gebhart/patrepeval huggingface dataset:
Studies on the Pathogenicity ofYersinia enterocolitica (1977)

Abstract Analysis of the pathogenicity of Yersinia enterocolitica was performed with an experimental model successfully produced in rabbits by intraduodenal inoculation with strains isolated from various sources. Pathogenic strains easily penetrated the epithelial linings of the intestinal mucous membrane into the target reticuloendothelial tissues of the intestine, such as the lamina propria and lymph follicles, where they multiplied within mononuclear cells and produced granuloma. Granuloma, in severe infections, underwent necrobiosis and sometimes progressed to ulceration accompanied by colony formation of the organisms. In mild infections, granulomatous lesions were localized in lymph follicles and never progressed to ulceration. Nonpathogenic strains were rapidly excreted without penetration of epithelial linings. Y. enterocolitica should be within the category of invasion type enteropathogenic bacteria such as Shigella and Salmonella . Pathogenic behavior of Y. enterocolitica is discussed in comparison with that of Shigella and Salmonella .
Androgen Receptor Rediscovered: The New Biology and Targeting the Androgen Receptor Therapeutically (2011)

Discoveries over the past decade suggest that castration-resistant prostate cancer (CRPC) is sensitive, but not resistant to, further manipulation of the androgen-androgen receptor (AR) axis. Several new therapies that target this axis have demonstrated clinical activity. In this article, preclinical and clinical findings occurring in the field of AR-targeted therapies are reviewed. Reviews of scientific and clinical development are divided into those occurring prereceptor (androgen production and conversion) and at the level of the receptor (AR aberrations and therapies targeting AR directly). Intracrine androgen production and AR amplification, among others, are among the principal aberrancies driving CRPC growth. Phase III data with abiraterone acetate and phase II data with MDV-3100, along with other similar therapies, confirm for the clinician that the scientific findings related to persistent AR signaling in a castrate milieu can be harnessed to produce significant clinical benefit for patients with the disease. Studies aimed at optimizing the timing of their use and exploring the mechanisms of resistance to these therapies are under way. The clinical success of therapies that directly target androgen synthesis as well as the most common aberrancies of the AR confirm that prostate cancer retains dependence on AR signaling, even in the castrate state.
Digital-to-analog conversion using electrooptic modulators (2003)

A photonic implementation of optical digital-to-analog converter is proposed using electrooptic polymer modulators. A 2-bit implementation at low frequencies is experimentally demonstrated at a conversion rate of 80 MS/s which is limited by the bandwidth of the photodetector and its associated electronics. Some of the technical issues that must be overcome to reach our goal of simultaneous high-speed (tens of gigasamples per second) and high-resolution (on the order of 12 bits) performance are discussed.
Reconstitution of signal transduction from the membrane to the nucleus in a baculovirus expression system: activation of Raf-1 leads to hypermodification of c-jun and c-fos via multiple pathways. (1995)

We have attempted to dissect signaling pathways involved in transmitting activating signals from the cell surface to the nucleus by reconstituting them in the baculovirus/Sf9 cell system. We have used this system to coexpress different combinations of the critical signaling proteins pp60v-src, p21v-ras, Raf-1 and ERK-1 and assayed the effects of resulting signaling cascades on the modifications of coexpressed transcription factors c-jun or c-fos. We observe that activation of ERK-1 via Raf-1 and p21ras dependent signals can result in the hyperphosphorylation of c-jun. In contrast, c-fos appears to be the target of two Raf-1 activated modifying signals: one independent of ERK-1 and the other dependent on ERK-1 stimulation. Thus, coexpression of c-fos with pp60v-src, p21v-ras or constitutively active forms of Raf-1 results in a dramatic reduction of its electrophoretic mobility in the absence of coexpressed ERK-1. Activation of this ERK-1-independent pathway together with the ERK-1 dependent pathway that modifies c-jun results in additional modification of c-fos. Our observation of a Raf-1 activated, ERK-independent signaling pathway is consistent with previous reports that constitutively active Raf-1 can, in some cell types, result in transformation or differentiation without activation of ERKs. Our data indicate the presence of multiple Raf-1 activated pathways that lead to modification of transcription factors.
Limited proteolysis and active-site studies of the first multienzyme component of the erythromycin-producing polyketide synthase. (1994)

