Does patenting always help new firm survival? Understanding heterogeneity among exit routes.

Abstract: While patents are a valuable resource ensuring the competitive advantage of firms, there is limited evidence on the role of patents in the survival and exit strategies of new firms. To fill the gap in the literature, we examine whether the effects of patenting on new firm survival vary according to exit routes (bankruptcy, merger, and voluntary liquidation), while considering the endogeneity of patenting. We use a large-scale sample of new firms in the Japanese manufacturing and information services sectors for the period 2003-2013. The findings indicate that new firms with a higher stock of patents are less likely to go bankrupt. Conversely, new firms with a higher stock of patents are more likely to exit via merger. These findings are consistent, regardless of whether patent stock is measured based on the patent applications or granted patents. Furthermore, we provide evidence that new firms with a higher stock of granted patents are more likely to voluntarily liquidate their businesses. Plain English Summary: Can new firms enjoy a "patent premium" in terms of survival and exit outcomes? The findings of this study indicate that (1) patenting reduces the risk of bankruptcy, and (2) it increases the odds of exit via merger and voluntary liquidation. On the one hand, patenting ensures that new firms obtain competitive advantages, and thus, survive in the product market. On the other hand, it enables new firms to pursue successful exit strategies in the markets for ideas. This study concludes that new firms can enjoy a patent premium in terms of survival and exit outcomes. In promoting sustainable economic growth via entrepreneurship, policymakers need to shift their focus from creating more firms to creating innovative firms.

Geometry Control of Wrinkle Structures Aligned on Hydrogel Surfaces.

Surface geometries in nature such as wrinkle structures have various functions. Attention has been paid to the fabrication method of the geometry and geometry control by external stimuli. This is because surface geometries as an active interface are able to contribute to the control of interactions with the external environment. In this study, aligned wrinkles were fabricated on the surface of stretched hydrogels in aqueous conditions by the electrophoretic formation of a polyion complex layer. The geometry of wrinkles was controlled by the stretching ratio and Young's modulus of hydrogels, and hierarchical wrinkle structures were fabricated after unloading the stretched hydrogels. Therefore, it can be a new wrinkle-formation method capable of transferring the initial elastic anisotropy of the substrate material to the wrinkle structure. Creation of thermoresponsive wrinkles that can transform their geometrical configuration reversibly was achieved by fabrication of aligned wrinkles on the surface of thermoresponsive hydrogels.

Hydrogel Adhesion by Wrinkling Films.

A novel adhesion control method for hydrogels utilizing swelling-induced wrinkling gel films is developed. Structures such as flat, crease, and wrinkle at the interface of adhered gels are controlled by swelling ratio of gel films. The role of microstructures at the gel-gel interface is investigated by adhesive strength measurement. Aligned wrinkles are fabricated with anisotropic swelling films. The adhesive strength of hydrogels with wrinkles parallel to tensile direction is larger than that with perpendicular wrinkles. Adhered gels detach without damage to their surfaces when the wrinkle structures are disrupted by peeling of the wrinkled film. Moreover, thermoresponsive film is used to control wrinkle structures at the adhered interface by temperature. The adhered interface is stable in cold water because of the existence of wrinkles; however, they detach in hot water due to wrinkle deformation. By using wrinkle structure at adhesive interfaces, both strong adhesion and easy detachment of hydrogels are achieved.

Electrophoretic fabrication of an active and selective wrinkle surface on hydrogels.

We developed a novel method for the fabrication of a wrinkle structure on the hydrogel surface in aqueous conditions by the electrophoretic formation of a polyion complex. The wrinkling wavelength was controlled by changing the electrophoresis conditions and Young's modulus of the hydrogels. It was possible to prepare the patterned and gradient wrinkle surface by modulating the electrode installation. An active wrinkle on the surface of the thermoresponsive hydrogel could be switched to a flat and wrinkle surface by changing the temperature.

Hydrogel Adhesion with Wrinkle Formation by Spatial Control of Polymer Networks.

