gebhart/patrepeval huggingface dataset:
Definition of the Bacillus subtilis PurR Operator Using Genetic and Bioinformatic Tools and Expansion of the PurR Regulon with glyA , guaC , pbuG , xpt-pbuX , yqhZ-folD , and pbuO (2001)

The expression of the pur operon, which encodes enzymes of the purine biosynthetic pathway in Bacillus subtilis, is subject to control by the purR gene product (PurR) and phosphoribosylpyrophosphate. This control is also exerted on the purA and purR genes. A consensus sequence for the binding of PurR, named the PurBox, has been suggested (M. Kilstrup, S. G. Jessing, S. B. Wichmand-Jørgensen, M. Madsen, and D. Nilsson, J. Bacteriol. 180:3900-3906, 1998). To determine whether the expression of other genes might be regulated by PurR, we performed a search for PurBox sequences in the B. subtilis genome sequence and found several candidate PurBoxes. By the use of transcriptional lacZ fusions, five selected genes or operons (glyA, yumD, yebB, xpt-pbuX, and yqhZ-folD), all having a putative PurBox in their upstream regulatory regions, were found to be regulated by PurR. Using a machine-learning algorithm developed for sequence pattern finding, we found that all of the genes identified as being PurR regulated have two PurBoxes in their upstream control regions. The two boxes are divergently oriented, forming a palindromic sequence with the inverted repeats separated by 16 or 17 nucleotides. A computerized search revealed one additional PurR-regulated gene, ytiP. The significance of the tandem PurBox motifs was demonstrated in vivo by deletion analysis and site-directed mutagenesis of the two PurBox sequences located upstream of glyA. All six genes or operons encode enzymes or transporters playing a role in purine nucleotide metabolism. Functional analysis showed that yebB encodes the previously characterized hypoxanthine-guanine permease PbuG and that ytiP encodes another guanine-hypoxanthine permease and is now named pbuO. yumD encodes a GMP reductase and is now named guaC.
Influenza Vaccines for the Future (2010)

New technologies can revolutionize influenza vaccine design, production, and delivery. In the near future, advances should reduce vaccine production time, provide enhanced protection, and end mismatches between vaccine strains and circulating viruses.
Transcriptional induction of two genes in human cells by beta interferon. (1984)

The binding of interferons to distinct cell surface receptors leads to the induction of synthesis of several unique polypeptides and their corresponding mRNAs (1-6). We have isolated two cDNAs that are complementary to nuclear RNA whose synthesis is induced from undetectable levels to maximal rates of transcription within 30-60 min after the addition of beta interferon to human fibroblasts or to HeLa cells. These results prove that a single polypeptide can, by binding to a specific plasma membrane receptor, promptly activate the transcription of a defined set of genes.
Development of retrovirus vectors useful for expressing genes in cultured murine embryonal cells and hematopoietic cells in vivo (1988)

A series of retrovirus vectors were constructed in which cellular promoter elements derived from the chicken beta-actin and human histone H4 genes were introduced within the proviral transcriptional unit of Moloney murine leukemia virus in order to promote expression of inserted sequences. Each of these vectors gave rise to high titer of virus capable of transferring the expected proviral structure to cells. Inclusion of normal 5' splice sequences or a portion of viral gag sequences in these constructions resulted in significant increases in virus titer. Each construction was transcriptionally active in NIH 3T3 cells and in undifferentiated F9 cells. One of the vectors, HSG-neo, which contained the human histone H4 promoter, was shown to be transcriptionally active in hematopoietic cells derived from long-term reconstituted bone marrow transplant recipients engrafted with transduced stem cells. These vectors should be of general use for obtaining efficient gene expression in embryonal and hematopoietic cells.
Purinergic control of red blood cell metabolism: novel strategies to improve red cell storage quality. (2017)

