Modeling microscopic environments for virtual reality

Abstract. Multiple physics phenomena and how they behave when the environment is 1000 times smaller on each axis were researched, and a simulation of such an environment was implemented within Unity, running in virtual reality in realtime. In biggest focus is drag, which resists objects’ movement through air or other matters. The results show that drag is much more significant in smaller scale and the calculation are required to be more complex than in normal scale in order to be accurate. A numerical solution was implemented to calculate the motion of a flying sphere that is affected by drag, and its drag coefficient affected by its current Reynolds number. Although an analytical solution for this scenario could not be found, the numerical solution was validated using a simplified scenario, where an object falls with a constant drag coefficient. The numerical solution was compared to an analytical solution in this scenario, and the numerical implementation was found to be sufficiently accurate. As gravity is constant regardless of scale, objects appear to fall very quickly in small scale. Therefore, a system was created to scale the passing of time such that the perceived speed of motion is the same regardless of scale, which allows the user to act naturally in this scaled down environment. This also allows us to experience the difference in the drag force first-hand. Other explored topics include visuals of the environment, surface tension and adhesive forces among other things. Of these other topics, surface tension was also implemented for the scenario of a sphere attempting to break through a flat water surface. Unity was found to be suitable for these tasks through bypassing the built-in physics and controlling the objects’ movement through a custom script. Although some phenomena were implemented successfully, it was also found that a complete simulation of all relevant phenomena could be a large undertaking. However, there remain other aspects worth exploring related to small-scale in order to reach a better understanding of it.Mikroskooppisten ympäristöjen mallinnus virtuaalitodellisuuteen. Tiivistelmä. Useita fysiikan ilmiöitä, ja miten ne käyttäytyvät, kun ympäristö on 1000 kertaa pienempi jokaisella akselilla tutkittiin, ja simulaatio sellaisesta ympäristöstä toteutettiin, joka pyörii virtuaalitodellisuudessa reaaliajassa. Huomion keskipisteenä on ilmanvastus, joka vastustaa esineiden liikettä ilman tai muun aineen läpi. Tulokset osoittavat, että ilmanvastus on paljon merkittävämpi pienessä mittakaavassa, ja sen laskelmat vaativat monimutkaisempia laskelmia kuin tavallisessa mittakaavassa ollakseen tarkkoja. Numeerinen ratkaisu toteutettiin laskemaan lentävän esineen liikkeen, johon vaikuttaa ilmanvastus, ja sen ilmanvastuskerroin perustuu esineen sen hetkiseen Reynolds numeroon. Vaikkakin analyyttistä ratkaisua tällä tilanteelle ei löytynyt, numeerisen ratkaisun pätevyys perusteltiin käyttäen yksinkertaistettua tilannetta, jossa esine putoaa vakio ilmanvastuskertoimella. Numeerista ratkaisua verrattiin analyyttiseen ratkaisuun tässä tilanteessa, ja numeerisen ratkaisun todettiin olevan riittävän tarkka. Koska painovoima on vakio riippumatta mittakaavasta, esineet vaikuttavat putoavan hyvin nopeasti pienessä mittakaavassa. Siitä syystä luotiin systeemi, joka muuttaa ajankulun nopeutta niin, että havaittu esineiden liikkeen nopeus on same riippumatta mittakaavasta, mikä sallii käyttäjän toimivan luonnollisesti tässä kutistetussa ympäristössä. Tämä myöskin mahdollistaa saamaan ensikäden kokemuksen erosta ilmanvastuksessa. Muita tutkittuja aiheita ovat ympäristön ulkonäkö, pintajännitys, adheesio ja muita aiheita. Näistä aiheista pintajännitys toteutettiin siinä tilanteessa, kun pallo pyrkii läpäisemään tasaisen veden pinnan. Unity todettiin olevan sopiva näihin tehtäviin ohittamalla sen sisäänrakennetun fysiikka toteutuksen ja ohjaamalla esineiden liikettä erillisen skriptin avulla. Joskin joitain ilmiöitä toteutettiin onnistuneesti, oli myös huomattavissa, että täysvaltainen jokaisen olennaisen ilmiön simulaatio voisi olla suuri urakka. Kuitenkin, pieneen mittakaavaan liittyviä ilmiöitä olisi kannattavaa tutkia lisää, jotta saisimme kokonaisemma kuvan siitä

