DOCSLIB.ORG

Targeted Tumour Theranostics in Mice Via Carbon Quantum Dots Structurally Mimicking Large Amino Acids

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Targeted Tumour Theranostics in Mice Via Carbon Quantum Dots Structurally Mimicking Large Amino Acids ARTICLES https://doi.org/10.1038/s41551-020-0540-y Targeted tumour theranostics in mice via carbon quantum dots structurally mimicking large amino acids Shuhua Li1,5, Wen Su 1,5, Hao Wu 1,5, Ting Yuan1, Chang Yuan1, Jun Liu2, Gang Deng2, Xingchun Gao2, Zeming Chen 2, Youmei Bao2, Fanglong Yuan1, Shixin Zhou3, Hongwei Tan1, Yunchao Li1, Xiaohong Li1, Louzhen Fan 1 ✉ , Jia Zhu 1 ✉ , Ann T. Chen4, Fuyao Liu2, Yu Zhou2, Miao Li2, Xingchen Zhai2 and Jiangbing Zhou 2,4 ✉ Strategies for selectively imaging and delivering drugs to tumours typically leverage differentially upregulated surface mol- ecules on cancer cells. Here, we show that intravenously injected carbon quantum dots, functionalized with multiple paired α-carboxyl and amino groups that bind to the large neutral amino acid transporter 1 (which is expressed in most tumours), selectively accumulate in human tumour xenografts in mice and in an orthotopic mouse model of human glioma. The function- alized quantum dots, which structurally mimic large amino acids and can be loaded with aromatic drugs through π–π stack- ing interactions, enabled—in the absence of detectable toxicity—near-infrared fluorescence and photoacoustic imaging of the tumours and a reduction in tumour burden after the targeted delivery of chemotherapeutics to the tumours. The versatility of functionalization and high tumour selectivity of the quantum dots make them broadly suitable for tumour-specific imaging and drug delivery. ancer is one of the most devastating diseases worldwide, with One promising approach to tumour-specific imaging and drug more than 14 million new cases every year. The incidence delivery leverages specific carrier transporters that are differentially of cancer is projected to continue to rise, with an estimated upregulated in cancer cells. Example transporters include large C 1 21.7 million new cases by 2030 (ref. ). In the current clinic, patients neutral amino acid transporter 1 (LAT1), alanine, serine, cysteine- with cancer typically receive a combination of treatments, includ- preferring transporter 2 (ASCT2) and glucose transporters11–14. ing surgical resection, chemotherapy and radiotherapy, which have In particular, LAT1—which mediates the transport of large neu- substantially increased the overall survival and quality of life of the tral amino acids—is promising, as it has been shown to be highly patients. However, the therapeutic effects of these treatments have expressed in a wide variety of tumours. In normal tissue, LAT1 is been greatly limited by their inability to selectively image and deliver expressed in only a few organs, including the placenta, BBB, spleen, therapeutics to tumours2,3. As a result, these treatments are unable testis and colon13. LAT1 has previously been targeted for cancer che- to maximize surgical resection or safely deliver chemotherapeutic motherapy using LAT1 inhibitors, such as 2-aminobicyclo-(2,2,1)- agents and radiotherapy without inducing significant side effects2,3. heptane-2-carboxylic acid (BCH)15. Unfortunately, BCH-mediated To enhance tumour-specific imaging and drug delivery, tar- chemotherapy has largely failed owing to a lack of potency and geted probes can be engineered through the conjugation of ligands specificity. BCH inhibits all four LATs, including LAT1, LAT2, that recognize receptor-like molecules, which are either highly LAT3 and LAT4, each of which has distinct physiological functions. expressed in cancer cells or enriched in the tumour microenviron- Effective inhibition of LAT1 requires high doses of BCH, which ment2. Although promising, this approach is limited4,5 by the rarity often induces significant toxicity15. LAT1 has also been targeted of molecules that are expressed in cancer cells but not in normal to enhance the delivery of chemotherapy drugs to tumours. It was tissues6,7 and, therefore, cargo agents can also accumulate in nor- shown that conjugation of aspartate enabled LAT1-mediated deliv- mal organs. Furthermore, cancers are typically heterogeneous ery, improving the accumulation of doxorubicin (DOX) in tumours across tissues and within tumours and are therefore unlikely to be by threefold to sixfold (ref. 16). successfully