Shadow estimation of gate-set properties from random sequences.

With quantum computing devices increasing in scale and complexity, there is a growing need for tools that obtain precise diagnostic information about quantum operations. However, current quantum devices are only capable of short unstructured gate sequences followed by native measurements. We accept this limitation and turn it into a new paradigm for characterizing quantum gate-sets. A single experiment-random sequence estimation-solves a wealth of estimation problems, with all complexity moved to classical post-processing. We derive robust channel variants of shadow estimation with close-to-optimal performance guarantees and use these as a primitive for partial, compressive and full process tomography as well as the learning of Pauli noise. We discuss applications to the quantum gate engineering cycle, and propose novel methods for the optimization of quantum gates and diagnosing cross-talk.

One T Gate Makes Distribution Learning Hard.

The task of learning a probability distribution from samples is ubiquitous across the natural sciences. The output distributions of local quantum circuits are of central importance in both quantum advantage proposals and a variety of quantum machine learning algorithms. In this work, we extensively characterize the learnability of output distributions of local quantum circuits. Firstly, we contrast learnability with simulatability by showing that Clifford circuit output distributions are efficiently learnable, while the injection of a single T gate renders the density modeling task hard for any depth d=n^{Ω(1)}. We further show that the task of generative modeling universal quantum circuits at any depth d=n^{Ω(1)} is hard for any learning algorithm, classical or quantum, and that for statistical query algorithms, even depth d=ω[log(n)] Clifford circuits are hard to learn. Our results show that one cannot use the output distributions of local quantum circuits to provide a separation between the power of quantum and classical generative modeling algorithms, and therefore provide evidence against quantum advantages for practically relevant probabilistic modeling tasks.

Laminin Immunostaining in Biopsies as a Useful Biomarker of Early Invasion in Actinic Cheilitis and Differential Diagnosis Between Actinic Cheilitis and Lip Cancer: New Insights.

BACKGROUND: Squamous cell carcinoma of the lip (LSCC) and oral cavity can be life-threatening if not diagnosed early. Precancerous lesions like actinic cheilitis (AC), can transform into LSCC. Laminin is a fundamental component for basement membrane (BM) and its integrity may prevent neoplastic invasion. Therefore, laminin immunostaining of BM may be useful in identifying early invasion in actinic cheilitis and thus in the differential diagnosis between AC and invasive LSCC or high-grade epithelial dysplasia (ED). MATERIALS AND METHODS: Biopsies from 46 patients with oral lesions were histologically analyzed and immunohistochemically stained for laminin-1. RESULTS: AC was diagnosed in 34 patients and LSCC in 12 patients, including 3 patients with AC and concomitant high-grade ED/in situ carcinoma. Laminin-1 immunostaining revealed intense and linear expression of the BM in AC with low-grade ED. Loss of laminin expression was observed in LSCC. Intracellular laminin expression in parabasal cells was noted in AC with high-grade ED/in situ carcinoma. CONCLUSION: Laminin immunostaining could be useful in identifying AC cases suspected of early invasion. It could also contribute to the histopathological differential diagnosis between AC with low- and high-grade ED and between AC and invasive LSCC. The findings of this study provide new insights into the mechanism involved in the progression process of AC into LSCC, encouraging preclinical studies that may document the stochastic role of laminin in this process.

Increased prevalence of metabolic syndrome in patients with bipolar disorder compared to a selected control group-a Northern Netherlands LifeLines population cohort study.

