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Across species, sperm maturation involves the dramatic reconfiguration of chromatin into highly compact nuclei that enhance hydrodynamic ability and ensure paternal genomic integrity. This process is mediated by the replacement of histones by sperm nuclear basic proteins, also referred to as protamines. In humans, a carefully balanced dosage between two known protamine genes is required for optimal fertility. However, it remains unknown how their proper balance is regulated and how defects in balance may lead to compromised fertility. Here, we show that a nucleolar protein, modulo , a homolog of nucleolin , mediates the histone-to-protamine transition during Drosophila spermatogenesis. We find that modulo mutants display nuclear compaction defects during late spermatogenesis due to decreased expression of autosomal protamine genes (including Mst77F ) and derepression of Y-linked multicopy Mst77F homologs ( Mst77Y ), leading to the mutant’s known sterility. Overexpression of Mst77Y in a wild-type background is sufficient to cause nuclear compaction defects, similar to modulo mutant, indicating that Mst77Y is a dominant-negative variant interfering with the process of histone-to-protamine transition. Interestingly, ectopic overexpression of Mst77Y caused decompaction of X-bearing spermatids nuclei more frequently than Y-bearing spermatid nuclei, although this did not greatly affect the sex ratio of offspring. We further show that modulo regulates these protamine genes at the step of transcript polyadenylation. We conclude that the regulation of protamines mediated by modulo , ensuring the expression of functional ones while repressing dominant-negative ones, is critical for male fertility.

PDF file - 1228KB, Supplementary Table SI. Primary antibody for western blot. Supplementary Table SII. Primary antibody for immunohistochemistry. Supplementary Table SIII. ShRNA for gene silencing. Supplementary Table SIV. Inhibitors for kinase inhibition. Supplemental Materials and Methods. Supplemental Figures and Legends. Supplementary Figure S1. IL-32 is overexpressing in GC specimens. Supplementary Figure S2. Ectopic overexpression of IL-32 promotes migration in TSGH9201 cells. Supplementary Figure S3. IL-32 enhances cell invasion and beta-catenin activity in a doxycycline-inducible expression system. Supplementary Figure S4. PI3K/AKT inhibitor (LY294002) diminishes IL-32-induced IL-8 expression. Supplementary Figure S5. Inhibition of phospho-AKT by MK-2206 attenuates expression of IL-32-induced downstream molecules as well as cell invasion ability. Supplementary Figure S6. Depletion of IL-32 in TSGH9201 and AGS cell lines. Supplementary Figure S7. Scatter plots of IL-32 and its downstream effectors in Spearman rank correlation analysis. Supplementary Figure S8. Rac GTPase signaling is partially involved in IL-32-induced cell migration. Supplementary Figure S9. HIF-1alpha mediated IL32-induced IL8, VEGF, MMP2 and MMP9 expression as well as cell invasion via a beta-catenin independent pathway.

Purpose: The proinflammatory cytokine interleukin-32 (IL-32) is a novel tumor marker highly expressed in various human carcinomas, including gastric cancer. However, its effects on prognosis of patients with gastric cancer and cancer metastasis are virtually unknown at present. The main aim of this study was to explore the clinical significance of IL-32 in gastric cancer and further elucidate the molecular mechanisms underlying IL-32–mediated migration and invasion.Experimental Design: Gastric cancer cells with ectopic expression or silencing of IL-32 were examined to identify downstream molecules and establish their effects on cell motility, invasion, and lung metastasis in vivo.Results: IL-32 was significantly upregulated in gastric cancer and positively correlated with aggressiveness of cancer and poor prognosis. Ectopic expression of IL-32 induced elongated morphology and increased cell migration and invasion via induction of IL-8, VEGF, matrix metalloproteinase 2 (MMP2), and MMP9 expression via phosphor-AKT/phospho-glycogen synthase kinase 3β/active β-catenin as well as hypoxia-inducible factor 1α (HIF-1α) signaling pathways. Conversely, depletion of IL-32 in gastric cancer cells reversed these effects and decreased lung colonization in vivo. Examination of gene expression datasets in oncomine and staining of gastric cancer specimens demonstrated the clinical significance of IL-32 and its downstream molecules by providing information on their coexpression patterns.Conclusions: IL-32 contributes to gastric cancer progression by increasing the metastatic potential resulting from AKT, β-catenin, and HIF-1α activation. Our results clearly suggest that IL-32 is an important mediator for gastric cancer metastasis and independent prognostic predictor of gastric cancer. Clin Cancer Res; 20(9); 2276–88. ©2014 AACR.