targeted using a single ligand6,7. The ligand–receptor Owing to their excellent biocompatibility, optical proper- approach is particularly limited for the imaging of brain tumours ties, drug loading capacity and low toxicity, carbon quantum dots and the delivery of drugs to them owing to the blood–brain barrier (CQDs) have recently emerged as a promising class of imaging (BBB)8–10. A strategy that enables selective imaging of solid tumours agents and drug carriers for various biomedical applications17–19. and the delivery of drugs to them, regardless of tumour origin and However, most of the previously reported CQDs suffer from non- location, is lacking. selective interactions with both tumour cells and normal cells17,18. 1College of Chemistry, Key Laboratories of Theoretical and Computational Photochemistry, and Radiopharmaceuticals, Ministry of Education, Beijing Normal University, Beijing, China. 2Department of Neurosurgery, Yale University, New Haven, CT, USA. 3Department of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. 4Department of Biomedical Engineering, Yale University, New Haven, CT, USA. 5These authors contributed equally: Shuhua Li, Wen Su, Hao Wu. ✉e-mail: [email protected]; [email protected]; [email protected] 704 NatURE BIOMEDIcal ENGINEERING | VOL 4 | July 2020 | 704–716 | www.nature.com/natbiomedeng NATURE BIOMEDICAL ENGINEERING ARTICLES a b HOOC COOH O CH2COOH HOOC HOOCH2C O CH2COOH O NH HN 2 COOH HOOCH2C O NH2 HO OH HO OH N COOH N N HOOCH2C HOOC O CH2COOH NH2 H H H H O N N N COOH H N N HOOCH2C H H H O NH CA HN NH N N N 2 N O N N N N N 0.21 nm –6H O N N N N 180 °C 2 –nH2O N N N N H H H H N N N N N N N N O N –nCO2 N N N N N N N N N HN NH N N N N O N N N N N H N O 2 CH COOH N N H H H H O HOOC 2 N N N H H HOOCH2C COOH H N O 2 CH COOH N N 2 N HO OH HOOC H2N O N O N CH2COOH HOOC NH H H H N O H H HOOCH C O 2 CH2COOH 2 COOH HOOC TAAQ LAAM TC-CQDs c d e 230 nm 4 3 1.0 3 ) (AU) ) (AU) 4 4 2 0 650 nm 0 ×1 ×1 ( 280 nm ( 2 0.2 1 Absorption (AU) 1 Intensity PA signal 0 0 0 200400 600800 1,000 600700 800 900 650700 750 800850 Wavelength (nm) Wavelength (nm) Wavelength (nm) Fig. 1 | Synthesis and characterization of LAAM TC-CQDs. a, Schematic and hypothetical steps (dashed line) of LAAM TC-CQD synthesis. Red dashed circles represent dehydration; purple dashed boxes represent –NH– groups. b, TEM and HRTEM image (inset) of LAAM TC-CQDs. Scale bars, 10 nm and 1 nm (inset). c, Ultraviolet–vis absorption. Inset: appearance of LAAM TC-CQDs under daylight. d, Fluorescence emission spectrum with an excitation wavelength of 600 nm. Inset: appearance of LAAM TC-CQDs under an ultraviolet beam of 365 nm. e, PA signal intensity and imaging (inset) of LAAM TC- CQDs. Measurement was performed at a concentration of 2 μg ml−1 and at an excitation wavelength of 640–850 nm. AU, arbitrary units. Here, we report large amino acid mimicking CQDs (LAAM CQDs) the crystalline G band at 1,605 cm−1 is stronger than the disordered −1 for selective imaging and drug delivery to tumours, regardless of D band at 1,365 cm , with a G-to-D intensity ratio (IG/ID) of 1.4 the origin and location, but not to normal tissue. LAAM CQDs are (Supplementary Fig. 4). An analysis using atomic force microscopy a group of CQDs with paired α-carboxyl and amino groups on their identified that LAAM TC-CQDs have a typical topographic height edge, which trigger multivalent interactions with LAT1. We found of 0.943 nm (Supplementary Fig. 5), suggesting that most of LAAM that LAAM TC-CQDs—a type of LAAM CQDs that were synthe- TC-CQDs consist of 2–3 graphene layers. Analysis of the X-ray sized using 1,4,5,8-tetraminoanthraquinone (TAAQ) and citric acid powder diffraction pattern revealed a broad (002) peak centred at (CA)—are capable of near-infrared (NIR) fluorescence and photo- ~26° (Supplementary Fig. 6), confirming the graphene structure of acoustic (PA) imaging and can also image and deliver chemother- LAAM TC-CQDs. apy drugs to tumours, including tumours in the brain. In contrast We determined the molecular structure of LAAM TC-CQDs. to traditional CQDs, LAAM CQDs have the ability to selectively First, we determined the amount of amino acid groups on the image and deliver therapeutic agents to tumours. This finding may edge of each LAAM TC-CQD using the classical ninhydrin reac- suggest a promising approach to selectively imaging and delivering tion21. After incubation at 60 °C for 10 min, amino acid groups react therapeutic agents to tumours. with