We prepared a novel wrinkled adhesive interface of hydrogels for strong adhesion via spatial control of polymer networks, including the density, distribution, and mobility of interactive units. A wrinkle structure was formed by the elasticity mismatch of hydrogels and adhesive polyion complex layers when electrophoresis was carried out between cationic and anionic semi-IPNs. The wrinkling wavelength of interfaces was controlled by Young's modulus of hydrogels. The role of wrinkle structure in adhesion was investigated by the measurement of the adhesive strength of hydrogels which were adhered under the compression, resulting in the disappearance of the wrinkle structure by compression that induced a decrease in adhesive strength. These results indicate that strong hydrogel adhesion was achieved by both the spatial design of interactive units and wrinkle formation.

Detection of ruminant meat and bone meal in feeds by sandwich ELISA with monoclonal antibodies.

A sensitive and reproducible enzyme-linked immunosorbent assay (ELISA) using two monoclonal antibodies directed against a synthetic peptide with an amino-acid sequence related to the C-terminus of bovine myoglobin and the whole molecule of sodium dodecyl sulphate (SDS)-denatured bovine myoglobin was adapted for detecting bovine myoglobin in contaminated feeds. The ELISA employed bovine meat extract of a known myoglobin concentration as a calibration standard and had an limit of detection (LOD) of 3.54 ng/ml and an limit of quantification (LOQ) of 11.0 ng/ml corresponding to 0.022% and 0.067% (wt/wt) bovine meat-and-bone-meal (MBM) mixed in 20-fold-diluted feed extracts, respectively. A cut-off threshold of 20.6 ng/ml bovine myoglobin was set to simplify ELISA and facilitate quick assessment of test results without a tedious calibration process. The ELISA was able to detect bovine MBM in artificially prepared model feeds, mixed botanical feeds, mixed botanical feeds with skimmed milk, fish meal, pork meal and pork/chicken meal at 0.1% (wt/wt). It was also able to detect sheep MBM in test feeds, but showed no reactivity to swine MBM, chicken MBM, skimmed milk or gelatine of bovine origin. The advantages of this method are the quick and easy extraction protocol of proteins from test feeds, using 100 mM sodium sulphide and 0.6% sodium dodecyl sulphate in the extraction solution and the effective detection of bovine and sheep MBM at 0.1% (wt/wt).

Transcatheter and percutaneous procedures for huge pelvic arteriovenous malformations causing high-output heart failure.

We present the case of a 63-year-old woman presenting with a huge pelvic and retroperitoneal high flow arteriovenous malformation (AVM) causing high-output heart failure, who was treated with combined therapies, including transarterial embolization with n-butyl cyanoacrylate-iodized oil mixture (NBCA-lip) and coils for the right ovarian, both internal iliac, 3rd and 4th lumber arteries, venous sclerotherapy using coils and ethanolamine oleate (EO) for the right ovarian and both internal iliac veins with balloon-occluded retrograde transvenous obliteration technique, and direct percutaneous sclerotherapy using the NBCA-lip and EO for the large nidus of AVM under outflow control using occlusion balloon catheters. .

Percutaneous gastrostomy tube placement using a balloon catheter in patients with head and neck cancer.

BACKGROUND: Patients with head and neck cancer frequently require gastrostomy feeding. The aim of this study was to evaluate the safety and feasibility of percutaneous radiologic gastrostomy with push-type gastrostomy tubes using a rupture-free balloon (RFB) catheter under computed tomography (CT) and fluoroscopic guidance in patients with head and neck cancer with swallowing disturbance or trismus. METHODS: Percutaneous CT and fluoroscopic gastrostomy placement of push-type gastrostomy tubes using a RFB catheter was performed in consecutive patients with head and neck cancer between April 2007 and July 2010. The technical success, procedure duration, and major or minor complications were evaluated. RESULTS: Twenty-one patients (14 men, 7 women; age range, 55-78 years; mean age, 69.3 years) underwent gastrostomy tube placement. The tumor location was the pharynx (n = 8), oral cavity (n = 7), and gingiva (n = 6). Gastrostomy was performed in 15 patients during treatment and 6 patients after treatment. Percutaneous radiologic gastrostomy was technically successful in all patients. The median procedure time was 35 ± 19 (interquartile range) minutes (range, 25-75). The average follow-up time interval was 221 days (range, 10-920 days). No major complications related to the procedure were encountered. No tubes failed because of blockage, and neither tube dislodgement nor intraperitoneal leakage occurred during the follow-up periods. CONCLUSION: Percutaneous CT and fluoroscopic-guided gastrostomy with push-type tubes using a RFB catheter is a relatively safe and effective means of gastric feeding, with high success and low complication rates in patients with head and neck cancer in whom endoscopy was not feasible.

