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Automated Exposure Notification for COVID-19. 针对COVID-19的自动暴露通知。
Pub Date : 2022-12-01
Leo Samuels, Novak Boskov, Andreas Francisco Oliveira, Edwin Sun, David Starobinski, Ari Trachtenberg, Manan Monga, Mayank Varia, Ran Canetti, Anand Devaiah, Gerald V Denis

In the current COVID-19 pandemic, various Automated Exposure Notification (AEN) systems have been proposed to help quickly identify potential contacts of infected individuals. All these systems try to leverage the current understanding of the following factors: transmission risk, technology to address risk modeling, system policies and privacy considerations. While AEN holds promise for mitigating the spread of COVID-19, using short-range communication channels (Bluetooth) in smartphones to detect close individual contacts may be inaccurate for modeling and informing transmission risk. This work finds that the current close contact definitions may be inadequate to reduce viral spread using AEN technology. Consequently, relying on distance measurements from Bluetooth Low-Energy may not be optimal for determining risks of exposure and protecting privacy. This paper's literature analysis suggests that AEN may perform better by using broadly accessible technologies to sense the respiratory activity, mask status, or environment of participants. Moreover, the paper remains cognizant that smartphone sensors can leak private information and thus recommends additional objectives for maintaining user privacy without compromising utility for population health. This literature review and analysis will simultaneously interest (i) health professionals who desire a fundamental understanding of the design and utility of AEN systems and (ii) technologists interested in understanding their epidemiological basis in the light of recent research. Ultimately, the two disparate communities need to understand each other to assess the value of AEN systems in mitigating viral spread, whether for the COVID-19 pandemic or for future ones.

在当前的COVID-19大流行中,已经提出了各种自动暴露通知(AEN)系统,以帮助快速识别受感染个体的潜在接触者。所有这些系统都试图利用当前对以下因素的理解:传输风险、解决风险建模的技术、系统策略和隐私考虑。虽然AEN有望缓解COVID-19的传播,但在智能手机中使用短距离通信通道(蓝牙)来检测密切的个人接触者,对于建模和通报传播风险可能是不准确的。这项工作发现,目前的密切接触者定义可能不足以使用AEN技术减少病毒传播。因此,依靠低功耗蓝牙的距离测量可能不是确定暴露风险和保护隐私的最佳选择。本文的文献分析表明,通过使用广泛可用的技术来感知参与者的呼吸活动、面罩状态或环境,AEN可能会表现得更好。此外,该论文仍然认识到智能手机传感器可能泄露私人信息,因此建议在不损害人口健康效用的情况下维护用户隐私的其他目标。这篇文献综述和分析将同时引起(i)希望对AEN系统的设计和效用有基本了解的卫生专业人员和(ii)有兴趣根据最近的研究了解其流行病学基础的技术人员的兴趣。最终,这两个不同的社区需要相互了解,以评估AEN系统在减轻病毒传播方面的价值,无论是针对COVID-19大流行还是未来的大流行。
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引用次数: 0
Structural Analysis of a New Saccharomyces cerevisiae α-glucosidase Homology Model and Identification of Potential Inhibitor Enzyme Docking Sites 一种新的酿酒酵母α-葡萄糖苷酶同源性模型的结构分析及潜在抑制剂酶对接位点的鉴定
Pub Date : 2020-10-01 DOI: 10.22186/JYI.38.4.27-33
J. Turner, L. Thomas, S. Kennedy
Publication date: October 2020 (Robinson et al., 1991). There have been countless studies on inhibition of the active site in α-glucosidase using sugar mimics, which lead to the creation of Acarbose and Miglitol medications (Clissold and Edwards, 1988; Laube, 2002; Scott and Spencer, 2000; Sels et. al., 1999). However, these drugs induce side effects, including gastrointestinal pain, and constipation/diarrhea (Aoki et. al., 2010). The use of sugar mimicking drugs brings about the complication of interaction with other naturally occurring sugar-binding enzymes, which can lead to gastrointestinal distress. The identification of natural allosteric inhibitors, which do not mimic sugars and bind to an area on the enzyme distinct from the active site, may reveal more potent inhibitors with fewer adverse effects; the inhibition studies of α-glucosidase in vitro and in vivo have created a pool of known and potential inhibitors with a