Unconventional Imaging: introduction to the feature issue.

This feature issue of Applied Optics is dedicated to the international meeting of Information Photonics 2020 (IP'20), which was held September 11-12, 2020, in Taipei, Taiwan. IP'20 covered a broad range of topics, including advanced display techniques, optical computing, and optical storage. This feature issue, however, limits topics to unconventional imaging techniques, such as digital holography, artificial-intelligence associated imaging, compressive imaging, and single-pixel imaging.

3D display by binary computer-generated holograms with localized random down-sampling and adaptive intensity accumulation.

In this paper, we proposed a new technique to realize a high-quality three-dimensional (3D) display by using binary holograms. First, we applied a localized random down-sampling (LRDS) mask to down-sample the object function and generated a binary CGH by direct sign-thresholding. Subsequently, we devised the display by adaptive intensity accumulation (AIA). In AIA, multiple CGHs of the same object are generated. However, selective sampling points of the same scene are removed according to the reconstructed image of previous binary CGHs as the second and more binary CGHs are generated. Finally, these holograms are sequentially displayed on a fast spatial light modulator, a digital micromirror device (DMD). Thus, a high-quality 3D image is reconstructed without artifacts and speckle noise.

Potential role of Candida albicans secreted aspartic protease 9 in serum induced-hyphal formation and interaction with oral epithelial cells.

INTRODUCTION: Candida albicans possesses the ability to switch rapidly between yeast to hyphal forms. Hyphal formation is a remarkable pathogenic characteristic, which allows C. albicans to invade into host cells. OBJECTIVES: This study was to investigate the role of the C. albicans SAP9 gene in hyphal formation and invasion ability. METHODS: The morphology of fungal cells in the hyphal-inducing liquid media (YPD+10% fetal bovine serum) was observed by the microscopy. And the morphology of the colony on solid agar plates of YPD+10% fetal bovine serum was photographed by the digital camera. The mRNA expressions of hypha-associated genes in serum medium were also analyzed by real time PCR. Then for the interaction between C. albicans and oral epithelial cells, endocytosis essay, invasion essay and damage assay were performed to compare the differences between the sap9Δ/Δ mutant strain and wild type strain. RESULTS: Compared with the wild type strain, the sap9Δ/Δ mutant strain exhibited a deficient yeast-to-hyphal morphological transition under serum hyphal-inducing conditions. Furthermore, the SAP9 knockout strain revealed a significant down-regulation of the expression of EFG1 (~40%), which is a transcription factor gene that mediates hyphae formation in C. albicans. Compared with the wild type strain, a 70% reduction in the endocytosis of the sap9Δ/Δ mutant strain by host cells was observed, as well as a 25% attenuation of active penetration and a 40% attenuation of host cell damage (P <0.05). CONCLUSIONS: Our data strongly suggests that C. albicans Sap9 is a potential hyphal-associated factor that responds to serum hyphal-inducing stimuli via a cAMP-protein kinase A pathway mediated by EFG1, and contributes to the process of invasion of Candida into the epithelial cells, leading to host cell damage.

Enhanced direct binary search algorithm for binary computer-generated Fresnel holograms.

The direct binary search (DBS) algorithm was originally invented for the synthesis of a binary Fourier hologram, and was applied for the generation of a binary Fresnel hologram recently. DBS performs quality evaluation on every pixel. Therefore, both the quality and diffraction efficiency of the generated binary hologram are better among various algorithms of the binary hologram. However, DBS is a time-consuming algorithm and thus is impractical for the generation of high-definition computer-generated holograms. In this paper, we proposed an enhanced DBS (E-DBS) method to speed up the hologram computation. E-DBS is based on the same pixelwise evaluation strategy of DBS, but the diffraction field of a single pixel is precomputed as a lookup table. In evaluating any pixel value, only a small area in the region of interest affected by the diffraction field of single pixel is calculated. In addition, it is also found that qualified results can be obtained by using only 4% of the area of the diffraction field. As a result, the computing complexity of E-DBS can be reduced by at least 2 orders of magnitude in contrast to conventional DBS.

R-loop formation at Snord116 mediates topotecan inhibition of Ube3a-antisense and allele-specific chromatin decondensation.