Sleep-disordered breathing with nighttime hypocapnia relates to daytime enhanced ventilatory response to exercise in patients with heart disease.

BACKGROUND: Sleep-disordered breathing (SDB) induces nighttime disturbance of arterial gases, such as carbon dioxide. However, it is still unclear whether nighttime SDB-related gas abnormality is related to respiratory dysregulation in daytime. Therefore, we examined the relationship between the arterial partial pressure of carbon dioxide (PaCO(2)) at nighttime and the respiratory response to exercise in daytime. METHODS: Eighteen men (age, mean ± SD; 55 ± 11 years) with heart disease underwent multichannel respiratory monitoring through the night with transdermal measurement of PaCO(2) (PtcCO(2)) reflecting PaCO(2) and a cardiopulmonary exercise test in daytime. The ventilatory equivalent (VE)/carbon dioxide production (VCO(2)) slope as an index of ventilatory response to exercise and peak oxygen consumption (VO(2)) were obtained with a cardiopulmonary exercise test. RESULTS: Of the 18 patients, 10 patients had obstructive SDB, 5 had central SDB, and 3 patients did not have SDB. The mean apnea-hypopnea index was 21 ± 17. Minimum nighttime saturation of O(2) was positively correlated with peak VO(2), but not with VE/VCO(2). Nighttime PtcCO(2) was not correlated with peak VO(2) but was negatively correlated with the VE/VCO(2) slope of the daytime cardiopulmonary exercise test (r=-0.53). CONCLUSION: Nighttime lowering of PaCO(2) in SDB is related to an abnormal ventilatory response to exercise testing in the daytime. This finding suggests that nighttime hyperventilation in SDB alters both nighttime and daytime pathophysiological conditions in patients with heart disease.

Computed tomography enteroclysis for recurrent severe gastrointestinal bleeding in a patient with vascular malformation of the small bowel.

This is a case study of a 66-year-old woman who had a vascular malformation of the small bowel that was visualized on computed tomography enteroclysis (CTE). She presented with repeated tarry stool and severe anemia. Although the source of bleeding was not identified on upper and lower gastrointestinal endoscopy, active bleeding was revealed by capsule endoscopy in the deep jejunum. The cause of bleeding was not found on capsule endoscopy. CTE was requested as double-balloon endoscopy would have been difficult because of strong adhesion of the small intestine. A continual subtle vascular malformation of the jejunum, starting from the third jejunal branch end, was demonstrated on CTE with dynamic contrast enhancement. Because this vascular malformation was considered the cause of small intestinal bleeding, selective arterial coil embolization was performed. After embolization, the repeated tarry stool disappeared and the severe anemia dramatically improved. CTE may be a safe and useful method for determining the cause of small intestinal bleeding and for subsequent therapy.

Clindamycin phosphate scavenges hydroxyl radical.

BACKGROUND: Clindamycin phosphate (CLDMP) is effective against Gram-positive and anaerobic bacteria, and is known to have anti-inflammatory properties. METHODS: To further study the anti-inflammatory properties of CLDMP, we examined the scavenging effects on superoxide anion and hydroxyl radical using an electron spin resonance (ESR) spin trapping method. RESULTS: In a hypoxanthine-xanthine oxidase reaction system, CLDMP did not scavenge superoxide anion. In a Fenton reaction system, however, CLDMP reduced the level of hydroxyl radical, and the scavenging activity of CLDMP against hydroxyl radical was more potent than that of mannitol. As the concentration which inhibits the formation of hydroxyl radical by 50% (IC(50)) of CLDMP was changed by the addition of a 10-fold amount of a spin trapping agent, 5,5-dimethyl-1-pyrroline-N-oxide, it is strongly suggested that CLDMP scavenges hydroxyl radical directly. CONCLUSION: This is the first report of the direct scavenging effect of CLDMP on hydroxyl radical, and the effect may improve the inflammatory response caused by invading bacteria.

