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A linearly ordered (LO) k-colouring of a hypergraph is a colouring of its vertices with colours 1, … , k such that each edge contains a unique maximal colour. Deciding whether an input hypergraph admits LO k-colouring with a fixed number of colours is NP-complete (and in the special case of graphs, LO colouring coincides with the usual graph colouring). Here, we investigate the complexity of approximating the "linearly ordered chromatic number" of a hypergraph. We prove that the following promise problem is NP-complete: Given a 3-uniform hypergraph, distinguish between the case that it is LO 3-colourable, and the case that it is not even LO 4-colourable. We prove this result by a combination of algebraic, topological, and combinatorial methods, building on and extending a topological approach for studying approximate graph colouring introduced by Krokhin, Opršal, Wrochna, and Živný (2023).

Goemans and Williamson designed a 0.878-approximation algorithm for Max-Cut in undirected graphs [JACM'95]. Khot, Kindler, Mosel, and O'Donnel showed that the approximation ratio of the Goemans-Williamson algorithm is optimal assuming Khot's Unique Games Conjecture [SICOMP'07]. In the problem of maximum cuts in directed graphs (Max-DiCut), in which we seek as many edges going from one particular side of the cut to the other, the situation is more complicated but the recent work of Brakensiek, Huang, Potechin, and Zwick showed that their 0.874-approximation algorithm is tight under the Unique Games Conjecture (up to a small delta)[FOCS'23]. We consider a promise version of the problem and design an SDP-based algorithm which, if given a directed graph G that has a directed cut of value rho, finds an undirected cut in G (ignoring edge directions) with value at least \rho.

Solid-state methods for cooling and heating promise a sustainable alternative to current compression cycles of greenhouse gases and inefficient fuel-burning heaters. Barocaloric effects (BCE) driven by hydrostatic pressure (p) are especially encouraging in terms of large adiabatic temperature changes (|¿T| ˜¿10 K) and isothermal entropy changes (|¿S| ˜¿100 J K-1 kg-1). However, BCE typically require large pressure shifts due to irreversibility issues, and sizeable |¿T| and |¿S| seldom are realized in a same material. Here, the existence of colossal and reversible BCE in LiCB11H12 is demonstrated near its order-disorder phase transition at ˜380 K. Specifically, for ¿p ˜ 0.23 (0.10) GPa, |¿Srev| = 280 (200) J K-1 kg-1 and |¿Trev| = 32 (10) K are measured, which individually rival with state-of-the-art BCE figures. Furthermore, pressure shifts of the order of 0.1 GPa yield huge reversible barocaloric strengths of ˜2 J K-1 kg-1 MPa-1. Molecular dynamics simulations are performed to quantify the role of lattice vibrations, molecular reorientations, and ion diffusion on the disclosed BCE. Interestingly, lattice vibrations are found to contribute the most to |¿S| while the diffusion of lithium ions, despite adding up only slightly to the entropy change, is crucial in enabling the molecular order–disorder phase transition., Postprint (published version)

A linearly ordered (LO) $k$-colouring of a hypergraph assigns to each vertex a colour from the set $\{0,1,\ldots,k-1\}$ in such a way that each hyperedge has a unique maximum element. Barto, Batistelli, and Berg conjectured that it is NP-hard to find an LO $k$-colouring of an LO 2-colourable 3-uniform hypergraph for any constant $k\geq 2$ [STACS'21] but even the case $k=3$ is still open. Nakajima and \v{Z}ivn\'{y} gave polynomial-time algorithms for finding, given an LO 2-colourable 3-uniform hypergraph, an LO colouring with $O^*(\sqrt{n})$ colours [ICALP'22] and an LO colouring with $O^*(\sqrt[3]{n})$ colours [ACM ToCT'23]. Very recently, Louis, Newman, and Ray gave an SDP-based algorithm with $O^*(\sqrt[5]{n})$ colours. We present two simple polynomial-time algorithms that find an LO colouring with $O(\log_2(n))$ colours, which is an exponential improvement., Comment: This paper is a merger of independent work by H{\aa}stad and Martinsson, and by Nakajima and \v{Z}ivn\'y respectively

