(AP) — Hong Kong police warned protesters on Thursday that they were moving “one step closer to terrorism” by sinking the city into chaos, as riot squads skirmished with militant students at major universities.Police spokesman Tse Chun-chung denied his department had been asked to enforce a possible curfew this weekend. A Chinese state media outlet later removed its tweet saying authorities were considering a weekend curfew that cited unidentified sources.“We are aware of the relevant report circulating online,” Tse said at a daily briefing, referring to the report as “false.” He said the authority to order a curfew lies with Hong Kong’s leader, Chief Executive Carrie Lam, and “that’s why police are not in a position to comment.”“The force is certainly capable and determined to control Hong Kong’s social unrest at the moment. We welcome any new measures that can help us to achieve the goal of restoring the public safety and order in Hong Kong,” Tse added.In unusually harsh language, he said students were turning university campuses into “weapons factories” and a “hotbed” of crime.“Their acts are another step closer to terrorism,” Tse said, warning of a major disaster if gasoline bombs stored on campuses were to catch fire.He said violence that broke out this week at Chinese University of Hong Kong is spreading to other campuses “like a cancer cell,” mentioning specifically Hong Kong University and Baptist University.“It’s time to wake up. No society can tolerate this much senseless violence,” he said.With no end to the protests in sight, the beleaguered police force is appointing a group of prison guards as special constables.Up to 100 officers from the Correctional Services Department who are already familiar with anti-riot equipment will be given additional training and deployed mainly to guard government premises.“The ongoing riots over the past few months, with their massive scale, simultaneous occurrence in various districts and grave severity of violence, make it necessary to strengthen the support for the police’s front-line officers,” a statement from the police spokesman’s office said.Residents endured a fourth day of traffic snarls and mass transit disruptions as protesters closed some main roads and rail networks.Police said protesters shot several arrows at them near Hong Kong Polytechnic University. No officers were injured, and six arrows were seized at the scene, police said.Life in this city of 7.5 million has been strained as thousands of commuters have been unable to get to work or endured lengthy commutes.The government appealed for employers to show flexibility. “For staff who cannot report for duty on time on account of conditions in road traffic or public transport services, employers should give due consideration to the circumstances,” a statement said.A business and high-end retail district in the center of the city was once again taken over by protesters at lunchtime, as it has been every day since Monday. Office workers watched from the sidewalks and overpasses as protesters littered the streets with bricks and other items to block traffic and police.At one point, a group of police swooped in and kicked the bricks to the curb along one major thoroughfare, but the standoff continued.The Education Bureau extended the suspension of classes for kindergarten to high school students until Monday. It ordered schools to remain open, though, to handle children whose parents need to send them to school.Protesters have hurled gasoline bombs and thrown objects off bridges onto roads below during clashes at campuses this week. The Chinese University of Hong Kong suspended classes for the rest of the year, and others asked students to switch to online learning.Students at Chinese University, site of some of the fiercest clashes where students hurled more than 400 firebombs at police on Tuesday, have barricaded themselves in the suburban campus.Early Thursday they used chainsaws to drop trees onto streets around the campus and prepared for a possible confrontation with police, who were not intervening.A major rail line connecting Kowloon to mainland China was closed for a second day and five major underground stations were shut along with seven light rail routes, the Transport Department announced.“Road-based transport services have been seriously affected this morning due to continued road blockages and damage to road facilities. In view of safety concerns and uncertain road conditions, buses can only provide limited services,” the department said.One of the main cross-harbor tunnels connecting Hong Kong Island to Kowloon and the rest of the city was closed after protesters set some of the toll booths on fire Wednesday night.Traffic was also disrupted because protesters have destroyed at least 240 traffic lights around the city.Anti-government protests have riven Hong Kong, and divided its people, for more than five months.The movement began over a now-withdrawn extradition bill that would have allowed criminal suspects to be sent to mainland China for trial. Activists saw it as another sign of an erosion of Hong Kong’s autonomy and freedoms, which China promised would be maintained for 50 years under a “one nation, two systems” principle when the former British colony returned to Chinese control in 1997.
Figuring out how much the U.S. government will spend this year on science got a little more complicated today after House Majority Leader Steny Hoyer (D-MD) said the 2009 spending bills would not be taken up until the end of the month. That’s likely to be after Congress approves billions of dollars for science as part of the stimulus package to be spent over the next 18 months. The convoluted schedule means federal science officials may get news of their windfall before they know how much their base budgets will be for 2009—adding confusion to an already uncertain, if hopeful, federal budget season for researchers. Congress must act by 6 March to extend a temporary spending measure for the fiscal year that began in October.
The Indian government had over the years quite intentionally opened up Singapore and Mauritius as jurisdictions that are attractive to channel funds into India. Related Items