The domain structure of the 6-deoxyerythronolide B synthase 1 component of the erythromycin-producing polyketide synthase from Saccharopolyspora erythraea has been investigated using limited proteolysis and active-site labeling. Trypsin, elastase, endoproteinase Glu-C, and endoproteinase Arg-C were used to cleave the multienzyme, and the sizes of the resulting fragments were assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The location of fragments within the primary structure was established by N-terminal sequence analysis. The cleavage pattern followed domain boundaries previously predicted on the basis of sequence alignments, but many predicted interdomain regions were not cleaved, even under the harshest conditions used. Initial proteolysis generated three large fragments: an N-terminal fragment (about 60 kDa) housing an acyltransferase-acyl carrier protein di-domain; a central fragment (about 90 kDa) containing a ketosynthase-acyltransferase di-domain; and a C-terminal fragment (about 220 kDa) containing the remaining six domains of the multienzyme, including the third acyltransferase. The intact multienzyme behaves as a dimer of molecular mass 660 kDa on gel filtration; and the C-terminal fragment remains dimeric. However, the N-terminal and central fragments appear to be monomeric species. After proteolysis of the multienzyme, the N-terminal di-domain was found to be specifically labeled after incubation with [14C]propionyl-CoA, providing the first evidence for its proposed role as a "loading domain" for the propionate starter unit. In contrast, the other two fragments were specifically acylated by [14C]methylmalonyl-CoA, indicating that both the other two acyltransferases remain enzymatically active after proteolysis.
Effect of phosphate on the parathyroid gland: direct and indirect? (1996)

Hyperparathyroidism is a common finding in patients with renal failure. Phosphorus retention is known to be an important factor in the development of secondary hyperparathyroidism. Exciting new work has demonstrated that a high extracellular phosphorus concentration directly stimulates parathyroid hormone secretion and synthesis. Dietary phosphorus also modulates parathyroid function indirectly by decreasing calcitriol production, and it interferes with the calcaemic response to parathyroid hormone. The information available suggests that the control exerted by phosphorus is critical, via indirect and direct actions, in preventing the development of secondary hyperparathyroidism.
Template-Grown NiFe/Cu/NiFe Nanowires for Spin Transfer Devices (2007)

We have developed a new reliable method combining template synthesis and nanolithography-based contacting technique to elaborate current perpendicular-to-plane giant magnetoresistance spin valve nanowires, which are very promising for the exploration of electrical spin transfer phenomena. The method allows the electrical connection of one single nanowire in a large assembly of wires embedded in anodic porous alumina supported on Si substrate with diameters and periodicities to be controllable to a large extent. Both magnetic excitations and switching phenomena driven by a spin-polarized current were clearly demonstrated in our electrodeposited NiFe/Cu/ NiFe trilayer nanowires. This novel approach promises to be of strong interest for subsequent fabrication of phase-locked arrays of spin transfer nano-oscillators with increased output power for microwave applications.
Measurement of Panic‐Like Responses Following Intravenous Infusion of Sodium Lactate in Panic‐Prone Rats (2003)

This unit describes a putative animal model for panic disorder. The basic premise is that pharmacological disruption of critical brain regions implicated in the circuitry of anxiety will lead to a condition similar to that of the human disorder. A clinically relevant test, the sodium lactate challenge, is utilized to assess parallels between the human condition and this rat model.
Nuclear and mitochondrial forms of human uracil-DNA glycosylase are encoded by the same gene (1993)

Recent cloning of a cDNA (UNG15) encoding human uracil-DNA glycosylase (UDG), indicated that the gene product of M(r) = 33,800 contains an N-terminal sequence of 77 amino acids not present in the presumed mature form of M(r) = 25,800. This led to the hypothesis that the N-terminal sequence might be involved in intracellular targeting. To examine this hypothesis, we analysed UDG from nuclei, mitochondria and cytosol by western blotting and high resolution gel filtration. An antibody that recognises a sequence in the mature form of the UNG protein detected all three forms, indicating that they are products of the same gene. The nuclear and mitochondrial form had an apparent M(r) = 27,500 and the cytosolic form an apparent M(r) = 38,000 by western blotting. Gel filtration gave essentially similar estimates. An antibody with specificity towards the presequence recognised the cytosolic form of M(r) = 38,000 only, indicating that the difference in size is due to the presequence. Immunofluorescence studies of HeLa cells clearly demonstrated that the major part of the UDG activity was localised in the nuclei. Transfection experiments with plasmids carrying full-length UNG15 cDNA or a truncated form of UNG15 encoding the presumed mature UNG protein demonstrated that the UNG presequence mediated sorting to the mitochondria, whereas UNG lacking the presequence was translocated to the nuclei. We conclude that the same gene encodes nuclear and mitochondrial uracil-DNA glycosylase and that the signals for mitochondrial translocation resides in the presequence, whereas signals for nuclear import are within the mature protein.
Thermodynamics of primary photosynthesis (2013)

