Miracle-dz/UniFAR-FTUs huggingface dataset:
Resonant Tunneling Diodes for Sub-Terahertz and Terahertz Oscillators

Resonant tunneling diodes (RTDs) have the potential for use as compact and coherent terahertz (THz) sources operating at room temperature. In this paper, sub-THz and THz oscillators with RTDs integrated on planar circuits are described. Fundamental oscillation up to 0.65 THz and harmonic oscillation up to 1.02 THz were obtained at room temperature in our recent study. Limiting factors for oscillation frequency and output power are theoretically analyzed including tunneling and transit-time effects and parasitic elements. Oscillation frequency and its dependence on RTD size are in good agreement with the measured results. Based on this result, it is shown that fundamental oscillation up to 2.3 THz and an output power of 60 µW at 1 THz are theoretically expected by improving the structures of the RTD and the antenna. Voltage-controlled oscillation, which is useful for the precise control of frequency, is observed in the RTD oscillators. Coherent power combining in an array configuration to achieve high output power as well as mutual injection locking between the array elements are also described.
A Review of Qualitative Research on the Childhood Cancer Experience From the Perspective of Siblings: A Need to Give Them a Voice

Researchers are increasingly adopting the qualitative research paradigm to study the world of siblings of children with cancer. The purpose of this review article is to identify the contributions of qualitative research in advancing the understanding of the childhood cancer experience from the perspective of siblings. Articles were selected for inclusion if (1) written in English; (2) published in a peer-reviewed journal between 1979 and present or, if a doctoral dissertation, easily accessible to the authors; (4) cited a specific qualitative research design or some type of qualitative research method of data collection and analysis; and (4) involved siblings of children with cancer as sole research participants or as research participants within the context of the family. Twenty-seven qualitative research studies were reviewed. Three themes emerged from an analysis of the primary findings: (1) changing lives, (2) intense feelings, and (3) unmet needs. Limitations in the conceptualization, research design, and research methods of the qualitative studies are discussed. Suggestions that will help researchers in conducting qualitative research with siblings are also presented.
Host Phylogeny Constrains Cross-Species Emergence and Establishment of Rabies Virus in Bats

Threats to and from Bats Bats appear to be able to host an assortment of alarming pathogens, which, if they do not extirpate the bats, have implications for human health (see the Perspective by Daszak). For example, exposure to bats is the main source of human rabies in the Americas. But rabies is not generally transmitted among people; humans are a dead end for the virus. Streicker et al. (p. 676, see the cover) show that rabies virus lineages tend to be specific for bat lineages. It seems that although rabies viruses have the potential for rapid evolution, this property alone is not enough to overcome genetic barriers, which inhibit the onward transmission of rabies virus into a new species. White-nose syndrome, an exotic fungal infection of bats, has, over the past 3 years, spread from upstate New York to West Virginia, killing on average 70% of the animals in a hibernating colony. The infection makes bats restless over winter when they should be dormant, which makes them exhaust their fat reserves, resulting in the death of over a million bats. Frick et al. (p. 679) have analyzed population data collected on bats in the northeastern United States for the past 30 years and show that, mainly owing to white-nose syndrome, the once abundant little brown bat is heading for regional extinction in the next 16 years or so. This scale of loss of an insectivorous mammal is expected to have repercussions for ecosystem integrity and for the economic costs of agricultural pest control. Rabies virus’ innate capacity to replicate and adapt cannot overcome host genetic barriers to cross-species transfer. For RNA viruses, rapid viral evolution and the biological similarity of closely related host species have been proposed as key determinants of the occurrence and long-term outcome of cross-species transmission. Using a data set of hundreds of rabies viruses sampled from 23 North American bat species, we present a general framework to quantify per capita rates of cross-species transmission and reconstruct historical patterns of viral establishment in new host species using molecular sequence data. These estimates demonstrate diminishing frequencies of both cross-species transmission and host shifts with increasing phylogenetic distance between bat species. Evolutionary constraints on viral host range indicate that host species barriers may trump the intrinsic mutability of RNA viruses in determining the fate of emerging host-virus interactions.
Residue centrality, functionally important residues, and active site shape: Analysis of enzyme and non‐enzyme families