Beta-phenylethylamine stimulates striatal acetylcholine release through activation of the AMPA glutamatergic pathway.

Using an in vivo intra-striatal microdialysis technique, we examined the effects of systemically administered beta-phenylethylamine (beta-PEA), a psychomotor stimulating trace amine, on striatal acetylcholine release in freely moving rats. Infusion of N-methyl-D-aspartic acid (NMDA; 10(-5) M) significantly increased acetylcholine release. In addition, locally applied amino-3-hydroxy-5-methylisozasole-4-propionic acid (AMPA; 10(-5) M) significantly increased acetylcholine release in the striatum. Intra-striatal application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10(-5) M), an AMPA-type glutamatergic receptor antagonist, had little effect on acetylcholine release, while application of MK-801 (10(-5) M, 10(-6) M), an NMDA-type glutamatergic receptor antagonist, significantly reduced acetylcholine release. Acetylcholine within striatal perfusate was significantly increased by intraperitoneal administration of beta-PEA in a dose-dependent manner. This increase in acetylcholine release was completely blocked by application of CNQX (10(-5) M) through the microdialysis probe into the striatum. However, increased acetylcholine response to systemic beta-PEA was unaltered by addition of MK-801 to the perfusion medium. These results suggest a regulatory function of beta-PEA, mediated by AMPA-type glutamatergic receptors, on the release of acetylcholine in the rat striatum.

Effects of beta-phenylethylamine on dopaminergic neurons of the ventral tegmental area in the rat: a combined electrophysiological and microdialysis study.

The effects of systemic administration of beta-phenylethylamine (beta-PEA) and microiontophoretically applied beta-PEA on the spontaneous discharge of dopamine (DA) neurons in the ventral tegmental area (VTA) of the anesthetized rat were examined. Intravenous administration of beta-PEA (1.0, 2.5, and 5.0 mg/kg) and microiontophoretic applications of beta-PEA caused inhibitory responses in DA neurons. Systemic administration and microiontophoretic applications of beta-PEA induced dose- or current-dependent responses. The systemic beta-PEA-induced inhibitory responses were reversed by pretreatment with the DA D(2) receptor antagonists haloperidol (0.5 mg/kg i.p.) and sulpiride (10 mg/kg i.p). Pretreatment with reserpine (5 mg/kg i.p. 24 h earlier) did not completely block the systemic administration of beta-PEA (2.5 mg/kg) inhibition. A microdialysis study of freely moving rats demonstrated that the extracellular DA level increased significantly in response to local application of beta-PEA (100 muM) in the VTA via a microdialysis probe, and local application of beta-PEA-stimulated somatodendritic DA release in the VTA. The beta-PEA-induced release of DA was calcium ion-independent and was enhanced by pretreatment with pertussis toxin. These findings indicate that beta-phenylethylamine inhibits DA neuron activity via DA D(2) autoreceptors in the rat VTA and that this inhibitory effect is mediated by the somatodendritic DA release.

Ingested cocoa can prevent high-fat diet-induced obesity by regulating the expression of genes for fatty acid metabolism.