OBJECTIVES: Metabolic syndrome (MetS) is highly prevalent among patients with bipolar disorder (BD). The aims of this cross-sectional study were to determine the prevalence of MetS in Dutch BD subjects and compare it with a control group, to examine the association of demographic and clinical characteristics with MetS in BD, and to determine the extent to which metabolic dysregulation is treated in those patients. METHODS: 493 Dutch adult patients (≥ 18 years) with BD receiving psychotropic drugs and 493 matched control subjects were compared using data from the biobank Lifelines. We determined MetS according to the National Cholesterol Education Program Adult Treatment Panel III-Adapted (NCEP ATP III-A) criteria. The difference in the prevalence of MetS and the associations with characteristics were analyzed with logistic regression. RESULTS: BD subjects (30.6%) showed a significantly higher prevalence of MetS compared to the control group (14.2%) (p < .001, OR:2.67, 95% CI:1.94-3.66). Univariate analysis showed that smoking, body mass index (BMI) and antidepressant drug use were associated with MetS. Multivariate analysis showed that smoking (OR:2.01) was independently associated with MetS in BD. For hypertension, hyperglycemia and lipid disorder pharmacological treatment was provided to respectively 69.5%, 24% and 18.4% of the BD subjects in our sample. LIMITATIONS: Duration of illness of BD subjects was unknown. CONCLUSIONS: This study demonstrated a higher prevalence of MetS in Dutch BD subjects compared to persons without BD. In addition, a remarkable undertreatment of some of the components of MetS was found.

Towards precision medicine: What are the stratification hypotheses to identify homogeneous inflammatory subgroups.

Diverse lines of research testify a link, presumably causal, between immune dysregulation and the development, course and clinical outcome of psychiatric disorders. However, there is a large heterogeneity among the patients' individual immune profile and this heterogeneity prevents the development of precise diagnostic tools and the identification of therapeutic targets. The aim of this review was to delineate possible subgroups of patients on the basis of clinical dimensions, investigating whether they could lead to particular immune signatures and tailored treatments. We discuss six clinical entry points; genetic liability to immune dysregulation, childhood maltreatment, metabolic syndrome, cognitive dysfunction, negative symptoms and treatment resistance. We describe the associated immune signature and outline the effects of anti-inflammatory drugs so far. Finally, we discuss advantages of this approach, challenges and future research directions.

Hypoxia-inducible factor 1-alpha and vascular endothelial growth factor in cartilage tumors.

Neoangiogenesis has been demonstrated in chondrosarcoma. Anti-angiogenic therapies are being tested in clinical trials for chondrosarcomas. Studies of the underlying mechanisms have been performed almost exclusively in cell lines. We immunostained 20 samples of chondrosarcoma and 20 samples of enchondromas with antibodies against hypoxia-inducible factor 1-alpha (HIF-1-alpha) and vascular endothelial growth factor (VEGF). The immunohistochemical staining of HIF-1-alpha and VEGF were highly correlated. Enchondromas were HIF-1-alpha and VEGF negative, whereas all chondrosarcoma exhibited HIF-1-alpha and VEGF immunostaining. HIF-1-alpha/VEGF double positive cases were almost exclusively chondrosarcomas with a high tumor grade. We suggest that HIF-1-alpha is a marker of malignancy in chondrosarcomas that correlates with tumor neo-angiogenesis. Our findings also suggest that a HIF-1-alpha/VEGF angiogenic pathway may exist in chondrosarcoma in vivo as in other malignant tumors. The inclusion of novel inhibitors to HIF-1-alpha and other factors may optimize anti-angiogenic interventions in chondrosarcoma.

Smad4 and epithelial-mesenchymal transition proteins in colorectal carcinoma: an immunohistochemical study.

Epithelial-mesenchymal transition (EMT) plays an important role in cancer metastasis. During EMT, tumor cells acquire the capacity to migrate and invade the stroma. Activation of the transforming growth factor-b (TGF-b) signaling pathway is of major importance for the initiation of EMT. Smad4, an essential protein of this pathway, is known to complex with multiple transcription factors (e.g. Snail-1, Slug, Twist-1), in various types of cancer, promoting the repression or activation of target genes. The role of Smad4 in colorectal cancer (CRC) is not straightforward so far. In the present study forty eight resected CRC tumor specimens were immunohistochemically examined in order to assess the expression of Smad4 and its association with E-cadherin, Snail-1, Slug, Twist-1 protein expression and with various pathological parameters. Smad4 was found to be positively correlated with Snail-1, Slug and Twist-1 expression (p < 0.001). On the other hand it was negatively correlated with the expression of E-cadherin (p < 0.001). Furthermore, lymphatic invasion could be clearly associated with Smad4 expression, a finding complying with the metastatic ability of EMT cells. In conclusion, Smad4 could be considered as a central component of EMT transition in human colorectal cancer that combines with transcriptional factors to reduce E-cadherin and alter the expression of the epithelial phenotype.

