text:
|Número de publicación||US5503770 A|
|Tipo de publicación||Concesión|
|Número de solicitud||US 08/336,236|
|Fecha de publicación||2 Abr 1996|
|Fecha de presentación||7 Nov 1994|
|Fecha de prioridad||7 Nov 1993|
|También publicado como||DE4439783A1, DE4439783C2|
|Número de publicación||08336236, 336236, US 5503770 A, US 5503770A, US-A-5503770, US5503770 A, US5503770A|
|Inventores||Tony James, Saman Sandanayake, Seiji Shinkai|
|Cesionario original||Research Development Corporation Of Japan|
|Exportar cita||BiBTeX, EndNote, RefMan|
|Citas de patentes (1), Otras citas (4), Citada por (118), Clasificaciones (12), Eventos legales (4)|
|Enlaces externos: USPTO, Cesión de USPTO, Espacenet|
The present invention relates to a novel fluorescent compound, and particularly, to a fluorescent compound suitable for use in the detection of saccharides or sugars such as glucose, and to saccharide-detection with such fluorescent compound.
Saccharides or sugars are organic compounds indispensable to living organisms and play important roles in information transmission, energy metabolism and structure formation in such organisms. For example, glucose, more particularly, D-glucose, is crucial as an energy source for a variety of cells in constructing various organs. Glucose is stored in the liver as glycogen, which is released in body fluids as needed for energy consumption. The production and the consumption of glucose are well balanced in the body fluids of a normal or healthy human being, maintaining the glucose concentration in the fluids constant. Thus, the detection of glucose in the blood or the urine provides valuable information for the diagnosis of such diseases as diabetes and adrenal insufficiency.
Glucose sensor using an enzyme is the best known practical measure for detecting saccharides. This technique includes decomposing glucose with the enzyme (glucose oxydase), and measuring the amount of hydrogen peroxide produced by the decomposition through an appropriate means (such as by an electrode). While this method is an established one, the enzyme, which originates from a living body, will irreversibly change in quality as time elapses and cannot be recycled for repeated use. The sample cannot be provided for other purposes of measurement as the glucose has already been decomposed. In addition, the conventional sensor is directed to the detection of the sugar only in an in vitro sample, i.e. a sample taken out of the living body. If it should be possible to detect saccharides at sites inside the living body, there would be obtained much information very useful for the diagnosis and treatment of diseases and the development of medicines. However, the current saccharide sensor is far from meeting such expectations.
The present invention provides a novel fluorescent compound which, among various possible uses, is particularly suitable for use in the detection of saccharides. Thus, according to the present invention, there is provided a compound which is capable of emitting fluorescence by combining with saccharides, said compound having a molecular structure comprising a fluorophore, at least one phenylboronic acid moiety, and at least one amine-providing nitrogen atom where the nitrogen atom is disposed in the vicinity of the phenylboronic acid moiety so as to interact intermolecularly with the boronic acid.
A typical compound falling within such structure defined by the present invention can be expressed by the following general formula (1): ##STR1##
In the above formula (1), F represents a fluorophore. Examples of the fluorophore include a number of atomic groups or functional groups containing π-electron systems. Preferred fluorophores include naphtyl, anthryl, pyrenyl and phenanthryl, which can be expressed by the following structural formulas (2), (3), (4) and (5), respectively. ##STR2##
The fluorophore-forming atomic or functional groups can be substituted ones as long as the substituent(s) do not adversely affect the fluorescence. For example, the substitution with sulfonic acid group(s) is preferable, particularly when the compound is to be dissolved in an aqueous fluid for the detection of saccharides contained therein, as it imparts the compound with water-solubility. The most preferred fluorophore is examplified by anthryl.
In the formula (1), R, combined with the nitrogen atom, denotes a lower aliphatic or aromatic functional group. In general R is an alkyl group having 1 to 4 carbon atoms, i.e. methyl, ethyl, propyl or butyl, or phenyl group.
In the formula (1), m is 0, 1 or 2. Thus the nitrogen atom in the compound of the present invention is disposed in the vicinity of the boronic acid moiety and the nitrogen atom is combined, through methylene group or ethylene group or directly, at the ortho position of the phenylboronic acid. Preferably m is i and thus the nitrogen is combined with the phenyl group through a methylene group.
In the formula (1), n is also 0, 1 or 2 where n+m is an integer of 2 or 3. Thus the nitrogen atom and the boronic acid are positioned not so far from the fluorophore. Preferably n is 1.
The phenyl group composing the phenylboronic acid may be substituted with an appropriate substituent or substituents as long as such substitution does not adversely affect the fluorescence. Examples of substituents are methyl, ethyl, propyl, butyl, phenyl, methoxy, ethoxy, butoxy and phenoxy groups.
The compound of the present invention as expressed by the formula (1) contains a fluorophore in its molecular structure but does not emit fluorescence in the absence of saccharides. It is understood this is because the fluorescence of the fluorophore is quenched by the unshared electron pair of the nitrogen atom: The electron of the nitrogen occupies the lowest excited singlet energy state of the fluorophore so as to supress the fluorescence. However, the compound of the present invention emits fluorescence of a high intensity, upon binding to saccharides. This phenomena can be accounted for as follows: The presence of saccharides produces a bond between the nitrogen atom(N) and the boron atom(B) to form a strong complex of the saccharide with the phenylboronic acid compound of the present invention, where the electron deficient boron atom has bound to the electron rich nitrogen. Thus, the unshared electron pair of the nitrogen atom will be utilized for bonding with the boron atom and will not contribute to the fluorescence-quenching electrogen transfer process, thereby expressing the intrinsic fluorescence of the compound.
A typical compound falling within the formula (1) of the present invention is the following compound of the formula (6), where F (the fluorphore) is anthryl, R is methyl and each of n and m is 1. ##STR3##
This compound features fluorescence of a highly increased intensity in the presence of monosaccharides, such as D-glucose and D-fructose. Thus, the compound is suitable for use in the detection of monosaccharides in general or even a specific monosaccharide. In the detection of a specific monosaccharide from a sample which may contain plural monosaccharides, the sample is generally subject to a pretreatment (e.g. a chromatography) for the separation of the monosaccharides, followed by the detection with the fluorescent compound of the present invention.
The detection with the fluorescent compound of the present invention is performed by adding the compound to the sample and by a photoscopic method, determining the increased intensity of the fluorescence due to the binding of the compound with the saccharide. Alternatively, the detection with the fluorescent compound of the present invention may be conducted by a chromatographic method where the compound of the present invention is supported on a supporting material through which the saccharide-containing sample is passed for the detection based on the increased fluorescent intensity due to the complex of the compound and the saccharide.