A linearly ordered (LO) k-colouring of an r-uniform hypergraph assigns an integer from {1, …, k} to every vertex so that, in every edge, the (multi)set of colours has a unique maximum. Equivalently, for r = 3, if two vertices in an edge are assigned the same colour, then the third vertex is assigned a larger colour (as opposed to a different colour, as in classic non-monochromatic colouring). Barto, Battistelli, and Berg [STACS'21] studied LO colourings on 3-uniform hypergraphs in the context of promise constraint satisfaction problems (PCSPs). We show two results. First, given a 3-uniform hypergraph that admits an LO 2-colouring, one can find in polynomial time an LO k-colouring with k = O(√{nlog log n}/log n), where n is the number of vertices of the input hypergraph. This is established by building on ideas from algorithms designed for approximate graph colourings. Second, given an r-uniform hypergraph that admits an LO 2-colouring, we establish NP-hardness of finding an LO 3-colouring for every constant uniformity r ≥ 5. In fact, we determine the precise relationship of polymorphism minions for all uniformities r ≥ 3, which reveals a key difference between r = 3,4 and r ≥ 5 and which may be of independent interest. Using the algebraic approach to PCSPs, we actually show a more general result establishing NP-hardness of finding an LO (k+1)-colouring for LO k-colourable r-uniform hypergraphs for k ≥ 2 and r ≥ 5.

Megumi Hamaguchi,1 Yukari Tsubata,1 Ken Yoshihara,1 Mika Nakao,1 Yoshihiro Amano,1 Kazuhisa Nakashima,1 Takamasa Hotta,2 Tamio Okimoto,1 Shunichi Hamaguchi,3 Akihisa Sutani,4 Takeshi Isobe1 1Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University, Izumo, Shimane, Japan; 2Department of Respiratory Medicine, Shimane Prefectural Central Hospital, Izumo, Shimane, Japan; 3Department of General Medicine, Shimane University, Izumo, Shimane, Japan; 4Sutani Respiratory Clinic, Izumo, Shimane, JapanCorrespondence: Megumi Hamaguchi, Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University, 89-1, Enyacho, Izumo-shi, Shimane, Japan, Tel/Fax +81-853-20-2581, Email hs1219@med.shimane-u.ac.jpPurpose: In Japan, both a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a 13-valent pneumococcal conjugate vaccine (PCV13) are available. Although randomized controlled trials have examined the effects of pneumococcal vaccines, few epidemiological studies have investigated the onset of pneumococcal pneumonia in general practice. In Izumo, Shimane Prefecture, Japan, a public subsidy for PPSV23 inoculation began in November 2012.Patients and Methods: The subjects were pneumonia patients aged 65 and over who were admitted to a hospital in Izumo. This retrospective study analyzed the following data extracted from medical records: pneumococcal pneumonia prevalence, pneumonia severity, mortality rate, PPSV23 vaccination rate, and length of hospital stay. The 2 years before the start of the public subsidy were defined as the early phase, and the 2 years after the subsidy initiation were defined as the late phase. We compared the two phases in terms of PPSV23 vaccination rate, prevalence and severity of pneumococcal pneumonia, and mortality rate.Results: We investigated data from a total of 1188 and 1086 patients in the early and late phases, respectively. The prevalence of pneumococcal pne

The 1-in-3 and Not-All-Equal satisfiability problems for Boolean CNF formulas are two well-known NP-hard problems. In contrast, the promise 1-in-3 vs. Not-All-Equal problem can be solved in polynomial time. In the present work, we investigate this constraint satisfaction problem in a regime where the promise is weakened from either side by a rainbow-free structure, and establish a complexity dichotomy for the resulting class of computational problems., Comment: Full version of a LICS 2024 paper; v2 has a different title, abstract, and introduction