Recent studies provide mixed results regarding whether the perception of facial attractiveness is increased or decreased by partial occlusion with a sanitary mask. One set of studies demonstrated that occluding the bottom half of a face increased facial attractiveness. This effect is thought to occur because the occluded area is interpolated by an average facial representation that is perceived as attractive. However, several groups of studies showed that partial occlusion can increase or decrease perceived attractiveness depending on the attractiveness of the original (unoccluded) face, due to regression to the mean. To reconcile this inconsistency, we propose that the occluded area is interpolated not by an average facial representation, but by a template of moderate attractiveness, shaped by the distribution of each viewer’s experience. This hypothesis predicts an interaction between occlusion and the attractiveness of the original face so that occluded attractive faces are rated as less attractive, while occluded unattractive faces are rated as more attractive. To examine this hypothesis, the present study used attractiveness-rating tasks with mask-free versus masked faces in own-race and other-races categories. Viewers were familiar with own-race faces and unfamiliar with other-races faces. If moderate-attractiveness interpolation were the explanatory factor, the interaction between the occlusion and the attractiveness of the original face should be found only in the rating of own-race faces. Consistent with this hypothesis, the interaction between the occlusion and the attractiveness of the original faces was significant only for the own-race faces. Specifically, wearing a sanitary mask decreased the facial attractiveness of attractive faces in the own-race, while it increased the attractiveness regardless of the level of facial attractiveness in other-races. These findings suggest that the occluded area of own-race faces is interpolated by a facial template of moderate attractiveness. The other-races template could be developed using familiar exemplars such as celebrities. Thus, interpolation by such a template should result in elevated attractiveness relative to that by an own-race template. Accordingly, the apparent inconsistency in the literature regarding the effect of partial occlusion on physical attractiveness can be explained in terms of differences in the template involving interpolation of the occluded area.

Meiotic drive is a phenomenon wherein a genetic element achieves a higher rate of transmission than dictated by Mendelian segregation (1-3). One proposed mechanism for meiotic drivers to achieve biased transmission is by sabotaging essential processes of gametogenesis (e.g. spermatogenesis), leading to demise of gametes that contain their opponents (1). Studies inD. simulanshave recently found that a set of meiotic driver genes contain a sequence homologous to protamines (4, 5), critical proteins that package sperm chromatin (6-8). However, the underlying mechanisms of drive and the relevance of protamine-like sequences in meiotic drive remain unknown. While studying the function of Modulo, the homolog of Nucleolin inDrosophila melanogaster(9, 10), we unexpectedly discovered Y-linked protamine genes function as a meiotic driver: we found thatmodulomutant’s known sterility is caused by deregulation of the autosomal protamine-like gene (Mst77F) and its Y chromosome-linked homolog (Mst77Y). Modulo regulates these genes at the step of polyadenylation of the transcripts. We show thatMst77Ylikely acts as a dominant-negative form ofMst77F, interfering with the process of histone-to-protamine transition, leading to nuclear decompaction. Overexpression ofMst77Yin a wild-type background is sufficient to cause nuclear decompaction and results in the biased demise of X chromosome-bearing sperm. We propose that dominant-negative protamine variants may be a common strategy found in male meiotic drive and may explain known rapid divergence of protamine genes.Significance statementProtamines are small, highly positively charged proteins that are required for packaging DNA to produce mature sperm with highly-condensed nuclei capable of fertilization. Even small changes in the dosage of protamines in humans is associated with infertility. Yet, despite their essential function, protamines are rapidly evolving. It has been speculated that protamines’ rapid divergence may be explained by their potential participation in genomic conflict. Our work implicates the involvement of Y chromosome-linked multicopy protamine-like genes in meiotic drive inDrosophila melanogaster. Our results suggest that dominant negative protamines can sabotage the process of nuclear compaction during spermiogenesis, revealing a potential cellular mechanism of sperm killing in meiotic drive.