In accordance with the concept of the present invention there can also be provided a compound which may selectively bind to a specific saccharide thereby producing a highly increased fluorescence. In particular the present invention provides a fluorescent compound having the following general formula (7): ##STR4##
In the above formula, n and m each denote 0, 1 or 2 with n+m being 2 or 3, F represents a fluorophore and R represents a lower aliphatic or aromatic functional group.
The compound of the formula (7) is characterized by its selective binding to glucose resulting in a strong fluorescence. The compound is therefore suitable for use in the detection of glucose.
In the formula (7), n and m each denote an integer, with n+m being 2 or 3. Either of n and m may be zero; thus n and m each denote 0, 1, 2 or 3. Preferably n+m is 2 where each of n and m is 0, 1 or 2, with both of n and m most preferably being 1. Such specific length of the methylene(CH2) moiety of the compound of the present invention expressed by the formula (7) provides a molecular structure adapted to bind to glucose through the two boronic acid moieties of the compound.
In the formula (7), the fluorophores are exemplified by a number of atomic groups or functional groups containing π-electron systems. As preferred fluorophores are included naphthyl, anthryl, pyrenyl and phenanthryl, which can be expressed by the aforesaid structural formulas (2), (3), (4) and (5), respectively.
The fluorophore-forming atomic or functional groups can be substituted ones as long as the substituent(s) will not adversely affect the fluorescence. For example, the substitution with sulfonic acid group(s) is preferable as it imparts the compound with water-solubility. The most preferred fluorophore is exemplified by anthryl.
In the formula (7), R, combined with the nitrogen atom, denotes a lower aliphatic or aromatic functional group. In general R is an alkyl group having i to 4 carbon atoms, i.e. methyl, ethyl, propyl or butyl, or phenyl group.
Preferred compounds of the present invention failing within the formula (7) are exemplified by the following compounds (8), (9), (10) and (11), of which the compound (8) is particularly preferable. ##STR5##
Surprisingly the compounds of the present invention, as typified by the compound (8), emit a strong fluorescence particularly in the presence of glucose in an aqueous solution of a concentration corresponding to those found in human body fluids(50-250mg/l or 0.0005M-0.0001M) and with a pH value of neutrality or near neutrality. Such strong fluorescence intensity does not change even in the coexistence with other saccharides such as galactose or fructose.
The emission of the strong fluorescence by the compound (7) of the invention in the presence of glucose can be construed as follows: The two boronic acid moieties as arranged in the structure of the formula (7) are suitable to bind covalently to the four hydroxyl groups (OH groups) at the 1, 2, 4 and 6 positions of glucose, thereby forming a stable 1:1 complex of the compound with glucose, in which the quenching by the nitrogen atom is assuredly prevented.
By contrast, other saccharides--such as fructose--may possibly bind only to one of the two boronic acid moieties, in which case there is observed only very weak fluorescence. In fact no substantial fluorescence can be observed by such saccharides as fructose or galactose in their concentrations as occurring in the human body fluids.
Thus, the compound of the present invention as typified by the formula (8) can emit a strong fluorescence specifically with glucose, due to the specific arrangement of the fluorophore, the two boronic acid moieties and the nitrogen atom, and therefore, is suitable for use in the detection of glucose. When the detection is made with a solution, the binding between glucose and the fluorescent compound can easily be cleaved by changing the pH of the solution through an appropriate acid, thereby restoring the glucose.
In general, the compound of the present invention can be prepared by allowing a phenylboronic acid having the ortho-position alkylhalogenated to react with a reagent composed of alkylaminomethyl group(s) bound to a fluorophore, in the present of a base under an appropriate solvent.
Through the application of the present invention saccharides such as glucose can be detected with very stable synthetic compound, in contrast to the conventional enzymatic method in which a rather unstable enzyme must be utilized for the detection of in glucose. Moreover, conducting the saccharide detection method with the compound of the present invention, a sample can be measured intact, i.e. without being decomposed as in the enzymatic method, and the sample can therefore be subjected to a further measurement or treatment.
The use of the compound of the present invention makes it possible to detect saccharide(s) by a spectroscopic means, without decomposing the saccharides. Thus, the technology has good prospects of developing into one in which the detection can be made in situ with respect to a specific region of an organ in the body. For example, by utilizing an optical fiber having the compound of the present invention coated on the tip thereof, the information on saccharide inside the body can be continuously monitored so as to provide useful clinical data.
FIG. 1 is a scheme illustrating the synthesis of a fluorescent compound of the present invention.
FIG. 2 demonstrates fluorescence intensities of the compound of the invention in the presence of monosaccharides.
FIG. 3 is a scheme illustrating the synthesis of another fluorescent compound of the present invention.
FIG. 4 demonstrates fluorescence intensities of the compound of the present invention in the presence of glucose and other monosaccharides.
It is noted that, in some of the chemical structural formulae given here, carbon atoms and hydrogen atoms as in methyl or methylene groups are omitted as conventionally done.
The invention is illustrated by the following examples for further understanding thereof.
The fluorescent compound of the formula (6) is prepared in accordance with the synthetic routes as shown in FIG. 1.
Firstly the phenylboronic acid is prepared as follows: Orthobromotoluene is reacted with magnesium (1.1 equivalents) in diethylether at 25° C. The Grignard reagent is added dropwise to a solution of trimethylborate (10 equivalents) in diethylether at -78° C. The mixture is stirred further 2 hours then allowed to warm to room temperature, and stirred further 2 hours. The diethylether is removed under reduced pressure, and the solid recrystallized from water. The product is boronic acid dried in a vacuum oven overnight.
The boronic anhydride is mixed with NBS (N-bromosuccinimide) (1.1 equivalents) and catalytic AIBN (azoisobutylnitrile) in carbonetetrachloride as solvent. The mixture is refluxed under radiation by a 200 W lamp for 2 hours. The solution is filtered when hot and the solvent removed to yeild the desired bromomethylboronic anhydride.
The bromomethylboronic anhydride is mixed with 9-metylaminomethylanthracene (2.1 equivalents) in chloroform and refluxed for 2 hours. The mixture is filtered when cool and the solvent is removed. The solid is then washed with diethylether and recrystallized from ethyl acetate, to give the desired product.
Analysis of the product: PMR (CDCl3): chemical shift (ppm) 2.2 (3H, s), 3.9 (2H, s), 4.5 (2H, s), 7.4 (4H, m), 8.0 (4H, m), 8.4 (1H, s). MS (SIMS negative): mass plus glycol minus 2 waters and 1 proton 410.
The compound of the formula (6) as prepared in Example 1 is measured for fluorescence in order to evaluate the applicability of the compound to saccharide detection.