The White House’s announcement yesterday that it wants to spend $1 billion to jump-start Vice President Joe Biden’s cancer moonshot is music to the ears of cancer researchers. Unclear, however, is how much existing money will be reshuffled at the National Institutes of Health (NIH) to support this year’s moonshot activities, and whether Congress will agree to new funding that the White House has proposed for 2017.Although researchers are “very excited and enthusiastic” about the $1 billion proposal, they have questions about exactly where the money will come from, says Jon Retzlaff, managing director for science policy and government affairs for the American Association for Cancer Research (AACR) in Philadelphia, Pennsylvania. A fact sheet says the White House plans to spend $195 million on “new cancer activities” at NIH in the current 2016 fiscal year, which began in October 2015. Presumably, most of the spending will occur at the National Cancer Institute (NCI), which got $264 million in new money this year (part of a $2 billion overall increase for NIH). NCI already funds the research areas that the fact sheet describes—cancer prevention, early detection, immunotherapy, tumor genomics, data sharing, and pediatric cancer. The money appears to be “a shot in the arm” for these existing programs, Retzlaff says.Sign up for our daily newsletterGet more great content like this delivered right to you!Country *AfghanistanAland IslandsAlbaniaAlgeriaAndorraAngolaAnguillaAntarcticaAntigua and BarbudaArgentinaArmeniaArubaAustraliaAustriaAzerbaijanBahamasBahrainBangladeshBarbadosBelarusBelgiumBelizeBeninBermudaBhutanBolivia, Plurinational State ofBonaire, Sint Eustatius and SabaBosnia and HerzegovinaBotswanaBouvet IslandBrazilBritish Indian Ocean TerritoryBrunei DarussalamBulgariaBurkina FasoBurundiCambodiaCameroonCanadaCape VerdeCayman IslandsCentral African RepublicChadChileChinaChristmas IslandCocos (Keeling) IslandsColombiaComorosCongoCongo, The Democratic Republic of theCook IslandsCosta RicaCote D’IvoireCroatiaCubaCuraçaoCyprusCzech RepublicDenmarkDjiboutiDominicaDominican RepublicEcuadorEgyptEl SalvadorEquatorial GuineaEritreaEstoniaEthiopiaFalkland Islands (Malvinas)Faroe IslandsFijiFinlandFranceFrench GuianaFrench PolynesiaFrench Southern TerritoriesGabonGambiaGeorgiaGermanyGhanaGibraltarGreeceGreenlandGrenadaGuadeloupeGuatemalaGuernseyGuineaGuinea-BissauGuyanaHaitiHeard Island and Mcdonald IslandsHoly See (Vatican City State)HondurasHong KongHungaryIcelandIndiaIndonesiaIran, Islamic Republic ofIraqIrelandIsle of ManIsraelItalyJamaicaJapanJerseyJordanKazakhstanKenyaKiribatiKorea, Democratic People’s Republic ofKorea, Republic ofKuwaitKyrgyzstanLao People’s Democratic RepublicLatviaLebanonLesothoLiberiaLibyan Arab JamahiriyaLiechtensteinLithuaniaLuxembourgMacaoMacedonia, The Former Yugoslav Republic ofMadagascarMalawiMalaysiaMaldivesMaliMaltaMartiniqueMauritaniaMauritiusMayotteMexicoMoldova, Republic ofMonacoMongoliaMontenegroMontserratMoroccoMozambiqueMyanmarNamibiaNauruNepalNetherlandsNew CaledoniaNew ZealandNicaraguaNigerNigeriaNiueNorfolk IslandNorwayOmanPakistanPalestinianPanamaPapua New GuineaParaguayPeruPhilippinesPitcairnPolandPortugalQatarReunionRomaniaRussian FederationRWANDASaint Barthélemy Saint Helena, Ascension and Tristan da CunhaSaint Kitts and NevisSaint LuciaSaint Martin (French part)Saint Pierre and MiquelonSaint Vincent and the GrenadinesSamoaSan MarinoSao Tome and PrincipeSaudi ArabiaSenegalSerbiaSeychellesSierra LeoneSingaporeSint Maarten (Dutch part)SlovakiaSloveniaSolomon IslandsSomaliaSouth AfricaSouth Georgia and the South Sandwich IslandsSouth SudanSpainSri LankaSudanSurinameSvalbard and Jan MayenSwazilandSwedenSwitzerlandSyrian Arab RepublicTaiwanTajikistanTanzania, United Republic ofThailandTimor-LesteTogoTokelauTongaTrinidad and TobagoTunisiaTurkeyTurkmenistanTurks and Caicos IslandsTuvaluUgandaUkraineUnited Arab EmiratesUnited KingdomUnited StatesUruguayUzbekistanVanuatuVenezuela, Bolivarian Republic ofVietnamVirgin Islands, BritishWallis and FutunaWestern SaharaYemenZambiaZimbabweI also wish to receive emails from AAAS/Science and Science advertisers, including information on products, services and special offers which may include but are not limited to news, careers information & upcoming events.Required fields are included by an asterisk(*)But one worry for biomedical researchers is that plumping up certain NCI programs partway into the fiscal year will force the institute to divert funds from other programs. For example, the pot of money allocated for investigator-initiated cancer research could grow more slowly; the fact sheet also does not mention what is envisioned for NCI’s cancer centers. Exactly what the moonshot could mean for nonmoonshot activities may become clearer on 11 February at the next meeting of NCI’s National Cancer Advisory Board (NCAB).Meanwhile, Biden plans to propose continuing the moonshot’s financial momentum in the White House’s FY 2017 budget request, due out 9 February. The White House says it will include a request to steer $75 million to the U.S. Food and Drug Administration (FDA) for moonshot activities, and $680 million for NIH. That could mean a 13% budget boost for NCI.The plan could be a hard sell in Congress, however, Retzlaff notes. That’s because it calls for using “mandatory funds” to pay for those increases. Mandatory funds aren’t funneled through the regular annual appropriations process. Instead, the money comes from dedicated sources approved by Congress—for example, the 21st Century Cures Act, a House bill to speed the development of new medicines, would give NIH $8.75 billion in new funding over 5 years by selling oil from the U.S. strategic petroleum reserve.Lawmakers generally don’t like mandatory spending because it preempts their oversight, Retzlaff notes. Another concern is what will happen if such funding ends after a few years. “There could be a cliff” after which the new research programs suddenly lose support, Retzlaff says. AACR’s hope, Retzlaff says, is that any new moonshot funding be sustained into 2018, 2019, and beyond. “We’d love to see a 10-year plan,” he says.One program outlined in the White House spending plan clearly is new: an FDA Virtual Oncology Center of Excellence that will “leverage the combined skills of regulatory scientists and reviewers” to speed the development of cancer drugs, screening, and diagnostics. Friends of Cancer Research, a patient advocacy group, took credit for that idea, writing that it will “break down decades’ old silos within FDA and make for a more efficient agency.” The plan also describes a Vice President’s Exceptional Opportunities in Cancer Research Fund that will fund “high-risk, high-return research” identified with help from researchers, advocates, and industry.Yesterday, Biden held the first meeting of an interagency task force to plan the moonshot. And NCAB will soon form a blue-ribbon panel to offer guidance.