The aim of the study was to examine the effects of environmental factors including disinfection on airborne microbiome during the coronavirus disease 2019 pandemic, we evaluated indoor and outdoor air collected from 19 classrooms regularly disinfected. Extracted bacterial and fungal DNA samples were sequenced using the Illumina MiSeq™ platform. Using bacterial DNA copy number concentrations from qPCR analysis, multiple linear regressions including environmental factors as predictors were performed. Microbial diversity and community composition were evaluated. Classrooms disinfected with spray ≤1 week before sampling had lower bacterial DNA concentration (3116 DNA copies/m

This study tests the influence of wearing a protective face mask on the perceived attractiveness of the wearer. Participants who identified as White, and who varied in their ideological stance toward mask wearing, rated the attractiveness of facial photographs. The photos varied in baseline attractiveness (low, medium, and high), race (White and Asian), and whether or not the face was wearing a protective mask. Attitudes regarding protective masks were measured after the rating task using a survey to identify participants as either pro- or anti-mask. The results showed that masked individuals of the same race were generally rated as more attractive than unmasked individuals, but that masked individuals of another race were rated as less attractive than unmasked individuals. Moreover, pro-mask participants rated masked individuals as generally more attractive than unmasked individuals, whereas anti-maskers rated masked individuals as less attractive. A control experiment, replicating the procedure but replacing the protective masks with a partially occluding notebook, showed that these effects were mask-specific. These results demonstrate that perceived attractiveness is affected by characteristics of the viewer (attitudes toward protective masks), their relationship to the target (same or different race), and by circumstances external to both (pandemic).

Updating spatial representations in visual and auditory working memory relies on common processes, and the modalities should compete for attentional resources. If competition occurs, one type of spatial information is presumably weighted over the other, irrespective of sensory modality. This study used incompatible spatial information conveyed from two different cue modalities to examine relative dominance in memory updating. Participants mentally manoeuvred a designated target in a matrix according to visual or auditory stimuli that were presented simultaneously, to identify a terminal location. Prior to the navigation task, the relative perceptual saliences of the visual cues were manipulated to be equal, superior, or inferior to the auditory cues. The results demonstrate that visual and auditory information competed for attentional resources, such that visual/auditory guidance was impaired by incongruent cues delivered from the other modality. Although visual bias was generally observed in working-memory navigation, stimuli of relatively high salience interfered with or facilitated other stimuli regardless of modality, demonstrating the processing symmetry of spatial updating in visual and auditory spatial working memory. Furthermore, this processing symmetry can be identified during the encoding of sensory inputs into working-memory representations. The results imply that auditory spatial updating is comparable to visual spatial updating in that salient stimuli receive a high priority when selecting inputs and are used when tracking spatial representations.