Arm aqueous solution of the compound (1.2×10-5 M) is prepared containing sodium chloride (0.05M). To the solution is added a saccharide (D-glucose or D-fructose) in a concentration of 0.05M to make the total volume of the resulting mixture 100 ml. The measurements are carried out by varying the pH from approx. 12 by the stepwise addition of HCl. The sample taken out the solution is subject to the measurement of fluorescence spectrum after the pH value is stabilized and then returned to the solution, followed by the addition of HCl to adjust the pH for further measurement. The fluorescence spectra are measured on a Hitachi Fluorophotospectrometer F-4500, in which UV is utilized for the excitation. The results are shown in FIG. 2.
As can be seen from FIG. 2, the compound of (6) is very low in fluorescence intensity over the pH range from about 3 to the higher pH, suggesting that the fluorescence due to anthracene is quenched. However, in the presence of the saccharides, the fluorescence is highly increased over a wide pH range of 4 to 10. It is therefore understood that the compound (6) can be used in the detection of saccharides through fluorescence.
The fluorescent compound of the formula (8) is prepared under the synthetic routes as shown in FIG. 3.
The orthomethyl boronic acid is bromiated with NBS in carbon tetrachloride with AIBN as initiator under reflux and lighting for 3 hours (Yield 60%) (i). The resulting orthobromomethyl boronic acid is then reacted with 2,2-dimethyl-1,3-propanediol in toluene with azeotropic removal of water overnight (Dean-Stark) (Yield quantitative) (ii).
The protected orthobromomethyl boronic acid is then reacted with the anthryl diamine and potassium carbonate in THF under reflux overnight (Yield 5% isolated) (iii).
The protecting group is removed in 33.3% MeOH/H2O at pH 7.77 and room temperature (iv).
Analysis of the product (protected diboronic acid): PMR (CDCl3, 300 MHz): chemical shift(ppm) 7.2-8.4(m, aromatic, 16H), 4.4(s, CH2 (anthrylic), 4H), 3.9(s, CH2 (benzylic), 4H), 3.6(s, CH2 (protecting group), 8H), 2.2(s, CH3 N, 6H), 0.9(s, CH3 (protecting group), 12H). MS (SIMS: NPOE): mass plus 668.
The compound of the formula (8) as prepared in Example 3 is measured for fluorescence in order to evaluate the applicability of the compound to glucose detection.
The diboronic acid compound (8) is dissolved in buffered (pH7.77, 0.01M KCl, 0. 00262M KH2 PO3 and 0.002642M Na3 HPO3) methanolic aqueous solution (33% methanol in water). Portions of saccharide are added into 100 ml of the solution and the fluorescence spactra are measured on a Hitachi F-4500 Fluorospectrophotometer with a Hewlett Packard VETRA 286/12 computer. UV (370nm) is utilized for the excitation.
The results are shown in FIG. 4, in which the abcissia represents logarithmic molar concentration of saccharide and the ordinate denotes relative fluorescence intensity. As can be seen from the figure, the compound (8) of the present invention emits a strong fluorescence particularly in the presence of glucose even in a relatively small concentration. It is particularly noted that the fluorescence intensity increases linearly with the saccharide concentration, in the range of 0.0005M to 0.001M corresponding to the glucose concentration normally to be measured in human body fluids. This trend holds not only in the case of the presence of glucose alone but also in the case of the presence of glucose concurrently with other saccharides such as galactose or fructose.
By contrast, the compound (8) develops almost no fluorescence in the presence of ethyleneglycol as control. With respect to galactose or fructose the compound does not exhibit any substantial fluorescence even in the maximum possible concentration of such saccharide in the body fluids (0.0001M), but develops the fluorescence only when the concentration of such saccharide is higher by one or two orders of magnitude. It is therefore understood that the compound (8) of the present invention can be used in the detection of glucose as it emits strong fluorescence particularly in the presence of glucose.
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|EP1462484A1 *||5 Mar 2004||29 Sep 2004||Universita Degli Studi di Firenze||Colouring agent containing a mono- or disaccharide|
|EP1557422A2||3 Ago 2001||27 Jul 2005||sensors for medecine and science, Inc||Detection of analytes in aqueous environments|
|EP1619229A1 *||20 Jul 2005||25 Ene 2006||Terumo Kabushiki Kaisha|
|EP2259061A2||7 Dic 2006||8 Dic 2010||The Regents of The University of California||Boronic acid derivatives|
|EP2292626A1||3 Ago 2001||9 Mar 2011||Sensors for Medicine and Science, Inc.||Detection of analytes in aqueous environments|
|EP2735320A1||22 Nov 2013||28 May 2014||Becton, Dickinson and Company||Glucose management and dialysis method and apparatus|
|WO2000035530A1||15 Dic 1999||22 Jun 2000||Minimed Inc||Insertion sets with micro-piercing members for use with medical devices and methods of using the same|
|WO2000043536A1 *||21 Ene 2000||27 Jul 2000||Lakowicz Joseph R||Glucose sensing using metal-ligand complexes|
|WO2001012727A1 *||13 Jul 2000||22 Feb 2001||Avecia Ltd||Detection of polyhydroxyl compounds|
|WO2001018543A1 *||6 Sep 2000||15 Mar 2001||Beckman Coulter Inc||Minimally invasive methods for measuring analytes in vivo|
|WO2001020334A1 *||15 Sep 2000||22 Mar 2001||Minimed Inc||Glucose sensing molecules having selected fluorescent properties|
|WO2001074968A2 *||30 Mar 2001||11 Oct 2001||Minimed Inc||Saccharide sensing molecules having enhanced fluorescent properties|
|WO2001075450A2 *||4 Abr 2001||11 Oct 2001||Univ California||Fluorescent lifetime assays for non-invasive quantification of analytes|
|WO2002012251A1||3 Ago 2001||14 Feb 2002||Sensors For Med & Science Inc||Detection of analytes in aqueous environments|
|WO2002025252A1 *||11 Sep 2001||28 Mar 2002||Avecia Ltd||A method for detecting fluoride|
|WO2002046752A2 *||5 Dic 2001||13 Jun 2002||Univ California||Optical determination of glucose utilizing boronic acid adducts|
|WO2002072588A2 *||21 Nov 2001||19 Sep 2002||Beckman Coulter Inc||Photo-induced electron transfer fluorescent sensor molecules|
|WO2003064434A1 *||29 Ene 2003||7 Ago 2003||Beckman Coulter Inc||Electrochemical saccharide sensor|
|WO2003074107A2||28 Feb 2003||12 Sep 2003||Medtronic Minimed Inc||Multilumen catheter|
|WO2003078424A1 *||14 Mar 2003||25 Sep 2003||Sensors For Med & Science Inc||Detection of glucose in solutions also containing an alpha-hydroxy acid or a beta-diketone|
|WO2006050164A1 *||31 Oct 2005||11 May 2006||Hu Jun||Analysis for glucose products using pyridinylboronic acid|
|WO2007067743A2||7 Dic 2006||14 Jun 2007||Univ California||Optical determination of glucose utilizing boronic acid adducts-ii|
|WO2008097747A1||28 Ene 2008||14 Ago 2008||Glumetrics Inc||Optical determination of ph and glucose|
|WO2009009756A2||11 Jul 2008||15 Ene 2009||Glumetrics Inc||Polyviologen boronic acid quenchers for use in analyte sensors|
|WO2011097586A1||7 Feb 2011||11 Ago 2011||Glumetrics, Inc.||Antioxidant protection of a chemical sensor|
|WO2012043177A1||7 Sep 2011||5 Abr 2012||Beans Laboratory||Florescent hydrogel, method for manufacturing same, and sensor for measuring saccharides using same|
|WO2013012687A2||12 Jul 2012||24 Ene 2013||Glumetrics, Inc.||Combinations of fluorphores and pyridinium boronic acid quenchers for use in analyte sensors|
|Clasificación de EE.UU.||252/301.16, 436/546, 252/301.22, 564/8, 436/800|
|Clasificación internacional||C09K11/06, C07F5/02|
|Clasificación cooperativa||C09K11/06, C07F5/025, Y10S436/80|
|Clasificación europea||C07F5/02C, C09K11/06|
|3 Ene 1995||AS||Assignment|
Owner name: RESEARCH DEVELOPMENT CORPORATION OF JAPAN, JAPAN
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:JAMES, TONY;SANDANAYAKE, SAMAN;SHINKAI, SEIJI;REEL/FRAME:007273/0531
Effective date: 19941219
|22 Sep 1999||FPAY||Fee payment|
Year of fee payment: 4
|17 Sep 2003||FPAY||Fee payment|
Year of fee payment: 8
|24 Sep 2007||FPAY||Fee payment|
Year of fee payment: 12