Taxonomic corrections and new records in vascular plants of Kyrgyzstan

A series of notes on distribution, taxonomy and nomenclature of some vascular plants in Kyrgyzstan is presented. Two new hybrids (Delphinium × pskemense Sennikov & Lazkov, Perovskia × intermedia Lazkov) are described. The variety Rhinactinidia limoniifolia var. brachyglossa Lazkov & Sennikov and forma Rubus praecox Bertol. f. rutiliflorus H.E.Weber & Sennikov are described for unusual morphotypes of these species. Five transfers from Pyrethrum to Richteria (R. brachanthemoides (Kamelin & Lazkov) Sennikov, R. neglecta (Tzvelev) Sennikov, R. sovetkinae (Kovalevsk.) Sennikov, R. sussamyrensis (Lazkov) Sennikov, R. sect. Trichanthemopsis (Tzvelev) Sennikov) are proposed in conformity with the phylogeny of Anthemideae. Nomenclature is discussed and lectotype is designated for Achillea biebersteinii Afan. Three transfers (Arctium nidulans (Regel) Sennikov, A. sect. Plagiocephalum (Rupr.) Sennikov, Harmsiella olgae (Regel) Sennikov) are proposed because of priority under the current phylogeny of Asteraceae and Lamiaceae. Ten native species (Centaurea chartolepis Greuter, Cousinia hamadae Juz., Hypopitys hypophegea (Wallr.) G.Don, Lemna turionifera Landolt, Lycopus exaltatus L. f., Portulaca granulatostellulata (Poelln.) C.Ricceri & P.V.Arrigoni, P. nitida (Danin & H.G.Baker) C.Ricceri & P.V.Arrigoni, Ranunculus acris L., Rubia laevissima Tschern., Zygophyllum miniatum Cham.) and two aliens (Calystegia spectabilis (Brummitt) Tzvelev, Rubus praecox Bertol.) are new to Kyrgyzstan. Ten species are new to certain mointain ranges. The presence of Sorbus turkestanica (Franch.) Hedl. in Kyrgyzstan is confirmed; this species and S. persica Hedl. are mapped anew for conservation purposes. Otostegia nikitinae Scharasch. and O. schennikovii Scharasch. are synonyms of Harmsiella olgae and therefore need no protection in Kyrgyzstan

Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2

The mammalian target of rapamycin (mTOR) regulates cell growth and survival by integrating nutrient and hormonal signals. These signaling functions are distributed between at least two distinct mTOR protein complexes: mTORC1 and mTORC2. mTORC1 is sensitive to the selective inhibitor rapamycin and activated by growth factor stimulation via the canonical phosphoinositide 3-kinase (PI3K)→Akt→mTOR pathway. Activated mTORC1 kinase up-regulates protein synthesis by phosphorylating key regulators of mRNA translation. By contrast, mTORC2 is resistant to rapamycin. Genetic studies have suggested that mTORC2 may phosphorylate Akt at S473, one of two phosphorylation sites required for Akt activation; this has been controversial, in part because RNA interference and gene knockouts produce distinct Akt phospho-isoforms. The central role of mTOR in controlling key cellular growth and survival pathways has sparked interest in discovering mTOR inhibitors that bind to the ATP site and therefore target both mTORC2 and mTORC1. We investigated mTOR signaling in cells and animals with two novel and specific mTOR kinase domain inhibitors (TORKinibs). Unlike rapamycin, these TORKinibs (PP242 and PP30) inhibit mTORC2, and we use them to show that pharmacological inhibition of mTOR blocks the phosphorylation of Akt at S473 and prevents its full activation. Furthermore, we show that TORKinibs inhibit proliferation of primary cells more completely than rapamycin. Surprisingly, we find that mTORC2 is not the basis for this enhanced activity, and we show that the TORKinib PP242 is a more effective mTORC1 inhibitor than rapamycin. Importantly, at the molecular level, PP242 inhibits cap-dependent translation under conditions in which rapamycin has no effect. Our findings identify new functional features of mTORC1 that are resistant to rapamycin but are effectively targeted by TORKinibs. These potent new pharmacological agents complement rapamycin in the study of mTOR and its role in normal physiology and human disease

Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrinCD11c/CD18 : characterization of the binding sites on ICAM-4

Intercellular adhesion molecule-4 (ICAM-4) is a unique member of the ICAM family due to its specific expression on erythroid cells and ability to interact with several types of integrins expressed on blood and endothelial cells. The first reported receptors for ICAM-4 were CD11a/CD18 and CD11b/CD18. In contrast to these two, the cellular ligands and the functional role of the third beta2-integrin, CD11c/CD18, have not been well defined. Here we show that ICAM-4 functions as a ligand for the monocyte/macrophage specific CD11c/CD18. Deletion of the individual immunoglobulin domains of ICAM-4 demonstrated that both its domains contain binding sites for CD11c/CD18. Analysis of a panel of ICAM-4 point mutants identified residues that affected binding to the integrin. By molecular modeling the important residues were predicted to cluster in two distinct but spatially close regions of the first domain with an extension to the second domain spatially distant from the other residues. We also identified two peptides derived from sequences of ICAM-4 that are capable of modulating the binding to CD11c/CD18. CD11c/CD18 is expressed on macrophages in spleen and bone marrow. Inhibition of erythrophagocytosis by anti-ICAM-4 and anti-integrin antibodies suggests a role for these interactions in removal of senescent red cells

