was paralleled by increased p21 expression at both gene and protein level in ER-positive cells, and decreased p53 expression in ERnegative cells. CGs slightly decreased Na+ K+ ATPase association with caveolae in ER-positive cells, but increased that in ER-negative cells. Knockdown of caveolin-1 (but not the planar lipid raft marker flotillin-1) potentiated the effects of CGs in ER-negative but not ER-positive cells. Pharmacological lipid raft disruption abrogated the effects of CGs in ER-positive cells, while raft augmentation did the opposite. In contrast, raft disruption did not alter CG effects in ER-negative cells, but augmentation potentiated their effects. Finally, we showed that ouabain transiently activated both Src and ERK in ER-negative cells, but induced delayed Src and ERK activation in ER-positive cells. Taken together, our results provide novel evidence that the powerful anti-proliferative effects of CGs in breast cancer cells involve modulations of the functional association between Na+ K+ ATPase and caveolin-1. We suggest that the Na+ K+ ATPase, caveolin-1 and their interaction in caveolae represent exciting targets for consideration in future breast cancer drug development strategies.
The Shikimate Pathway — A Metabolic Tree with Many Branche (1990)

(1990). The Shikimate Pathway — A Metabolic Tree with Many Branche. Critical Reviews in Biochemistry and Molecular Biology: Vol. 25, No. 5, pp. 307-384.
Spatial and temporal targeting of gene expression in Drosophila by means of a tetracycline-dependent transactivator system (1998)

In order to evaluate the efficiency of the tetracycline-regulated gene expression system in Drosophila, we have generated transgenic lines expressing a tetracycline-controlled transactivator protein (tTA), with specific expression patterns during embryonic and larval development. These lines were used to direct expression of a tTA-responsive promoter fused to the coding region of either the beta-galactosidase or the homeotic protein Antennapedia (ANTP), under various conditions of tetracycline treatment. We found that expression of beta-galactosidase can be efficiently inhibited in embryos and larvae with tetracycline provided in the food, and that a simple removal of the larvae from tetracycline exposure results in the induction of the enzyme in a time- and concentration-dependent manner. Similar treatments can be used to prevent the lethality associated with the ectopic expression of ANTP in embryos and, subsequently, to control the timing of expression of the homeoprotein ANTP specifically in the antennal imaginal disc. Our results show that the expression of a gene placed under the control of a tetracycline-responsive promoter can be tightly controlled, both spatially by the regulatory sequences driving the expression of tTA and temporally by tetracycline. This provides the basis of a versatile binary system for controlling gene expression in Drosophila, with an additional level of regulation as compared to the general method using the yeast transcription factor GAL4.
Strategies for the Treatment of Sepsis (1997)

A remarkable number of clinical trials have been performed in the past decade to evaluate drugs for the treatment of sepsis. The mechanism of action of most of these agents is based on one of two unproved assumptions relating to sepsis in humans. The first is that endotoxin (bacterial lipopolysaccharide) contributes to the morbidity and mortality caused by infection with gram-negative bacteria. The second assumption is that a major part of the pathophysiology in patients with sepsis is due to an overproduction of one or many secondarily induced host mediators. The evidence for these widespread beliefs is that when lipopolysaccharide . . .
Emergence of Serotype V Group B Streptococcal Infection among Infants and Adults (1995)

Journal Article Emergence of Serotype V Group B Streptococcal Infection among Infants and Adults Get access Lee H. Harrison, Lee H. Harrison Johns Hopkins University School of Hygiene and Public Health, Maryland Department of Health and Mental Hygiene, and University of Maryland School of MedicineBaltimore Reprints or correspondence: Dr. Lee H. Harrison, Johns Hopkins University, 615 N. Wolfe sc, Room 5515, Baltimore, MD 21205. Search for other works by this author on: Oxford Academic PubMed Google Scholar Diane M. Dwyer, Diane M. Dwyer Johns Hopkins University School of Hygiene and Public Health, Maryland Department of Health and Mental Hygiene, and University of Maryland School of MedicineBaltimore Search for other works by this author on: Oxford Academic PubMed Google Scholar Judith A. Johnson Judith A. Johnson Johns Hopkins University School of Hygiene and Public Health, Maryland Department of Health and Mental Hygiene, and University of Maryland School of MedicineBaltimore Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 171, Issue 2, February 1995, Page 513, https://doi.org/10.1093/infdis/171.2.513 Published: 01 February 1995
Long-lived cytotoxic T lymphocyte memory in mucosal tissues after mucosal but not systemic immunization. (1996)