The representation of protein structures as small‐world networks facilitates the search for topological determinants, which may relate to functionally important residues. Here, we aimed to investigate the performance of residue centrality, viewed as a family fold characteristic, in identifying functionally important residues in protein families. Our study is based on 46 families, including 29 enzyme and 17 non‐enzyme families. A total of 80% of these central positions corresponded to active site residues or residues in direct contact with these sites. For enzyme families, this percentage increased to 91%, while for non‐enzyme families the percentage decreased substantially to 48%. A total of 70% of these central positions are located in catalytic sites in the enzyme families, 64% are in hetero‐atom binding sites in those families binding hetero‐atoms, and only 16% belong to protein–protein interfaces in families with protein–protein interaction data. These differences reflect the active site shape: enzyme active sites locate in surface clefts, hetero‐atom binding residues are in deep cavities, while protein–protein interactions involve a more planar configuration. On the other hand, not all surface cavities or clefts are comprised of central residues. Thus, closeness centrality identifies functionally important residues in enzymes. While here we focus on binding sites, we expect to identify key residues for the integration and transmission of the information to the rest of the protein, reflecting the relationship between fold and function. Residue centrality is more conserved than the protein sequence, emphasizing the robustness of protein structures.
Association of Apolipoprotein A5 Gene Polymorphisms with Metabolic Syndrome in the Korean Population.

AIMS Functional defects of the ApoA5 protein have been identified as risk factors for hypertriglyceridemia, vascular diseases and susceptibility to metabolic syndrome (MetS). These associations are neither strong nor consistent in all populations studied. In this study, we investigated the association between the ApoA5 -1131T>C and -12,238T>C polymorphic loci in Korean patients with MetS. METHODS A total of 1074 subjects, including 415 patients with MetS and 659 healthy control subjects, were enrolled to investigate the affect of ApoA5 polymorphisms on risk of MetS. Genotyping of the ApoA5 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism techniques. RESULTS The CC genotype and the dominant (TT vs. TC+CC) and recessive (TT+TC vs. CC) models of the -1131T>C polymorphism were associated with increased MetS susceptibility (p < 0.001, p = 0.018, and p = 0.002, respectively). The association was male-specific when stratified by gender. With regard to the -12,238T>C polymorphism, the TC and CC genotypes and the dominant (TT vs. TC+CC) and recessive (TT+TC vs. CC) models were frequently found in the patient group, compared with the control group (p = 0.001, p < 0.001, p < 0.001, and p = 0.031, respectively). The T-C, C-T, and C-C haplotypes of the ApoA5 -1131T>C and -12,238T>C polymorphisms were associated with an increased risk for MetS (p < 0.001, p = 0.001, and p < 0.001, respectively). The variant of the ApoA5 -1131T>C polymorphism was also associated with increased triglyceride (TG) levels. Dominant models of ApoA5 -1131T>C and -12,238T>C polymorphisms were associated with the risk components of MetS by the stratification analysis. CONCLUSION The -1131C and -12,238C variants and the C-containing haplotypes of ApoA5 -1131T>C and -12,238T>C polymorphisms were associated with higher risk for MetS in the Korean population. The -1131C variant was also associated with the increased level of TG.
Uneventful Femtosecond Laser-assisted Flap Creation in a Patient With Postoperative PRK Corneal Haze.

