gebhart/patrepeval huggingface dataset:
Ambient Molecular Imaging and Depth Profiling of Live Tissue by Infrared Laser Ablation Electrospray Ionization Mass Spectrometry (2008)

Mass spectrometry in conjunction with atmospheric pressure ionization methods enables the in vivo investigation of biochemical changes with high specificity and sensitivity. Laser ablation electrospray ionization (LAESI) is a recently introduced ambient ionization method suited for the analysis of biological samples with sufficient water content. With LAESI mass spectrometric analysis of chimeric Aphelandra squarrosa leaf tissue, we identify the metabolites characteristic for the green and yellow sectors of variegation. Significant parts of the related biosynthetic pathways (e.g., kaempferol biosynthesis) are ascertained from the detected metabolites and metabolomic databases. Scanning electron microscopy of the ablated areas indicates the feasibility of both two-dimensional imaging and depth profiling with a approximately 350 microm lateral and approximately 50 microm depth resolution. Molecular distributions of some endogenous metabolites show chemical contrast between the sectors of variegation and quantitative changes as the ablation reaches the epidermal and mesophyll layers. Our results demonstrate that LAESI mass spectrometry opens a new way for ambient molecular imaging and depth profiling of metabolites in biological tissues and live organisms.
Experimentation of electrostatically actuated monochip micropump for drug delivery (1999)

The objective of the MICROMED CNRS project is the design of a complete microsystem usable in the treatment in vivo of hypertensives. The microsystem which corresponds with this objective includes different elements such as pressure sensors, a drug reservoir, a monitoring chip and a drug delivery system that necessitates the use of a dosing micropump able to deliver daily does of few microliters in several shots. We will focus here on the micropump:microfabrication technology, assembly and test. The fact that the fluid actuating membrane, the input and output fluid gates, and the two passive microvalues are together on a single silicon chip of 1 cm<SUP>3</SUP> area makes this pump original. The fabrication technology combines the techniques of microelectronics and MEMS: micromachining for the square membrane and the fluid gates, sacrificial oxide layers and LPCVD polysilicon deposition for the microvalves. The assembly of the different parts is based on existing techniques like anodic bonding, gluing with adhesive films...we have investigated the fabrication of the micro pump with an electrostatic actuation. Tests are in progress for the first prototypes on a specific experimentation set- up in order to: (i) study the flowing of different fluids into the pump, (ii) study the directionality of the valves by plotting the flow rate/pressure (Phi) (P) diagram, (iii) study the pump functionality.
Blur and the perception of depth at occlusions (2016)

The depth ordering of two surfaces, one occluding the other, can in principle be determined from the correlation between the occlusion border's blur and the blur of the two surfaces. If the border is blurred, the blurrier surface is nearer; if the border is sharp, the sharper surface is nearer. Previous research has found that observers do not use this informative cue. We reexamined this finding. Using a multiplane display, we confirmed the previous finding: Our observers did not accurately judge depth order when the blur was rendered and the stimulus presented on one plane. We then presented the same simulated scenes on multiple planes, each at a different focal distance, so the blur was created by the optics of the eye. Performance was now much better, which shows that depth order can be reliably determined from blur information but only when the optical effects are similar to those in natural viewing. We asked what the critical differences were in the single- and multiplane cases. We found that chromatic aberration provides useful information but accommodative microfluctuations do not. In addition, we examined how image formation is affected by occlusions and observed some interesting phenomena that allow the eye to see around and through occluding objects and may allow observers to estimate depth in da Vinci stereopsis, where one eye's view is blocked. Finally, we evaluated how accurately different rendering and displaying techniques reproduce the retinal images that occur in real occlusions. We discuss implications for computer graphics.
Effects of Oxido‐Reductants on Rheological Properties of Wheat Flour Dough and Comparison with Some Characteristics of Extruded Noodles (1999)