Nonreciprocal reconfigurable microwave optomechanical circuit.

Nonreciprocal microwave devices are ubiquitous in radar and radio communication and indispensable in the readout chains of superconducting quantum circuits. Since they commonly rely on ferrite materials requiring large magnetic fields that make them bulky and lossy, there has been significant interest in magnetic-field-free on-chip alternatives, such as those recently implemented using the Josephson nonlinearity. Here, we realize reconfigurable nonreciprocal transmission between two microwave modes using purely optomechanical interactions in a superconducting electromechanical circuit. The scheme relies on the interference in two mechanical modes that mediate coupling between the microwave cavities and requires no magnetic field. We analyse the isolation, transmission and the noise properties of this nonreciprocal circuit. Finally, we show how quantum-limited circulators can be realized with the same principle. All-optomechanically mediated nonreciprocity demonstrated here can also be extended to directional amplifiers, and it forms the basis towards realizing topological states of light and sound.Nonreciprocal optical devices traditionally rely on magnetic fields and magnetic-free approaches are rather recent. Here, Bernier et al. propose and demonstrate a purely optomechanical circulator with reconfigurable transmission without the need for direct coupling between input and output modes.

Perceptually accurate display of two greyscale images as a single colour image.

Life scientists often desire to display the signal from two different molecular probes as a single colour image, so as to convey information about the probes' relative concentrations as well as their spatial corelationship. Traditionally, such colour images are created through a merge display, where each greyscale signal is assigned to different channels of an RGB colour image. However, human perception of colour and greyscale intensity is not equivalent. Thus, a merged image display conveys to the typical viewer only a subset of the absolute and relative intensity information present in and between two greyscale images. The Commission Internationale de l'Eclairage L*a*b* colour space (CIELAB) has been designed to specify colours according to the perceptually defined quantities of hue (perceived colour) and luminosity (perceived brightness). Here, we use the CIELAB colour space to encode two dimensions of information about two greyscale images within these two perceptual dimensions of a single colour image. We term our method a Perceptually Uniform Projection display and show using biological image examples how these displays convey more information about two greyscale signals than comparable RGB colour space-based techniques.

Histological and biochemical evidence related to the collagen quality in torn rotator cuff tendons.

This study investigates the histological background of torn rotator cuff tendons, evaluates the stability of newly synthesized collagen by measuring the hydro-xyproline content and attempts to correlate these findings with the clinical outcome after reconstruction of the rotator cuff. Sixty-one patients underwent reconstruction for a -rotator cuff tear. They were evaluated preoperatively with the Constant-Murley score, MRI and ultrasound. Biopsy samples were taken from chronic rotator cuff tears and histological analysis was performed. Hydroxyprolin presence was evaluated in various -tissues. Mean follow-up was 46 months. Histological analysis revealed collagen fragmentation and thinning (90.2% of patients), myxoid degeneration (88%), hyaline degeneration (50.8%), chondroid metaplasia (44.3%), calcification (24.7%), fatty infiltration (20.4%) and vascular proliferation (62.3%). Hydroxyproline was under-represented in newly synthesized collagen in 57% of patients. In the majority of the patients with a low hydroxyproline/collagen ratio the histological findings were abnormal. None of the findings was related to the clinical outcome with a statistical significance. Histological and biochemical findings reflected the poor quality of the tendon. The good clinical outcome did not depend on the histological or biochemical findings but rather on the meticulous surgical reconstruction and physical therapy.

Apolipoprotein A-I inhibits experimental colitis and colitis-propelled carcinogenesis.

