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Objective This study aimed to evaluate whether the methane (CH4) to carbon dioxide (CO2) ratio (CH4/CO2) and methane-related traits obtained by the sniffer method can be used as indicators for genetic selection of Holstein cows with lower CH4 emissions. Methods The sniffer method was used to simultaneously measure the concentrations of CH4 and CO2 during milking in each milking box of the automatic milking system to obtain CH4/CO2. Methane-related traits, which included CH4 emissions, CH4 per energy-corrected milk, methane conversion factor (MCF), and residual CH4, were calculated. First, we investigated the impact of the model with and without body weight (BW) on the lactation stage and parity for predicting methane-related traits using a first on-farm dataset (Farm 1; 400 records for 74 Holstein cows). Second, we estimated the genetic parameters for CH4/CO2 and methane-related traits using a second on-farm dataset (Farm 2; 520 records for 182 Holstein cows). Third, we compared the repeatability and environmental effects on these traits in both farm datasets. Results The data from Farm 1 revealed that MCF can be reliably evaluated during the lactation stage and parity, even when BW is excluded from the model. Farm 2 data revealed low heritability and moderate repeatability for CH4/CO2 (0.12 and 0.46, respectively) and MCF (0.13 and 0.38, respectively). In addition, the estimated genetic correlation of milk yield with CH4/CO2 was low (0.07) and that with MCF was moderate (−0.53). The on-farm data indicated that CH4/CO2 and MCF could be evaluated consistently during the lactation stage and parity with moderate repeatability on both farms. Conclusion This study demonstrated the on-farm applicability of the sniffer method for selecting cows with low CH4 emissions.

Non-typhoidal Salmonella (NTS) rarely causes bacteremia and subsequent focal infections as an extraintestinal complication, even in immunocompetent adults. A 25-year-old man was hospitalized for several days with difficulty moving due to fever, acute buttock pain, and shivering. He had no recent or current respiratory symptoms and no clear gastrointestinal symptoms. Physical examination revealed mild redness around the left buttock and difficulty raising the left lower extremity due to pain, in addition to which blood tests showed high levels of inflammatory markers. His clinical course and laboratory findings suggested sepsis, and magnetic resonance imaging revealed a high-intensity area in the left piriformis muscle on diffusion-weighted imaging; therefore, acute piriformis pyomyositis was strongly suggested. Cephazolin was started upon hospitalization; however, blood and stool cultures proved positive for NTS, and the antibiotics were changed to ceftriaxone. Follow-up MRI showed a signal in the left piriformis muscle and newly developed left pyogenic sacroiliitis. On the 25th hospital day, a colonoscopy was performed to identify the portal of entry for bacteremia, which revealed a longitudinal ulcer in the sigmoid colon in the healing process. His buttock pain gradually improved, and the antibiotics were switched to oral levofloxacin, which enabled him to continue treatment in an outpatient setting. Finally, the patient completed seven weeks of antimicrobial therapy and returned to daily life without leaving any residual disability. Invasive NTS infection due to bacteremia is rare among immunocompetent adults. Piriformis pyomyositis and subsequent pyogenic sacroiliitis should be added to the differential diagnosis of acute febrile buttock pain. In the case of NTS bacteremia, the entry site must be identified for source control. Additionally, the background of the host, especially in such an immunocompetent case, needs to be clarified; therefore, the patient should be closely examined.

For a commercial laser inertial fusion energy reactor, a highly repetitive operation in which many fuel pellets must be illuminated by laser spots. One of the most efficient ways to achieve this is to control the laser pointing by following fluctuations of the target position. The paper shows the precise control of laser pointing in the horizontal direction with a repetition rate of 10 Hz. Free-falling test pellets of 1 mm in diameter have been illuminated by a laser of 1.6 mm in diameter with cancellation of horizontal fluctuation over 4 mm. The difference in centroids between the laser spot and the illuminated test pellets is 86 μ m (standard deviation). This corresponds to a 92% engagement within a 0.15 mm difference, which is a condition for successful nuclear fusions at the Hamamatsu facility. This is the proof-of-principle demonstration of the target-supply tracking and homing laser at a repetition rate of 10 Hz for the actualization of a commercial reactor.