domain: chemistry


AE-1652E Wide range, High speed and High accuracy Digital resistance checker
A wide range from low resistor to high resistor measurement is achieved by the highly precise and wonderful speed Optimum for the on a sorting machine,taping machine and painting conveyor For chip MELF and lead typs resistor of B,C,D,F,G,K and M class
- Ultra high accuracy and high stability by the measuring method rejected thermoelectromotive force.
- High stability by the improvement of noise immunity for the isolated circuit between analog and digital part.
- Available to make the high speed and ultra-high stable measurement by the setting function of average time on measuring value for each range.
- Range of measurement for absolute value : 0.000mΩ ～ 125.00MΩ for % : -9.999% ～ +2.5000% / -99.99% ～ +25.00%
- Available to select the function for contact check “before measurement”, “after measurement” or “non-contact check”
- 【New functions】Contact check function while measurements. (Always)
※Available to improve reliable measurement.
- RS-232C and Centronics interface are built-in as standard equipment.【GP-IB is option】
- Transfer function of setting date is built-in as standard equipment. (Available to transfer the same setting data to another set of AE-1652E)
- The checking circuit of the abnormal measuring current and voltage is built-in.


text:
Explorer: The Lost Islands: Bk.2 (BOK)
Sendes vanligvis innen 7-15 dager
Explorer, the exciting graphic anthology series which launched in Spring 2012 with The Mystery Boxes, continues with an incredible roster of comics artists who create amazing new stories around the theme of hidden places in volume two of the series, The Lost Islands. Edited by the New York Times bestselling comics creator, Kazu Kibuishi, this new collection includes well-written, beautifully illustrated stories by Kazu (Amulet), Jason Caffoe (Flight), Raina Telgemeier (Drama and Smile), Dave Roman (Astronaut Academy), Jake Parker (Missile Mouse), Michel Gagne (The Saga of Rex), Katie and Steven Shanahan (Flight), and up-and-coming new artist, Chrystin Garland. Explorer: The Lost Islands is bound to generate the same kind of reviewer and bookseller enthusiasm as the first volume did.
|Utgitt||2013||Forfatter||Chrystin Garland, Dave Roman, Jake Parker, Jason Caffoe, Katie Shanahan, Kazu Kibuishi, Michel Gagne, Raina Telgemeier, Steven Shanahan|
Abrams Books For Young Readers
|Antall sider||128||Leverandør||Bertram Trading Ltd|
|Emner og form||Comic strip fiction / graphic novels (Children's / Teenage)|

domain: library


Updated solid design protects the entire underside of your Gold Wing from road debris and the elements out on the open road. Made of thicker 3.2 mm 5052 aluminium, this solid, one piece belly pan/engine plate is easy to remove for oil changes. Simply remove 3 bolts and dismount. Easy 20 minute install with no drilling involved. Includes mounting brackets and hardware for installation.
New front mounting brackets updated for easy install using front crash bar bolts. No bending required. See additional images above.
Made for 2018+ Gold Wing 6-Speed Manual & DCT Models
Works with all highway pegs.
3.2 mm thickness
20 min easy install
Made in the U.S.A.


We are here for your questions anytime 24/7, welcome your consultation.Get Price
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Eicher introduces 3 reefer trucks - Pro 1059XP, Pro 1100XP and Pro 6025
Eicher Truck & Buses has expanded its product portfolio with the introduction of three new fully built reefer (refrigerated) trucks - Pro 1059XP, Pro 1110XP & Pro 6025. These products will help the company provide fully built, ready to use solutions for cold chain logistics.
The trucks come with an ARAI-approved design in 14 ft, 20 ft and 24 ft options. They range from a gross vehicle weight (GVW) of 7 tonnes to 25 tonnes. The refrigeration unit is claimed to have an operating temperature range of -25 C to +25 C under ambient conditions of +50 C.
The Eicher Pro 1110XP is powered by an E413 BS-III engine that develops 113 BHP @ 2,800 rpm and 400 Nm of torque @ 1,400-1,600 rpm. It has a 5-speed ET 4055 gearbox, a 310 mm diameter clutch, a fuel tank capacity of 190 litres and a battery of 12V- 100Ah. It comes with a wheelbase measuring 4,300 mm, a ground clearance of 220 mm and a 26% gradeability.
The Pro 1059 XP is available with a E413 BS-III engine that puts out 94 BHP @ 2,800 rpm, and 285 Nm of torque @ 1,400-1,600 rpm. The engine is mated to an ET 30SS 5-speed gearbox and a 275 mm clutch. The truck has a wheelbase measuring 3,515 mm, a ground clearance of 210 mm and a 26% gradeability. It has a fuel tank capacity of 60 litres and a battery of 12V- 100Ah.
The Eicher Pro Eicher Pro 6025 is powered by a VEDX 5, 5-litre, BS-III engine that produces 207 BHP @ 2,200 rpm and 825 Nm of torque. It uses an ET 9056 6-speed gearbox, a 395 mm clutch and a 24V battery. The truck has a wheelbase measuring 5,300 mm, ground clearance 265 mm of and a gradeability of 22.5 %.The truck also has a fuel tank capacity of 415 litres.
Eicher has been providing truck chassis to various players in the logistics industry for building reefer containers. However, with the demand rising, the company took the step to provide fully built reefer trucks.
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|Eicher launches Pro 8031XM, displays Pro 6025T trucks at EXCON 2015||Aditya||Commercial Vehicles||0||26th November 2015 14:40|
|Volvo-Eicher launches Pro 6000 series truck||Aditya||Commercial Vehicles||1||20th January 2015 18:28|
|The Eicher Pro series: New range of Buses & Trucks||Stratos||Commercial Vehicles||35||31st August 2014 14:15|
|Eicher launches a 14.5 ton truck - The Eicher 11.14||GTO||Commercial Vehicles||18||30th April 2012 17:51|
|Eicher introduces a "rear engine semi low floor" Bus||GTO||Commercial Vehicles||16||21st October 2011 22:54|


Jul 01, 2015
WASHINGTON [MENL] -- After four years, the United States has decided to liftits partial military embargo on Bahrain.
Jun 29, 2015
WASHINGTON [MENL] -- The United States has been wooing Middle Eastmilitaries with an advanced anti-tank guided missile.
LONDON [MENL] -- Germany has approved another arms export package for theGulf Cooperation Council.
Jun 24, 2015
NICOSIA [MENL] -- The Lebanese military has been awaiting another shipmentof French weapons and combat platforms.


text:
Are you ready to rrrrumble?!? In our five-sided showdown ring we have five heavyweight historical author contenders ready to battle for your applause!!
In order of time period, from most recent …
In corner No. 1 in the crystal beaded flapper dress, it’s Piper “Pay the Piper” Huguley representing the beginning of the 20th century in the United States (1900-1930)!
In corner No. 2 in the metallic gold bias-cut gown it’s Joanna “Magnate-o” Shupe representing America’s Gilded Age (1870s-1900)!
In corner No. 3 in the whalebone corset and bustle, it’s Jennifer “McFists” McQuiston representing the Victorian era in the United Kingdom (1830s-1900)!
In corner No. 4 in the dampened chemise and straw bonnet, it’sLenora “Final Count” Bell representing the Regency period in the United Kingdom (1811-1820s)!
And in corner No. 5, wearing the pink silk robe and carrying a wicked-looking sword, it’s Jeannie “Sting Like a Bee” Linrepresenting Tang Dynasty China (eighth century-ninth century)!
And the crowd goes wild as these historically garbed ladies pump their fists, trash-talk their opponents and … wait, folks, there’s the bell for Round 1…
Find out more and enter to win books from all five authors at USA TODAY’s Happy Ever After blog!