ABSTRACT The effects of oxido‐reductants on the rheological properties of wheat flour dough were evaluated by using a capillary rheometer and an oscillatory rheometer at three temperatures. The oxidants potassium iodate (KIO 3 ) and l ‐ascorbic acid ( l ‐AA) significantly increased the apparent viscosity and G ′ and decreased loss tangent at low temperatures of 30 and 60°C due to enhanced formation of disulfide bonds. The reductant glutathione (GSH) had the opposite effect. Heating caused the gelatinization of starch, which diminished the effects of the oxido‐reductants and produced doughs with similar rheological properties at 80°C. The correlation between dough rheology and characteristics of extruded noodles was also studied.
Nutrition and breast cancer (2003)

The major risk factors for breast cancer are hormone-related, and the only well-established diet-related risk factors for breast cancer are obesity and alcohol consumption. Obesity increases breast cancer risk in postmenopausal women by around 30%, probably by increasing serum concentrations of bioavailable oestradiol. Moderate alcohol intakes increase breast cancer risk by about 7% per alcoholic drink per day, perhaps also by increasing oestrogen levels. Populations with high fat intakes generally have high rates of breast cancer, but studies of individual women have not confirmed an association of high fat diets with breast cancer risk. Phyto-oestrogens can affect hormone metabolism, but data on phyto-oestrogen consumption and breast cancer risk are inconsistent. Nutrition might affect breast cancer risk by altering levels of growth factors such as insulin-like growth factor-I. Current dietary advice should be to avoid obesity, limit alcohol intake, and maintain a varied diet.
Reversal of experimental diabetic neuropathy by VEGF gene transfer (2001)

The pathogenetic basis for diabetic neuropathy has been enigmatic. Using two different animal models of diabetes, we have investigated the hypothesis that experimental diabetic neuropathy results from destruction of the vasa nervorum and can be reversed by administration of an angiogenic growth factor. Nerve blood flow, as measured by laser Doppler imaging or direct detection of a locally administered fluorescent lectin analogue, was markedly attenuated in rats with streptozotocin-induced diabetes, consistent with a profound reduction in the number of vessels observed. A severe peripheral neuropathy developed in parallel, characterized by significant slowing of motor and sensory nerve conduction velocities, compared with nondiabetic control animals. In contrast, 4 weeks after intramuscular gene transfer of plasmid DNA encoding VEGF-1 or VEGF-2, vascularity and blood flow in the nerves of treated animals were similar to those of nondiabetic control rats; constitutive overexpression of both transgenes resulted in restoration of large and small fiber peripheral nerve function. Similar experiments performed in a rabbit model of alloxan-induced diabetes produced comparable results. These findings support the notion that diabetic neuropathy results from microvascular ischemia involving the vasa nervorum and suggest the feasibility of a novel treatment strategy for patients in whom peripheral neuropathy constitutes a secondary complication of diabetes.
Pharmaceutical Development of AAV-Based Gene Therapy Products for the Eye (2018)

A resurgence of interest and investment in the field of gene therapy, driven in large part by advances in viral vector technology, has recently culminated in United States Food and Drug Administration approval of the first gene therapy product targeting a disease caused by mutations in a single gene. This product, LUXTURNA™ (voretigene neparvovec-rzyl; Spark Therapeutics, Inc., Philadelphia, PA), delivers a normal copy of the RPE65 gene to retinal cells for the treatment of biallelic RPE65 mutation-associated retinal dystrophy, a blinding disease. Many additional gene therapy programs targeting both inherited retinal diseases and other ocular diseases are in development, owing to an improved understanding of the genetic basis of ocular disease and the unique properties of the ocular compartment that make it amenable to local gene therapy. Here we review the growing body of literature that describes both the design and development of ocular gene therapy products, with a particular emphasis on target and vector selection, and chemistry, manufacturing, and controls.
Identification of the intimin-binding domain of Tir of enteropathogenic Escherichia coli (1999)