specific flavonoid scaffold (Kim et. al., 2000; Singh et. al., 2014; Tadera et. al., 2006; Xu, 2010). Flavonoids consist of two specific chemical moieties: a benzopyran containing the A and C-rings, and a phenyl group referred to as the B-ring (Figure 1) (Panche et. al., 2016). Several flavonoids have previously been studied for inhibitory effects on α-glucosidase (Proença et al., 2017). Our goal is to identify and confirm how and where these compounds are binding to α-glucosidase as well as to verify their inhibitory mechanism because this will broaden the understanding of how allosteric inhibition of α-glucosidase works at the molecular level and inform future drug design. After investigating published research and compiling a list of natural inhibitors with IC50 values similar to acarbose, we decided on a series of flavonoids was identified for docking INTRODUCTION α-glucosidase (EC 3.2.1.20) is a digestive enzyme which aids in the hydrolysis of α(1-4)-linked α-D-glucose molecules at the terminal end of polysaccharides (Jeske et. al., 2018). Inhibiting this protein slows the release of free glucose in the small intestines. The therapeutic advantage of inhibiting α-glucosidase is that it can be used to treat certain diseases associated with abnormally high blood glucose concentrations, such as Type II diabetes (diabetes mellitus). Those with diabetes mellitus do not secrete enough insulin following a meal, resulting in post-prandial hyperglycemia (Alberti and Zimmet, 1998). Inhibiting α-glucosidase can stop the body from entering a state of hyperglycemia by slowing the initial absorption of glucose in the blood stream, giving insulin a more manageable increase in blood-glucose levels Structural Analysis of a New Saccharomyces cerevisiae α-glucosidase Homology Model and Identification of Potential Inhibitor Enzyme Docking Sites
出版日期:2020年10月(Robinson et al., 1991)。利用糖模拟物抑制α-葡萄糖苷酶活性位点的研究不计其数,由此产生了阿卡波糖和米格列醇类药物(Clissold and Edwards, 1988;Laube, 2002;Scott and Spencer, 2000;Sels等人,1999)。然而,这些药物会产生副作用,包括胃肠道疼痛和便秘/腹泻(Aoki et. al., 2010)。使用糖模拟药物会带来与其他天然存在的糖结合酶相互作用的复杂性,这可能导致胃肠道不适。天然变构抑制剂的鉴定,不模仿糖和结合酶的活性部位不同的区域,可能揭示更有效的抑制剂和更少的不良反应;体外和体内对α-葡萄糖苷酶的抑制研究已经创建了一个已知的和潜在的抑制剂库,具有特定的类黄酮支架(Kim et. al., 2000;Singh等人,2014;Tadera et al., 2006;徐,2010)。类黄酮由两个特定的化学成分组成:含有a环和c环的苯并吡喃,以及被称为b环的苯基(图1)(Panche等人,2016)。之前已经研究了几种黄酮类化合物对α-葡萄糖苷酶的抑制作用(proenpada et al., 2017)。我们的目标是确定和确认这些化合物如何以及在哪里与α-葡萄糖苷酶结合,并验证它们的抑制机制,因为这将扩大对α-葡萄糖苷酶变构抑制如何在分子水平上起作用的理解,并为未来的药物设计提供信息。介绍α-葡萄糖苷酶(EC 3.2.1.20)是一种帮助水解多糖末端α(1-4)-连接的α- d -葡萄糖分子的消化酶(Jeske et. al., 2018)。抑制这种蛋白质会减缓小肠中游离葡萄糖的释放。抑制α-葡萄糖苷酶的治疗优势是可用于治疗与异常高血糖浓度相关的某些疾病,如II型糖尿病(糖尿病)。糖尿病患者进餐后分泌的胰岛素不足,导致餐后高血糖(Alberti and Zimmet, 1998)。抑制α-葡萄糖苷酶可以通过减缓血液中葡萄糖的初始吸收来阻止机体进入高血糖状态,使胰岛素更易控制血糖水平的升高。一种新的酿酒酵母α-葡萄糖苷酶同源性模型的结构分析及潜在抑制剂酶对接位点的鉴定
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引用次数: 2
Does Providing Hiding Spaces for Zebrafish in Large Groups Reduce Aggressive Behaviour? 为大群斑马鱼提供隐藏空间会减少它们的攻击行为吗?
Pub Date : 2020-10-01 DOI: 10.22186/jyi.38.5.43-56
Aleksandra Czezyk, C. Burn, Claire Russell
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引用次数: 2
The Engineering of Natural Killer Cells as an Emerging Adoptive Cancer Immunotherapy 自然杀伤细胞工程作为一种新兴的过继性癌症免疫疗法
Pub Date : 2020-10-01 DOI: 10.22186/jyi.38.5.36-42
P. Senthil, Hariharan Balakrishnan
T cells and but need to be genetically modified to recognize and kill targets. This can be achieved by introducing CARs into NK cells and cell lines. Scientists also face the challenge of properly manufacturing engineered NK cells. If successful, CAR NK cells could be safer, cheaper, easier to produce, and more widely applicable than T cells. This review focuses on recent advances in NK cell engineering and discusses how NK cells contribute to new immunotherapeutic approaches for treatment against refractory hematological malignancies.
