Domain engineering algorithm for practical and effective photon sources.

We introduce a method for shaping the spectral response of nonlinear light sources by tailoring the quasi-phase matching. Our algorithm relies on engineering the poling to accurately trace a generated target signal field amplitude to determine the desired nonlinearity profile. The proposed poling algorithm results in a poling pattern that is more robust to manufacture, as all domain inversions are of equal width. The poling pattern is verified using a nonlinear beam propagation method simulation. This approach is applied to achieve Gaussian-shaped phase matching along a potassium titanyl phosphate (KTP) crystal in order to generate pure heralded single photons of spectral purity ~0.996-this is highly desirable for heralded single photon quantum optics.

Pain during Fallopian-tube patency testing by hysterosalpingo-foam sonography.

OBJECTIVES: To evaluate perception of pain during Fallopian-tube patency testing by hysterosalpingo-foam sonography (HyFoSy). METHODS: In this cross-sectional study, 216 consecutive women presenting at a university fertility clinic for HyFoSy examination were included. Patients were instructed to take ibuprofen 1 hour before the procedure. Immediately after the procedure, patients filled in a questionnaire concerning discomfort or pain experienced during the process, including a visual analog scale (VAS) score for perception of pain. RESULTS: The median VAS score for perception of pain during transvaginal ultrasound examination and during HyFoSy examination was 1.5 (95% CI, 1.2-1.7) and 3.6 (95% CI, 3.0-4.0), respectively. One-third of women reported that the level of discomfort or pain during HyFoSy examination was similar to that during the preceding transvaginal ultrasound examination and 48% of women considered HyFoSy examination to be neutral/unpleasant, but not painful. There was an inverse association between both patients' age and parity and the pain experienced. CONCLUSIONS: HyFoSy examination is tolerated well and allows for reliable tubal patency testing without exposing the patient to ionizing radiation in an outpatient setting with a low technical failure rate.

Monolithic phononic crystals with a surface acoustic band gap from surface phonon-polariton coupling.

We theoretically and experimentally demonstrate the existence of complete surface acoustic wave band gaps in surface phonon-polariton phononic crystals, in a completely monolithic structure formed from a two-dimensional honeycomb array of hexagonal shape domain-inverted inclusions in single crystal piezoelectric Z-cut lithium niobate. The band gaps appear at a frequency of about twice the Bragg band gap at the center of the Brillouin zone, formed through phonon-polariton coupling. The structure is mechanically, electromagnetically, and topographically homogeneous, without any physical alteration of the surface, offering an ideal platform for many acoustic wave applications for photonics, phononics, and microfluidics.

PROMISE: effect of protein supplementation on fat-free mass preservation after bariatric surgery, a randomized double-blind placebo-controlled trial.

INTRODUCTION: Protein malnutrition after bariatric surgery is a severe complication and leads to significant morbidity. Previous studies have shown that protein intake and physical activity are the most important factors in the preservation of fat-free mass during weight loss. Low protein intake is very common in patients undergoing bariatric surgery despite dietary counseling. Protein powder supplements might help patients to achieve the protein intake recommendations after bariatric surgery and could therefore contribute to preserve fat-free mass. This double-blind randomized placebo-controlled intervention study aims to assess the effect of a daily consumed clear protein powder shake during the first 6 months after bariatric surgery on fat-free mass loss in the first 12 months after laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS AND ANALYSIS: Inclusion will take place at the outpatient clinic of the bariatric expertise center for obesity of the Maasstad Hospital. Patients will be randomly assigned to either the intervention or control group before surgery. The intervention group will receive a clear protein powder shake of 200 ml containing 20 g of whey protein dissolved in water which should be taken daily during the first 6 months after LRYGB on top of their normal postoperative diet. The control group will receive an isocaloric, clear, placebo shake containing maltodextrine. Postoperative rehabilitation and physiotherapeutical guidance will be standardized and similar in both groups. Also, both groups will receive the same dietary advice from specialized dieticians. The main study parameter is the percentage of fat-free mass loss 6 months after surgery, assessed by multi-frequency bioelectrical impedance analysis (MF-BIA). ETHICS AND DISSEMINATION: The protocol, version 2 (February 20, 2022) has been approved by the Medical Research Ethics Committees United (MEC-U) (NL 80414.100.22). The results of this study will be submitted to peer-reviewed journals. TRIAL REGISTRATION: ClinicalTrials.gov NCT05570474. Registered on October 5, 2022.

