© 1963-2012 IEEE. We present the design and experimental demonstration of a programmable subwavelength coil array, which can manipulate the evanescent magnetic field leading to a precisely controlled electric-field pattern at an image plane in the near-field zone. A synthesis methodology is outlined for 2-D near-field manipulations. Simulation based on a full-wave electromagnetic solver clearly demonstrates the focused electric-field pattern, and its implementation is discussed. An example of a three-layer subwavelength coil array with 48 units is fabricated and measured. The consensus of the measured results with the simulated and synthesized results verified the presented synthesis method. Such a device, capable of producing a programmable magnetic field and electric field, respectively, in orthogonal planes, will find applications in biomedical devices such as neural stimulation, and potentially other areas such as noncontact charging.

We present the design and experimental demonstration of a magnetic screen, which can pattern magnetic field into 256 programmable spots of small sub-wavelength dimension. A design methodology is outlined for designing a near-field plate to achieve a desired focus, and its implementation is discussed. Simulation using a full-wave electromagnetic solver clearly demonstrates focused magnetic field spots and that the presented structure has a stronger magnetic field compared with a conventional coil at the same focusing distance. A sample of thickness 2.1 mm with 16 layers, in which there are 32 unclosed loops for focusing on each of the eight layers and optimized guiding strips on the other eight layers, is fabricated and measured. The measurement results agree well with the simulation results. Finally, the response of the magnetic screen in the time domain is measured and computed showing the screen can be operated under pulse excitation. Such a device, capable of producing a programmable focused magnetic field, will find applications in biomedical devices, near-field imaging systems, data storage, and electromechanical actuators. © 1963-2012 IEEE.

Conventional materials vary their electromagnetic properties in response to the frequency of an incoming wave, but these responses generally remain unchanged at the same frequency unless nonlinearity is involved. Waveform-selective metasurfaces, recently developed by integrating several circuit elements with planar subwavelength periodic structures, allowed us to distinguish different waves even at the same frequency depending on how long the waves continued, namely, on their pulse widths. These materials were thus expected to give us an additional degree of freedom to control electromagnetic waves. However, all the past studies were demonstrated with waves at a normal angle only, although in reality electromagnetic waves scatter from various structures or boundaries and therefore illuminate the metasurfaces at oblique angles. Here we study angular dependences of waveform-selective metasurfaces both numerically and experimentally. We demonstrate that, if designed properly, capacitor-based waveform-selective metasurfaces more effectively absorb short pulses than continuous waves (CWs) for a wide range of the incident angle, while inductor-based metasurfaces absorb CWs more strongly. Our study is expected to be usefully exploited for applying the concept of waveform selectivity to a wide range of existing microwave devices to expand their functionalities or performances in response to pulse width as a new capability.

Electromagnetic properties depend on the composition of materials, i.e. either angstrom scales of molecules or, for metamaterials, subwavelength periodic structures. Each material behaves differently in accordance with the frequency of an incoming electromagnetic wave due to the frequency dispersion or the resonance of the periodic structures. This indicates that if the frequency is fixed, the material always responds in the same manner unless it has nonlinearity. However, such nonlinearity is controlled by the magnitude of the incoming wave or other bias. Therefore, it is difficult to distinguish different incoming waves at the same frequency. Here we present a new concept of circuit-based metasurfaces to selectively absorb or transmit specific types of waveforms even at the same frequency. The metasurfaces, integrated with schottky diodes as well as either capacitors or inductors, selectively absorb short or long pulses, respectively. The two types of circuit elements are then combined to absorb or transmit specific waveforms in between. This waveform selectivity gives us another degree of freedom to control electromagnetic waves in various fields including wireless communications, as our simulation reveals that the metasurfaces are capable of varying bit error rates in response to different waveforms.

Objectives

The past decade has seen tremendous progress in the development of biomedical agents that are effective as pre-exposure prophylaxis (PrEP) for HIV prevention. To expand the choice of products and delivery methods, new medications and delivery methods are under development. Future trials of non-inferiority, given the high efficacy of ARV-based PrEP products as they become current or future standard of care, would require a large number of participants and long follow-up time that may not be feasible. This motivates the construction of a counterfactual estimate that approximates incidence for a randomized concurrent control group receiving no PrEP.

Methods

We propose an approach that is to enroll a cohort of prospective PrEP users and aug-ment screening for HIV with laboratory markers of duration of HIV infection to indicate recent infections. We discuss the assumptions under which these data would yield an estimate of the counterfactual HIV incidence and develop sample size and power calculations for comparisons to incidence observed on an investigational PrEP agent.

Results

We consider two hypothetical trials for men who have sex with men (MSM) and transgender women (TGW) from different regions and young women in sub-Saharan Africa. The calculated sample sizes are reasonable and yield desirable power in simulation studies.

Conclusions

Future one-arm trials with counterfactual placebo incidence based on a recency assay can be conducted with reasonable total screening sample sizes and adequate power to determine treatment efficacy.

Constructing single atom catalysts with fine-tuned coordination environments can be a promising strategy to achieve satisfactory catalytic performance. Herein, via a simple calcination temperature-control strategy, CeO2 supported Pt single atom catalysts with precisely controlled coordination environments are successfully fabricated. The joint experimental and theoretical analysis reveals that the Pt single atoms on Pt1/CeO2 prepared at 550 °C (Pt/CeO2-550) are mainly located at the edge sites of CeO2 with a Pt-O coordination number of ca. 5, while those prepared at 800 °C (Pt/CeO2-800) are predominantly located at distorted Ce substitution sites on CeO2 terrace with a Pt-O coordination number of ca. 4. Pt/CeO2-550 and Pt/CeO2-800 with different Pt1-CeO2 coordination environments exhibit a reversal of activity trend in CO oxidation and NH3 oxidation due to their different privileges in reactants activation and H2O desorption, suggesting that the catalytic performance of Pt single atom catalysts in different target reactions can be maximized by optimizing their local coordination structures.

