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Protein Kinase N1 ply of androgen-responsive serum response aspect motion gives understanding for novel prostate cancer medicine approach | killexams.com real Questions and Pass4sure dumps

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    Magee JA, Chang LW, Stormo GD, Milbrandt J. Direct, androgen receptor-mediated regulation of the FKBP5 gene by means of a distal enhancer factor. Endocrinology. 2006;147:590–8.

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    Taniguchi T, Kawamata T, Mukai H, Hasegawa H, Isagawa T, Yasuda M, et al. Phosphorylation of tau is regulated via PKN. J Biol Chem. 2001;276:10025–31.

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    Takanaga H, Mukai H, Shibata H, Toshimori M, Ono Y. PKN interacts with a paraneoplastic cerebellar degeneration-linked antigen, which is a viable transcription component. Exp mobile Res. 1998;241:363–72.

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    Shibata H, Oda H, Mukai H, Oishi okay, Misaki k, Ohkubo H, et al. interaction of PKN with a neuron-certain simple helix-loop-helix transcription component, NDRF/NeuroD2. brain Res Mol brain Res. 1999;74:126–34.

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    Marshall JL, Kindler H, Deeken J, Bhargava P, Vogelzang NJ, Rizvi N, et al. side I ordeal of orally administered CEP-701, a novel neurotrophin receptor-linked tyrosine kinase inhibitor. invest novel drugs. 2005;23:31–7.

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    Knapper S, Burnett AK, Littlewood T, Kell WJ, Agrawal S, Chopra R, et al. A section 2 ordeal of the FLT3 inhibitor lestaurtinib (CEP701) as first-line remedy for older patients with acute myeloid leukemia not considered healthy for intensive chemotherapy. Blood. 2006;108:3262–70.

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    Jilg CA, Ketscher A, Metzger E, Hummel B, Willmann D, Russeler V, et al. PRK1/PKN1 controls migration and metastasis of androgen-unbiased prostate melanoma cells. Oncotarget. 2014;5:12646–sixty four.

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    Kohler J, Erlenkamp G, Eberlin A, Rumpf T, Slynko I, Metzger E, et al. Lestaurtinib inhibits histone phosphorylation and androgen-elegant gene expression in prostate melanoma cells. PLoS ONE. 2012;7:e34973.

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    Hexner EO, Serdikoff C, Jan M, Swider CR, Robinson C, Yang S, et al. Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of simple erythroid cells from sufferers with myeloproliferative problems. Blood. 2008;111:5663–seventy one.

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    Iyer R, Evans AE, Qi X, Ho R, Minturn JE, Zhao H, et al. Lestaurtinib enhances the antitumor efficacy of chemotherapy in murine xenograft fashions of neuroblastoma. Clin melanoma Res. 2010;16:1478–85.

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    Kim JY, Banerjee T, Vinckevicius A, Luo Q, Parker JB, Baker MR, et al. a job for WDR5 in integrating threonine eleven phosphorylation to lysine four methylation on histone H3 flawless the route through androgen signaling and in prostate melanoma. Mol mobile. 2014;54:613–25.

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    Metzger E, Yin N, Wissmann M, Kunowska N, Fischer ok, Friedrichs N, et al. Phosphorylation of histone H3 at threonine eleven establishes a novel chromatin tag for transcriptional legislation. Nat mobile Biol. 2008;10:53–60.

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    Collins C, Carducci MA, Eisenberger MA, Isaacs JT, Partin AW, Pili R, et al. Preclinical and medical experiences with the multi-kinase inhibitor CEP-701 as treatment for prostate cancer panoply the inadequacy of PSA response as a major endpoint. melanoma Biol Ther. 2007;6:1360–7.

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    Liu S, Kumari S, Hu Q, Senapati D, Venkadakrishnan VB, Wang D, et al. A complete analysis of coregulator recruitment, androgen receptor function and gene expression in prostate melanoma. Elife. 2017;6:e28482.