Affinity purification of a framework 1 engineered mouse/human chimeric IgA2 antibody from tobacco.

Complex multimeric proteins such as dimeric and secretory immunoglobulin A (IgA) can be difficult to produce in heterologous systems, although this has been achieved using several platforms including plants. As well as topical mucosal applications, dimeric IgA (dIgA), and secretory IgA (sIgA) can be used in tumor and anti-viral therapy, where their more potent cell-killing properties may increase their efficacy compared to current drugs based on IgG. However, the development of therapeutic IgA formats is hampered by the need to co-express four different polypeptides, and the inability to purify such molecules using conventional protein A or protein G affinity chromatography. The light chain (LC)-specific affinity ligand protein L is a potential alternative, but it only recognizes certain kappa light chain (LC(κ)) subtypes. To overcome these limitations, we have adapted a framework-grafting approach to introduce LCs that bind protein L into any IgA. As a model, we used the chimeric anti-human chorionic gonadotropin (hCG) antibody cPIPP, since this contains a murine LC((κ)) subtype that does not bind protein L. Grafting was achieved by replacing selected framework region 1 (FR1) residues in the cPIPP LC(κ) variable domain with corresponding residues from LC(κ) subtypes that can bind protein L. The grafted antibody variants were successfully purified by protein L affinity chromatography. These modifications affected neither their antigen-binding properties nor the yields achieved by transient expression in tobacco plants. Our results therefore show that LC FR1 grafting can be used as generic strategy for the purification of IgA molecules.

Pitfall in the diagnosis of endometrial cancer: case report of an endometrioid adenocarcinoma arising from uterine adenomyosis.

BACKGROUND: The development of cancer from adenomyotic foci is a rare occurrence. The diagnosis is frequently delayed because of the absence of tumor in the eutopic endometrium. CASE REPORT: We present a case of a 64-year-old postmenopausal woman with irregular vaginal bleeding and dull abdominal pain. Hysteroscopy was negative and hormonal treatment was continued. Nine months later, persisting symptoms necessitated endometrial biopsy revealing an atrophic endometrium. Hydrosonography suggested an endometrial polyp of 14 x 7 mm with a surrounding regular thin endometrium and a diffusely inhomogeneous ultrasonographic pattern throughout the myometrium. Hysteroscopic excision of the endometrial polyp was performed. Biopsies obtained during operative hysteroscopy showed a well differentiated endometrioid endometrial carcinoma. A laparoscopically assisted vaginal hysterectomy with bilateral salpingo-oophorectomy, pelvic lymphadenectomy and peritoneal cytology was performed. Pathologic examination revealed an atrophic endometrium and a Stage IB (FIGO 2009) well differentiated endometrioid endometrial carcinoma with prominent squamous differentiation originating from nodular adenomyosis. This ectopic localization of the endometrioid carcinoma added to a diagnostic delay of 12 months. CONCLUSION: Endometrial cancer arising from uterine adenomyosis may be difficult to diagnose. Awareness of this entity and careful ultrasonography are likely to reduce diagnostic delay.

Clinical characterization of non-small-cell lung cancer tumors showing neuroendocrine differentiation features.

In most cases of small-cell lung carcinomas (SCLC) phenotypic features compatible with a neuroendocrine differentiation status can be identified by monoclonal (MOC) antibody-based immunohistological procedures. Similar features can be recognized only in a minority of non-SCLC tumors. During a period of 30 months, all diagnostic non-SCLC biopsies (141 cases) were prospectively analysed for the presence of markers indicative for neuroendocrine differentiation. In 31% of all cases, such a presence could be noticed. Neuroendocrine differentiation (50% to 100% positive-staining tumor cells) was recognized more frequently in adenocarcinoma when compared to large-cell and squamous-cell carcinoma (chi 2 = 9.31, 2 degrees of freedom, P less than 0.01). To investigate whether the clinical behavior of these "neuroendocrine" non-SCLC cases mimics SCLC, a multivariate analysis for prognostic factors was performed. Among other prognostic factors, biopsies containing more than 50% positive-staining tumor cells with the MOC antibody-1 (MOC-1) were recognized as negative prognostic factors.

