gebhart/patrepeval huggingface dataset:
Structure and function of matrix metalloproteinases and TIMPs (2006)

Matrix metalloproteinases (MMPs), also called matrixins, function in the extracellular environment of cells and degrade both matrix and non-matrix proteins. They play central roles in morphogenesis, wound healing, tissue repair and remodelling in response to injury, e.g. after myocardial infarction, and in progression of diseases such as atheroma, arthritis, cancer and chronic tissue ulcers. They are multi-domain proteins and their activities are regulated by tissue inhibitors of metalloproteinases (TIMPs). This review introduces the members of the MMP family and discusses their domain structure and function, proenyme activation, the mechanism of inhibition by TIMPs and their significance in physiology and pathology.
A Neural Cell-Type-Specific Expression System Using Recombinant Adenovirus Vectors (1996)

We demonstrated neural cell-type-specific gene expression using an adenovirus vector, which is useful for delivering foreign genes into quiescent neural cells. We produced eight recombinant replication-defective adenoviruses carrying the lacZ reporter gene driven by various promoters, including those of the L7/PCP2 gene (highly restricted expression in cerebellar Purkinje cells), and the myelin basic protein (in oligodendrocytes) gene. We demonstrated in vitro and in vivo promoter-driven, neural cell-type-specific gene expression by recombinant adenoviruses. The genes were transferred into these recombinant adenoviruses and expressed with high levels of efficiency in vitro and in vivo. In primary culture, the recombinant adenoviruses AdexL7-NL-LacZ and AdexMBP-NL-LacZ appeared to be expressed in a Purkinje cell and oligodendrocyte-specific manner. Introduction of 10(8) pfu of these viruses into the adult rat cerebellum by stereotactic injection yielded neural cell-type-specific expression without apparent toxicity to the animals. Thus, adenovirus vectors are useful for cell-type-specific therapeutic uses and in studies requiring neural cell-type-specific gene expression.
Biological nitrogen fixation in non-legume plants (2013)

Understanding the molecular mechanism of BNF outside the legume-rhizobium symbiosis could have important agronomic implications and enable the use of N-fertilizers to be reduced or even avoided. Indeed, in the short term, improved understanding could lead to more sustainable exploitation of the biodiversity of nitrogen-fixing organisms and, in the longer term, to the transfer of endosymbiotic nitrogen-fixation capacities to major non-legume crops.
ESTABLISHMENT OF AN EFFICIENT MEDIUM FOR ANTHER CULTURE OF RICE THROUGH COMPARATIVE EXPERIMENTS ON THE NITROGEN SOURCES (1975)

The experiments have revealed that (NH4)2SO4 combined with KNO3 at low concentration is of advantage to the formation, growth and differentiation of pollen callus in rice, whereas the high concentration of (NH4)2SO4, whether used separately or in combination with KNO3, obviously inhibits the pollen callus formation. The optimum NH4+ concen- tration is about 7.0 mM (equal to 3.5 mM (NH4)2SO4). A basic medium containing 3.5 mM (NH4)2SO4 and 28 mM KNO3 as nitrogen sources has been established. On such medium the frequency of the pollen callus formation is higher than that on Millers me- dium, and the differentiation of shoot from pollen callus is satisfactory.
<italic>Brief Communication:</italic> Immunotherapy of Lethal Metastases by Lymphocytes Sensitized Against Tumor Cells In Vitro<xref ref-type="fn" rid="fn2">2</xref> (1975)

To learn whether tumor metastases can be prevented by the immune system, we developed a model for the treatment of mice with syngeneic lymphocytes sensitized against tumor cells in vitro. Mice were given subcutaneously tumor cells that spontaneously metastasized to the lungs. The tumors developing locally were surgically removed and the mice were inoculated with sensitized lymphocytes 1 day later. Prevention of death by lung metastases was the measure of immunotherapy. Only approximately equal to 30-40 percent of mice receiving control treatment survived, whereas approximately equal to 70 percent survived that received lymphocytes sensitized in vitro against the tumor cells. Hence sensitization of syngeneic lymphocytes against tumor cells in vitro and injection of the lymphocytes into the host after removal of a local tumor prevented the development of lethal metastases.
Heat-stable antigen (CD24) as ligand for mouse P-selectin (1994)