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  • China prisoners of judgment of right and wrong rally urges Congress to stand in union for human ri … | killexams.com real Questions and Pass4sure dumps

    twelve months ago these days, Liu Xiaobo, the 2010 Nobel Peace Prize Laureate, died whereas in detention in China. His wife Liu Xia, who changed into not ever charged with a criminal offense, became launched this week after spending eight years under house arrest. “For decades Liu Xaobo fought at no cost expression, justice and liberty in China and he is silent a magnificent image for flawless those who battle for generic human rights,” stated Francisco Bencosme of Amnesty foreign, speakme at the day before today’s rally on the US Capitol to reverence Liu Xiaobo and to deliver attention to Prisoners of conscience in China and around the world.

    members of Congress, human rights leaders and representatives from impacted communities challenged americans and fellow participants of Congress to now not forget, to now not ignore the wrong of those falsely accused and to now not let human rights defenders stand alone. regrettably, there are tens of heaps of people unjustly imprisoned in China because of their peaceable expression of political, religious or different carefully held beliefs.

    “the usa has a righteous responsibility to communicate out in opposition t China’s brazen push aside for primary freedoms,” spoke of Congresswoman Nancy Pelosi. “probably the most excruciating torture to those in prison is to inform prisoners that no person remembers them or why they are in detention center. They understand you're there. They salute your courage. They pray to your safety and they hope they can abridge the time unless you're free.”

    each Reps.Tom McGovern (D-Mass.) and Randy Hultgren (R-unwell.), co-chairs of the Tom Lantos Human Rights commission, spoke on the rally. This fee created the Defending liberty undertaking in 2012, in partnership with six civil society groups, to inspire individuals of Congress to select and recommend for a specific prisoner of judgment of right and wrong. moreover, McGovern and Hultgren lately introduced H.Res.750, a bipartisan determination that calls to establish a Prisoners of righteous sense Day.

    Former Congressman straightforward Wolf of 21Wilberforce issued a clarion name. “it's captious that they aid prisoners of conscience. i would quiz every workplace in the Senate and the condominium to undertake a prisoner of judgment of right and wrong. Write to them. Write to their households. And to my fellow americans, write to your Senator or Congressman and express assist for H.Res.750.”

    different speakers that encouraged the crowd to mug for human rights covered Senator Ted Cruz (R-TX), Dr. Tenzin Dorjee, Chair of the united states fee on overseas religious Freedom, Carl Gershman, President of countrywide Endowment for Democracy, Sophie Richardson of Human Rights Watch, Pastor Wang Dao representing China help, and Elyse Anderson speakme on behalf of Sen. Rubio (R-FL).

    To live trained extra about prisoners of righteous sense, the Defending liberty venture orH.Res.750, contact any of the rally sponsors: 21Wilberforce, Amnesty overseas,the Lantos foundation for Human Rights and Justice, liberty condo and China help.

    TAKE action here

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    Contact:Lou Ann Sabatier[email protected](703) 216-2941


    local weather trade Is Already Worsening Droughts in many methods: Nature receives It incorrect — And commandeer | killexams.com real Questions and Pass4sure dumps

    A incorrect novel article in Nature has a title that sums up its controversial conclusion, “Little change in international drought during the terminal 60 years.”

    I commonly select a piece of writing at odds with the vast literature in two ways. How neatly does it cite and respond to the literature? What attain the different main experts within the container say? This novel article comes up short in both areas.

    Kevin Trenberth, former head of the local weather evaluation constituent of the national core for Atmospheric analysis, has despatched me a powerful critique which is printed beneath. NCAR’s Aiguo Dai moreover despatched me a critique.

    the brand novel article with ease ignores or dismisses a substantial volume of the drought literature and focuses as a substitute on one slender metric of soil moisture. however as I wrote closing year in a observation that reviewed a lot of the concurrent literature for Nature, “The next dirt Bowl” (subs. req’d, plenary textual content right here), climate change worsens droughts in three synergistic ways:

    A simple prediction of climate science is that many parts of the world will adventure longer and deeper droughts, because of the synergistic results of drying, warming and the melting of snow and ice.