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are oppositely imprinted autism-spectrum disorders with known genetic bases, but complex epigenetic mechanisms underlie their pathogenesis. The PWS/AS locus on 15q11-q13 is regulated by an imprinting control region that is maternally methylated and silenced. The PWS imprinting control region is the promoter for a one megabase paternal transcript encoding the ubiquitous protein-coding Snrpn gene and multiple neuron-specific noncoding RNAs, including the PWS-related Snord116 repetitive locus of small nucleolar RNAs and host genes, and the antisense transcript to AS-causing ubiquitin ligase encoding Ube3a (Ube3a-ATS). Neuron-specific transcriptional progression through Ube3a-ATS correlates with paternal Ube3a silencing and chromatin decondensation. Interestingly, topoisomerase inhibitors, including topotecan, were recently identified in an unbiased drug screen for compounds that could reverse the silent paternal allele of Ube3a in neurons, but the mechanism of topotecan action on the PWS/AS locus is unknown. Here, we demonstrate that topotecan treatment stabilizes the formation of RNA:DNA hybrids (R loops) at G-skewed repeat elements within paternal Snord116, corresponding to increased chromatin decondensation and inhibition of Ube3a-ATS expression. Neural precursor cells from paternal Snord116 deletion mice exhibit increased Ube3a-ATS levels in differentiated neurons and show a reduced effect of topotecan compared with wild-type neurons. These results demonstrate that the AS candidate drug topotecan acts predominantly through stabilizing R loops and chromatin decondensation at the paternally expressed PWS Snord116 locus. Our study holds promise for targeted therapies to the Snord116 locus for both AS and PWS.

A Prader-Willi locus lncRNA cloud modulates diurnal genes and energy expenditure.

Prader-Willi syndrome (PWS), a genetic disorder of obesity, intellectual disability and sleep abnormalities, is caused by loss of non-coding RNAs on paternal chromosome 15q11-q13. The imprinted minimal PWS locus encompasses a long non-coding RNA (lncRNA) transcript processed into multiple SNORD116 small nucleolar RNAs and the spliced exons of the host gene, 116HG. However, both the molecular function and the disease relevance of the spliced lncRNA 116HG are unknown. Here, we show that 116HG forms a subnuclear RNA cloud that co-purifies with the transcriptional activator RBBP5 and active metabolic genes, remains tethered to the site of its transcription and increases in size in post-natal neurons and during sleep. Snord116del mice lacking 116HG exhibited increased energy expenditure corresponding to the dysregulation of diurnally expressed Mtor and circadian genes Clock, Cry1 and Per2. These combined genomic and metabolic analyses demonstrate that 116HG regulates the diurnal energy expenditure of the brain. These novel molecular insights into the energy imbalance in PWS should lead to improved therapies and understanding of lncRNA roles in complex neurodevelopmental and metabolic disorders.

Coherence experiments in single-pixel digital holography.

In optical scanning holography (OSH), the coherence properties of the acquired holograms depend on the single-pixel size, i.e., the active area of the photodetector. For the first time, to the best of our knowledge, we have demonstrated coherent, partial coherent, and incoherent three-dimensional (3D) imaging by experiment in such a single-pixel digital holographic recording system. We have found, for the incoherent mode of OSH, in which the detector of the largest active area is applied, the 3D location of a diffusely reflecting object can be successfully retrieved without speckle noise. For the partial coherent mode employing a smaller pixel size of the detector, significant speckles and randomly distributed bright spots appear among the reconstructed images. For the coherent mode of OSH when the size of the pixel is vanishingly small, the bright spots disappear. However, the speckle remains and the signal-to-noise ratio is low.

Catastrophic antiphospholipid syndrome presenting with pulmonary hemorrhage: case report.

This is a case report of catastrophic antiphospholipid syndrome (APLS) involving the rare manifestation of pulmonary hemorrhage. This rare variant of APLS is frequently life threatening despite medical therapy. The pathogenesis of pulmonary hemorrhage in catastrophic APLS remains incompletely understood. The optimal approach to managing pulmonary hemorrhage in the setting of catastrophic APLS is still unclear, however this case report demonstrates the success of combination therapy with anticoagulation, corticosteroids and plasma exchange.

Population-genetic properties of differentiated human copy-number polymorphisms.

Copy-number variants (CNVs) can reach appreciable frequencies in the human population, and recent discoveries have shown that several of these copy-number polymorphisms (CNPs) are associated with human diseases, including lupus, psoriasis, Crohn disease, and obesity. Despite new advances, significant biases remain in terms of CNP discovery and genotyping. We developed a method based on single-channel intensity data and benchmarked against copy numbers determined from sequencing read depth to successfully obtain CNP genotypes for 1495 CNPs from 487 human DNA samples of diverse ethnic backgrounds. This microarray contained CNPs in segmental duplication-rich regions and insertions of sequences not represented in the reference genome assembly or on standard SNP microarray platforms. We observe that CNPs in segmental duplications are more likely to be population differentiated than CNPs in unique regions (p = 0.015) and that biallelic CNPs show greater stratification when compared to frequency-matched SNPs (p = 0.0026). Although biallelic CNPs show a strong correlation of copy number with flanking SNP genotypes, the majority of multicopy CNPs do not (40% with r > 0.8). We selected a subset of CNPs for further characterization in 1876 additional samples from 62 populations; this revealed striking population-differentiated structural variants in genes of clinical significance such as OCLN, a tight junction protein involved in hepatitis C viral entry. Our microarray design allows these variants to be rapidly tested for disease association and our results suggest that CNPs (especially those that cannot be imputed from SNP genotypes) might have contributed disproportionately to human diversity and selection.