domain: history


text:
Disclaimer: We hope you’ll love the products we recommend. RelaxLikeABoss.com may earn a commission on qualifying purchases from Amazon Associates.
If you suffer from neuropathy, you know how debilitating the condition can be. The tingling, burning, and numbness in your extremities can make it difficult to perform even the simplest tasks. And when traditional treatments like medication and physical therapy don’t provide relief, you may feel like you’re out of options.
But there is hope. A foot massager for neuropathy can help ease your symptoms and give you back some of your quality of life. In this post, we’ll review the best foot massagers for neuropathy on the market and help you choose the right one for you.Discover Your FREE Personalized Moon Reading Now
We’ll start by discussing what neuropathy is and how a foot massager can help. Then we’ll review some of the top-rated products and explain what sets them apart. Finally, we’ll give you some tips on how to get the most out of your foot massager.
So if you’re ready to find relief from neuropathy pain, keep reading.
Table of Contents
Our Top Choice
- Powerful motor that provides a deep and relaxing massage
- Offers 3 levels of intensity and 5 modes of operation
- It has a quiet mode that is perfect for relaxing
- Easy to use with its intuitive controls
How A Foot Massager Can Help?
A foot massager can help in several ways. It can relieve pain, increase circulation, and reduce stress. All of these benefits can lead to improved overall health.
Pain relief is one of the most common reasons people use a foot massager. If you have any type of pain in your feet, whether it’s from a recent injury or chronic condition, a foot massager can help. The massage action can increase blood flow to the area and help reduce inflammation. This can lead to reduced pain and improved mobility.
Circulation is another important benefit of a foot massager. If you have poor circulation, it can lead to several health problems. Massaging your feet with a foot massager can help improve circulation and prevent these problems from occurring.Discover Your FREE Personalized Moon Reading Now
Finally, stress relief is another important benefit of using a foot massager. If you’re constantly under stress, it can take a toll on your health. A foot massager can help you relax and reduce stress. This can lead to improved overall health and well-being.
Now that we’ve reviewed some of the benefits of using a foot massager, let’s take a look at some of the top-rated products on the market.
9 Best Foot Massager for Neuropathy – Reviews
The Cloud Massage Shiatsu Foot Massager Machine is a great way to reduce inflammation, stimulate muscle recovery, provide pain relief, or offer pure and thorough relaxation after a long day. With its adjustable base, it can be positioned with amazing comfort to work the muscles of your feet, ankles, or calves! It also features 5 modes; a rolling massage, compression therapy, a sway function, heat therapy, or the quiet mode for calming relaxation.Discover Your FREE Personalized Moon Reading Now
- Can help reduce inflammation
- Stimulates muscle recovery
- 3 levels of intensity to choose from
- 5 modes for different types of massage
- Heated option included
- If not positioned correctly, may not massage desired areas fully
- May be too intense for some people
RENPHO Shiatsu Foot and Calf Massager is great for those who are looking for a foot and calf massager machine that can provide a variety of functions. With the adjustable support bar, you can place this shiatsu foot massager machine with heat in a proper position and massage your feet, ankle, calf, leg, and arm, which can relieve foot discomforts. Additionally, the washable sleeves help keep a clean and healthy environment, making it suitable for whole family use. Furthermore, this electric foot and calf massager allows you to adjust each function with multiple choices to massage areas of your foot( Bottom, instep, full foot)-3 Heating mode, 4 powerful squeeze intensity, and 3 Kneading Intensity. All of these functions above can work independently.Discover Your FREE Personalized Moon Reading Now
- Adjustable support bar and washable sleeves
- 8 squeeze units and 4 intensity levels
- 3 heating modes and 3 kneading intensity levels
- Remote control and magnetic storage
- The heating goes up to 140 Fahrenheit degrees
- Automatically shuts off after a set amount of time
- Pricey compared to other foot massagers on the market
Best Choice Products Therapeutic Shiatsu Foot Massager is ideal for those who suffer from pain in their feet or other parts of their body. The massager specifically targets all areas of your feet to help with different parts of the body through a variety of techniques including pulsing, kneading and rolling. The remote allows you to easily control the power, speed, and massage direction, as well as the mode settings between automatic, custom, and manual. The space-saving structure makes it easy to take on the go, and the built-in handle makes it easy to carry. The massager is also easy to clean with a removable cover.Discover Your FREE Personalized Moon Reading Now
- Convenient remote control
- Specifically targets all areas of your feet
- 3 different modes for different parts of the feet
- Space-saving structure
- Built-in handle for easy transport
- Easy to clean
- May be too intense for some people
- The arch massage may not be effective for everyone
- May take some time to get used to the heat settings
The HoMedics Shiatsu Air 2.0 Foot Massager is a great way to relieve pain and tension in your feet. The deep-kneading nodes provide a Shiatsu massage that can help to relieve aching muscles, while the air compression massage gently squeezes your feet for a relaxing experience. The optional heat setting provides additional comfort for tired muscles, and the removable, washable lining makes it easy to keep your massager clean. The Shiatsu Air 2.0 Foot Massager comes with a 2-year limited warranty.Discover Your FREE Personalized Moon Reading Now
- Shiatsu massage provides relief for aching muscles
- 3-speed options
- Optional heat
- Washable interior liner
- May be too big for some people’s feet/feet may hang over the edge
- No remote control
This Acupressure and Reflexology Foot Massager from Sharper Image is the perfect way to rejuvenate tired feet! It combines heat, acupoint nodes, shiatsu, and compression for the best massage you can get anywhere. The heating function helps relieve pain in tired muscles and reduces foot pain, while the acupressure nodes and compression feature soothe your heels and balls of feet. The shiatsu node rolls over the arches for an all-around amazing foot massage. It’s perfect for travel, too – after a long day on your feet, there’s nothing better than this massager to soothe tired and sore muscles. Plus, it’s great for plantar fasciitis and other ailments.Discover Your FREE Personalized Moon Reading Now
- Perfect for plantar fasciitis and other ailments
- Soothes muscles with heat
- Acupressure nodes relieve pain
- Reflexology and shiatsu massage for tired feet
- Compact and perfect for travel
- Satisfaction guaranteed
- Not for use on open wounds or broken skin
- Doesn’t hit arches
Brookstone Therasqueeze Foot Massager is perfect for those who want a full-coverage, deep-kneading, rolling massage. With four unique massage programs and three intensity levels, you can customize your massage experience to fit your needs. The convenient grab-and-go handle makes it easy to move around, and the removable, washable liners make cleaning a breeze. With a 1-year limited warranty, the Brookstone Therasqueeze Foot Massager is a great choice for anyone looking for a complete massage experience.Discover Your FREE Personalized Moon Reading Now
- Rolling massage from calf to toe
- 4 unique massage programs
- 3 intensity levels
- Adjustable tilt for nearly any seated position
- Convenient grab-and-go handle
- Removable, washable liners
- May be too intense for some users
- Can be difficult to get in and out of if you have limited mobility
This Nekteck Shiatsu Foot Massager Machine is a great way to relax and reduce stress after a long day. It features multiple preset massage modes, heat function, and adjustable air compression intensity, so you can customize your massage experience to your liking. The built-in air compression technology helps boost blood circulation in your feet and legs, and the soothing heat function provides additional relief for tense and stressed muscles. The deep-kneading nodes mimic the techniques of a professional masseur, and the detachable foot cover is machine washable for your convenience.Discover Your FREE Personalized Moon Reading Now
- Relieves pain and tension in the feet
- Helps improve circulation
- Can be used on both feet at the same time
- Some people may find the massaging action too strong
- May not be suitable for people with diabetes or other conditions
- May cause bruising or other injuries if used too forcefully
The TheraFlow Foot Massager Roller is a great way to relieve tension and pain in your feet. The 11.2” x 8” foot massage roller features 2 different types of acupressure nubs and 5 rows that work together to provide a deep, relaxing massage. The arched design mirrors the natural curvature of the feet for increased comfort, and the non-slip strips at the bottom prevent the massager from flipping over and protecting your floor. The reflexology chart and detailed user instructions provide you with all the tools necessary to achieve better foot health and enjoy deeply relaxing massages.Discover Your FREE Personalized Moon Reading Now
- Effective at relieving tension and pain
- It is made of high-quality materials and is very durable.
- It is easy to use and portable, so you can take it with you wherever you go.
- Some users have found that the roller is too hard, making it difficult to use.
- Others have found that the roller slips and does not stay in place.
The Miko Foot Massager Machine is a great way to relieve tired feet and improve blood flow. It is equipped with heat, deep-kneading, compression, rolling, subtle vibrating, a built-in timer, 5 pressure settings, washable foot liners, and 2 wireless remotes. The patented massage technique provides a rolling and shiatsu massage to the bottom and sides of the feet while air pressure applies pressure to all parts of the foot. The heat will relax tense muscles to target specific pressure points. The Miko Foot Massager Machine is a great way to relieve pain from plantar fasciitis, neuropathy, diabetes, chronic pain, muscle tension, tough knots, and other pains as well. It is also comfortable and convenient to use while watching TV, reading, working at the office, or just relaxing. The Miko Foot Massager Machine is also backed by a full 1 year coverage on all products.Discover Your FREE Personalized Moon Reading Now
- It has multiple settings that allow you to customize your massage experience, including heat and vibration.
- It has a deep-kneading massage function
- The machine is portable and easy to use
- A bit pricey, so it may not be within everyone’s budget.
- Some may find the vibration settings to be too strong.
Overall, there are a lot of great foot massagers on the market that can provide relief from pain and tension. If you are looking for a massager that is portable and easy to use, the Cloud Massage Shiatsu Foot Massager Machine is a great option. If you are looking for a more affordable option, the TheraFlow Foot Massager Roller is a great choice. Whichever massager you choose, make sure to read the instructions carefully to avoid any injuries.Discover Your FREE Personalized Moon Reading Now
Foot Massager for Neuropathy Buying Guide: What to Look For?
When buying a foot massager for neuropathy, there are several things you should look for to ensure you get the best possible product. Here are some factors to keep in mind:
1. Ease of use: Look for a foot massager that is easy to use, so you can get the most out of your sessions. The controls should be simple, and the device should be easy to set up and operate.
2. Effectiveness: Choose a foot massager that has been proven to be effective in relieving neuropathic pain. Look for reviews from other users to get an idea of how well the massager works.Discover Your FREE Personalized Moon Reading Now
3. Safety: Make sure the foot massager you choose is safe to use. Avoid products that use electricity or heat, as these can be dangerous for people with neuropathy.
4. Portability: If you plan on traveling with your foot massager, look for a portable model that is easy to take with you.
5. Price: Foot massagers can range in price from around $30 to over $100. Choose the one that fits your budget and needs.Discover Your FREE Personalized Moon Reading Now
6. Guarantee: Some foot massagers come with a money-back satisfaction guarantee. This can be a good way to try out a new product without risk.
7. Features: Some foot massagers come with additional features, such as Shiatsu massage or infrared heat. These can help relieve pain and promote relaxation.
8. Brand: There are many different brands of foot massagers on the market. Do some research to find the one that has a good reputation and offers a quality product.Discover Your FREE Personalized Moon Reading Now
Keep these factors in mind to help you find the best possible product for your needs.
What is neuropathy?
Neuropathy is a general term for a disorder of the nervous system. It can affect any part of the nervous system, including the brain, spinal cord, and nerves. Neuropathy can be caused by many different conditions, including diabetes, cancer, shingles, and alcoholism. Symptoms of neuropathy can include pain, numbness, tingling, and weakness. Treatment for neuropathy depends on the underlying cause of the condition. In some cases, treatment may include pain relief, physical therapy, and medications.
Are foot massagers good for neuropathy?
There is no one-size-fits-all answer to this question, as the best type of treatment for neuropathy will vary depending on the underlying cause of the condition. Some users, on the other hand, may find that a foot massager helps to alleviate pain and other symptoms linked with neuropathy. If you’re thinking about using a foot massager for neuropathy, it’s critical to discuss it with your doctor first to verify that it’s safe for you.Discover Your FREE Personalized Moon Reading Now
Can diabetics use an electric foot massager?
Yes, diabetics can use electric foot massagers. But it is important to consult with a physician before using one, as diabetic nerve damage can cause sensitive skin and reduced circulation. If you have any concerns, ask your doctor if an electric foot massager is right for you.
Read more: Best Shoulder Brace for PainDiscover Your FREE Personalized Moon Reading Now