ninhydrin, leading to the formation of the purple-coloured product diketohydrindylidene diketohydrindamine, also known Results as Ruhemann’s purple (RP), which has a maximum absorption at Synthesis and characterization of LAAM TC-CQDs. LAAM 570 nm. By measuring the absorption of RP, one can therefore cal- TC-CQDs were synthesized by mixing TAAQ with CA in aque- culate the amount of amino acids. The ninhydrin reaction is unique ous solution, followed by hydrothermal treatment at 180 °C for 2 h in that the production of RP depends on the amount of primary (Fig. 1a). The reactant was purified using silica-gel column chroma- amino acid groups on the edge but not the structure of backbone, tography, resulting in a clear blue solution.
Load more

Recommended publications
  • Real-Time Geopotentiometry with Synchronously Linked Optical Lattice Clocks
    1 Real-time geopotentiometry with synchronously linked optical lattice clocks Tetsushi Takano1,2, Masao Takamoto2,3,4, Ichiro Ushijima2,3,4, Noriaki Ohmae1,2,3, Tomoya Akatsuka2,3,4, Atsushi Yamaguchi2,3,4, Yuki Kuroishi5, Hiroshi Munekane5, Basara Miyahara5 & Hidetoshi Katori1,2,3,4 1Department of Applied Physics, Graduate School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan. 2Innovative Space-Time Project, ERATO, Japan Science and Technology Agency, Bunkyo-ku, Tokyo 113-8656, Japan. 3Quantum Metrology Laboratory, RIKEN, Wako-shi, Saitama 351-0198, Japan. 4RIKEN Center for Advanced Photonics, Wako-shi, Saitama 351-0198, Japan. 5Geospatial Information Authority of Japan, Tsukuba-shi, Ibaraki 305-0811, Japan. According to the Einstein’s theory of relativity, the passage of time changes in a gravitational field1,2. On earth, raising a clock by one centimetre increases its tick rate by 1.1 parts in 1018, enabling optical clocks1,3,4 to perform precision geodesy5. Here, we demonstrate geopotentiometry by determining the height difference of master and slave clocks4 separated by 15 km with uncertainty of 5 cm. The subharmonic of the master clock is delivered through a telecom fibre6 to phase- lock and synchronously interrogate7 the slave clock. This protocol rejects laser noise in the comparison of two clocks, which improves the stability of measuring the gravitational red shift. Such phase-coherently operated clocks facilitate proposals for linking clocks8,9 and interferometers10. Over half a year, 11 2 measurements determine the fractional frequency difference between the two clocks to be 1,652.9(5.9)×10-18, or a height difference of 1,516(5) cm, consistent with an independent measurement by levelling and gravimetry.
    [Show full text]
  • Einstein's Gravitational Field
    Einstein’s gravitational field Abstract: There exists some confusion, as evidenced in the literature, regarding the nature the gravitational field in Einstein’s General Theory of Relativity. It is argued here that this confusion is a result of a change in interpretation of the gravitational field. Einstein identified the existence of gravity with the inertial motion of accelerating bodies (i.e. bodies in free-fall) whereas contemporary physicists identify the existence of gravity with space-time curvature (i.e. tidal forces). The interpretation of gravity as a curvature in space-time is an interpretation Einstein did not agree with. 1 Author: Peter M. Brown e-mail: [email protected] 2 INTRODUCTION Einstein’s General Theory of Relativity (EGR) has been credited as the greatest intellectual achievement of the 20th Century. This accomplishment is reflected in Time Magazine’s December 31, 1999 issue 1, which declares Einstein the Person of the Century. Indeed, Einstein is often taken as the model of genius for his work in relativity. It is widely assumed that, according to Einstein’s general theory of relativity, gravitation is a curvature in space-time. There is a well- accepted definition of space-time curvature. As stated by Thorne 2 space-time curvature and tidal gravity are the same thing expressed in different languages, the former in the language of relativity, the later in the language of Newtonian gravity. However one of the main tenants of general relativity is the Principle of Equivalence: A uniform gravitational field is equivalent to a uniformly accelerating frame of reference. This implies that one can create a uniform gravitational field simply by changing one’s frame of reference from an inertial frame of reference to an accelerating frame, which is rather difficult idea to accept.
