Scalable stable comb-to-tone integrated RF photonic drive for superconducting qubits.

The recent advent of quantum computing has the potential to overhaul security, communications, and scientific modeling. Superconducting qubits are a leading platform that is advancing noise-tolerant intermediate-scale quantum processors. The implementation requires scaling to large numbers of superconducting qubits, circuit depths, and gate speeds, wherein high-purity RF signal generation and effective cabling transport are desirable. Fiber photonic-enhanced RF signal generation has demonstrated the principle of addressing both signal generation and transport requirements, supporting intermediate qubit numbers and robust packaging efforts; however, fiber-based approaches to RF signal distribution are often bounded by their phase instability. Here, we present a silicon photonic integrated circuit-based version of a photonic-enhanced RF signal generator that demonstrates the requisite stability, as well as a path towards the necessary signal fidelity.

Progressive nodule-like lesions on bilateral lower limbs.

Pancreatic panniculitis is a rare disease characterized by subcutaneous fat necrosis. It could be the result of an associated pancreatic tumor. Herein, we reported a 63-year-old man who presented with progressive bilateral lower limb edema accompanied with nodule-like lesions for 1 month. His serum lipase was 3,927 U/L (normal, 0-160 U/L). Histopathology of the skin specimen revealed lobular panniculitis, favoring a diagnosis of pancreatic panniculitis. Abdominal computed tomography (CT) scan with contrast showed a huge mass in his left upper quadrant. Endoscopic ultrasound showed a mixed echoic tumor, measuring 11.9 × 7.8 cm in dimensions, originating from the pancreatic tail. Biopsy performed via an endoscopic ultrasound showed a poorly differentiated acinar cell carcinoma. Because of the unresectable status of the tumor, the patient underwent chemotherapy with paclitaxel and gemcitabine. After chemotherapy, his skin lesions improved progressively. It is important to treat pancreatic panniculitis with its underlying pancreatic disease.

Behçet's disease-induced massive small intestinal bleeding successfully treated with adalimumab.

We herein report a case of Behçet's disease in a 27-year-old female who suffered from generalized skin rashes for one week. After hospitalization, massive bloody stools accompanying hypovolemic shock occurred. Emergency abdominal computed tomography-angiography failed to detect the bleeding source. Esophagogastroduodenoscopy also demonstrated no definite bleeding points. Ileocolonoscopy showed multiple large and deep ulcers with some blood coating and mild oozing in the terminal ileum. We initially performed epinephrine injection and hemoclips for her intestinal bleeding. However, massive bloody stools still continued. Thus, we prescribed a loading dose of 160 mg adalimumab followed by weekly 80 mg adalimumab subcutaneous injections to the patient. Following this treatment, her gastrointestinal bleeding gradually subsided and completely stopped within a few days. After three-week therapy with adalimumab, capsule endoscopy showed several healing ulcers without bleeding in the distal to the terminal ileum. She continues to be treated with adalimumab, azathioprine, and mesalazine without recurrent bleeding.

Phenotypical heterogeneity in RAG-deficient patients from a highly consanguineous population.

Mutations affecting recombination activation genes RAG1 and RAG2 are associated with variable phenotypes, depending on the residual recombinase activity. The aim of this study is to describe a variety of clinical phenotypes in RAG-deficient patients from the highly consanguineous Egyptian population. Thirty-one patients with RAG mutations (from 28 families) were included from 2013 to 2017. On the basis of clinical, immunological and genetic data, patients were subdivided into three groups; classical T- B- severe combined immunodeficiency (SCID), Omenn syndrome (OS) and atypical SCID. Nineteen patients presented with typical T- B- SCID; among these, five patients carried a homozygous RAG2 mutation G35V and five others carried two homozygous RAG2 mutations (T215I and R229Q) that were detected together. Four novel mutations were reported in the T- B- SCID group; three in RAG1 (A565P, N591Pfs*14 and K621E) and one in RAG2 (F29S). Seven patients presented with OS and a novel RAG2 mutation (C419W) was documented in one patient. The atypical SCID group comprised five patients. Two had normal B cell counts; one had a previously undescribed RAG2 mutation (V327D). The other three patients presented with autoimmune cytopaenias and features of combined immunodeficiency and were diagnosed at a relatively late age and with a substantial diagnostic delay; one patient had a novel RAG1 mutation (C335R). PID disorders are frequent among Egyptian children because of the high consanguinity. RAG mutations stand behind several variable phenotypes, including classical SCID, OS, atypical SCID with autoimmunity and T- B+ CID.