By Elie DolginJan. 16, 2019 , 2:15 PM TDP-43Nuclear pore To halt brain diseases, drugs take aim at protein traffic jams that kill neurons Fixing traffic jamsThe flow of molecules through pores in the nucleus is key to the health of cells, particularly neurons. Traffic problems may contribute to amyotrophic later- al sclerosis (ALS) and other brain diseases.NormalImportin proteins bring TDP-43and other cargo from the cytoplasmthrough the nuclear pore, whereasexportins take molecules out.ALSIn some ALS cases, abnormal RNAmade by a mutant C9orf72 geneprevents RanGAP from mediatingnuclear import, leading to proteinbuildup in stress granules.ALS + drugA possible drug, KPT-350, impairsthe specific exportin XPO1 and maynormalize nuclear traffic of proteinsor bust up stress granules. C9orf72 RNAKPT-350 V. ALTOUNIAN/SCIENCE KIRSTIN MAULDING RanGAPImportinExportinRan Chris Henderson, Biogen A false-color atomic force micrograph shows the complex pores (green rings) that closely regulate traffic in the cell between the nucleus and cytoplasm. Here’s a drug with a body of rationale, and we’re optimistic about getting this into trials. The team’s result would upend neuroscientists’ understanding of ALS and brain disease in general, and others were on the same trail. In 2015, two more research teams reported that defects in the cell’s nuclear transport system were hallmark features not only of ALS, but also of frontotemporal dementia (FTD), another progressive brain disease caused by C9orf72 mutations. Scientists would soon link dysfunctional trafficking across the nuclear divide to other neurodegenerative diseases—Alzheimer’s, Huntington, spinocerebellar ataxia—and even to normal aging. In all those ailments, the resulting abnormal pileups of proteins somehow become rogue neuronal killers.”I often get queasy when someone makes a discovery and tries to explain the rest of the world with it,” says Rothstein, a neurologist who directs the Johns Hopkins Brain Science Institute. But here, he says, it seems to be true.The findings are not merely academic. They are inspiring therapeutic efforts to address the cause of general age-related neurodegeneration—a goal that has largely eluded drug developers. If the gradual loss of nucleocytoplasmic transport is a conserved feature of the aging brain, says Sami Barmada, a neurologist at the University of Michigan in Ann Arbor, preventing it “might be a really broad and effective therapy.”Several biotech companies have jumped on that idea, exploring it in animal models and planning the first human trials this year. Chief among them: Biogen in Cambridge, Massachusetts, which in 2018 bought the rights to develop a drug compound called KPT-350 that directly targets the nuclear transport pathway. The research underpinning that drug’s action is brand new. But, “The biology is there,” says Chris Henderson, head of neuromuscular and movement disorders research at Biogen. “Here’s a drug with a body of rationale,” he adds, “and we’re optimistic about getting this into trials.”Crossing the nuclear borderThe lipid membrane that divides the DNA-packed nucleus from the rest of the cell is like an international border busy with two-way industrial traffic. DNA-binding proteins and other molecules are constantly flowing into the nucleus to help turn genes on and off, for example. The messenger RNAs produced by those genes stream the other way, into the cytoplasm to protein-assembly platforms. The cell must regulate that traffic through entry points known as nuclear pores. Choke off those portals and it stands to reason cells will suffer.The first hints that disrupted nuclear transport might underpin ALS came in 2010, when researchers at King’s College London, working with human nerve cancer cells, experimentally blocked the expression of proteins involved in the import business. The result was something also seen in cells from ALS patients: clumps of a protein called TDP-43 building up in the cytoplasm.Few ALS researchers paid much attention to that early report. What might be gumming up the gears of the transport machinery in ALS patients wasn’t clear, and the researchers couldn’t say whether the buildup of TDP-43—a protein that normally binds both DNA and RNA inside the nucleus to regulate multiple steps in gene expression—was actually killing neurons or was just a consequence of a different toxic process. It would take another 5 years—and Lloyd’s and Rothstein’s study of the flies with telltale eyes—for ALS scientists to take nuclear transport more seriously. The compound eyes of the common fruit fly are normally brick red. But in neurologist Tom Lloyd’s lab at Johns Hopkins University School of Medicine in Baltimore, Maryland, many of the fly eyes are pocked with white and black specks, a sign that neurons in each of their 800-odd eye units are shriveling away and dying.Those flies have the genetic equivalent of amyotrophic lateral sclerosis (ALS), the debilitating neurodegenerative disorder also known as Lou Gehrig’s disease, and their eyes offer a window into the soul of the disease process. By measuring the extent of damage to each insect’s eyes, researchers can quickly gauge whether a drug, genetic modification, or some other therapeutic intervention helps stop neuronal loss.Those eyes have also offered an answer to the central mystery of ALS: just what kills neurons—and, ultimately, the patient.Sign up for our daily newsletterGet more great content like this delivered right to you!Country *AfghanistanAland IslandsAlbaniaAlgeriaAndorraAngolaAnguillaAntarcticaAntigua and BarbudaArgentinaArmeniaArubaAustraliaAustriaAzerbaijanBahamasBahrainBangladeshBarbadosBelarusBelgiumBelizeBeninBermudaBhutanBolivia, Plurinational State ofBonaire, Sint Eustatius and SabaBosnia and HerzegovinaBotswanaBouvet IslandBrazilBritish Indian Ocean TerritoryBrunei DarussalamBulgariaBurkina FasoBurundiCambodiaCameroonCanadaCape VerdeCayman IslandsCentral African RepublicChadChileChinaChristmas IslandCocos (Keeling) IslandsColombiaComorosCongoCongo, The Democratic Republic of theCook IslandsCosta RicaCote D’IvoireCroatiaCubaCuraçaoCyprusCzech RepublicDenmarkDjiboutiDominicaDominican RepublicEcuadorEgyptEl SalvadorEquatorial GuineaEritreaEstoniaEthiopiaFalkland Islands (Malvinas)Faroe IslandsFijiFinlandFranceFrench GuianaFrench PolynesiaFrench Southern TerritoriesGabonGambiaGeorgiaGermanyGhanaGibraltarGreeceGreenlandGrenadaGuadeloupeGuatemalaGuernseyGuineaGuinea-BissauGuyanaHaitiHeard Island and Mcdonald IslandsHoly See (Vatican City State)HondurasHong KongHungaryIcelandIndiaIndonesiaIran, Islamic Republic ofIraqIrelandIsle of ManIsraelItalyJamaicaJapanJerseyJordanKazakhstanKenyaKiribatiKorea, Democratic People’s Republic ofKorea, Republic ofKuwaitKyrgyzstanLao People’s Democratic RepublicLatviaLebanonLesothoLiberiaLibyan Arab JamahiriyaLiechtensteinLithuaniaLuxembourgMacaoMacedonia, The Former Yugoslav Republic ofMadagascarMalawiMalaysiaMaldivesMaliMaltaMartiniqueMauritaniaMauritiusMayotteMexicoMoldova, Republic ofMonacoMongoliaMontenegroMontserratMoroccoMozambiqueMyanmarNamibiaNauruNepalNetherlandsNew CaledoniaNew ZealandNicaraguaNigerNigeriaNiueNorfolk IslandNorwayOmanPakistanPalestinianPanamaPapua New GuineaParaguayPeruPhilippinesPitcairnPolandPortugalQatarReunionRomaniaRussian FederationRWANDASaint Barthélemy Saint Helena, Ascension and Tristan da CunhaSaint Kitts and NevisSaint LuciaSaint Martin (French part)Saint Pierre and MiquelonSaint Vincent and the GrenadinesSamoaSan MarinoSao Tome and PrincipeSaudi ArabiaSenegalSerbiaSeychellesSierra LeoneSingaporeSint Maarten (Dutch part)SlovakiaSloveniaSolomon IslandsSomaliaSouth AfricaSouth Georgia and the South Sandwich IslandsSouth SudanSpainSri LankaSudanSurinameSvalbard and Jan MayenSwazilandSwedenSwitzerlandSyrian Arab RepublicTaiwanTajikistanTanzania, United Republic ofThailandTimor-LesteTogoTokelauTongaTrinidad and TobagoTunisiaTurkeyTurkmenistanTurks and Caicos IslandsTuvaluUgandaUkraineUnited Arab EmiratesUnited KingdomUnited StatesUruguayUzbekistanVanuatuVenezuela, Bolivarian Republic ofVietnamVirgin Islands, BritishWallis and FutunaWestern SaharaYemenZambiaZimbabweI also wish to