The induction and maintenance of long-term CTL memory at mucosal surfaces may be a critical component of protection against mucosal pathogens and is one goal towards development of effective mucosal vaccines. In these studies we have functionally evaluated short and long-term CTL memory in systemic and respiratory or genital-associated lymphoid tissues following mucosal or systemic routes of immunization. Our results indicate that shortly after immunizing mice with a recombinant adenovirus vector expressing glycoprotein B (gB) of herpes simplex virus (AdgB8), gB-specific CTL memory responses were observed in systemic and mucosal immune compartments regardless of the route of inoculation. In contrast, several months after immunization, anamnestic CTL responses compartmentalized exclusively to mucosal or systemic lymphoid tissues after mucosal or systemic immunization, respectively. Furthermore, the compartmentalized CTL memory responses in mucosal tissues were functionally observed for longer than 1.5 yr after intranasal immunization, and CTL precursor frequencies one year after immunization were comparable to those seen shortly after immunization. Therefore, to our knowledge, this is the first functional demonstration that the maintenance of anti-viral memory CTL in mucosal tissues is dependent on the route of immunization and the time of assessment. These results have important implications for our understanding of the development, maintenance, and compartmentalization of functional T cell memory and the development and evaluation of vaccines for mucosal pathogens, such as HSV and HIV.
Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles (2003)

HIV pseudotypes bearing native hepatitis C virus (HCV) glycoproteins (strain H and Con1) are infectious for the human hepatoma cell lines Huh-7 and PLC/PR5. Infectivity depends on coexpression of both E1 and E2 glycoproteins, is pH-dependent, and can be neutralized by mAbs mapping to amino acids 412-447 within E2. Cell-surface expression of one or all of the candidate receptor molecules (CD81, low-density lipoprotein receptor, scavenger receptor class B type 1, and dendritic cell-specific intercellular adhesion molecule 3 grabbing nonintegrin) failed to confer permissivity to HIV-HCV pseudotype infection. However, HIV-HCV pseudotype infectivity was inhibited by a recombinant soluble form of CD81 and a mAb specific for CD81, suggesting that CD81 may be a component of a receptor complex.
Direct sequence spread spectrum Walsh-QPSK modulation (1998)

We present Walsh-quadrature phase-shift keying (Walsh-QPSK) pseudonoise (PN) modulation schemes for both coherent and noncoherent direct-sequence code-division multiple-access (DS-CDMA) systems, wherein the PN spreading sequences for in-phase and quadrature data in a conventional QPSK PN modulation scheme are coded by Walsh sequences indexed by a special rule to reduce the envelope variation of the transmitted signal. The signal characteristics of the two schemes are analyzed when a rectangular-shaped PN chip pulse is used, and it is shown that the proposed coherent DS-CDMA system has a constant envelope even in the presence of a transmitted phase reference. We simulate the signals to obtain the envelope variations when a spectrally efficient shaped PN chip pulse is used, and compare the results with those of conventional QPSK and orthogonal QPSK (OQPSK) PN modulation schemes. The results show that both the noncoherent and coherent Walsh-QPSK schemes have smaller envelope variations than the conventional noncoherent QPSK and OQPSK PN modulation schemes, even though in the coherent Walsh-QPSK scheme the pilot channel is added to the signal channel.
TT-seq maps the human transient transcriptome (2016)

Pervasive transcription of the genome produces both stable and transient RNAs. We developed transient transcriptome sequencing (TT-seq), a protocol that uniformly maps the entire range of RNA-producing units and estimates rates of RNA synthesis and degradation. Application of TT-seq to human K562 cells recovers stable messenger RNAs and long intergenic noncoding RNAs and additionally maps transient enhancer, antisense, and promoter-associated RNAs. TT-seq analysis shows that enhancer RNAs are short-lived and lack U1 motifs and secondary structure. TT-seq also maps transient RNA downstream of polyadenylation sites and uncovers sites of transcription termination; we found, on average, four transcription termination sites, distributed in a window with a median width of ~3300 base pairs. Termination sites coincide with a DNA motif associated with pausing of RNA polymerase before its release from the genome.
Clinical Significance of In Vitro Replication–Enhancing Mutations of the Hepatitis C Virus (HCV) Replicon in Patients with Chronic HCV Infection (2005)

Specific mutations leading to enhanced replication in the replicon system were detected in 5 of 26 patients in vivo and were not associated with baseline HCV RNA concentrations but were associated with a slower decrease in HCV RNA concentration during IFN- alpha -based therapy. Quasi-species heterogeneity of NS5A correlated with baseline HCV RNA concentrations.
Insights from Pim1 structure for anti-cancer drug design (2012)

