gebhart/patrepeval huggingface dataset:
Noninvasive Bioluminescence Imaging of Herpes Simplex Virus Type 1 Infection and Therapy in Living Mice (2002)

Mouse models of herpes simplex virus type 1 (HSV-1) infection provide significant insights into viral and host genes that regulate disease pathogenesis, but conventional methods to determine the full extent of viral spread and replication typically require the sacrifice of infected animals. To develop a noninvasive method for detecting HSV-1 in living mice, we used a strain KOS HSV-1 recombinant that expresses firefly (Photinus pyralis) and Renilla (Renilla reniformis) luciferase reporter proteins and monitored infection with a cooled charge-coupled device camera. Viral infection in mouse footpads, peritoneal cavity, brain, and eyes could be detected by bioluminescence imaging of firefly luciferase. The activity of Renilla luciferase could be imaged after direct administration of substrate to infected eyes but not following the systemic delivery of substrate. The magnitude of bioluminescence from firefly luciferase measured in vivo correlated directly with input titers of recombinant virus used for infection. Treatment of infected mice with valacyclovir, a potent inhibitor of HSV-1 replication, produced dose-dependent decreases in firefly luciferase activity that correlated with changes in viral titers. These data demonstrate that bioluminescence imaging can be used for noninvasive, real-time monitoring of HSV-1 infection and therapy in living mice.
Antisense oligonucleotides and spinal muscular atrophy: skipping along: Figure 1. (2010)

Antisense oligonucleotides (ASOs) can be used to alter the splicing of a gene and either restore production of a required protein or eliminate a toxic product. In this issue of Genes & Development, Hua and colleagues (pp. 1634-1644) show that ASOs directed against an intron splice silencer (ISS) in the survival motor neuron 2 (SMN2) gene alter the amount of full-length SMN transcript in the nervous system, restoring SMN to levels that could correct spinal muscular atrophy (SMA).
The effect of specific growth rate on protein synthesis and secretion in the filamentous fungus Trichoderma reesei (2005)

Trichoderma reesei was cultivated in chemostat cultures on lactose-containing medium. The cultures were characterized for growth, consumption of the carbon source and protein production. Secreted proteins were produced most efficiently at low specific growth rates, 0.022-0.033 h(-1), the highest specific rate of total protein production being 4.1 mg g(-1) h(-1) at the specific growth rate 0.031 h(-1). At low specific growth rates, up to 29 % of the proteins produced were extracellular, in comparison to only 6-8 % at high specific growth rates, 0.045-0.066 h(-1). To analyse protein synthesis and secretion in more detail, metabolic labelling of proteins was applied to analyse production of the major secreted protein, cellobiohydrolase I (CBHI, Cel7A). Intracellular and extracellular labelled CBHI was quantified and analysed for pI isoforms in two-dimensional gels, and the synthesis and secretion rates of the molecule were determined. Both the specific rates of CBHI synthesis and secretion were highest at low specific growth rates, the optimum being at 0.031 h(-1). However, at low specific growth rates the secretion rate/synthesis rate ratio was significantly lower than that at high specific growth rates, indicating that at low growth rates the capacity of cells to transport the protein becomes limiting. In accordance with the high level of protein production and limitation in the secretory capacity, the transcript levels of the unfolded protein response (UPR) target genes pdi1 and bip1 as well as the gene encoding the UPR transcription factor hac1 were induced.
Computerized decision support systems: an overview (1998)

Computerized clinical decision support systems (CDSS) are an area of technology that attract much interest. In the past, the prohibitive cost of the high performance systems needed to run such systems effectively confined their use to large research and teaching units. The decreasing price and increasing power of personal computers is making their widespread use more possible. CDSS are divided into active and passive systems. Passive systems make information available should the clinician specifically request it, whereas active systems process information and interact with clinical data. Active CDSS may use rules based upon simple logic or systems based upon probability. A variety of active CDSS systems have been shown to have a positive effect on patient outcome. Such an effect has yet to be clearly demonstrated for passive CDSS. CDSS should be carefully designed, so that they are accurate, safe, useful and accessible to the clinician. In this way, their utility can be maximized. Medical knowledge is expanding rapidly, and it is unlikely that the clinician of the future will know even a small proportion of it. It is thus important that information is available in a digestible form and in close proximity to the clinical context. CDSS are likely to be one of the major ways to deliver such data.
Human Plasmacytoid Dendritic Cells Activated by CpG Oligodeoxynucleotides Induce the Generation of CD4+CD25+ Regulatory T Cells (2004)

