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Hypericum perforatum
|Hypericum perforatum
|Scientific classification
|H. perforatum
|Binomial name
| Hypericum perforatum
Hypericum perforatum, known as perforate St John's-wort,[1] common Saint John's wort and St John's wort (/ˈsɪndʒənzwɜːrt/ SIN-jənz-wurt),[note 1] is a flowering plant in the family Hypericaceae. The common name "St John's wort" may be used to refer to any species of the genus Hypericum. Therefore, Hypericum perforatum is sometimes called "common St John's wort" or "perforate St John's wort" in order to differentiate it. It is a medicinal herb with antidepressant activity and potent anti-inflammatory properties as an arachidonate 5-lipoxygenase inhibitor and COX-1 inhibitor.[3][4][5]
Botanical description
Hypericum perforatum is native to parts of Europe and Asia[6] but has spread worldwide as a cosmopolitan invasive weed, including to temperate regions of India, China, Canada, Africa, and the United States.
The common name "St John's wort" comes from its traditional flowering and harvesting on St John's Day, 24 June. The genus name Hypericum is derived from the Greek words hyper (above) and eikon (picture), in reference to the tradition of hanging plants over religious icons in the home during St John's Day, to ward off evil.
Perforate St John's wort is a herbaceous perennial plant with extensive, creeping rhizomes. Its stems are erect, branched in the upper section, and can grow to 1 m high. It has opposite, stalkless, narrow, oblong leaves that are 1–2 cm long.[7]:176 The leaves are yellow-green in color, with scattered translucent dots of glandular tissue.[8] The dots are conspicuous when held up to the light, giving the leaves the 'perforated' appearance to which the plant's Latin name refers. The flowers measure up to 2.5 cm across, have five petals, and are colored bright yellow with conspicuous black dots.[9]:339 The flowers appear in broad cymes at the ends of the upper branches, between late spring and early to mid summer. The sepals are pointed, with black glandular dots. There are many stamens, which are united at the base into three bundles. The pollen grains are ellipsoidal.[2]
When flower buds (not the flowers themselves) or seed pods are crushed, a reddish/purple liquid is produced.[10]
St John's wort reproduces both vegetatively and sexually. It thrives in areas with either a winter- or summer-dominant rainfall pattern; however, distribution is restricted by temperatures too low for seed germination or seedling survival. Altitudes greater than 1500 m, rainfall less than 500 mm, and a daily mean temperature greater than 24 degrees C are considered limiting thresholds. Depending on environmental and climatic conditions, and rosette age, St John's wort will alter growth form and habit to promote survival. Summer rains are particularly effective in allowing the plant to grow vegetatively, following defoliation by insects or grazing.
The seeds can persist for decades in the soil seed bank, germinating following disturbance.[11]
Invasive species
Although Hypericum perforatum is grown commercially in some regions of south east Europe, it is listed as a noxious weed in more than twenty countries and has introduced populations in South and North America, India, New Zealand, Australia, and South Africa.[11] In pastures, St John's wort acts as both a toxic and invasive weed. It replaces native plant communities and forage vegetation to the extent of making productive land nonviable[12] or becoming an invasive species in natural habitats and ecosystems. Ingestion by livestock such as horses, sheep, and cattle can cause photosensitization, central nervous system depression, spontaneous abortion or death.[12][13] Effective herbicides for control of Hypericum include 2,4-D, picloram, and glyphosate. In western North America three beetles Chrysolina quadrigemina, Chrysolina hyperici and Agrilus hyperici have been introduced as biocontrol agents.[14]
- Full plant
- Seedlings
- Fruit
- Blossom
Medical uses
Major depressive disorder
Studies have supported the efficacy of St John's wort as a treatment for depression in humans.[5][15] A 2015 meta-analysis review concluded that it has superior efficacy to placebo in treating depression; is as effective as standard antidepressant pharmaceuticals for treating depression; and has fewer adverse effects than other antidepressants. The authors concluded that it is difficult to assign a place for St. John's wort in the treatment of depression owing to limitations in the available evidence base, including large variations in efficacy seen in trials performed in German-speaking relative to other countries.[16] It is proposed that the mechanism of action of St. John's wort is due to the inhibition of reuptake of certain neurotransmitters.[2]
A 2008 Cochrane review of 29 clinical trials concluded that it was superior to placebo in patients with major depression, as effective as standard antidepressants and had fewer side-effects.[17] According to the National Center for Complementary and Integrative Health (NCCIH) of the National Institutes of Health, it "may help some types of depression, though the evidence is not definitive"; can limit the efficacy of prescription medicines; and psychosis can occur as a rare side effect. The NCCIH notes that combining St John's wort with certain prescription antidepressants can lead to a "potentially life-threatening increase of serotonin," a brain chemical targeted by antidepressants.[18] A 2016 review came to the same conclusions as the 2008 Cochrane review, but noted that the quality of evidence in regards to both effectiveness and incidence of adverse effects was reduced relative to that for conventional antidepressants.[19]
In Germany, St. John's wort is sometimes prescribed for mild to moderate depression, especially in children and adolescents.[20][21]
Side effects
St John's wort is generally well tolerated, with an adverse effect profile similar to placebo.[22] Commonly reported adverse effects include gastrointestinal symptoms (nausea, abdominal pain, loss of appetite, and diarrhea), dizziness, confusion, fatigue, sedation, dry mouth, restlessness, and headache.[23][24][25] The organ systems associated with adverse drug reactions to St John's wort and fluoxetine (a SSRI) have a similar incidence profile;[26] most of these reactions involve the central nervous system.[26] St John's wort also decreases the levels of estrogens, such as estradiol, by speeding up its metabolism, and should not be taken by women on contraceptive pills as it upregulates the CYP3A4 cytochrome of the P450 system in the liver.[27]
St John's wort may rarely cause photosensitivity. This can lead to visual sensitivity to light and to sunburns in situations that would not normally cause them.[22]
St John's wort is associated with aggravating psychosis in people who have schizophrenia.[28]
St. John's wort has interactions with medications such as SSRI antidepressants, warfarin, and birth control. Combining both St John's wort and SSRI antidepressants could lead to increased serotonin levels causing serotonin syndrome.[29] Combining estrogen containing oral contraceptives with St John's wort can lead to decreased efficacy of the contraceptive and eventually unplanned pregnancies.[30] St. John's wort has been known to decrease the blood concentrations of immunosuppressants (Cyclosporine & Tacrolimus), sedatives (Midazolam & Alprazolam), anticoagulants (Phenprocoumon), chemotherapy drugs (Irinotecan) and other medications.[31] These are just a few of the drug interactions that St John's wort possesses. It is also known to decrease the efficacy of HIV medications, cholesterol medications, as well as transplant medications.[32]
Consumption of St. John's wort is discouraged for those with bipolar disorder. There is concern that people with bipolar depression taking St. John's wort may be at a higher risk for mania.[33]
St John's wort has been shown to cause multiple drug interactions through induction of the cytochrome P450 enzymes CYP3A4 and CYP1A2. This drug-metabolizing enzyme induction results in the increased metabolism of certain drugs, leading to decreased plasma concentration and potential clinical effect.[34] The principal constituents thought to be responsible are hyperforin and amentoflavone. There is strong evidence that the mechanism of action of these interactions is activation of the pregnane X receptor.[35]
St John's wort has also been shown to cause drug interactions through the induction of the P-glycoprotein efflux transporter. Increased P-glycoprotein expression results in decreased absorption and increased clearance of certain drugs, leading to lower plasma concentrations and impaired clinical efficacy.[36]
|Non-nucleoside reverse transcriptase inhibitors, protease inhibitors
|Alprazolam, midazolam
|Hormonal contraception
|Combined oral contraceptives
|Calcineurin inhibitors, cyclosporine, tacrolimus
|Amiodarone, flecainide, mexiletine
|Metoprolol, carvedilol
|Calcium channel blockers
|Verapamil, diltiazem, amlodipine
|Statins (cholesterol-reducing medications)
|Lovastatin, simvastatin, atorvastatin
|Digoxin, methadone, omeprazole, phenobarbital, theophylline, warfarin, levodopa, buprenorphine, irinotecan
|Reference: Rossi, 2005; Micromedex
For a complete list, see CYP3A4 ligands and CYP2C9 ligands.