    [Show full text]
  • Underwater Survey for Oil and Gas Industry: a Review of Close Range Optical Methods
    remote sensing Review Underwater Survey for Oil and Gas Industry: A Review of Close Range Optical Methods Bertrand Chemisky 1,*, Fabio Menna 2 , Erica Nocerino 1 and Pierre Drap 1 1 LIS UMR 7020, Aix-Marseille Université, CNRS, Université De Toulon, 13397 Marseille, France; [email protected] (E.N.); [email protected] (P.D.) 2 3D Optical Metrology (3DOM) Unit, Bruno Kessler Foundation (FBK), Via Sommarive 18, 38123 Trento, Italy; [email protected] * Correspondence: [email protected] Abstract: In both the industrial and scientific fields, the need for very high-resolution cartographic data is constantly increasing. With the aging of offshore subsea assets, it is very important to plan and maintain the longevity of structures, equipment, and systems. Inspection, maintenance, and repair (IMR) of subsea structures are key components of an overall integrity management system that aims to reduce the risk of failure and extend the life of installations. The acquisition of very detailed data during the inspection phase is a technological challenge, especially since offshore installations are sometimes deployed in extreme conditions (e.g., depth, hydrodynamics, visibility). After a review of high resolution mapping techniques for underwater environment, this article will focus on optical sensors that can satisfy the requirements of the offshore industry by assessing their relevance and degree of maturity. These requirements concern the resolution and accuracy but also cost, ease of implementation, and qualification. With the evolution of embedded computing resources, in-vehicle optical survey solutions are becoming increasingly important in the landscape of large-scale mapping solutions and more and more off-the-shelf systems are now available.
    [Show full text]
  • Just What Did Archimedes Say About Buoyancy?
    Just What Did Archimedes Say About Buoyancy? Erlend H. Graf, SUNY, Stony Brook, NY “A body immersed in a fluid is buoyed What Archimedes Really Said up with a force equal to the weight of Going back to the source,5 Archimedes’ On Float- the displaced fluid.” So goes a venerable ing Bodies, Book I contains a number of statements textbook1 statement of the hydrostatic and proofs that are relevant to the present discussion. principle that bears Archimedes’ name. Archimedes considers three cases separately, namely, Archimedes’ principle is often proved for objects with a density equal to that of the fluid, ob- the special case of a right-circular cylinder jects “lighter” (less dense) than the fluid, and objects or rectangular solid by considering the “heavier” (more dense) than the fluid. difference in hydrostatic forces between He proves the following propositions: the (flat, horizontal) upper and lower sur- faces, and then generalized by the even “Proposition 3. Of solids those which, size for size, are of equal weight with a fluid will, if let down in- more venerable “it can be shown…” that to the fluid, be immersed so that they do not pro- the principle is in fact true for bodies of ject above the surface but do not sink lower. arbitrary shape. “Proposition 4. A solid lighter than a fluid will, if im- mersed in it, not be completely submerged, but rom time to time in this journal,2,3,4 the ques- part of it will project above the surface. tion has arisen as to how to deal with an im- “Proposition 5.
    [Show full text]
  • PRESSURE 68 Kg 136 Kg Pressure: a Normal Force Exerted by a Fluid Per Unit Area
    CLASS Second Unit PRESSURE 68 kg 136 kg Pressure: A normal force exerted by a fluid per unit area 2 Afeet=300cm 0.23 kgf/cm2 0.46 kgf/cm2 P=68/300=0.23 kgf/cm2 The normal stress (or “pressure”) on the feet of a chubby person is much greater than on the feet of a slim person. Some basic pressure 2 gages. • Absolute pressure: The actual pressure at a given position. It is measured relative to absolute vacuum (i.e., absolute zero pressure). • Gage pressure: The difference between the absolute pressure and the local atmospheric pressure. Most pressure-measuring devices are calibrated to read zero in the atmosphere, and so they indicate gage pressure. • Vacuum pressures: Pressures below atmospheric pressure. Throughout this text, the pressure P will denote absolute pressure unless specified otherwise. 3 Other Pressure Measurement Devices • Bourdon tube: Consists of a hollow metal tube bent like a hook whose end is closed and connected to a dial indicator needle. • Pressure transducers: Use various techniques to convert the pressure effect to an electrical effect such as a change in voltage, resistance, or capacitance. • Pressure transducers are smaller and faster, and they can be more sensitive, reliable, and precise than their mechanical counterparts. • Strain-gage pressure transducers: Work by having a diaphragm deflect between two chambers open to the pressure inputs. • Piezoelectric transducers: Also called solid- state pressure transducers, work on the principle that an electric potential is generated in a crystalline substance when it is subjected to mechanical pressure. Various types of Bourdon tubes used to measure pressure.