To the Editor: Flap creation is the most crucial step of LASIK and the introduction of the femtosecond laser led to the production of uniform flaps enhancing the accuracy and reproducibility of LASIK.1,2 However, intrastromal corneal opacity (such as scar and haze) raised controversies regarding the efficacy of the technique in such cases because it can interfere with laser tissue disruption, causing gas breakthrough and/or irregular flaps in some cases.3,4 In our case, a patient with corneal stromal haze underwent uneventful femtosecond laser-assisted flap creation during LASIK. A 31-year-old man who had undergone photorefractive keratectomy with mitomycin C in his right eye 6 years earlier presented to our institute for consultation because of hyperopic astigmatism regression. Ocular history revealed amblyopia of the right eye, whereas his medical history was unremarkable. At presentation, uncorrected distance visual acuity was 20/125 in the right eye and 20/20 in the left eye, whereas corrected distance visual acuity was 20/25 (manifest refraction: +5.25 -5.25 35) and 20/20 (manifest refraction: +0.75 -0.50 35), respectively. Slit-lamp examination revealed a peripheral ring of stromal haze formed in a denser temporal semi-arcus (Figure 1A). Corneal haze was extended within a maximum depth of 116 μm as estimated using anterior segment optical coherence tomography (Visante OCT 3.0; Carl Zeiss Meditec, Inc., Jena, Germany) (Figure 1B). Central corneal thickness was 541 and 542 μm for the right and left eye, respectively. LASIK was proposed as an enhancement treatment because photorefractive keratectomy led to significant regression of the initial refractive error and haze
Differential expression of angiogenic and vasodilatory factors by invasive trophoblast giant cells depending on depth of invasion

The uterine bed undergoes remarkable changes during pregnancy, including proliferation and decidualization of the uterine stroma and remodeling and angiogenesis of the maternal vasculature. Fetal‐derived trophoblast giant cells invade into the uterus where they gain access to the maternal blood circulation to ensure sufficient nutrient supply of the embryo. In serial sections through early‐ to mid‐gestation conceptuses, we have determined the exact distance of trophoblast invasion and the expression of angiogenic, vasodilatory, and anticoagulative factors that are likely to influence remodeling and redirection of the maternal circulatory system. Trophoblast derivatives were detected at a distance as far as ∼300 μm from the placental border, where they are allocated exclusively along the mid‐line of the decidua. The farthest invading cells characteristically expressed proliferin and proliferin‐related protein, hormones that affect endothelial cell migration and vascularization. Occasionally, these cells replaced the normal vascular endothelium and acquired a “pseudo‐endothelial” shape. Complete vascular disintegration was observed 50–80 μm outside of the placental border where maternal blood was entirely lined by a trophoblast giant cell‐derived network of blood sinuses. This transition in blood space lining correlated with trophoblast expression of various vasodilatory and anticoagulative factors that are likely to promote blood flow toward the placenta. Analysis of teratocarcinoma‐like tumors demonstrated that trophoblast giant cell‐induced promotion and redirection of blood flow is not restricted to the uterine environment. These results show that trophoblast giant cells have the intrinsic capacity to attract and increase blood flow and to gradually displace the vascular endothelium resulting in the formation of canals entirely lined by trophoblast cells. Developmental Dynamics 227:185–191, 2003. © 2003 Wiley‐Liss, Inc.
Newborn Identification

he use of footprints for t infant identification in newborn nurseries is wellestablished, based on experience with fingerprints. However, studies of the accuracy of newborn footprints reveal that the majority of prints are technically inadequate for purposes of identification. 2,3 Because of the inadequate quality of footprints and the availability of better identification techniques (DNA genotyping and human leukocyte antigen tests), the American Academy of Pediatrics (AAP) and the American College of Obstetricians and Gynecologists (ACOG) in 1983 stated that &dquo;individual hospitals may want to continue the practice of footprinting or fingerprinting, but universal use of this practice is
Spatial tethering of kinases to their substrates relaxes evolutionary constraints on specificity

Signal transduction proteins are often multi‐domain proteins that arose through the fusion of previously independent proteins. How such a change in the spatial arrangement of proteins impacts their evolution and the selective pressures acting on individual residues is largely unknown. We explored this problem in the context of bacterial two‐component signalling pathways, which typically involve a sensor histidine kinase that specifically phosphorylates a single cognate response regulator. Although usually found as separate proteins, these proteins are sometimes fused into a so‐called hybrid histidine kinase. Here, we demonstrate that the isolated kinase domains of hybrid kinases exhibit a dramatic reduction in phosphotransfer specificity in vitro relative to canonical histidine kinases. However, hybrid kinases phosphotransfer almost exclusively to their covalently attached response regulator domain, whose effective concentration exceeds that of all soluble response regulators. These findings indicate that the fused response regulator in a hybrid kinase normally prevents detrimental cross‐talk between pathways. More generally, our results shed light on how the spatial properties of signalling pathways can significantly affect their evolution, with additional implications for the design of synthetic signalling systems.
The Effects of Load Carriage on Spinal Curvature and Posture

