Physical mechanism of core-collapse supernovae that neutrinos drive.

The current understanding of the mechanism of core-collapse supernovae (CCSNe), one of the most energetic events in the universe associated with the death of massive stars and the main formation channel of compact objects such as neutron stars and black holes, is reviewed for broad readers from different disciplines of science who may not be familiar with the object. Therefore, we emphasize the physical aspects than the results of individual model simulations, although large-scale high-fidelity simulations have played the most important roles in the progress we have witnessed in the past few decades. It is now believed that neutrinos are the most important agent in producing the commonest type of CCSNe. The so-called neutrino-heating mechanism will be the focus of this review and its crucial ingredients in micro- and macrophysics and in numerics will be explained one by one. We will also try to elucidate the remaining issues.

[Cowden syndrome in a male patient with metachronous triple cancers and various clinical features:a case report].

A 66-year-old male patient with a thyroid and nasopharyngeal cancer history visited our hospital because of a positive fecal occult blood test. Total colonoscopy detected sessile or subpedunculated polyps in the ascending colon, sigmoid colon, and rectum. These polyps were endoscopically resected, and the rectal polyp was pathologically diagnosed as adenocarcinoma in adenoma and the others as adenomas. Additionally, multiple sessile lesions were revealed in the sigmoid colon and rectum. A complete gastrointestinal tract examination revealed multiple foci of glycogenic acanthosis in the esophagus, multiple sessile lesions in the stomach, multiple sessile lesions, clubbings (rod-shaped lesions), and venous malformations in the small bowel. Mucocutaneous examination indicated hemangiomas on the body trunk, patchy pigmentation on the glans penis, and keratotic papules in the inguinal region. The National Comprehensive Cancer Network diagnostic criteria for Cowden syndrome were used in this case. The patient met four major and two minor criteria;thus, Cowden syndrome was diagnosed. Moreover, the patient was had phosphatase and tensin homolog deleted on chromosome 10 gene mutation. This is the first reported case of metachronal triple cancers in a male patient with Cowden syndrome, and our results indicate the importance of cancer surveillance.

Time-strain inseparability in multiaxial stress relaxation of supramolecular gels formed via host-guest interactions.

Supramolecular hydrogels utilizing host-guest interactions (HG gels) exhibit large deformability and pronounced viscoelasticity. The inclusion complexes between ß-cyclodextrin (host) and adamantane (guest) units on the water-soluble polymers form transient bonds. The HG gels show significant stress relaxation with finite equilibrium stress following the step strain. The stress relaxation process reflects the detachment dynamics of the transient bonds which sustain the initial stress, while the finite equilibrium stress is preserved by the permanent topological cross-links with a rotaxane structure. Nonlinear stress relaxation experiments in biaxial stretching with various combinations of two orthogonal strains unambiguously reveal that time and strain effects on stress are not separable. The relaxation is accelerated for a short time frame (<102 s) with an increase in the magnitude of strain, whereas it is retarded for a longer time window with an increase in the anisotropy of the imposed biaxial strain. The time-strain inseparability in the HG gels is in contrast to the simple nonlinear viscoelasticity of a dual cross-link gel with covalent and transient cross-links in which the separability was previously validated by the same assessment. We currently interpret that the significant susceptibility of the detachment dynamics to the deformation type results from the structural characteristics of the HG gels, i.e., the host and guest moieties covalently connected to the network chains, the considerably low concentrations (<0.1 M) of these moieties, and the slidability of the permanent rotaxane cross-links.

Synergetic improvement in the mechanical properties of polyurethanes with movable crosslinking and hydrogen bonds.

