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Cryo-EM map interpretation and protein model-building using iterative map segmentation. 利用迭代图分割进行低温电子显微镜图解读和蛋白质模型构建。
IF 4.5 Pub Date : 2020-01-01 Epub Date: 2019-10-24 DOI: 10.1002/pro.3740
Thomas C Terwilliger, Paul D Adams, Pavel V Afonine, Oleg V Sobolev

A procedure for building protein chains into maps produced by single-particle electron cryo-microscopy (cryo-EM) is described. The procedure is similar to the way an experienced structural biologist might analyze a map, focusing first on secondary structure elements such as helices and sheets, then varying the contour level to identify connections between these elements. Since the high density in a map typically follows the main-chain of the protein, the main-chain connection between secondary structure elements can often be identified as the unbranched path between them with the highest minimum value along the path. This chain-tracing procedure is then combined with finding side-chain positions based on the presence of density extending away from the main path of the chain, allowing generation of a Cα model. The Cα model is converted to an all-atom model and is refined against the map. We show that this procedure is as effective as other existing methods for interpretation of cryo-EM maps and that it is considerably faster and produces models with fewer chain breaks than our previous methods that were based on approaches developed for crystallographic maps.

本文介绍了将蛋白质链构建到单粒子电子低温显微镜(cryo-EM)绘制的图谱中的程序。该程序类似于经验丰富的结构生物学家分析图谱的方法,首先关注二级结构元素(如螺旋和片层),然后改变等高线水平以识别这些元素之间的联系。由于图谱中的高密度通常沿着蛋白质的主链,因此二级结构元素之间的主链连接通常可以识别为它们之间沿路径最小值最高的无分支路径。然后,根据从主链路径延伸出的密度,将这种链追踪程序与寻找侧链位置相结合,从而生成 Cα 模型。Cα 模型被转换为全原子模型,并根据图谱进行细化。我们的研究表明,该方法与其他现有的低温电子显微镜图谱解释方法一样有效,而且与我们以前基于晶体图谱开发的方法相比,该方法速度更快,生成的模型断链更少。
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引用次数: 0
Trading Your Health: Assessing the Need for Domestic Regulation of Telemedicine and Ability to Conform to U.S. Trade Agreements 健康交易:评估国内远程医疗监管的必要性和遵守美国贸易协议的能力
Pub Date : 2018-02-01 DOI: 10.2139/ssrn.3116354
Marilyn Higdon
International telemedicine services have existed virtually outside the U.S. regulatory matrix for over a decade. This lack of regulation has opened the door for dangerous and possibly life-threatening situations to arise, leaving little to no available recourse for injured consumers. Regulation is often cast as an antonym of liberalization and a dirty word under the current political and economic zeitgeist. Despite this common misconception, regulation can be imposed without threatening liberalized trade or breaching current free-trade agreements. All current trade agreements, by nature, seek to increase liberalization and globalization by reducing barriers to trade. However, lack of commitment, provisions allowing for domestic regulation of services, and specific exceptions within the agreements leave the door open for the U.S. to impose a regulatory matrix governing telemedicine without breaching the obligations of our current free-trade agreements. Telemedicine’s value cannot be denied. Nonetheless, trading healthcare services, and thereby the health and safety of Americans, cannot continue unchecked. If executed properly, regulations can both serve U.S. free-trade interests and protect patient-consumers.