receive emails from AAAS/Science and Science advertisers, including information on products, services and special offers which may include but are not limited to news, careers information & upcoming events.Required fields are included by an asterisk(*)The flies carry a mutation found in about 40% of ALS patients who have a family history of the disease, and in about 10% of sporadic cases. The mutation, in a gene called C9orf72, consists of hundreds or thousands of extra copies of a short DNA sequence, just six bases long. They lead to unusually large strands of RNA that glom onto hundreds of proteins in the cell nucleus, putting them out of action. Some of those RNA-ensnared proteins, Lloyd and his Hopkins colleague Jeffrey Rothstein hypothesized, might hold the key to ALS.Over many months, the researchers systematically studied the role of each protein by developing fly strains carrying both the ALS mutation and an incapacitated or hyperactive version of each protein’s gene. One set of flies, bred to have elevated levels of a protein called RanGAP, stood out. Fifteen days after the flies emerged from their pupal casings, their eyes remained a pure burnt sienna. RanGAP “was by far the most potent suppressor of neurodegeneration,” Lloyd says. What was known about its function was tantalizing: It serves as a courier, helping shuttle other proteins across the membrane that divides the cell nucleus from the cytoplasm. For example, treatment with KPT-350 preserved the health of axons, the long, signal-transmitting extensions of nerve cells, and improved the motor functions of mice with a multiple sclerosis–like condition, a team led by neuroscientist Jeffery Haines at the Icahn School of Medicine at Mount Sinai in New York City showed. And in the Hopkins group’s hands, the drug kept alive mouse neurons harboring the mutation associated with Huntington.”There’s still a lot that needs to be explored about why the nuclear pore complex is so susceptible to problems in different types of neurons in different brain regions causing multiple different diseases,” says Gavin Daigle, a former postdoc in Rothstein’s lab who worked on the Huntington project and helped link disrupted pore function to Alzheimer’s disease before joining AbbVie in Cambridge. But he stresses that all the research is showing one thing: “This is a pathway that can be targeted.”The results proved enough to convince Biogen, which bought the rights to test the drug in humans. “The package of preclinical data that Karyopharm was able to amass really justifies the excitement,” says Laura Fanning, R&D project leader for KPT-350 at Biogen (which has renamed the molecule BIIB100). “It’s not just a blip of efficacy in one strain of mice. It’s a broad base of evidence,” she says. A first-in-human dose-escalation study of KPT-350 could begin in ALS patients later this year. If the drug shows promise against that disease, Biogen may expand its clinical testing to other conditions, Henderson says.Moving into the clinicAlthough the drug seems to work in the laboratory, why or how is not at all clear. “The story started to get murkier as more data has come in,” notes Haines, now at Regeneron Pharmaceuticals in Tarrytown, New York. Initially, most scientists assumed that because it blocks XPO1, the drug prevents proteins such as TDP-43 from piling up in the cytoplasm by trapping them in the nucleus. But last year, Dormann’s team and another led by Philip Thomas, a biochemist at the University of Texas Southwestern Medical Center in Dallas, independently reported that TDP-43 and another protein called FUS seem to exit the nucleus by passive diffusion, not through XPO1-mediated transport. (FUS also clumps in the cytoplasm of motor neurons in some patients with ALS or FTD.)So if KPT-350 is not acting directly on the transport system, what is it doing? “It looks like the drug is targeting some more general neurotoxic pathway,” Dormann says, “but it remains to be clarified what the mechanism really is and which nuclear transport defects we’re correcting with this drug.”One possibility, recent research suggests, is that the drug actually targets tiny, dense packets of protein and RNA that form during times of cellular stress. In healthy cells, those membraneless “stress granules” generally break down and their components disperse after a viral infection, thermal shock, or some other environmental insult has passed. Not so in the diseased neurons of people with ALS or FTD. In those cells, the stress granules persist and turn sticky, recruiting proteins such as TDP-43 and FUS and eventually transforming into solid, toxic aggregates.Over the past year, several research teams have shown that components of the nuclear transport machinery—including importers, exporters, and parts of the nuclear pore itself—also can get tangled up in those aggregates. The transportation system falters, and as more TDP-43 and other proteins are added to the stress granules, a feedback loop takes hold that grinds the molecular traffic to a halt. “TDP-43 is not just a victim of nucleo-cytoplasmic transport defects,” says Wilfried Rossoll, a neuroscientist at the Mayo Clinic in Jacksonville, Florida. “It’s also a perpetrator.”In August 2018, findings from a study led by neurobiologist Ludo Van Den Bosch of VIB–Catholic University of Leuven in Belgium suggested that the transport protein XPO1 itself may play a role in stress granules. That means a drug such as KPT-350 may serve primarily as a stress granule buster, and any impact on transport may be secondary. “Things are more complicated than initially presented,” says Van Den Bosch, who has collaborated with Karyopharm.The open questions about KPT-350 have not discouraged other groups from pursuing additional strategies to sort out nuclear traffic problems. In 2017, for example, Guillaume Hautbergue and his colleagues at the University of Sheffield in the United Kingdom implicated another export factor in the neuronal loss experienced by ALS flies with the C9orf72 mutation. Hautbergue is working on ways to target that protein to prevent the export of mutant RNAs produced by the gene.Other researchers are focusing on breaking up stress granules. That approach should free up transport factors and pore proteins held hostage in those granules, allowing them to return to their usual posts in the cell, explains James Shorter, a protein biochemist at the University of Pennsylvania. He is developing a way to equip cells with a gene for making a “disaggregase” protein and has begun to test the therapeutic strategy in a mouse model of ALS.A few drug companies, including Denali Therapeutics of South San Francisco, California, and Aquinnah Pharmaceuticals of Cambridge, are looking for small molecules that can do basically the same thing. Those therapies may not directly target the nuclear transport pathway, but they would get the job done, says Aquinnah co-founder and Chief Scientific Officer Ben Wolozin, a neuropharmacologist at Boston University’s School of Medicine, because dismantling stress granules helps restore healthy nuclear transport. “This is all part of an integrated biological response,” Wolozin says.Aquinnah hopes to begin to evaluate its lead compound in ALS patients this year, about the same time that Biogen is aiming to get KPT-350 into the clinic. For now, Biogen scientists are still trying to pin down what the drug is doing in various genetic models of the disease, including the flies with marred eyes. But to some extent, Henderson says, knowing the exact mechanism of action doesn’t really matter. “The relevant experiment,” he concludes, “is in the human patient.” The normal compound fly eye (left) is marred by cell death in a strain (right) with a mutation causing amyotrophic lateral sclerosis. Cytoplasm Stress granule H.OBERLEITHNER, UNIVERSITY HOSPITAL OF MUENSTER/Science Source The Hopkins team’s result electrified colleagues in part because it had identified a transport protein, RanGAP, as key to neurodegeneration. The team showed in both the fly model of ALS and in cells from human patients that the lengthy RNA readouts produced by the mutant C9orf72 gene