The thermodynamics of photosynthesis has been much discussed, but recent articles have pointed to some confusion on the subject. The aim of this review is to clarify a limited part of this state of affairs.
Thyroid function in breast cancer patients. (2010)

Significant differences in fT3/fT4 as well as TRAK levels were observed among breast cancer patients, women with benign breast tumours and healthy controls. Further studies using larger patient groups are part of ongoing research.
Localization of the immunologic activity in the superantigen Staphylococcal enterotoxin B using truncated recombinant fusion proteins (1992)

The exotoxins of certain strains of Staphylococcus aureus strains are able both to stimulate potent proliferation and induce anergy in T lymphocytes expressing the appropriate T cell Ag receptor V beta gene elements. Although T cell activation by the S. aureus enterotoxins requires the presence of accessory cells bearing class II Ag of the MHC, unlike the peptide fragments of nominal Ag, they contact the external surfaces of both the class II MHC and TCR molecules. This paper investigates the immunologically active domains of S. aureus enterotoxin B (SEB) using truncated fragments of rSEB expressed as a fusion protein with protein A. The results of the experiments reported here indicate that the minimal fragment of SEB able to stimulate and induce anergy in hemagglutinin-reactive human T cells expressing V beta 3.1 gene elements is located in the amino-terminal portion of the molecule within residues 1-138. Deletion of the first 30 amino acid residues renders rSEB unable to stimulate T cells expressing V beta 3.1, whereas polyclonal T cells still respond to this molecule. This implies that the stimulation of several TCR-V beta families may be caused by the interaction with different regions of the toxin. The localization of immunologically active sites in the bacterial enterotoxins is needed to investigate both their biology and potential application as immunomodulatory agents.
Molecular definition of de novo and genetically transmitted WAGR-associated rearrangements of 11p13 (1989)

We describe a family in whom the phenotypically normal father carries a balanced insertional translocation, ins(14;11)(q23;p12p14). This individual fathered three mentally retarded children, two with a del(11)(p13) and one with a dup(11)(p13). Two other cases of a de novo del(11)(p13) are also described. All four del(11)(p13) cases presented with WAGR, a complex syndrome associated with a predisposition to Wilms' tumor (WT), aniridia (A), genitourinary abnormalities (G), and mental retardation (R). Using an approach combining karyotype analysis, determination of the gene copy number, and RFLP studies employing five 11p13 DNA markers, we were able to define the chromosomal rearrangement involved in each case. Analysis of these WAGR deletions provides further subdivision of band p13 on chromosome 11.
Differential regulation of the fibroblast growth factor (FGF) family by α2-macroglobulin: evidence for selective modulation of FGF-2–induced angiogenesis (2001)

The fibroblast growth factor (FGF) family has an important role in processes such as angiogenesis, wound healing, and development in which precise control of proteinase activity is important. The human plasma proteinase inhibitor alpha(2)-macroglobulin (alpha(2)M) regulates cellular growth by binding and modulating the activity of many cytokines and growth factors. These studies investigate the ability of native and activated alpha(2)M (alpha(2)M*) to bind to members of the FGF family. Both alpha(2)M and alpha(2)M* bind specifically and saturably to FGF-1, -2, -4, and -6, although the binding to alpha(2)M* is of significantly higher affinity. Neither alpha(2)M nor alpha(2)M* bind to FGF-5, -7, -9, or -10. FGF-2 was chosen for more extensive study in view of its important role in angiogenesis. It was demonstrated that FGF-2 binds to the previously identified TGF-beta binding site. The alpha(2)M* inhibits FGF-2-dependent fetal bovine heart endothelial cell proliferation in a dose-dependent manner. Unexpectedly, alpha(2)M* does not affect FGF-2-induced vascular tubule formation on Matrigel basement membrane matrix or collagen gels. Further studies demonstrate that FGF-2 partitions between fluid-phase alpha(2)M* and solid-phase Matrigel or collagen. These studies suggest that the ability of alpha(2)M* to modulate the activity of FGF-2 is dependent on an interplay with extracellular matrix components. (Blood. 2001;97:3450-3457)
In(Ti1/2M1/2)O3(MO)m Compounds (M=Zn or Mg, m: Natural Number): Synthesis and Crystal Structures (1993)