Heat-stable antigen (HSA)/CD24 is a cell surface molecule expressed by many cell types in the mouse. The molecule has an unusual structure because of its small protein core and extensive glycosylation. In order to study the functional role of the HSA-associated glycoconjugates we have isolated different forms of HSA. Using lectin analysis we provide evidence for extensive heterogeneity in carbohydrate composition and sialic acid linkage. Several HSA forms were recognized by mouse P-selectin-IgG but not E-selectin-IgG in ELISA. As expected, P-selectin-IgG also bound to L2/HNK-1-positive neural glycoproteins (L2-glycoproteins) and sulfatides but not to gangliosides and other control glycoproteins. The binding of P-selectin-IgG to L2-glycoproteins and HSA required bivalent cations. The reactivity to HSA was sensitive to sialidase treatment whereas the binding to L2-glycoproteins was not. Studies with alpha 2-6 sialytransferase indicated that alpha 2-6 linked sialic acid was not involved in the P-selectin binding to HSA. Surprisingly, an L2/HNK-1 specific antibody was found to cross-react with some HSA glycoforms and its binding correlated with P-selectin-IgG reactivity. L2/HNK-1-positive or L2/HNK-1-negative HSA glycoforms were also analyzed after coating to polystyrene beads. Only the L2/HNK-1-positive HSA coated beads were reactive with P-selectin-IgG and could bind to activated bend3 endothelioma cells expressing P-selectin whereas the L2/HNK-1-negative HSA beads did not. It is suggested that in its L2/HNK-1 modified form the HSA molecule on leukocytes could represent a ligand for P-selectin on endothelial cells or platelets.
The Bystander Effect of the Nitroreductase/CB 1954 Enzyme/Prodrug System Is Due to a Cell-Permeable Metabolite (1997)

The bystander effect is an important part of tumor kill using gene-directed enzyme prodrug therapy (GDEPT). Recently, we have described a novel enzyme prodrug system using bacterial nitroreductase and the prodrug CB1954 (NTR/CB1954). We demonstrate here the presence of a cell-permeable cytotoxic activity in the conditioned growth medium of nitroreductase (NTR)-transduced cells treated with CB1954 and show that its appearance corresponds to the appearance of two metabolites of CB1954 previously identified (Friedlos et al., 1992). The degree of bystander effect and the degree of transferred cytotoxicity correlates with the level of NTR enzyme expression. Two other prodrugs for NTR show little bystander killing and do not produce detectable cell permeable metabolites. The elucidation of the mechanism of the bystander effect may allow the more effective use of NTR/CB1954.
DsbA-DsbB Interaction through Their Active Site Cysteines (1995)

Formation of disulfide bonds in Escherichia coli envelope proteins is facilitated by the Dsb system, which is thought to consist of at least two components, a periplasmic soluble enzyme (DsbA) and a membrane-bound factor (DsbB). Although it is believed that DsbA directly oxidizes substrate cysteines and DsbB reoxidizes DsbA to allow multiple rounds of reactions, direct evidence for the DsbA-DsbB interaction has been lacking. We examined intracellular activities of mutant forms of DsbA, DsbA30S and DsbA33S, in which one of its active site cysteines (Cys30 or Cys33, respectively) has been replaced by serine. The DsbA33S protein was found to dominantly interfere with the disulfide bonds formation and to form intermolecular disulfide bonds with numerous other proteins when cells were grown in media containing low molecular weight disulfides such as GSSG. In the absence of added GSSG, DsbA33S protein remained specifically disulfide-bonded with DsbB. These in vivo results not only confirm the previous findings that Cys30 of DsbA is hyper-reactive in vitro but provide evidence that DsbA indeed interacts selectively with DsbB. We propose that the Cys30-mediated DsbA-DsbB complex represents an intermediate state of DsbA-DsbB recycling reaction that has been fixed because of the absence of Cys33 on DsbA.
A cytochrome c–GFP fusion is not released from mitochondria into the cytoplasm upon expression of Bax in yeast cells (2000)

