This paper gives a geometric interpretation of bordered Heegaard Floer homology for manifolds with torus boundary. If M is such a manifold, we show that the type D structure CFD(M ) may be viewed as a set of immersed curves decorated with local systems in ∂M . These curves-with-decoration are invariants of the underlying three-manifold up to regular homotopy of the curves and isomorphism of the local systems. Given two such manifolds and a homeomorphism h between the boundary tori, the Heegaard Floer homology of the closed manifold obtained by gluing with h is obtained from the Lagrangian intersection Floer homology of the curve-sets. This machinery has several applications: We establish that the dimension of HF decreases under a certain class of degree one maps (pinches) and we establish that the existence of an essential separating torus gives rise to a lower bound on the dimension of HF . In particular, it follows that a prime rational homology sphere Y with HF (Y ) < 5 must be geometric. Other results include a new proof of Eftekhary's theorem that L-space homology spheres are atoroidal; a complete characterisation of toroidal L-spaces in terms of gluing data; and a proof of a conjecture of Hom, Lidman, and Vafaee on satellite L-space knots.

Intratumor heterogeneity may contribute to the ambiguous clinical results on PD-L1 status as a predictor for immunotherapy response in patients with HNSCC. This decreases the utility of PD-L1 expression from single tumour biopsies as a predictive biomarker. In this prospective study, intratumor heterogeneity of PD-L1 expression in HNSCC was investigated with both Tumour Proportion Score (TPS) and Combined Positive Score (CPS). Thirty-three whole surgical specimens from 28 patients with HNSCC were included. PD-L1 expression in six random core biopsies from each surgical specimen was used to assess the concordance between multiple biopsies and the negative predictive value of a single negative core biopsy. With 1% cut off, 36% of the specimens were concordant with TPS and 52% with CPS. With a 50% cut-off value the concordance was 70% with TPS and 55% with CPS. Defining a tumour as positive if just a single-one of the biopsies was positive, the negative predictive value (NPV) of a single negative core biopsy was 38.9 and 0% (1% cut off), and 79.9% and 62.8% (50% cut off) for TPS and CPS, respectively. In conclusion, PD-L1 positivity varies markedly within the tumour, both with TPS and CPS, challenging the utility of this biomarker.

Background: Amphipathic helices preferentially bind highly curved lipid membranes, providing a method of protein sorting. Results: Curvature sensing requires the insertion of hydrophobic residues and is modulated by electrostatic interactions. Conclusion:The relative strength of hydrophobic and electrostatic membrane interactions determines whether helix-containing proteins sense curvature. Significance: Sensing cannot be described through simple physicochemical properties but depends on the total sum of membrane interactions.

Methods for site-selective chemistry on proteins are in high demand for the synthesis of chemically modified biopharmaceuticals, as well as for applications in chemical biology, biosensors and more. Inadvertent N-terminal gluconoylation has been reported during expression of proteins with an N-terminal His tag. Here we report the development of this side-reaction into a general method for highly selective N-terminal acylation of proteins to introduce functional groups. We identify an optimized N-terminal sequence, GHHHn− for the reaction with gluconolactone and 4-methoxyphenyl esters as acylating agents, facilitating the introduction of functionalities in a highly selective and efficient manner. Azides, biotin or a fluorophore are introduced at the N-termini of four unrelated proteins by effective and selective acylation with the 4-methoxyphenyl esters. This Gly-Hisn tag adds the unique capability for highly selective N-terminal chemical acylation of expressed proteins. We anticipate that it can find wide application in chemical biology and for biopharmaceuticals.

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Major surgery evokes an endocrine stress response, characterized by increased serum cortisol, plasma adrenaline and noradrenaline. Furthermore, surgical stress is accompanied by lymphopenia and granulocytosis in peripheral blood. The changes in peripheral white blood cells have been demonstrated after surgery as well as after cortisol infusion. The aim of the present study was to investigate to which tissues/organs peripheral blood lymphocytes are redistributed after major surgery. From 20 rabbits lymphocytes were isolated from peripheral blood, labelled with indium-111-tropolene and reinjected intravenously into the rabbits. Ten of the rabbits underwent major surgery (upper laparatomy) during general anaesthesia, while the control group (n = 10) was anaesthetized without surgery. The endocrine stress response to surgery was measured as serum cortisol, plasma adrenaline and noradrenaline. The redistribution of lymphocytes was imaged with a gamma camera and calculated with a connected computer before, 2, 4, and 7 h after the skin incision. Compared to preoperative values, laparotomy resulted in an increase in serum cortisol from 116.6 to 461.9 nmol/l (mean) and a decrease in the fraction/percentage of lymphocytes in peripheral blood from 43.8% to 14.7% 7 h after surgery. Simultaneously, the activity of the heart and lungs together decreased to 76.1% of initial values, while the spleen activity was unaffected. The radioactivity of the lymphatic tissue increased to 137.8% and 134.7%, respectively, 4 and 7 h after the start of surgery. The results indicate that major surgery induces a redistribution of lymphocytes from peripheral blood to lymphatic tissue. It is suggested that the endocrine stress response may be of major importance.

A CT scan is not a valid criterion for sinus surgery in CF patients.

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