seemed to stick to RanGAP near the nuclear pore and put the protein out of commission. The loss of functioning RanGAP spurred a backup of the nuclear import system, resulting in the cytoplasmic buildup of proteins such as TDP-43—cluttering a cell like bags of rotting trash during a garbage strike.Just as galvanizing was the team’s finding that a potential drug could preserve neuronal health, at least in the flies. “All of a sudden it threw a potential treatment approach into the ring,” says Dorothee Dormann, a biochemist from Ludwig Maximilian University in Munich, Germany.The team had no drug that could boost levels of RanGAP in the cytoplasm and restore enough inflow to rescue the eye neurons. But Lloyd reasoned that blocking outflow of TDP-43 and other nuclear proteins may have the same beneficial effect. An experimental compound called KPT-276 was known to selectively inhibit a key nuclear export protein called exportin 1 (XPO1). The approach was a hack of sorts, marrying two wrongs—defective inflow and outflow—to make a right, but it worked. When Lloyd gave KPT-276 to his ALS flies, their eyes remained pristine.From cancer fighter to brain protectorKPT is the experimental compound code used by Karyopharm Therapeutics, a small drug company in Newton, Massachusetts. Karyopharm formed in 2008 to develop XPO1 inhibitors for treating cancer, the idea being to trigger a buildup of tumor suppressor proteins in the nucleus, where they carry out their anticancer watchdog function. A decade on, the company’s first clinical candidate, a drug for multiple myeloma, is widely expected to win marketing approval in the coming months.Chemists at Karyopharm developed a suite of XPO1 inhibitors, including KPT-276 and a relative called KPT-350, that had an important attribute: They crossed the blood-brain barrier more readily than other candidates. KPT-350 proved more potent and less toxic in preclinical testing, so the firm looked for ways to use it to treat brain disease and injury.Lloyd’s and Rothstein’s results piqued the company’s interest. When Sharon Tamir, its head of neurodegenerative and infectious diseases at the time, learned that the Hopkins researchers were working with KPT-276 and not KPT-350, she called them up to propose a collaboration using the “better” compound. Meanwhile, she began to distribute KPT-350 to other groups in Japan, Belgium, and across the United States. Collectively, those scientists showed the drug’s neuroprotective effects across a range of human cell, fly, and rodent models of ALS, Huntington, and other brain diseases.
‘We cannot afford to fail’ as SEA Games host – Duterte Philsteel returns as major sponsor of PBA Robbie Manalang remained a force to reckon with as AMA Online Education finally ended its drought with a 96-93 win over Batangas-EAC in the 2018 PBA D-League Aspirants’ Cup Monday at JCSGO Gym in Cubao.Manalang, the former Adamson playmaker, sizzled anew in his second game for the Titans, finishing with a conference-high 40 points on 8-of-16 shooting from three-point zone.ADVERTISEMENT Don’t miss out on the latest news and information. Do we want to be champions or GROs? – Sotto Sports Related Videospowered by AdSparcRead Next BeautyMNL open its first mall pop-up packed with freebies, discounts, and other exclusives MOST READ The Titans, who also paraded new signees Arvin Tolentino and Kyles Lao, finally won after four tries.The Generals slumped to 0-4.FEATURED STORIESSPORTSSEA Games: Biñan football stadium stands out in preparedness, completionSPORTSPrivate companies step in to help SEA Games hostingSPORTSBoxers Pacquiao, Petecio torchbearers for SEA Games openingIn the second game, Gamboa-St. Clare whipped Jose Rizal U, 93-76, for its third straight win.The Titans almost lost the game after leading by as many as 28 points as Cedric de Joya, Cedric Ablaza, and Jerome Garcia moved the Generals to within 95-93 in the final 11.0 seconds. Robredo: True leaders perform well despite having ‘uninspiring’ boss PLAY LIST 02:49Robredo: True leaders perform well despite having ‘uninspiring’ boss02:42PH underwater hockey team aims to make waves in SEA Games01:44Philippines marks anniversary of massacre with calls for justice01:19Fire erupts in Barangay Tatalon in Quezon City01:07Trump talks impeachment while meeting NCAA athletes02:49World-class track facilities installed at NCC for SEA Games PH military to look into China’s possible security threat to power grid LATEST STORIES Hotel says PH coach apologized for ‘kikiam for breakfast’ claim Ethel Booba on hotel’s clarification that ‘kikiam’ is ‘chicken sausage’: ‘Kung di pa pansinin, baka isipin nila ok lang’ ‘A complete lie:’ Drilon refutes ‘blabbermouth’ Salo’s claims Martinez could only muster a split from the foul line to keep the door open for Batangas-EAC in the last 9.9 ticks, but Earvin Mendoza and Garcia both muffed their attempts that could have forced overtime.“Maybe the players just got tired,” said AMA coach Mark Herrera. “But we got players who can score. At least now, we have options where we can go in our games.”Meanwhile, Mila’s Lechon has decided to withdraw from the league, citing internal problems.Team owner Aika Salanguit made the announcement to discontinue the Mighty Roasters’ campaign in their maiden conference.Mila’s Lechon ended its stint with a 0-4 card and an average losing margin of 26.3 points—RANDOLPH B. LEONGSON, INQUIRER.NETADVERTISEMENT SEA Games: PH still winless in netball after loss to Thais View comments
Manchester United have been warned against making a hasty decision in their manager hunt, with Paul Ince offering up Roberto Di Matteo as a warning amid mounting calls for Ole Gunnar Solskjaer to be handed a permanent deal.The Red Devils opted to make a change in the dugout in December, with Jose Mourinho relieved of his duties after failing to deliver the results and performances expected of him.Treble-winning hero Solskjaer was handed the reins on an interim basis, and has opened his reign at Old Trafford with eight successive victories across all competitions – with United back in the hunt for a top-four finish in the Premier League. Article continues below Editors’ Picks Man Utd ready to spend big on Sancho and Haaland in January Who is Marcus Thuram? Lilian’s son who is top of the Bundesliga with Borussia Monchengladbach Brazil, beware! Messi and Argentina out for revenge after Copa controversy Best player in MLS? Zlatan wasn’t even the best player in LA! The Norwegian has put himself in the frame to land a long-term contract, but Ince has urged the Red Devils to ensure that they appoint the “right person” rather than one with strong ties to the club who has delivered short-term success – as Di Matteo did when landing the FA Cup and Champions League at Chelsea in 2012.“Solskjaer has come in and lifted the cloud over Manchester,” former United star Ince told Match of the Day.“The players are playing with a lot of freedom. The shackles have been released. They’re playing entertaining, attacking, progressive football which the fans have been crying out for quite a while.“It’s a big job, Manchester United. It’s not about now, it’s about the future. To bridge the gap between Man City and Liverpool is a massive job.“All Ole can do is keep on winning, hopefully win a trophy, get into the Champions League spots — or win the Champions League — then he’s asking questions of Ed Woodward.“I think it’s easy to give him a season. Chelsea did that with Di Matteo.“He came in, won the Champions League, won the FA Cup, lasted three or four months. The next man for Manchester United has to be the right person. So they’ve got to make a decision at the end of the season.”While Solskjaer remains the favoured choice of many to guide United beyond the end of the 2018-19 campaign, several other names remain in the frame.Speculation regarding an approach for Tottenham head coach Mauricio Pochettino continues to rage, with the Argentine considered to be lacking the backing he requires in north London to fulfil his trophy-chasing ambition. Check out Goal’s Premier League 2019-20 fantasy football podcast for game tips, debate and rivalries.