In combination with other drugs that may elevate 5-HT (serotonin) levels in the central nervous system (CNS), St John's wort may contribute to serotonin syndrome, a potentially life-threatening adverse drug reaction.[37]
|MAOIs, TCAs, SSRIs, SNRIs, mirtazapine
|Tramadol, pethidine (meperidine), Levorphanol
|CNS stimulants
|Phentermine, diethylpropion, amphetamines, sibutramine, cocaine
|5-HT1 agonists
|Psychedelic drugs
|Methylenedioxymethamphetamine (MDMA), LSD, Dimethyltryptamine (DMT), MDA, 6-APB
|Selegiline, tryptophan, buspirone, lithium, linezolid, 5-HTP, dextromethorphan
Mechanism of action
St. John's wort, similarly to other herbs, contains a whole host of different chemical constituents that may be pertinent to its therapeutic effects.[38] Hyperforin and adhyperforin, two phloroglucinol constituents of St John's wort, are TRPC6 receptor agonists and, consequently, they induce noncompetitive reuptake inhibition of monoamines (specifically, dopamine, norepinephrine, and serotonin), GABA, and glutamate when they activate this ion channel.[15][39][40] In humans, the active ingredient hyperforin is also an inhibitor of PTGS1, arachidonate 5-lipoxygenase, SLCO1B1 and an inducer of cMOAT.[39][40][41] Hyperforin is also a anti-inflammatory compound with anti-angiogenic, antibiotic, and neurotrophic properties.[39][40][41] Hyperforin also has an antagonistic effect on NMDA receptors, a type of glutamate receptor.[40] Moreover, St John's wort is known to downregulate the β1 adrenoceptor and upregulate postsynaptic 5-HT1A and 5-HT2A receptors, both of which are a type of serotonin receptor.[15] Other compounds may also play a role in St John's wort's antidepressant effects. Such compounds include: oligomeric procyanidines, flavonoids (quercetin), hypericin, and pseudohypericin.[15][42][43][44]
| Conc.[38]
|log P
[Note 1]
[Note 2]
[Note 3]
[Note 4]
[Note 5]
|t1/2[47] (h)
|Tmax[47] (h)
|Cmax[47] (mM)
|CSS[47] (mM)
|Notes/Biological activity[Note 6]
|Phloroglucinols (2-5%)
|Inhibits reuptake of: 5-HT, DA, NE, GABA and Glu via TRPC6 activation[48]
|Serves as a TRPC6 and PXR agonist. Reuptake inhibitor of 5-HT (205nM), DA (102nM), NE (80nM), GABA (184nM), Glu (829nM), Gly and Ch (8.5μM). Angiogenesis, COX-1 (300nM), 5-LO (90nM), SIRT1 (15μM), SIRT2 (28μM) and MRSA (1.86μM) inhibitor.
|Naphthodianthrones (0.03-3%)
| -
(3.4 μM)
|- (8.5 μM)
| -
(8.7 μM)
|Is a topoisomerase II,[52] PKA (10μM), PKC (27nM), CK1 (3μM), CK2 (6nM), MAPK (4nM), EGFR (35nM), InsR (29nM), PI3K (180nM), DBH (12.4μM), DNA polymerase A (14.7μM), HIV-1 RT (770nM), COMT, MAOA (68μM) and MAOB (420μM), succinoxidase (8.2μM), GSR (2.1nM), GPx (5.2μM), GST (6.6μM) and CuZnSOD (5.25μM) inhibitor.[47][51] Binds to the NMDA receptor (Ki=1.1μM), μ-opioid, κ-opioid, δ-opioid, 5-HT6, CRF1, NPY-Y1, NPY-Y2 and σ receptors.[51] Exhibits light-dependent inhibitory effects on HIV-1 and cancers.[51]
|Photosensitiser and antiretroviral like hypericin.[54][55] PKC inhibitory effects in vitro.[56]
|Flavonoids (2-12%)
| Amentoflavone
| -
(35 nM)
|- (24.3 μM)
| -
(4.8 μM)
|Serves as a fatty acid synthase (FASN) inhibitor,[58][59][60] kappa opioid antagonist,[61] and a negative allosteric modulator at the benzodiazepine site of the GABAA receptor.[62]
|Benzodiazepine receptor ligand (Ki=4μM) with anxiolytic effects.[63] Also has anti-inflammatory, anticancer, cancer-preventing and antioxidant effects.[64][65]
|Anticancer, antioxidant, cardioprotective and antimicrobial.[66][67] Cannabinoid receptor CB1 ligand.[68]
|Found in higher concentrations in Green tea. Antioxidant. CB1 receptor ligand (Ki=35.7 μM).[68]
|-[69] (3.87μM)
|Has anti-fungal effects in vitro (against the plant pathogens P. guepini and Drechslera),[70] neuroprotective effects via the PI3K/Akt/Bad/BclXL signalling pathway in vitro,[71] anti-inflammatory effects via NF-κB inhibition in vitro,[72] D2 receptor-dependent antidepressant-like effects in vivo,[73] and antiglucocorticoid-like effects in vitro.[74]
|+/-[Note 7]
|Inhibits the following: inflammation (via NF-κB and STAT1 inhibition),[76] cancer, HDAC,[77] bacteria, viruses, protozoa and fungi.[78] It is also known to prevent cardiovascular disease and cancer.[78]
|Has anti-inflammatory, anticancer, anti-allergic and antioxidant effects.[79][80] May also have positive effects on people with autism spectrum disorders.[81] Potent non-selective competitive inhibitor of PDE1-5.[82]
| -
(7.5 μM)
| - (47 μM)
| - (24 μM)
| - (22 μM)
|Has anti-cancer, anti-inflammatory, anti-allergic, anti-asthmatic, antihypertensive, analgesic, neuroprotective, gastroprotective, anti-diabetic, cardiovascular disease-preventing, antioxidant, antidepressant-like (in rat models of depression), anxiolytic-like, sedative, antimicrobial and athletic performance-promoting effects.[84] Non-selective PDE1-4 inhibitor that is slightly selective for PDE3/4 over PDE1/2.[85]
|Has anticancer, cardioprotective, nephroprotective, antioxidant, anti-inflammatory, antidiabetic, procognitive and antilipidaemic effects.[86]
|Phenolic acids (~0.1%)
|Caffeic acid
|Anticancer, hepatoprotective, antibacterial and antioxidant effects reported.[88]
|Chlorogenic acid
|Antibacterial, anticancer and antioxidant effects have been demonstrated.[89]
|Molecular weight in g•mol−1.
|Elimination half-life in hours
|Time to peak plasma concentration in hours
|Peak plasma concentration in mM
|Steady state plasma concentration in mM
|Partition coefficient. These values are experimental values taken from ChemSpider and [90] (the access dates are both 13–15 December 2013) where available or, if they are not available approximations are taken from [www.chemaxon.com/download/marvin/for-end-users/ ChemAxon MarvinSketch] 6.1.4 & [91]
|Polar surface area of the molecule in question in square angstroms (Å2). Obtained from PubChem (the access date is 13 December 2013).
|These values pertain to the approximation concentration (in %) of the constituents in the fresh plant material
|Indicates inhibition of the enzyme in question.
|Indicates an inductive effect on the enzyme in question.
|No effect on the enzyme in question.
|5-hydroxytryptamine — synonym for serotonin.
|γ-aminobutyric acid
|Pharmacokinetic data for ECG comes from a study[92] of its pharmacokinetics after oral administration of green tea.
|Comes from this source.[50]
|Pharmacokinetic data for quercetin comes from a study[93] using pure oral quercetin, not a St John's wort extract.
- ↑ In brackets is the IC50/EC50 value depending on whether it is an inhibitory or inductive action being exhibited, respectively.
- ↑ As with last note
- ↑ As with last note
- ↑ As with last note
- ↑ As with last note
- ↑ Values given in brackets are IC50/EC50 depending on whether it's an inhibitory or inductive action the compound displays towards the biologic target in question. If it pertains to bacterial growth inhibition the value is MIC50
- ↑ Depends on the time frame: short-term administration causes inhibition; long-term causes induction via PXR
In large doses, St John's wort is poisonous to grazing livestock (cattle, sheep, goats, horses).[12] Behavioural signs of poisoning are general restlessness and skin irritation. Restlessness is often indicated by pawing of the ground, headshaking, head rubbing, and occasional hindlimb weakness with knuckling over, panting, confusion, and depression. Mania and hyperactivity may also result, including running in circles until exhausted. Observations of thick wort infestations by Australian graziers include the appearance of circular patches giving hillsides a 'crop circle' appearance, it is presumed, from this phenomenon. Animals typically seek shade and have reduced appetite. Hypersensitivity to water has been noted, and convulsions may occur following a knock to the head. Although general aversion to water is noted, some may seek water for relief.
Severe skin irritation is physically apparent, with reddening of non-pigmented and unprotected areas. This subsequently leads to itch and rubbing, followed by further inflammation, exudation, and scab formation. Lesions and inflammation that occur are said to resemble the conditions seen in foot and mouth disease. Sheep have been observed to have face swelling, dermatitis, and wool falling off due to rubbing. Lactating animals may cease or have reduced milk production; pregnant animals may abort. Lesions on udders are often apparent. Horses may show signs of anorexia, depression (with a comatose state), dilated pupils, and injected conjunctiva.
Increased respiration and heart rate is typically observed while one of the early signs of St John's wort poisoning is an abnormal increase in body temperature. Affected animals will lose weight, or fail to gain weight; young animals are more affected than old animals. In severe cases death may occur, as a direct result of starvation, or because of secondary disease or septicaemia of lesions. Some affected animals may accidentally drown. Poor performance of suckling lambs (pigmented and non-pigmented) has been noted, suggesting a reduction in the milk production, or the transmission of a toxin in the milk.
Most clinical signs in animals are caused by photosensitisation.[94] Plants may induce either primary or secondary photosensitisation:
- primary photosensitisation directly from chemicals contained in ingested plants
- secondary photosensitisation from plant-associated damage to the liver.
Araya and Ford (1981) explored changes in liver function and concluded there was no evidence of Hypericum-related effect on the excretory capacity of the liver, or any interference was minimal and temporary. However, evidence of liver damage in blood plasma has been found at high and long rates of dosage.
Photosensitisation causes skin inflammation by a mechanism involving a pigment or photodynamic compound, which when activated by a certain wavelength of light leads to oxidation reactions in vivo. This leads to lesions of tissue, particularly noticeable on and around parts of skin exposed to light. Lightly covered or poorly pigmented areas are most conspicuous. Removal of affected animals from sunlight results in reduced symptoms of poisoning.