domain: medical


The term "disk space" is sometimes called "disk quota" or "data storage", still all these words refer to the exact same thing - the amount of info that you can upload to a cloud hosting account. The total size of what you have is estimated by accumulating the storage space consumed by the entire content in your account, the most obvious being the data files that you upload. Two other things are frequently overlooked by various users, though - e-mails and also databases. Big attachments or databases of large script-driven sites can sometimes require a lot of storage space as well. To use a more familiar analogy, the hard disk space of your computer system is taken not only by files that you download, but additionally by documents you generate along with software programs you install. In the same way, many things are counted towards the hdd space your information takes on a website hosting server, not only the uploads.
Disk Space in Cloud Hosting
Our cloud hosting
plans were made with the notion that shortage of storage space shouldn't be something that should obstruct the development of your sites. That's why we have used a technique which is distinct from the one that most web hosting providers apply - rather than making all the accounts using one server and subsequently running out of storage space, we employ a cloud hosting platform in which the storage is taken care of by a wide collection of servers. Because of this, we can easily attach more machines whenever they are necessary or more hard disks, so as to offer more disk space for the files of our customers. Separate clusters manage the emails as well as your databases, so not only are you able to develop your web sites without having to worry about hard drive space, but also all the servers will perform faster and better considering the fact that every service features its own storage space and an individual server doesn't handle different kinds of files.
Disk Space in Semi-dedicated Servers
With our semi-dedicated server
plans, the hard disk capacity attribute is unrestricted, so that you're able to center on building your websites the way you'd like them to be and never be concerned about getting to a restriction. Unlike lots of hosting providers that generate your accounts on one server, we employ an in-house built cloud platform, that allows us to supply truly unlimited hdd space for every single account. With a single machine, there's a restricted number of HDDs that can be used, not mentioning that the most popular hosting Control Panels weren't meant to work with a large number of servers simultaneously. Our platform, however, functions with clusters of servers for the web site databases, files and emails, and our in-house made Hepsia Control Panel was designed to work with it. We are able to install as many servers to any of the clusters as required at any time, so the hdd space is practically limitless.
Disk Space in VPS Servers
The disk space that we provide with our VPS servers
varies based on the plan that you choose at the time you sign up. By using a more powerful server, you are able to effortlessly manage a variety of sites, which means extra content, so the superior the VPS package, the more disk storage you will have available. Switching from one plan to another takes just a couple of mouse-clicks and it does not involve any service interruption. Your web site files, databases and emails will share the the whole amount of space the server comes with, but if you'd rather to have fixed quotas, you are able to pick cPanel or DirectAdmin for the hosting Control Panel during the ordering process. Each of the instruments will allow you to set up hosting accounts with limited hdd storage and when necessary, even to allot space from one account to a different one. With the third solution that you'll find on the order page, the Hepsia Control Panel, all domain names will share the space.
Disk Space in Dedicated Servers
With all the disk storage that we supply with all of our dedicated servers
, we guarantee that you will be able to manage every site irrespective of its volume. You'll get at least 500 GB storage, that you can use as you see fit - even for personal file depository. By default, you will have two hard disks, which can be used separately, so as to make use of their full storage capacity, or they can be in RAID so that one will be a duplicate the other in real time to guarantee that you won't waste important information in case of a hardware breakdown. You're also given the option to add additional drives and increase the whole HDD storage at your disposal even more. This will allow you to build a file or image depository portal without a problem if you would like. With the cPanel and DirectAdmin hosting Control Panels that we provide, you are able to make an independent account for each and every domain that you host on the server and pre-define a quota for the storage space it'll be allowed to use. When you go for the 3rd choice, our in-house built Hepsia Control Panel, all of your domain names will be operated in one place and they will share the full server hard disk storage.


