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.

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.

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.

An investigation into the effectiveness of compressed straw blocks in reducing abnormal behaviour in growing pigs.

The provision of manipulable material to pigs is a legal requirement to ensure their good welfare. Loose straw is edible, chewable, investigable and manipulable, and has been proven to be effective in reducing abnormal behaviour. However, it is incompatible with slatted systems and therefore not a viable option for many intensive units. Thus, there is a need to identify enrichment materials that are as effective as loose straw and compatible with slatted floors. This study investigated the viability of using compressed straw blocks on a commercial farm in terms of cost and effectiveness in reducing biting relative to plastic hanging toys. A total of 880 slaughter pigs were used, among which half (n = 440, 8 groups) were provided with commercial pig toys (TOY) and the other half (n = 440, 8 groups) were provided compressed straw blocks (STRAW BLOCK). Animals were separated according to sex to investigate whether there was a higher propensity to tail and ear bite depending on sex. Pigs were monitored from weaning to slaughter, with tails being examined post scalding and any condemnations recorded at the abattoir. Throughout their life, the tails and ears of all pigs were examined individually, and behavioural observations of each pig group were conducted fortnightly. Salivary cortisol was also obtained from a subsample of pigs from each group every fortnight to monitor stress levels. The highest straw usage was recorded in the second weaner stage (39 to 67 days after weaning). Enrichment type or sex had no effect on tail lesion scores or cold carcass weight recorded at the abattoir. There was also no effect of enrichment type or sex on body, tail, or ear lesion scores during either the weaner (0 to 39 days after weaning) or finisher stage (67 to145 days after weaning). Female pigs showed more biting behaviour than males, and female pigs that were provided STRAW BLOCK performed better than those provided TOY. In both the weaner and finisher accommodation, more instances of interaction were recorded with TOY pens as enrichment than with STRAW BLOCK, but the interaction duration was not recorded. There was no effect of sex on either stage. More instances of aggression were observed with the TOY than with STRAW BLOCK in the weaner stage (P < 0.05). Enrichment type or sex had no effect on cortisol levels. Thus, relative to plastic hanging toys, compressed straw blocks provided in this manner did not benefit pig welfare.

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.

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.

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.

GATA3 targets semaphorin 3B in mammary epithelial cells to suppress breast cancer progression and metastasis.

Semaphorin 3B (SEMA3B) is a secreted axonal guidance molecule that is expressed during development and throughout adulthood. Recently, SEMA3B has emerged as a tumor suppressor in non-neuronal cells. Here, we show that SEMA3B is a direct target of GATA3 transcriptional activity. GATA3 is a key transcription factor that regulates genes involved in mammary luminal cell differentiation and tumor suppression. We show that GATA3 relies on SEMA3B for suppression of tumor growth. Loss of SEMA3B renders GATA3 inactive and promotes aggressive breast cancer development. Overexpression of SEMA3B in cells lacking GATA3 induces a GATA3-like phenotype and higher levels of SEMA3B are associated with better cancer patient prognosis. Moreover, SEMA3B interferes with activation of LIM kinases (LIMK1 and LIMK2) to abrogate breast cancer progression. Our data provide new insights into the role of SEMA3B in mammary gland and provides a new branch of GATA3 signaling that is pivotal for inhibition of breast cancer progression and metastasis.

Long-term event-free and overall survival after risk-adapted melphalan and SCT for systemic light chain amyloidosis.

Stem cell transplantation (SCT), an effective therapy for amyloid light chain (AL) amyloidosis patients, is associated with low treatment-related mortality (TRM) with appropriate patient selection and risk-adapted dosing of melphalan (RA-SCT). Consolidation after SCT increases hematologic complete response (CR) rates and may improve overall survival (OS) for patients with

2D Tl-Pb compounds on Ge(1 1 1) surface: atomic arrangement and electronic band structure.

Structural transformations and evolution of the electron band structure in the (Tl, Pb)/Ge(1 1 1) system have been studied using low-energy electron diffraction, scanning tunneling microscopy, angle-resolved photoelectron spectroscopy and density functional theory calculations. The two 2D Tl-Pb compounds on Ge(1 1 1), [Formula: see text]-(Tl, Pb) and [Formula: see text]-(Tl, Pb), have been found and their composition, atomic arrangement and electron properties has been characterized. The (Tl, Pb)/Ge(1 1 1)[Formula: see text] compound is almost identical to the alike (Tl, Pb)/Si(1 1 1)[Formula: see text] system from the viewpoint of its atomic structure and electronic properties. They contain 1.0 ML of Tl atoms arranged into a honeycomb network of chained trimers and 1/3 ML of Pb atoms occupying the centers of the honeycomb units. The (Tl, Pb)/Ge(1 1 1)[Formula: see text] compound contains six Tl atoms and seven Pb atoms per [Formula: see text] unit cell (i.e. ∼0.67 ML Tl and ∼0.78 ML Pb). Its atomic structure can be visualized as consisting of Pb hexagons surrounded by Tl trimers. The (Tl, Pb)/Ge(1 1 1)[Formula: see text] and (Tl, Pb)/Ge(1 1 1)[Formula: see text] compounds are metallic and their band structures contain spin-split surface-state bands. By analogy with the (Tl, Pb)/Si(1 1 1)[Formula: see text], these (Tl, Pb)/Ge(1 1 1) compounds are believed to be promising objects for prospective studies of superconductivity in one-atom-layer systems.