In both humans with long-standing ulcerative colitis and mouse models of colitis-associated carcinogenesis (CAC), tumors develop predominantly in the distal part of the large intestine but the biological basis of this intriguing pathology remains unknown. Herein we report intrinsic differences in gene expression between proximal and distal colon in the mouse, which are augmented during dextran sodium sulfate (DSS)/azoxymethane (AOM)-induced CAC. Functional enrichment of differentially expressed genes identified discrete biological pathways operating in proximal vs distal intestine and revealed a cluster of genes involved in lipid metabolism to be associated with the disease-resistant proximal colon. Guided by this finding, we have further interrogated the expression and function of one of these genes, apolipoprotein A-I (ApoA-I), a major component of high-density lipoprotein. We show that ApoA-I is expressed at higher levels in the proximal compared with the distal part of the colon and its ablation in mice results in exaggerated DSS-induced colitis and disruption of epithelial architecture in larger areas of the large intestine. Conversely, treatment with an ApoA-I mimetic peptide ameliorated the phenotypic, histopathological and inflammatory manifestations of the disease. Genetic interference with ApoA-I levels in vivo impacted on the number, size and distribution of AOM/DSS-induced colon tumors. Mechanistically, ApoA-I was found to modulate signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB activation in response to the bacterial product lipopolysaccharide with concomitant impairment in the production of the pathogenic cytokine interleukin-6. Collectively, these data demonstrate a novel protective role for ApoA-I in colitis and CAC and unravel an unprecedented link between lipid metabolic processes and intestinal pathologies.

Mutation profile of KRAS and BRAF genes in patients with colorectal cancer: association with morphological and prognostic criteria.

KRAS and BRAF mutations are well-recognized molecular alterations during colorectal carcinogenesis, but there is little agreement on their effect on tumor characteristics. Therefore, we aimed to evaluate the distribution of the most common KRAS and BRAF mutations in Greek patients with colorectal cancer and their possible associations with clinical histopathological parameters. In this study, 322 and 188 colorectal carcinomas were used for the mutation analysis of KRAS (exon 2) and BRAF (exon 15) genes, respectively. The mutational status of both genes was evaluated by polymerase chain reaction and sequencing analysis. Although the overall frequency of KRAS mutations (36.6%) seemed to be similar to those reported for other populations, the rate of point mutations at codon 13 was significantly lower (12%) in Greek patients with colorectal cancer and associated with male gender (P < 0.05). Tumors with G>T codon 12 transversions and G>C transitions showed more frequent lymph node metastasis (P < 0.05, P < 0.005, respectively). The rate of KRAS mutations gradually decreased with increasing histological grade (P < 0.05), as opposed to BRAF mutations, which were strongly associated with poorly differentiated tumors (P < 0.005). Additionally, we found that the histological features of preexisting adenoma were associated with the absence of BRAF mutations, in contrast to KRAS (P < 0.05). Our data suggested that there seems to be a correlation between morphological criteria and discrete genetic pathways in colorectal carcinogenesis. Moreover, ethnic or geographic factors may have an impact on genetic background of colorectal carcinomas, and specific types of KRAS mutations may influence the metastatic potential of colorectal tumors.

Aurora B kinase in Hodgkin lymphoma: immunohistochemical pattern of expression in neoplastic Hodgkin and Reed-Sternberg cells.

Aurora B is a member of the chromosomal passenger complex, which is essential for proper completion of mitosis and cell division (cytokinesis). Inappropriate chromosomal segregation and cytokinesis due to deregulated expression of chromosome passenger proteins may lead to aneuploidy and cancer including lymphomas. According to our knowledge there are extremely limited studies investigating the immunohistochemical expression of Aurora B in tumor specimens of Hodgkin lymphoma. Our purpose was to characterize the expression of Aurora B in biopsies of Hodgkin lymphomas, and to evaluate the pattern of immunoreactivity in neoplastic Hodgkin and Reed-Sternberg cells (RS cells). We examined Aurora B immunoreactivity in paraffin sections of 15 samples of Hodgkin lymphomas, obtained from 15 patients, 8 men and 7 women. Ten were of nodular sclerosis type and five were of mixed cellularity. Our results showed immunoexpression of Aurora B in mononuclear lymphoid cells as well as in bi- and multinucleated RS cells. In addition, positive neoplastic cells in mitosis were observed, whereas a subpopulation without evidence of immunoreaction was also detected in each case. Taken together our results point to a possible association between Aurora B expression and mitotic deregulation in Hodgkin lymphoma, which may provide novel targets for treatment.