Detection in body fluids
Hypericin, pseudohypericin, and hyperforin may be quantitated in plasma as confirmation of usage and to estimate the dosage. These three active substituents have plasma elimination half-lives within a range of 15–60 hours in humans. None of the three has been detected in urine specimens.[95]
Chemical constituents
The plant contains the following:[38][46]
- Flavonoids (e.g. epigallocatechin, rutin, hyperoside, isoquercetin, quercitrin, quercetin, amentoflavone, biapigenin, astilbin, myricetin, miquelianin, kaempferol, luteolin)
- Phenolic acids (e.g. chlorogenic acid, caffeic acid, p-coumaric acid, ferulic acid, p-hydroxybenzoic acid, vanillic acid)
- Naphthodianthrones (e.g. hypericin, pseudohypericin, protohypericin, protopseudohypericin)
- Phloroglucinols (e.g. hyperforin, adhyperforin)
- Tannins (unspecified, proanthocyanidins reported)
- Volatile oils (e.g. 2-methyloctane, nonane, 2-methyldecane, undecane, α-pinene, β-pinene, α-terpineol, geraniol, myrcene, limonene, caryophyllene, humulene)
- Saturated fatty acids (e.g. isovaleric acid (3-methylbutanoic acid), myristic acid, palmitic acid, stearic acid)
- Alkanols (e.g. 1-tetracosanol, 1-hexacosanol)
- Vitamins & their analogues (e.g. carotenoids, choline, nicotinamide, nicotinic acid)
- Miscellaneous others (e.g. pectin, β-sitosterol, hexadecane, triacontane, kielcorin, norathyriol)
The naphthodianthrones hypericin and pseudohypericin along with the phloroglucinol derivative hyperforin are thought to be among the numerous active constituents.[2][96][97][98] It also contains essential oils composed mainly of sesquiterpenes.[2]
- Pseudohypericin
- Kielcorin
- Norathyriol
St John's wort is being studied for effectiveness in the treatment of certain somatoform disorders. Results from the initial studies are mixed and still inconclusive; some research has found no effectiveness, other research has found a slight lightening of symptoms. Further study is needed and is being performed.
A major constituent chemical, hyperforin, may be useful for treatment of alcoholism, although dosage, safety and efficacy have not been studied.[99][100] Hyperforin has also displayed antibacterial properties against Gram-positive bacteria, although dosage, safety and efficacy has not been studied.[101] Herbal medicine has also employed lipophilic extracts from St John's wort as a topical remedy for wounds, abrasions, burns, and muscle pain.[100] The positive effects that have been observed are generally attributed to hyperforin due to its possible antibacterial and anti-inflammatory effects.[100] For this reason hyperforin may be useful in the treatment of infected wounds and inflammatory skin diseases.[100] In response to hyperforin's incorporation into a new bath oil, a study to assess potential skin irritation was conducted which found good skin tolerance of St John's wort.[100]
Hypericin and pseudohypericin have shown both antiviral and antibacterial activities. It is believed that these molecules bind non-specifically to viral and cellular membranes and can result in photo-oxidation of the pathogens to kill them.[2]
Concentrations of bioactive substances can be altered by regulating the environment during plant growth like different levels of UV-B radiation, for instance.[102]
See also
- ↑ "BSBI List 2007". Botanical Society of Britain and Ireland. Archived from the original (xls) on 2015-02-25. Retrieved 2014-10-17.
- 1 2 3 4 5 6 Mehta, Sweety (2012-12-18). "Pharmacognosy of St. John's Wort". Pharmaxchange.info. Retrieved 2014-02-16.
- ↑ "Enzymes". Hyperforin. Human Metabolome Database. 3.6. University of Alberta. 30 June 2013. Retrieved 12 December 2014.
Hyperforin is found in alcoholic beverages. Hyperforin is a constituent of Hypericum perforatum (St John's Wort) Hyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum (St John's wort). The structure of hyperforin was elucidated by a research group from the Shemyakin Institute of Bio-organic Chemistry (USSR Academy of Sciences in Moscow) and published in 1975. Hyperforin is a prenylated phloroglucinol derivative. Total synthesis of hyperforin has not yet been accomplished, despite attempts by several research groups. Hyperforin has been shown to exhibit anti-inflammatory, anti-tumor, antibiotic and anti-depressant functions (PMID 17696442 , 21751836 , 12725578 , 12018529 )
1. Arachidonate 5-lipoxygenase ...Specific function: Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes ...
2. Prostaglandin G/H synthase 1 ... General function: Involved in peroxidase activity
- ↑ Wölfle U, Seelinger G, Schempp CM (2014). "Topical application of St. John's wort (Hypericum perforatum)". Planta Med. 80 (2-3): 109–20. doi:10.1055/s-0033-1351019. PMID 24214835.
Anti-inflammatory mechanisms of hyperforin have been described as inhibition of cyclooxygenase-1 (but not COX-2) and 5-lipoxygenase at low concentrations of 0.3 µmol/L and 1.2 µmol/L, respectively [52], and of PGE2 production in vitro [53] and in vivo with superior efficiency (ED50 = 1 mg/kg) compared to indomethacin (5 mg/kg) [54]. Hyperforin turned out to be a novel type of 5-lipoxygenase inhibitor with high effectivity in vivo [55] and suppressed oxidative bursts in polymorphonuclear cells at 1.8 µmol/L in vitro [56]. Inhibition of IFN-γ production, strong downregulation of CXCR3 expression on activated T cells, and downregulation of matrix metalloproteinase 9 expression caused Cabrelle et al. [57] to test the effectivity of hyperforin in a rat model of experimental allergic encephalomyelitis (EAE). Hyperforin attenuated the symptoms significantly, and the authors discussed hyperforin as a putative therapeutic molecule for the treatment of autoimmune inflammatory diseases sustained by Th1 cells.
- 1 2 Klemow KM, Bartlow A, Crawford J, Kocher N, Shah J, Ritsick M (2011). "Chapter 11: Medical Attributes of St. John's Wort (Hypericum perforatum)". In Benzie IF, Sissi WG. Herbal Medicine Biomolecular and Clinical Aspects. (2nd ed.). CRC Press. ISBN 9781439807163. Retrieved 3 December 2014.
- ↑ "Hypericum perforatum L.". Retrieved 19 August 2015.
- ↑ Rose, F (2006). The wild flower key. Frederick Warne. ISBN 9780723251750.
- ↑ Zobayed SM, Afreen F, Goto E, Kozai T (2006). "Plant–Environment Interactions: Accumulation of Hypericin in Dark Glands of Hypericum perforatum". Annals of Botany. 98 (4): 793–804. doi:10.1093/aob/mcl169.
- ↑ Stace, C.A. (2010). New flora of the British isles (Third ed.). Cambridge, U.K.: Cambridge University Press. ISBN 9780521707725.
- ↑ "St John's wort Hypericum perforatum". Project Noah. 2013. Archived from the original on 8 August 2016. Retrieved 8 August 2016.
- 1 2 "SPECIES: Hypericum perforatum" (PDF). Fire Effects Information System.
- 1 2 3 "Archived copy". Archived from the original on 31 March 2016. Retrieved 2015-10-19.|Hypericum perforatum
- ↑ Watt, John Mitchell; Breyer-Brandwijk, Maria Gerdina: The Medicinal and Poisonous Plants of Southern and Eastern Africa 2nd ed Pub. E & S Livingstone 1962
- ↑ John L. Harper (2010). Population Biology of Plants. Blackburn Press. ISBN 978-1-932846-24-9.
- 1 2 3 4 Nathan PJ (2001). "Hypericum perforatum (St John's Wort): a non-selective reuptake inhibitor? A review of the recent advances in its pharmacology". J. Psychopharmacol. 15 (1): 47–54. doi:10.1177/026988110101500109. PMID 11277608.
- ↑ Linde K, Kriston L, Rücker G, Jamila S, Schumann I, Meissner K, Sigterman K, Schneider A (February 2015). "Efficacy and acceptability of pharmacological treatments for depressive disorders in primary care: systematic review and network meta-analysis". Ann Fam Med. 13 (1): 69–79. doi:10.1370/afm.1687. PMC 4291268. PMID 25583895.
In network meta-analysis, tricyclic and tetracyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), a serotonin-noradrenaline reuptake inhibitor (SNRI; venlafaxine), a low-dose serotonin antagonist and reuptake inhibitor (SARI; trazodone) and hypericum extracts were found to be significantly superior to placebo, with estimated odds ratios between 1.69 and 2.03. There were no statistically significant differences between these drug classes. Reversible inhibitors of monoaminoxidase A (rMAO-As) and hypericum extracts were associated with significantly fewer dropouts because of adverse effects compared with TCAs, SSRIs, the SNRI, a noradrenaline reuptake inhibitor (NRI), and noradrenergic and specific serotonergic antidepressant agents (NaSSAs). ... TCAs and SSRIs have the most solid evidence base. Further agents (hypericum, rMAO-As, SNRI, NRI, NaSSAs, SARI) showed some positive results, but limitations of the currently available evidence makes a clear recommendation on their place in clinical practice difficult.
- ↑ Linde K, Berner MM, Kriston L (2008). Linde K, ed. "St John's wort for major depression". Cochrane Database Syst Rev (4): CD000448. doi:10.1002/14651858.CD000448.pub3. PMID 18843608.
- ↑ "National Institute for Complementary and Integrative Health: St. John's Wort". Retrieved 2015-02-05.
- ↑ Apaydin EA, Maher AR, Shanman R, Booth MS, Miles JN, Sorbero ME, Hempel S (2016). "A systematic review of St. John's wort for major depressive disorder". Syst Rev. 5 (1): 148. doi:10.1186/s13643-016-0325-2. PMID 27589952.