Abstract Repellent coatings are critical for the development of biomedical and analytical devices to prevent nonspecific protein and cell adhesion. In this study, prevelex (polyampholytes containing phosphate and amine units) was synthesized for the fine coating of microdevices for cell culture. The dip-coating of the prevelex on hydrophobic substrates altered their surfaces to be highly hydrophilic and electrically neutral. The range of prebake temperature (50–150 °C) after dip-coating was moderate and within a preferable range to treat typical materials for cell culture such as polystyrene and polydimethylsiloxane. Scanning electron microscopy revealed a conformal and ultra-thin film coating on the micro/nano structures. When compared with poly(2-hydroxyethyl methacrylate) and poly(2-methacryloyloxyethyl phosphorylcholine), prevelex exhibited better characteristics for coating on microwell array devices, thereby facilitating the formation of spheroids with uniform diameters using various cell types. Furthermore, to examine cellular functionalities, mouse embryonic epithelial and mesenchymal cells were seeded in a prevelex-coated microwell array device. The two types of cells formed hair follicle germ-like aggregates in the device. The aggregates were then transplanted to generate de novo hair follicles in nude mice. The coating material provided a robust and fine coating approach for the preparation of non-fouling surfaces for tissue engineering and biomedical applications.

Abstract We give a precise definition of BPS vortex loops in 3D non-abelian gauge theories with N $$ \mathcal{N} $$ = 2 SUSY by the path integral over fields with a prescribed singular behavior. We compute the expectation value of a BPS vortex loop on an ellipsoid. Using the result we revisit the known equivalence between Wilson and vortex loops in pure Chern-Simons theory. Naive computations of expectation values in N $$ \mathcal{N} $$ = 2 theory leads to an unwanted shift of parameters in the rule of correspondence. We resolve the problem by relating the shift to the global anomaly of N $$ \mathcal{N} $$ = 2 SUSY quantum mechanics. For theories with U(N) gauge group we also develop an alternative description of vortex loops in terms of 1D N $$ \mathcal{N} $$ = 2 SUSY quantum mechanics on their worldline. For vortex loops in N $$ \mathcal{N} $$ = 4 theories, our construction reproduces some of the quiver GLSMs of Assel and Gomis.

Abstract Background Paroxysmal sympathetic hyperactivity (PSH) may occur after acquired brain injury. The clinical presentation of PSH results from increased sympathetic overdrive, including transient paroxysms of tachycardia, hypertension, hyperventilation, hyperthermia, dystonic posturing, and excessive sweating. The exact pathophysiology of PSH, however, remains unclear, and no definitive treatment is available. Herein, the authors report a case of PSH in a male patient who experienced acute brain swelling after acquired head injury, for which a good clinical outcome was achieved due to multimodal treatment. The ensuing discussion also addresses the pathophysiology of PSH. Case presentation An 18-year-old man was transported to the authors’ hospital after experiencing a traumatic brain injury. On admission, computed tomography revealed cerebral herniation due to diffuse brain edema in the left parietal lobe. Emergency decompressive craniotomy and internal decompression were performed. After surgery, anti-edema therapy (glycerol and mannitol) was continued. Ten days postoperatively, PSH was diagnosed in accordance with the PSH assessment score (20 points). Vecuronium, fentanyl, morphine, propofol, dexmedetomidine, and a calcium channel blocker were administered; however, the drug effect was insufficient. Thirty-two days postsurgery, the patient gradually recovered from the adrenergic symptoms of PSH, and head computed tomography performed 32 days after surgery revealed improvement in diffuse brain edema. Ultimately, the patient fully recovered and lived independently at home. Conclusions Considering the pathophysiology of PSH, cerebral contusion, acute brain swelling, and secondary mechanisms of brain injury may trigger sympathetic nerve-enhancing regions and cause hyperexcitation of the sympathetic nervous system, resulting in PSH. The outcome of the present case demonstrates that PSH can be reversed if it is identified early and before it becomes irreversible, that is, post the development of hypoxic encephalopathy or widespread brain damage. Appropriate management, including decompression craniotomy for brain swelling and multidisciplinary treatment, leads to good clinical outcomes.