T细胞,但需要经过基因修饰才能识别和杀死目标。这可以通过将CAR引入NK细胞和细胞系来实现。科学家们还面临着正确制造工程NK细胞的挑战。如果成功,CAR NK细胞可能比T细胞更安全、更便宜、更容易生产,应用范围更广。本文综述了NK细胞工程的最新进展,并讨论了NK细胞如何为治疗难治性血液系统恶性肿瘤的新免疫治疗方法做出贡献。
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引用次数: 2
A Novel Nickel-Titanium Wire-Actuated Prosthetic Motor Clutch 一种新型镍钛丝驱动的修复电机离合器
Pub Date : 2020-09-01 DOI: 10.22186/jyi.38.3.18-23
A. Chan, Jacob Altholz, R. Weir, Matthew L. Davidson
Publication date: September 202
公布日期:202年9月
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引用次数: 0
Aflatoxin and Its Toxic Tragedies in Kenya 黄曲霉毒素及其在肯尼亚的毒性悲剧
Pub Date : 2020-08-01 DOI: 10.22186/jyi.38.2.10-12
Kaiming Tan
are essential to prevent future aflatoxin outbreaks.
对预防未来黄曲霉毒素爆发至关重要。
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引用次数: 2
Finding Probable Frequency Sums to Reduce the Key Space of Homophonic Substitution Ciphers 寻找可能频率和以减小谐音替换密码的密钥空间
Pub Date : 2020-07-01 DOI: 10.22186/jyi.38.1.1-5
Floe Foxon
Publication date: July 2020 Clearly, brute-force decryption attempts are an inefficient means of decryption. Fortunately, patterns in the distribution of letter frequencies in languages may be used to immediately identify which cipher characters are likely to represent which plaintext characters. For example, the letter ‘e’ is the most frequent letter in English text (Friedman, 1938), therefore the most frequent cipher character in a given monoalphabetic substitution cipher text likely represents the letter ‘e’. This frequency analysis approach may be repeated for all character frequencies in the cipher text for complete decryption. Homophonic substitution ciphers circumvent frequency analysis by mapping each character in a plaintext alphabet to multiple cipher characters (e.g. a {e, !}, b {~, q}, c {z, X}, etc.). In this way, the ciphertext alphabet is greater than the plaintext alphabet, and the frequency distribution of ciphertext characters does not immediately resemble that of the underlying plaintext language. For a cipher of this kind with two unique homophones mapped to each character of the plaintext English alphabet, there are ~1.2 × 1060 possible keys. A machine capable of one trillion decryption attempts per second would take ~3.8 × 1040 years to brute-force the entire key space. Decrypting such a cipher exhaustively in a reasonable amount of time is far beyond the current technological grasp of cryptanalysts (Diffie and Hellman, 1977), and consequently many homophonic substitution ciphers remain unsolved (Kahn, 2005). Arguably, the strongest decryption method for homophonic substitution ciphers is the hill-climbing algorithm (Dhavare et al., 2013), wherein a parent key is generated and used to decrypt the ciphertext, and the fitness of this decryption attempt is measured. The key is then modified, and another decryption attempt is made with this modified key. If the fitness of the modified attempt is better than the initial attempt, the modified key is carried forward; otherwise, INTRODUCTION Substitution ciphers are a form of encryption whereby each character in a plaintext message is substituted for a corresponding cipher character. These cryptograms have existed in various forms for millennia (Whitman and Herbert, 2017) and, for some time, were secure means of exchanging data and information due to the nature of their encryption (Singh, 2000). For a plaintext alphabet of 26 characters like the English language, a