New homologous compounds In 1+ x (Ti 1/2 Zn 1/2 ) 1- x O 3 (ZnO) m ( m =1–11, 0&lt; x ≤1) having LuFeO 3 (ZnO) m -type and In(Ti 1/2 Mg 1/2 )O 3 (MgO) having spinel-type are synthesized. The relations between the crystal structures of InAO 3 (MO) or In(Ti 1/2 M 1/2 )O 3 (MO) (A=Fe, Ga, or Al, M=Zn or Mg) and the constituent cation elements are discussed. The crystal structures of the homologous compounds LuFeO 3 (ZnO) m are compared with those of (In 2 S 3 ) n (ZnS) m ( m , n : natural number).
F-Prostanoid Receptor Regulation of Fibroblast Growth Factor 2 Signaling in Endometrial Adenocarcinoma Cells (2007)

Prostaglandin (PG) F(2alpha) is a potent bioactive lipid in the female reproductive tract, and exerts its function after coupling with its heptahelical G-protein-coupled receptor [F-series-prostanoid (FP) receptor] to initiate cell signaling and target gene transcription. In the present study, we found elevated expression of fibroblast growth factor (FGF) 2, FGF receptor 1 (FGFR1), and FP receptor, colocalized within the neoplastic epithelial cells of endometrial adenocarcinomas. We investigated a role for PGF(2alpha)-FP receptor interaction in modulating FGF2 expression and signaling using an endometrial adenocarcinoma cell line stably expressing the FP receptor to the levels detected in endometrial adenocarcinomas (FPS cells) and endometrial adenocarcinoma tissue explants. PGF(2alpha)-FP receptor activation rapidly induced FGF2 mRNA expression, and elevated FGF2 protein expression and secretion into the culture medium in FPS cells and endometrial adenocarcinoma explants. The effect of PGF(2alpha) on the expression and secretion of FGF2 could be abolished by treatment of FPS cells and endometrial tissues with an FP receptor antagonist (AL8810) and inhibitor of ERK (PD98059). Furthermore, we have shown that FGF2 can promote the expression of FGF2 and cyclooxygenase-2, and enhance proliferation of endometrial adenocarcinoma cells via the FGFR1 and ERK pathways, thereby establishing a positive feedback loop to regulate neoplastic epithelial cell function in endometrial adenocarcinomas.
Force controlled and teleoperated endoscopic grasper for minimally invasive surgery-experimental performance evaluation (1999)

Minimally invasive surgery generates new user interfaces which create visual and haptic distortion when compared to traditional surgery. In order to regain the tactile and kinesthetic information that is lost, a computerized force feedback endoscopic surgical grasper (FREG) was developed with computer control and a haptic user interface. The system uses standard unmodified grasper shafts and tips. The FREG can control grasping forces either by surgeon teleoperation control, or under software control. The FREG performance was evaluated using an automated palpation function (programmed series of compressions) in which the grasper measures mechanical properties of the grasped materials. The material parameters obtained from measurements showed the ability of the FREG to discriminate between different types of normal soft tissues (small bowel, lung, spleen, liver, colon, and stomach) and different kinds of artificial soft tissue replication materials (latex/silicone) for simulation purposes. In addition, subjective tests of ranking stiffness of silicone materials using the FREG teleoperation mode showed significant improvement in the performance compared to the standard endoscopic grasper. Moreover, the FREG performance was closer to the performance of the human hand than the standard endoscopic grasper. The FREG as a tool incorporating the force feedback teleoperation technology may provide the basis for application in telesurgery, clinical endoscopic surgery, surgical training, and research.
Synthesis, Characterization, and Preliminary in Vivo Tests of New Poly(ethylene glycol) Conjugates of the Antitumor Agent 10-Amino-7-ethylcamptothecin (2004)