OBJECTIVE: We previously found that ingested cocoa decreased visceral adipose tissue weight in rat. To elucidate the molecular mechanisms of that effect, we carried out experiments aimed at analyzing biochemical parameters and gene expression profiles. METHODS: Rats were fed either of two high-fat diets, differing only in supplementation with real or mimetic cocoa. On day 21, body weights, mesenteric white adipose tissue weights, and concentrations of serum triacylglycerol were measured. To investigate the molecular mechanisms underlying the effects of cocoa on lipid metabolism and triacylglycerol accumulation, we examined gene expression profiles in liver and mesenteric white adipose tissues using the GeneChip microarray system. RESULTS: Final body weights and mesenteric white adipose tissue weights were significantly lower in rats fed the real cocoa diet than in those fed the mimetic cocoa diet (P<0.05), and serum triacylglycerol concentrations tended to be lower in rats fed the real cocoa diet (P=0.072). DNA microarray analysis showed that cocoa ingestion suppressed the expression of genes for enzymes involved in fatty acid synthesis in liver and white adipose tissues. In white adipose tissue, cocoa ingestion also decreased the expression of genes for fatty acid transport-relating molecules, whereas it upregulated the expression of genes for uncoupling protein-2 as a thermogenesis factor. CONCLUSIONS: Ingested cocoa can prevent high-fat diet-induced obesity by modulating lipid metabolism, especially by decreasing fatty acid synthesis and transport systems, and enhancement of part of the thermogenesis mechanism in liver and white adipose tissue.

Oral streptococci exhibit diverse susceptibility to human beta-defensin-2: antimicrobial effects of hBD-2 on oral streptococci.

We examined the antimicrobial effects of human beta-defensin-2 (hBD-2) on 17 species of oral streptococci to investigate the involvement of antimicrobial peptide activity in oral microflora development and the clinical use of the antimicrobial peptide for oral microflora control. Oral streptococci exhibit diverse levels of susceptibility to human beta-defensin-2 (hBD-2). Two major cariogenic bacterial species, Streptococcus mutans ( S. mutans) and S. sobrinus, were found to be susceptible to the peptide, indicating that it is a potential therapeutic agent for preventing dental caries. S. mitis exhibited the lowest susceptibility to the peptide. S. mitis is a major indigenous bacterium in the oral microflora, and our results suggest that it might possess a certain resistance mechanism against hBD-2.

Effect of a topical steroid on gene expressions for chemokines in mice with contact hypersensitivity.

Effects of a topical corticosteroid drug, diflucortolone valerate, on the mRNA expressions for four CC- and four CXC-chemokines, which have been reported to be associated with recruitment of different kinds of proinflammatory and inflammatory cells, were investigated by RT-PCR in mice with 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) response. All of the eight gene expressions were clearly up-regulated in the lesion site of the CHS response up to 24 h post-challenge of TNCB at which ear swelling response reached a peak, so that heavy infiltration of inflammatory cells consisting mainly of mononuclear cells and neutrophils was likely induced by these chemokines. Topical treatment with diflucortolone valerate suppressed completely the infiltrates as well as the ear swelling response. In addition, the up-regulation of gene expressions for these eight chemokines were suppressed by the treatment, indicating that the corticosteroid drug attenuates the expression of chemokine genes essential for orientating nonspecific skin response to hapten-specific CHS response through the recruitment of inflammatory cells from the circulation into the tissue site.

[Significance of intracellular cytokines levels in peripheral lymphocytes for evaluation of surgical stress after hepatectomy in patients with hepatocellular carcinoma].

It is difficult to evaluate surgical stress of patients with hepatocellular carcinoma (HCC). Cytokine production from the liver is decreased due to the liver dysfunction that is usually associated with HCCs. Therefore, we evaluated surgical stress after hepatectomy by measuring intracellular cytokines of lymphocytes in peripheral blood. We examined 22 patients with digestive cancers (8 with HCC, 10 with gastric cancer, and 4 with esophageal cancer). The concentrations of serum IL-6 levels 6 h after hepatectomy, gastrectomy, and esophagectomy were 268 +/- 84, 309 +/- 93, and 1,323 +/- 364 pg/ml, respectively. There was no significant difference between hepatectomy and gastrectomy, though based on clinical observations, it is estimated the surgical stress of hepatectomy was greater than that of gastrectomy. Conversely, the percentage of CD4+IL-6+ cells 6 h after surgery was 8.5 +/- 2.8, 3.3 +/- 0.6, and 7.8 +/- 3.4%, respectively. The percentage of CD4+IL-6+ cells after hepatectomy was significantly higher than that after gastrectomy. We estimated that the percentage of CD4+IL-6+ cells was an appropriate indicator of surgical stress on HCC, because the percentage of CD4+IL-6+ cells correlated well with the duration of surgery more than did the serum IL-6 levels. These results suggest that the percentage of CD4+IL-6+ cells may help in accurately evaluating surgical stress in patients with liver dysfunctions such as HCC.