    [Show full text]
  • A Set of Virtual Experiments of Fluids, Waves, Thermodynamics, Optics, and Modern Physics for Virtual Teaching of Introductory P
    Virtual Experiments Physics III A Set of Virtual Experiments of Fluids, Waves, Thermodynamics, Optics, and Modern Physics for Virtual Teaching of Introductory Physics *Neel Haldolaarachchige Department of Physical Science, Bergen Community College, Paramus, NJ 07652 Kalani Hettiarachchilage Department of Physics, Seton Hall University, South Orange, NJ 07962 January 02, 2020 *Corresponding Author: [email protected] ABSTRACT This is the third series of the lab manuals for virtual teaching of introductory physics classes. This covers fluids, waves, thermodynamics, optics, interference, photoelectric effect, atomic spectra and radiation concepts. A few of these labs can be used within Physics I and a few other labs within Physics II depending on the syllabi of Physics I and II classes. Virtual experiments in this lab manual and our previous Physics I (arXiv.2012.09151) and Physics II (arXiv.2012.13278) lab manuals were designed for 2.45 hrs long lab classes (algebra-based and calculus-based). However, all the virtual labs in these three series can be easily simplified to align with conceptual type or short time physics lab classes as desired. All the virtual experiments were based on open education resource (OER) type simulations. Virtual experiments were designed to simulate in-person physical lab experiments. Student learning outcomes (understand, apply, analyze and evaluate) were studied with detailed lab reports per each experiment and end of the semester written exam which was based on experiments. Special emphasis was given to
    [Show full text]
  • Sea and Space Connections Astronauts Routinely Use Underwater Habitats to Train for Future Space Missions. There Are Ma
    Week 2: Sea and Space Connections Astronauts routinely use underwater habitats to train for future space missions. There are many parallels to living under the water and living in outer space. The most common two are weightlessness and living in an environment with different air pressures. While living in underwater habitats the air pressure is higher than normal, living in space there is almost a complete absence of air pressure or a vacuum, each environments have special considerations for those living there. Astronauts use training in the water to get used to being weightless while they are working. This may seem silly until someone actually tries to do physical work and every time they push against an object, they start floating backwards! The last training mission was performed in Aquarius off the coast of Key Largo, Fl. Below is a picture of the NEEMO XVIII group of astronauts that trained in Aquarius. Let us look at the importance air pressure and what exactly does weightlessness mean. Photo courtesy of NASA NEEMO Exercise 1: Potato Stabbing Materials: -potato -plastic straw (preferably not the bendy straws) If you use a bendy straw cut off the bendy part of the straw First have the students hypothesize what will happen when they stab the potato. Have the students try to stab a hole in the potato with the straw ends open. (The straw should collapse and not penetrate the potato). Now have the students hypothesize what is going to happen if they hold one end of the straw and stab the potato again. This time have the students stab the potato while sealing off the end of the potato with their thumb.