A linearly ordered (LO) $k$-colouring of a hypergraph is a colouring of its vertices with colours $1, \dots, k$ such that each edge contains a unique maximal colour. Deciding whether an input hypergraph admits LO $k$-colouring with a fixed number of colours is NP-complete (and in the special case of graphs, LO colouring coincides with the usual graph colouring). Here, we investigate the complexity of approximating the `linearly ordered chromatic number' of a hypergraph. We prove that the following promise problem is NP-complete: Given a 3-uniform hypergraph, distinguish between the case that it is LO $3$-colourable, and the case that it is not even LO $4$-colourable. We prove this result by a combination of algebraic, topological, and combinatorial methods, building on and extending a topological approach for studying approximate graph colouring introduced by Krokhin, Opr\v{s}al, Wrochna, and \v{Z}ivn\'y (2023)., Comment: full version of a paper accepted to STACS 2024 (Track A)

We present polynomial-time SDP-based algorithms for the following problem: For fixed $k \leq \ell$, given a real number $\epsilon>0$ and a graph $G$ that admits a $k$-colouring with a $\rho$-fraction of the edges coloured properly, it returns an $\ell$-colouring of $G$ with an $(\alpha \rho - \epsilon)$-fraction of the edges coloured properly in polynomial time in $G$ and $1 / \epsilon$. Our algorithms are based on the algorithms of Frieze and Jerrum [Algorithmica'97] and of Karger, Motwani and Sudan [JACM'98]. For $k = 2, \ell = 3$, our algorithm achieves an approximation ratio $\alpha = 1$, which is the best possible. When $k$ is fixed and $\ell$ grows large, our algorithm achieves an approximation ratio of $\alpha = 1 - o(1 / \ell)$. When $k, \ell$ are both large, our algorithm achieves an approximation ratio of $\alpha = 1 - 1 / \ell + 2 \ln \ell / k \ell - o(\ln \ell / k \ell) - O(1 / k^2)$; if we fix $d = \ell - k$ and allow $k, \ell$ to grow large, this is $\alpha = 1 - 1 / \ell + 2 \ln \ell / k \ell - o(\ln \ell / k \ell)$. By extending the results of Khot, Kindler, Mossel and O'Donnell [SICOMP'07] to the promise setting, we show that for large $k$ and $\ell$, assuming Khot's Unique Games Conjecture (UGC), it is \NP-hard to achieve an approximation ratio $\alpha$ greater than $1 - 1 / \ell + 2 \ln \ell / k \ell + o(\ln \ell / k \ell)$, provided that $\ell$ is bounded by a function that is $o(\exp(\sqrt[3]{k}))$. For the case where $d = \ell - k$ is fixed, this bound matches the performance of our algorithm up to $o(\ln \ell / k \ell)$. Furthermore, by extending the results of Guruswami and Sinop [ToC'13] to the promise setting, we prove that it is NP-hard to achieve an approximation ratio greater than $1 - 1 / \ell + 8 \ln \ell / k \ell + o(\ln \ell / k \ell)$, provided again that $\ell$ is bounded as before (but this time without assuming the UGC).

An unusual case of a salivary gland tumor which was formed in the mandible is described. The tumor was successfully removed by block resection of the ascending ramus of the mandible and histologically diagnosed as an acinic cell carcinoma. The clinical, radiographic and histologic findings indicated the central origin of the tumor.

A method is described for the extraction and determination of pontamine blue exuded in the skin of rabbits, in order to measure increased vascular permeability to protein. It involves four procedures, viz., (1) homogenization of the skin treated with hot trichloroacetic acid solution, (2) precipitation of gelatinized collagen with phosphotungstic acid, (3) lipid extraction with ethanol and (4) elution of the dye adsorbed to protein with aqueous pyridine and its spectrophotometric determination. Its successful application to the skin response, induced by histamine, indicates that the method can be used for the quantitative study of substances that affect vascular permeability.