Transfusion of stored blood is regarded as one of the great advances in modern medicine. However, during storage in the blood bank, red blood cells (RBCs) undergo a series of biochemical and biomechanical changes that affect cell morphology and physiology and potentially impair transfusion safety and efficacy. Despite reassuring evidence from clinical trials, it is universally accepted that the storage lesion(s) results in the altered physiology of long-stored RBCs and helps explain the rapid clearance of up to one-fourth of long-stored RBCs from the recipient's bloodstream at 24 hours after administration. These considerations explain the importance of understanding and mitigating the storage lesion. With the emergence of new technologies that have enabled large-scale and in-depth screening of the RBC metabolome and proteome, recent studies have provided novel insights into the molecule-level metabolic changes underpinning the accumulation of storage lesions to RBCs in the blood bank and alternative storage strategies to mitigate such lesion(s). These approaches borrow from recent insights on the biochemistry of RBC adaptation to high altitude hypoxia. We recently conducted investigations in genetically modified mice and revealed novel insights into the role of adenosine signalling in response to hypoxia as a previously unrecognised cascade regulating RBC glucose metabolism and increasing O<sub>2</sub> release, while decreasing inflammation and tissue injuries in animal models. Here, we will discuss the molecular mechanisms underlying the role of purinergic molecules, including adenosine and adenosine triphosphate in manipulating RBCs and blood vessels in response to hypoxia. We will also speculate about new therapeutic possibilities to improve the quality of stored RBCs and the prognosis after transfusion.
Serotonin receptor affinity of cathinone and related analogs (1982)

A series of cathinone (alpha-aminopropiophenone) analogues was examined using the isolated rat fundus preparation. (S)-(-)-Cathinone possesses twice the serotonin receptor affinity of (+/-)-cathinone and four times the affinity of racemic amphetamine. Several derivatives of cathinone were found to either possess a lower affinity than the parent compound or did not interact with the receptors in a competitive manner. Several novel analogues, 1-(aminomethyl)-3,4-dihydronaphthalene hydrochloride (3), 4-(aminomethyl)-3-chromene hydrochloride (4b), as well as its 6-methoxy derivative, a, interact with serotonin receptors but in a fashion which is, most likely, dissimilar to the interaction of the substituted cathinone analogues.
Enhanced Thermal Stability of Al-Pillared Smectites Modified with Ce and La (2000)

Abstract A commercial bentonite (primarily smectite) from Fischer Scientific Company (F bentonite) and a natural bentonite from Peru (P bentonite) were used in the preparation of pillared clays with polyoxymetal cations of Al that were subsequently modified with Ce and La. Several Al/metal ratios (5 and 9) were used to investigate the effects on the thermal and hydrothermal stability of these synthetic clays. The structure of these materials was studied by X-ray diffraction. Isotherms were determined by N 2 adsorption. Thermal stability was determined using thermogravimetric (TG) measurements and ara-monia-TPD (temperature programmed desorption) was used to obtain acidity data. These materials exhibited basal spacings from 16 to 20 Å, with surface areas from 239 to 347 m 2 g −1 , with microporosity contributing from 50 to 80% of the total surface area. Pillared clays prepared from F bentonite generally showed larger basal spacings and surface areas than those prepared from P bentonite. Pillared clays modified with Ce or La did not show any apparent structural changes relative to the Al-pillared clays. Pillared clays modified with Ce and La had similar acid properties as Al-pillared clays. In contrast, the thermal and hydrothermal stabilities of these materials were greater than Al-pillared clays. However, Ce-pillared clay appears to be more effective than La-pillared clay in delaying the dehydroxylation of pillared clays with increasing temperature. The intercalation of Ce and La into Al-pillared clays improved the thermal stability, which may increase the utility of these materials as catalysts.
Diagnostic Value of Cytokines and Chemokines in Lyme Neuroborreliosis (2013)

The aims of the present study were to assess the concentrations of different cytokines and chemokines in blood serum and cerebrospinal fluid (CSF) samples of patients with Lyme neuroborreliosis and to identify the possible marker(s) that would enable a distinction between clinically evident and suspected Lyme neuroborreliosis, as well as between Lyme neuroborreliosis and tick-borne encephalitis (TBE). Our additional interest was to evaluate the relationship between cytokine and chemokine concentrations and Borrelia burgdorferi sensu lato isolation from CSF, as well as intrathecal synthesis of specific borrelial antibodies. We found that higher concentrations of CXCL13 and lower concentrations of interleukin 10 (IL-10) in serum were associated with higher odds for clinically evident Lyme neuroborreliosis compared to suspected Lyme neuroborreliosis, as well as to TBE. The concentrations of IL-2, IL-5, IL-6, IL-10, and CXCL13 in the CSF were higher in patients with evident Lyme neuroborreliosis than in those who were only suspected to have the disease. A comparison of CSF cytokine and chemokine levels in patients with and without intrathecal synthesis of specific borrelial antibodies revealed that CXCL13 CSF concentration is significantly associated with intrathecal synthesis of borrelial antibodies. A comparison of the cytokine and chemokine CSF concentrations in patients with clinically evident Lyme neuroborreliosis according to CSF culture results revealed that higher concentrations of gamma interferon (IFN-γ) were associated with lower odds of Borrelia isolation. Although several differences in the blood serum and CSF concentrations of various cytokines and chemokines between the groups were found, the distinctive power of the majority of these findings is low. Further research on well-defined groups of patients is needed to appraise the potential diagnostic usefulness of these concentrations.
GENETICS OF RESISTANCE TO DOWNY MILDEW IN CUCUMBERS. (1993)