Polyurethane (PU) materials with movable crosslinking were prepared by a typical two-step synthetic process using an acetylated γ-cyclodextrin (TAcγCD) diol compound. The soft segment of PU is polytetrahydrofuran (PTHF), and the hard segment consists of hexamethylene diisocyanate (HDI) and 1,3-propylene glycol (POD). The synthesized PU materials exhibited the typical mechanical characteristics of a movable crosslinking network, and the presence of hydrogen bonds from the urethane bonds resulted in a synergistic effect. Two kinds of noncovalent bond crosslinking increased the Young's modulus of the material without affecting its toughness. Fourier transform infrared spectroscopy and X-ray scattering measurements were performed to analyze the effect of introducing movable crosslinking on the internal hydrogen bond and the microphase separation structure of PU, and the results showed that the carbonyl groups on TAcγCD could form hydrogen bonds with the PU chains and that the introduction of movable crosslinking weakened the hydrogen bonds between the hard segments of PU. When stretched, the movable crosslinking of the PU materials suppressed the orientation of polymer chains (shish-kebab orientation) in the tensile direction. The mechanical properties of the movable crosslinked PU materials show promise for future application in the industrial field.

Multi-energy dissipation mechanisms in supramolecular hydrogels with fast and slow relaxation modes.

Reversible cross-links by non-covalent bonds have been widely used to produce supramolecular hydrogels that are both tough and functional. While various supramolecular hydrogels with several kinds of reversible cross-links have been designed for many years, a universal design that would allow control of mechanical and functional properties remains unavailable. The physical properties of reversible cross-links are usually quantified by thermodynamics, dynamics, and bond energies. Herein, we investigated the relationship between the molecular mobility and mechanical toughness of supramolecular hydrogels consisting of two kinetically distinct reversible cross-links via host-guest interactions. The molecular mobility was quantified as the second-order average relaxation time (〈τ〉w) of the reversible cross-links. We discovered that hydrogels combining fast (〈τ〉w = 1.8 or 18 s) and slowly (〈τ〉w = 6.6 × 103 or 9.5 × 103 s) reversible cross-links showed increased toughness compared to hydrogels with only one type of cross-link because relaxation processes in the former occurred with wide timescales.

[A case of chronic enteropathy associated with SLCO2A1 gene diagnosed by capsule endoscopy and successfully treated by ferric carboxymaltose].

Chronic non-specific multiple ulcers of the small intestine is a disease condition postulated in Japan. It is an uncommon gastrointestinal disease that causes chronic anemia and hypoalbuminemia by causing numerous ulcers without any histopathologically identifiable features. In recent years, it has been revealed that the mutations of SLCO2A1, which codes the prostaglandin transporter protein, are the cause of this disease;it is called the new name "chronic enteropathy associated with SLCO2A1 gene." The ileum, except the terminal ileum, is the most common place making it difficult to identify major lesions. Other than conservative treatments, such as nutrition therapy and iron supplements, no effective treatment has been identified so far. We present a case of chronic non-specific multiple ulcers of the small intestine diagnosed by capsule endoscopy and effectively treated by ferric carboxymaltose. A 48-year-old female had chronic iron deficiency anemia since around the age of 15. Because of severe anemia, the patient had upper and lower endoscopy at the age of 47 to find the source of the bleeding, but it was not detected. Except for the terminal ileum, the capsule endoscopy revealed ring-like ulcers, tape-like ulcers, and oblique ulcer scars in the ileum. Genetic analysis showed a homozygous mutation in intron 7, c.940+1G>A, indicating a definitive diagnosis of non-specific multiple ulcers of the small intestine. Anemia and anemia-related symptoms such as general malaise persisted despite continuous oral administration of iron drugs. Three intravenous injections of ferric carboxymaltose increased hemoglobin and enhanced the symptoms.

Supramolecular Biocomposite Hydrogels Formed by Cellulose and Host-Guest Polymers Assisted by Calcium Ion Complexes.