An unusual mucoepidermoid tumor which occurred in the mandible is described. The tumor was successfully removed by hemimandibulectomy and neck dissection. The clinical, radiographic and histologic findings indicated the central origin of the tumor. The most probable source was assumed to be the inclusion of the retromolar mucous glands in the mandible during the course of development.

An unusual case of a salivary gland tumor which was formed in the mandible is described. The tumor was successfully removed by block resection of the ascending ramus of the mandible and histologically diagnosed as an acinic cell carcinoma. The clinical, radiographic and histologic findings indicated the central origin of the tumor.

An unusual mucoepidermoid tumor which occurred in the mandible is described. The tumor was successfully removed by hemimandibulectomy and neck dissection. The clinical, radiographic and histologic findings indicated the central origin of the tumor. The most probable source was assumed to be the inclusion of the retromolar mucous glands in the mandible during the course of development.

A method is described for the extraction and determination of pontamine blue exuded in the skin of rabbits, in order to measure increased vascular permeability to protein. It involves four procedures, viz., (1) homogenization of the skin treated with hot trichloroacetic acid solution, (2) precipitation of gelatinized collagen with phosphotungstic acid, (3) lipid extraction with ethanol and (4) elution of the dye adsorbed to protein with aqueous pyridine and its spectrophotometric determination. Its successful application to the skin response, induced by histamine, indicates that the method can be used for the quantitative study of substances that affect vascular permeability.

The complexity of the promise constraint satisfaction problem $\operatorname{PCSP}(\mathbf{A},\mathbf{B})$ is largely unknown, even for symmetric $\mathbf{A}$ and $\mathbf{B}$, except for the case when $\mathbf{A}$ and $\mathbf{B}$ are Boolean. First, we establish a dichotomy for $\operatorname{PCSP}(\mathbf{A},\mathbf{B})$ where $\mathbf{A}, \mathbf{B}$ are symmetric, $\mathbf{B}$ is functional (i.e. any $r-1$ elements of an $r$-ary tuple uniquely determines the last one), and $(\mathbf{A},\mathbf{B})$ satisfies technical conditions we introduce called dependency and additivity. This result implies a dichotomy for $\operatorname{PCSP}(\mathbf{A},\mathbf{B})$ with $\mathbf{A},\mathbf{B}$ symmetric and $\mathbf{B}$ functional if (i) $\mathbf{A}$ is Boolean, or (ii) $\mathbf{A}$ is a hypergraph of a small uniformity, or (iii) $\mathbf{A}$ has a relation $R^{\mathbf{A}}$ of arity at least 3 such that the hypergraph diameter of $(A, R^{\mathbf{A}})$ is at most 1. Second, we show that for $\operatorname{PCSP}(\mathbf{A},\mathbf{B})$, where $\mathbf{A}$ and $\mathbf{B}$ contain a single relation, $\mathbf{A}$ satisfies a technical condition called balancedness, and $\mathbf{B}$ is arbitrary, the combined basic linear programming relaxation (BLP) and the affine integer programming relaxation (AIP) is no more powerful than the (in general strictly weaker) AIP relaxation. Balanced $\mathbf{A}$ include symmetric $\mathbf{A}$ or, more generally, $\mathbf{A}$ preserved by a transitive permutation group., Comment: Full version (with stronger results) of a LICS'23 paper