Open inguinal hernia repair with the use of polyglycolic acid/trimethylene carbonate mesh: gross and pathologic assessment of the inguinal area at reoperation for recurrence.

PURPOSE: Our group tried to test the hypothesis of using a totally absorbable material for open inguinal hernia repair. However, the increased incidence of recurrences alleviated our initial enthusiasm regarding the technique. The purpose of the present study was to attain both gross and microscopic data that could at least in part justify the hernia repair failure from a patient included in our initial pilot study and was re-operated for recurrence. METHODS: A 65-year-old male patient was diagnosed clinically with a recurrence 24 months after open inguinal hernia repair with the use of polyglycolic acid/trimethylene carbonate mesh. The patient was operated for the recurrence upon our group on July 2012. The gross appearance of the inguinal area as well as the degree of chronic inflammation provoked by the used mesh as depicted by the pathologic analysis of specimens obtained intraoperatively were assessed. RESULTS: An open tension-free repair with the use of a non-absorbable mesh under spinal anesthetic was undertaken. Intraoperatively, after the division of the external oblique aponeurosis, only minor fibrotic reaction was observed a finding that was additionally confirmed pathologically. CONCLUSION: Polyglycolic acid/trimethylene carbonate mesh used for inguinal hernia repair was associated with a minimal inflammatory host reaction in the inguinal area at 3 years verified both grossly and microscopically.

Insulin-induced electrochemical changes in pleura are associated with the location within the pleural cavity.

AIM: We investigated the effects of insulin on the electrophysiology of sheep pleural specimens obtained from the upper and lower parts of the pleural cavity and the insulin receptor abundance in these regions. MATERIALS AND METHODS: Sheep pleural specimens were obtained from the upper and lower lung lobes and from the 1st-4th and 8th-12th ribs and were mounted between Ussing chambers. Insulin 10(-7) M was added on the mesothelial surface with Insulin Receptor (IR) inhibitor in some experiments. Trans-mesothelial Resistance (R(™)) was determined. Immunohistochemistry for the presence of IR differences was performed. RESULTS: Insulin increased the R(™) of all pleural regions. Higher R(™) increase was demonstrated in lower lobe visceral and in caudal parietal specimens. The R(™) increase demonstrated in caudal parietal had the tendency to be higher than that observed in the lower lobe visceral specimens. IR inhibitor abolished insulin's effect in all regions. Immunostaining was more intense for parietal and for caudal parietal specimens when compared with the visceral and lower lobe visceral specimens. CONCLUSION: Insulin induces electrochemical alterations that vary depending on the location of specimens within the pleural cavity which possibly is not correlated with insulin receptors variations.

Permeability alterations after surgical trauma in normal rabbit peritoneum.

BACKGROUND: To investigate whether surgical trauma in a rabbit adhesion formation model and the administration of normal saline (N/S), icodextrin (ID) and/or dimetindene maleate (DM) changes the permeability of the normal rabbit parietal peritoneum. MATERIALS AND METHODS: A total of 45 female rabbits were operated on for adhesion formation and were euthanized 10 days later. In some rabbits, ID or N/S was instilled intraabdominally during operation, whereas in others DM was infused intravenously. In others, ID plus DM or no agent was used. Specimens were obtained postoperatively and were mounted between Ussing chambers. Amiloride was used to investigate Na(+) channels. Transmesothelial resistance (R(TM)) was determined as a permeability indicator. RESULTS: Amiloride increased the R(TM) of both surfaces. Surgical trauma increased R(TM) and partially inhibited the effect of amiloride. ID and N/S increased R(TM) and inhibited the effect of amiloride. Use of DM did not change R(TM) and did not inhibit the effect of amiloride. Use of ID plus DM slightly increased R(TM), but the effect of amiloride was blocked. CONCLUSIONS: Surgical trauma impairs the permeability of the normal rabbit parietal peritoneum. ID or N/S surmounted this effect, but DM did not, suggesting that surgical trauma is a diffuse process. Antiadhesion measures influence peritoneal physiology.