Katayama et al. report a vibrational spectroscopic study using ATR–FTIR of the human M2 muscarinic acetylcholine receptor (M2R). Their work involves an extensive comparison of agonists, antagonists, and inverse agonists, in which they show that they C = O stretching amide–I band is correlated with the ligand binding efficiency.

In the diagnosis of an intracranial dural arteriovenous fistula (DAVF), arterial spin labeling (ASL), a sequence of magnetic resonance imaging (MRI) to depict high-blood-flow intracranial lesions, has been reported as a useful and noninvasive tool, not only to predict the presence of cortical venous drainage and draining veins, but also to confirm persistent obliteration after treatment. However, such utility of ASL has not been reported in DAVF of the craniocervical junction (CCJDAVF) because of the rarity of this disease and uncertainty in the acquisition of precise images.We report a case of CCJDAVF presenting with myelopathy. Preoperative ASL images showed an abnormal high-intensity signal in the craniocervical junction, consistent with the anterior spinal vein and draining veins, which were also identified by digital subtraction angiography. After successful surgical treatment for the disease, MRI and 4-dimensional computed tomography angiography (4DCTA) confirmed complete disappearance of CCJDAVF. The ASL images also showed no abnormal intensity signal. The patient was followed-up using ASL, and no recurrence of high-intensity signal was observed.As repetitive image examination is mandatory in the follow-up of a patient with DAVF to exclude recurrence, ASL is highly beneficial because of the unnecessity of an exogenous contrast medium and high credibility to depict the disease. The craniocervical junction may be out of the field of view in routine MRI. Special attention must be paid to setting the field of view and post labeling delay (PLD) to obtain precise images of ASL in CCJDAVF.

Abstract In response to the challenges imposed by the COVID-19 pandemic, governments worldwide adopted a variety of strategies that include not just preventive or mitigation strategies adopted to “flatten the curve”, but also interventions aiming to mitigate economic and social impacts of the pandemic. RAP`s special issue gathered 17 reflexive, timely and relevant contributions of different governmental approaches to the COVID-19 pandemic. In this paper we highlight similarities and differences in governmental responses across countries and regions. We uncover and discuss broad themes covered in the symposium, focusing on: (a) impacts of social distancing strategies; (b) economic-relief responses; c) the role of bargaining, collaboration and coordination across levels of governance; (d) key actors and their role in the pandemic response; (e) pandemic and socio-economic inequalities; and (f) context, policy responses and effectiveness. The symposium adds to an extensive body of knowledge that has been produced on the topic of policy responses to COVID-19 pandemic offering more diverse contextual and comparative analysis.

Background: Scalp arteriovenous fistula (SAVF) is relatively rare; due to its rarity, there is currently no established consensus on the treatment strategies of SAVF. Case description: A 30-year-old male presented with a pulsating mass on his right forehead. He underwent left selective amygdalohippocampectomy for left temporal lobe epilepsy 18 years prior. Cerebral angiography showed three fistula points that were fed by the bilateral superficial temporal arteries (STA) and an expanding drainage vein. We diagnosed the patient with SAVF. Because the fistula gathered in the midline of the forehead, we planned the treatment with surgical treatment alone. First, the proximal side of the right STA, the main feeder to the fistula, was released and clamped. The fistulas made up of the three shunt points of the STAs on both sides were then detected under a microscope. Then, each of the three feeders from the STAs on both sides was clamped. Three feeding arteries and drainage veins were coagulated, and the fistula was removed. Finally, the patient was discharged without complications, including scalp necrosis, infection, and recurrence of the pulsating mass. Conclusions: In our case, SAVF may have occurred after craniotomy or frequent minor head trauma. In direct surgery of SAVF, reliable identification and exposure of the feeder and fistula under a microscope without bleeding are the key. Direct surgery with a small skin incision is possible to cure SAVF completely, especially in cases where a fistula is present.