To obtain a potent and selective Pim1 inhibitor as a lead compound, the authors propose the development of compounds which simultaneously interact with both the ATP binding site (Lys67, Glu121 and Phe49) and substrate binding residues (Asp128, Asp131 and Glu171). The development of Pim1 inhibitors could lead to new therapeutic options for a number of hematological malignancies and prostate cancer in the future.
Mixture-model adaptation for SMT (2007)

We describe a mixture-model approach to adapting a Statistical Machine Translation System for new domains, using weights that depend on text distances to mixture components. We investigate a number of variants on this approach, including cross-domain versus dynamic adaptation; linear versus loglinear mixtures; language and translation model adaptation; different methods of assigning weights; and granularity of the source unit being adapted to. The best methods achieve gains of approximately one BLEU percentage point over a state-of-the art non-adapted baseline system.
Purification and biochemical characterization of tubulin from the budding yeast Saccharomyces cerevisiae (1993)

We describe a method for isolating milligram quantities of assembly-competent tubulin from the budding yeast Saccharomyces cerevisiae. The tubulin is > 95% purified and free of contaminating enzyme activities. As a result, it has been possible to determine the yeast tubulin equilibrium-binding constant for Mg-GTP and the tubulin GTPase activity under nonassembling and assembling conditions. We also determined the critical concentration for yeast tubulin polymerization and found it to be significantly lower than that for bovine brain tubulin under identical conditions. Similarly, the dynamic properties both of individual yeast microtubules and of bulk microtubule suspensions were significantly different from those of bovine brain microtubules free of microtubule-associated proteins. The data suggest that the properties of the yeast tubulin may reflect the particular functional requirements of the yeast cell. With this method, it is now possible to introduce any desired tubulin gene mutation into the budding yeast and correlate the phenotypic effects of the mutation in cells with the effects of the mutation on the biochemical and polymerization properties of the tubulin.
Cyclic guanidines. XVI. Synthesis and biological activities of tetracyclic imidazo(2,1-b)quinazolinone derivatives. (1985)

Tetracyclic imidazo [2, 1-b] quinazolinone derivatives (18) with a modified or unmodified alkylene chain were prepared and evaluated for their ability to inhibit platelet aggregation. Most of the compounds were very potent except for some compounds substituted with an amino or a hydroxy group. The structure-activity relationships are discussed.
Effect of adsorbed protein on hydroxyapatite zeta potential and Streptococcus mutans adherence (1983)

The adherence of Streptococcus mutans PK1 to hydroxyapatite disks pretreated with various acidic and basic proteins in imidazole buffer was studied. Adsorption of a basic protein onto an hydroxyapatite disk enhanced or had no effect on bacterial adherence, whereas adsorption of an acidic protein reduced adherence. The effect of adsorbed protein on bacterial adherence was of both short and long range. The long-range effect of the acidic proteins in reducing the number of bacteria adhering to hydroxyapatite was related to protein adsorption causing an increase in surface net negative charge, as shown by zeta potential measurement. Basic protein produced a net positive surface charge which facilitated adherence. Within the acidic protein group, the acidic residue percentage of the adsorbed protein was negatively correlated with the number of bacteria adhering, whereas the nonpolar residue percentage was positively correlated with bacterial adherence. Within the basic protein group, the basic residue percentage was correlated with the number of cells adhering. These results indicate the involvement of short-range hydrophobic and ionic interactions in bacterial adherence to protein-coated hydroxyapatite.
Th17 and natural Treg cell population dynamics in systemic lupus erythematosus (2009)

SLE flare might be linked to the expansion of the Th17 cell population and the depletion of natural Treg cell subpopulations. Expansion of the Th17 cell population might be related to a distinct cytokine environment in active SLE. Th17 cells and microenvironmental IL-17A are involved in vascular inflammation in SLE. Antagonism of Th17 cells by IL-17A-blocking antibodies should be explored as a treatment of SLE.
Variant Hepatocyte Nuclear Factor 1 is required for visceral endoderm specification (1999)