Nonlinear FM-AM conversion due to stimulated Brillouin scattering.

We report an effect potentially harmful occurring in regenerative amplifiers due to stimulated Brillouin scattering (SBS). Most high energy laser facilities use phase-modulated pulses to prevent the transverse SBS effect in large optical components and to smooth the focal spot on target. However, this kind of pulse format may undergo a detrimental effect known as frequency modulation to amplitude modulation (FM-AM) conversion in the presence of spectral distortions. In the present letter, we show experimentally and numerically, that SBS can also potentially be created in the regenerative amplifier located in the front-end. In this scenario, some of the side bands of the pulse reflected by regen end-cavity mirror may act as a seed for SBS in an optical component, if the pulse spectrum contains frequency components exactly separated by the Brillouin frequency shift. This self-seeded SBS induces amplitude modulation with a nonlinear dependence that may be detrimental during down-stream propagation. However, we show that a careful choice of the modulation frequencies can mitigate this effect.

Creating virtual 3-dimensional models for teaching pre-clinical tooth preparation: Students' usages and perceptions.

PURPOSE: This research aimed to evaluate the students' usage and perceptions of using smartphones in their general dental education and learning tooth preparation with the individually designed virtual 3D instructional models in the pre-clinical removable partial denture course. MATERIALS AND METHODS: Second-year dental students were asked to voluntarily participate in a survey to investigate their demographic information, general usages of smartphones, perception of smartphones usage in dental education (construct 1) and perception of individually designed virtual 3D instructional models (construct 2). Students' responses of general usages of the smartphones were compared with their demographic and educational backgrounds using nonparametric Kruskal-Wallis test (for age) and Fisher's exact test (for sex, race and educational background). The sums of scores of the construct 1 and construct 2 were tested for associations with student's demographic and educational backgrounds using the Pearson product-moment correlation (for age), t test (for sex and educational background) or one-way ANOVA F test (for race) (α = .05). RESULTS: A 75% response rate (N = 90) was achieved in this study, and all 90 participants owned smartphones. Students' responses to general usages of the smartphones were not significantly influenced by their demographic background. For the construct 1, more than 73% of participants responded either agree or strongly agree to the usage of smartphones in general dental education and pre-clinical setting; however, only 49% of participants responded the same way in the clinical setting. For the construct 2, 48 of 90 participants viewed the 3D models, and more than 73% of these 48 participants responded either agree or strongly agree to the usage of the 3D models in the pre-clinical course. Student's demographic background did not have significant influence on the sums of scores of the construct 1 and construct 2. CONCLUSIONS: Within the limitations of this study, high usages and ownerships of smartphones were found amongst the students surveyed. The individually designed virtual 3D instructional models as supplemental teaching materials in the pre-clinical course were perceived positively by the students.

Effect of smile index and incisal edge position on perception of attractiveness in different age groups.

Changes in occlusal vertical dimension (OVD) and age have been found to affect Smile Index (SI, width/height of smile). Limited information is available regarding the aesthetic effects of these changes. The objective of this study was to evaluate the attractiveness of digitally manipulated smile images with differences in SI and incisal edge position (IEP) judged by respondents in different age groups. A total of 12 smile images were generated with varying SI (3·5, 5·3, 7·2, 9·0) and IEP (High, Medium, Low). Fifty respondents each in four age groups (15-24, 25-39, 40-54, 55+) evaluated the attractiveness of the 12 images using a 0-10 visual analog scale (VAS, 10 being most attractive). A repeated-measures three-factorial mixed model assessed differences. SI, IEP and age of respondents were found to significantly influence attractiveness score (P < 0·01 for all). With all age groups combined, SI = 7·2/IEP = Medium was most attractive (VAS = 7·22), followed by SI = 9·0/IEP = Medium, and SI = 5·3/IEP = Medium (VAS = 6·53 and 6·48, respectively). SI = 3·5/IEP = High and SI = 3·5/IEP = Low were least attractive (VAS = 1·99 and VAS = 2·58, respectively). Age group significantly influenced aesthetic perception, with younger respondents more critical in differences in SI and IEP. SI and IEP significantly influenced attractiveness of the smile in all respondent age groups. Low SI (i.e. 3·5) combined with high or low IEP was unattractive. Medium SI to high SI (i.e. 5·3-9·0) combined with medium IEP were considered attractive.