A linearly ordered (LO) $k$-colouring of an $r$-uniform hypergraph assigns an integer from $\{1, \ldots, k \}$ to every vertex so that, in every edge, the (multi)set of colours has a unique maximum. Equivalently, for $r=3$, if two vertices in an edge are assigned the same colour, then the third vertex is assigned a larger colour (as opposed to a different colour, as in classic non-monochromatic colouring). Barto, Battistelli, and Berg [STACS'21] studied LO colourings on $3$-uniform hypergraphs in the context of promise constraint satisfaction problems (PCSPs). We show two results. First, given a 3-uniform hypergraph that admits an LO $2$-colouring, one can find in polynomial time an LO $k$-colouring with $k=O(\sqrt[3]{n \log \log n / \log n})$. Second, given an $r$-uniform hypergraph that admits an LO $2$-colouring, we establish NP-hardness of finding an LO $k$-colouring for every constant uniformity $r\geq k+2$. In fact, we determine relationships between polymorphism minions for all uniformities $r\geq 3$, which reveals a key difference between $r

The Fisher integral is the normalizing constant of a statistical model on the special orthogonal group. In this paper, we discuss a system of differential equations for the Fisher integral. Especially, we explicitly give a set of linear differential operators which generates the annihilating ideal of the Fisher integral, and we show that the annihilating ideal is a maximal left ideal of the ring of differential operators with polynomial coefficients. The Fisher integral for diagonal matrices is related to the hypergeometric function of matrix arguments. We also give a new approach to get differential operators annihilating the Fisher integral for the diagonal matrix.

Background : Although platinum-combination chemotherapy is widely used to treat advanced non-small cell lung cancer (NSCLC), not all elderly patients benefit from this regimen. In this retrospective study, we aimed to evaluate whether the Glasgow Prognostic Score (GPS), an indicator of systemic inflammation and malnutrition, could predict the tolerability and efficacy of platinum-combination chemotherapy among elderly patients with NSCLC. Methods : The eligibility criteria included patients aged ≥ 70 years with NSCLC treated with first-line platinum-combination chemotherapy at Shimane University Hospital between January 2015 and December 2018. Results : Thirty-two patients with NSCLC (median age, 74 years) were included. The GPS scores were 0–1 for 19 patients and 2 for 13 patients. Four chemotherapy cycles were completed by 57.9% and 30.8% of patients in the GPS 0–1 and GPS 2 groups, respectively. The GPS 0–1 group experienced better outcomes than the GPS 2 group (response rate : 26% vs. 15%, P = 0.67 ; median progression-free survival : 4.1 vs. 2.1 months, P = 0.0026 ; median overall survival : 22.8 vs. 9.6 months, P = 0.0092). Conclusions : Platinum-combination chemotherapy demonstrated promising efficacy among elderly NSCLC patients with a GPS 0–1. Therefore, GPS may be crucial in determining whether treatments recommended for younger patients are suitable for older patients with NSCLC.

Traditional refrigeration technologies based on compression cycles of greenhouse gases pose serious threats to the environment and cannot be downscaled to electronic device dimensions. Solid-state cooling exploits the thermal response of caloric materials to changes in the applied external fields (i.e., magnetic, electric and/or mechanical stress) and represents a promising alternative to current refrigeration methods. However, most of the caloric materials known to date present relatively small adiabatic temperature changes (|¿T|~1 to 10 K) and/or limiting irreversibility issues resulting from significant phase-transition hysteresis. Here, we predict by using molecular dynamics simulations the existence of colossal barocaloric effects induced by pressure (isothermal entropy changes of |¿S|~100 J K-1 kg-1) in the energy material Li2B12H12. Specifically, we estimate |¿S|=367 J K-1 kg-1 and |¿T|=43 K for a small pressure shift of P = 0.1 GPa at T=480 K. The disclosed colossal barocaloric effects are originated by a fairly reversible order–disorder phase transformation involving coexistence of Li+ diffusion and (BH)-212 reorientational motion at high temperatures., Peer Reviewed, Postprint (published version)

We have performed angle-resolved photoemission spectroscopy (ARPES) on layered ternary compounds ZrGeXc (X-c = S, Se, and Te) with square Ge lattices. ARPES measurements with bulk-sensitive soft-x-ray photons revealed a quasi-two-dimensional bulk-band structure with the bulk nodal loops protected by glide mirror symmetry of the crystal lattice. Moreover, high-resolution ARPES measurements near the Fermi level with vacuum-ultraviolet photons combined with first-principles band-structure calculations elucidated a Diracnode-arc surface state traversing a tiny spin-orbit gap associated with the nodal loops. We found that this surface state commonly exists in ZrGeXc despite the difference in the shape of nodal loops. The present results suggest that the spin-orbit coupling and the multiple nodal loops cooperatively play a key role in creating the exotic Dirac-node-arc surface states in this class of topological line-node semimetals.

