gebhart/patrepeval huggingface dataset:
Modulation of innate immunity by copolymer‐1 leads to neuroprotection in murine HIV‐1 encephalitis (2007)

Virus-infected and immune-competent mononuclear phagocytes (MP; perivascular macrophages and microglia) drive the neuropathogenesis of human immunodeficiency virus type 1 (HIV-1) infection. Modulation of the MP phenotype from neurodestructive to neuroprotective underlies adjunctive therapeutic strategies for human disease. We reasoned that, as Copolymer-1 (Cop-1) can induce neuroprotective activities in a number of neuroinflammatory and neurodegenerative disorders, it could directly modulate HIV-1-infected MP neurotoxic activities. We now demonstrate that, in laboratory assays, Cop-1-stimulated virus-infected human monocyte-derived macrophages (MDM) protect against neuronal injury. Severe combined immune-deficient (SCID) mice were stereotactically injected with HIV-1-infected human MDM, into the basal ganglia, to induce HIV-1 encephalitis (HIVE). Cop-1 was administered subcutaneously for 7 days. In HIVE mice, Cop-1 treatment led to anti-inflammatory and neuroprotective responses. Reduced micro- and astrogliosis, and conserved NeuN/MAP-2 levels were observed in virus-affected brain regions in Cop-1-treated mice. These were linked to interleukin-10 and brain-derived neurotrophic factor expression and downregulation of inducible nitric oxide synthase. The data, taken together, demonstrate that Cop-1 can modulate innate immunity and, as such, improve disease outcomes in an animal model of HIVE.
Fluorescence Lifetime of Organic Thin Films Alternately Deposited with Diamine Derivative and Aluminum Quinoline (1997)

Fluorescence lifetimes of organic thin films alternately deposited with diamine derivative (TPD) and aluminium quinoline (Alq3) were measured. The alternating deposition structure was shown to enhance the emission from Alq3 in spite of imperfect film structures. Energy transfer from TPD to Alq3 was evidenced by the correlation between lifetime and period number. It was found to be a competitive process with the TPD radiation process, and its rate of TPD radiation was estimated to be 1.2×10 10 s -1 . The authors suggested that the presence of the region mixed with TPD and Alq3 at the TPD/Alq3 interface plays an important role in the electroluminescence (EL) process. The Alq3 exciton confinement was clarified experimentally since the component of the faster fluorescence lifetime of Alq3 increased in the short-wavelength region. In addition, the authors proposed a possible EL model based on the suppression of the thermal inactivation of Alq3 excitons during their diffusion.
New Use of a Three-Dimensional Pellet Culture System for Human Intervertebral Disc Cells (2001)

Study Design. Human intervertebral disc cells were cultured in a new three-dimensional “pellet culture” system as an alternative to conventional alginate bead microspheres. Histologic, biochemical, and immunohistologic assays were performed to characterize this new culturing method for disc cells. The feasibility of using the pellet culture system to study effects of gene therapy was also assessed. Objectives. To characterize a new and simpler, three-dimensional culture system for human intervertebral disc cells and to assess the feasibility of its use for gene therapy and tissue engineering studies. Summary of Background Data. The alginate microsphere three-dimensional culture system has been the most utilized culture method for disc cells, but it is technically difficult and has some disadvantages. Recently, the “pellet culture” method, a simpler three-dimensional culture system, was described for bone marrow stromal cells. This simpler method might be useful for in vitro and in vivo studies of disc cells as well as for delivery of exogenous genes. Methods. Isolated human intervertebral disc cells were centrifuged at low speeds to form aggregates and allowed to grow as pellets for up to 3 weeks. At various times these pellet cultures were analyzed grossly, histologically, and immunohistologically. Their ability to incorporate [35S]sulfate in their response to TGF-β1 was also analyzed. The ability of these pellets to deliver and express exogenous genes in vivo was analyzed by implantation of pellet cultures in muscles of SCID mice. Results. Within several days the intervertebral disc cells were able to form mature three-dimensional aggregates that were each well encapsulated by a fibrous capsule. These pellets successfully synthesized proteoglycan and collagen Type II matrix as determined by histology and immunohistochemistry. In response to TGF-β1, the pellets increased synthesis of proteoglycan and collagen Type II. When implanted into thigh muscles of SCID mice, the pellets remained aggregated and expressed the β-galactosidase marker gene in vivo for up to 2 weeks. Conclusions. The pellet culture system is a new and technically simple method to culture human intervertebral disc cells. The majority of the human intervertebraldisc cells retained their native phenotype in this threedimensional system and expressed a marker gene both in vitro and in vivo. Thus, this pellet system might be useful for in vitro and in vivo biochemical studies as well as for studies involving gene therapy and tissue engineering.
Transgenic expression of VpreB-3 under the control of the immunoglobulin heavy chain enhancer and SV40 promoter. (1996)