To study Bax-induced release of cytochrome c in vivo, we have expressed a cytochrome c-GFP (green fluorescent protein) fusion in Saccharomyces cerevisiae cells null for the expression of the endogenous cytochrome. We show here that cytochrome c-GFP is efficiently localised to mitochondria and able to function as an electron carrier between complexes III and IV of the respiratory chain. Strikingly, while natural cytochrome c is released into the cytoplasm upon expression of Bax, the cytochrome c-GFP fusion is not. Nevertheless, cells co-expressing Bax and the cytochrome c-GFP fusion die, indicating that mitochondrial release of cytochrome c is not essential for cell death to occur in yeast. The failure to release cytochrome c-GFP is presumed to arise from increased bulk due to the GFP moiety. We propose that in intact yeast cells, Bax-induced release of cytochrome c into the cytoplasm occurs through a selective pore and not as a consequence of the non-specific breakage of the mitochondrial outer membrane.
Significant improvement of stiff‐person syndrome after paraspinal injection of botulinum toxin A (1993)

Following several months of low back pain, a 36-year-old man developed progressive stiffness of the abdominal, low back, and thigh muscles. On examination, these muscles demonstrated marked hypertonia consistent with the clinical diagnosis of stiff-person syndrome. The patient demonstrated increased lumbar lordosis and had focal hyperhidrosis at different sites. Electromyography showed continuous activity of the paraspinal and thigh muscles, and serum and cerebrospinal fluid antibodies to glutamic acid decarboxylase (GAD) were markedly elevated. Diazepam and Lioresal offered partial pain relief. Paraspinal muscle administration of botulinum toxin A reduced the tone of paraspinal and thigh muscles significantly and resulted in marked improvement of ambulation and cessation of pain.
On-line path planning for an autonomous vehicle in an obstacle filled environment (2008)

The 2007 Darpa Urban Challenge called for a kinematic vehicle path planning method that could navigate and park in an obstacle-filled environment with realistic vehicle constraints. Key capabilities include minimum-time trajectories with both forward and reverse segments, and obstacle avoidance. An algorithm which generalizes the collocation method is developed and used to optimally control a differentially flat parameterization of the kinematic car. The singularity inherent in the differentially flat formulation is addressed without any constraints imposed on the state space. Experimental data is presented showing this algorithm running on Alice, the Caltech autonomous vehicle. The flexibility of the algorithm developed in this paper allows it to be applied to a large group of practical optimal control problems.
Twice‐weekly administration of peginterferon‐α‐2b improves viral kinetics in patients with chronic hepatitis C genotype 1 (2003)

The decline in hepatitis C viral load on treatment with peginterferon-alpha-2b is not continuous. The aim of this study was to investigate whether twice weekly dosing of peginterferon-alpha-2b may improve viral kinetics. Ten interferon-naïve patients with chronic hepatitis C (genotype 1a or b) were randomized to receive either 1.0 microg/kg peginterferon-alpha-2b once (group A) or twice weekly (group B) for 4 weeks. Viral load and serum concentrations of peginterferon-alpha-2b were measured. Peginterferon-alpha-2b reached maximal blood concentrations 24 h after the first dose, followed by a linear decline during the subsequent days. On the day before administration of the next dose, peginterferon-alpha-2b was undetectable in nine patients in group A (once weekly dosing). The same pattern was observed during the next 3 weeks of therapy. In group B (twice weekly dosing) peginterferon-alpha-2b was detectable at any given time point and higher than in group A (P between 0.01 and <0.0001). Viral load decreased in all patients within 2 days after the first dose of peginterferon-alpha-2b, but increased again on day 3. In group A, it further increased until day 7. A similar pattern was observed in the second week. In contrast, in group B, viral load decreased again on day 4 and remained lower until the end of the study (P < 0.001). To achieve continuous drug exposure and to improve initial viral clearance, peginterferon-alpha-2b has to be given at least two times weekly.
Systemic inflammation and neurodegeneration in a mouse model of multiple sulfatase deficiency (2007)

Sulfatases are involved in several biological functions such as degradation of macromolecules in the lysosomes. In patients with multiple sulfatase deficiency, mutations in the SUMF1 gene cause a reduction of sulfatase activities because of a posttranslational modification defect. We have generated a mouse line carrying a null mutation in the Sumf1 gene. Sulfatase activities are completely absent in Sumf1(-/-) mice, indicating that Sumf1 is indispensable for sulfatase activation and that mammals, differently from bacteria, have a single sulfatase modification system. Similarly to multiple sulfatase deficiency patients, Sumf1(-/-) mice display frequent early mortality, congenital growth retardation, skeletal abnormalities, and neurological defects. All examined tissues showed progressive cell vacuolization and significant lysosomal storage of glycosaminoglycans. Sumf1(-/-) mice showed a generalized inflammatory process characterized by a massive presence of highly vacuolated macrophages, which are the main site of lysosomal storage. Activated microglia were detected in the cerebellum and brain cortex associated with remarkable astroglyosis and neuronal cell loss. Between 4 and 6 months of age, we detected a strong increase in the expression levels of inflammatory cytokines and of apoptotic markers in both the CNS and liver, demonstrating that inflammation and apoptosis occur at the late stage of disease and suggesting that they play an important role in both the systemic and CNS phenotypes observed in lysosomal disorders. This mouse model, in which the function of an entire protein family has been silenced, offers a unique opportunity to study sulfatase function and the mechanisms underlying lysosomal storage diseases.
Sphingosine kinase 1/S1P receptor signaling axis controls glial proliferation in mice with Sandhoff disease (2008)