Purpose We assessed the efficacy of palonosetron (PAL) in comparison to granisetron (GRA) for the treatment of CINV using the self-assessment questionnaires. In addition, we analyzed the serum levels of emetic various biomarkers. Methods We conducted a randomized study of 70 patients naïve to chemotherapy. The primary endpoint was the late phase score on the MAT questionnaire. The plasma concentrations of the biomarkers were measured on days 1 and 3. Results There were no statistical differences in the scores on the questionnaires, but the mean values in response to PAL were higher than those in response to GRA. The value of ghrelin on day 1 was significantly higher for GRA than for PAL. Conclusions For the primary endpoint, the score of the late phase on the MAT questionnaire was not statistically different between the PAL and GRA treatment groups. Further studies are needed to clarify the role of ghrelin for the treatment of CINV.

Background Various procedures for bronchoalveolar lavage (BAL) have been developed. BAL needs a wedge between the bronchoscope and the inner surface of the bronchus. The feasibility of performing BAL at the targeted position cannot be determined until immediately before the procedure. We examined BAL performed using a balloon catheter to evaluate the stability of the procedure itself and quality of the specimen obtained. Methods The main inclusion criteria were diffuse lung disease with a shadow in the B5a area. The tip of a disposable balloon catheter was passed through the orifice of the B5a bronchus, and the balloon was expanded at the B5a bronchus. A 50-mL syringe containing saline was instilled, and gentle hand suction was performed. This procedure was repeated two more times (total: 150 mL). Results In all the 13 patients, the balloon of the catheter was inflated at the B5a bronchus. The median recovery rate was 34.92% ± 13.22%. These values were comparable to previously obtained BAL data (control group, N = 56) from our facility. The BAL fluid findings and final diagnosis, with the exception of one undiagnosed case, were consistent. Overall, four patients suffered an adverse event during BAL (hypoxemia). All cases were managed by increasing the oxygen flow rate, and the adverse event did not affect the subsequent examinations. Conclusions Using a balloon catheter enabled us to perform BAL at the intended bronchus. The quality of the obtained specimen was also acceptable.

We have performed angle-resolved photoemission spectroscopy (ARPES) on layered ternary compounds ZrGeXc (X-c = S, Se, and Te) with square Ge lattices. ARPES measurements with bulk-sensitive soft-x-ray photons revealed a quasi-two-dimensional bulk-band structure with the bulk nodal loops protected by glide mirror symmetry of the crystal lattice. Moreover, high-resolution ARPES measurements near the Fermi level with vacuum-ultraviolet photons combined with first-principles band-structure calculations elucidated a Diracnode-arc surface state traversing a tiny spin-orbit gap associated with the nodal loops. We found that this surface state commonly exists in ZrGeXc despite the difference in the shape of nodal loops. The present results suggest that the spin-orbit coupling and the multiple nodal loops cooperatively play a key role in creating the exotic Dirac-node-arc surface states in this class of topological line-node semimetals.