Noting that the aftermath of the global financial crisis has left many advanced economies with very high sovereign debt ratios and some emerging markets with high debt, this report considers whether there are ways to expand fiscal space that do not involve countries paying down debt or promising to do so in the future, to make fiscal consolidation more growth-friendly. It explains that policymakers argue that their fiscal space is limited and that it would be difficult to take advantage of the opportunity of low interest rates to undertake fiscal expansion, and it considers a ways to raise fiscal space that does not require contractionary fiscal policy and whether there is a way to make fiscal consolidation more growth-friendly to produce larger gains in fiscal space. It argues that debt management policies may provide an answer to expanding fiscal space for a given path of primary fiscal balances by reducing the risk that a sovereign may default in bad states and generate a payoff in terms of reduced to real borrowing costs. It describes two debt management policies: issuance of GDP-linked debt and issuance of longer maturity bonds, as opposed to short-term debt. It focuses on the effect of these debt management policies on real borrowing costs and default risk for the sovereign and details the literature on GDP-linked debt and the maturity structure and how the report fills gaps in the literature; how uncertainty affects fiscal space and how debt management can play a role in increasing it, with estimates and simulations of potential gains in fiscal space flowing from debt management; and the sensitivity of the findings to underlying assumptions and policy implications.

Supplemental material, sj-docx-1-qjp-10.1177_17470218221103253 for Processing symmetry between visual and auditory spatial representations in updating working memory by Tomoki Maezawa and Jun I Kawahara in Quarterly Journal of Experimental Psychology

Supplemental material, sj-docx-1-qjp-10.1177_17470218221103253 for Processing symmetry between visual and auditory spatial representations in updating working memory by Tomoki Maezawa and Jun I Kawahara in Quarterly Journal of Experimental Psychology

Wearing face masks in public has become the norm in many countries post-2020. Although mask-wearing is effective in controlling infection, it has the negative side effect of occluding the mask wearer’s facial expressions. The purpose of this study was to investigate the effects of wearing transparent masks on the perception of facial expressions. Participants were required to categorize the perceived facial emotion of female (Experiment 1) and male (Experiment 2) faces with different facial expressions and to rate the perceived emotion intensity of the faces. Based on the group, the participants were assigned to, the faces were presented with a surgical mask, a transparent mask, or without a mask. The results showed that wearing a surgical mask impaired the performance of reading facial expressions, both with respect to recognition and perceived intensity of facial emotions. Specifically, the impairments were robustly observed in fear and happy faces for emotion recognition, and in happy faces for perceived intensity of emotion in Experiments 1 and 2. However, the impairments were moderated by wearing a transparent mask instead of a surgical mask. During the coronavirus disease 2019 (COVID-19) pandemic, the transparent mask can be used in a range of situations where face-to-face communication is important.

The allocation of attention is affected by internal emotional states, such as anxiety and depression. The attention captured by real images of negative faces can be quantified by emotional probe tasks. The present study investigated whether attentional bias toward drawings of negative faces (line drawings and cartoon faces) differs from that of real faces. Non-clinical university students indicated their levels of anxiety and depression via self-report questionnaires, and completed a probe discrimination task under three face image conditions in a between-participants design. Significant correlations were found between bias scores and scores on the self-reported BDI-II under the real face condition. However, two types of face drawings were only weakly correlated with self-report scores. In our probe task to investigate attentional bias to facial stimuli in nonclinical adults, the strength of the relationship between depression and attentional bias to negative face was stronger for real faces than for face drawings.

Although visual and auditory inputs are initially processed in separate perception systems, studies have built on the idea that to maintain spatial information these modalities share a component of working memory. The present study used working memory navigation tasks to examine functional similarities and dissimilarities in the performance of updating tasks. Participants mentally updated the spatial location of a target in a virtual array in response to sequential pictorial and sonant directional cues before identifying the target's final location. We predicted that if working memory representations are modality-specific, mixed-modality cues would demonstrate a cost of modality switching relative to unimodal cues. The results indicate that updating performance using visual unimodal cues positively correlated with that using auditory unimodal cues. Task performance using unimodal cues was comparable to that using mixed modality cues. The results of a subsequent experiment involving updating of target traces were consistent with those of the preceding experiments and support the view of modality-nonspecific memory.