Recently we isolated a novel gene, VpreB-3 gene from the cDNA library of a pre-B cell clone. This gene is selectively expressed in pre-B and bone marrow-derived B cell lines. Its products are associated with the immunoglobulin heavy (IgH) chain in pre-B cell line. In the present study, to address the role of VpreB-3 on B cell development, transgenic mice carrying the VpreB-3 gene under the control of the IgH enhancer and SV40 promoter were produced. The transgenic mice expressed the VpreB-3 gene in bone marrow and spleen at a high level compared with control mice. In the thymus, the expression of the transgene was also detected, although its level was low. Flow cytometry analysis revealed that the frequency of CD45R+ and mu+ B cells were reduced in the bone marrow of 2 of the 11 transgenic mice and also reduced in the spleen of 1 of the transgenic mice. Furthermore, the results of a stromal cell-dependent B cell culture assay suggested that early B cell development, the differentiation from CD45R- B progenitor cells to CD45R+ pro-B cells, was delayed in the bone marrow cultures of 3 of the 5 transgenic mice compared with the control mice. These results suggested that VpreB-3 products may play some role in early B cell development at the stage of CD45R- B progenitor cells before the expression of surface mu chains.
Decreased expression of a novel lncRNA CADM1-AS1 is associated with poor prognosis in patients with clear cell renal cell carcinomas. (2014)

The clear cell renal cell carcinoma (ccRCC) is the most common subtype in renal cell carcinomas. Rapidly accumulating studies show that the long non-coding RNAs (lncRNAs) may play essential roles in cancers. In this study, we investigated the expression pattern of a novel lncRNA CADM1-AS1 in ccRCC by quantitative real time PCR. The results showed that CADM1-AS1 expression was down-regulated in tumor tissues in 64 patients with ccRCC compared with adjacent non-tumor tissues. Furthermore, the expression of CADM1-AS1 was positively correlated with the expression of mRNA CADM1 in ccRCC specimens (R = 0.611, P <0.0001). Decreased CADM1-AS1 expression was correlated with the progression of AJCC stage (P = 0.039) and worse survival of ccRCC patients (P <0.05). Also, multivariate analysis identified low CADM1-AS1 expression as an independent prognostic factor for ccRCC (P <0.001, HR = 0.211, 95% CI = 0.088-0.504). In addition, we used small interfering RNA (siRNA) to evaluate the biological function of CADM1-AS1 in vitro. The results showed that CADM1-AS1 expression was positively associated with CADM1 mRNA expression in 786-O cells and ACHN cells. Functional experiments demonstrated markedly enhanced ability of growth and migration, and reduced apoptotic rate in CADM1-AS1 knocking down in 786-O cells. Conversely, overexpression of CADM1-AS1 showed a significant decrease in growth and migration, along with an increase in apoptotic rate in ACHN cells. In conclusion, our data demonstrated CADM1-AS1 is a new tumor suppressor in ccRCC which regulates cell proliferation, apoptosis and migration via the expression pattern of "CADM1-AS1/CADM1 mRNA gene pairs". CADM1-AS1 may be a potential biomarker and therapeutic target in patients with ccRCC.
Carbohydrate, protein and amino acid status of Glycine‐Glomus‐Bradyrhizobium symbioses (1989)