Human marginal zone B cells are not an activated B cell subset: strong expression of CD21 as a putative mediator for rapid B cell activation.

In the human spleen the marginal zone (MZ) contains medium-sized B cells with a distinct immunophenotype. A main function attributed to the MZ is its involvement in the primary response to blood-borne antigens, in particular to thymus-independent antigens type 2. In this study the presence of antigens related to activation and proliferation was evaluated in human spleens by immunohistochemical staining. It appeared that MZ B cells do not show interleukin 2 receptor expression, and are in G0 phase of the cell cycle, as demonstrated by the lack of Ki-67 reactivity. The most interesting finding is the high CD21 expression by MZ B cells in the absence of IgD expression. As the CD21 antigen has been shown to be involved in B cell activation in close linkage with IgM, it can be suggested that MZ B cells are particularly well equipped for rapid and easy activation in a primary immune response.

Cell density modulates growth, extracellular matrix, and protein synthesis of cultured rat mesangial cells.

Mesangial cell (MC) hyperplasia and accumulation of extracellular matrix are hallmarks of chronic glomerular disease. The present in vitro study examined the effects of cell density on growth, extracellular matrix formation, and protein synthesis of cultured rat MCs. A negative linear relationship was found between initial plating density and DNA synthesis per cell after 24 hours incubation in medium with 10% fetal calf serum (range: 1 x 10(3) to 7 x 10(5) MCs/2cm2, r = 0.996, P < 0.001). Enzyme-linked immunosorbent assay of the amount of fibronectin in the conditioned medium after 72 hours showed a negative relationship with increasing cell density. In contrast, the amount of cell-associated fibronectin increased to maximal values in confluent cultures, and no further increase was seen at supraconfluency. The relative collagen synthesis in the conditioned medium and cell layer--assessed by collagenase digestion after 5 hours [3H]proline pulse labeling--showed a similar pattern. Secreted collagen decreased with increasing cell density from 3.4% to 0.2% of total protein synthesis. In contrast, cell-associated collagen increased from 1.1% to 11.8% of newly synthesized protein until confluency followed by a decrease to 4.2% at supraconfluency. Specific immunoprecipitation of collagen types I, III, and IV revealed a significant (twofold) increase in collagen I synthesis per cell at confluency. Collagen III and IV synthesis was not affected by cell density. Specific protein expression in both the medium and cell layer were analyzed by two-dimensional polyacrylamide gel electrophoresis (150 to 20 kd, pI 5.0 to 7.0) after 20 hours steady-state metabolic labeling with [35S]methionine. Supraconfluent MCs displayed overexpression of 10, underexpression of four, new expression of five, and changed mobility of three different intracellular proteins. Of interest was the overexpression of two proteins (89 kd, pI 5.31 and 72 kd, pI 5.32) that were identified by immunoblotting as the stress proteins heat-shock protein 90 and glucose-related protein 78, respectively. The progressive increase of cell-associated fibronectin and collagens, particularly collagen type I, in confluent MCs resembles extracellular matrix accumulation in glomerular disease. The increased expression of stress proteins in supraconfluent MCs is of interest in view of the analogy between glomerulosclerosis and atherosclerosis in which stress proteins are expressed in high concentrations.

Immuno-architecture of human fetal lymphoid tissues.