国际远程医疗服务实际上已经在美国监管体系之外存在了十多年。这种监管的缺失为危险和可能危及生命的情况的出现打开了大门,受伤的消费者几乎没有可用的追索权。在当前的政治和经济时代精神下,监管往往被视为自由化的反义词和一个肮脏的词。尽管存在这种普遍的误解,但监管可以在不威胁自由化贸易或违反现行自由贸易协定的情况下实施。目前所有的贸易协定,从本质上讲,都力求通过减少贸易壁垒来增加自由化和全球化。然而,缺乏承诺,允许国内服务监管的条款,以及协议中的特定例外,为美国在不违反我们当前自由贸易协定义务的情况下实施远程医疗监管矩阵敞开了大门。远程医疗的价值不容否认。然而,医疗服务贸易,以及由此带来的美国人的健康和安全,不能继续不受控制。如果执行得当,监管既能服务于美国的自由贸易利益,又能保护患者和消费者。
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引用次数: 0
The Telephone Consumer Protection Act of 1991: Adapting Consumer Protection to Changing Technology 1991年电话消费者保护法:使消费者保护适应不断变化的技术
Pub Date : 2013-09-17 DOI: 10.2139/SSRN.2327266
Daniel B. Heidtke, Jessica Stewart, S. Waller
In the late 1980’s, spurred on by advances in technology, the telemarketing industry began aggressively seeking out consumers in the hundreds of thousands. Companies began using machines that automatically dialed consumers and delivered prerecorded messages (“robocalls”). Marketers also took advantage of another new and increasingly available piece of technology known as the facsimile machine (“fax machine”). With the fax machine, marketers could now send tens of thousands of unsolicited advertisements (“junk fax”) each week to consumers across the nation. Consumers and businesses became overwhelmed with unsolicited telemarketing calls and advertisements. Calls for action grew louder. States enacted laws, but could not reach the interstate practices of telemarketers. After reviewing and debating ten different pieces of legislation, Congress enacted the Telephone Consumer Protection Act of 1991 (“TCPA”). The primary focus of this report is the Telephone Consumer Protection Act of 1991. The TCPA was born out of abusive telemarketing practices, made more intrusive by advances in technology. Originally, the TCPA imposed restrictions on the use of telephones for unsolicited advertising by telephone and fax. The TCPA has since been expanded and adapted by administrative rule, judicial interpretation, and congressional amendment. The original purpose of the TCPA was to regulate certain uses of technology that are abusive, invasive, and potentially dangerous. The TCPA effectively regulates these abuses by prohibiting certain technologies altogether, rather than focusing specifically on the content of the messages being delivered. The expansion of the TCPA into areas outside of telemarketing and new technologies over the years is consistent with its original purpose. Private parties are largely responsible for the enforcement of the TCPA, and have done so primarily through the class action mechanism. While this has drawn some criticism because of the provision of high statutory damages, the threat of class action has provided a significant deterrent to violators. Historically the government has only enforced the TCPA to a limited extent, yet the statute has been relatively successful in reducing the conduct it was enacted to regulate. Technology is again rapidly changing and a number of trends are emerging. The number of entities that are operating in intentional disregard of the TCPA are growing, and they are using technology to help evade detection and enforcement. According to the FTC, about 59% of phone spam cannot be traced or blocked because the phone calls are routed through “a web of automatic dialers, caller ID spoofing and voice-over-Internet protocols.” Although the traditional scheme of TCPA enforcement, with its strong reliance on the private right of action, has been successful in the past, two main issues are becoming clear. The private right of action is limited in both incentivizing lawsuits against, and deterring the actions of, intentio