- ↑ Dörks, M; Langner, I; Dittmann, U; Timmer, A; Garbe, E (August 2013). "Antidepressant drug use and off-label prescribing in children and adolescents in Germany: results from a large population-based cohort study.". European Child & Adolescent Psychiatry. 22 (8): 511–8. doi:10.1007/s00787-013-0395-9. PMID 23455627.
- ↑ Fegert JM, Kölch M, Zito JM, Glaeske G, Janhsen K (February–April 2006). "Antidepressant use in children and adolescents in Germany". J Child Adolesc Psychopharmacol. 16 (1-2): 197–206. doi:10.1089/cap.2006.16.197. PMID 16553540.
- 1 2 Ernst E, Rand JI, Barnes J, Stevinson C (1998). "Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.)". Eur. J. Clin. Pharmacol. 54 (8): 589–94. doi:10.1007/s002280050519. PMID 9860144.
- ↑ Barnes, J; Anderson, LA; Phillipson, JD (2002). Herbal Medicines: A guide for healthcare professionals (2nd ed.). London, UK: Pharmaceutical Press. ISBN 9780853692898.
- ↑ Parker V, Wong AH, Boon HS, Seeman MV (2001). "Adverse reactions to St John's Wort". Can J Psychiatry. 46 (1): 77–9. PMID 11221494.
- ↑ Greeson, JM; Sanford, B; Monti, DA (Feb 2001). "St. John's wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature.". Psychopharmacology. 153 (4): 402–14. doi:10.1007/s002130000625. PMID 11243487.
- 1 2 Hoban, Claire L.; Byard, Roger W.; Musgrave, Ian F. (Jul 2015). "A comparison of patterns of spontaneous adverse drug reaction reporting with St. John's Wort and fluoxetine during the period 2000-2013". Clinical and Experimental Pharmacology and Physiology. 42: 747–51. doi:10.1111/1440-1681.12424. PMID 25988866. Retrieved 7 June 2015.
The organ systems affected by ADRs to St John's Wort and fluoxetine have a similar profile, with the majority of cases affecting the central nervous system (45.2%, 61.7%).
- ↑ Barr Laboratories, Inc. (March 2008). "ESTRACE TABLETS, (estradiol tablets, USP)" (PDF). wcrx.com. Retrieved 27 January 2010.
- ↑ Singh, Simon and Edzard Ernst (2008). Trick or Treatment: The Undeniable Facts About Alternative Medicine. W. W. Norton & Company. p. 218. ISBN 978-0-393-33778-5.
- ↑ Borrelli, F; Izzo, AA (December 2009). "Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observations.". The AAPS Journal. 11 (4): 710–27. doi:10.1208/s12248-009-9146-8. PMID 19859815.
- ↑ Russo, Emilio; Scicchitano, Francesca; Whalley, Benjamin J.; Mazzitello, Carmela; Ciriaco, Miriam; Esposito, Stefania; Patanè, Marinella; Upton, Roy; Pugliese, Michela; Chimirri, Serafina; Mammì, Maria; Palleria, Caterina; De Sarro, Giovambattista (May 2014). "Hypericum perforatum: pharmacokinetic, mechanism of action, tolerability, and clinical drug-drug interactions.". Phytotherapy Research. 28 (5): 643–655. doi:10.1002/ptr.5050. PMID 23897801.
- ↑ Skalli, Souad; Zaid, Abdelhamid; Soulaymani, Rachida (December 2007). "Drug Interactions With Herbal Medicines". Ther Drug Monit. 29 (6): 3.
- ↑ Tirona, RG; Bailey, DG (June 2006). "Herbal product-drug interactions mediated by induction.". British Journal of Clinical Pharmacology. 61 (6): 677–81. doi:10.1111/j.1365-2125.2006.02684.x. PMID 16722828.
- ↑ "St. John's wort - University of Maryland Medical Center". University of Maryland Medical Center. umm.edu. 24 June 2013. Retrieved 3 January 2014.
- ↑ Wenk M, Todesco L, Krähenbühl S (2004). "Effect of St John's wort on the activities of CYP1A2, CYP3A4, CYP2D6, N-acetyltransferase 2, and xanthine oxidase in healthy males and females" (PDF). Br J Clin Pharmacol. 57 (4): 495–499. doi:10.1111/j.1365-2125.2003.02049.x. PMC 1884478. PMID 15025748.
- ↑ Kober M, Pohl K, Efferth T (2008). "Molecular mechanisms underlying St. John's wort drug interactions". Curr. Drug Metab. 9 (10): 1027–37. PMID 19075619.
- ↑ Gurley BJ, Swain A, Williams DK, Barone G, Battu SK (2008). "Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics". Mol Nutr Food Res. 52 (7): 772–9. doi:10.1002/mnfr.200700081. PMC 2562898. PMID 18214850.
- 1 2 Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
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- ↑ Butterweck V (2003). "Mechanism of action of St John's wort in depression : what is known?" (PDF). CNS Drugs. 17 (8): 539–62. doi:10.2165/00023210-200317080-00001. PMID 12775192.
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- ↑ "St. John's wort". Natural Standard. Cambridge, MA. Retrieved 13 December 2013.
- 1 2 Greeson JM, Sanford B, Monti DA (February 2001). "St. John's wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature" (PDF). Psychopharmacology. 153 (4): 402–414. doi:10.1007/s002130000625. PMID 11243487.
- 1 2 3 4 5 6 Anzenbacher, Pavel; Zanger, Ulrich M., eds. (2012). Metabolism of Drugs and Other Xenobiotics. Weinheim, Germany: Wiley-VCH. doi:10.1002/9783527630905. ISBN 978-3-527-63090-5.
- ↑ Jensen AG, Hansen SH, Nielsen EO (2001). "Adhyperforin as a contributor to the effect of Hypericum perforatum L. in biochemical models of antidepressant activity". Life Sci. 68 (14): 1593–1605. doi:10.1016/S0024-3205(01)00946-8. PMID 11263672.
- 1 2 Krusekopf S, Roots I (2005). "St. John's wort and its constituent hyperforin concordantly regulate expression of genes encoding enzymes involved in basic cellular pathways". Pharmacogenet. Genomics. 15 (11): 817–829. doi:10.1097/01.fpc.0000175597.60066.3d. PMID 16220113.
- 1 2 3 Obach RS (2000). "Inhibition of human cytochrome P450 enzymes by constituents of St. John's Wort, an herbal preparation used in the treatment of depression" (PDF). J. Pharmacol. Exp. Ther. 294 (1): 88–95. PMID 10871299.
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- ↑ Peebles KA, Baker RK, Kurz EU, Schneider BJ, Kroll DJ (2001). "Catalytic inhibition of human DNA topoisomerase IIalpha by hypericin, a naphthodianthrone from St. John's wort (Hypericum perforatum)". Biochem. Pharmacol. 62 (8): 1059–1070. doi:10.1016/S0006-2952(01)00759-6. PMID 11597574.
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- ↑ Meruelo D, Lavie G, Lavie D (1988). "Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin" (PDF). Proc. Natl. Acad. Sci. U.S.A. 85 (14): 5230–5234. doi:10.1073/pnas.85.14.5230. PMC 281723. PMID 2839837.
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- ↑ Berger A, Venturelli S, Kallnischkies M, Böcker A, Busch C, Weiland T, Noor S, Leischner C, Weiss TS, Lauer UM, Bischoff SC, Bitzer M (2013). "Kaempferol, a new nutrition-derived pan-inhibitor of human histone deacetylases". J. Nutr. Biochem. 24 (6): 977–985. doi:10.1016/j.jnutbio.2012.07.001. PMID 23159065.
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- ↑ Seelinger G, Merfort I, Schempp CM (2008). "Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin". Planta Med. 74 (14): 1667–1677. doi:10.1055/s-0028-1088314. PMID 18937165.
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- ↑ Theoharides TC, Asadi S, Panagiotidou S (April–June 2012). "A case series of a luteolin formulation (NeuroProtek®) in children with autism spectrum disorders". Int J Immunopathol Pharmacol. 25 (2): 317–323. PMID 22697063.
- ↑ Yu MC, Chen JH, Lai CY, Han CY, Ko WC (2010). "Luteolin, a non-selective competitive inhibitor of phosphodiesterases 1-5, displaced [3H]-rolipram from high-affinity rolipram binding sites and reversed xylazine/ketamine-induced anesthesia". Eur. J. Pharmacol. 627 (1-3): 269–275. doi:10.1016/j.ejphar.2009.10.031. PMID 19853596.
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- ↑ Ko WC, Shih CM, Lai YH, Chen JH, Huang HL (2004). "Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig and their structure-activity relationships". Biochem. Pharmacol. 68 (10): 2087–2094. doi:10.1016/j.bcp.2004.06.030. PMID 15476679.
- ↑ Chua LS (2013). "A review on plant-based rutin extraction methods and its pharmacological activities". J Ethnopharmacol. 150 (3): 805–817. doi:10.1016/j.jep.2013.10.036. PMID 24184193.
- ↑ Jaikang, C; Niwatananun, K; Narongchai, P; Narongchai, S; Chaiyasut, C (August 2011). "Inhibitory effect of caffeic acid and its derivatives on human liver cytochrome P450 3A4 activity". Journal of Medicinal Plants Research. 5 (15): 3530–3536.
- ↑ Hou, J; Fu, J; Zhang, ZM; Zhu, HL. "Biological activities and chemical modifications of caffeic acid derivatives". Fudan University Journal of Medical Sciences. 38 (6): 546–552. doi:10.3969/j.issn.1672-8467.2011.06.017.