Spleen, thymus and lymph node of human fetuses from the 12th to the 38rd week (spleen from 9 weeks) were investigated in an immunohistological study on B5-fixed paraffin embedded tissues, employing a panel of recently developed monoclonal antibodies, reactive with antigens resistant against fixation and paraffin embedment. The monoclonal antibodies included were MT1, MT2, MB1, MB2, MB3, LN1, LN2, LN3, LeuM1, Leu7, VIE-G4, together with polyclonal antibodies reactive with immunoglobulin heavy and light chains, and with lysozyme and S100-protein. The preservation of morphological detail together with immunoperoxidase staining of cellular subsets, allowed an accurate determination of the ontogenic development of the different cell types in situ, in relation to their micro-environment. The use of paraffin tissue reactive (monoclonal) antibodies gives an extra dimension to the study of fetal lymphoid tissues. This is of particular advantage in studies on very fragile tissues as in early embryonal and fetal ontogeny.

Immaturity of the human splenic marginal zone in infancy. Possible contribution to the deficient infant immune response.

The immune response to polysaccharide Ag as present in the capsule of certain virulent bacteria has been demonstrated to be related to a functionally intact spleen. This immune response is almost completely defective in infancy. Because of this the development of cellular compartments in the human spleen was studied immunohistologically in frozen and paraffin tissue sections of 32 infant spleens (less than 2 y of age) and 6 spleens from children. Six cases of sudden infant death syndrome and 7 cases of infection or sepsis which were included showed no significant differences compared to the other cases. Whereas all other cellular compartments have completed their maturation to an adult-type immunophenotype and morphology within the first 5 mo, the infant marginal zone B cells show essentially different features compared to the adult situation. The main characteristics of the infant marginal zone B cells are the absence of CD21-(C3d/EBV-R) expression and the high percentage of cells strongly coexpressing IgM and IgD. As the marginal zone is supposed to be the site of the initiation of the immune response to polysaccharide Ag, there is a remarkable coincidence between the first appearance of MZ B cells with adult features, and the time of acquisition of the ability to mount an immune response to polysaccharides, including encapsulated bacteria.

Vasoactive agents affect growth and protein synthesis of cultured rat mesangial cells.

Mesangial cell (MC) proliferation and extracellular matrix (ECM) formation are hallmarks of chronic glomerular disease. The present in vitro study examined the effects of the vasoactive agents angiotensin II (Ang II), arginine vasopressin (AVP), and serotonin (5-HT) on growth and protein biosynthesis of cultured rat MCs after 72 hours of incubation. AVP and 5-HT (10(-6) M) significantly increased DNA synthesis and growth of quiescent subconfluent MCs to levels of 25 and 45%, respectively, of the optimal stimulatory effect of 10% fetal calf serum (FCS) (both P less than 0.001). The mitogenic effect of Ang II was 10% of the 10% FCS effect (P less than 0.01). ECM production was studied by ELISA assay for fibronectin (FN) secreted into the culture medium (SeFN) and cell-associated FN, that is, intra- and pericellular FN (CaFN). In all incubations, highly significant negative linear relationships were found between the numbers of MCs per well and quantities of both SeFN and CaFN after normalization of the data by logarithmic transformation (SeFN: r values greater than -0.9705; CaFN: r greater than -0.9620; P less than 0.001). Thus, increasing cell densities progressively suppressed ECM formation by MCs. The ECM production was found to be independent of growth activity. AVP significantly increased SeFN (P less than 0.05) and decreased CaFN (P less than 0.001) in subconfluent cultures; Ang II and 5-HT had no effect. Metabolic labeling with 35S-methionine (18 hr, 200 microCi/ml medium) and 2-D electrophoresis of MC lysates resulted in resolution of greater than 500 different radiolabeled intracellular proteins in molecular weight from 110 to 20 Kd over an isoelectric interval of 5.0 to 7.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue distribution of the C3d/EBV-receptor: CD21 monoclonal antibodies reactive with a variety of epithelial cells, medullary thymocytes, and peripheral T-cells.