Inflammatory bowel disease (IBD) consists of two major idiopathic gastrointestinal diseases: ulcerative colitis and Crohn's disease. Although a significant advance has been achieved in the treatment of IBD, there remains a particular population of patients that are refractory to the conventional treatments, including the biologic agents. Studies have revealed the importance of “mucosal healing” in improving the prognosis of those difficult-to-treat patients, which indicates the proper and complete regeneration of the damaged intestinal tissue. In this regard, organoid-based regenerative medicine may have the potential to dramatically promote the achievement of mucosal healing in refractory IBD patients, and thereby improve their long-term prognosis as well. So far, studies have shown that hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) may have some beneficial effect on IBD patients through their transplantation or transfusion. Recent advance in stem cell biology has added intestinal stem cells (ISCs) as a new player in this field. It has been shown that ISCs can be grown in vitro as organoids and that those ex-vivo cultured organoids can be employed as donor cells for transplantation studies. Further studies using mice colitis models have shown that ex-vivo cultured organoids can engraft onto the colitic ulcers and reconstruct the crypt-villus structures. Such transplantation of organoids may not only facilitate the regeneration of the refractory ulcers that may persist in IBD patients but may also reduce the risk of developing colitis-associated cancers. Endoscopy-assisted transplantation of organoids may, therefore, become one of the alternative therapies for refractory IBD patients. Keywords: Intestinal stem cells, Organoids, Ulcerative colitis, Crohn's disease, Organoid medicine

Inflammatory bowel disease (IBD) is an idiopathic, multi-etiological disease characterized by inflammation and mucosal destruction of the gastrointestinal tract. Despite the remarkable advance in immunomodulating therapies, there still remains a certain population of patients who are refractory to conventional as well as biologic therapies and fail to achieve mucosal healing. To improve the prognosis of those patients, at least 2 types of stem cells have been tested for their potential therapeutic use. Transplantation of hematopoietic stem cells or mesenchymal stem cells have been tested in several clinical studies, but their beneficial effect still remains controversial. In this review, we would like to overview the recent clinical challenges of stem cell-based therapies in IBD and also introduce our new therapeutic plan of intestinal stem cell transplantation for IBD, based on our ex vivo intestinal organoid culture technique.

Copper is an essential transition metal for all eukaryotes. In mammals, intestinal copper absorption is mediated by the ATP7A copper transporter, whereas copper excretion occurs predominantly through the biliary route and is mediated by the paralog ATP7B. Both transporters have been shown to be recycled actively between the endosomal network and the plasma membrane by a molecular machinery known as the COMMD/CCDC22/CCDC93 or CCC complex. In fact, mutations in COMMD1 can lead to impaired biliary copper excretion and liver pathology in dogs and in mice with liver-specific Commd1 deficiency, recapitulating aspects of this phenotype. Nonetheless, the role of the CCC complex in intestinal copper absorption in vivo has not been studied, and the potential redundancy of various COMMD family members has not been tested. In this study, we examined copper homeostasis in enterocyte-specific and hepatocyte-specific COMMD gene-deficient mice. We found that, in contrast to effects in cell lines in culture, COMMD protein deficiency induced minimal changes in ATP7A in enterocytes and did not lead to altered copper levels under low- or high-copper diets, suggesting that regulation of ATP7A in enterocytes is not of physiological consequence. By contrast, deficiency of any of three COMMD genes (Commd1, Commd6 or Commd9) resulted in hepatic copper accumulation under high-copper diets. We found that each of these deficiencies caused destabilization of the entire CCC complex and suggest that this might explain their shared phenotype. Overall, we conclude that the CCC complex plays an important role in ATP7B endosomal recycling and function.

In this protocol, we describe our methods to isolate crypts from patients' biopsy samples and to culture human intestinal stem cells as it’s called “organoid.” Beyond that, we describe how to dissociate organoids cells into single cells for single-cell analysis as a further application. This protocol should provide investigators sufficient tools to generate human organoids from biopsy samples and to accomplish a stable in-vitro assay system.