- ↑ Zhao Y, Wang J, Ballevre O, Luo H, Zhang W (2012). "Antihypertensive effects and mechanisms of chlorogenic acids". Hypertens. Res. 35 (4): 370–374. doi:10.1038/hr.2011.195. PMID 22072103.
- ↑
- ↑ http://www.acdlabs.com/resources/freeware/chemsketch/ACDChemSketch
- ↑ Lee MJ, Maliakal P, Chen L, Meng X, Bondoc FY, Prabhu S, Lambert G, Mohr S, Yang CS (2002). "Pharmacokinetics of tea catechins after ingestion of green tea and (−)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability" (PDF). Cancer Epidemiol. Biomarkers Prev. 11 (10 Pt 1): 1025–1032. PMID 12376503.
- ↑ Walle T, Walle UK, Halushka PV (2001). "Carbon dioxide is the major metabolite of quercetin in humans" (PDF). J. Nutr. 131 (10): 2648–2652. PMID 11584085.
- ↑ St John's wort effects on animals Archived 26 February 2015 at the Wayback Machine.
- ↑ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1445–1446.
- ↑ Umek A, Kreft S, Kartnig T, Heydel B (1999). "Quantitative phytochemical analyses of six hypericum species growing in slovenia". Planta Med. 65 (4): 388–90. doi:10.1055/s-2006-960798. PMID 17260265.
- ↑ Tatsis EC, Boeren S, Exarchou V, Troganis AN, Vervoort J, Gerothanassis IP (2007). "Identification of the major constituents of Hypericum perforatum by LC/SPE/NMR and/or LC/MS". Phytochemistry. 68 (3): 383–93. doi:10.1016/j.phytochem.2006.11.026. PMID 17196625.
- ↑ Schwob I, Bessière JM, Viano J.Composition of the essential oils of Hypericum perforatum L. from southeastern France.C R Biol. 2002;325:781-5.
- ↑ Kumar V, Mdzinarishvili A, Kiewert C, Abbruscato T, Bickel U, van der Schyf CJ, Klein J (2006). "NMDA receptor-antagonistic properties of hyperforin, a constituent of St. John's Wort" (PDF). J. Pharmacol. Sci. 102 (1): 47–54. doi:10.1254/jphs.FP0060378. PMID 16936454.
- 1 2 3 4 5 Reuter J, Huyke C, Scheuvens H, Ploch M, Neumann K, Jakob T, Schempp CM (2008). "Skin tolerance of a new bath oil containing St. John's wort extract". Skin Pharmacol Physiol. 21 (6): 306–311. doi:10.1159/000148223. PMID 18667843.
- ↑ Cecchini C, Cresci A, Coman MM, Ricciutelli M, Sagratini G, Vittori S, Lucarini D, Maggi F (2007). "Antimicrobial activity of seven hypericum entities from central Italy". Planta Med. 73 (6): 564–6. doi:10.1055/s-2007-967198. PMID 17516331.
- ↑ Germ M, Stibilj V, Kreft S, Gaberščik A, Kreft I (2010). "Flavonoid, tannin and hypericin concentrations in the leaves of St. John's wort (Hypericum perforatum L.) are affected by UV-B radiation levels". Food Chemistry. 122: 471–474. doi:10.1016/j.foodchem.2010.03.008.
Further reading
- British Herbal Medicine Association Scientific Committee (1983). British Herbal Pharmacopoeia. West Yorkshire: British Herbal Medicine Association. ISBN 0-903032-07-4.
- Müller, Walter (2005). St. John's Wort and its Active Principles in Depression and Anxiety. Basel: Birkhäuser. doi:10.1007/b137619. ISBN 978-3-7643-6160-0.
External links
|Wikispecies has information related to: Hypericum perforatum
|Wikimedia Commons has media related to Hypericum perforatum.
- "St. John's wort: MedlinePlus Supplements". U.S. National Library of Medicine. Retrieved 7 October 2009.
- Species Profile — St. Johnswort (Hypericum perforatum), National Invasive Species Information Center, United States National Agricultural Library. Lists general information and resources for St John's wort.


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As promised here are (finally) some pictures of lovely BESTA storage from Ikea on our dining room wall.
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Dir. Freddie Francis
After the discovery of a prehistoric troglodyte in a cave in primmest, quaintest England, Dr Brockton and her team of anthropologists attempt to communicate with it. The local townsfolk however, are not happy about a potentially dangerous Neanderthal residing so near to their quintessentially quaint English village. A botched plan to get rid of the creature results in it causing all sorts of havoc and mayhem in the local village. Can Dr Brockton and her immaculately shaped eyebrows put a stop to naughty Trog's antics before civilisation crumbles? Can she heck!
Trog is really only significant and of any remote historical interest because it marked Joan Crawford's last ever big-screen role. It was the second film she worked on 'as a favour' for her friend, filmmaker Herman Cohen. Hey, a girl's gotta eat, right? Their other outing together was Berserk! Despite the absolute humiliation Crawford must have undergone making such drivel, she still throws herself into her role as the pert, unflappable and chic pant-suit wearing Dr Brockton with gusto. Aided no doubt by her trusty hip flask of 100% proof vodka.
Director Freddie Francis, who was already a reputable cinematographer and director of such horror titles as The Skull, Paranoiac, Dracula Has Risen From The Grave and The Evil of Frankenstein, doesn't fare much better, failing to inject any sort of life or sense of momentum into the laborious tale. His direction feels stunted and uninspired, and aside from the mildly creepy opening, in which several men fall foul of the titular beast as they explore an eerily lit cave in the English countryside (!), exhibits no flair or imagination whatsoever, and his obvious indifference to the material ensures events simply trundle along at a corpse's pace.
The film begins intriguingly enough with the same uneasy, stiff English malaise that wafts throughout the likes of Amicus and Tigon films; that bizarre juxtaposition of contemporary setting with an oddly cold, slightly gothic atmosphere. After our jaunty spelunking team are set upon by a briefly glimpsed 'thing', events quickly move on as Dr Brocton arrives with her hypogun and tranquilises the cave-man-beast and takes him back to her clinic for research. Henceforth the film becomes a combination of inane scenes featuring Crawford 'taming' the troglodyte and an even more inane series of court hearings in which disgruntled villagers demand the creature is exterminated. After all, his presence runs the risk of bringing property prices down.
Hammy acting, over enthusiasm and hopelessly overwrought emoting soon become the order of the day, ensuring Trog falls firmly into the category of 'so bad, it's good.' In what other film would you see a montage of Joan Crawford playing catch with a man in a pelt and cheap gorilla mask? Said montage also features Trog listening to music, playing with toys, being rewarded, and gently reprimanded when he gets a little rough ("Bad Trog!" scolds Joan Crawford, and we really believe she means it).
|"Get me my hypogun, quickly!"
Some vague attempts at moralising and the faintest whiff of social commentary are thrown into the mix. No, really! You see, because Dr Brockton is a woman, and a fairly feisty one at that, no one trusts her to be able to run the experiments and control Trog. So many women in the Sixties and Seventies faced similar hardships. Unfortunately we don't get as far as seeing Crawford burn her bra, though there are a couple of courtroom scenes which would have provided the perfect platform for such a show of rebellion. And certainly would have livened things up a bit. The authorities only believe Trog shouldn't be put down when several male scientists validate Brockton's approach, which was regarded by many as mollycoddling an untameable man-beast.
Stiff dialogue between characters often strays into attempts at moralising, though it's all so outdated the result is just laughable. A few mildly interesting debates about Darwinism and Creationism are tossed into the already wordy mix. It would appear scriptwriter Aben Kandel views 'mother earth' and nature as monstrous, and if I may put on my 'over analytical' hat for a moment; that sure was a vaginal looking cave Trog came out of. Trog is not created in God's image, he is a product of evolution – a 'concept' those pesky god-fearing villagers don't accept. He is of the earth; mother earth. These aspects of the script, and the maltreatment of Dr Brockton, because she is a woman, provide a rather interesting anti-feminist slant to proceedings. Is it because of a woman's 'meddling' all this damage has been done? Is that what they're saying? Is it? I must know!
There is some subversive humour in how the civilised society Trog finds himself in, though no fault of his own, treat him in such an uncivilised way. The conclusion? Trog is a sentential being who can actually be reasoned with, but not in the face of civilised society, who only want to destroy him. Oh the irony.
Best enjoyed with a stiff drink.


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junkmycar needed a new logo design and created a contest on 99designs.
A winner was selected from 19 designs submitted by 12 freelance designers.
Junk my Car (junkmycar.com)
We are a free junk vehicle removal & recycling service in the USA and Canada. We remove Cars, Trucks and Motorcycles at this time. Our company is technology driven, fun, and fast-paced. Our top priority is exceptional customer service.
We target anyone who has a junk vehicle they need taken away. Many of our customers are under time constraints and search the web for a solution to their problem. They also use our service to get vehicles off the roads in metro or highway environments to avoid fees and fines. Also eco-conscience people my be interested in recycling their vehicle.
We are looking for two holiday themed logos for our website. You can add in images around the logo or slightly modify the logo to make it represent the holiday more.
Example Ideas: Cornucopia, autumn leaves, pumpkin, etc.
Christmas / New Years
Example Ideas: Snow flakes, presents, kazoo and party hat, etc.
I have attached two concepts for an idea of what we are looking for, however we would like them to be of a higher quality and much more creative.
I have also attached the headerlogo.jpg which is the file we would like you to modify.
If you have any questions please ask, just submit your entries and I will rate and comment them.
Find out how a design contest works or learn more about our logo design services.