Enteropathogenic Escherichia coli (EPEC) attaches intimately to mammalian cells via a bacterial outer membrane adhesion molecule, intimin, and its receptor in the host cell membrane, Tir. Tir is a bacterial protein translocated into the host cell membrane and tyrosine phosphorylated after insertion. Tir-intimin binding induces organized actin polymerization beneath the adherent bacteria, resulting in the formation of pedestal-like structures. A series of Tir deletion derivatives were constructed to analyse which Tir domains are involved in intimin binding. We have localized the intimin-binding domain (IBD) of Tir using a yeast two-hybrid system and a gel-overlay approach to a region of 109 amino acids that is predicted to be exposed on the surface of the plasma membrane. A truncated Tir protein lacking this domain was translocated to the host cell membrane and tyrosine phosphorylated, but failed to bind intimin or to induce either actin polymerization or Tir accumulation beneath the bacteria. These results indicate that only a small region of Tir is needed to bind intimin and support the predicted topology for Tir, with both N- and C-terminal regions in the mammalian cell cytosol. They also confirm that Tir-intimin interactions are needed for cytoskeletal organization. We have also identified N-terminal regions involved in Tir stability and Tir secretion to the media.
Control of AMPK-related kinases by USP9X and atypical Lys29/Lys33-linked polyubiquitin chains (2008)

AMPK (AMP-activated protein kinase)-related kinases regulate cell polarity as well as proliferation and are activated by the LKB1-tumour suppressor kinase. In the present study we demonstrate that the AMPK-related kinases, NUAK1 (AMPK-related kinase 5) and MARK4 (microtubule-affinity-regulating kinase 4), are polyubiquitinated in vivo and interact with the deubiquitinating enzyme USP9X (ubiquitin specific protease-9). Knockdown of USP9X increased polyubiquitination of NUAK1 and MARK4, whereas overexpression of USP9X inhibited ubiquitination. USP9X, catalysed the removal of polyubiquitin chains from wild-type NUAK1, but not from a non-USP9X-binding mutant. Topological analysis revealed that ubiquitin monomers attached to NUAK1 and MARK4 are linked by Lys(29) and/or Lys(33) rather than the more common Lys(48)/Lys(63). We find that AMPK and other AMPK-related kinases are also polyubiquitinated in cells. We identified non-USP9X-binding mutants of NUAK1 and MARK4 and find that these are hyper-ubiquitinated and not phosphorylated at their T-loop residue targeted by LKB1 when expressed in cells, suggesting that polyubiquitination may inhibit these enzymes. The results of the present study demonstrate that NUAK1 and MARK4 are substrates of USP9X and provide the first evidence that AMPK family kinases are regulated by unusual Lys(29)/Lys(33)-linked polyubiquitin chains.
The Dexamethasone Suppression Test and Suicide Prediction (2001)

In efforts to predict and prevent suicidal behavior in patients with major depressive disorder, HPA-axis hyperactivity, as reflected in DST results, may provide a tool that is considerably more powerful than the clinical predictors currently in use. Research on the pathophysiology of suicidal behavior in major depressive disorder should emphasize the HPA axis and its interplay with the serotonin system.
Implementing a nationwide energy management system (2002)

The Swedish operator Telia has been working with energy management for a number of years. The driving forces have been increased competition because of market deregulation, changes to the network structure and stringent requirements for reliability. Optimizing the operating costs of the network is today's challenge. Energy management has evolved from technical specifications to open systems and now process support from the energy management system. This paper deals with the different aspects of implementing and operating a nationwide energy management system within Telia's network in Sweden.
The cloning of tumor-associated gene MAGE in human hepatocellular cell line (2002)

Aim To clone the whole cDNA of tumor associated gene MAGE 1 in human hepatocellar carcinoma cell line HHCC. Methods PCR primer amplifying MAGE 1 gene was designed according to the data in GenBank and the whole cDNA of MAGE 1 was amplified by RT PCR. The PCR product was inserted into the plasmid pUC19 after being digested with restrictive endonucleases. The DNA was sent for sequencing. The result of sequencing and DNA sequence in GenBank was analyzed homologously by BLAST. Results Three clones were obtained, they were: MAGE 1(whole sequence), MAGE 6(463 bp)and a new clone(homology of 93% to MAGE 6, but different from any reported MAGE gene sequence), respectively. Conclusion Several MAGE genes are expressed in human hepatocellular carcinoma cell line HHCC and perhaps there are new MAGE genes. The study provides more date for the researching expression mode of MAGE gene and their targeting site in anticancer immnotherapy.
Antifungal activity of ajoene, a constituent of garlic (Allium sativum) (1990)