Summary: ATOH1 is a master transcription factor for the secretory lineage differentiation of intestinal epithelial cells (IECs). However, the comprehensive contribution of ATOH1+ secretory lineage IECs to the homeostasis, repair, and tumorigenesis of the intestinal epithelium remains uncertain. Through our ATOH1+ cell-lineage tracing, we show here that a definite number of ATOH1+ IECs retain stem cell properties and can form ATOH1+IEC-derived clonal ribbons (ATOH1+ICRs) under completely homeostatic conditions. Interestingly, colonic ATOH1+ IECs appeared to exhibit their stem cell function more frequently compared with those of the small intestine. Consistently, the formation of ATOH1+ICRs was significantly enhanced upon dextran sodium sulfate colitis-induced mucosal damage. In addition, colonic ATOH1+ IECs acquired tumor stem cell-like properties in the azoxymethane-DSS tumor model. Our results reveal an unexpected contribution of colonic ATOH1+ IECs to maintaining the stem cell population under both homeostatic and pathologic conditions and further illustrate the high plasticity of the crypt-intrinsic stem cell hierarchy.

The data on the immunohistochemical analysis of conditional Notch ligand knockout mice is presented. Targeted deletion of Jag1, Dll1, Dll4, or Dll1 plus Dll4 in Lgr5+ve cells was induced by a Cre-mediated gene recombination, and differentiation or proliferation of the intestinal epithelial cells was examined by immunohistochemistry. These data are the extension of the data presented and discussed in the paper entitled “Indispensable role of non-canonical Notch signaling in the proliferation of Apc-deficient intestinal tumors“ (Nakata et al., Submitted for publication) [1].

In recent years, many seismic retrofitting methods have been performed to improve the structural performance and prevent the brittle failure of structural members. In the case of steel structures, slender seismic braces have been widely used for buildings, towers, and bridges. The brace connections should resist the full plastic axial tension load to ensure adequate plastic deformation performance for vibration energy absorption. However, certain connections do not satisfy these requirements. Recently, carbon fiber reinforced plastic (CFRP) has been used extensively to strengthen existing structures because of its high-strength, high elastic modulus, and light-weight characteristics. In this paper, we investigate the applicability of CFRP strengthening for brace connections and gusset plates with stepped surfaces using the vacuum-assisted resin transfer molding technique as a pilot demonstration. Stepped surfaces can be eliminated by using alternative CFRP layers to straighten the structural CFRP layers in order to effectively transfer the axial stress. Eventually, it is shown that CFRP strengthening can improve the connection strength and plastic deformation with 3% elongation, even if the CFRP is molded on the stepped surface.

Passive systems that utilize a natural power such as a pond, plant, or microorganisms, is expected to be a cost-effective method for acid mine drainage (AMD) treatment. The Ningyo-toge mine, a non-operational uranium mine located in Okayama Prefecture, Japan, generates AMD containing arsenic and iron. To quantitatively study arsenic and iron ion removal in an artificial wetland and pond, chemical reactions were modeled and incorporated into the GETFLOWS (general-purpose terrestrial fluid-flow simulator) software. The chemical reaction models consisted of arsenite and ferrous oxidation equations and arsenic adsorption on ferrihydrite. The X-ray diffraction analysis of sediment samples showed ferrihydrite patterns. These results were consistent with the model for arsenite/ferrous oxidation and arsenic adsorption on ferrihydrite. Geofluid simulation was conducted to simulate mass transfer with the utilized topographic model, inlet flow rate, precipitation, and evaporation. The measured arsenic and iron ions concentrations in solution samples from the wetland and pond, fitted well with the model. This indicated that the main removal mechanism was the oxidation of arsenite/ferrous ions and that arsenic was removed by adsorption rather than dilution.

Because an array ground penetrating radar (GPR) electrically switches any antenna combinations sequentially in milliseconds, both common-offset gather (COG) and multi-offset gather (MOG) data can be acquired almost seamlessly. The main objective of this study was therefore to determine if COG and MOG surveys by array GPR, which allows 110 different antenna combinations, could detect a wetting front during vertical field infiltration. An infiltration experiment was conducted in an experimental field inside Tottori Sand Dune, Japan. Time-lapse radargrams of COG and MOG by array GPR clearly show the wetting front evolution with time. Reflection signals in MOG radargrams agree well with two-way travel times predicted from dielectric constant observed independently with a soil moisture sensor. This study confirms the usefulness of array GPR for monitoring and quantifying the infiltration process in the field.