Alpha 2-adrenoceptor modulates the release of acetylcholine from the rostral ventrolateral medulla in response to morphine.

The present study examined the role of the noradrenergic system in the modulation of acetylcholine (ACh) release in the rostral ventrolateral medulla (RVLM) using in vivo microdialysis of morphine. The basal level of ACh was 325.0 +/- 21.1 fmol/20 microl/15 min in the presence of neostigmine (10 microM). Intraperitoneal (i.p.) administration of 5 and 10 mg/kg morphine significantly increased ACh release by the RVLM. This enhancement was reversed by naloxone (1 mg/kg, i.p.). In addition, pretreatment with yohimbine (0.5 mg/kg, i.p.) or prazosin (0.2 mg/kg, i.p.) attenuated the systemic morphine-induced release of ACh in the RVLM. However, propranolol (0.2 mg/kg, i.p.) did not affect the morphine-induced ACh release. The addition of morphine (10(-4) M) to the perfusion medium increased the ACh release by 72.4% of the predrug values. The increased ACh release induced by local application of morphine was attenuated by pretreatment with yohimbine, but not prazosin. These findings suggest that morphine exerts an indirect stimulatory effect on the release of ACh by the RVLM and that the morphine-induced increase in ACh release is modulated by alpha2-adrenoceptors in freely moving rats.

Characterization of muscarinic receptor subtypes in the rostral ventrolateral medulla and effects on morphine-induced antinociception in rats.

The present study investigated the role of muscarinic receptor subtypes in the nucleus reticularis gigantocellularis/nucleus reticularis gigantocellularis alpha of the rat rostral ventrolateral medulla in morphine-induced antinociception. The antinociceptive effects of morphine were evoked by systemic administration or microinjection into the nucleus reticularis gigantocellularis/nucleus reticularis gigantocellularis alpha. Administration of morphine produced antinociception for hot plate and tail immersion responses to noxious heat stimuli. These effects were antagonized by prior exposure to naloxone and inhibited by mecamylamine pretreatment. Morphine-induced antinociception was significantly inhibited by atropine in a dose-dependent manner. Muscarinic toxin-1 and pirenzepine inhibited morphine-induced antinociception for both the hot plate and tail immersion tests. At a dose of 5 nmol/site, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) also inhibited morphine-induced antinociception, although low doses of this drug did not significantly affect hot plate test response latency when morphine was systemically administered. These results suggest that the antinociceptive effects induced by morphine in part involve the muscarinic M(1) and M(3) receptors of the rat nucleus reticularis gigantocellularis/nucleus reticularis gigantocellularis alpha.

Kinetic profiles of sequential gene expressions for chemokines in mice with contact hypersensitivity.

Using cDNA microarray technology, the expression of chemokine genes in the elicitation site of 2,4,6-trinitrochlorobenzene-induced contact hypersensitivity (CHS) was examined in mice. Of the 33 genes analyzed, levels of 11 gene expressions changed, and these can be assigned to four groups based on their kinetic patterns; (1) LARC/CCL20 whose mRNA level increased rapidly at 3 h post-challenge and then gradually decreased, (2) JE/CCL2, MARC/CCL7, MIP-1gamma/CCL9, monocyte chemoattractant protein (MCP)-5/CCL12, ELC/CCL19 and BRAK/CXCL14 whose mRNA levels increased with time and reached the maximum at 6-9 h post-challenge, (3) LIX/CXCL5, Mig/CXCL9 and IP-10/CXCL10 whose mRNA levels increased gradually at least up to 12 h post challenge, and (4) SLC/CCL21 whose mRNA level decreased gradually with time after challenge. The findings suggest that sequential expression of chemokine genes is essential for orientating non-specific skin response to hapten-specific CHS response through the recruitment of inflammatory cells such as neutrophils, monocytes/macrophages and T-cells from the circulation into the tissue site.