Soybean [ Glycine max (L.) Merr. cv. Amsoy 71] plants were inoculated with either the vesicular‐arbuscular mycorrhizal (VAM) fungus Glomus fasciculatum , with a strain of Bradyrhizobium japonicum . or with both endophytes together. Non‐inoculated plants were fertilized with levels of N and P that resulted in plant growth similar to that following infection by Bradyrhizobium or Glomus , respectively. In general, plants colonized by Glomus contained more pinitol (1 d ‐3‐O‐methyl‐ chiro ‐inositol) but less starch than corresponding P‐fertilized soybeans, while nodulated soybeans contained more pinitol and sucrose in the roots than corresponding N‐fertilized plants. Compared to nutrient‐amended soybeans, increases or decreases in free amino acids in symbiotically grown plants tended to follow transient changes in N content and endophyte activity. The exception to this was the elevated levels of methionine in nodulated roots or aspartate and arginine in Glomus ‐inoculated roots regardless of N level. There were both quantitative and qualitative changes in the proteins found in inoculated soybeans, especially in infected roots where nodulins (nodule‐specific proteins) and endomycorrhizins (mycorrhiza‐specific proteins) were detected by polyacrylamide gel eletrophoresis. Five nodulins (11.8% of root proteins) were detected with molecular weights of 14, 34, 40, 41 and 100 kDa. Five endomycorrhizins (5.1% of root proteins) were detected with molecular weights of 16, 17, 18, 22 and 30 kDa. Differences in nutrient uptake and allocation in symbiotic plants could not be duplicated by fertilizer input alone, although nutrient addition could lead to similar growth rates and dry weight accumulation. These findings suggest that the quality and quantity of plant carbohydrates, proteins and amino acids shift in response to the physiological changes resulting from infection by N 2 ‐fixing bacteria or endomycorrhizal fungi.
On prioritized coding for real-time streaming under packet erasures (2013)

We consider a real-time streaming system where high and low priority messages arrive at the source according to a periodic pattern, are transmitted over a packet erasure channel, and need to be decoded at the sink within a fixed delay. For a window-based erasure model, we show an upper bound on message sizes that can be asymptotically achieved with a proportional time-invariant intra-session code. For i.i.d. random erasures, we provide an upper bound on message sizes given probabilities of decoding the high and low priority messages respectively, and compare with the performance of our proportional coding scheme.
Gastric H,K-ATPASE as Therapeutic Target (1988)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
A Drilling Rate Model for Roller Cone Bits and Its Application (2010)

Abstract Modeling bit performance is a scientific approach to optimizing drilling performance. Drilling rate or rate of penetration (ROP) is one of bit performance indexes. Several ROP models for roller cone bits have been developed over the years. However, there exist errors to some extent between these models and the field. This is because of the technical complexity of the bit-rock interaction. This paper introduces a new ROP model based on the interaction mechanism between drill bit and rock. The ROP model takes into account bit structure, especially cutting structure, and drilling parameters, such as WOB, RPM, and bit wear. The paper then focuses on applications of the ROP model in predicting drilling rate and rock compressive strength with drilling well data from Western Canada. Simulations were carried out using the ROP model for roller cone bits with two sets of offset well drilling data. The predicted ROP and rock strength when the model is used in an inverted mode were compared with field data or results from log rock strength data respectively. The comparison shows the ROP model can predict drilling operational ROP and rock compressive strength well. The ROP model is different from others in that it takes into account the bit cutting structure in more detail. The model can reflect the effects of different number of inserts and insert shape on ROP. The model is especially useful when selecting a roller cone bit with same IADC code but with different insert features and designs, and can be used in optimizing the drilling parameters in a planning mode and predicting the unconfined compressive strength in an inverted mode.
A monthly consumption indicator for Germany based on Internet search query data (2011)

This study introduces a monthly coincident indicator for consumption in Germany based on Google Trends data on web search activity. In real-time nowcasting experiments the indicator outperforms common survey-based indicators in predicting consumption. Unlike those indicators, it provides predictive information beyond that already captured in other macroeconomic variables.
Gene therapy and translational cancer research. (1999)

The Pathology B and Experimental Therapeutics-2 study sections sponsored a workshop devoted to recent advances in gene therapy and translational research relevant to cancer. The workshop was highlighted by a historical perspective of gene therapy by Dr. Theodore Friedman (University of California,
Resistance to Anti-Angiogenic Therapy in Cancer—Alterations to Anti-VEGF Pathway (2018)