Plasmacytoid dendritic cells (PDCs) are key effectors in host innate immunity and orchestrate adaptive immune responses. CpG oligodeoxynucleotides (ODN) have potent immunostimulatory effects on PDCs through TLR9 recognition and signaling. Little is known about the effects of CpG ODN on human PDC-mediated T cell priming. Here we show that type B CpG ODN effectively promotes PDCs to prime allogeneic naive CD4(+)CD25(-) T cells to differentiate into CD4(+)CD25(+) regulatory T (Treg) cells. The CD4(+)CD25(+) T cells induced by CpG ODN-activated PDCs express forkhead transcription factor 3 and produce IL-10, TGF-beta, IFN-gamma, and IL-6, but low IL-2 and IL-4. These CD4(+)CD25(+) T cells are hyporesponsive to secondary alloantigen stimulation and strongly inhibit proliferation of autologous or allogeneic naive CD4(+) T cells in an Ag-nonspecific manner. CpG ODN-activated PDCs require direct contact with T cells to induce CD4(+)CD25(+) Treg cells. Interestingly, IL-10 and TGF-beta were undetectable in the supernatants of CpG ODN-stimulated PDC cultures. Both CpG-A and CpG-C ODN-activated PDCs similarly induced the generation of CD4(+)CD25(+) Treg cells with strong immune suppressive function. This study demonstrates that TLR9 stimulation can promote PDC-mediated generation of CD4(+)CD25(+) Treg cells and suggests PDCs may play an important role in the maintenance of immunological tolerance.
Alignment-insensitive technique for wideband tuning of an unmodified semiconductor laser (1988)

Using simple optical components and an unmodified commercial semiconductor laser, a frequency-selective self-aligning optical-feedback technique has been devised that allows a semiconductor laser to be tuned to and scanned about any optical frequency within the laser gain curve. This technique employs a graded-index rod lens cat's eye and an intracavity étalon.
Determinants of the Host Range Restriction of Replication of Bovine Parainfluenza Virus Type 3 in Rhesus Monkeys Are Polygenic (2002)

The Kansas strain of bovine parainfluenza virus type 3 (BPIV3) is 100- to 1,000-fold restricted in replication in the respiratory tracts of nonhuman primates compared to human PIV3 (HPIV3), an important pathogen of infants and young children. BPIV3 is also restricted in replication in human infants and children, yet it is immunogenic and is currently being evaluated in clinical trials as a vaccine candidate to protect against illness caused by HPIV3. We have examined the genetic basis for the host range attenuation phenotype of BPIV3 by exchanging each open reading frame (ORF) of a recombinant wild-type HPIV3 with the analogous ORF from BPIV3, with the caveats that the multiple ORFs of the P gene were exchanged as a single unit and that the HN and F genes were exchanged as a single unit. Recombinant chimeric bovine-human PIV3s were recovered from cDNA, and the levels of viral replication in vitro and in the respiratory tract of rhesus monkeys were determined. Recombinant chimeric HPIV3s bearing the BPIV3 N or P ORF were highly attenuated in the upper and lower respiratory tracts of monkeys, whereas those bearing the BPIV3 M or L ORF or the F and HN genes were only moderately attenuated. This indicates that the genetic determinants of the host range restriction of replication of BPIV3 for primates are polygenic, with the major determinants being the N and P ORFs. Monkeys immunized with these bovine-human chimeric viruses, including the more highly attenuated ones, developed higher levels of HPIV3 hemagglutination-inhibiting serum antibodies than did monkeys immunized with BPIV3 and were protected from challenge with wild-type HPIV3. Furthermore, host range determinants could be combined with attenuating point mutations to achieve an increased level of attenuation. Thus, chimeric recombinant bovine-human PIV3 viruses that manifest different levels of attenuation in rhesus monkeys are available for evaluation as vaccine candidates to protect infants from the severe lower respiratory tract disease caused by HPIV3.
InfraStructs (2013)