Two sets of sisters will try and bring home the Origin trophy for their respective states when the Women’s Open State of Origin (SOO) series gets underway today at the Port Macquarie Regional Sports Stadium.Laura and Sarah Peattie will don the sky blues jersey of New South Wales while Toowoomba twins, Gemma and Nikki Etheridge, will be flying the flag for Queensland.Both sets of sisters are Australian representatives.Sarah, Nikki and Gemma were Australian teammates in the mixed opens division at April’s Trans-Tasman Test Series in Mudgee, while Laura is in the Australian under 18’s Girls squad.But this will be the first time the two sets of sisters are playing together for their respective states.Gemma made her debut for Queensland in the 2006 State of Origin series and Nikki followed suit in 2008.It is the debut for both Laura and Sarah for New South Wales.“It’s probably the best part about it,” Sarah said about playing with her younger sister.“I was more excited for her to be in the team than myself.”Sarah, 19, and Laura, 18, are the youngest members of NSW’s women’s opens.Their family and club-mates from Manly have made the trek to Port Macquarie to watch the girls in action.Sarah said NSW were confident of winning the women’s opens division but they can’t take Queensland lightly.“They have a lot of great names in there and some of them are the best in Australia. It is going to be the toughest game we have played.“It will be a big battle.”The State of Origin also pits best mates Alicia Quirk and Emilee Cherry against each other.Quirk and Cherry have virtually been inseparable in 2012.They both were members of the winning Australian Trans-Tasman women’s opens team and the pair are in the Australian women’s rugby sevens side.Both will line-up opposite each other for the first time at state opens level.Quirk took to Twitter earlier this morning to express her thoughts on playing Cherry match.“@RebeccaTavo @emilee_cherry churrr tavs!! Go the blues. Toughest battle against bestest friend! #gameon,” Quirk posted on the social networking site.The first Women’s Open SOO match gets underway at 6.35pm.Make sure you stay up to date with these websites for all the State of Origin action: State of Origin – www.soo.mytouchfooty.comTouch Football Australia – www.austouch.com.auTouch Football Australia’s YouTube channel – www.youtube.com/touchfootballausTwitter: www.twitter.com/touchfootyausFacebook: www.facebook.com/touchfootballaustraliaRelated LinksFamily matters
Kirk Herbstreit.The College Football Playoff race is just getting started, but there are some teams already behind the 8-ball. If you have a loss in the first four games, you are playing with fire.A one-loss team pretty much has to win out and win its conference title game to guarantee a shot at the playoff. Getting in with two losses is possible, but unlikely.Michigan lost its season opener at Notre Dame, which caused many to eliminate the Wolverines from the playoff chase. Kirk Herbstreit is not counting them out though.Appearing on SportsCenter this morning, Herbstreit gave his reasoning why Michigan, which has won three-straight games, is still alive for the CFP.“When you lose early, fans get frustrated and Michigan to me was that team in Week 1,” Herbstreit said. “They lost the game (to Notre Dame) and not only lost the game, they didn’t look very good on offense. Jim Harbaugh since then has gone to work after that disappointing loss in Week 1 … so don’t forget about Michigan.”Now, Herbstreit is technically correct. If Michigan runs the table and wins the Big Ten, there’s no way they wouldn’t make the playoff with a 12-1 record.However, winning out is unlikely. The Wolverines have to play road games at Ohio State and Penn State and host Wisconsin and Michigan State. The odds of them winning all four of those contests is slim.Michigan does look much-improved from Week 1 until now, but it looks like another playoff-less year for Jim Harbaugh and company.[ 247Sports ]
zoom Norwegian owner and operator of Very Large Gac Carriers (VLGC) Avance Gas has revealed plans to drydock another newbuilding, namely the Hull 1077 named Chinook.The vessel is due for delivery from Jiangnan Shipyard on 21st of September, 2015 and will be drydocked in Singapore upon delivery as a precautionary measure.“After reviewing available documentation related to the stern tube bearings for the ship, Avance Gas is of the opinion that sufficient precautions have not been taken to assure that the ship is in acceptable condition. The seller and the builder have not agreed to Avance Gas’ request to carry out visual inspection of stern tube bearings prior to delivery, as the ship has been approved by class in accordance with the shipbuilding contract,” Avance Gas explained.The drydocking, which is estimated to cost approx. $400,000, is aimed at ruling out the possibility of defects to the stern tube bearings. As a result, Avance Gas said that the ship would be 10-20 days delayed in entering commercial service.The company added that it has received sufficient documentation that hull 1078 (Pampero) is in acceptable condition and that she is expected to be delivered in late October 2015, as previously reported.The announement comes in the wake of two previous newbuildings that had to be repaired earlier this year. Namely, VLGCs Breeze and Monsoon had to complete their warranty repairs related to defective stern tube bearings.