    [Show full text]
  • Marine Litter on the Floor of Deep Submarine Canyons Of
    Progress in Oceanography 134 (2015) 379–403 Contents lists available at ScienceDirect Progress in Oceanography journal homepage: www.elsevier.com/locate/pocean Marine litter on the floor of deep submarine canyons of the Northwestern Mediterranean Sea: The role of hydrodynamic processes ⇑ Xavier Tubau a, Miquel Canals a, , Galderic Lastras a, Xavier Rayo a, Jesus Rivera b, David Amblas a a GRC Geociències Marines, Departament d’Estratigrafia, Paleontologia i Geociències Marines, Facultat de Geologia, Universitat de Barcelona, E-08028 Barcelona, Spain b Instituto Español de Oceanografía (IEO), C/Corazón de María, 8, E-28002 Madrid, Spain article info abstract Article history: Marine litter represents a widespread type of pollution in the World’s Oceans. This study is based on Received 14 November 2014 direct observation of the seafloor by means of Remotely Operated Vehicle (ROV) dives and reports litter Received in revised form 31 March 2015 abundance, type and distribution in three large submarine canyons of the NW Mediterranean Sea, namely Accepted 31 March 2015 Cap de Creus, La Fonera and Blanes canyons. Our ultimate objective is establishing the links between Available online 8 April 2015 active hydrodynamic processes and litter distribution, thus going beyond previous, essentially descriptive studies. Litter was monitored using the Liropus 2000 ROV. Litter items were identified in 24 of the 26 dives car- ried out in the study area, at depths ranging from 140 to 1731 m. Relative abundance of litter objects by type, size and apparent weight, and distribution of litter in relation to depth and canyon environments (i.e. floor and flanks) were analysed.
    [Show full text]
  • 1 What Is a Fluid?
    Physics 106 Lecture 13 Fluid Mechanics SJ 7th Ed.: Chap 14.1 to 14.5 • What is a fluid? • Pressure • Pressure varies with depth • Pascal’s principle • Methods for measuring pressure • Buoyant forces • Archimedes principle • Fluid dyypnamics assumptions • An ideal fluid • Continuity Equation • Bernoulli’s Equation What is a fluid? Solids: strong intermolecular forces definite volume and shape rigid crystal lattices, as if atoms on stiff springs deforms elastically (strain) due to moderate stress (pressure) in any direction Fluids: substances that can “flow” no definite shape molecules are randomly arranged, held by weak cohesive intermolecular forces and by the walls of a container liquids and gases are both fluids Liquids: definite volume but no definite shape often almost incompressible under pressure (from all sides) can not resist tension or shearing (crosswise) stress no long range ordering but near neighbor molecules can be held weakly together Gases: neither volume nor shape are fixed molecules move independently of each other comparatively easy to compress: density depends on temperature and pressure Fluid Statics - fluids at rest (mechanical equilibrium) Fluid Dynamics – fluid flow (continuity, energy conservation) 1 Mass and Density • Density is mass per unit volume at a point: Δm m ρ ≡ or ρ ≡ • scalar V V • units are kg/m3, gm/cm3.. Δ 3 3 • ρwater= 1000 kg/m = 1.0 gm/cm • Volume and density vary with temperature - slightly in liquids • The average molecular spacing in gases is much greater than in liquids. Force & Pressure • The pressure P on a “small” area ΔA is the ratio of the magnitude of the net force to the area ΔF P = or P = F / A ΔA G G PΔA nˆ ΔF = PΔA = PΔAnˆ • Pressure is a scalar while force is a vector • The direction of the force producing a pressure is perpendicular to some area of interest • At a point in a fluid (in mechanical equilibrium) the pressure is the same in h any direction Pressure units: 1 Pascal (Pa) = 1 Newton/m2 (SI) 1 PSI (Pound/sq.
    [Show full text]
  • The Fluid States
    CK-12 Physics Concepts - Intermediate Answer Key Chapter 11: The Fluid States 11.1 Pressure in Fluids Practice Questions 1. Why do the streams of water at the bottom of the bottle go the farthest? 2. Why does water stop flowing out of the top hole even before the water level falls below it? Answers 1. At the bottom of the bottle there is more water pushing down and therefore more pressure coming out of the holes. 2. As the water level falls there isn't as much water pushing down and therefore less pressure to push water out of the holes. Additional Practice Problems: Questions 1. Calculate the pressure produced by a force of 800. N acting on an area of 2.00 m2. 2. A swimming pool of width 9.0 m and length 24.0 m is filled with water to a depth of 3.0 m. Calculate pressure on the bottom of the pool due to the water. 3. What is the pressure on the side wall of the pool at the junction with the bottom of the pool in the previous problem? Answers 퐹 800푁 400푁 1. 푃 = ∶ 푃 = = = 400푃푎 퐴 2푚2 푚2 푘푔 푚 2. Using 퐹 = 푎ℎ푝 ∶ (9.0푚 ∗ 24.0푚) ∗ 3푚 ∗ 1000 ∗ 9.8 = ퟔ. ퟑ × ퟏퟎퟔ 푷풂 푚3 푠2 푘푔 푚 3. Using 푃 = 푝ℎ ∶ 1000 ∗ 9.8 ∗ 3.0푚 = 29400 푃푎 = ퟐ. ퟗퟒ × ퟏퟎퟒ 푷풂 푚3 푠2 1 Review Questions 1. If you push the head of a nail against your skin and then push the point of the same nail against your skin with the same force, the point of the nail may pierce your skin while the head of the nail will not.