monoalphabetic substitution cipher key which maps each of these to different singular cipher characters (e.g. a e, b h, c z, etc.) is concealed by the vast size of the key space, or the number of possible mixed alphabet cipher keys. In this case, the key space is 26! ≈ 4 × 1026. A single machine capable of one billion decryption attempts per second would take ~13 billion years to brute-force every solution of such a cipher, which implies trying every possible key exhaustively. This number is comparable to the age of the o
显然,暴力破解尝试是一种低效的解密方式。幸运的是,语言中字母频率分布的模式可以用来立即识别哪些密码字符可能表示哪些明文字符。例如,字母“e”是英文文本中最常见的字母(Friedman, 1938),因此在给定的单字母替换密码文本中最常见的密码字符可能代表字母“e”。这种频率分析方法可以对密文中的所有字符频率重复,以完成解密。谐音替代密码通过将明文字母表中的每个字符映射到多个密码字符(例如a {e, !}, b {~, q}, c {z, X}等)来规避频率分析。这样,密文字母表大于明文字母表,并且密文字符的频率分布不会立即与底层明文语言的频率分布相似。对于这种密码,两个唯一的同音异义字映射到明文英文字母表的每个字符,有大约1.2 × 1060个可能的密钥。一台每秒能够进行1万亿次解密尝试的机器将需要3.8 × 1040年的时间来暴力破解整个密钥空间。在合理的时间内彻底解密这样的密码远远超出了密码分析人员目前的技术掌握(Diffie和Hellman, 1977),因此许多同音替代密码仍然没有解决(Kahn, 2005)。可以说,同音替换密码的最强解密方法是爬坡算法(dhahavare et al., 2013),该算法生成父密钥并用于解密密文,并测量该解密尝试的适合度。然后修改密钥,并使用修改后的密钥进行另一次解密尝试。如果修改后的尝试的适应度优于初始尝试,则将修改后的密钥结转;替换密码是一种加密形式,明文消息中的每个字符都被替换为相应的密码字符。这些密码已经以各种形式存在了数千年(Whitman和Herbert, 2017),并且在一段时间内,由于其加密的性质,它们是交换数据和信息的安全手段(Singh, 2000)。对于像英语这样的26个字符的明文字母表,将这些字符中的每个映射到不同的单个密码字符(例如a e, b h, c z等)的单字母替换密码密钥被密钥空间的巨大大小或可能的混合字母密码密钥的数量所隐藏。在本例中,键空间为26!≈4 × 1026。一台每秒能够进行10亿次解密尝试的机器将需要大约130亿年的时间来破解这样一个密码,这意味着要用尽可能的方法尝试每一个密钥。这个数字与可观测宇宙的年龄相当(Planck Collaboration et al., 2016)。寻找可能频率和以减小谐音替换密码的密钥空间
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引用次数: 0
Effects of Cat and Dog Interactions on Urban Wildlife Admitted to a Wildlife Center in Wisconsin 猫狗互动对威斯康星州野生动物中心接纳的城市野生动物的影响
Pub Date : 2020-06-01 DOI: 10.22186/jyi.38.6.61-66
Makayla Timm, N. Kime
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引用次数: 3
Optimal Targeting of a Tumor through Proton Beam Therapy 通过质子束治疗肿瘤的最佳靶向
Pub Date : 2020-03-01 DOI: 10.22186/jyi.37.3.32-37
K. Pant, C. Campbell
Publication date: March 2020 the prostate, esophagus, lung and liver. A large number of pediatric patients with central nervous system (CNS) tumors also benefit from PBT (Gondi et al., 2016). Protons interact with matter in three different ways: interactions with atomic electrons, interactions with the atomic nucleus, and interactions with the atom as a whole (Verhey et al., 1998). Protons that interact with the nucleus may produce Bremsstrahlung radiation, but this occurs so infrequently that its effects are negligible. There is also the possibility that protons will collide with an atom and produce secondary protons, neutrons, or excited nuclei, although these interactions are also rare. Protons primarily lose kinetic energy as they traverse matter via inelastic Coulombic interactions with atomic orbital electrons, which also deflect the proton trajectory (Newhauser and Zhang, 2015). The deflection due to a single interaction is generally quite small as the mass of a proton is much larger than that of an electron. However, the cumulative effect of many such interactions can be significant. The most complete theory of multiple Coulombic scattering was proposed by Molière (1947). Many simplifications of this theory have been proposed, although this simplicity often reduces the accuracy in modeling Coulombic scattering at large angles. Gottschalk et al. (1993) approximated Molière’s theory to take the form of a Gaussian function, assuming the small angle approximation in which sin(θ)≈θ:
出版日期:2020年3月前列腺、食道、肺和肝。大量患有中枢神经系统(CNS)肿瘤的儿科患者也受益于PBT (Gondi et al., 2016)。质子以三种不同的方式与物质相互作用:与原子电子的相互作用,与原子核的相互作用,以及与整个原子的相互作用(Verhey et al., 1998)。质子与原子核相互作用可能产生轫致辐射,但这种情况很少发生,其影响可以忽略不计。也有可能质子与原子碰撞并产生二次质子、中子或激发态原子核,尽管这些相互作用也很罕见。质子通过与原子轨道电子的非弹性库仑相互作用穿越物质时主要失去动能,这也会使质子轨迹偏斜(Newhauser和Zhang, 2015)。由于质子的质量比电子的质量大得多,单次相互作用引起的偏转通常相当小。然而,许多这样的相互作用的累积效应可能是显著的。最完整的多重库仑散射理论是由moli(1947)提出的。人们对这一理论进行了许多简化,尽管这种简化往往会降低大角度库仑散射建模的准确性。Gottschalk et al.(1993)将moli的理论近似为高斯函数的形式,假设sin(θ)≈θ的小角度近似:
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引用次数: 0
Engineering a Cell-Penetrating Anti-HER2 Monoclonal Antibody for Efficient Delivery of Gold Nanoparticles into Cancer Cells To Enhance X-Ray Cancer Radiation Therapy 设计一种细胞穿透性抗her2单克隆抗体,有效地将金纳米颗粒递送到癌细胞中,以增强x射线癌症放疗
Pub Date : 2020-02-01 DOI: 10.22186/jyi.38.2.13-22
Kevin Guo, R. Hawkins, Bo-Sheng Wu
13 INTRODUCTION Cancer heat therapy, also referred to as nanoparticle hyperthermia, utilizes the strong light absorptive properties of gold nanoparticles (GNPs) to create heat and free radicals in a small localized region to burn away cancer after GNPs absorb high energy photons from radiation (Kaur et al., 2016). Therefore, GNPs have been considered as good candidates to enhance the effect of cancer radiation therapy (Jain et al., 2012; Hu et al., 2015; Saha et al., 2016). Gold nanoparticles are gold coordination complexes with outstanding cytotoxic properties. When internalized into cells, these gold compounds can trigger direct mitochondrial damage and induce apoptosis (Gamberi, 2013). GNPs are small particles that can penetrate not only cancer cells, but also healthy tissues. Accumulation of these inherently toxic particles in healthy cells would lead to unwanted side effects and reduce the effective compound concentration at the tumor site. This lack of tumor selectivity can be addressed by attaching monoclonal antibodies (mAbs) that recognize specific cancer cell-surface proteins to the relatively large surface area of GNPs (Fay and Scott, 2011). The HER2 receptor is overexpressed in about 30% of breast cancers and regulates important pathways involved in cell survival and proliferation. Therapeutic antibodies targeting the HER2 receptor have provided satisfactory results. Additionally, HER2-targeted nanoparticles were exploited to deliver drug to tumor sites (Mazzucchelli et al., 2014). Therefore, in this study, an anti-HER2 antibody targeting HER2 receptor was conjugated to GNPs in order to specifically deliver nanoparticles to breast cancer cells for photothermal ablation. Journal of Young Investigators Research
癌症热疗法,也被称为纳米粒子热疗,利用金纳米粒子(GNPs)的强光吸收特性,在GNPs吸收来自辐射的高能光子后,在小局部区域产生热量和自由基,从而燃烧掉癌症(Kaur等,2016)。因此,GNPs被认为是增强癌症放射治疗效果的良好候选者(Jain et al., 2012;Hu et al., 2015;萨哈等人,2016)。金纳米颗粒是具有优异细胞毒性的金配位配合物。当被内化到细胞中时,这些金化合物可以直接引发线粒体损伤并诱导细胞凋亡(Gamberi, 2013)。GNPs是一种小颗粒,不仅能穿透癌细胞,还能穿透健康组织。这些固有毒性颗粒在健康细胞中的积累将导致不必要的副作用,并降低肿瘤部位的有效化合物浓度。这种肿瘤选择性的缺乏可以通过将识别特定癌细胞表面蛋白的单克隆抗体(mab)附着在GNPs相对较大的表面积上来解决(Fay和Scott, 2011)。HER2受体在大约30%的乳腺癌中过度表达,并调节与细胞存活和增殖有关的重要途径。靶向HER2受体的治疗性抗体提供了令人满意的结果。此外,利用靶向her2的纳米颗粒将药物输送到肿瘤部位(Mazzucchelli等人,2014)。因此,在本研究中,我们将靶向HER2受体的抗HER2抗体偶联到GNPs上,以便特异性地将纳米颗粒递送到乳腺癌细胞中进行光热消融。青年调查研究杂志
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引用次数: 1
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Journal of young investigators
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