Hydrogels are biocompatible polymer networks; however, they have the disadvantage of having poor mechanical properties. Herein, the mechanical properties of host-guest hydrogels were increased by adding a filler and incorporating other noncovalent interactions. Cellulose was added as a filler to the hydrogels to afford a composite. Citric acid-modified cellulose (CAC) with many carboxyl groups was used instead of conventional cellulose. The preparation began with mixing an acrylamide-based αCD host polymer (p-αCD) and a dodecanoic acid guest polymer (p-AADA) to form supramolecular hydrogels (p-αCD/p-AADA). However, when CAC was directly added to p-αCD/p-AADA to form biocomposite hydrogels (p-αCD/p-AADA/CAC), it showed weaker mechanical properties than p-αCD/p-AADA itself. This was caused by the strong intramolecular hydrogen bonding (H-bonding) within the CAC, which prevented the CAC reinforcing p-αCD/p-AADA in p-αCD/p-AADA/CAC. Then, calcium chloride solution (CaCl2) was used to form calcium ion (Ca2+) complexes between the CAC and p-αCD/p-AADA. This approach successfully created supramolecular biocomposite hydrogels assisted by Ca2+ complexes (p-αCD/p-AADA/CAC/Ca2+) with improved mechanical properties relative to p-αCD/p-AADA hydrogels; the toughness was increased 6-fold, from 1 to 6 MJ/m3. The mechanical properties were improved because of the disruption of the intramolecular H-bonding within the CAC by Ca2+ and subsequent complex formation between the carboxyl groups of CAC and p-AADA. This mechanism is a new approach for improving the mechanical properties of hydrogels that can be broadly applied as biomaterials.

Predictive Factors for Rebleeding after Negative Capsule Endoscopy among Patients with Overt Obscure Gastrointestinal Bleeding.

BACKGROUND: Although capsule endoscopy (CE) is useful to evaluate obscure gastrointestinal bleeding (OGIB), CE does not always identify the responsible lesions in patients with overt OGIB. OBJECTIVES: To identify factors predictive of rebleeding after negative CE in patients with overt OGIB. METHODS: We retrospectively analyzed the clinical data of 221 patients who underwent CE for overt OGIB. Among 120 patients with negative CE findings, clinical course of 112 patients after CE was followed-up. Clinical factors associated with rebleeding after negative CE and lesions responsible for rebleeding were investigated. RESULTS: Rebleeding was identified in 37 patients (33.0%) during follow-up after negative CE, and 36 patients (32.1%) developed rebleeding within 24 months after negative CE. Multivariate analyses showed that ongoing overt OGIB (OR 2.67; 95% CI 1.07-5.80; p = 0.036) and severe anemia at the initial CE examination (OR 2.54; 95% CI 1.33-4.96; p = 0.005) were independent factors -associated with rebleeding. Rebleeding source was detected in 13 patients. CONCLUSIONS: Rebleeding is not a rare condition among patients with overt OGIB after negative CE. Patients with ongoing overt OGIB or severe anemia at the initial CE examination seem to have a higher risk of rebleeding.

Risk factors for reflux esophagitis after eradication of Helicobacter pylori.

Objective: While there is an association between successful eradication of Helicobacter pylori (HP) and reflux esophagitis (RE), risk factors associated with RE remain obscure. The aim of this study is to determine risk factors associated with the development of RE after HP eradication.Materials and methods: Among all patients treated with successful HP eradication from 2008 to 2016, we retrospectively analyzed those who were free from RE at initial esophagogastroduodenoscopy (EGD) and who were followed up with EGD after eradication. Patients were classified according to the presence or absence of RE at the follow-up EGD. RE was defined as mucosal breaks proximal to the squamous-columnar junction. Demographic data, underlying diseases, medications and endoscopic findings at the initial EGD were compared between patients with and without RE.Results: Among 1575 patients, 142 (9.0%) had RE at the follow-up EGD. The time interval from HP eradication until EGD ranged from 4 to 24 months. The endoscopic grade of RE was higher in males than in females. Multivariate analysis revealed that male sex (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.24), body mass index ≥25 kg/m2 (OR, 2.91; 95% CI, 2.00-4.22), use of calcium channel blockers (OR, 1.70; 95% CI, 1.12-2.55), and hiatal hernia (OR, 3.46; 95% CI, 2.41-5.00) were associated with the development of RE.Conclusions: Calcium channel blocker use was found to be a risk factor for the development of RE after eradication of HP.