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Walnut/Secure Distributed Computing/E Capabilities
From Erights
E Capabilities
E has no pointer arithmetic. E has no mutable statics. E has an API carefully thought out to prevent capability leaks. This would make it a capability secure language for single-processor applications. But E goes a step further. It takes the concept of a secure, unforgeable object reference and extends it to distributed objects:
- The communication links are encrypted. Third parties cannot get inside the connection.
- The objects are unfindable without a proper reference received (directly or indirectly) from the creator of the object. You must have the key to unlock the door.
- No object can pretend to be the object you are trying to contact because identity cannot be hijacked.
These aspects of E protocol can be understood better by looking at the URI that identifies an E object to other objects outside its own vat.
A closer look at E capability URIs
The whole E approach to security is disorienting to anyone steeped in traditional computer security lore. On the other hand, anyone with a background in object-oriented programming will find it to be a natural extension of the OO discipline. Another entire book is needed on the philosophy of security exemplified by object capabilities and E. The closest thing to such a Philosophy of Security known to the author is a requirements document for the shared virtual 3D world Croquet. Croquet needs to be both very user friendly and very secure, and so requires the kind of seriousness that object-capabilities enable.
Security as an inexpensive lunch
There is no such thing as a free lunch, but this does not rule out the possibility of lunches at bargain prices. When programming in E, you are automatically working in a capability secure environment. All references are secure references. All powers are accessible only through capabilities. Making an E program secure is largely a matter of thinking about the architecture before you code, and doing a security audit after you code. When designing and auditing you use a small number of principles for scrutinizing the design:
Principle of Least Authority (POLA) for Computer Programs
The Principle of Least Authority (known henceforth as POLA), which has been used by human beings instinctively for thousands of years, translates to computer programs fairly straightforwardly: never give an object more authority than it needs. In particular, if an object may be running on a remote untrusted machine, think very carefully about the minimum set of authorities it needs, and give it capabilities only on facets (described later) that ensure it gets no more. A simple word processor needs read and write access to the one file it is being used to edit, and it needs read-only access on all the system fonts. It does not need any access to anything else. Do not give it access to anything else. If it asks for something else, it is lying to you, and you should not trust it.
Principle of Hardware Software Ownership
When developing software, remember that the person who controls the hardware always, at the end of the day, controls the software. Hence, if you send someone a piece of a distributed program to run on their own equipment, that person totally and utterly owns everything that resides on his machine. They can modify the code you gave them, or rewrite it from scratch yet make it look from the outside like it is identical. You must therefore think carefully about what features of your system you really trust on that remote machine. A key feature of E that enhances its reliability is that objects which are manufactured in a particular vat remain resident in that vat, so that the objects remain as reliable as the objectMakers used to produce them. Only transparent immutables (immutables that don't encapsulate anything) actually move across computational boundaries.
Many people have made the error of believing this principle of hardware ownership can be circumvented. At the time of this writing, the music recording industry is throwing away truly fabulous sums of money on schemes that assume they can somehow control data after it has arrived on a user's own hardware. Microsoft is busily developing Palladium (uh, I mean, NGSCB). Intel is busily developing TCP (uh, I think they changed the name to La Grande). Their fate has already been foretold in the fate of the popular game Diablo I: authoritative representations of data were allowed to reside on user computers, assuming that the object code was too difficult to understand to be hacked and that the Diablo client code would always behave as the designers intended. They were 99% correct, which in the computer security field means they were 100% wrong. Today, 99% of the people who hack Diablo I don't understand the object code. But somewhere some single individual figured it out and posted the result on the Web. Now your grandmother can sabotage shared Diablo I games as quickly and easily as the most accomplished hacker in history. For Diablo II, the developers had learned the lesson. Authoritative information is stored only on the server, giving them the beginnings of true security.
Not only does hardware own the software, so too does the underlying operating system. As we have stated repeatedly here, E enables the construction of extremely secure computing systems. However, E systems can still be attacked from below, by viruses granted authority by the operating system underneath the E world. Such attacks can only be prevented by completing the security regime, either with capability-based operating systems, or with computers on which only capability-secure programs are allowed. There is one open-source capability-based OS under development, at www.eros-os.org.
Denial Of Service Attacks
One form of attack that even E cannot defend against is denial of service (DOS). In a denial of service, someone simply swamps your system with requests, making your system unable to operate. Such attacks take many forms, but the key limitation in such attacks is this: such an attack can never steal your secret data or gain control of your sensitive operations. If DOS were the only kind of attack possible, the world would be a vastly better place. Indeed, if only DOS attacks were possible, even most modern DOS attacks would fail, because the serious DOS attacks require that the attacker first gain control of hundreds of computers that belong to other people, by using attacks far more invasive and damaging than DOS itself.


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Store Directory
|Retailers: To submit your store listing for our directory, please submit your application. If you already have an account, click here to login.
|Your search results for "9796-0123"
Please Note: If you are searching for a particular Marcus Fabrics print from a past collection, we're happy to try to help you locate it. Because we have so many prints available, we're best able to assist you if you'll SEND A SWATCH of the print (instead of a written description), Attn: Customer Service. Be sure to include your name, address, phone and email address.


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Welcome visitor you can login or create an account.
Your shopping cart is empty!
All it's missing is some whipped cream and a cherry on top!
Approx. 64 Pieces per Pound.
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Minardil wrote:Gimli's adoration for Galadriel is very much based on the 'courtly love' model
I think "courtly love" is a good description, but remember that eroticism constrained and denied by the demands duty, the traditions of chivalry, and the limitations imposed by differing stations are a central part of the "courtly love" model. The Knight DESIRES the Queen or at least has romantic love for her, but his duty to the King forbids him from acting on that desire, so he goes on impossible quests and bears her favor and wins tournaments in her honor instead. That sounds like a pretty good description of Gimli's affection for Galadriel.
The argument that Fili is a gorilla and that it is somehow "impossible" for Dwarves and Elves to feel attraction towards each other is just completely wrong.
It's no more wrong than implying that it's a fairly normal thing (which is what PJ's films have done in a way).
Anyway, what completely burns me up about this whole Tauriel/Kili affair is that it was GIMLI who's stance was supposed to be softened toward the Elves, after becoming enamoured of Galadriel and befriending Legolas. It was a major part of Gimli's character arc, and was portrayed (at least in the book) as a thing never before heard of. It's part of what made Gimli a special character. The "three golden hairs" scene on the boat, with Legolas's subsequent reaction, remains one of my favorite parts of the entire LotR trilogy. The Kili/Tauriel nonsense, by contrast, makes me roll my eyes every time I see it. Now people are going to see these films in chronological order and think that Kili, instead of Gimli, was the first Dwarf who was able to overcome millenia of hostility between Dwarves and Elves. They've neutered Gimli's character arc by including this Kili foolishness.


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274 systems found
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Finding software can be overwhelming. We've helped hundreds of dedicated Apple users choose the right PM software so they can manage their projects from a Mac computer and automate tasks.
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Businesses across industries are increasingly looking to adopt project management (PM) software. Indeed, between 2014 and 2015, the number of first-time, small-business buyers who contacted Software Advice in search of a PM system rose 14 percent.
Prospective buyers have several purchase considerations, including which operating system (OS) the software supports. While Windows products previously dominated the workplace, the increasing popularity of iPhones, iPads and iMacs means that more and more businesses are looking for project management software for Mac devices.
Additionally, with the prevalence of cloud-based PM platforms (the majority of which can run on any operating system), dedicated Apple users have more options than ever before.
In this guide, we'll cover:
What Is Mac Project Management Software?
Is a Cloud-Based PM System Right for You?
Common Mac PM Software Capabilities
Key Considerations
Native Mac products are designed to run on the Apple operating system, and provide a consistent user experience across Apple devices. This means the user interface (UI)—how people experience, interact with and understand the product's content—remains largely unchanged across Mac devices, so as to deliver a uniform look and feel.
There are some industries, such as software and technology, which tend to lean more heavily on Apple products and find a greater return on investment with native Mac solutions. However, many PM software vendors are now designing cloud-based, OS-agnostic solutions so as to reach a greater audience; as a result, there are relatively few Mac-only PM tools available in the market.
Thus, buyers who are looking for PM solutions that will work on Apple's operating system should consider OS-agnostic products hosted in the cloud.
Cloud-based PM platforms, which deliver "Software-as-a-Service" (SaaS), are accessible through an Internet browser on any compatible device, making them extremely versatile tools. These systems have a lower upfront cost, since buyers don't pay for the license to own the software outright (typically, a monthly subscription fee is paid, priced per user, to use the software). Traditional on-premise solutions tend to be more expensive up front, since the user pays for the license to own and operate the software in perpetuity.
However, as you can see in the chart below, the long-term costs for both licensing models eventually converge.
Another cost consideration: Cloud software is hosted offsite, on the vendor's servers, and the subscription fee normally covers maintenance, updates and limited support. Conversely, on-premise software is hosted on the user's servers, and additional fees typically apply for updates, maintenance and so on. This means that less (if any) of an organization's internal IT staff and resources are dedicated to software upkeep when a cloud system is used.
To estimate the total cost of ownership for deploying a cloud-based or on-premise solution at your business, check out our Total Cost of Ownership Calculator.
Some PM tools are stand-alone (or "best-of-breed") systems, specializing in one aspect of project management, such as task management or time tracking. However, most are comprehensive suites helping to support all stages of the project life cycle, including:
Additionally, these systems act as a centralized hub, storing files and project communications, which makes it easy for teams to view a project's history. This is especially useful for all organizations practicing project risk management. It can also help specialized teams in certain industries, such as design firms or software developers, that need access to decisions surrounding version changes, new releases and issues or bug fixes (among other things).
