The impact of visual exploration on judgments of whether a gap is crossable.

When observers look down into a gap in the ground plane, their judgments of the widest gap they can step across (gapmax) decrease as gap depth increases (Y. Jiang & L. S. Mark, 1994). This study investigated the possibility that Jiang and Mark's viewing conditions did not afford observers a sufficient opportunity to perform exploratory movements needed to detect information about gap width. Experiment 1 showed that the gap depth by gaze interaction disappeared only when restrictions were not imposed on observers' exploratory activities (eye, head, and body movements). Experiment 2 showed that observers tended to see the vertical surface as slanted away from them, which made the bottom of the surface appear farther away from them than the top. Only when observers were able to view the gap binocularly under conditions that did not restrict exploratory activity did their slant perception improve and their gapmax judgments no longer covary with gap depth. The data indicate that the exploratory movements of prospective actors are essential for the pickup of information about their action capabilities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serum Collected from Preeclamptic Pregnancies Drives Vasoconstriction of Human Omental Arteries—A Novel Ex Vivo Model of Preeclampsia for Therapeutic Development

New-onset maternal hypertension is a hallmark of preeclampsia, driven by widespread endothelial dysfunction and systemic vasoconstriction. Here, we set out to create a new ex vivo model using preeclamptic serum to cause injury to the endothelium, mimicking vascular dysfunction in preeclampsia and offering the potential to evaluate candidate therapeutic interventions. Human omental arteries were collected at caesarean section from normotensive pregnant patients at term (n = 9). Serum was collected from pregnancies complicated by preterm preeclampsia (birth < 34 weeks’ gestation, n = 16), term preeclampsia (birth > 37 weeks’ gestation, n = 5), and healthy gestation-matched controls (preterm n = 16, term n = 12). Using wire myography, we performed ex vivo whole vessel assessment where human omental arteries were treated with increasing doses of each serum treatment (2–20%) and vasoreactivity was assessed. All pregnant serum treatments successfully drove vasoconstriction; no significant difference was observed in the degree of vasoconstriction when exposed to preeclamptic or control serum. We further demonstrated the ability of esomeprazole (a candidate therapeutic for preeclampsia; 0.1–100 µM) to drive vasorelaxation of pre-constricted vessels (only with serum from preeclamptic patients). In summary, we describe a novel human physiological model of preeclamptic vascular constriction. We demonstrate its exciting potential to screen drugs for their therapeutic potential as treatment for vasoconstriction induced by preeclampsia.     

Loss of Fer Jeopardizes Metabolic Plasticity and Mitochondrial Homeostasis in Lung and Breast Carcinoma Cells

Metabolic plasticity is a hallmark of the ability of metastatic cancer cells to survive under stressful conditions. The intracellular Fer kinase is a selective constituent of the reprogramed mitochondria and metabolic system of cancer cells. In the current work, we deciphered the modulatory roles of Fer in the reprogrammed metabolic systems of metastatic, lung (H358), non-small cell lung cancer (NSCLC), and breast (MDA-MB-231), triple-negative breast cancer (TNBC), carcinoma cells. We show that H358 cells devoid of Fer (H358ΔFer), strictly depend on glucose for their proliferation and growth, and fail to compensate for glucose withdrawal by oxidizing and metabolizing glutamine. Furthermore, glucose deficiency caused increased reactive oxygen species (ROS) production and induction of a DNA damage response (DDR), accompanied by the onset of apoptosis and attenuated cell-cycle progression. Analysis of mitochondrial function revealed impaired respiratory and electron transport chain (ETC) complex 1 (comp. I) activity in the Fer-deficient H358ΔFer cells. This was manifested by decreased levels of NAD⁺ and ATP and relatively low abundance of tricarboxylic acid (TCA) cycle metabolites. Impaired electron transport chain comp. I activity and dependence on glucose were also confirmed in Fer-deficient, MDA-MB-231ΔFer cells. Although both H358ΔFer and MDA-MB-231ΔFer cells showed a decreased aspartate level, this seemed to be compensated by the predominance of pyrimidines synthesis over the urea cycle progression. Notably, absence of Fer significantly impeded the growth of H358ΔFer and MDA-MB-231ΔFer xenografts in mice provided with a carb-deficient, ketogenic diet. Thus, Fer plays a key role in the sustention of metabolic plasticity of malignant cells. In compliance with this notion, targeting Fer attenuates the progression of H358 and MDA-MB-231 tumors, an effect that is potentiated by a glucose-restrictive diet.     

Diosmin Mitigates Cyclophosphamide Induced Premature Ovarian Insufficiency in Rat Model

The current study was designed to investigate the protective role of diosmin against cyclophosphamide-induced premature ovarian insufficiency (POI). Female Swiss albino rats received a single intraperitoneal dose of cyclophosphamide (200 mg/kg) followed by 8 mg/kg/day for the next 15 consecutive days either alone or in combination with oral diosmin at 50 or 100 mg/kg. Histopathological examination of ovarian tissues, hormonal assays for follicle stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH), assessment of the oxidative stress status, as well as measurement of the relative expression of miRNA-145 and its target genes [vascular endothelial growth factor B (VEGF-B) and regulator of cell cycle (RGC32)] were performed. Diosmin treatment ameliorated the levels of E2, AMH, and oxidative stress markers. Additionally, both low and high diosmin doses significantly reduced the histopathological alterations and nearly preserved the normal ovarian reserve. MiRNA-145 expression was upregulated after treatment with diosmin high dose. miRNA-145 target genes were over-expressed after both low and high diosmin administration. Based on our findings, diosmin has a dose-dependent protective effect against cyclophosphamide-induced ovarian toxicity in rats.     