Solvent-Free Photoresponsive Artificial Muscles Rapidly Driven by Molecular Machines.

We prepared photoresponsive actuators as both hydrogels and dry gels consisting of 4-arm poly(ethylene glycol) (PEG) cross-linked by a [c2]daisy chain, which is a double-threaded [2]rotaxane dimer with α-cyclodextrin (αCD) and stilbene. The obtained gels showed fast and large deformation triggered by UV irradiation in both wet and dry states. The UV/vis spectroscopy results, NMR measurements and tensile tests on the gels revealed that the actuation is driven by photoisomerization of the stilbene unit in the [c2]daisy chain. The responsiveness of these gels depends on the molecular weight of the 4-arm PEG. These results suggest that αCD recognizes trans-stilbene prior to UV irradiation to maintain the length of the PEG chain in the polymer network and that photoisomerization allows αCD to leave the cis-stilbene moiety and move onto the PEG chain because the association constant of αCD with cis-stilbene is quite low. Thus, the sliding motion of the αCD unit shrinks the [c2]daisy chain, leading to the contraction of the gels. In both wet and dry states, these actuations are repeatable through reversible photoisomerization of the stilbene moiety using different wavelengths of UV-light irradiation and can be used to perform bending and lifting actions (for 15 times heavier weight compared to the dry gel).

Continuing use of antithrombotic medications for patients with bleeding gastroduodenal ulcer requiring endoscopic hemostasis: a case-control study.

OBJECTIVE: The aim of this study was to compare clinical characteristics and outcomes of bleeding gastroduodenal ulcer between patients taking antithrombotic medications and those not taking antithrombotic medications. METHODS: We performed a case-control study of 346 patients with endoscopically verified bleeding gastroduodenal ulcer, which included 173 cases taking antithrombotic medications throughout peri-bleeding period and 173 age- and sex-matched controls not taking antithrombotic medications. RESULTS: The cases showed less frequent Helicobacter pylori (H. pylori) infections (45.1% versus 60.7%, p = .005), more frequent duodenal location (31.8% versus 19.1%, p = .009), and more frequent rebleeding (13.9% versus 5.8%, p = .02) than the controls. Multivariate analysis revealed that duodenal location (odds ratio [OR] 3.01, 95% confidence interval [CI] 1.37-6.65) and use of antithrombotic medications (OR 2.47, 95% CI 1.13-5.77) were independent factors for rebleeding. However, there were no differences in clinical outcomes, including final successful endoscopic hemostasis, need for surgical intervention, and mortality between cases and controls. Thromboembolic events did not occur in any cases and controls during the periendoscopic period. CONCLUSIONS: Low prevalence of H. pylori infection, frequent duodenal location, and high rebleeding rate are characteristics of patients with bleeding gastroduodenal ulcer under antithrombotic medications. Continuation of antithrombotic medications can be accepted for bleeding gastroduodenal ulcer.

Supramolecular Polymeric Materials Containing Cyclodextrins.

Smart design of polymeric materials may lead to intelligent materials exhibiting unique functional properties. Looking at nature, living systems use specific and reversible intermolecular interactions in realizing complex functions. Hence reversible bonds based on selective molecular recognition can impart artificial materials with unique functional properties. This review mainly focuses on supramolecular polymeric materials based on cyclodextrin-based host-guest interactions. Polymeric materials using molecular recognition at polymer main chain, side chain, and termini are described. Polymers carrying host and guest residues exhibit unique properties such as: 1) formation of macroscopic self-assembly of polymer gels carrying host and guest residues; 2) stimuli-responsive self-healing properties due to the reversible nature of host-guest interactions; and 3) macroscopic motion of artificial muscle cross-linked by host-guest interaction controlled by external stimuli. An overview of recent developments in this new frontier between materials science and life science is given.