The Clinical Frailty Scale is a useful tool for predicting postoperative complications following elective colon cancer surgery at the age of 80 years and above: A prospective, multicentre observational study

Aim Identification of the risks of postoperative complications may be challenging in older patients with heterogeneous physical and cognitive status. The aim of this multicentre, observational study was to identify variables that affect the outcomes of colon cancer surgery and, especially, to find tools to quantify the risks related to surgery. Method Patients aged >= 80 years with electively operated Stage I-III colon cancer were recruited. The prospectively collected data included comorbidities, results of the onco-geriatric screening tool (G8), Clinical Frailty Scale (CFS), Charlson Comorbidity Index (CCI) and Mini Nutritional Assessment-Short Form (MNA-SF), and operative and postoperative outcomes. Results A total of 161 patients (mean 84.5 years, range 80-97, 60% female) were included. History of cerebral stroke (64% vs. 37%, p = 0.02), albumin level 31-34 g/l compared with >= 35 g/l (57% vs. 32%, p = 0.007), CFS 3-4 and 5-9 compared with CFS 1-2 (49% and 47% vs. 16%, respectively) and American Society of Anesthesiologists score >3 (77% vs. 28%, P = 0.006) were related to a higher risk of complications. In multivariate logistic regression analysis CFS >= 3 (OR 6.06, 95% CI 1.88-19.5, p = 0.003) and albumin level 31-34 g/l (OR 3.88, 1.61-9.38, p = 0.003) were significantly associated with postoperative complications. Severe complications were more common in patients with chronic obstructive pulmonary disease (43% vs. 13%, p = 0.047), renal failure (25% vs. 12%, p = 0.021), albumin level 31-34 g/l (26% vs. 8%, p = 0.014) and CCI >6 (23% vs. 10%, p = 0.034). Conclusion Surgery on physically and cognitively fit aged colon cancer patients with CFS 1-2 can lead to excellent operative outcomes similar to those of younger patients. The CFS could be a useful screening tool for predicting postoperative complications.Peer reviewe

Plasma osteopontin concentrations in preeclampsia - is there an association with endothelial injury?

Background: It has been previously reported that plasma osteopontin (OPN) concentrations are increased in cardiovascular disorders. The goal of the present study was to determine plasma OPN concentrations in healthy pregnant women and preeclamptic patients, and to investigate their relationship to the clinical characteristics of the study subjects and to markers of inflammation [C-reactive protein (CRP)], endothelial activation [von Willebrand factor antigen (VWF: Ag)] or endothelial injury (fibronectin), oxidative stress [malondialdehyde (MDA)] and trophoblast debris (cell-free fetal DNA). Methods: Forty-four patients with preeclampsia and 44 healthy pregnant women matched for age and gestational age were involved in this case-control study. Plasma OPN concentrations were measured with ELISA. Serum CRP concentrations were determined with an autoanalyzer using the manufacturer's reagents. Plasma VWF: Ag was quantified by ELISA, while plasma fibronectin concentrations were measured by nephelometry. Plasma MDA concentrations were estimated by the thiobarbituric acid-based colorimetric assay. The amount of cell-free fetal DNA in maternal plasma was determined by quantitative real-time PCR analysis of the sex-determining region Y (SRY) gene. For statistical analyses, non-parametric methods were applied. Results: Serum levels of CRP, as well as plasma concentrations of VWF: Ag, fibronectin, MDA and cell-free fetal DNA were significantly higher in preeclamptic patients than in healthy pregnant women. There was no significant difference in plasma OPN concentrations between controls and the preeclamptic group. However, preeclamptic patients with plasma fibronectin concentrations in the upper quartile had significantly higher plasma OPN concentrations than those below the 75th percentile, as well as healthy pregnant women [median (interquartile range): 9.38 (8.10-11.99) vs. 7.54 (6.31-9.40) and 7.40 (6.51-8.80) ng/mL, respectively, p < 0.05 for both]. Furthermore, in preeclamptic patients, plasma OPN concentrations showed a significant positive linear association with plasma fibronectin (Spearman R = 0.38, standardized regression coefficient (beta) = 0.41, p < 0.05 for both). Conclusions: Plasma OPN concentrations are increased in preeclamptic patients with extensive endothelial injury. However, further studies are warranted to explore the relationship between OPN and endothelial damage. Clin Chem Lab Med 2010;48: 181-7

Dysfunction of complement receptors CR3 (CD11b/18) and CR4 (CD11c/18) in pre-eclampsia : a genetic and functional study