Bioactive peptides with ACE-I and antioxidant activity produced from milk proteolysis

In this study, milk was hydrolyzed using protease (Asperigillus oryzae), trypsin, pepsin, or papain at concentrations of 0.001, 0.005, or 0.01 g/100 g milk for 30 or 60 min to produce angiotensin-converting enzyme inhibitory and antioxidant peptides. Results showed that the proteolysis, antioxidant, and ACE-I activity gradually increased with the increase in the enzyme concentration and hydrolysis time. The protease-treated milk had the highest proteolytic and ACE-I activity, while the papain-treated milk had the lowest. The papain-treated milk exhibited the greatest Fe²⁺ chelating activity. The use of trypsin at concentration of 0.001 g/100 g milk for 60 min produced ACE-I and antioxidant activity without changes in the technological properties of milk.     

Evaluation of carbon-fiber-reinforced thermoplastic matrices in a flat braid process

An investigation was conducted to evaluate the effect of blending thermoplastic filament fibers with carbon filament fibers in varying yarn forms to study the efficiency of matrix wetting and infiltration into a laminate. Poly(etheretherketone) (PEEK) and poly(phenylene sulfide) (PPS) were studied in commingled, DREF, and powder form, as a flat triaxial braid. The as-braided and laminated specimens were both subjected to tensile testing and optical microscopy to establish the efficiency of the impregnation process. It was observed that both thermoplastic matrices commingled with carbon yarn maximized the tensile properties and produced the best quality laminate. To impart the best translational properties of the thermoplastic matrix to the carbon/thermoplastic composite, improvements are necessary in the commingling and powder infiltration processes.     

Pantoprazole Attenuates MAPK (ERK1/2, JNK,p38)–NF-κB and Apoptosis Signaling Pathways after Renal Ischemia/Reperfusion Injury in Rats

Ischemia/reperfusion injury (IRI) in the kidney is the most common cause of acute renal dysfunction through different cell damage mechanisms. This study aimed to investigate, on molecular basics for the first time, the effect of pantoprazole on renal IRI in rats. Different biochemical parameters and oxidative stress markers were assessed. ELISA was used to estimate proinflammatory cytokines. qRT-PCR and western blot were used to investigate the gene and protein expression. Renal histopathological examination was also performed. IRI resulted in tissue damage, elevation of serum levels of creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, IL-1β, up-regulation of NF-κB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it up-regulated the expression of the Bax gene and down-regulated the expression of the Bcl-2 gene. Treatment of the injured rats with pantoprazole, either single dose or multiple doses, significantly alleviated IRI-induced biochemical and histopathological changes, attenuated the levels of proinflammatory cytokines, down-regulated the expression of NF-κB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins, and the Bax gene, and up-regulated Bcl-2 gene expression. Moreover, treatment with pantoprazole multiple doses has an ameliorative effect that is greater than pantoprazole single-dose. In conclusion, pantoprazole diminished renal IRI via suppression of apoptosis, attenuation of the pro-inflammatory cytokines’ levels, and inhibition of the intracellular signaling pathway MAPK (ERK1/2, JNK, p38)–NF-κB.     

Modulation of Mesenchymal Stem Cells for Enhanced Therapeutic Utility in Ischemic Vascular Diseases

Mesenchymal stem cells are multipotent stem cells isolated from various tissue sources, including but not limited to bone marrow, adipose, umbilical cord, and Wharton Jelly. Although cell-mediated mechanisms have been reported, the therapeutic effect of MSCs is now recognized to be primarily mediated via paracrine effects through the secretion of bioactive molecules, known as the “secretome”. The regenerative benefit of the secretome has been attributed to trophic factors and cytokines that play neuroprotective, anti-angiogenic/pro-angiogenic, anti-inflammatory, and immune-modulatory roles. The advancement of autologous MSCs therapy can be hindered when introduced back into a hostile/disease environment. Barriers include impaired endogenous MSCs function, limited post-transplantation cell viability, and altered immune-modulatory efficiency. Although secretome-based therapeutics have gained popularity, many translational hurdles, including the heterogeneity of MSCs, limited proliferation potential, and the complex nature of the secretome, have impeded the progress. This review will discuss the experimental and clinical impact of restoring the functional capabilities of MSCs prior to transplantation and the progress in secretome therapies involving extracellular vesicles. Modulation and utilization of MSCs–secretome are most likely to serve as an effective strategy for promoting their ultimate success as therapeutic modulators.     

Incorporating domain knowledge into attribute‐oriented data mining

It is frequently the case that data mining is carried out in an environment which contains noisy and missing data. This is particularly likely to be true when the data were originally collected for different purposes, as is commonly the case in data warehousing. In this paper we discuss the use of domain knowledge, e.g., integrity constraints or a concept hierarchy, to re‐engineer the database and allocate sets to which missing or unacceptable outlying data may belong. Attribute‐oriented knowledge discovery has proved to be a powerful approach for mining multi‐level data in large databases. Such methods are set‐oriented in that attribute values are considered to belong to subsets of the domain. These subsets may be provided directly by the database or derived from a knowledge base using inductive logic programming to re‐engineer the database. In this paper we develop an algorithm which allows us to aggregate imprecise data and use it for multi‐level rule induction and knowledge discovery. ©2000 John Wiley & Sons, Inc.