Highly Flexible, Tough, and Self-Healing Supramolecular Polymeric Materials Using Host-Guest Interaction.

Flexible, tough, and self-healable polymeric materials are promising to be a solution to the energy problem by substituting for conventional heavy materials. A fusion of supramolecular chemistry and polymer chemistry is a powerful method to create such intelligent materials. Here, a supramolecular polymeric material using multipoint molecular recognition between cyclodextrin (CD) and hydrophobic guest molecules at polymer side chain is reported. A transparent, flexible, and tough hydrogel (host-guest gel) is formed by a simple preparation procedure. The host-guest gel shows self-healing property in both wet state and dry state due to reversible nature of host-guest interaction. The practical utility of the host-guest gel as a scratch curable coating is demonstrated.

Whipple's disease diagnosed using electron microscopy and polymerase chain reaction.

A 50-year-old man presented with bloody diarrhea and 25-kg weight loss over 3 months. Upper and lower endoscopy showed diffuse shaggy white villi in the duodenum and terminal ileum. In addition, capsule endoscopy and double-balloon enteroscopy revealed shaggy white villi in the entire small intestine. Histological examination of biopsy specimens found the lamina propria of the duodenal and intestinal mucosa to be densely infiltrated by rich foamy macrophages that were periodic acid-Schiff-positive. Electron microscopy showed numerous bacilli in the lamina propria. Tropheryma whipplei DNA was detected in the specimens by polymerase chain reaction. Based on these findings, the patient was diagnosed with Whipple's disease. He was treated with a 2-week course of ceftriaxone followed by trimethoprim-sulfamethoxazole. At the 2-month follow up, diffuse white shaggy villi improved dramatically.

Radical polymerization by a supramolecular catalyst: cyclodextrin with a RAFT reagent.

Supramolecular catalysts have received a great deal of attention because they improve the selectivity and efficiency of reactions. Catalysts with host molecules exhibit specific reaction properties and recognize substrates via host-guest interactions. Here, we examined radical polymerization reactions with a chain transfer agent (CTA) that has α-cyclodextrin (α-CD) as a host molecule (α-CD-CTA). Prior to the polymerization of N,N-dimethylacrylamide (DMA), we investigated the complex formation of α-CD with DMA. Single X-ray analysis demonstrated that α-CD includes DMA inside its cavity. When DMA was polymerized in the presence of α-CD-CTA using 2,2'-azobis[2-(2-imidazolin-2-yl)propane dihydrochloride (VA-044) as an initiator in an aqueous solution, poly(DMA) was obtained in good yield and with narrow molecular weight distribution. In contrast, the polymerization of DMA without α-CD-CTA produced more widely distributed polymers. In the presence of 1,6-hexanediol (C6 diol) which works as a competitive molecule by being included in the α-CD cavity, the reaction yield was lower than that without C6 diol.

Supramolecular polymeric materials via cyclodextrin-guest interactions.