Objective To study genetic variants and their function within genes coding for complement receptors in pre-eclampsia. Design A case-control study. Setting Pre-eclampsia is a common vascular disease of pregnancy. The clearance of placenta-derived material is one of the functions of the complement system in pregnancy. Population We genotyped 500 women with pre-eclamptic pregnancies and 190 pregnant women without pre-eclampsia, as controls, from the FINNPEC cohort, and 122 women with pre-eclamptic pregnancies and 1905 controls from the national FINRISK cohort. Methods The functional consequences of genotypes discovered by targeted exomic sequencing were explored by analysing the binding of the main ligand iC3b to mutated CR3 or CR4, which were transiently expressed on the surface of COS-1 cells. Main outcome measures Allele frequencies were compared between pre-eclamptic pregnancies and controls in genetic studies. The functional consequences of selected variants were measured by binding assays. Results The most significantly pre-eclampsia-linked CR3 variant M441K (P = 4.27E-4, OR = 1.401, 95% CI = 1.167-1.682) displayed a trend of increased adhesion to iC3b (P = 0.051). The CR4 variant A251T was found to enhance the adhesion of CR4 to iC3b, whereas W48R resulted in a decrease of the binding of CR4 to iC3b. Conclusions Results suggest that changes in complement-facilitated phagocytosis are associated with pre-eclampsia. Further studies are needed to ascertain whether aberrant CR3 and CR4 activity leads to altered pro- and anti-inflammatory cytokine responses in individuals carrying the associated variants, and the role of these receptors in pre-eclampsia pathogenesis. Tweetable abstract Genetic variants of complement receptors CR3 and CR4 have functional consequences that are associated with pre-eclampsia.Peer reviewe

Unique Exercise Lactate Profile in Muscle phosphofructokinase Deficiency (Tarui Disease); Difference Compared with McArdle Disease

Introduction: Glycogen storage disease V (GSDV, McArdle disease) and GSDVII (Tarui disease) are the most common of the rare disorders of glycogen metabolism. Both are associated with low lactate levels on exercise. Our aim was to find out whether lactate response associated with exercise testing could distinguish between these disorders. Methods: Two siblings with Tarui disease, two patients with McArdle disease and eight healthy controls were tested on spiroergometric exercise tests with follow-up of venous lactate and ammonia. Results: A late increase of lactate about three times the basal level was seen 10-30 min after exercise in patients with Tarui disease being higher than in McArdle disease and lower than in the controls. Ammonia was increased in Tarui disease. Discussion: Our results suggest that follow-up of lactate associated with exercise testing can be utilized in diagnostics to distinguish between different GSD diseases.Peer reviewe

One-year functional outcomes of patients aged 80 years or more undergoing colonic cancer surgery: prospective, multicentre observational study

Background: Older patients are at high risk of experiencing delayed functional recovery after surgical treatment. This study aimed to identify factors that predict changes in the level of support for activities of daily living and mobility 1 year after colonic cancer surgery.Methods: This was a multicentre, observational study conforming to STROBE guidelines. The prospective data included pre-and postoperative mobility and need for support in daily activities, co-morbidities, onco-geriatric screening tool (G8), clinical frailty scale (CFS), operative data, and postoperative surgical outcomes.Results: A total of 167 patients aged 80 years or more with colonic cancer were recruited. After surgery, 30 per cent and 22 per cent of all patients had increased need for support and decreased motility. Multivariableanalysis with all patients demonstrated that preoperative support in daily activities outside the home (OR 3.23, 95 per cent c.i. 1.06 to 9.80, P = 0.039) was associated with an increased support at follow-up. A history of cognitive impairment (3.15, 1.06 to 9.34, P = 0.038) haemoglobin less than 120 g/l (7.48, 1.97 to 28.4, P = 0.003) and discharge to other medical facilities (4.72, 1.39 to 16.0, P = 0.013) were independently associated with declined mobility. With functionally independent patients, haemoglobin less than 120 g/l (8.31, 1.76 to 39.2, P = 0.008) and discharge to other medical facilities (4.38, 1.20 to 16.0, P = 0.026) were associated with declined mobility.Conclusion: Increased need for support before surgery, cognitive impairment, preoperative anaemia, and discharge to other medical facilities predicts an increased need for support or declined mobility 1 year after colonic cancer surgery. Preoperative assessment and optimization should focus on anaemia correction, nutritional status, and mobility with detailed rehabilitation plan.Greater increased need for support before surgery, cognitive impairment, preoperative anaemia, and discharge to other medical facilities predicted an increased need for support or declined mobility 1 year after colonic cancer surgery. Preoperative assessment and optimization should especially focus on anaemia correction, nutritional status, and mobility with a detailed rehabilitation plan.</p