Mapping and sequencing of structural variation from eight human genomes.

Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale--particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence map of human structural variation--a standard for genotyping platforms and a prelude to future individual genome sequencing projects.

Vignetting-free computer-generated Fresnel holograms by mask shifting.

In computer-generated Fresnel holography, direct sampling (DS) and simple shading (SS) are two common ways to generate sampled Fresnel zone plates (FZPs) on the hologram plane. Nevertheless, either aliasing or vignetting, or both, will occur in the reconstructed image when the DS method or the SS method is applied. To avoid vignetting together with aliasing in the two sampling methods, either the object size or the object distance must be restricted in generating the holograms. In this paper we propose a mask-shifting (MS) method to generate the sampled FZPs. The main concept of the MS method is that the center of the FZP can be shifted relative to the center of the mask against the FZP when the FZP is at the margin of the hologram. The shifting of the mask will result in only a phase shift and will not change the intensity distribution of the reconstructed point. Thus, by using the MS method, aliasing and vignetting are simultaneously alleviated in any combination of object size and object distance.

Predicting walking function of patients one month poststroke using modified Rivermead mobility index on admission.

Being able to predict walking ability of patients with stroke at an early stage is useful in formulating realistic rehabilitation goals and facilitating early discharge planning, which are beneficial not only to the patients but their family members and health care providers. This study aimed to use the modified Rivermead mobility index (MRMI) of the stroke patients on day 3 of their admission to predict their independent walking ability on day 28 postadmission. A total of 232 patients with acute stroke who were admitted to the acute hospital were recruited. Fifty-three percent of them (n = 123) were able to achieve independent walking ability after 28 days of admission whereas 47.0% of them (n = 109) failed to do so. The receiver operating characteristics curve analysis was performed. The optimal cutoff score with the highest sum of sensitivity and specificity was found to be 18.5 (sensitivity, 85.0%; specificity, 75.0%) and the area under the curve was .880. In conclusion, MRMI on day 3 of admission maybe useful in predicting independent walking ability 1 month after stroke.

Characterization of missing human genome sequences and copy-number polymorphic insertions.

The extent of human genomic structural variation suggests that there must be portions of the genome yet to be discovered, annotated and characterized at the sequence level. We present a resource and analysis of 2,363 new insertion sequences corresponding to 720 genomic loci. We found that a substantial fraction of these sequences are either missing, fragmented or misassigned when compared to recent de novo sequence assemblies from short-read next-generation sequence data. We determined that 18-37% of these new insertions are copy-number polymorphic, including loci that show extensive population stratification among Europeans, Asians and Africans. Complete sequencing of 156 of these insertions identified new exons and conserved noncoding sequences not yet represented in the reference genome. We developed a method to accurately genotype these new insertions by mapping next-generation sequencing datasets to the breakpoint, thereby providing a means to characterize copy-number status for regions previously inaccessible to single-nucleotide polymorphism microarrays.

Intensity image-embedded binary holograms.

Past research has demonstrated that, by downsampling the source object scene in multiple directions, a binary Fresnel hologram can be generated to preserve favorable quality on the reconstructed image. In this paper, we will show that a binary hologram generated with such an approach is also insensitive to noise contamination. On this basis, we propose a method to embed an intensity image into the binary hologram. To prevent the embedded information from being tampered or retrieved with unauthorized means, scrambling is applied to relocate each pixel to a unique position in the binary hologram according to a random assignment that is only known with the availability of a descrambling key. Experimental results demonstrate that our proposed method is capable of embedding an intensity image that is one quarter the size of the binary hologram without causing observable degradation on the reconstructed image. In addition, the embedded image can be retrieved with acceptable quality even if the binary hologram is damaged and contaminated with noise.

Asymmetric cryptosystem based on optical scanning cryptography and elliptic curve algorithm.