The first part of the new cruise ship Genting Dream, being built for Genting Hong Kong’s new cruise brand Dream Cruises, has been floated out of Meyer Werft’s building dock at Papenburg, Germany, on Saturday.The first of the vessel’s two section was moored for fitting and will be joined with the second section in the following months.Genting Dream will feature a length of 335m, a width of 39,7m, and will be capable of carrying a total of 3,400 passengers and 2,000 crew members. The 150,000-ton vessel will have the largest guest space ratio of 45 tons per guest as well as the highest crew-to-guest ratio at 1.7 of any Asia Pacific ship.The vessel is expected to be delivered to the company in November 2016.Genting Dream, Dream Cruises’ first vessel, is designed for the Asian market. The cruise ship will sail to Guangzhou and Sanya in China, and Pearl Delta and Hainan in Hong Kong, as well as Nansha Port, Halong Bay, Danang, Shenzhen and Zhuhai.The company’s second cruise ship, the future World Dream, is expected to join her sister vessel in November 2017.World Maritime News Staff, Video: Inselvideo
zoomImage Courtesy: Norsepower Ship classification society DNV GL has issued a type approval design certificate for Norsepower’s auxiliary wind propulsion system Rotor Sail Solution.As noted by Norsepower, Rotor Sail Solution is the first auxiliary wind propulsion system onboard a commercial ship to receive the certificate.The approval was issued by DNV GL in February 2019 after a design assessment of Norsepower’s 30-meter by 5-meter rotor sail, two of which have been installed onboard the Maersk Pelican LR2 tanker.The certification means that vessels operating Norsepower’s Rotor Sail Solution are technically capable of safely navigating ‘all operational and environmental situations’.Norsepower’s Rotor Sail Solution has already been installed on three vessels and has achieved over 35,000 hours in operation, saving more than 4,500 tonnes of CO2 in the process. The solution has delivered independently verified fuel savings with potential of up to 20%, according to the company.“Having a type approval design certificate is very important to us,” Norsepower CEO Tuomas Riski said.“Clearly, it [the type approval design certificate] provides shipowners, operators, and charterers with a level of assurance when investing in the Rotor Sail Solution, but in the long term, it removes yet another hurdle to the realisation of renewable wind energy propulsion systems at a scale that supports shipping’s transformation to a low carbon transport sector.”“To help reduce shipping’s environmental impact we will need many different fuel and technology options, which is why we were very pleased that Norsepower asked us to be part of this innovative wind propulsion project,” Geir Dugstad, director of ship classification and technical director at DNV GL, added.
NEW YORK — U.S. stocks are rising Friday, reversing a three-day losing streak as investors digest news of a potential resolution to the U.S.’s trade war with China.U.S. officials are reportedly preparing a deal that could be signed within a month, according to news agency Bloomberg. The trade war between the world’s largest economies has raised prices for consumers and companies. It’s also deepened concerns that escalating tariffs could worsen the global economy’s slowdown.President Donald Trump held off a threat to impose higher tariffs on $200 billion of Chinese products as negotiations continued. Washington accuses Beijing of stealing foreign companies’ technology or pressuring them to hand it over.Technology and bank stocks led the early gains. Retailers also rose. Gap surged on plans to spin off its Old Navy brand. Foot Locker rose after reporting strong financial results and a solid forecast.Investors have remained confident in the strength of the U.S. economy, despite weak economic reports. Consumer spending in December took its biggest tumble in nine years. Disappointing retails sales was another sign that growth slowed at the end of 2018.KEEPING SCORE: The Dow Jones Industrial Average rose 90 points, or 0.4 per cent, to 26,008 as of 10:45 a.m. The S&P 500 index and Nasdaq composite were up 0.5 per cent.OLD NAVY SAILING AWAY: Gap surged 18 per cent after it told investors it will spin off its Old Navy brand into a separate company. The retailer will retain its namesake brand, along with Banana Republic and others, in a new, yet to be named company.The split comes as Old Navy has thrived while Gap struggles with increasing competition from the likes of Target and Amazon.RUNNING START: Foot Locker jumped 8 per cent after the footwear and athletic apparel retailer blew past investor expectations for the fourth quarter. The company also expects double-digit profit growth in 2019.Damian J. Troise, The Associated Press
NICOSIA, Cyprus — The chief executive of Cyprus’ largest bank says he will quit his position in September after nearly six years to take up a “commercial opportunity” in the U.K.John Patrick Hourican, the CEO of Bank of Cyprus, said Monday that he leaves the bank in “its strongest capital position in living memory. He led its recovery from near-bankruptcy in 2013 when a banking crisis forced Cyprus to seek a rescue deal from international creditors.Hourican noted that the bank’s bad loans have been whittled down from 15 billion euros to 4.8 billion euros over six years.He cited family matters as a key reason for his departure. He said the bank’s strong balance sheet is “a good moment” to consider his succession.The Associated Press
Shelters in the city are stretched beyond capacity, with some 4,200 people from the buffer zone between Gori and the South Ossetian boundary registered as being internally displaced.More than 1,000 people are taking refuge in a UNHCR-tented camp that was just set up five days ago, another 1,000 are staying with host families and roughly 2,000 others are spread out among nearly two dozen collective centres.“Our initial assessment indicates that some 450 people arrived from their villages within the last week due to massive intimidation by marauding militias,” agency spokesperson Ron Redmond told reporters in Geneva.The remaining internally displaced persons (IDPs) were on their way home from the capital Tbilisi and other parts of the country where they had sought refuge during the conflict, but could not travel into the buffer zone beyond Gori.The most recent arrivals, reportedly from the village of Beloti in the buffer zone, told UNHCR that more than half of its 200 inhabitants fled in the early stages of the crisis, which broke out on 8 August.“Those who remained behind are now leaving due to beatings, harassment, looting and burning of houses,” Mr. Redmond said. “Some told UNHCR they had been travelling on foot and in hiding for more than two weeks before reaching Gori and the UNHCR-tented camp.”Reportedly, 20 elderly and bedridden people remained in the village, and an IDP said that villagers left buckets of water behind for them before fleeing.The uprooted have expressed anxiety over the future of their families, the safety of their villages and the conditions of their homes, harvest and livestock to UNHCR personnel.Nearly 160,000 people were displaced during the conflict, with some 128,000 uprooted within Georgia. Most of the roughly 30,000 who fled to Russia have since returned to South Ossetia. 2 September 2008The United Nations High Commissioner for Refugees (UNHCR) today expressed concern over the humanitarian conditions facing people in and around the town of Gori, which lies just south of the border of the separatist region of South Ossetia.