Insulin-induced electrophysiology changes in human pleura are mediated via its receptor.

BACKGROUND: Insulin directly changes the sheep pleural electrophysiology. The aim of this study was to investigate whether insulin induces similar effects in human pleura, to clarify insulin receptor's involvement, and to demonstrate if glibenclamide (hypoglycemic agent) reverses this effect. METHODS: Human parietal pleural specimens were mounted in Ussing chambers. Solutions containing insulin or glibenclamide and insulin with anti-insulin antibody, anti-insulin receptor antibody, and glibenclamide were used. The transmesothelial resistance (R(TM)) was determined. Immunohistochemistry for the presence of Insulin Receptors (IRa, IRb) was also performed. RESULTS: Insulin increased R(TM) within 1st min (P = .016), when added mesothelially which was inhibited by the anti-insulin and anti-insulin receptor antibodies. Glibenclamide also eliminated the insulin-induced changes. Immunohistochemistry verified the presence of IRa and IRb. CONCLUSION: Insulin induces electrochemical changes in humans as in sheep via interaction with its receptor. This effect is abolished by glibenclamide.

Insulin alters the permeability of sheep pleura.

AIM: Insulin promotes ion transportation across epithelia, mainly kidneys, leading to water and electrolyte abnormalities, possibly causing 'insulin oedema syndrome', which rarely presents as pleural effusion. Direct stimulation of sheep pleura by insulin and the possible electrophysiology mechanisms involved were investigated. MATERIAL AND METHODS: Sheep visceral and parietal pleural specimens were mounted between Ussing chambers. Insulin solutions (10 (-9) to 10 (-5) M), L-NAME, Nitroprussid sodium, amiloride and ouabain were used. Trans-mesothelial Resistance was determined. Immunohistochemistry for presence of Insulin Receptors was performed. RESULTS: Insulin increased Trans-mesothelial Resistance within 1st minute when added mesothelially of visceral (p=0.008) and parietal pleura (p=0.046) for concentrations higher than 10 (-7) M. L-NAME or Nitroprussid sodium didn't but amiloride and ouabain inhibited insulin's effect. Immunohistochemistry revealed the presence of Insulin Receptors. CONCLUSION: Insulin changes the permeability of sheep pleura by altering its electrophysiology and may interfere in pleural effusion formation. Involvement of Insulin Receptors may be suggested.

Chemoembolization facilitates limb salvage surgery in stage III soft tissue sarcoma.

A 26 year-old male was referred to our unit because of a stage III soft tissue sarcoma in the shoulder girdle-axillary area and reduced forearm-distal arm strength. Imaging studies revealed that the tumor encompassed the axillary artery and brachial plexus. We chemoembolized it using vincristine, adriamycin and cyclophosphamide (VAC) plus gel foam and performed limb salvage surgery (LSS) afterwards. The patient received adjuvant chemotherapy (ifosfamide/mesna, adriamycin, and dacarbazine/MAID) and finally radiation therapy (RT; 6500 cGy total dose). Thirty-six months after the operation the patient remains free of disease, without local recurrence and excellent neurological recovery and functional rehabilitation. In stage III soft tissue sarcomas, especially in proximity with major nerve/arterial bundles, a multimodality approach is mandatory; chemoembolization is very effective in shrinking the tumor and defining its margins so as to make feasible a LSS.