Current understanding holds that Klinefelter syndrome (KS) is not inherited, but arises randomly during meiosis. Whether there is any genetic basis for the origin of KS is unknown. Here, guided by our identification of some USP26 variations apparently associated with KS, we found that knockout of Usp26 in male mice resulted in the production of 41, XXY offspring. USP26 protein is localized at the XY body, and the disruption of Usp26 causes incomplete sex chromosome pairing by destabilizing TEX11. The unpaired sex chromosomes then result in XY aneuploid spermatozoa. Consistent with our mouse results, a clinical study shows that some USP26 variations increase the proportion of XY aneuploid spermatozoa in fertile men, and we identified two families with KS offspring wherein the father of the KS patient harbored a USP26-mutated haplotype, further supporting that paternal USP26 mutation can cause KS offspring production. Thus, some KS should originate from XY spermatozoa, and paternal USP26 mutations increase the risk of producing KS offspring.

Azoospermia is one of the major reproductive disorders which cause male infertility in humans; however, the etiology of this disease is largely unknown. In the present study, six missense mutations of WT1 gene were detected in 529 human patients with non-obstructive azoospermia (NOA), indicating a strong association between WT1 mutation and NOA. The Wilms tumor gene, Wt1, is specifically expressed in Sertoli cells (SCs) which support spermatogenesis. To examine the functions of this gene in spermatogenesis, Wt1 was deleted in adult testis using Wt1(flox) and Cre-ER(TM) mice strains. We found that inactivation of Wt1 resulted in massive germ cell death and only SCs were present in most of the seminiferous tubules which was very similar to NOA in humans. In investigating the potential mechanism for this, histological studies revealed that the blood-testis barrier (BTB) was disrupted in Wt1 deficient testes. In vitro studies demonstrated that Wt1 was essential for cell polarity maintenance in SCs. Further studies found that the expression of cell polarity associated genes (Par6b and E-cadherin) and Wnt signaling genes (Wnt4, Wnt11) were downregulated in Wt1 deficient SCs, and that the expression of Par6b and E-cadherin was regulated by Wnt4. Our findings suggest that Wt1 is important in spermatogenesis by regulating the polarity of SCs via Wnt signaling pathway and that WT1 mutation is one of the genetic causes of NOA in humans.

Incomplete penetrance of congenital heart defects (CHDs) was observed in a mouse model. We hypothesized that the contribution of a major genetic locus modulates the manifestation of the CHDs. After genome-wide linkage mapping, fine mapping, and high-throughput targeted sequencing, a recessive frameshift mutation of the heterogeneous nuclear ribonucleoprotein A1 (Hnrnpa1) gene was confirmed (Hnrnpa1ct). Hnrnpa1 was expressed in both the first heart field (FHF) and second heart field (SHF) at the cardiac crescent stage but was only maintained in SHF progenitors after heart tube formation. Hnrnpa1ct/ct homozygous mutants displayed complete CHD penetrance, including truncated and incomplete looped heart tube at E9.5, ventricular septal defect (VSD) and persistent truncus arteriosus (PTA) at E13.5, and VSD and double outlet right ventricle at P0. Impaired development of the dorsal mesocardium and sinoatrial node progenitors was also observed. Loss of Hnrnpa1 expression leads to dysregulation of cardiac transcription networks and multiple signaling pathways, including BMP, FGF, and Notch in the SHF. Finally, two rare heterozygous mutations of HNRNPA1 were detected in human CHDs. These findings suggest a role of Hnrnpa1 in embryonic heart development in mice and humans.

Gastrointestinal stromal tumors (GIST) arise within the interstitial cell of Cajal (ICC) lineage due to activating KIT/PDGFRA mutations. Both ICC and GIST possess primary cilia (PC), which coordinate PDGFRA and Hedgehog signaling, regulators of gastrointestinal mesenchymal development. Therefore, we hypothesized that Hedgehog signaling may be altered in human GIST and controls KIT expression. Quantitative RT-PCR, microarrays, and next generation sequencing were used to describe Hedgehog/PC-related genes in purified human ICC and GIST. Genetic and pharmacologic approaches were employed to investigate the effects of GLI manipulation on KIT expression and GIST cell viability. We report that Hedgehog pathway and PC components are expressed in ICC and GIST and subject to dysregulation during GIST oncogenesis, irrespective of KIT/PDGFRA mutation status. Using genomic profiling, 10.2% of 186 GIST studied had potentially deleterious genomic alterations in 5 Hedgehog-related genes analyzed, including in the PTCH1 tumor suppressor (1.6%). Expression of the predominantly repressive GLI isoform, GLI3, was inversely correlated with KIT mRNA levels in GIST cells and non-KIT/non-PDGFRA mutant GIST. Overexpression of the 83-kDa repressive form of GLI3 or small interfering RNA-mediated knockdown of the activating isoforms GLI1/2 reduced KIT mRNA. Treatment with GLI1/2 inhibitors, including arsenic trioxide, significantly increased GLI3 binding to the KIT promoter, decreased KIT expression, and reduced viability in imatinib-sensitive and imatinib-resistant GIST cells. These data offer new evidence that genes necessary for Hedgehog signaling and PC function in ICC are dysregulated in GIST. Hedgehog signaling activates KIT expression irrespective of mutation status, offering a novel approach to treat imatinib-resistant GIST.