We introduce InfraStructs , material-based tags that embed information inside digitally fabricated objects for imaging in the Terahertz region. Terahertz imaging can safely penetrate many common materials, opening up new possibilities for encoding hidden information as part of the fabrication process. We outline the design, fabrication, imaging, and data processing steps to fabricate information inside physical objects. Prototype tag designs are presented for location encoding, pose estimation, object identification, data storage, and authentication. We provide detailed analysis of the constraints and performance considerations for designing InfraStruct tags. Future application scenarios range from production line inventory, to customized game accessories, to mobile robotics.
Characterization of the effectiveness of hexose transporters for transporting xylose during glucose and xylose co‐fermentation by a recombinant Saccharomyces yeast (2004)

We have developed recombinant Saccharomyces yeasts that can effectively co-ferment glucose and xylose to ethanol. However, these yeasts still ferment glucose more efficiently than xylose. The transport of xylose could be one of the steps limiting the fermentation of xylose. In this study, we characterized the changes in the expression pattern of the hexose transporter and related genes during co-fermentation of glucose and xylose using one of our recombinant yeasts, Saccharomyces cerevisiae 424A(LNH-ST). The transcription of the hexose transporter and related genes was strongly influenced by the presence of glucose; HXT1, HXT2 and HXT3 were greatly activated by glucose and HXT5, HXT7 and AGT1 were significantly repressed by glucose. We also examined the effectiveness of individual transporters encoded by HXT1, HXT2, HXT4, HXT5, HXT7 and GAL2 genes for transporting xylose during co-fermentation of glucose and xylose in a Saccharomyces hxt degrees mutant (RE700A). We compared these hxt degrees derivatives to RE700A wild-type strain (S. cerevisiae MC996A) where all of them contained the same xylose metabolizing genes present in our xylose-fermenting yeasts such as 424A(LNH-ST). Our results showed that recombinant RE700A containing the cloned HXT7 or HXT5 were substantially more effective for fermenting xylose to ethanol. In addition, we found that the efficiency of transporters for intracellular accumulation of xylose was as follows: HXT7 > HXT5 > GAL2 > WT > HXT1 > HXT4 > > > RE700A. Furthermore, we provided evidence that the Saccharomyces galactose transporter system could be a highly effective xylose transporter. The information reported here should be of great importance for improving the Saccharomyces yeast transport of xylose.
Topical Nepafenac Inhibits Ocular Neovascularization (2003)

Topical nepafenac inhibits CNV and ischemia-induced retinal neovascularization by decreasing production of VEGF. The absence of effect in rho/VEGF transgenic mice is consistent with this mechanism. Topical nepafenac may provide an effective new treatment for ocular neovascularization. The excellent corneal penetration of nepafenac certainly plays an important role in this effect. It is possible that other antiangiogenic agents are also amenable to topical application after formulations are identified that maximize their corneal penetration. Because of the many advantages of the topical route of delivery, this is a possible topic for exploration.
Laboratory Medicine: The Selection and Interpretation of Clinical Laboratory Studies (1994)

Part 1 Analytic principles of laboratory medicine: laboratory-based medical practice technical evaluation of laboratory studies diagnostic classification evaluation of the medical utility of classification studies. Part 2 Physiologic principles of laboratory medicine: assessment of organ function immunity and immunologic assays markers of tissue injury monitoring therapeutic drug monitoring assessment of nutritional status neoplasia geriatrics. Part 3 The clinical laboratory medical practice: haematopoietic system haemostatic system immunodeficiency connective tissue diseases heart lungs liver and biliary tract exocrine pancreas and alimentary tract kidneys and urinary tract nervous system dsylipidemias hyperuricemia and gout hereditary haemochromatosis porphyria alcohol drugs of abuse poisons anterior pituitary.
Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease (2016)