    Precipitation patterns are anticipated to shift, expanding the desiccate subtropics. What precipitation there is will probably are available in fierce deluges, resulting in runoff as opposed to drought alleviation. Warming motives improved evaporation and, once the floor is dry, the sun’s power goes into baking the soil, leading to an extra boost in air temp- erature. it is why, as an instance, so many temperature facts had been set for the USA within the Nineteen Thirties grime Bowl; and why, in 2011, drought-afflicted Texas saw the hottest summer time ever recorded for a US state. finally, many areas are anticipated to ogle earlier snowmelt, so less water might live saved on mountain tops for the summer season desiccate season. delivered to natural climatic model, such because the El Niño–La Niña cycle, these components will intensify seasonal or decade-long droughts. besides the fact that children the models don’t flawless coincide on the specifics, the objective drying tendencies are clear.

    there's effortlessly limited doubt that many desiccate areas tolerate gotten drier and/or warmed up and/or seen earlier snowmelt.

    I believe it unearthly to pretension that there is limited trade in international drought during the terminal 60 years when there are so many reviews and analyses to the contradictory directly linking extreme droughts to climate exchange:

  • NOAA Bombshell (Hoerling et al 10/eleven): Human-caused local weather trade Already an famous constituent in additional everyday Mediterranean Droughts
  • examine (10/10): global warming is driving multiplied frequency of fierce dank or desiccate summer climate in southeast, so droughts and deluges are more likely to worsen
  • USGS skilled Explains How global Warming probably Contributes to East Africa’s Brutal Drought
  • the world bank’s must-examine novel document, “flip Down the warmth: Why a 4°C warmer World should live prevented,” receives this appropriate:

    One affected region is the Mediterranean, which experienced 10 of the 12 driest winters when you admiration that 1902 in exactly the remaining 20 years (Hoerling et al. 2012). Anthropogenic greenhouse gasoline and aerosol forcing are key causal factors with admire to the downward wintry weather precipitation trend in the Mediterranean (Hoerling et al. 2012)…. East Africa has experienced a style towards extended drought frequencies considering the Seventies, linked to warmer sea surface temperatures within the Indian-Pacific warm pool (Funk 2012), which are at least partly brought on by greenhouse fuel forcing (Gleckler et al. 2012). furthermore, a prefatory anatomize of the Texas drought sustain in 2011 concluded that the event become roughly 20 instances extra doubtless now than in the 1960s (Rupp, Mote, Massey, Rye, and Allen 2012).

    You won’t discover any of these reports referenced within the novel Nature article. that you could find Funk 2012 and Rupp et al 2012 within the The Bulletin of the American Meteorological Society particular challenge, “Explaining extreme activities of 2011 from a climate viewpoint.”

    I find it's principally striking that Nature would post this piece when three months ago its sister booklet, Nature local weather change, published a bit via Dai, “expanding drought beneath international warming in observations and model” it truly is utterly at odds with it. there's with no exertion no approach each of these papers can live genuine — and yet the brand novel Nature piece by no means discusses the nature climate exchange piece.

    Dai’s paper notes:

    old facts of precipitation, streamflow and drought indices flawless panoply increased aridity seeing that 1950 over many land areas….

    I conclude that the followed international aridity alterations up to 2010 are in keeping with model predictions, which imply extreme and frequent droughts in the next 30– ninety years over many land areas as a consequence of both lowered precipitation and/ or improved evaporation.

    the novel Nature paper dismisses outdated toil by using Dai, unjustifiably in keeping with Dai and Trenberth, but after all, Dai’s Nature climate exchange goes much further in reconciling models with observations. Nature shouldn’t tolerate published this novel paper without a major endeavor first to reconcile these two papers.

    I suppose it unlikely that the brand novel paper will secure up. here's what Trenberth sent me:

    A “drought” in respectable science

    Kevin Trenberth

    the brand novel paper these days posted in Nature by means of Sheffield et al “Little alternate in international drought over the past 60 years” [Nature 491 15 Nov 2012 435–440] has completed some excellent work. nonetheless it attain not need been posted in Nature. It has 38 pages of dense supplementary cloth, for heaven’s sake. turned into that reviewed? probably now not.

    The conclusions of the paper are likely incorrect. The paper re-examines the Palmer Drought Severity Index (PDSI) in distinctive formulations and the route it changes over time. however, this has been completed earlier than in references embedded within the paper:

    24. Dai, A. traits and developments in various forms of the Palmer Drought Severity Index flawless through 1900–2008. J. Geophys. Res. 116, D12115 (2011).