With the expanse of PM tools on the market, it's important to keep the following considerations in mind when selecting a system that fits your needs:
Integration options. PM software should easily integrate with existing business applications (e.g., email, accounting and data storage programs, such as Dropbox). Integrating your PM system with your accounting platform is especially important, as it will help streamline your project financials, including budgeting, job costing, billing and invoicing. Be sure to discuss any integration requirements with vendors prior to purchasing a system.
Industry needs. If your organization uses Apple hardware and software, then native Mac project management software might be right for you. However, if your industry is one that experiences frequent change and/or your company is growing, then a cloud-based solution may be a smarter investment: You'll find a greater variety of options that can be used across multiple platforms.
Mobility/remote access. With remote work becoming more commonplace, cloud solutions facilitate a working environment that is standardized, collaborative and transparent and that keeps remote workers accountable. Cloud solutions can be accessed from multiple devices, helping project teams stay connected. And features such as activity streams and in-app or email notifications help team members stay apprised of project updates and changes.


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Je veux ces chaises!
Contemporaines avec une touche rétro, j'adore!
I want them all!!
Contemporary with a retro touch, I love them!
from Vioski
Saturday, February 28, 2009
I'm in love again
Posted by Set Carré at 4:17 PM
Labels: Home sweet Home, Trouvailles - Finds
3 comments:
- Cristin said...
Oh - they are gorgeous! We're in the market for new side chairs! I love the green one... off to go browsing for chairs!
- March 1, 2009 at 7:11 PM
- sunshine said...
Hi Camille!
I found your blog through the Sew, Mama, Sew stash interviews. I love these chairs, they look like they're smiling or grinning.
I'm in PEI and just started quilting last fall, but I've fallen for it 100%. I look forward to browsing the rest of your blog and new postings. I just started a blog of my own recently, it's at http://cuttingedgequilt.blogspot.com/
Cheers, Christine
- March 17, 2009 at 8:10 AM
- Pfeiffer Photos said...
Those are so fantastic! Found you from a twitter tweet...nice blog! :)
- March 21, 2009 at 10:48 PM
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The Erasmus for Young Entrepreneurs is your chance to learn how to start and run your own business. Find out about the programme through Angela's story at the end get some very useful tips!
Is there an entrepreneur inside you trying to get out? Avoid getting lost in a jungle of red tape and find out about the procedures and requirements in other countries.
What better way to find a job than creating your own?


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Only hotels in Clayton are listed below. Find cheap and discounted hotel/motel rates in or nearby Clayton, CA for your business or personal leisure travel. We show the best Clayton California hotel rooms. Review the Clayton hotel list below to find the perfect lodging. We also have a map of the Clayton hotels. Group booking? Search Clayton Group Hotel Rates
The Clayton center is approximately the area of Sleep Train Pavilion and 1 mile north of Mount Diablo State Park.
How should we direct your call?


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Is a taste of ice cream or a sip of hot coffee sometimes a painful experience for you? Does brushing or flossing make you wince occasionally? If so, you may have a common problem called "sensitive teeth".
For millions of people, sensitive teeth can make life miserable. The pain and discomfort make even favorite hot or cold foods impossible to enjoy. All is not lost. In many cases, sensitive teeth can be successfully treated bringing long sought after relief.
What Causes Sensitive Teeth?
The part of the tooth we can see is covered by a layer of enamel that protects the softer dentine underneath. If the dentine is exposed, a tooth can become sensitive. This usually happens where the tooth and the gum meet and the enamel layer is much thinner.
Here are Some Causes of Teeth Sensitivity.
Toothbrush abrasion – brushing too hard, and brushing from side to side, can cause dentine to be worn away, particularly where the teeth meet the gums. The freshly exposed dentine may then become sensitive.
Dental erosion – this is loss of tooth enamel caused by attacks of acid from acidic food and drinks. If enamel is worn away the dentine underneath is exposed, which may lead to sensitivity.
Gum recession – gums may naturally recede (shrink back), and the roots will become exposed and can be more sensitive. Root surfaces do not have an enamel layer to protect them.
Gum disease – a build-up of plaque or tartar can cause the gum to recede down the tooth and even destroy the bony support of the tooth. Pockets can form in the gums around the tooth, making the area difficult to keep clean and the problem worse.
Tooth grinding – this is a habit which involves clenching and grinding the teeth together. This can cause the enamel of the teeth to be worn away, making the teeth sensitive.
Other Causes of Dental Pain from Teeth Sensitivity
A cracked tooth or filling – a cracked tooth is one that has become broken. A crack can run from the biting surface of a tooth down towards the root. Extreme temperatures, especially cold, may cause discomfort.
Tooth bleaching – some patients have sensitivity for a short time during or after having their teeth bleached. Discuss this with your dentist before having treatment
Preventing Sensitive Teeth (Dentin Hypersensitivity)
The key to preventing tooth sensitivity is to keep the gums from receding. Reducing the pressure we use to brush our teeth helps tremendously. The problem with this is that our tooth brushing is an unconsciously ingrained habit reinforced after decades of brushing and therefore nearly impossible to change.
Dentists advise people to use an advanced electric toothbrushes (plaque remover). These toothbrushes feature pressure sensors that stop the brush when you apply too much pressure. Another option is the Alert toothbrush, which activates a warning light when you brush too hard.
5 Home Remedies for Sensitive Teeth
Bring on the desensitizing toothpaste. Unfortunately, widespread tooth sensitivity due to enamel abrasion or gum-line recession can't be treated with dental fillings. Instead, try brushing with a desensitizing toothpaste, which you can buy over the counter. These special toothpastes contain ingredients that diminish sensitivity by filling channels (known as tubules) in the dentin.
Try putting some of the toothpaste on your finger or on a cotton swab and spreading it over the sensitive spots before you go to bed. Spit, but don't rinse. Within a few weeks, your teeth should begin to feel less sensitive.
Try a fluoride rinse. Fluoride rinses, available without a prescription at your local pharmacy or in the dental section of grocery stores, can help decrease sensitivity, especially for people plagued with decay problems. Use it once a day. Swish it around in your mouth, then spit it out.
Sometimes, people with sensitive teeth need a stronger fluoride rinse or gel than the ones available over the counter. For example, some treatments for gum disease, such as root planing (which reduces plaque), can leave sensitive teeth even more sensitive than usual. In such situations, dentists can apply a fluoride gel that helps relieve the problem.
Keep your teeth clean. Plaque, the white gummy substance that forms on teeth, produces an acid that irritates teeth, especially if your choppers are naturally sensitive. Wage a daily attack against plaque by brushing at least twice, preferably right after eating and especially before bed, and flossing at least once.
Use a soft toothbrush. Often, people actually cause tooth sensitivity by brushing with too much force and/or brushing with a hard-bristled brush, which can damage the protective tooth enamel. When the gum-line recedes (often as a natural part of the aging process), exposed dentin becomes even more vulnerable to toothbrush abrasion. Use a brush with the softest bristles you can find, and apply only a small amount of pressure when brushing (actually, a lighter touch also allows the bristles to move more freely and do their job more effectively than when you press too hard).
Say, "Enough!" to snuff. Chewing tobacco, also known as "dip" or "snuff," is a popular habit in some groups, especially among many male teenagers. They mistakenly believe it's less harmful than smoking cigarettes. However, in addition to causing mouth cancers, chewing tobacco causes the gums to recede, a major cause of gum sensitivity and decay. Just as there is no safe cigarette, there is no safe tobacco.
Habits like sucking on hard candy, while certainly healthier than chewing snuff, can also cause enamel abrasion and tooth sensitivity.
Treating Sensitive Teeth
Sensitive teeth can be treated. Your dentist may suggest that you try a desensitizing toothpaste, which contains compounds that help block transmission of sensation from the tooth surface to the nerve. Desensitizing toothpaste usually requires several applications before the sensitivity is reduced. When choosing toothpaste or any other dental care products, look for those that display the American Dental Association's Seal of Acceptance–your assurance that products have met ADA criteria for safety and effectiveness.
If the desensitizing toothpaste does not ease your discomfort, your dentist may suggest in-office techniques. A fluoride gel, which strengthens tooth enamel and reduces the transmission of sensations, may be applied to the sensitive areas of the teeth.
If receding gums cause the sensitivity, your dentist may use agents that bond to the tooth root to "seal" the sensitive teeth. The sealer usually is composed of a plastic material.
In cases where hypersensitivity is severe and persistent and cannot be treated by other means, your dentist may recommend endodontic (root canal) treatment to eliminate the problem.


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Update: Twitter for BlackBerry smartphones v2.0 is now available in BlackBerry App World!
Hot on the heels of the official release of Twitter® for BlackBerry® smartphones v1.1 is the latest beta version of Twitter for BlackBerry smartphones – version 2.0 – which is available in BlackBerry® Beta Zone today.
Another release already, you say? Our Twitter app team here at Research In Motion® (RIM®) has adopted an iterative development approach, which means smaller scoped releases will be available to you on a more frequent basis. This means you get access to more features, faster!
What's New in v2.0?
The focus of this iteration is simplified navigation. You'll notice that the navigation bar has a sleek new look with simplified access to popular Twitter features. For instance, we've combined the 'Search', 'Find People', and 'Popular Topics' screens into a new Single Search Screen. Now you can search for Tweets and people from a single location, as well as view Trends and Saved Searches, unifying the entire Twitter Search experience.
Another great feature for BlackBerry® 6 users: Twitter Search works with the universal search feature on your BlackBerry smartphone! Search for anything and the universal search tool will pull in relevant results from your entire BlackBerry smartphone, including all Search categories within Twitter.