Microleakage of Lithium Disilicate Crown Margins Finished on Direct Restorative Materials.

OBJECTIVE: For some esthetic clinical situations, it is necessary to finish crown margins on direct restorative materials to preserve tissue integrity, bonding integrity, and biological width. The purpose of this research was to investigate microleakage at the interface between bonded lithium disilicate crowns and various direct restorative materials in a class III and class V position. METHODS AND MATERIALS: Class III or class V restorations were prepared on one side of extracted incisors with either Tetric EvoCeram, Tetric Evoceram Bulk, Fuji II LC, or Tetric Evoflow. The teeth were prepared for and received a lithium disilicate crown. After load fatiguing, the specimens were thermo-cycled with a fuchsin dye and sectioned. The depth and area of dye penetration were measured with a dimensional grid in micrometers using stereomicroscopy and reported as mean dye depth and area (µm) ± SD. The comparison of multiple categorical independent variables with ratio scale dependent variables was evaluated with an analysis of variance and Tukey's post hoc analysis. RESULTS: A statistically significant higher dye penetration was noted for all treatment groups compared with the positive control (side opposite the restoration after sagittal sectioning was used as positive control) regardless of material or placement area (p<0.05). In comparing treatment groups, the Tetric EvoFlow experienced a statistically higher dye penetration than did the other treatment groups regardless of material or placement area (p<0.05). There was no statistically significant difference between the Tetric EvoCeram, Tetric Evoceram Bulk, and Fuji II LC materials regardless of placement area (p>0.05). CONCLUSIONS: Within the limitations of this study, it can be concluded that flowable composite materials as finish lines that interact with resin cements could lead to exacerbated interfacial degradation. Finishing lithium disilicate all-ceramic crowns on flowable resin composite materials in the esthetic zone should be used with caution. If necessary, finishing lithium disilicate all-ceramic crowns on nanofilled resin composite or resin-modified glass ionomer materials seems to provide the least dye penetration depth and area.

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.

Epigenetic silencing of GDF1 disrupts SMAD signaling to reinforce gastric cancer development.

Accumulating evidence reveals the effectiveness of epigenetic therapy in gastric cancer. However, the molecular mechanisms and targets underlying such therapeutic responses remain elusive. Herein, we report an aberrant yet therapeutically rectifiable epigenetic signaling in gastric carcinogenesis. Administration of DNA-demethylating drug 5-aza-2'-deoxycytidine (5-aza-dC) reduced gastric cancer incidence by ~74% (P < 0.05) in N-nitroso-N-methylurea-treated mice. Through genome-wide methylation scanning, novel promoter hypermethylation-silenced and drug-targeted genes were identified in the resected murine stomach tumors and tissues. We uncovered that growth/differentiation factor 1 (Gdf1), a member of the transforming growth factor-ß superfamily, was silenced by promoter hypermethylation in control tumor-bearing mice, but became reactivated in 5-aza-dC-treated mice (P < 0.05). In parallel, the downregulated SMAD2/3 phosphorylation in gastric cancer was revived by 5-aza-dC in vivo. Such hypermethylation-dependent silencing and 5-aza-dC-mediated reactivation of GDF1-SMAD2/3 activity was conserved in human gastric cancer cells (P < 0.05). Subsequent functional characterization further revealed the antiproliferative activity of GDF1, which was exerted through activation of SMAD2/3/4-mediated signaling, transcriptional controls on p15, p21 and c-Myc cell-cycle regulators and phosphorylation of retinoblastoma protein. Clinically, hypermethylation and loss of GDF1 was significantly associated with reduced phosphorylated-SMAD2/3 and poor survival in stomach cancer patients (P < 0.05). Taken together, we demonstrated a causal relationship between DNA methylation and a tumor-suppressive pathway in gastric cancer. Epigenetic silencing of GDF1 abrogates the growth-inhibitory SMAD signaling and renders proliferation advantage to gastric epithelial cells during carcinogenesis. This study lends support to epigenetic therapy for gastric cancer chemoprevention and identifies a potential biomarker for prognosis.

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.