CALGARY — Rules imposed on foreign state-owned investment in the oil sands are having some unintended consequences in the oilpatch, says a new study by the University of Calgary’s School of Public Policy.The report analyzes share prices of oil sands companies since the regulations were announced in December 2012. That’s when the Harper government approved Chinese-owned CNOOC Ltd.’s $15-billion takeover of Calgary-based Nexen Inc., but imposed limitations on further ownership of oil sands resources by state-owned firms.The study shows that between the announcement and March of this year, oil sands stocks were about 20 per cent lower than what would have otherwise been expected. For junior firms, it was about a 30 per cent hit.“The findings of this paper indicate the federal government’s policy change has resulted in the material destruction of shareholder wealth,” the study’s authors wrote.The biggest impact has been on junior oil sands companies, whose stocks dropped by as much as 50 per cent in the first half of 2013, diverging greatly from where oil prices and the wider stock market were heading at the time. Senior and intermediate players showed steadier performance.“There’s a significant cost and that cost is borne disproportionately by juniors,” Eugene Beaulieu, director of the school’s international economics program, said in an interview.The study was co-authored by Matthew Saunders, a senior analyst with early-stage oilsands firm Laricina Energy.Small oilsands companies rely on outside investment to grow their operations much more than their larger counterparts. Much of that financing comes from joint ventures in which a partner buys a ownership stake in a project and reaps a proportionate share of its returns. In theory, those types of deals are still allowed under Ottawa’s new rules, provided the foreign state-owned entity doesn’t have control. Put in practice, that investment seems to be slowing.“Joint ventures and other kinds of investments that weren’t targeted by the policy have been affected,” said Beaulieu. “It wasn’t intended by the policy, but it seems to be having that effect.”Beaulieu said he understands the need for the Investment Canada Act to address concerns about foreign ownership of Canadian resources. But a lack of clarity over how those restrictions are applied is scaring away investment.“That uncertainty creates consequences for the investment climate,” he said.“We have to have transparent and clear rules on how it operates and I think targeting ownership instead of targeting behaviour is not the right approach.”Citing figures from the Canadian Energy Research Institute, the study’s authors say about $100 billion in investment will be needed in the oil sands over the next five years.The report also cites a warning last fall from Jim Prentice, a former federal industry minister who is now running to become Alberta premier.Prentice, then a senior executive at the Canadian Imperial Bank of Commerce, told a London conference that foreign investment in Canada’s energy sector had dropped 92% year over year.“Canada must make clear to the world that it continues to be open for business. This isn’t a criticism of the government’s new policy. It is more a question of tone,” he said.“Not everyone is getting the message that Canada remains open to the world. In fact, some are coming to believe the opposite.”However, federal Natural Resources Minister Greg Rickford took issue with that assessment.“Canada is open for business, but that does not mean we’re for sale to foreign governments,” the minister said in a emailed statement.“With our new rules, we have made a clear distinction between free market private investment and entities controlled or influenced by foreign governments,” he said, adding that foreign government entities would not be permitted to acquire control of a Canadian oil sands business unless there are “exceptional circumstances.”“Our balanced approach ensures that foreign investment transactions are reviewed on their merits based on the long-term interests of the Canadian economy,” he said.Canadian Press
State Intelligence chief Sisira Mendis has resigned from his post with immediate effect.His resignation comes after he made a statement to the Parliament Select Committee (PSC) on the Easter Sunday attacks. There were reports earlier that he had been sacked. Last week Sisira Mendis had told the PSC that the President had failed to hold regular security review meetings to assess the potential threat from extremists.The President was later said to have been outraged over Mendis being questioned by the PSC and over the session being open to the media. The President said that he will not allow any current officer to be summoned before the PSC and that his stand has been communicated to the cabinet.The President also said that he has been informed by the Attorney General that the PSC proceedings will hamper ongoing cases filed on the Easter Sunday attacks. (Colombo Gazette) Among the officials questioned so far are the Defence Secretary, intelligence chief, Police chief and former Defence Secretary. Yesterday the President had he cannot approve the PSC grilling security officials.At a meeting with Senior Ranks of Sri Lanka Police the President said the Attorney General had informed him, there are five cases on the 04/21 attacks before the Supreme Court and appointing a PSC at such a time sets a negative impact on the process undertaken by the Supreme Court.The PSC on the Easter Sunday attacks has been meeting over the past few days. However the Defence Ministry said that he had resigned.
AddThis Sharing ButtonsShare to TwitterTwitterShare to FacebookFacebookShare to RedditRedditShare to 電子郵件Email US stocks end mostly lower after UPS, GE and others issue disappointing results by The Associated Press Posted Jan 17, 2014 2:13 pm MDT NEW YORK, N.Y. – Weak earnings from big U.S. companies are nudging the stock market lower.United Parcel Service, General Electric and others issued disappointing results or forecasts.The Standard & Poor’s 500 index fell seven points, or 0.4 per cent, to close at 1,838 Friday.The Nasdaq fell 21 points, or 0.5 per cent, to 4,197.The Dow Jones industrial average rose, but mostly because of large gains in American Express and Visa.The Dow rose 41 points, or 0.3 per cent, to 16,458. Without the gains from Amex and Visa, the average would have been much lower.Amex reported late Thursday that its income more than doubled in the fourth quarter.Student loan company SLM fell 10 per cent after its earnings missed expectations. The stock fell the most in the S&P 500 index.
IRISH PEOPLE FOUNDED new companies at a faster rate last month than any other equivalent time since the end of the boom.New figures show that a total of 1,518 companies were started in the State last month, higher than any other July figures since 2007.The figure is also an 11% increase on the same month in 2013, when 1,371 companies were founded.The figure means that Ireland is now becoming home to around 49 new companies every single day.Professional services was the most vibrant sector in July, accounting for 22% of new company formation, followed by the wholesale/retail segment with 10%, and construction start-ups at 9%.Location, location, locationUnsurprisingly, Dublin led the pack in terms of new company location, and was home to a majority of start-ups with 51% of the total, followed by Cork on 8% and Limerick (4%).The numbers were compiled by credit and business risk analyst Vision-net.ie.Managing director Christine Cullen said that the month’s figures were “further positive signs of economic renewal”. July’s company start-up figures are the highest seen in that month in seven years and are indicative of greater business confidence. The strong increase in start-ups will also have a knock-on effect in the wider economy such as in job creation or improving B2B trading.InsolvenciesCullen said that sectors which struggled during the recession are becoming increasingly hardy, with insolvencies in the motoring sector down by 86% compared to the same time last year.In construction, insolvencies fell by 47% and by 29% in real estate.There wasn’t good news across the board, however, with the embattled retail sector seeing 31 businesses collapse during July, up 139% on 2013.Cullen said: “A decline in insolvencies in the motoring, construction and real estate sectors is encouraging. This decline indicates that these industries are gradually becoming more resilient.”Dublin again had the lion’s share of insolvencies, accounting for 46% of the total, followed by 13% in Cork and 6% in Galway. There were no company wind-ups in Carlow, Leitrim, Waterford and Longford.Read: Why are construction start-ups outpacing other sectors?>Read: Moving on up – construction start-ups rise by almost 40%>