We study theoretically the electronic band structure of (PbSe)(5)(Bi2Se3)(6), which consists of an ordinary insulator PbSe and a topological insulator Bi2Se3. The first-principles calculations show that this material has a gapped Dirac-cone energy dispersion inside the bulk, which originates from the topological states of Bi2Se3 layers encapsulated by PbSe layers. Furthermore, we calculate the band structures of (BixPb1-x Se)(5)(Bi2Se3)(6) with Bi-Pb antisite defects included in the PbSe layers. The result shows that a high density of Bi-Pb defects can exist in real materials, consistent with the experimentally estimated x of more than 30%. The BiPb defects strongly modify the band alignment between Bi2Se3 and PbSe layers, while the topological interface states of Bi2Se3 are kept as a gapped Dirac-cone-like dispersion.

Background: Alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9, given every 2 weeks (Q2W), significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in Japanese hypercholesterolemic patients on background statin. We evaluated alirocumab 150 mg every 4 weeks (Q4W) in patients on lowest-dose statin or non-statin lipid-lowering therapy (LLT). Methods: ODYSSEY NIPPON was a double-blind study conducted in Japanese patients with LDL-C≥100 mg/dL (heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with coronary heart disease) or ≥120 mg/dL (non-familial hypercholesterolemia, Japan Atherosclerosis Society category III) on atorvastatin 5 mg/day or non-statin LLT. Patients were randomized (1:1:1) to subcutaneous alirocumab 150 mg Q4W, alirocumab 150 mg Q2W, or placebo for the 12-week double-blind treatment period (DBTP), followed by a 52-week open-label treatment period (OLTP). At entry into the OLTP, patients received alirocumab 150 mg Q4W, with possible up-titration to 150 mg Q2W at Week 24. Results: Least-square mean percent change in LDL-C from baseline at Week 12 (primary efficacy endpoint) was -43.8% for alirocumab Q4W, -70.1% for Q2W, and -4.3% for placebo. During the OLTP, mean LDL-C change from baseline was -45.1% at Week 20, with a further reduction at Week 36, with achieved levels maintained to Week 64. Percent of patients with≥1 adverse event (DBTP) was 51.9% with alirocumab Q4W, 47.2% with Q2W, and 46.4% with placebo. Most common adverse events were infections and infestations (25.9%, 22.6%, 17.9%, respectively), gastrointestinal disorders (13.0%, 9.4%, 12.5%), nervous system disorders (5.6%, 7.5%, 10.7%), and general disorders and administration-site conditions (3.7%, 11.3%, 5.4%). Conclusions: Hypercholesterolemic Japanese patients who tolerate only lowest-strength dose statin or non-statin LLT can achieve robust LDL-C reduction with alirocumab 150 mg Q4W, in addition to thei

We study theoretically the electronic band structure of (PbSe)(5)(Bi2Se3)(6), which consists of an ordinary insulator PbSe and a topological insulator Bi2Se3. The first-principles calculations show that this material has a gapped Dirac-cone energy dispersion inside the bulk, which originates from the topological states of Bi2Se3 layers encapsulated by PbSe layers. Furthermore, we calculate the band structures of (BixPb1-x Se)(5)(Bi2Se3)(6) with Bi-Pb antisite defects included in the PbSe layers. The result shows that a high density of Bi-Pb defects can exist in real materials, consistent with the experimentally estimated x of more than 30%. The BiPb defects strongly modify the band alignment between Bi2Se3 and PbSe layers, while the topological interface states of Bi2Se3 are kept as a gapped Dirac-cone-like dispersion.

Nonlinear optical nanostructured materials are gaining increased interest as optical limiters for various applications, although many of them suffer from reduced efficiencies at high‐light fluences due to photoinduced deterioration. The nonlinear optical properties of ferrite core/shell nanoparticles showing their robustness for ultrafast optical limiting applications are reported. At 100 fs ultrashort laser pulses the effective two‐photon absorption (2PA) coefficient shows a nonmonotonic dependence on the shell thickness, with a maximum value obtained for thin shells. In view of the local electric field confinement, this indicates that core/shell is an advantageous morphology to improve the nonlinear optical parameters, exhibiting excellent optical limiting performance with effective 2PA coefficients in the range of 10−12 cm W−1 (100 fs excitation), and optical limiting threshold fluences in the range of 1.7 J cm−2. These values are comparable to or better than most of the recently reported optical limiting materials. The quality of the open aperture Z‐scan data recorded from repeat measurements at intensities as high as 35 TW cm−2, indicates their considerably high optical damage thresholds in a toluene dispersion, ensuring their robustness in practical applications. Thus, the high photostability combined with the remarkable nonlinear optical properties makes these nanoparticles excellent candidates for ultrafast optical limiting applications.