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Ribbed Knit Trouser
A must have piece for your mid season/winter wardrobe! Made with a mid-heavy weight knit with an elastic waistband and slight cropped leg, this is the ultimate comfort piece to get you through the colder months. Dress it down with a sweatshirt, or wear it with a crisp cotton shirt for a day out.
One size, suitable for sizes M-L / model is size M

domain: design


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"These results raise concerns about the quality of care for adolescent depression," concluded a team led by Briannon O'Connor, who conducted the study while at New York University School of Medicine.
One expert wasn't surprised by the findings.
"Most adolescents who are depressed do not receive any treatment whatsoever for their impairments for many reasons, including lack of access to care, stigma, and a workplace shortage of trained child and adolescent psychiatrists," said Dr. Aaron Krasner, chief of the Adolescent Transitional Living Service at Silver Hill Hospital in New Canaan, Conn.
As the study authors explained, major depression affects 12 percent of teens, and as many as 26 percent of young people experience at least mild depression. Prompt treatment is crucial because failure to relieve depression increases the risk of recurrent depression and more impaired functioning in the long term, the researchers said.
By Healthfinder.gov - Read Full Article

domain: news


SysAdmins have a storied reputation: Wire whisperers. Oracles. Superheroes. Herders of cats. IT legends.
From network security and server provisioning to maintaining and troubleshooting hardware, apps, operating systems, infrastructure and sometimes even
frustratingly stupid confused coworkers, they adeptly handle it all and have been doing so since the UNIX-enabled proliferation of microcomputers in the late 1970s.
In celebration of SysAdmin Day on July 28, CDW tapped into the collective wisdom of the Spiceworks IT community to answer the phrase “When I started in IT, _______.” Hundreds of responses and more than 18,000 votes from 1,400 community members paint a colorful history of the SysAdmin.
We’ve selected some of the top responses to explore the evolution of the SysAdmin from the days of minis, micros and star networks to LANs, WANs and VPNs; from terminals to workstations to PCs to mobile, virtual and beyond.
Buckle up, because we’re in for a ride. Let’s go!
“When I started in IT, thick coax was cutting-edge.”
Commonly used in connecting home video equipment, coaxial cable was for a time a staple in networking. We’ve all heard of Ethernet, and by the early 1980s it was the dominant network technology. However, early versions of the tech relied on coaxial cabling to connect devices — known as “thicknet” — called 10BASE5.
“… our networking was by serial cable or token ring with BNC connectors.”
With a maximum length of 185 meters and a node limit of 30 (often connected with BNC connectors), this 10 megabits per second technology was quickly replaced by twisted-pair cable technology, which we commonly see in networking applications today. Now, there’s no more fussing with fragile BNC connections and appallingly slow speeds. With technology like NBASE-T boasting speeds of up to 5 gigabits per second over 100 meters, coupled with solutions like hyperconvergence and virtualization, the foundations of data center and networking tech have evolved dramatically.
“… ‘Mac’ was something you called a guy you didn’t know.”
Now here’s an old-school SysAdmin response. Media access control (MAC) addresses have an interesting history: The granddaddy of this tech was known as the PuP, PARC Universal Packet, and was one of the earliest internetwork protocol suites. It was created by researchers at Xerox PARC in the mid-1970s. The problem with this tech, however, was that it did not separate the layers that identify a computer both inside and outside the network (in modern terms, MAC and IP addresses, respectively) and was thus difficult to implement. By separating these layers, the MAC address was born and could now be used for far more than colloquially addressing strangers in public.
Nope, wrong Mac. This game has way better graphics than I remembered. via GIPHY
SysAdmins still use MAC addresses, but networking technology has greatly evolved into things such as SD-WAN. The future of networking points toward systems that will allow SysAdmins to implement an intent-based model for more flexible resource allocation.
“When I started in IT, 330MB was more than enough for a hard drive.”
These days, 330MB is barely enough to cover a solid range of reaction GIFs, but having hundreds of megabytes at your command in the early days of PC computing meant (you thought) you could store a nearly infinite supply of (text-based) data … the future is now!
“… floppy disks were actually floppy!”
“… I had to punch holes on my floppy disk to double its memory.”
“… there were no hard drives, OS had to be loaded on floppy disks before you could do anything!”
For almost 40 years, the floppy disk remained a popular data format, initially used as a primary data storage mechanism (think a pre-HDD) and later mostly as a file transfer system. Who remembers backing up your OS and files with 100-plus floppies? Good times.
You all go ahead, this backup is almost done. via FailBlog
Not that anyone younger than 20 will remember, but before Zip disks and the 1.44MB floppy-but-not-really varietals, there were these bad boys:
You can see some hard sectoring of the floppy disks in the photo above. Let's be glad these aren't enjoying a hipster renaissance like vinyl. via Wikimedia Commons
The 8-inch floppy was pioneered in the early 1970s and featured a whopping 80 kilobytes of data storage. And, much like our astute Spiceworks contributor noted, in the early days you would physically punch a hole in the disk, a concept known as “hard sectoring,” so the computer could reference sector locations, a practice that allowed faster read and write times in many cases. They even sold peripherals to assist with hard-sectoring! Missed opportunity for the classic hole punch lobby.
Toward the end of their popularity, thanks to devices like flash drives and optical storage, floppy disks were created in several variants that enabled upward of 750MB of storage.
For today’s SysAdmin, some storage solutions now are cloud-based, scalable, and far more flexible, forgiving and spacious than a 3.5-, 5.25- or 8-inch circle of fussy, hole-punched plastic.
HARDWARE & SOFTWARE
“When I started in IT, RAM was measured in kilobytes, not mega or giga.”
Random access memory (not to be confused with that Daft Punk album) was developed back in 1947, when data was stored within electrically charged spots on the surface of a cathode-ray tube. The idea behind it was to store frequently used instructions for programs to increase the overall speed of a system. Before that, computers used mechanical counters to store information. Before that, the Earth was still cooling and George Washington was riding dinosaurs.
The modern SysAdmin still takes full advantage of RAM’s evolution (some machines now boast upward of 32 gigabytes of RAM), but there are far more options than before: Some technologies are even blurring the lines between system memory and storage.
“… you could press ‘Turbo’ on the CPU.”
What a solid bit of trickery this was (thanks, gaming industry) and a great indicator that the Spiceworks submitter got into the SysAdmin game in the early days!
This “futuristic” feature from the 1980s was essentially an over-marketed way of selling a “compatibility mode.” A long time ago, you had what amounted to one choice for a computer: the IBM personal computer. Often (especially in gaming), programmers would use the CPU’s frequency for in-game timing. As chips became faster and more varied, many of these games became unplayable. Enter the turbo button. This created two operating states for the CPU — normal and reduced speed (“turbo”). Yes, you read that right: Perhaps counterintuitively, the turbo button was used to slow down the computer, not speed it up. Sad trombone. While I certainly felt like a bona fide NeoTokyo cyberpunk when I pressed the family PC’s turbo button, to be honest it felt silly then too.
When does this happen in the article? Now. Whatever you're reading now, is happening now. via GIPHY
The turbo button has long since disappeared from modern computers and is largely a sentimental piece of nostalgia for most SysAdmins, but it looks like someone (or something) has figured out the modern-day turbo button: Just kill all Java processes.
“… GUI? It was all command line!”
“… BASIC was a bleeding-edge programming language.”
Oh, you need a graphical user interface? Don’t be a WIMP. OG SysAdmins cut their teeth on systems that didn’t offer such a visual, broad level of n00b-friendliness. Long before they were oohing and ahhing over Bliss, SysAdmins were furrowing their brows in front of screens that displayed only text information — this, an evolution from human dialogue over teleprinter (TTY) machines, became known as the command-line interface.
So...where do I put the emojis? via GIPHY
However, before there was a Beginner’s All-purpose Symbolic Instruction Code (BASIC), nearly every computer relied on custom-built software — not a very scalable system. Enter BASIC, invented at Dartmouth College in 1964. This evolved CLI language unified machines and formed the functional, philosophical basis of most of today’s software.
Even though the video display terminal was introduced in the 1960s, the CLI (think MS-DOS, for example) was the dominant method of interacting with most computer systems until the 1980s, when, coupled with the explosion of personal computers, the GUI took off and began to forever stamp the phrase “Have you tried turning it off and on again?” into the troubleshooting center of every SysAdmin’s frontal lobe.
Many SysAdmins still prefer the expert-friendly (versus beginner-friendly) command-line systems for quick access and manipulating key parts of a network. Additionally, the 53-year-old BASIC remains popular today. There’s even a Nintendo 3DS game based on the BASIC engine that allows you to program your own games.
“When I started in IT, phones couldn’t connect to the internet.”
“… dial-up was my only internet option.”
“… Facebook didn’t exist!”
Three responses, three generations of SysAdmin. At the dawn of the internet, when it wasn’t yet called “the internet,” it was known as ARPANET. Its creation involved the use of what were known as leased lines, which were private communications channels that did not have a telephone number and whose lines were permanently connected to each other (“dedicated”).
Initially these were local area networks (LANs). As infrastructure developed, networks grew and became connected over large distances (wide area networks, WANs). Leased-line technology was replaced by networks that existed on the public switched telephone network (PSTN). Thus dial-up internet was born, prompting a generation’s worth of “get off the phone, I’m online!” and fond memories of that special connection tone.
Side by side with leaps in hardware processing power and the explosion of the personal computer, the internet developed faster connections, better programming languages and interfaces, and a TON of cute pictures of cats and babies, which — along with Facebook, blossoming across the internet since 2004 — is the primary use of the internet today, probably.
Literally the end-game vision of Tim Berners Lee. via GIPHY
SysAdmins have come a long way from 1-kilobyte RAM chips and floppy disk-based operating systems, but one thing has never changed: They’ve always been IT legends.