    25. van der Schrier, G., Jones, P. D. & Briffa, ok. R. The sensitivity of the PDSI to the Thornthwaite and Penman–Monteith parameterizations for competencies evapotranspiration. J. Geophys. Res. 116, D03106 (2011).

    And brushed aside with “contemporary stories tolerate claimed that there's limited change between the PDSIs that consume the Thornthwaite and PM algorithms (PDSI_Th and PDSI_PM, respectively)24,25 but this can moreover live attributed to inconsistencies in the forcing statistics sets and simulation configuration(see Supplementary guidance).” sure, but at the least one of the crucial supplementary material in this respect is wrong.

    The primary PDSI_th depends on temperature to crudely assay the atmospheric claim for moisture from the soil and thus evapotranspiration. It can live calibrated to each and every enviornment and it works moderately well however it isn't perfect. it's widespread that specific evaporation depends on solar radiation and other power sources, as well as floor wind speeds and humidity besides temperature. The issue is these fields are often not available in enough pleasant, furthermore every day fields are required.

    The Sheffield et al Figs. S12-S14 imply that the “little drying” conclusion is likely as a result of using the CRU precipitation records, which has fewer than 1500 raingauges for the concurrent years and which differs considerably from the GPCC and GPCP precipitation products that tolerate many greater gauge statistics for the final 10–20 years. The authors execute a colossal deal of their findings, however truly van der Schrier et al. tolerate made similar conclusions in their previously posted papers the consume of the selfsame CRU facts set because the forcing. There are moreover most famous concerns about the reconstruction of the photo voltaic radiation facts, which relies upon a august deal on how clouds tolerate modified.

    one more key aspect is that whereas their outdated effects with PDSI had been compared with other related but impartial information, such as soil moisture, streamflow, and grace satellite statistics, Sheffield et al. made handiest an in depth comparison of a lot of forcing information for the PDSI calculations.

    one other famous constituent now not regarded, is that precipitation on land is controlled to a large degree by ENSO: in gauge with La Niña, as skilled in recent years, there is greater rain on land and so the past 2 years had been the wettest on list. that says nothing about even if the extent and intensity of drought is more suitable or no longer when it occurs, and so the ENSO signal should live removed earlier than looking at developments linked to climate exchange.

    Sheffield et al tolerate uncovered some minor issues with Dai (2011) but not anything that clarify the transformations within the effects. It is pellucid from flawless this that there are foremost concerns with the “forcing” facts for the more complicated sort of PDSI, and as a result there is silent a lot of advantage within the easier but self calibrated edition of PDSI_th.

    The bottom line is that local weather alternate provides added heat to the gear and that an abominable lot of warmth goes into drying. A natural drought for whatever thing understanding sets in sooner, becomes greater severe, and might live is longer lasting and extra huge subsequently.

    Dai sent me a protracted clarification of a major flaw in Sheffield et al, which I’ll summarize as “they normalized away the fresh drying.” I believe Nature must reconcile these papers, however except then, one should silent likely retain on with the large and transforming into literature on the huge and transforming into upward push in aridity over many components of the realm.

    at last, this evaluation doesn't undercut the colossal and turning out to live literature on the desultory to future generations of dirt-Bowlification — see “We’re Already Topping dirt Bowl Temperatures — think about What’ll seize area If They Fail To cease 10°F Warming.”


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    People enjoy the estate tax a whole lot more when they learn how wealth is distributed | killexams.com real questions and Pass4sure dumps

    Proposals to extend taxes on the wealthy are having a moment: Polling shows Democrats and Republicans coming together in back of steep taxes on the wealth and income of the super-rich. While the specifics of the proposals are new, the universal public sentiment toward soaking the affluent is a long-standing one, according to Gallup polling.

    But there's one sort of tax on millionaires that Americans tolerate consistently been skeptical of -- the estate tax. Polling typically shows that a majority of Americans favor repealing this tax completely.

    Part of this is due to Republicans' success in branding the tax a "death tax" that unfairly confiscates wealth from Americans at the time of a family member's death. But research out of Sweden suggests there's another factor driving opposition to the estate tax: Many people may simply live unaware of basic facts about inherited wealth.

    In the study, researchers from Linnaeus University and the Paris School of Economics administered a nationally-representative survey to Swedish adults. The survey included questions about the respondents' back for an estate tax, which Sweden had until 2004, when it was abolished.