Sphingosine-1-phosphate (S1P) is a lipid-signaling molecule produced by sphingosine kinase in response to a wide number of stimuli. By acting through a family of widely expressed G protein-coupled receptors, S1P regulates diverse physiological processes. Here we examined the role of S1P signaling in neurodegeneration using a mouse model of Sandhoff disease, a prototypical neuronopathic lysosomal storage disorder. When sphingosine kinase 1 (Sphk1) was deleted in Sandhoff disease mice, a milder disease course occurred, with decreased proliferation of glial cells and less-pronounced astrogliosis. A similar result of milder disease course and reduced astroglial proliferation was obtained by deletion of the gene for the S1P(3) receptor, a G protein-coupled receptor enriched in astrocytes. Our studies demonstrate a functional role of S1P synthesis and receptor expression in astrocyte proliferation leading to astrogliosis during the terminal stages of neurodegeneration in Sandhoff disease mice. Because astrocyte responses are involved in many types of neurodegeneration, the Sphk1/S1P receptor signaling axis may be generally important during the pathogenesis of neurodegenerative diseases.
A meta-analysis of the association between poultry and egg consumption and the risk of brain cancer (2019)

Poultry consumption, as well as egg consumption for brain cancer risk remains an important topic. The objective of this meta-analysis is to investigate the role of poultry and egg consumption for brain cancer risk. All articles about poultry and egg consumption for brain cancer were retrieved from PubMed, Web of knowledge and Wan Fang Med Online. The data was analyzed using Stata 12.0 software. Ten articles (6 articles for poultry and 5 articles for egg) were included. For poultry consumption, the summarized relative risk (RR) was 0.901 (95%CI= 0.703-1.154) for brain cancer risk, with high between-study heterogeneity (I2= 60.7%, P=0.018). Four studies reported the association between poultry consumption and glioma risk, yielding a RR of 0.873 (95%CI= 0.737-1.034, I2= 0.0%, P=0.838). The association between egg consumption and brain cancer risk was not significant (RR= 0.998, 95%CI= 0.552-1.805), with significant heterogeneity (I2= 82.6%, P&lt; 0.001). The pooled RR for glioma risk was 1.472 (95%CI= 0.935-2.316). In summary, our results concluded that poultry and egg consumption may be not associated with the risk of brain cancer. Due to the limited quality of evidence currently available, more studies related to poultry and egg consumption for brain cancer is necessary.
Activation of toll‐like receptor‐9 induces progression of renal disease in MRL‐Fas(lpr) mice (2004)

How bacterial or viral infections trigger flares of autoimmunity is poorly understood. As toll-like receptor (TLR)-9 activation by exogenous or endogenous CpG-DNA may contribute to disease activity of systemic lupus erythematosus, we examined the effects of CpG-oligodeoxynucleotides (ODN) or DNA derived from Escherichia coli (E. coli) on the course of nephritis in MRL(lpr/lpr) mice. In kidneys of these mice, TLR9 localized to glomerular, tubulointerstitial, and perivascular infiltrates. After intraperitoneal injection labeled CpG-ODN localized to glomerular and interstitial macrophages and dendritic cells in nephritic kidneys of MRL(lpr/lpr) mice but not in healthy MRL controls. Furthermore, murine J774 macrophages and splenocytes from MRL(lpr/lpr) mice, but not tubular epithelial cells, renal fibroblasts, or mesangial cells, expressed TLR9 and up-regulated CCL5/RANTES mRNA upon stimulation with CpG-ODN in vitro. In vivo both E. coli DNA and CpG-ODN increased serum DNA autoantibodies of the IgG2a isotype in MRL(lpr/lpr) mice. This was associated with progression of mild to crescentic glomerulonephritis, interstitial fibrosis, and heavy proteinuria. CpG-ODN increased renal CCL2/MCP-1 and CCL5/RANTES expression associated with increased glomerular and interstitial leukocyte recruitment. In contrast control GpC-ODN had no effect. We conclude that TLR9 activation triggers disease activity of systemic autoimmunity, for example, lupus nephritis, and that adaptive and innate immune mechanisms contribute to the CpG-DNA-induced progression of lupus nephritis.
Direct calorimetric verification of thermodynamic instability of lead halide hybrid perovskites (2016)