Anti-angiogenic therapy is one of the promising strategies for many types of solid cancers. Bevacizumab (Avastin), a recombinant humanized monoclonal antibody of vascular endothelial growth factor (VEGF) A, was approved for the first time as an anti-angiogenic drug for the treatment of metastatic colorectal cancer (CRC) by the Food and Drug Administration (FDA) in 2004. In addition, the other VEGF pathway inhibitors including small molecule tyrosine kinase inhibitors (sunitinib, sorafenib, and pazopanib), a soluble VEGF decoy receptor (aflibercept), and a humanized monoclonal antibody of VEGF receptor 2 (VEGFR2) (ramucirumab) have been approved for cancer therapy. Although many types of VEGF pathway inhibitors can improve survival in most cancer patients, some patients have little or no beneficial effect from them. The primary or acquired resistance towards many oncological drugs, including anti-VEGF inhibitors, is a common problem in cancer treatment. This review summarizes the proposed alternative mechanisms of angiogenesis other than the VEGF pathway. These mechanisms are involved in the development of resistance to anti-VEGF therapies in cancer patients.
Activation of Mitogen-activated Protein Kinase by H2O2 (1996)

The mitogen-activated protein kinase (MAPK) family is comprised of key regulatory proteins that control the cellular response to both proliferation and stress signals. In this study we investigated the factors controlling MAPK activation by H2O2 and explored the impact of altering the pathways to kinase activation on cell survival following H2O2 exposure. Potent activation (10-20-fold) of extracellular signal-regulated protein kinase (ERK2) occurred within 10 min of H2O2 treatment, whereupon rapid inactivation ensued. H2O2 activated ERK2 in several cell types and also moderately activated (3-5-fold) both c-Jun N-terminal kinase and p38/RK/CSBP. Additionally, H2O2 increased the mRNA expression of MAPK-dependent genes c-jun, c-fos, and MAPK phosphatase-1. Suramin pretreatment completely inhibited H2O2 stimulation of ERK2, highlighting a role for growth factor receptors in this activation. Further, ERK2 activation by H2O2 was blocked by pretreatment with either N-acetyl-cysteine, o-phenanthroline, or mannitol, indicating that metal-catalyzed free radical formation mediates the initiation of signal transduction by H2O2. H2O2-stimulated activation of ERK2 was abolished in PC12 cells by inducible or constitutive expression of the dominant negative Ras-N-17 allele. Interestingly, PC12/Ras-N-17 cells were more sensitive than wild-type PC12 cells to H2O2 toxicity. Moreover, NIH 3T3 cells expressing constitutively active MAPK kinase (MEK, the immediate upstream regulator of ERK) were more resistant to H2O2 toxicity, while those expressing kinase-defective MEK were more sensitive, than cells expressing wild-type MEK. Taken together, these studies provide insight into mechanisms of MAPK regulation by H2O2 and suggest that ERK plays a critical role in cell survival following oxidant injury.
Identification of Framework Residues in a Secreted Recombinant Antibody Fragment That Control Production Level and Localization inEscherichia coli (1997)

The monoclonal antibody 5T4, directed against a human tumor-associated antigen, was expressed as a secreted Fab superantigen fusion protein in Escherichia coli. The product is a putative agent for immunotherapy of non-small cell lung cancer. During fermentation, most of the fusion protein leaked out from the periplasm to the growth medium at a level of approximately 40 mg/liter. This level was notably low compared with similar products containing identical CH1, CL, and superantigen moieties, and the Fv framework was therefore engineered. Using hybrid molecules, the light chain was found to limit high expression levels. Substituting five residues in VL increased the level almost 15 times, exceeding 500 mg/liter in the growth medium. Here, the substitutions Phe-10 --> Ser, Thr-45 --> Lys, Thr-77 --> Ser, and Leu-78 --> Val were most powerful. In addition, replacing four VH residues diminished cell lysis during fermentation. Thereby the product was preferentially located in the periplasm instead of the growth medium, and the total yield was more than 700 mg/liter. All engineered products retained a high affinity for the tumor-associated antigen. It is suggested that at least some of the identified framework residues generally have to be replaced to obtain high level production of recombinant Fab products in E. coli.
Methyl Substitution of a Rexinoid Agonist Improves Potency and Reveals Site of Lipid Toxicity (2014)