Strontium hydroxyapatite in situ gel-forming system - a new approach for minimally invasive bone augmentation.

OBJECTIVES: To achieve ideal functional and aesthetic requirements, ridge augmentation is often required before dental implant placement. Bone augmentation (especially vertical), which normally consists of complex and invasive surgeries, still remains challenge. This study seeks to investigate the feasibility of an injectable in situ gel-forming system containing strontium hydroxyapatite (SrHA) and alginate for minimally invasive bone augmentation in a rat calvarial model. MATERIAL AND METHODS: SrHA-alginate solution was prepared by mixing SrHA powder with alginate solution (20 mg/mL) to the final concentration of 0.5% (w/v). Each animal received a 200-µL single subperiosteal injection of either SrHA-alginate solution or alginate solution. The new bone formation was assessed at 0, 4, and 8 weeks histologically and radiologically. RESULTS: The SrHA-alginate solution materials could form solid gel once injected. As such, no sutures were required to close the injection site. Significantly greater amount of new bone formation was observed in the SrHA-alginate group compared with the alginate group both by micro-CT and by histological section. The newly formed bone in the SrHA-alginate group originated both from the underlying original bone and from the elevated periosteum. A 2.3-fold increase of the vertical bone height was observed in the SrHA-alginate group compared with 1.3-fold increase in the alginate group. CONCLUSIONS: Rat calvarial bone augmentation was achieved by a single subperiosteal injection of SrHA-alginate solution without any administration of stem cells or growth factors. The in situ gel-forming material may hold potential therapeutic benefits for local bone augmentation in a minimally invasive manner.

Novel bioresorbable strontium hydroxyapatite membrane for guided bone regeneration.

OBJECTIVES: Membrane materials have been widely used for guided bone regeneration (GBR). However, due to bio-functional limitation of the current membranes, the ideal resorbable membrane that can stimulate bone regeneration has yet to be developed. This study seeks to investigate the effects of a strontium hydroxyapatite (SrHA)-containing membrane for GBR. MATERIAL AND METHODS: Strontium hydroxyapatite powder was synthesized and mixed with gelatin solution to the final concentration of 10 mg/ml (Sr10) and 20 mg/ml (Sr20). Approximately 100-µm-thick membranes were fabricated, and the mechanical properties and strontium ion release pattern were analyzed. Rat bone marrow stromal cell (BMSC) responses were investigated in vitro. Bilaterial rat calvarial defects were used in vivo to compare the SrHA membranes against commercially available collagen membranes and evaluated radiologically and histologically. RESULTS: Strontium hydroxyapatite membranes exhibited higher elasticity and strength than the collagen membrane, and slow strontium ion release was also confirmed. No BMSC cytotoxicity was found on the SrHA membranes, and the alkaline phosphatase positively stained area was significantly greater than the collagen membrane at earlier time point. At 4 weeks, both micro-CT and histological analyses revealed that the Sr20 group yielded significantly greater bone formation. CONCLUSIONS: The SrHA-containing membrane developed in this study was found to be a biocompatible material that can stimulate BMSC differentiation as well as bone regeneration and maturation in rat calvarial defects at early time point compared with collagen membrane. The best result was observed in Sr20 group, which can be potentially effective for GBR.

Immune escape from NY-ESO-1-specific T-cell therapy via loss of heterozygosity in the MHC.

Adoptive immunotherapy of tumors with T cells specific for the cancer-testis antigen NY-ESO-1 has shown great promise in preclinical models and in early stage clinical trials. Tumor persistence or recurrence after NY-ESO-1-specific therapy occurs, however, and the mechanisms of recurrence remain poorly defined. In a murine xenograft model of NY-ESO-1(+) multiple myeloma, we observed tumor recurrence after adoptive transfer of CD8(+) T cells genetically redirected to the prototypic NY-ESO-1157-165 peptide presented by HLA-A*02:01. Analysis of the myeloma cells that had escaped from T-cell control revealed intact expression of NY-ESO-1 and B2M, but selective, complete loss of HLA-A*02:01 expression from the cell surface. Loss of heterozygosity (LOH) in the major histocompatibility complex (MHC) involving the HLA-A locus was identified in the tumor cells, and further analysis revealed selective loss of the allele encoding HLA-A*02:01. Although LOH involving the MHC has not been described in myeloma patients with persistent or recurrent disease after immune therapies such as allogeneic hematopoietic cell transplantation (HCT), it has been described in patients with acute myelogenous leukemia who relapsed after allogeneic HCT. These results suggest that MHC loss should be evaluated in patients with myeloma and other cancers who relapse after adoptive NY-ESO-1-specific T-cell therapy.