Genetic and molecular evidence indicates that visceral endoderm, an extraembryonic cell lineage, is required for gastrulation, early anterior neural patterning, cell death and specification of posterior mesodermal cell fates. We show that variant Hepatocyte Nuclear Factor 1 (vHNF1), a homeodomain-containing transcription factor first expressed in the primitive endoderm, is required for the specification of visceral endoderm. vHnf1-deficient mouse embryos develop normally to the blastocyst stage, start implantation, but die soon afterwards, with abnormal or absent extraembryonic region, poorly organised ectoderm and no discernible visceral or parietal endoderm. However, immunostaining analysis of E5.5 nullizygous mutant embryos revealed the presence of parietal endoderm-like cells lying on an abnormal basal membrane. Homozygous mutant blastocyst outgrowths or differentiated embryonic stem cells do not express early or late visceral endoderm markers. In addition, in vHnf1 null embryoid bodies there is no activation of the transcription factors HNF-4alpha1, HNF1alpha and HNF-3gamma. Aggregation of vHnf1-deficient embryonic stem cells with wild-type tetraploid embryos, which contribute exclusively to extraembryonic tissues, rescues periimplantation lethality and allows development to progress to early organogenesis. Our results place vHNF1 in a preeminent position in the regulatory network that specifies the visceral endoderm and highlight the importance of this cell lineage for proper growth and differentiation of primitive ectoderm in pregastrulating embryos.
<title>Computerized characterization of contrast enhancement patterns for classifying pulmonary nodules</title> (2000)

This paper presents a computerized approach to characterize pulmonary nodules as benign or malignant based on contrast enhancement patterns extracted from serial three-dimensional (3-D) thoracic CT images. In this approach the registration procedure of sequential 3-D pulmonary images consisted of the rigid transformation between two sequential region-of-interest (ROI) images including the pulmonary nodule. The normalized mutual information was used as a voxel-based similarity measure in the registration. After the motion correction between successive ROI images, the enhancement rate within a core of the segmented 3-D nodule image was estimated from the difference between the pre- and post-contrast images. We analyzed a data set of twelve 3-D thoracic CT images with pulmonary nodules in this study. Based on the Wilcoxon rank sum test, the median enhancement of the malignant lesions was significantly higher than that of the benign lesions (p less than 0.01). The preliminary results of the approach are very promising in characterizing pulmonary nodules based on quantitative measures of the contrast enhancement.
Effects of Nanofiber/Stem Cell Composite on Wound Healing in Acute Full-Thickness Skin Wounds (2011)

Acute full-thickness skin wounds (FTSW) caused by extensive burns or high-energy trauma are not adequately addressed by current clinical treatments. This study hypothesized that biomimetic nanofiber scaffolds (NFSs) functionalized with rich attachment of bone-marrow-derived mesenchymal stem cells (BM-MSCs) can promote wound healing in acute FTSW. Results in a rat model showed that both NFS and BM-MSCs contributed to the wound healing. Wounds in NFS group with a higher density of BM-MSCs achieved complete closure 8 days earlier than the control group. Implanted BM-MSCs were found to promote epithelial edge ingrowth and collagen synthesis. The colocation of BM-MSCs (tagged with quantum-dots) with the expression of keratin 10 and filaggrin indicated the participation of BM-MSCs in epidermal differentiation at early and intermediate stages under the local wounding environment. Overall, this study suggests a great potential of using NFS/BM-MSC composites for the treatment of acute FTSW.
Combined effect of promoter polymorphisms in the dopamine D4 receptor and the serotonin transporter genes in heroin dependence. (2005)

Dopamine D4 receptor (DRD4) and serotonin transporter (SERT) gene polymorphisms were studied, as possible genetic risk factors for substance dependence. The case-control study involved a large cohort (n = 362) of healthy Caucasian population, and an initial sample of 73 substance dependent patients (including a subgroup of 53 heroin dependents). Improved methods were applied for genotype detection of the DRD4 polymorphisms (exon 3 48 bp VNTR; -521 C/T SNP and 120 bp duplication in the 5' flanking region) and the SERT gene polymorphisms (5-hydroxytriptamin transporter linked polymorphic region [5-HTTLPR] in the 5' flanking region and the intron 2 VNTR [STin2]). Association between the -521 C/T SNP of the DRD4 promoter region and substance dependence was significant in the subgroup of heroin dependents (p = 0.044). The other analyzed polymorphisms did not show any significant association, but an interaction between -521 C/T SNP of DRD4 and the 5-HTTLPR polymorphisms was observed. Association between the -521 CC vs. CT or TT genotypes and heroin dependence was enhanced in the presence of short (s or 14-repeat) 5-HTTLPR allele (p 0.01). The odds ratio of 2.14 observed for the -521 CC genotype increased to 4.82 in double homozygotes of -521 CC and 5-HTTLPR ss, emphasizing the importance of combined analysis of polymorphisms in the dopaminergic and serotonergic systems in heroin dependence. However, due to the limited size of our sample these results should be interpreted with caution.
Myrinet: a gigabit-per-second local area network (1995)

The Myrinet local area network employs the same technology used for packet communication and switching within massively parallel processors. In realizing this distributed MPP network, we developed specialized communication channels, cut-through switches, host interfaces, and software. To our knowledge, Myrinet demonstrates the highest performance per unit cost of any current LAN.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>