Study Design. This is a repeated-measures design where the subjects acted as their own controls. Curvature of the spine, as well as mean trunk and head flexion were noted twice during 21 minutes of load carriage: in rested and fatigued conditions. Objective. To determine if spinal curvature and posture were affected by mild fatigue in load carriage. Summary of Background Data. Researchers have found a link between load carriage and low back problems. Changes in gait and posture resulting from load carriage are largely a result of the body’s attempt to increase stability. Methods. Apparently healthy females (n = 25) carried a 9-kg backpack at 1.79 m/s for 21 minutes around a 200-m circuit. The pack had spring-loaded displacement rods intended to measure displacement from the pack to the spine. Subjects were filmed (60 Hz) and displacement data were collected during minute 3 (rested condition) and minute 18 (fatigued condition). Results. The MANOVA revealed that the thoracic to lumbar region cubic curve significantly increased as subjects fatigued. Rested trunk and head angles were not significantly different from the fatigued condition. Trunk and head angles were not indicative of spinal curvature at 18 minutes; therefore, they may not be the best measures of fatigue during load carriage. Conclusions. Spine and back health may be adversely affected by load carriage sooner than was previously thought, and it may be important to use spinal curvature as a measure of posture for future load carriage studies.
Replacement of conserved threonines by alanine residues in high mobility group protein HMG-I(Y): effect on DNA binding affinity.

A threonine residue at the beginning of each DNA-binding domain of HMG-I (residue numbers 21, 53, and 78) is conserved among mammalian species and proposed to help stabilize the A.T-hook DNA-binding motif. Phosphorylation of threonines number 53 and 78 of human HMG-I(Y) both in vivo and in vitro leads to a 20 fold reduction in the proteins DNA binding affinity. Recombinant human HMG-I proteins were engineered to contain alanine instead of the conserved threonine in each DNA-binding domain. The DNA dissociation constant of each protein was assayed at various salt concentrations by competition with the fluorescent dye Hoechst 33258 for an AT-rich DNA substrate. Replacement of these threonines did not affect the equilibrium binding of these proteins to DNA as compared with wild-type HMG-I and HMG-Y. Molecular modelling of analogous peptides supported this finding. We conclude that these threonines are not directly important for A.T-hook DNA-binding and are conserved phosphorylation sites for down regulation of DNA binding by the A.T-hook motif in the HMG-I(Y) proteins.
Reduction of interchannel interference noise in a two-channel grating-based OCDMA system using a nonlinear optical loop mirror

We show that a nonlinear optical switch can be used to suppress the interchannel noise generated under multiuser operation within a coherent, direct-sequence optical code-division multiple-access (OCDMA) system. By incorporating a simple nonlinear optical loop mirror (NOLM) within the receiver, we demonstrate a 3.6-dB power penalty reduction in a two-channel 1.25-Gb/s 64-chip 160-Gchip/s grating-based direct-sequence OCDMA system. Even greater improvements in system performance were obtained at a data rate of 2.5 Gb/s, where the noise due to the overlap of adjacent decoded data bits also needs to be suppressed. In both instances, the system performance under two-channel operation with nonlinear filtering was shown to be comparable to that achieved under single-channel operation using the conventional matched-filter approach.
Mutations in RPGR and RP2 account for 15% of males with simplex retinal degenerative disease.