    [Show full text]
  • The Effect of Apparent Molecular Weight and Components of Agar on Gel Formation
    Food Sci. Technol. Res., 7 (4), 280–284, 2001 The Effect of Apparent Molecular Weight and Components of Agar on Gel Formation Hisashi SUZUKI,1 Yoshinori SAWAI1 and Mitsuro TAKADA2 1Food Processing Technology Center, Gifu Prefectural Research Institute of Industrial Product Technology, 47, Kitaoyobi, Kasamatsu-cho, Hashima-gun, Gifu 501-6064, Japan 2Gifu Prefectural Institute of Health and Environmental Sciences, 1-1, Naka-fudogaoka, Kakamigahara city, Gifu 504-0838, Japan Received December 11, 2000; Accepted July 10, 2001 The relation between apparent molecular weight and physical properties of agar gel and sol were investigated. Agar was extracted from seven kinds of red seaweed, Gelidium, Pterocladia and Gracilaria, which were collected in dif- ferent seas. The apparent weight-average molecular weight (AMw) and apparent molecular weight distribution of agar were measured by a high temperature type gel permeation chromatograph. Gel strength and melting point of agar gel, and the viscosity of agar sol were measured. The gel strength of agar gel from each seaweed increased with increasing AMw, and it was found that 3,6-anhydro-L-galactose and sulfate group affected gel formation. These results were also suggested by endothermic peaks of differential scanning calorimetry accompanying the gel-to-sol transition. The melting point of agar gel and the viscosity of its sol also increased with increasing AMw. Keywords: agar, gel formation, apparent molecular weight Agar is a polysaccharide which is extracted with hot water weight. In the case of agar, since gelation of aqueous solution from a red seaweed such as Gelidium or Gracilaria species. It usually occurs at about 40 to 50˚C, measurement of the apparent consists of agarose and agaropectin.
    [Show full text]
  • Ornlkdiac-91 Ndp-056 Carbon Dioxide, Hydrographic, and Chemical Data Obtained During the Rn Meteor Cruise 18/1 in the North Atla
    ORNLKDIAC-91 NDP-056 CARBON DIOXIDE, HYDROGRAPHIC, AND CHEMICAL DATA OBTAINED DURING THE RN METEOR CRUISE 18/1 IN THE NORTH ATLANTIC OCEAN (WOCE SECTION AlE, SEPTEMBER 1991) Contributed by Kenneth M. Johnson*, Bernd Schneider**, Lutger Mintrop***,and Douglas W. R. Wallace*, *Brookhaven National Laboratory Upton, New York, U.S.A. **Institut fur Ostseeforschung Rostock-Warnemunde, Germany ***Institutfur Meereskunde Kiel, Germany Prepared by Alexander Kozyr**** Carbon Dioxide Information Analysis Center Oak Ridge National Laboratory Oak Ridge, Tennessee, U.S.A. ****Energy, Environment, and Resources Center The University of Tennessee, Knoxville, Tennessee, U.S.A. Environmental Sciences Division Publication No. 4543 Date Published: July 1996 Prepared for the Global Change Research Program Environmental Sciences Division Office of Health and Environmental Research U.S. Department of Energy Budget Activity Numbers KP 05 02 00 0 and KP 05 05 00 0 Prepared by the Carbon Dioxide Information Analysis Center OAK RIDGE NATIONAL LABORATORY Oak Ridge, Tennessee 37831-6335 managed by M LOCKHEED MARTIN ENERGY RESEARCH CORP. for the U.S. DEPARTMENT OF ENERGY under contract DE-AC05-960R22464 DISCLAIMER This report was prepared as an account of work sponsored by an agency of the United States Government. Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liabiiity or responsibility for the accuracy, completeness, or use- fulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any spe- cific commercial product, process, or service by trade name, trademark, manufac- turer, or otherwise does not necessarily constitute or imply its endorsement, rrcom- mendktion, or favoring by the United States Government or any agency thereof.
    [Show full text]