A study was conducted to determine the inheritance of resistance to downy mildew caused by Pseudoperonospora cubensis in the cucumber genotypes; cv. Beit Alpha, line 1902 M and line THG-1. The common cultivated cultivar in Egypt Beit Alpha was found to be highly susceptible to downy mildew infection. Two crosses were made as follows: 1-“line 1902 M“X”Beit Alpha“ 2-”line TMG-1“ ×“Beit Alpha”. The resulting F 1 , F 2 and backcross generations of the first cross and F 1 and F 2 populations of the second cross were observed for downy mildew reactions in the field under natural infestiation conditions. Susceptibility of the F 1 populations to downy mildew was completely dominant in both crosses. Segregation ratios of the F 2 and backcrose populations of the cross “line 1902 M × Beit Alpha” indicated that two pairs of recessive genes controlled the tolerance reaction of Line 1902 to the fungus. Segregation ratio for reaction to downy mildew in the F 2 population of cross “line TMG-1 × Beit Alpha” indicated that three pairs of recessive genes were controlled the resistance reaction to the fungus. The following tentative genotypes for downy mildew reactions are proposed: Cv. Beit Alpha: Dm 1 Dm 1 Dm 2 Dm 2 Dm 3 Dm 3 (Suscceptible), Line 1902 M: dm 1 dm 1 dm 2 dm 2 Dm 3 Dm 3 (Tolerant) and Line TMG-1 dm 1 dm 1 dm 2 dm 2 dm 3 dm 3 (Resistant).
Anaplasma platys Diagnosis in Dogs: Comparison Between Morphological and Molecular Tests (2007)

Anaplasma platys is related to the appearance of inclusion bodies in blood platelets; however, this may be a nonspecific occurrence as there are nonparasitic inclusion bodies within these figured elements. Aiming to validate the morphological diagnosis for A platys, 101 dogs were selected due to the appearance of inclusion bodies, independently from suggestive parasites, which were submitted to polymerase chain reaction (PCR) carried out in 2 stages. The first stage consisted of the utilization of initialing sequences or specific primers for the detection of some species of the Anaplasmataceae family, such as: Ehrlichia canis, Ehrlichia chaffeensis, Ehrlichia muris, Ehrlichia ruminantium, Anaplasma phagocytophilum,
Suppressor of cytokine signaling 3 regulates CD8 T-cell proliferation by inhibition of interleukins 6 and 27 (2007)

Suppressor of cytokine signaling (SOCS) proteins regulate the intensity and duration of cytokine responses. SOCS3 is expressed in peripheral T cells, and recent reports have suggested that overexpression of SOCS3 modulates antigen- and/or costimulation-induced T-cell activation. To study the role of SOCS3 in the regulation of T-cell activation, we used a conditional gene-targeting strategy to generate mice that lack SOCS3 in T/natural killer T cells (Socs3(DeltaLck/DeltaLck) mice). SOCS3-deficient CD8 T cells showed greater proliferation than wild-type cells in response to T-cell receptor (TCR) ligation despite normal activation of signaling pathways downstream from TCR or CD28 receptors. Signaling in response to the gp130 cytokines interleukin (IL)-6 and IL-27 was prolonged in Socs3(DeltaLck/DeltaLck) T cells, and T cells from gp130(Y757F/Y757F) mice, in which the SOCS3-binding site on gp130 is ablated, showed a striking similarity to SOCS3-deficient CD8 T cells. Although the proliferative defect of Socs3(DeltaLck/DeltaLck) T cells was not rescued in the absence of IL-6, suppression of IL-27 signaling was found to substantially reduce anti-CD3-induced proliferation. We conclude that enhanced responses to TCR ligation by SOCS3-deficient CD8 T cells are not caused by aberrant TCR-signaling pathways but, rather, that increased IL-27 signaling drives unregulated proliferation in the absence of SOCS3.
Isolation and characterization of a mouse interleukin cDNA clone that expresses B-cell stimulatory factor 1 activities and T-cell- and mast-cell-stimulating activities. (1986)