Despite the high antitumor activity of camptothecins, few derivatives have been developed and tested for human treatment of solid tumors, due to unpredictable toxicity mainly connected to their poor water solubility. We report the conjugation of the antitumor agent 10-amino-7-hydroxy camptothecin (SN-392) to linear or branched poly(ethylene glycol)s (PEGs) of different loading capacity through a tri- or tetrapeptide spacer selectively cleaved by lysosomal enzymes (cathepsins). A synthetic strategy based on the chemoselective acylation of the aromatic amino group in the presence of the unprotected C20 tertiary alcohol allowed high overall yields. Two conjugates demonstrated good stability at physiological pH and in mouse plasma (nonspecific proteases) but slowly released the drug payload in the presence of the lysosomal enzyme cathepsin B1. Compound 3, selected for in vivo experiments, was very active against P388, P388/ADM leukaemia, and Meth A fibrosarcoma cell lines, scoring T/C% values comparable with the camptothecin derivative CPT-11. Pharmacokinetic studies indicated that 3 acts as a reservoir of 10-amino-7-ethylcamptothecin, as the mean residence time (MRT) is about 3-fold higher than that of the free drug.
Demethylation-Induced Developmental Pleiotropy in Arabidopsis (1996)

The function of DNA methylation in higher plants was investigated by expression of a complementary DNA encoding a cytosine methyltransferase (MET1) from Arabidopsis thaliana as an antisense RNA in transgenic plants. This expression resulted in a 34 to 71 percent reduction in total genomic cytosine methylation. Loss of methylation was observed in both repetitive DNA and single-copy gene sequences. Developmental effects included altered heterochrony, changes in meristem identity and organ number, and female sterility. Cytosine demethylation prolonged both vegetative and reproductive phases of development. These findings implicate DNA methylation in establishing or maintaining epigenetic developmental states in the meristem.
Facile Synthesis of Ultrathin and Single‐Crystalline Au Nanowires (2009)

Au nanowires have attracted significant interest in nanomaterials research owing to their chemical stability and high conductivity for potential nanoelectronic applications. However, previous syntheses yielded only polycrystalline Au nanowires with diameters larger than 10 nm. Very recent advances in solution-phase synthesis have led to the formation of ultrathin single-crystalline Au nanowires with diameters of less than 10 nm. This Focus Review summarizes the synthesis, characterization, and transport studies of these ultrathin single-crystalline Au nanowires for potential electronic device applications.
Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR (2018)

Daratumumab, a CD38 human monoclonal antibody, demonstrated significant clinical activity in combination with bortezomib and dexamethasone <i>versus</i> bortezomib and dexamethasone alone in the primary analysis of CASTOR, a phase 3 study in relapsed and/or refractory multiple myeloma. A <i>post hoc</i> analysis based on treatment history and longer follow up is presented. After 19.4 (range: 0-27.7) months of median follow up, daratumumab plus bortezomib and dexamethasone prolonged progression-free survival (median: 16.7 <i>versus</i> 7.1 months; hazard ratio, 0.31; 95% confidence interval, 0.24-0.39; <i>P</i><0.0001) and improved the overall response rate (83.8% <i>versus</i> 63.2%; <i>P</i><0.0001) compared with bortezomib and dexamethasone alone. The progression-free survival benefit of daratumumab plus bortezomib and dexamethasone was most apparent in patients with 1 prior line of therapy (median: not reached <i>versus</i> 7.9 months; hazard ratio, 0.19; 95% con fidence interval, 0.12-0.29; <i>P</i><0.0001). Daratumumab plus bortezomib and dexamethasone was also superior to bortezomib and dexamethasone alone in subgroups based on prior treatment exposure (bortezomib, thalidomide, or lenalidomide), lenalidomide-refractory status, time since last therapy (≤12, >12, ≤6, or >6 months), or cytogenetic risk. Minimal residual disease-negative rates were >2.5-fold higher with daratumumab across subgroups. The safety profile of daratumumab plus bortezomib and dexamethasone remained consistent with longer follow up. Daratumumab plus bortezomib and dexamethasone demonstrated significant clinical activity across clinically relevant subgroups and provided the greatest benefit to patients treated at first relapse. Trial registration: <i>clinicaltrials.gov identifier: 02136134</i>.