Human noroviruses are the primary causative agents of acute gastroenteritis and a pressing public health burden worldwide. There are currently no vaccines or small molecule therapeutics available for the treatment or prophylaxis of norovirus infections. Norovirus 3CL protease plays a vital role in viral replication by generating structural and nonstructural proteins via the cleavage of the viral polyprotein. Thus, molecules that inhibit the viral protease may have potential therapeutic value. We describe herein the structure-based design, synthesis, and in vitro and cell-based evaluation of the first class of oxadiazole-based, permeable macrocyclic inhibitors of norovirus 3CL protease.
Enhanced contact hypersensitivity and antiviral immune responses in vivo by keratinocyte‐targeted overexpression of IL‐15 (2004)

IL-15 is involved in lymphocyte homeostasis. To investigate the role of IL-15 in the skin in vivo, mice were generated that overexpress IL-15 in keratinocytes, resulting in increased IL-15 protein levels in the skin but not elevated IL-15 serum concentrations. Keratin 14 (K14)-IL-15 transgenic (tg) mice showed increased contact hypersensitivity (CHS) responses. Transfer of primed wild-type (wt) and tg T cells into naive wt or tg recipients indicated that skin-derived IL-15 enhanced the induction but not the elicitation phase of CHS. Tg mice could be sensitized even by suboptimal hapten concentrations. Accordingly, Langerhans cells (LC) from tg skin were identified as potent allostimulators, suggesting the involvement of IL-15-stimulated LC in the induction of adaptive immunity. Overexpression of IL-15 also strengthened innate immunity since tg mice infected with human HSV type I developed significantly smaller HSV skin lesions. In addition, tg mice resisted re-infection with HSV more effectively than wt mice did, which was associated with an elevated anti-HSV Ab production. Accordingly, injection of serum from re-infected tg mice protected naive recipients significantly from epicutaneous HSV infection, indicating that anti-HSV Ab produced by tg mice play an important role in resistance in vivo. Together, our results show that overexpression of IL-15 in the epidermis enhances both innate and adaptive cutaneous immunity.
CTLA4Ig inhibits alloantibody responses to repeated blood transfusions. (1996)

Allosensitization is a fundamental problem that limits the effectiveness of blood transfusions. Patients who receive multiple transfusions of blood or blood components frequently develop alloantibodies against donor alloantigens. Allosensitized patients are refractory to further transfusion and difficult to transplant successfully. CTLA4Ig fusion protein, which blocks the CD28-B7 costimulatory pathway in T-lymphocyte activation, was tested for its capacity to inhibit allosensitization to blood transfusions. Groups of LEW (RT1') rats were transfused with ACI blood (RT1a) together with L6 (a human immunoglobulin G1 [IgG1] antibody as isotype control) or CTLA4Ig in different doses (0.004, 0.02, 0.1, and 0.5 mg). Rats were retransfused with ACI blood after 28 and 84 days without any additional CTLA4Ig therapy. Weekly sera samples were tested for alloantibody against donor leukocytes using flow cytometry. CTLA4Ig caused a dose-dependent decrease in the IgM alloantibody response against donor major histocompatibility complex (MHC) class I antigens. In addition, 0.02-, 0.1-, and 0.50-mg doses of CTLA4Ig totally inhibited the IgG responses to the first transfusion, and this immunosuppressive effect persisted for the second and third transfusions. To study the capacity of CTLA4Ig to prevent a secondary immune response, three groups of LEW rats were transfused with ACI blood with no accompanying treatment. Animals were retransfused 28 days later with ACI blood together with L6 control antibody or 0.5 or 2.5 mg CTLA4Ig. CTLA4Ig, but not L6, prevented an increase in IgG alloantibody response despite repeated transfusions. The effects of CTLA4Ig treatment on helper T-lymphocyte proliferation was tested by limiting dilution analysis (LDA). Peripheral blood cells taken 30 days after blood transfusion and CTLA4Ig treatment contained significantly decreased donor-specific T-lymphocyte precursors compared with L6-treated rats. These data support the idea that blocking the B7/CD28 signal of T-lymphocyte activation by CTLA4Ig treatment at the time of transfusion may be an important therapeutic tool to inhibit alloantibody responses to blood transfusions.
Forensic video reconstruction (2004)