    Some respondents received factual information about wealth inheritance in Sweden, in three bullet points:

    "Inherited wealth represents about half of flawless wealth in the population."

    "Those with the highest incomes inherit the most."

    "A majority of Swedish billionaires tolerate inherited their fortunes."

    Other respondents were not given this information.

    The researchers found that the group receiving the factual information was significantly more likely to back the estate tax than the respondents who didn't; among the group not receiving the factual information, back for an inheritance tax stood at about 25 percent. But back among the other group was 33 percent, significance the factual information boosted back for an inheritance tax by about 8 percentage points. This inequity remained even after controlling for a number of demographic and economic variables.

    "Our results hint that a greater availability and exposure to research findings about the wealth distribution can tolerate real effects on the political back for taxation," the researchers conclude. One implication of their study: back for an estate tax in wealthy countries may live low simply because many people don't understand how inherited wealth works.

    Washington Post Graphic

    Washington Post graphic -

    Pollsters tolerate observed similar dynamics at play in tax discussions in the United States. In 2017, for instance, a HuffPost/YouGov poll asked whether the estate tax should live abolished. Half of the respondents were additionally told that the tax only affects estates over $5 million. Among that group, back for keeping the tax (46 percent) was nearly 20 percentage points higher than it was among the group not receiving factual information (27 percent).

    That survey moreover revealed that many Americans had incorrect notions about the estate tax. Only 37 percent of respondents knew that the tax only affects a few families (less than 0.1 percent of people who die) each year. Thirty percent believed, incorrectly, that "most" families were matter to the tax. Sixty-three percent incorrectly believed that poor and middle-class families were primarily affected by the tax, even though it only applied to estates over $5 million at the time the survey was administered.

    More broadly, other research has shown that Americans tolerate a poor understanding of how wealth is distributed in this country. For instance, a 2010 study found that Americans believed that the bottom 60 percent of the country owned a limited over 20 percent of the nation's total wealth. In reality, the bottom 60 percent owns about 1 percent of the country's total wealth. Ninety percent of wealth in the United States is held by the richest 20 percent of families, with the richest 1 percent owning 40 percent of it.

    The dynamics of wealth inheritance are moreover not widely understood. A 2012 Pew Research hub survey, for instance, found that the public was split on whether wealthy in the United States were affluent because they worked hard for their money, or because they were born into wealthy families. But a 2017 study published by Thomas Piketty and colleagues estimated that in 2010, roughly 60 percent of private wealth held in the United States had been inherited, rather than worked for. It's worth noting that this partake is higher than what some earlier estimates pegged it at, but Piketty and his colleagues bid their method for measuring inherited wealth is superior.

    Taken together, much of the best available evidence suggests that the median dollar of wealth in the United States has been inherited by someone in the richest 5 percent of families. It moreover suggests that most Americans don't realize this is the case, which may partly interpret why back for abolishing the estate tax is so high.

    In recent days, U.S. lawmakers tolerate presented voters with two drastically different options for taxing inheritance. Sen. Bernie Sanders, I-Vt., introduced a bill that would extend the tax rate for the richest 0.2 percent of estates, while Senate Republicans introduced legislation to repeal the estate tax entirely. The research out of Sweden suggests that voters' response to the measures will hinge, in part, on how well they understand the route wealth works in the United States.


    Protein Kinase N1 control of androgen-responsive serum response factor action provides rationale for novel prostate cancer treatment strategy | killexams.com real questions and Pass4sure dumps

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    Olmos D, Brewer D, Clark J, Danila DC, Parker C, Attard G, et al. Prognostic value of blood mRNA expression signatures in castration-resistant prostate cancer: a prospective, two-stage study. Lancet Oncol. 2012;13:1114–24.

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    Kajimoto K, Shao D, Takagi H, Maceri G, Zablocki D, Mukai H, et al. Hypotonic swelling-induced activation of PKN1 mediates cell survival in cardiac myocytes. Am J Physiol Heart Circ Physiol. 2011;300:H191–200.


  • New role for Japan | killexams.com real questions and Pass4sure dumps

    ANALYSIS/OPINION:

    Japan emerged from World War II as a crushed survivor of its own ambition and cruelty, despised by the Asia it described as a “partner” in the Greater East Asia Co-Prosperity Sphere. Asia was a very junior “partner” indeed.