A cDNA sequence coding for a unique mouse interleukin that expresses B-cell-, T-cell, and mast-cell-stimulating activities has been isolated from a mouse helper T-cell cDNA library. The library, constructed in the pcD expression vector, was screened by transfecting COS monkey cells with DNA pools to express the products encoded by full-length cDNA inserts. By assaying the transfected cell supernatants, we identified clones encoding a factor that stimulates T-cell and mast cell lines. This factor also induces Ia expression on resting B cells and enhances IgG1 and IgE production by B cells, two properties of B-cell-stimulatory factor 1. The DNA sequence codes for a polypeptide of 140 amino acid residues including a putative signal peptide. These results demonstrate that a single cDNA clone distinct from interleukin 2 and interleukin 3 encodes a polypeptide with multiple biological activities.
Surface-plasmon-induced enhancement of magneto-optical Kerr effect in all-nickel subwavelength nanogratings (2010)

Enhancement of transversal magneto-optical Kerr effect (TKE) is controlled experimentally in magnetoplasmonic subwavelength nanogratings made of nickel films by resonant excitation of surface plasmon-polaritons (SPPs). Almost one order of magnitude increase of the TKE value is observed in the spectral range of Wood’s anomaly corresponding to the fulfillment of the phase-matching conditions for SPP excitation.
Doubly Phosphorylated Peptide Vaccines to Protect Transgenic P301S Mice against Alzheimer’s Disease Like Tau Aggregation (2014)

Intracellular neurofibrillary tangles and extracellular senile plaques are potential targets for active and passive immunotherapies. In this study we used the transgenic mouse model P301S for active immunizations with peptide vaccines composed of a double phosphorylated tau neoepitope (pSer202/pThr205, pThr212/pSer214, pThr231/pSer235) and an immunomodulatory T cell epitope from the tetanus toxin or tuberculosis antigen Ag85B. Importantly, the designed vaccine combining Alzheimer's disease (AD) specific B cell epitopes with foreign (bacterial) T cell epitopes induced fast immune responses with high IgG₁ titers after prophylactic immunization that subsequently decreased over the observation period. The effectiveness of the immunization was surveyed by evaluating the animal behavior, as well as the pathology in the brain by biochemical and histochemical techniques. Immunized mice clearly lived longer with reduced paralysis than placebo-treated mice. Additionally, they performed significantly better in rotarod and beam walk tests at the age of 20 weeks, indicating that the disease development was slowed down. Forty-eight weeks old vaccinated mice passed the beam walk test significantly better than control animals, which together with the increased survival rates undoubtedly prove the treatment effect. In conclusion, the data provide strong evidence that active immune therapies can reduce toxic effects of deposits formed in AD.
First Example of Phosphoramidate Approach Applied to a 4‘-Substituted Purine Nucleoside (4‘-Azidoadenosine):  Conversion of an Inactive Nucleoside to a Submicromolar Compound versus Hepatitis C Virus (2007)

We report on the synthesis of the anti hepatitis C virus (HCV) agent 4'-azidoadenosine (1) and the application of the phosphoramidate ProTide technology to this nucleoside. The synthesis of 1 was achieved through an epoxide intermediate followed by regio- and stereoselective ring opening by azidotrimethylsilane in the presence of a Lewis acid. Compound 1 did not inhibit HCV replication in cell culture at concentrations up to 0.1 mM. However, a submicromolar active agent could be derived from 1 by the application of the ProTide technology. All the phosphoramidates prepared were L-alanine derivatives with variations in the aryl moiety and in the ester part of the amino acid. The benzyl ester and the l-naphthyl phosphate (18) had the best activity in replicon assay. Phosphoramidates (18-21) achieved a significant improvement in antiviral potency over the parent nucleoside (1) with no increase in cytotoxicity.
Precise control of the blue-shift of the wavelength in InGaAs-InGaAsP multiple quantum wells using a sputtered SiO/sub 2/ technique (2003)