A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas.

BACKGROUND: This study evaluated the addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinoma first-line therapy. METHODS: Patients with advanced biliary adenocarcinomas received gemcitabine 1000 mg m(-2) and cisplatin 25 mg m(-2) on a 2 weeks on/1 week off cycle and sorafenib 400 mg twice daily. After the initial 16 patients were enrolled, the chemotherapy doses were amended in view of grade 3 and 4 hand-foot skin reaction and haematologic toxicity. Subsequently, 21 patients received gemcitabine 800 mg m(-2), cisplatin 20 mg m(-2) and sorafenib 400 mg. The primary end point was an improvement in 6-month progression-free survival (PFS6) from historical 57-77% (90% power, type I error of 10%). Pretreatment pERK, evaluated by immunostaining, was correlated with clinical outcome. RESULTS: A total of 39 patients were accrued. The most common grade 3-4 toxicities noted in >10% of patients were fatigue, elevated liver function tests and haematologic toxicities including thromboemboli, hyponatraemia and hypophosphataemia. Six-month progression-free survival was 51% (95% confidence interval (CI) 34-66%). Median PFS and overall survival were 6.5 (95% CI: 3.5-8.3) and 14.4 months (95% CI: 11.6-19.2 months), respectively. No correlation was observed between pERK and outcomes. CONCLUSION: The addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinomas did not improve efficacy over historical data, and toxicity was increased.

Surveillance of avian influenza A(H7N9) virus infection in humans and detection of the first imported human case in Taiwan, 3 April to 10 May 2013.

On 3 April 2013, suspected and confirmed cases of influenza A(H7N9) virus infection became notifiable in the primary care sector in Taiwan, and detection of the virus became part of the surveillance of severe community-acquired pneumonia. On 24 April, the first imported case, reported through both surveillance systems, was confirmed in a man returning from China by sequencing from endotracheal aspirates after two negative throat swabs. Three of 139 contacts were ill and tested influenza A(H7N9)-negative.

Glucose-6-phosphatase dependent substrate transport in the glycogen storage disease type-1a mouse.

Glycogen storage disease type 1a (GSD-1a) is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. A G6Pase knockout mouse which mimics the pathophysiology of human GSD-1a patients was created to understand the pathogenesis of this disorder, to delineate the mechanisms of G6Pase catalysis, and to develop future therapeutic approaches. By examining G6Pase in the liver and kidney, the primary gluconeogenic tissues, we demonstrate that glucose-6-P transport and hydrolysis are performed by separate proteins which are tightly coupled. We propose a modified translocase catalytic unit model for G6Pase catalysis.

Broken even-odd symmetry in self-selection of distances between nanoclusters due to the presence or absence of topological solitons.

Depositing particles randomly on a 1D lattice is expected to result in an equal number of particle pairs separated by even or odd lattice units. Unexpectedly, the even-odd symmetry is broken in the self-selection of distances between indium magic-number clusters on a Si(100)-2×1 reconstructed surface. Cluster pairs separated by even units are less abundant because they are linked by silicon atomic chains carrying topological solitons, which induce local strain and create localized electronic states with higher energy. Our findings reveal a unique particle-particle interaction mediated by the presence or absence of topological solitons on alternate lattices.

Population dose from medical exposure in Taiwan for 2008.