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Guys, we have found a fluffy doggie that has been winning the hearts of millions of people lately with its human-like expressions. Yes, you have read that right! This fluffy dog has been getting the attention of people from the time his picture went viral.
His name is Kokoro and he lives in Japan. Surprisingly, he has 120k followers on Instagram and he is even more popular on Twitter. You can scroll down to see this little star.

domain: pet


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I’m not ashamed to admit that at the age of 19 I still love Shrek. It’s one of my childhood favourites, and I still quote the movies years on. I absolutely loved Gingy. Okay, I’ll admit that’s partly due to the fact that I used to love shouting “THE MUFFIN MAN? THE MUFFIN MAN!” over and over, but hey, he’s a talking gingerbread man- pretty cool, right? So how would you like to make your very own Gingy?
Even if you aren’t a fan of Shrek, these techniques can be used to create a regular gingerbread man. Whatever you decide to do, I hope you enjoy it as much I did!
This tutorial is a little more advanced than most of my others, but that isn’t to say that it’s not possible for beginners. If I can do it with a cold and a moody toddler around, I’m sure you can!
What you’ll need:
- Polymer clay (white, orange, brown, purple, blue)
- Cutting tool
- A link
- Clay varnish
- Liquid clay
- Dark brown pastel or eyeshadow
- Small dotting tool
- An old toothbrush
- Gingerbread essence (optional)
First of all, combine some orange, brown and white clay and mix it up until you have a colour similar to the one above. I’m sorry I can’t be more helpful at this point, I didn’t measure the amounts of each, but just experiment until you get something that resembles a gingerbread colour.
If you’re adding essence to your clay, do it now. Just use a few drops- we can use more later. Then roll the clay out until it is around one centimetre thick.
Cut out the main pieces of the body. The legs and arms should be separate from the main body. Smooth down the edges with your fingertips.
Take your toothbrush and apply medium pressure whilst digging the bristles over all of the clay. This gives it a biscuit-like texture and also rounds the edges out slightly. If your man loses shape too much, simply push it back into place with your fingers.
Use your cutting tool and your dotting tool to add texture to Gingy’s broken legs. They need to look like they’ve snapped, so make it look as if pieces have broken away and that there are little crumbs left over.
Softly press the arms into place- enough so that they stick but not so hard that the lines disappear. Going over the joins with the toothbrush again may help.
Take your paintbrush and pastel/eyeshadow and add shading. I began by brushing around the outside and blending it inwards, so that he looks baked.
Repeat the last step over the rest of the body. It doesn’t have to be perfect.
Use your dotting tool to poke a hole in the top of his head, making sure that it is big enough to fit your link through.
Begin to add your details by rolling up very small pieces of white clay and sticking them in place using liquid clay. Here I have done his legs by connecting them to the rest of the body.
Continue to add your white details, such as the icing and the eyes.
I combined purple clay with a little white so that it’s light, then I used my dotting tool to create shallow holes where the “gumdrop buttons” should go. I then rolled the clay into little balls and stuck them in place.
I’ll admit that this part was quite time consuming for me. I rolled out one long piece of red clay, cut off the excess, then connected the ends. I used my dotting tool to mould it into a mouth shape and stuck it in place.
I mixed up some blue clay with a little white, rolled some into small sausage shapes and stuck them on to form eyebrows. Try your best to get the correct expression. Bake the whole thing for 10 minutes on gas mark 4. This should harden it up without baking it completely.
Roll out some more clay for the backing (I used more ginger clay, but you can use whatever you like- after all, it isn’t going to be seen much). Lay your Gingy on top and cut around him as neatly as possible, making sure that none of it is visible from the front. Stick the backing on with more liquid clay, go over the hole you made earlier for the link, and bake the whole thing for a further 20 minutes.
Step sixteen (optional):
Once he had cooled down I brushed some more gingerbread essence all over.
Brush on a thin later of varnish and leave to dry.
Just add your link through the hole and you’re all finished! Yaaaay!
Thank you for reading. Please comment below with any questions or to let me know how your Gingy turned out. Check out the rest of my site for more tutorials. Have a great day!

domain: hobby