A series of 4′-ethynyl (4′-E) nucleoside analogs were designed, synthesized, and identified as being active against a wide spectrum of human immunodeficiency viruses (HIV), including a variety of laboratory strains of HIV-1, HIV-2, and primary clinical HIV-1 isolates. Among such analogs examined, 4′-E-2′-deoxycytidine (4′-E-dC), 4′-E-2′-deoxyadenosine (4′-E-dA), 4′-E-2′-deoxyribofuranosyl-2,6-diaminopurine, and 4′-E-2′-deoxyguanosine were the most potent and blocked HIV-1 replication with 50% effective concentrations ranging from 0.0003 to 0.01 μM in vitro with favorable cellular toxicity profiles (selectivity indices ranging 458 to 2,600). These 4′-E analogs also suppressed replication of various drug-resistant HIV-1 clones, including HIV-1M41L/T215Y, HIV-1K65R, HIV-1L74V, HIV-1M41L/T69S-S-G/T215Y, and HIV-1A62V/V75I/F77L/F116Y/Q151M. Moreover, these analogs inhibited the replication of multidrug-resistant clinical HIV-1 strains carrying a variety of drug resistance-related amino acid substitutions isolated from HIV-1-infected individuals for whom 10 or 11 different anti-HIV-1 agents had failed. The 4′-E analogs also blocked the replication of a non-nucleoside reverse transcriptase inhibitor-resistant clone, HIV-1Y181C, and showed an HIV-1 inhibition profile similar to that of zidovudine in time-of-drug-addition assays. The antiviral activity of 4′-E-thymidine and 4′-E-dC was blocked by the addition of thymidine and 2′-deoxycytidine, respectively, while that of 4′-E-dA was not affected by 2′-deoxyadenosine, similar to the antiviral activity reversion feature of 2′,3′-dideoxynucleosides, strongly suggesting that 4′-Eanalogs belong to the family of nucleoside reverse transcriptase inhibitors. Further development of 4′-E analogs as potential therapeutics for infection with multidrug-resistant HIV-1 is warranted.

Digital tomosynthesis is a novel technique that allows easy and swift volume data acquisition in selected regions of the body. However, many radiologists and technologists are unfamiliar with this technique and the potential artifacts related to data acquisition. Digital tomosynthesis requires a single linear sweep of the x-ray tube assembly with corresponding tomographic reconstruction of large-area flat-panel detector radiographic data. Standard acquisition parameters include sweep angle, sweep direction, patient barrier-object distance, number of projections, and total radiation dose. Potential acquisition-related artifacts include blurring-ripple, ghost artifact-distortion, poor spatial resolution, image noise, and metallic artifact. A comprehensive understanding of the relationships between acquisition parameters and potential associated artifacts is critical to optimizing acquisition technique and avoiding misinterpretation of artifacts. Sweep direction should be chosen on the basis of the anatomy of interest and the purpose of the examination so as to reduce the influence of blurring-ripple, ghost artifact-distortion, and metallic artifact. Adjusting the sweep angle, number of projections, and radiation dose will optimize depth resolution, avoid ripple in the sections of interest, and reduce unnecessary radiation exposure without compromising image quality. Thus, it is important that the radiologist and technologist establish appropriate protocols for different examination types to allow optimal utilization of this novel imaging technique.

Multidetector coronary computed tomography (CT), which is widely performed to assess coronary artery disease noninvasively and accurately, provides excellent image quality. Use of electrocardiography (ECG)-controlled tube current modulation and low tube voltage can reduce patient exposure to nephrotoxic contrast media and carcinogenic radiation when using standard coronary CT with a retrospective ECG-gated helical scan. Various imaging techniques are expected to overcome the limitations of standard coronary CT, which also include insufficient spatial and temporal resolution, beam-hardening artifacts, limited coronary plaque characterization, and an inability to allow functional assessment of coronary stenosis. Use of a step-and-shoot scan, iterative reconstruction, and a high-pitch dual-source helical scan can further reduce radiation dose. Dual-energy CT can improve contrast medium enhancement and reasonably reduce the contrast dose when combined with noise reduction with the use of iterative reconstruction. High-definition CT can improve spatial resolution and diagnostic evaluation of small or peripheral coronary vessels and coronary stents. Dual-source CT and a motion correction algorithm can improve temporal resolution and reduce coronary motion artifacts. Whole-heart coverage with 320-detector CT and an intelligent boundary registration algorithm can eliminate stair-step artifacts. By decreasing beam hardening and enabling material decomposition, dual-energy CT is expected to remove or reduce the depiction of coronary calcification to improve intraluminal evaluation of calcified vessels and to provide detailed analysis of coronary plaque components and accurate qualitative and quantitative assessment of myocardial perfusion. Fractional flow reserve derived from coronary CT is a state-of-the-art noninvasive technique for accurately identifying myocardial ischemia beyond coronary CT. Understanding these techniques is important to enhance the value of coronary CT for assessment of coronary artery disease.

To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P[4.94E-20, odds ratio (OR) [1.90)

The authors report on the field emission from an aligned carbon nanotube (CNT) bundle grown by thermal chemical vapor deposition. The CNT bundle showed a low-threshold electric field of 2.0V∕μm that produced a current density of 10mA∕cm2, sustainable evolution of current density up to 2.8A∕cm2 at 2.9V∕μm, and good emission stability without degradation for 200h of continuous dc emission. By calculating the electric-field distribution, it was found that the electric field was significantly higher at the edge of the CNT bundle than at the center. The excellent field-emission properties of the aligned CNT bundle were attributed to the edge effect and the high-density structure.