PURPOSE To determine the proportion of male patients presenting simplex retinal degenerative disease (RD: retinitis pigmentosa [RP] or cone/cone-rod dystrophy [COD/CORD]) with mutations in the X-linked retinal degeneration genes RPGR and RP2. METHODS Simplex males were defined as patients with no known affected family members. Patients were excluded if they had a family history of parental consanguinity. Blood samples from a total of 214 simplex males with a diagnosis of retinal degeneration were collected for genetic analysis. The patients were screened for mutations in RPGR and RP2 by direct sequencing of PCR-amplified genomic DNA. RESULTS We identified pathogenic mutations in 32 of the 214 patients screened (15%). Of the 29 patients with a diagnosis of COD/CORD, four mutations were identified in the ORF15 mutational hotspot of the RPGR gene. Of the 185 RP patients, three patients had mutations in RP2 and 25 had RPGR mutations (including 12 in the ORF15 region). CONCLUSIONS This study represents mutation screening of RPGR and RP2 in the largest cohort, to date, of simplex males affected with RP or COD/CORD. Our results demonstrate a substantial contribution of RPGR mutations to retinal degenerations, and in particular, to simplex RP. Based on our findings, we suggest that RPGR should be considered as a first tier gene for screening isolated males with retinal degeneration.
Stool as Appropriate Sample for the Diagnosis of Mycobacterium tuberculosis by Gene Xpert Test

Background: Diagnosis of pediatric pulmonary tuberculosis (PTB) is a challenge. Symptoms are nonspecific. Young children are unable to expectorate sputum samples; the procedures for obtaining respiratory samples are invasive. Thus Mycobacterium tuberculosis cultures and smears often are not performed. Stool samples were used as an alternative to respiratory samples for the diagnosis of pediatric PTB using stool Xpert MTB/RIF and its sensitivity for detecting the DNA of MTB in stool was determined. Methods: The study was a laboratory-based cross-sectional prospective design. Stool specimen was collected from PTB suspected children (Mycobacterium tuberculosis DNA can be detected in stool using Xpert testing with a higher sensitivity. Therefore stool which can easily be obtained is an appropriate alternative sample for the diagnosis of PTB using Xpert assay for children unable to give respiratory samples. Furthermore Xpert turn round time is less than 2 hours.
Effect of Bowel Cleansing for Colonoscopy on Fecal Calprotectin Levels in Pediatric Patients

ABSTRACT The recent development of easily applicable fecal surrogate markers of intestinal inflammation, such as fecal calprotectin (FC), has provided a new means for objectively assessing disease activity in patients with chronic inflammatory bowel disease. Because the use of these markers is about to emerge, it is important to be aware of the possible limitations of measurements. We assessed levels of FC during bowel cleansing. In patients with high FC levels at baseline, the values measured during bowel cleansing varied considerably, remaining high or even returning to normal. Thus, stool sampling for FC assessment is not recommended during bowel preparation for colonoscopy.
Role of HER2 gene overexpression in breast carcinoma

The HER2 proto‐oncogene encodes a transmembrane glycoprotein of 185 kDa (p185HER2) with intrinsic tyrosine kinase activity. Amplification of the HER2 gene and overexpression of its product induce cell transformation. Numerous studies have demonstrated the prognostic relevance of p185HER2, which is overexpressed in 10% to 40% of human breast tumors. Recent data suggest that p185HER2 is a ligand orphan receptor that amplifies the signal provided by other receptors of the HER family by heterodimerizing with them. Ligand‐dependent activation of HER1, HER3, and HER4 by EGF or heregulin results in heterodimerization and, thereby, HER2 activation. HER2 overexpression is associated with breast cancer patient responsiveness to doxorubicin, to cyclophosphamide, methotrexate, and fluorouracil (CMF), and to paclitaxel, whereas tamoxifen was found to be ineffective and even detrimental in patients with HER2‐positive tumors. In vitro analyses have shown that the role of HER2 overexpression in determining the sensitivity of cancer cells to drugs is complex, and molecules involved in its signaling pathway are probably the actual protagonists of the sensitivity to drugs. The association of HER2 overexpression with human tumors, its extracellular accessibility, as well as its involvement in tumor aggressiveness are all factors that make this receptor an appropriate target for tumor‐specific therapies. A number of approaches are being investigated as possible therapeutic strategies that target HER2: (1) growth inhibitory antibodies, which can be used alone or in combination with standard chemotherapeutics; (2) tyrosine kinase inhibitors (TKI), which have been developed in an effort to block receptor activity because phosphorylation is the key event leading to activation and initiation of the signaling pathway; and (3) active immunotherapy, because the HER2 oncoprotein is immunogenic in some breast carcinoma patients. J. Cell. Physiol. 182:150–162, 2000. © 2000 Wiley‐Liss, Inc.