(2E,4E,6Z,8E)-8-(3',4'-Dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid, 9cUAB30, is a selective rexinoid that displays substantial chemopreventive capacity with little toxicity. 4-Methyl-UAB30, an analogue of 9cUAB30, is a potent RXR agonist but caused increased lipid biosynthesis unlike 9cUAB30. To evaluate how methyl substitution influenced potency and lipid biosynthesis, we synthesized four 9cUAB30 homologues with methyl substitutions at the 5-, 6-, 7-, or 8-position of the tetralone ring. The syntheses and biological evaluations of these new analogues are reported here along with the X-ray crystal structures of each homologue bound to the ligand binding domain of hRXRα. We demonstrate that each homologue of 9cUAB30 is a more potent agonist, but only the 7-methyl-9cUAB30 caused severe hyperlipidemia in rats. On the basis of the X-ray crystal structures of these new rexinoids and bexarotene (Targretin) bound to hRXRα-LBD, we reveal that each rexinoid, which induced hyperlipidemia, had methyl groups that interacted with helix 7 residues of the LBD.
CRISPR-Cas9-based mutagenesis frequently provokes on-target mRNA misregulation (2019)

Abstract The introduction of insertion-deletions (INDELs) by non-homologous end-joining (NHEJ) pathway underlies the mechanistic basis of CRISPR-Cas9-directed genome editing. Selective gene ablation using CRISPR-Cas9 is achieved by installation of a premature termination codon (PTC) from a frameshift-inducing INDEL that elicits nonsense-mediated decay (NMD) of the mutant mRNA. Here, by examining the mRNA and protein products of CRISPR targeted genes in a cell line panel with presumed gene knockouts, we detect the production of foreign mRNAs or proteins in ~50% of the cell lines. We demonstrate that these aberrant protein products stem from the introduction of INDELs that promote internal ribosomal entry, convert pseudo-mRNAs (alternatively spliced mRNAs with a PTC) into protein encoding molecules, or induce exon skipping by disruption of exon splicing enhancers (ESEs). Our results reveal challenges to manipulating gene expression outcomes using INDEL-based mutagenesis and strategies useful in mitigating their impact on intended genome-editing outcomes.
Toxicity of Peppermint Monoterpenes to the Variegated Cutworm (Lepidoptera: Noctuidae) (1990)

Toxicity of five monoterpenes to the variegated cutworm, Peridroma saucia Hubner, was evaluated. Larvae fed for 6 d from the beginning of the fifth stadium on semi defined artificial diet fortified with pule gone (0.05%, 0.1%), menthol (0.1%, 0.2%), or menthone (0.2%) weighed less than controls. Reduced growth was the result of feeding inhibition in larvae fed menthone and pule gone and to molting abnormalities in larvae receiving menthol. Menthol completely inhibited pupation at doses approximating those in peppermint (0.05-0.2% wet wt). Limonene (0.2%), menthone (0.1%, 0.2%), and pule gone (0.1%) also inhibited pupation. Growth, feeding, and pupation were not affected when larvae ingested limonene (0.05% or 0.1%) or α-pinene (0.05-0.2%). Growth, maximum weight, and pupal weight of neonate larvae fed artificial diet fortified with menthol, menthone (0.05%), Iimonene (0.05%), α-pinene (0.05%), or pule gone (0.025%) did not differ from those of controls. However, larval mortality was significantly higher in menthone and pule gone treatments than in the controls. The median lethal dose for pule gone applied topically to sixth instars was 1,077 μg/g; for menthone, 2,478 μg/g; and for a-pinene, 7,925 μg/g. Piperonyl butoxide synergized the latter two effects. Suspensions of midgut microsomesfrom sixth instars metabolized all five monoterpenes as indicated by disappearance of NADPH.
Architecture and memory requirements for stand-alone and hierarchical MPEG2 HDTV-decoders with synchronous DRAMs (2002)

The architecture of dedicated MPEG2 HDTV-decoders for stand-alone and hierarchical transmission has been investigated. The high demands on the video memory in terms of memory capacity and data rate are met by using synchronous DRAMs and adapting the data accesses to the properties of the memory devices. Thus compact implementations for consumer and professional decoders become possible.