Background: Statins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), which can produce substantial and sustained reductions of low-density lipoprotein cholesterol (LDL-C). Methods: The randomized, double-blind, placebo-controlled, parallel-group, phase 3 ODYSSEY NIPPON study will explore alirocumab 150 mg every 4 weeks (Q4W) in 163 Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin (5 mg/day) or are receiving a non-statin lipid-lowering therapy (LLT) (fenofibrate, bezafibrate, ezetimibe, or diet therapy alone). Hypercholesterolemia is defined as LDL-C ≥ 100 mg/dL (2.6 mmol/L) in patients with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with a history of documented coronary heart disease, or ≥120 mg/dL (3.1 mmol/L) in patients with non-familial hypercholesterolemia classified as primary prevention category III (i.e. high-risk patients). During the 12-week double-blind treatment period, patients will be randomized (1:1:1) to receive alirocumab subcutaneously (SC) 150 mg Q4W alternating with placebo for alirocumab Q4W, or alirocumab 150 mg SC every 2 weeks (Q2W), or SC placebo Q2W. The primary efficacy endpoint is the percentage change in calculated LDL-C from baseline to week 12. The long-term safety and tolerability of alirocumab will also be investigated. Discussion: The ODYSSEY NIPPON study will provide insights into the efficacy and safety of alirocumab 150 mg Q4W or 150 mg Q2W among Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin, or are receiving a non-statin LLT (including diet therapy alone).

CONTEXT: Euphorbia hirta L. (Euphorbiaceae) has been used as a folk remedy in Southeast Asia for the treatment of various ailments. OBJECTIVE: The current study evaluates the cytotoxicity, cell-cycle arrest, and apoptotic induction by E. hirta in MCF-7 breast cancer cells. MATERIALS AND METHODS: Cytotoxic activity of methanol extract of whole part of E. hirta was determined by the MTT assay at various concentrations ranging from 1.96 to 250.00 µg/mL in MCF-7 cells. Cell morphology was assessed by light and fluorescence microscopy. Apoptosis and cell-cycle distribution were determined by annexin V staining and flow cytometry. DNA fragmentation, caspase activity, and reactive oxygen species (ROS) assays were performed using the commercially available kits. To identify the cytotoxic fraction, E. hirta extract was subjected to bioassay-guided fractionation. RESULTS: Euphorbia hirta exhibited significant inhibition of the survival of MCF-7 cells and the half inhibitory concentration (IC50) values was 25.26 µg/mL at 24 h. Microscopic studies showed that E. hirta-treated cells exhibited marked morphological features characteristic of apoptosis. Euphorbia hirta extract also had an ignorable influence on the LDH leakage and generating intracellular ROS. The flow cytometry study confirmed that E. hirta extract induced apoptosis in MCF-7 cells. Euphorbia hirta also resulted in DNA fragmentation in MCF-7 cells. Moreover, E. hirta treatment resulted in the accumulation of cells at the S and G2/M phases as well as apoptosis. The caspase activity study revealed that E. hirta extract induced apoptosis through the caspase-3-independent pathway by the activation of caspase-2, 6, 8, and 9. Euphorbia hirta hexane fraction, namely HFsub4 fraction, demonstrated highest activity among all the fractions tested with an IC50 value of 10.01 µg/mL at 24 h. DISCUSSION AND CONCLUSION: This study revealed that E. hirta induced apoptotic cell de