Use of the sputtered SiO/sub 2/ technique for quantum well intermixing, a post-growth technique which modifies the quantum well profile, to introduce a blue-shift of the optical absorption edge, makes it possible to integrate the passive and active components monolithically and therefore allow extensive photonic integration which is cost effective and flexible. Although the different bandgaps can be implemented by several sputter-annealing cycles, it is tedious and less reliable. In this paper, we report a new technique to achieve the different bandgaps in a single stage sputtering-annealing step. The technique is simple, reliable, and more importantly, the tuning of the wavelength is precise.
In situ localization of the per clock protein during development of Drosophila melanogaster. (1988)

The per locus influences biological rhythms in Drosophila melanogaster. In this study, per transcripts and proteins were localized in situ in pupae and adults. Earlier genetic studies have demonstrated that per expression is required in the brain for circadian locomotor activity rhythms and in the thorax for ultradian rhythmicity of the Drosophila courtship song. per RNA and proteins were detected in a restricted group of cells in the eyes and optic lobes of the adult brain and in many cell bodies in the adult and pupal thoracic ganglia. per products were also found in the pupal ring gland complex, a tissue involved in rhythmic aspects of Drosophila development. Abundant expression was seen in gonadal tissue. No biological clock phenotypes have been reported for this tissue in any of the per mutants, per protein mapped to different subcellular locations in different tissues. The protein accumulated in or around nuclei in some cells and appeared to be cytoplasmic in others.
P2X7 Receptor-Dependent Blebbing and the Activation of Rho-Effector Kinases, Caspases, and IL-1β Release (2003)

In response to ATP binding, the P2X7R facilitates cation channel activation, nonspecific pore formation, rapid changes in plasma membrane morphology, and secretion of IL-1 beta from LPS-primed macrophages. To investigate the relationship between the P2X7R-dependent changes in plasma membrane organization and the release of IL-1 beta, we generated time-lapse movies of ATP-stimulated BAC1 murine macrophages in conjunction with biochemical analyses of IL-1 beta release. Similar image analyses in human embryonic kidney 293 cells expressing recombinant P2X7R (HEK-P2X7) permitted comparison of P2X7R-dependent effects in macrophage vs nonmacrophage backgrounds. Whereas HEK-P2X7 cells exhibit zeiotic blebbing within 5 min of ATP treatment, BAC1 macrophages initiated a distinct "tethered" blebbing 10 min after ATP addition. This blebbing was comparably induced by the P2X7R-selective agonist BzATP and was blocked by P2X7R inhibitors KN-62 and oxidized ATP. Blebbing was initiated at ATP concentrations > or = 3 mM, but optimal IL-1 beta release occurred at 1 mM ATP. P2X7R-dependent blebbing was abrogated in the presence of Rho-effector kinase inhibitors Fasudil and Y-27632, but ATP-induced IL-1 beta release was unaffected. ATP-induced activation of RhoA could be detected in both HEK-P2X7 cells and BAC1 murine macrophages. Thus, P2X7R activation signals distinct, novel membrane blebbing events (dependent on RhoA activation and Rho-effector kinase activity) and simultaneously initiates release of IL-1 beta. Our observations that blebbing and IL-1 beta release are dissociable suggest these events occur via parallel rather than convergent signaling pathways.
A novel methodology for assignment of disulfide bond pairings in proteins (1997)

A novel methodology is described for the assignment of disulfide bonds in proteins of known sequence. The denatured protein is subjected to limited reduction by tris(2-carboxyethyl)phosphine (TCEP) in pH 3.0 citrate buffer to produce a mixture of partially reduced protein isomers; the nascent sulfhydryls are immediately cyanylated by 1-cyano-4-dimethylamino-pyridinium tetrafluoroborate (CDAP) under the same buffered conditions. The cyanylated protein isomers, separated by and collected from reversed-phase HPLC, are subjected to cleavage of the peptide bonds on the N-terminal side of cyanylated cysteines in aqueous ammonia to form truncated peptides that are still linked by residual disulfide bonds. The remaining disulfide bonds are then completely reduced to give a mixture of peptides that can be mass mapped by MALDI-MS. The masses of the resulting peptide fragments are related to the location of the paired cysteines that had undergone reduction, cyanylation, and cleavage. A side reaction, beta-elimination, often accompanies cleavage and produces overlapped peptides that provide complementary confirmation for the assignment. This strategy minimizes disulfide bond scrambling and is simple, fast, and sensitive. The feasibility of the new approach is demonstrated in the analysis of model proteins that contain various disulfide bond linkages, including adjacent cysteines. Experimental conditions are optimized for protein partial reduction, sulfhydryl cyanylation, and chemical cleavage reactions.