Ajoene, a compound derived from garlic (Allium sativum L.), inhibited spore germination of some fungi, namely, Alternaria solani, Alternaria tenuissima, Alternaria triticina, Alternaria sp., Colletotrichum sp., Curvularia sp., Fusarium lini, Fusarium oxysporum, Fusarium semitectum, and Fusarium udum, which cause serious diseases in some important crop plants in India. The compound was very effective in checking spore germination at a concentration of 25 μg/mL in some of the above fungi and, in most cases, there was 100% inhibition of germination at 100 μg/mL. It is quite likely that the compound may be useful in controlling disease(s) under field conditions.
SLEEP AND METABOLIC CONTROL: WAKING TO A PROBLEM? (2006)

1. The aim of the present review is to outline: (i) the association between sleep and metabolism; (ii) how sleep duration influences the development of disease; and (iii) how sex differences, ageing and obesity may potentially influence the relationship between sleep, metabolic control and subsequent disease. 2. Sleep is associated with a number of endocrine changes, including a change in insulin action in healthy young individuals. Sleep duration shows a prospective U-shaped relationship with all-cause mortality, cardiovascular disease and Type 2 diabetes. 3. Chronic sleep restriction is becoming more common. Experimental sleep restriction impedes daytime glucose control and increases appetite. 4. The sex hormones oestrogen and testosterone influence sleep duration and quality and may account for sex differences in the prevalence of sleep-related disorders. 5. Ageing is associated with a decreased sleep duration, decreased muscle mass and impaired insulin action. 6. Obesity impairs insulin action and is associated with the incidence and severity of obstructive sleep apnoea. 7. Sleep plays an integral role in metabolic control. Consequently, insufficient sleep may represent a modifiable risk factor for the development of Type 2 diabetes. The challenge ahead is to identify how sex differences, ageing and obesity could potentially influence the relationship between sleep and metabolism.
Transgenic mammalian species, generated by somatic cell cloning, in biomedicine, biopharmaceutical industry and human nutrition/dietetics - recent achievements (2011)

Somatic cell cloning technology in mammals promotes the multiplication of productively-valuable genetically engineered individuals, and consequently allows also for standardization of transgenic farm animal-derived products, which, in the context of market requirements, will have growing significance. Gene farming is one of the most promising areas in modern biotechnology. The use of live bioreactors for the expression of human genes in the lactating mammary gland of transgenic animals seems to be the most cost-effective method for the production/processing of valuable recombinant therapeutic proteins. Among the transgenic farm livestock species used so far, cattle, goats, sheep, pigs and rabbits are useful candidates for the expression of tens to hundreds of grams of genetically-engineered proteins or xenogeneic biopreparations in the milk. At the beginning of the new millennium, a revolution in the treatment of disease is taking shape due to the emergence of new therapies based on recombinant human proteins. The ever-growing demand for such pharmaceutical or nutriceutical proteins is an important driving force for the development of safe and large-scale production platforms. The aim of this paper is to present an overall survey of the state of the art in investigations which provide the current knowledge for deciphering the possibilities of practical application of the transgenic mammalian species generated by somatic cell cloning in biomedicine, the biopharmaceutical industry, human nutrition/dietetics and agriculture.
Vasopressin and the Cardiovascular System (1986)