In addition to the new black chrome color scheme, you'll notice there's a new "Compose Tweet" button located on the Nav Bar that acts as a single touch-point for composing Tweets from anywhere in the app.
Sign up for the BlackBerry Beta Zone today and post a comment to let us know what you think. Also, keep an eye out here for subsequent releases coming soon!


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CEDAR RAPIDS, Iowa — So much for Iowa Nice. It's more like Iowa Nasty.
In a state whose Midwestern civility usually extends to politics, the Republican presidential campaign has become an acerbic affair. Negative ads fill TV and radio. Attacks are all over the Internet and in material stuffed in mailboxes. Many of the candidates are bashing each other with abandon.
It's a reflection of the crowded GOP field and the volatile race to emerge as the Republican challenger to President Barack Obama in November. To the dismay of many voters, it's also probably only going to get worse when there are fewer candidates and the contest moves to New Hampshire, South Carolina and beyond.
"If they go negative, they aren't getting my vote," says Ginger Allsup, a 45-year-old Oskaloosa bakery worker.
That's a risk campaigns in Iowa are willing to take, given the high stakes and state of the race ahead of Tuesday's caucuses that kick off the fight for the GOP nomination.
Only three candidates typically make it out of Iowa with enough momentum and money to continue. Polls are showing that most hopefuls are bunched tightly behind former Massachusetts Gov. Mitt Romney. Desperate to break from the pack, they're whacking away in hopes of sinking opponents and wooing undecided voters.
Usually, presidential candidates and their allies take care to be congenial in Iowa, which has a record of rewarding candidates who stay above the fray. It's a state where campaigns seek to make positive first impressions by promoting their own policies and offering subtle comparisons.
By the time New Hampshire comes around, the field usually has narrowed and those left standing try to differentiate themselves even more, in a sharper and often more personal tone. It only escalates from there when voting turns to South Carolina, which has a long history of go-for-the-jugular politics.
But Iowa is different this year.
It's partly because of a Supreme Court decision that allowed unions, corporations and individuals to spend unlimited amounts of money to advocate for the election or defeat of candidates. As a result, new outside groups, known as super PACs (political action committees), that are aligned with the candidates sprang up. These groups have paid for an avalanche of hard-hitting TV and radio ads, as well as aggressive literature in mailboxes and harsh messages online.
What about the candidate? They're hardly holding their tongues. Sometimes, they're using language that Republicans often reserve for Democrats
"She doesn't like Muslims, she hates them, she wants to go get 'em," Texas Rep. Ron Paul said about Minnesota Rep. Michele Bachmann. "Dangerous" is how Bachmann describes Paul's foreign policy.
In other cases, they use humor to try to blunt the force of the attacks.
Asked about Newt Gingrich's failure to get on the Virginia ballot, Romney likened the former House speaker's political operations to an out-of-control chocolate factory from a half-century-old "I Love Lucy" episode.
"Cute" was Gingrich's reply.
He then issued a challenge as he visited a chocolate factory the day after Romney's poke: "Here I am in the chocolate factory. And now that I have the courage to come to the chocolate factory, I hope Gov. Romney will have the courage to debate me one on one and defend his negative ads."
Candidates are being harder on some rivals than others as they look to peel off support from certain blocs.
"I am a consistent conservative. I have always been pro-life. I have always been pro-traditional marriage. I have always been a fiscal conservative. I have never been for global warming," Texas Gov. Rick Perry said this past week in response to a voter's question. He then added, "I'm glad you gave me the opportunity to reflect my differences with Mitt."
Perry was much sharper hours later as he fought for support from Christian conservative voters also being courted heavily by former Pennsylvania Sen. Rick Santorum.
Said Perry: "He is what I call a serial earmarker," referring to the special spending projects that members of Congress seek.
Santorum, who is rising in polls and may end up being Romney's prime challenger in Iowa, said Romney had no track record of success. "In fact, he's only run as a moderate or a liberal," Santorum said.
Running ahead in polls, Romney took care not to initiate attacks and only weighed in when asked questions. But he did give pointed responses.
"I don't think Ron Paul represents the mainstream of Republican thought with regards to issues, particularly in foreign policy,' Romney said, seeking to marginalize his closest pursuer in most polls.
There's a reason candidates are assailing each other: It can work.
Consider Gingrich's up-and-down December.
He was flying high in polls at the start of the month. Then he was pounded by at least $4 million in negative TV ads in Iowa, most run by Romney allies and some by Paul's campaign. The ads cited both personal flaws and professional missteps.
Mailings described him as "as a 30-year Washington insider" who has "taken both sides on core Republican issues." His infidelity is highlighted in emails circulating among conservatives. In addition, a video he once recorded with then-House Speaker Nancy Pelosi, D-Calif., urging action on climate change blankets the Internet.
At campaign events, Bachmann, Paul and others spread those same messages.
"I had been leaning toward Newt," said Jean Fredsall, a 67-year-old retired social worker from Cedar Rapids. "But then I was reminded of his baggage."
But negative advertising also can backfire, particularly in a crowded field in Iowa.
In 2004, former Vermont Gov. Howard Dean and then-Missouri Rep. Dick Gephardt were the front-runners to win the Democratic nomination. Looking to seal the deal, each ran blistering ads just before Iowa voted. Both ended up losing voters and the nomination. Massachusetts Sen. John Kerry and then North Carolina Sen. John Edwards got the coveted tickets out of the leadoff caucus state.
The lesson: Those who run negative ads risk driving up their own negative perceptions in voters' minds.
Republican Mike Huckabee probably was mindful of it four years later.
Rising in the polls just before the caucuses, the former Arkansas governor was the target of criticism. But while pundits called for him to go on the attack himself, the most Huckabee did was tease a negative ad during a news conference. Then, he shelved it before it ever ran.
"It's not worth it," he said, adding: "It's never too late to do the right thing."
Iowans ended up rewarding him with a caucus victory, though John McCain captured the nomination.
Four years later, that lesson seems lost.


text:
The late Sir M. Digby Watt, Architect (from the 2 June 1877 Illustrated London News)
Sir Matthew Digby Wyatt (1820-1877) was a prominent member of the Wyatt dynasty of architects. He was Secretary of the Great Exhibition in 1851, and collaborated with Isambard Kingdom Brunel on Paddington Station (1852-54), where his scheme "introduced a Moresque note" (Curl 210).
As Surveyor of the East India Company, he also collaborated with Sir George Gilbert Scott on the India Office, advising his climb-down in the Battle of the Styles (see Turnor 84-85), and designing, for example, its magnificent Durbar courtyard there (1867). This is seen as his masterpiece, "a tour de force of Italian Renaissance architecture and Minton's majolica" (Waterhouse and Robinson, "Wyatt, Sir Matthew Digby"). It is perfectly clear from this exotic space that he was much influenced by Owen Jones, with whom he was closely associated (see Stuart Durant's commentary on the station, last paragraph).
Amongst other works, he designed the Jewish Cemetery at West Ham, with its circular (listed) Rothschild Mausoleum of 1866. He won the RIBA Gold Medal in 1866 (Allinson 10), and in 1869 was appointed the first Slade Professor of Fine Art at Cambridge. He also served as Vice-President of the RIBA.
Architectural works
- Paddington Station (with Brunel) (1852-54)
- India Office (with Scott)
- Fireplace, Clare College, Cambridge
Book design and illumination
Allinson, Kenneth. Architecture and Architects of London. London: Architectural Press, 2008. Print.
Beckwith, Alice H. R. H. Victorian Bibliomania. Exhibition catalogue. Providence. Rhode Island: Museum of Art, Rhode Island School of Design, 1987. [Twenty-fifth anniversary e-version on this site,]
Curl, James Stevens. Victorian Architecture. Newton Abbot: David & Charles, 1990. Print.
Robinson, John Martin. The Wyatts: An Architectural Dynasty. Oxford: Oxford University Press, 1979. Print.
"Rothschild Mausoleum, Jewish Cemetery." British Listed Buildings. Web. 8 February 2013.
Turnor, Reginald. Nineteenth Century Architecture in Britain. London: Batsford, 1950. Print.
Waterhouse, Paul, rev. by John Martin Robinson. "Wyatt, Sir Matthew Digby (1820-1877)." Oxford Dictionary of National Biography. Online ed. Web. 8 February 2013.
Last modified 20 May 2017


text:
Technically, the Mets could run the table this week and be back in the race before they return home. There is also enough time left where they could pick up a game a week and be there in the end.
That's all possible, but the Mets have given us no indication either scenario will happen. They haven't played well enough on the road to think such a hot streak is in the cards. They also haven't played consistently enough to give reason to believe the methodical way would work, either.
The Mets, losers of 12 of 17 games since the All-Star break, have shown no inclination of turning things around. They have Johan Santana (8-5, 3.11) hoping to rebound against a seven-run outing in his last start against St. Louis.
That game came on the heels of a stretch in which he went 3-0 with a 0.58 ERA.
Santana has pitched well in eight starts against the Braves since joining the Mets – a sparkling 1.79 ERA – but is a dismal 2-4 because of a lack of run support, getting two or fewer runs in each game.
The Mets' struggles started prior to the All-Star break as they have lost 15 of 21 games, including two of three to the Braves at Citi Field. They saved the worse for Sunday when they were pummeled, 14-1, by Arizona (they have lost five of six to the Diamondbacks in the last two weeks).
"It definitely hurts your pride a little bit when you perform in that manner,'' manager Jerry Manuel said. "We didn't pitch, we didn't hit, we didn't play defense.''