We propose an asymmetric cryptosystem based on optical scanning cryptography (OSC) and elliptic curve cryptography (ECC) algorithm. In the encryption stage of OSC, an object is encrypted to cosine and sine holograms by two pupil functions calculated via ECC algorithm from sender's biometric image, which is sender's private key. With the ECC algorithm, these holograms are encrypted to ciphertext, which is sent to the receiver. In the stage of decryption, the encrypted holograms can be decrypted by receiver's biometric private key which is different from the sender's private key. The approach is an asymmetric cryptosystem which solves the problem of the management and dispatch of keys in OSC and has more security strength than the conventional OSC. The feasibility of the proposed method has been convincingly verified by numerical and experiment results.

The fine-scale and complex architecture of human copy-number variation.

Despite considerable excitement over the potential functional significance of copy-number variants (CNVs), we still lack knowledge of the fine-scale architecture of the large majority of CNV regions in the human genome. In this study, we used a high-resolution array-based comparative genomic hybridization (aCGH) platform that targeted known CNV regions of the human genome at approximately 1 kb resolution to interrogate the genomic DNAs of 30 individuals from four HapMap populations. Our results revealed that 1020 of 1153 CNV loci (88%) were actually smaller in size than what is recorded in the Database of Genomic Variants based on previously published studies. A reduction in size of more than 50% was observed for 876 CNV regions (76%). We conclude that the total genomic content of currently known common human CNVs is likely smaller than previously thought. In addition, approximately 8% of the CNV regions observed in multiple individuals exhibited genomic architectural complexity in the form of smaller CNVs within larger ones and CNVs with interindividual variation in breakpoints. Future association studies that aim to capture the potential influences of CNVs on disease phenotypes will need to consider how to best ascertain this previously uncharacterized complexity.

Holographic video at 40 frames per second for 4-million object points.

We propose a fast method for generating digital Fresnel holograms based on an interpolated wavefront-recording plane (IWRP) approach. Our method can be divided into two stages. First, a small, virtual IWRP is derived in a computational-free manner. Second, the IWRP is expanded into a Fresnel hologram with a pair of fast Fourier transform processes, which are realized with the graphic processing unit (GPU). We demonstrate state-of-the-art experimental results, capable of generating a 2048 x 2048 Fresnel hologram of around 4 × 10(6) object points at a rate of over 40 frames per second.

Dysmetabolic hyperferritinemia is associated with normal transferrin saturation, mild hepatic iron overload, and elevated hepcidin.

Hyperferritinemia is common in individuals with the metabolic syndrome (dysmetabolic hyperferritinemia), but its pathophysiology and the degree to which it reflects tissue iron overload remains unclear. We conducted a cross-sectional study evaluating ten cases with dysmetabolic hyperferritinemia for liver iron overload and compared their serum iron indices and urine hepcidin levels to healthy controls. Seven out of ten cases had mild hepatic iron overload by magnetic resonance imaging (MRI) (median, 75 micromol/g dry weight). Cases had higher serum ferritin than controls (median, 672 microg/L vs. 105 microg/L, p < 0.001), but the median transferrin saturation was not significantly different (38% vs. 36%, p = 0.5). Urinary hepcidin was elevated in dysmetabolic hyperferritinemia (median; 1,584 g/mg of creatinine vs. 799 ng/mg of creatinine, p = 0.05). Dysmetabolic hyperferritinemia is characterized by hyperferritinemia with normal transferrin saturation, elevated hepcidin levels, and mild liver iron overload in a subset of patients.

Computer generation of binary Fresnel holography.

Binarization of Fresnel holograms by direct thresholding based on the polarity of the fringe pattern is studied. It is found that if the hologram is binarized (i.e., for black and white hologram pixels) in this manner, only the edges of the object are preserved in the reconstructed image. To alleviate the errors caused by binarization, the use of error diffusion has been routinely employed. However, the reconstructed image using such standard technique is heavily contaminated with random noise. In this paper, we propose a novel noniterative method for generating Fresnel holograms that are suitable for binarization. Our method is capable of preserving good visual quality on the reconstructed images.

Complex Fresnel hologram display using a single SLM.

We propose a novel optical method to display a complex Fresnel hologram using a single spatial light modulator (SLM). The method consists of a standard coherent image processing system with a sinusoidal grating at the Fourier plane. Two or three position-shifted amplitude holograms displayed at the input plane of the processing system can be coupled via the grating and will be precisely overlapped at the system's output plane. As a result, we can synthesize a complex hologram that is free of the twin image and the zero-order light using a single SLM. Because the twin image is not removed via filtering, the full bandwidth of the SLM can be utilized for displaying on-axis holograms. In addition, the degree of freedom of the synthesized complex hologram display can be extended by involving more than three amplitude holograms.