CONSPECTUS: Cyclodextrins (CDs) have many attractive functions, including molecular recognition, hydrolysis, catalysis, and polymerization. One of the most important uses of CDs is for the molecular recognition of hydrophobic organic guest molecules in aqueous solutions. CDs are desirable host molecules because they are environmentally benign and offer diverse functions. This Account demonstrates some of the great advances in the development of supramolecular materials through host-guest interactions within the last 10 years. In 1990, we developed topological supramolecular complexes with CDs, polyrotaxane, and CD tubes, and these preparation methods take advantage of self-organization between the CDs and the polymers. The combination of polyrotaxane with αCD forms a hydrogel through the interaction of αCDs with the OH groups on poly(ethylene glycol). We categorized these polyrotaxane chemistries within main chain type complexes. At the same time, we studied the interactions of side chain type supramolecular complexes with CDs. In these systems the guest molecules modified the polymers and selectively formed inclusion complexes with CDs. The systems that used low molecular weight compounds did not show such selectivity with CDs. The multivalency available within the complex cooperatively enhances the selective binding of CD with guest molecules via the polymer side chains, a phenomenon that is analogous to binding patterns observed in antigen-antibody complexes. To incorporate the molecular recognition properties of CDs within the polymer side chains, we first prepared stimuli-responsive sol-gel switching materials through host-guest interactions. We chose azobenzene derivatives for their response to light and ferrocene derivatives for their response to redox conditions. The supramolecular materials were both redox-responsive and self-healing, and these properties resulted from host-guest interactions. These sol-gels with built in switches gave us insight for creating materials that were self-healing or could serve as artificial muscle. Furthermore, we developed another self-healing material with CD inclusion complexes that showed selective self-healing properties after its surface was cut. These CD self-healing materials do not include chemical cross-linkers; instead the inclusion complex of CDs with guest molecules stabilized the material's strength. However, by introducing chemical cross-linkers into the hydrogels, we produced materials that could expand and contract. The chemical cross-linked hydrogels with responsive groups bent in response to external stimuli, and the cross-linkers controlled the ratio of inclusion complexes. Furthermore, we used the molecular recognition of CDs to achieve macroscopic self-assemblies, and this chemistry can direct these macroscopic objects into even larger aggregated structures. As we have demonstrated, reversible host-guest interactions have tremendous potential for the creation of a wide variety of functional materials.

Macroscopic self-assembly based on complementary interactions between nucleobase pairs.

We have created a selective macroscopic self-assembly process by using polymer gels modified with complementary DNA oligonucleotides or nucleobases. The hydrogels modified with complementary DNA oligonucleotides adhered to each other by simple contact. The organogels modified with complementary nucleobases selectively formed macroscopic assemblies by agitation in nonpolar organic solvents. The adhesion strength of each gel was estimated semi-quantitatively by stress-strain measurements. We achieved direct adhesion between macroscopic materials both in water and in organic media, based on complementary hydrogen bonds.

A Light-Controlled Release System Based on Molecular Recognition of Cyclodextrins.

This Communication describes a new light-controlled release system based on molecular recognition of cyclodextrins. Azobenzene (Azo) residue is employed as a photoresponsive guest residue because it can switch the partner from α-cyclodextrin (αCD) to ß-cyclodextrin (ßCD) by irradiation with UV light. Poly(sodium acrylate)s possessing αCD, ßCD, and Azo residues (pAαCD, pAßCD, and pAAzo, respectively) are mixed in aqueous solutions to form aggregates through the formation of inclusion complexes of Azo with αCD and/or ßCD. A chemical cargo, 1-pyrenemethylammonium chloride (PyMA), is contained in the aggregates, and its release behavior is investigated by dialysis experiments under UV irradiation. These data indicate that the amount of PyMA released for the pAαCD/pAßCD/pAAzo ternary mixture is approximately three times as high as those for the pAαCD/pAAzo and pAßCD/pAAzo binary mixtures because of the light-controlled rearrangement of inclusion complexes.

Self-Healing, Expansion-Contraction, and Shape-Memory Properties of a Preorganized Supramolecular Hydrogel through Host-Guest Interactions.

Supramolecular materials cross-linked between polymer chains by noncovalent bonds have the potential to provide dynamic functions that are not produced by covalently cross-linked polymeric materials. We focused on the formation of supramolecular polymeric materials through host-guest interactions: a powerful method for the creation of nonconventional materials. We employed two different kinds of host-guest inclusion complexes of ß-cyclodextrin (ßCD) with adamantane (Ad) and ferrocene (Fc) to bind polymers together to form a supramolecular hydrogel (ßCD-Ad-Fc gel). The ßCD-Ad-Fc gel showed self-healing ability when damaged and responded to redox stimuli by expansion or contraction. Moreover, the ßCD-Ad-Fc gel showed a redox-responsive shape-morphing effect. We thus succeeded in deriving three functions from the introduction of two kinds of functional units into a supramolecular material.