Anesthetized rats of different strains show a hypotensive response to administration of an antagonist of the V1 receptors for vasopressin [d(CH2)5DAVP]. Such an effect is not seen in conscious, water-replete animals or in Long-Evans rats challenged with a subcutaneous injection of polyethylene glycol (PEG) to cause isosmotic hypovolemia. However, Long-Evans rats experiencing a similar volume reduction due to water deprivation show hyperosmolality and exhibit a small hypotensive response to d(CH2)5DAVP. Inhibition of the renin-angiotensin system following administration of d(CH2)5DAVP causes a greater hypotension in PEG-treated than in water-deprived Long-Evans rats. In both experimental conditions, the fall in blood pressure is greater than when captopril administration precedes that of d(CH2)5DAVP, indicating that prolonged administration of d(CH2)5DAVP may be interfering with mechanisms other than those mediated by peripheral V1 receptors. However, administration of d(CH2)5DAVP and captopril to water-deprived Long-Evans rats rarely causes the profound hypotension seen in water-deprived Brattleboro rats given captopril alone. In some adrenalectomized Wistar rats, following withdrawal of salt supplementation, the hypotensive response to d(CH2)5DAVP is the greatest seen in any experimental model. These results indicate that AVP is overtly involved in the support of blood pressure in various hypotensive states and, more importantly, may be responsible for the maintenance of a "normal" blood pressure in some conditions. However, the involvement of AVP in cardiovascular regulation in the majority of normotensive conditions is intriguingly subtle.
Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease (2004)

Oncogenic ras alleles are among the most common mutations found in patients with acute myeloid leukemia (AML). Previously, the role of oncogenic ras in cancer was assessed in model systems overexpressing oncogenic ras from heterologous promoters. However, there is increasing evidence that subtle differences in gene dosage and regulation of gene expression from endogenous promoters play critical roles in cancer pathogenesis. We characterized the role of oncogenic K-ras expressed from its endogenous promoter in the hematopoietic system using a conditional allele and IFN-inducible, Cre-mediated recombination. Mice developed a completely penetrant myeloproliferative syndrome characterized by leukocytosis with normal maturation of myeloid lineage cells; myeloid hyperplasia in bone marrow; and extramedullary hematopoiesis in the spleen and liver. Flow cytometry confirmed the myeloproliferative phenotype. Genotypic and Western blot analysis demonstrated Cre-mediated excision and expression, respectively, of the oncogenic K-ras allele. Bone marrow cells formed growth factor–independent colonies in methylcellulose cultures, but the myeloproliferative disease was not transplantable into secondary recipients. Thus, oncogenic K-ras induces a myeloproliferative disorder but not AML, indicating that additional mutations are required for AML development. This model system will be useful for assessing the contribution of cooperating mutations in AML and testing ras inhibitors in vivo.
Estimation of cross‐directional properties: Scanning vs. Stationary Sensors (1995)

Abstract Periodic time‐varying Kalman filter equations for problems involving scanning sensors are solved using “lifting” techniques common for multirate systems. The solution to this problem is used to compare the performance of scanning sensors vs. stationary sensors in the estimation of cross‐directional properties. Furthermore, controller performance is examined when the outputs from the Kalman filter are used as inputs to a state feedback control law. Although adding sensors may significantly enhance the estimates of cross‐directional properties, feedback of these improved estimates may translate to lower levels of improvement in cross‐directional variations.
Engagement of CD44 Promotes Rac Activation and CD44 Cleavage during Tumor Cell Migration (2004)

CD44 is a major cell surface adhesion molecule for hyaluronan, a component of the extracellular matrix, and is implicated in tumor metastasis and invasion. We reported previously that hyaluronan oligosaccharides induce CD44 cleavage from tumor cells. Here we show that engagement of CD44 promotes CD44 cleavage and tumor cell migration, both of which were suppressed by a metalloproteinase inhibitor KB-R7785 and tissue inhibitor of metalloproteinases-1 (TIMP-1) but not by TIMP-2. We also present evidence that blockade of metalloproteinase-disintegrin ADAM10 (a disintegrin and metalloproteinase 10) by RNA interference suppresses CD44 cleavage induced by its ligation. Engagement of CD44 concurrently induced activation of the small GTPase Rac1 and led to drastic changes in cell morphology and actin cytoskeleton with redistribution of CD44 to newly generated membrane ruffling areas. A fluorescence resonance energy transfer approach to visualize GTP-bound Rac1 in living cells revealed the localization of the active Rac1 in the leading edge of the membrane ruffling areas upon ligation of CD44. Taken together, our results indicate that the cleavage of CD44 catalyzed by ADAM10 is augmented by the intracellular signaling elicited by engagement of CD44, through Rac-mediated cytoskeletal rearrangement, and suggest that CD44 cleavage contributes to the migration and invasion of tumor cells.