PURPOSE: The largest contribution to the population dose from man-made ionizing radiation sources is the medical exposure. Exposure to patients from medical examinations is of interest because it is a global indicator for the quality of radiology practice. Due to the different healthcare systems and the considerable variations in the equipment and manpower in radiology, the population dose from medical exposure varies by a large extent in different countries. This dose from different diagnostic procedures provides information that can be used to establish national reference levels. It is also useful to determine the priority in terms of dose reduction so as to optimize the protection of patients in a cost-effective manner. In the present work, the collective effective doses due to different medical modalities were estimated for the Taiwan population in 2008. METHODS: The collective effective dose from medical exposure was calculated using information on the number of procedures and the average effective dose per procedure. The frequency of procedures was extracted from the National Health Insurance (NHI) research database. The enrollment of Taiwan population in the NHI program was 99.48% in 2008. The average effective dose per procedure was derived from hospital surveys, measured data, and published results. RESULTS: Estimates of the collective effective dose were made for different medical modalities, i.e., the conventional radiography and fluoroscopy, computed tomography, interventional fluoroscopy, nuclear medicine, and dental radiography. Each modality was further divided into relevant classes by the body part or organ system. Among 23 037 031 Taiwan population in 2008, the annual examination frequencies per 1000 population were 550, 55.1, 15.6, 13.6, and 112 for the conventional radiography and fluoroscopy, computed tomography, interventional fluoroscopy, nuclear medicine, and dental radiography, respectively. The corresponding collective effective doses were 3277, 8608, 2743, 2303, and 28 man-Sv, respectively. Thus, the average effective dose per caput was 0.74 mSv, which was in the range of 0.3-1.5 mSv for the 12 European countries estimated for 2008. CONCLUSIONS: In the period from 1997 to 2008, the procedure frequency per 1000 population increased by a factor of 2.3 for computed tomography, 2.2 for interventional fluoroscopy, 1.8 for conventional radiography and fluoroscopy, and 1.5 for nuclear medicine. It demonstrated that the medical utilization of imaging facilities raised rapidly.

Genomic indicators in the blood predict drug-induced liver injury.

Genomic biomarkers for the detection of drug-induced liver injury (DILI) from blood are urgently needed for monitoring drug safety. We used a unique data set as part of the Food and Drug Administration led MicroArray Quality Control Phase-II (MAQC-II) project consisting of gene expression data from the two tissues (blood and liver) to test cross-tissue predictability of genomic indicators to a form of chemically induced liver injury. We then use the genomic indicators from the blood as biomarkers for prediction of acetaminophen-induced liver injury and show that the cross-tissue predictability of a response to the pharmaceutical agent (accuracy as high as 92.1%) is better than, or at least comparable to, that of non-therapeutic compounds. We provide a database of gene expression for the highly informative predictors, which brings biological context to the possible mechanisms involved in DILI. Pathway-based predictors were associated with inflammation, angiogenesis, Toll-like receptor signaling, apoptosis, and mitochondrial damage. The results show for the first time and support the hypothesis that genomic indicators in the blood can serve as potential diagnostic biomarkers predictive of DILI.

Blood gene expression signatures predict exposure levels.

To respond to potential adverse exposures properly, health care providers need accurate indicators of exposure levels. The indicators are particularly important in the case of acetaminophen (APAP) intoxication, the leading cause of liver failure in the U.S. We hypothesized that gene expression patterns derived from blood cells would provide useful indicators of acute exposure levels. To test this hypothesis, we used a blood gene expression data set from rats exposed to APAP to train classifiers in two prediction algorithms and to extract patterns for prediction using a profiling algorithm. Prediction accuracy was tested on a blinded, independent rat blood test data set and ranged from 88.9% to 95.8%. Genomic markers outperformed predictions based on traditional clinical parameters. The expression profiles of the predictor genes from the patterns extracted from the blood exhibited remarkable (97% accuracy) transtissue APAP exposure prediction when liver gene expression data were used as a test set. Analysis of human samples revealed separation of APAP-intoxicated patients from control individuals based on blood expression levels of human orthologs of the rat discriminatory genes. The major biological signal in the discriminating genes was activation of an inflammatory response after exposure to toxic doses of APAP. These results support the hypothesis that gene expression data from peripheral blood cells can provide valuable information about exposure levels, well before liver damage is detected by classical parameters. It also supports the potential use of genomic markers in the blood as surrogates for clinical markers of potential acute liver damage.

Inhibition of synthesis of alpha-fetoprotein by glucocorticoids in cultured hepatoma cells.

alpha-Fetoprotein (AFP) synthesis was studied in the presence and absence of glucocorticoids in rat hepatoma Mc-A-RH-7777 cells. Radioimmunoassay of media from cell cultures grown in the presence of glucocorticoid (dexamethasone or cortisol) showed a reduction in AFP, an increase in albumin, and no significant change in transferrin accumulation, as compared to controls. Labeling experiments with L-[35S]methionine indicated that in both cells and media of dexamethasone-treated cultures there was a 50--80% reduction in polypeptide precipitated by anti-AFP serum, as compared with controls; no change was seen in polypeptide precipitated by anti-transferrin serum. Pulse and pulse-chase experiments demonstrated that dexamethasone inhibited the synthesis of AFP but not its secretion. The half-time for secretion of AFP in the presence and absence of dexamethasone was 43 min.