    The Japanese military that fought World War II is remembered for the rape and pillage not only of Nanking but in the sacking of Manila, “the Pearl of the Orient” that Douglas MacArthur had declared an open city and evacuated his army to save it. Japanese troops leveled it to a smoking ruin.

    When the war was over, the novel Japan, under the tutelage of MacArthur, declared never again, and adopted a constitution, silent in force, that abjures flawless military force. But that’s only partake of the story. Tokyo, encouraged and further tutored by the United States, now commands one of the most powerful military establishments in the world. Its weapons research evolution sets the pace in some areas.

    The Japan Self-Defense Forces, established in 1954, ranks as the world’s fourth most-powerful military in conventional capabilities, with the eighth-largest military budget. In recent years Japan has participated in United Nations peacekeeping operations, and its highly trained and equipped amphibious rapid deployment brigade — which expects to train 3,000 men by the nearby of next month — has just completed a joint exercise with U.S. forces.

    Rising icy War tensions in Europe and Asia, coupled with leftist-inspired strikes and demonstrations in Japan, prompted conservative leaders to question the unilateral renunciation of flawless military capabilities in the submission treaty with the United States and the Allies. When many American occupation troops were moved to Korean War duty, Japan developed a nearby mutual defense relationship with the United States.

    Encouraged by the Americans, the Japanese government in 1950 authorized the establishment of a National Police Reserve, consisting of 75,000 men equipped with light infantry weapons. In 1952, Coastal Safety Force, the waterborne counterpart of the police reserve, was organized and in 2006 the Japanese military establishment became the full-fledged cabinet-level Ministry of Defense.

    A year later Japanese military operations were revised from “miscellaneous regulations” to “basic duties,” finally recognizing that the nation’s military was no longer restricted solely to defense. Japanese ships are now dispatched worldwide, for example, to deal with pirates who tolerate imperiled commercial shipping. Japan established its first postwar overseas groundwork at Djibouti, in Somalia, in 2010.

    Japan and the United States conducted their largest military exercise, called Keen Sword, terminal year, with 47,000 American seamen, Marines and airmen joined by 47,000 Japanese. A naval supply ship and frigate of the Royal Canadian Navy moreover participated in simulations of air combat, ballistic missile defense and amphibious landings.

    In 2004, at the behest of the United States, Japan deployed troops to Iraq in the U.S.-led reconstruction of Iraq. This was the first time since the nearby of World War II that Japan had sent troops abroad, except for a few minor U.N. peacekeeping deployments.

    Last December the government adopted a budget for fiscal 2019 that includes 100 trillion yen, or $900 billion, for the military. There is no secret about what motivates Japanese policy to turn its back on the postwar professions of neutrality and to reject the concept of any military establishment. It’s the growing perceived threat from Communist China.

    In addition to conventional weaponry, the defense budget for fiscal 2018 included funds to purchase mid- to long-range air-launched cruise missiles. Defense Minister Itsunori Onodera said they would live used exclusively for defense as “stand-off missiles that can live fired beyond the range of enemy threats.” But the budget allocated another $20 million for the purchase of Joint Strike Missiles for its American-made F-35A stealth fighters and $270,000 for research on modifying existing Japanese Mitsubishi F-15J fighters to carry long-range anti-ship missiles and extended-range air-to-surface standoff missiles.

    The Ministry of Defense is developing supersonic glide bombs to strengthen the defense of Japan’s remote islands, including the Senkaku Islands between Japan and Korea. The anti-surface strike capability will assist in amphibious landing and recapture operations on remote islands. Japan’s Defense Ministry has moreover allocated $57 million for research and evolution of a hypersonic missile which could travel five times the hurry of sound, Mach 5, or faster. A scramjet engine prototype, jet-fuel technology and heat-resistant materials will live built by 2025.

    Japanese public sentiment about flawless this is sharply divided. The Japanese people relish their novel reputation as peace-loving folk who wouldn’t harm a flit — or dispatch a flying missile. But it’s a novel world out there, as well as a novel Japan.

    The Washington Times observation Policy The Washington Times welcomes your comments on Spot.im, their third-party provider. gladden read their observation Policy before commenting.


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