Although the advantage of using arbitrarily-shaped polyhedral meshes for the industrial flow applications is clear, their employment to two-phase flows is rather limited due to difficulty in deriving and implementing algorithms without overwhelming complexity on such meshes. We present a numerical method based on the VOF (Volume of Fluid) method which works on arbitrarily-shaped three-dimensional polyhedral meshes with comparable accuracy to the methods for structured meshes. We extend the THINC (Tangent of Hyperbola Interface Capturing) method and the RDF (Reconstructed Distance Function) method respectively, to solve the advection equation of the color function and to estimate the interface curvature on polyhedral meshes without laborious geometric arithmetics.

Reports have suggested that the two Notch ligands, Dll1 and Dll4, are indispensable to maintain the homeostasis of the intestinal epithelium. However, within the intestinal epithelium, the precise distribution of the cells that express those ligands at the protein level remains largely unknown. Here, we show a series of immunohistochemical analysis through which we successfully identified mice intestinal epithelial cells (IECs) that endogenously express Dll1 or Dll4. Results showed that Dll1-positive (Dll1+ve) IECs reside exclusively within the crypt, whereas Dll4-positive (Dll4+ve) IECs can locate both in the crypt and in the villus of the small intestine. Also in the colon, Dll1+ve IECs resided at the lower part of the crypt, whereas Dll4+ve IECs resided at both upper and lower part of the crypt, including the surface epithelium. Both Dll1+ve and Dll4+ve IECs were ATOH1-positive, but Hes1-negative cells, and located adjacent to Hes1-positive cells within the crypts. A sub-population of both Dll1+ve and Dll4+ve IECs appeared to co-express Muc2, but rarely co-expressed other secretory lineage markers. However, as compared to Dll1+ve IECs, Dll4+ve IECs included larger number of Muc2-postive IECs, suggesting that Dll4 is more preferentially expressed by goblet cells. Also, we identified that Dll4 is expressed in the Paneth cells of the small intestine, whereas Dll1 and Dll4 is expressed in the c-kit-positive IECs of the colon, indicating that Dll1+ve and Dll4+ve IECs may contribute to constitute the intestinal stem cell niche. Compared to the normal colon, analysis of DSS-colitis showed that number of Dll1+ve IECs significantly decrease in the elongated crypts of the inflamed colonic mucosa. In sharp contrast, number of Dll4+ve IECs showed a significant increase in those crypts, which was accompanied by the increase in number of Hes1-positive IECs. Those Dll4+ve IECs were mostly found adjacent to the Hes1-positive IECs, suggesting that Dll4 may act as a major Notch ligand in the crypts of the inflamed colonic mucosa. Our results illustrate distinct expression patterns of Dll1 and Dll4 within the intestinal epithelium, and suggest that these two ligands may have different roles in normal and inflamed mucosa.

Background: Perianeurysmal cyst formation after endovascular treatment of cerebral aneurysms is a rare complication; however, the number of reports has gradually increased in recent years due to the development of several endovascular treatments. Case Description: We present a case of delayed perianeurysmal cyst enlargement 8 years after endovascular treatment for multiple recurrences of a large cerebral aneurysm in the anterior communicating artery. The patient presented with obstructive hydrocephalus caused by an enlarged perianeurysmal cyst. The patient underwent cyst fenestration using neuroendoscopy and ventriculoperitoneal shunting, recovered from the clinical symptoms, and had a good prognosis. Histopathological findings showed that the cyst wall contained a fibrotic layer under the monoependymal layer with hemosiderosis without evidence of neovascularization or inflammatory cell infiltration. These findings suggest that the origin of the perianeurysmal cyst wall is not the aneurysm itself but the adjacent brain tissue. Conclusion: Perianeurysmal cysts can develop during long-term follow-up, and clinicians should consider surgical treatment, including cyst fenestration, using neuro-endoscopy if the cyst presents with clinical symptoms. [ABSTRACT FROM AUTHOR]