The CD21 antigen has been described to represent CR2, the receptor for the complement fragment C3d and also the receptor for the Epstein-Barr virus (EBV). Monoclonal antibodies B2, HB5, and B-ly4 belong to the CD21 cluster, recognizing different epitopes of the CD21-molecule. Immunohistology of lymphoid tissues employing these antibodies showed the known staining of B cells and dendritic reticulum cells. Surprisingly, B2, but not HB5 or B-ly4, stained a distinct spot in the cytoplasm of a major proportion of medullary thymocytes, in almost all peripheral blood lymphocytes, and in a substantial amount of cells in T-cell areas of peripheral lymphoid tissues. This distinct cytoplasmic B2 staining was confirmed by immuno-electronmicroscopy. A similar B2+ cytoplasmic dot was observed in B-lymphoblastic lymphomas. Staining of non-lymphoid tissues showed reactivity with all three CD21 mAb with epithelial cells of skin, lung, esophagus, jejunum, colon, pancreas, tonsil, adrenal cortex, renal tubuli, and parotid glands, and with hepatocytes and tongue muscle. In addition, endothelial cells of small vessels showed B2 staining. One possible explanation for our results is, that apart from the presence of B cells and follicular dendritic cells, a CD21-molecule may be expressed by other cell types. However, a maybe more likely explanation may be that the recognized epitopes are not exclusively associated with the C3d/EBV-receptor, but also with other structures. In particular should the possibility be recognized of cross-reactivity with CR2-related proteins, encoded by the large gene family, to which CR2 belongs.

Heparins modulate extracellular matrix and protein synthesis of cultured rat mesangial cells.

Heparins blunt the development of glomerulosclerosis in several disease models in the rat and this protective effect may be related to suppression of glomerular cell proliferation. In this study the direct effect of heparins on another key event in glomerulosclerosis, extracellular matrix (ECM) deposition, was examined. Standard heparin (hep) and non-anticoagulant N-desulfated acetylated heparin (DSA-hep) significantly reduced the fibronectin content in the conditioned media of subconfluent, confluent, and supraconfluent rat glomerular mesangial cells (MCs) in culture, as assessed by a sandwich ELISA technique. Both heparins significantly increased the amount of cell-associated fibronectin in sparse and subconfluent MCs. DSA-hep, but not hep, increased the fibronectin content of ECM formed by confluent and supraconfluent MCs. Using 3H-proline pulse-labeling, Hep and DSA-hep were found to significantly decrease cell-associated collagen in subconfluent but not in confluent MCs. No effects were seen on newly synthesized collagen secreted into the culture medium. Neither hep nor DSA-hep affected total protein synthesis, studied by metabolic labeling with 35S-methionine. High resolution 2-D electrophoresis (molecular weight range, 120 to 10 Kd; isoelectric interval, 5.0 to 7.0) revealed one particular intracellular protein (molecular weight 54 Kd, pI 5.91) which was consistently overexpressed in hep. Both heparins affected an identical set of another 19 different intracellular MC proteins (over-/underexpression or shift to higher molecular weights). In conclusion, the present data demonstrate the profound direct metabolic effects of hep and DSA-hep.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunohistochemical study of extracellular matrix in acute galactosamine hepatitis in rats.

A single injection of D-galactosamine hydrochloride induces acute self-limiting liver disease in rats that morphologically resembles drug-induced hepatitis in human beings. In this immunohistochemical study we examined the localization and expression of the hepatic extracellular matrix components fibronectin, laminin, collagen type I, collagen type III and collagen type IV and of the cell surface receptors (integrins) for fibronectin and laminin. Sections of liver tissue obtained at intervals of 6, 12, 18, 24, 30, 36, 48 and 72 hr and 7 and 21 days after galactosamine administration were immunostained with a panel of polyclonal monospecific antibodies and studied independently by two of us. Fibronectin was the first extracellular matrix component found to be increased, 12 hr after galactosamine injection, followed by collagen type III, and, in a later phase, collagen type IV, type I and laminin. Increased deposition of extracellular matrix was found in areas with liver cell necrosis and along sinusoids. Extracellular matrix immunoreactivity reached a maximum at 36 to 48 hr and decreased thereafter to preinjury levels 3 wk after galactosamine. Immunostaining for the fibronectin and laminin receptors revealed tissue localization identical to that of their ligands. However, the intensity of staining was opposite of that for the extracellular matrix, with a decrease of immunoreactivity after 24 to 48 hr. The observed sequence of changes in hepatic extracellular matrix proteins after galactosamine injection resembles the repair reaction in other tissues and may reflect the particular function that each carries out during the process of liver healing after toxic injury.