Hybrid perovskites, especially methylammonium lead iodide (MAPbI3), exhibit excellent solar power conversion efficiencies. However, their application is plagued by poor chemical and structural stability. Using direct calorimetric measurement of heats of formation, MAPbI3 is shown to be thermodynamically unstable with respect to decomposition to lead iodide and methylammonium iodide, even in the absence of ambient air or light or heat-induced defects, thus limiting its long-term use in devices. The formation enthalpy from binary halide components becomes less favorable in the order MAPbCl3, MAPbBr3, MAPbI3, with only the chloride having a negative heat of formation. Optimizing the geometric match of constituents as measured by the Goldschmidt tolerance factor provides a potentially quantifiable thermodynamic guide for seeking chemical substitutions to enhance stability.
Opposite side floating gate SOI FLASH memory cell (2000)

An opposite side floating gate SOI FLASH memory cell has been proposed for advanced device scaling. The new structure has the read gate and floating gate on the opposite sides of the active silicon film. It allows the use of a thick tunneling oxide to prevent charge leakage and a thin gate oxide for device scaling. The functionality of the device is demonstrated through the analysis of threshold voltage shift before and after programming. The effects of various parameters such as front and back gate oxide thickness, silicon film thickness and channel doping on device performance have been studied and a possible way to fabricate the device is proposed.
Intraislet Endothelial Cells Contribute to Revascularization of Transplanted Pancreatic Islets (2004)

Pancreatic islet transplantation is an emerging therapy for type 1 diabetes. To survive and function, transplanted islets must revascularize because islet isolation severs arterial and venous connections; the current paradigm is that islet revascularization originates from the transplant recipient. Because isolated islets retain intraislet endothelial cells, we determined whether these endothelial cells contribute to the revascularization using a murine model with tagged endothelial cells (lacZ knock-in to Flk-1/VEGFR2 gene) and using transplanted human islets. At 3-5 weeks after transplantation beneath the renal capsule, we found that islets were revascularized and that the transplant recipient vasculature indeed contributed to the revascularization process. Using the lacZ-tagged endothelial cell model, we found that intraislet endothelial cells not only survived after transplantation but became a functional part of revascularized islet graft. A similar contribution of intraislet endothelial cells was also seen with human islets transplanted into an immunodeficient mouse model. In the murine model, individual blood vessels within the islet graft consisted of donor or recipient endothelial cells or were a chimera of donor and recipient endothelial cells, indicating that both sources of endothelial cells contribute to the new vasculature. These observations suggest that interventions to activate, amplify, or sustain intraislet endothelial cells before and after transplantation may facilitate islet revascularization, enhance islet survival, and improve islet transplantation.
Development of freeze-dried biosynthetic Factor VIII: I. A case study in the optimization of formulation (2009)

The purpose of this paper was to identify an optimal formulation, free of any human or animal derived protein, which stabilizes biosynthetic Factor VIII (rAHF) during freeze drying and storage. Factor VIII activity in samples stored at temperatures between 25 degrees C and 60 degrees C was determined using the one-stage activated partial thromboplastin time assay. Various formulations containing different combinations of a stabilizer and a bulking agent were screened for acceptable freeze-drying behavior, elegance of the resulting product, and stability during processing and storage. Degradation of freeze-dried rAHF followed the 'square root of time' kinetics. Stability of rAHF was found to increase with increasing protein concentration, indicating a self-protection effect. The addition of the antioxidant, glutathione was also shown to enhance storage stability. Given the constraint of high residual levels of NaCl from purification, the lead formulation employed mannitol as a bulking agent and trehalose as the general stabilizer. This formulation allowed an elegant product to be produced which more than met the stability requirements. However, it was also shown that elimination of residual NaCl allowed a much shorter freeze-drying cycle to produce an elegant product with greatly enhanced stability.