This paper describes an application that enables quick reconstruction of interconnected events, sparsely captured by one or more surveillance cameras. Unlike related efforts, our approach does not require indexing, advance knowledge of potential search criteria, nor a solution to the generalized object-recognition problem. Instead, we strategically pair the intelligence and skill of a human investigator with the speed and flexibility of a parallel image search engine that exploits local storage and processing capabilities distributed across large collections of video recording devices. The result is a system for fast, interactive, brute-force video searching which is both effective and highly scalable.
MHC heterozygosity confers a selective advantage against multiple-strain infections (2002)

Genetic heterozygosity is thought to enhance resistance of hosts to infectious diseases, but few tests of this idea exist. In particular, heterozygosity at the MHC, the highly polymorphic loci that control immunological recognition of pathogens, is suspected to confer a selective advantage by enhancing resistance to infectious diseases (the "heterozygote advantage" hypothesis). To test this hypothesis, we released mice into large population enclosures and challenged them with multiple strains of Salmonella and one of Listeria. We found that during Salmonella infections with three avirulent strains, MHC heterozygotes had greater survival and weight than homozygotes (unlike sham controls), and they were more likely to clear chronic Salmonella infection than homozygotes. In laboratory experiments, we found that MHC heterozygosity enhanced the clearance of multiple-strain Salmonella infections. Yet, contrary to what is widely assumed, the benefits of heterozygosity were due to resistance being dominant rather than overdominant, i.e., heterozygotes were more resistant than the average of parental homozygotes, but they were not more resistant than both. The fact that MHC heterozygotes were more resistant to infection and had higher fitness than homozygotes provides a functional explanation for MHC-disassortative mating preferences.
Role of cytokines in the gene expression of amyloid β–protein precursor: Identification of a 5'-UTR-Binding nuclear factor and its implications in Alzheimer's disease (2003)

One of the major neuropathological characteristics of Alzheimer's disease (AD) is the brain depositions of senile plaques that are mainly composed of toxic amyloid beta-peptide (Abeta), which is generated from a family of Abeta containing precursor proteins (AbetaPP; 695-770 amino acids). The role of cytokines and growth factors has been implicated in the pathogenesis of AD. Our goal is to determine the mode of action of cytokines on the regulation of betaPP gene expression. Here we studied the effect of different cytokines on the activity of 5'-untranslated region (5'-UTR) of betaPP mRNA in human astrocytic cells (U-373). We compared betaPP-5'-UTR activity in the presence of interleukin-1 (IL-1alpha and IL-1beta), transforming growth factor (TGF-beta1) and tumor necrosis factor TNF-alpha1. The astrocytic cells, which were treated separately with these agents, were transfected with either the vector (pSV2CAT) or pSV2UTR-CAT construct containing 90 bp of AbetaPP 5'-UTR +54 to 144 bp). This region was cloned upstream of a reporter chloramphenicol acetyl transferase gene (CAT). Our results indicate that the treatment of pSV2UTR-CAT-transfected cells with either IL-1alpha, IL-1beta, TGF-beta1 or TNF-alpha1 stimulated reporter gene activity in a factor-specific manner. This was consistent with their effects on elevating AbetaPP protein levels. Transfection of the same cells with the pSV2CAT vector lacking 5'-UTR resulted in a reduced reporter gene activity with all treatments studied. DNA-gel shift experiments indicate that the 54/144 region binds to a nuclear protein(s) in a cell type specific manner. These results suggest that 5'-UTR of the AbetaPP gene can respond to the stimulation of different cytokines, which likely regulate AbetaPP transcription and translation via regulatory elements present in the AbetaPP promoter and in 5'-UTR, respectively. The characterization of AbetaPP regulatory elements, including the 5'-UTR, will accelerate the development of novel agents against new targets for AD.
ChemInform Abstract: Synthesis and Aromatase‐Inhibitory Activity of Imidazolyl‐1,3,5‐ triazine Derivatives. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.