20世纪80年代末,在技术进步的推动下,电话营销行业开始积极地寻找成千上万的消费者。公司开始使用自动拨打消费者电话并传送预先录制好的信息的机器(“自动电话”)。市场营销人员还利用了另一种日益普及的新技术,即传真机(fax machine)。有了传真机,营销人员现在每周可以向全国各地的消费者发送数以万计的未经请求的广告(“垃圾传真”)。消费者和企业被不请自来的电话营销电话和广告淹没。要求采取行动的呼声越来越高。各州制定了相关法律,但无法触及州际电话营销的做法。在审查和辩论了十项不同的立法之后,国会颁布了1991年《电话消费者保护法》(TCPA)。本报告的主要焦点是1991年的电话消费者保护法。TCPA诞生于滥用的电话营销行为,并因技术进步而更具侵入性。最初,TCPA对使用电话进行未经请求的电话和传真广告施加了限制。此后,TCPA通过行政规则、司法解释和国会修正案得到了扩展和调整。TCPA最初的目的是规范某些滥用、侵入性和潜在危险的技术使用。TCPA通过全面禁止某些技术,而不是特别关注所传递信息的内容,有效地控制了这些滥用行为。多年来,TCPA扩展到电话营销和新技术以外的领域,这与它最初的目的是一致的。私人当事方主要负责TCPA的执行,并且主要通过集体诉讼机制来执行。虽然由于规定了高额的法定损害赔偿,这招致了一些批评,但集体诉讼的威胁对违规者起到了很大的威慑作用。从历史上看,政府只是在有限的范围内执行了TCPA,但该法规在减少其制定监管的行为方面相对成功。技术再次快速变化,许多趋势正在出现。故意无视《对外贸易法》开展活动的实体越来越多,它们利用技术手段帮助逃避侦查和执法。据美国联邦贸易委员会称,大约59%的垃圾电话无法被追踪或拦截,因为这些电话是通过“一个由自动拨号器、来电显示欺骗和互联网语音协议组成的网络”进行路由的。尽管传统的TCPA执行方案(强烈依赖私人诉权)在过去取得了成功,但两个主要问题正在变得清晰起来。私人诉权在激励针对故意违法者的诉讼和阻止故意违法者的行为方面是有限的;联邦通信委员会的执法受到其缓慢进程的限制。为了使TCPA在20年后保持相关性,可以进行某些修改和改进。我们建议提高政府的执法力度,增加对法规的统一解释。公平交易委员会最近为解决自动电话问题而进行的技术竞赛是值得赞扬的,对于目前暴露于未经请求的商业信息(如短信和电子邮件)的其他类型的媒体,也应该效仿。为了使TCPA在未来继续保持相关性,本报告建议:1。加强政府对TCPA的执行,向各州总检察长提供更大的激励,以提起TCPA案件,并授权联邦贸易委员会根据TCPA提起诉讼;2. 通过鼓励更频繁和更快的FCC规则制定程序,增加TCPA应用的统一性;3.继续保护手机,要求与手机进行任何通信(电话或短信)都必须事先得到明确同意;4. 对垃圾传真建立业务关系设定期限;5. 为传真广播公司制定激励措施,以确定他们代表客户发送的传真是否违反了TCPA;6. 拒绝移除或以其他方式修改私人诉讼权利的努力;和7。对支持调用方标识操作的实体施加额外限制。
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引用次数: 5
Suitability and Non-Maleficence: A Proposal for Insurance Producer Regulatory Reform 适当性与非恶意性:保险企业监管改革的建议
Pub Date : 2013-01-01 DOI: 10.2139/ssrn.2282681
M. Franke
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引用次数: 0
Antitrust (Over-?) Confidence 反垄断(超过- ?)信心
Pub Date : 2008-01-25 DOI: 10.2139/SSRN.1086440
T. Lambert, Joshua D. Wright
On October 5, 2007, a group of antitrust scholars convened on Chicago's Near North Side to discuss monopolization law. In the course of their freewheeling but fascinating conversation, a number of broad themes emerged. Those themes can best be understood in contrast to a body of antitrust scholarship that was born six miles to the south, at the University of Chicago. Most notably, the North Side discussants demonstrate a hearty confidence in the antitrust enterprise - a confidence that is not shared by Chicago School scholars, who generally advocate a more modest antitrust. As scholars who are more sympathetic to Chicago School views, we are somewhat skeptical. While we applaud many the of the insights and inquiries raised during the conversation, and certainly this sort of discussion in general, our task in this article is to draft a critical analysis of the October 5 conversation. In particular, we critique the North Side discussants' vision of a big antitrust that would place equal emphasis on Sections 1 and 2 of the Sherman Act and would expand private enforcement of Section 2.
2007年10月5日,一群反垄断学者聚集在芝加哥近北区讨论反垄断法。在他们畅所欲言却引人入胜的谈话中,出现了许多广泛的主题。要想理解这些主题,最好的办法是与诞生于6英里以南的芝加哥大学(University of Chicago)的反垄断研究机构进行对比。最值得注意的是,北区的讨论者对反垄断事业表现出了由衷的信心——这种信心是芝加哥学派学者所没有的,他们通常主张更温和的反垄断。作为更赞同芝加哥学派观点的学者,我们多少有些怀疑。虽然我们赞赏谈话中提出的许多见解和疑问,当然也赞赏这种讨论,但我们在本文中的任务是起草一份对10月5日谈话的批判性分析。特别是,我们批评北侧讨论者关于大型反垄断的观点,该观点将同等强调《谢尔曼法》第1条和第2条,并扩大第2条的私人执行。
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引用次数: 0
An unfulfilled promise of the Medicaid Act: enforcing Medicaid recipients' right to health care. 《医疗补助法案》未兑现的承诺:加强医疗补助受助人获得医疗保健的权利。
Pub Date : 2005-01-01
Frederick H Cohen
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引用次数: 0
Cloning human beings and the consumer of the future: a worthwhile endeavor or a nightmare come true? 克隆人类和未来消费者:值得努力还是噩梦成真?
Pub Date : 2001-01-01
A Frankel
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引用次数: 0
Federally funded stem cell research: a good deal for the taxpayer and consumer. 联邦政府资助的干细胞研究:对纳税人和消费者来说都是一笔好交易。
Pub Date : 2001-01-01
D A Resnikoff
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Loyola consumer law review
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