The study sought to determine as to which among the three proposed apparatuses namely: localized aqueous solution lamp, localized aqueous solution mini fan and localized aqueous solution Ferris wheel best demonstrated electrical conductivity of aqueous solutions and its effectiveness. It also sought to find out the perception of students when these localized apparatuses have been utilized in the activity. The respondents of this study were the 123 Grade 7 students of Pantao National High School, school year 2018-2019. The researcher utilized the descriptive method. The researcher also used validated questionnaires that measured the performance and perception of the students. The statistical tool used in the study includes, mean, t-test for independent data, weighted mean, Spearman rank correlation coefficient and ANOVA. The result of the study indicated that the posttest performance of the students did not meet expectationswhereas, their pretest performance was generally in satisfactory level. The marked improvement of their performance was attributed from the utilization of locally made apparatuses. Moreover, the study revealed that the three apparatuses had different effects among the students where, localized aqueous solution lamp had better effect on students, while localized aqueous solution mini fan was as good as miniature Ferris wheel. Further, the extent of perception among students on the utilization of localized apparatuses in terms of motivation, cognition and interaction was high. &nbsp

Control of open-shell character of meso-meso linked porphyrin meso-oxy radical dimers has been demonstrated by core metalation. Namely, NiII -porphyrin dimer 6Ni exhibits a clear 1 H NMR spectrum and a distorted but rather coplanar quinonoidal structure consisting of two ruffled porphyrin rings, in accordance with the previous report. Freebase dimer 6H2 shows a similar quinonoidal structure in the solid state but displays slightly broader and temperature-dependent 1 H NMR spectra, indicating a partial diradical character in solution that increases at high temperature. In sharp contrast, bis-imidazole-coordinated ZnII -porphyrin dimer 6ZnIm2 exhibits a perpendicular structure consisting of two planar ZnII -porphyrins and has been characterized as a distinct open-shell diradical on the basis of its non-observable 1 H NMR signals, a clear ESR signal, and a characteristic absorption spectrum reaching about 1700 nm. Despite the distinct diradical character, 6ZnIm2 is an extremely stable molecule.

Increased Crabp2 levels have been found in various types of cancer, and are associated with poor patients’ survival. Although Crabp2 is found to be overexpressed in lung cancer, its role in metastasis of lung cancer is unclear. In this study, Crabp2 was overexpressed in high-metastatic C10F4 than low-metastatic lung cancer cells. Analysis of clinical samples revealed that high CRABP2 levels were correlated with lymph node metastases, poor overall survival, and increased recurrence. Knockdown of Crabp2 decreased migration, invasion, anoikis resistance, and in vivo metastasis. Crabp2 was co-immunoprecipitated with HuR, and overexpression of Crabp2 increased HuR levels, which promoted integrin β1/FAK/ERK signaling. Inhibition of HuR or integrin β1/FAK/ERK signaling reversed the promoting effect of Crabp2 in migration, invasion, and anoikis resistance. Knockdown of Crabp2 further inhibited the growth of cancer cells as compared with that by gemcitabine or irinotecan alone. The expression of Crabp2 in human lung tumors was correlated with stress marker CHOP. In conclusion, our findings have identified the promoting role of Crabp2 in anoikis resistance and metastasis. CRABP2 may serve as a prognostic marker and targeting CRABP2 may be exploited as a modality to reduce metastasis.

Connexin, a four-pass transmembrane protein, contributes to assembly of gap junctions among neighboring cells and thus facilitates gap junctional intercellular communication (GJIC). Traditionally, the roles of connexins were thought to mediate formation of hemichannels and GJIC assembly for transportation of ions and small molecules. Many studies have observed loss of GJIC, due to reduced expression or altered cytoplasmic localization of connexins, in primary tumor cells. Connexins are generally considered tumor-suppressive. However, recent studies of clinical samples suggested a different role of connexins in that expression levels and membrane localization of connexins, including Connexin 43 (Cx43, GJA1) and Connexin 26 (Cx26, GJB2), were found to be enhanced in metastatic lesions of cancer patients. Cx43- and Cx26-mediated GJIC was found to promote cancer cell migration and adhesion to the pulmonary endothelium. Regulatory circuits involved in the induction of connexins and their functional effects have also been reported in various types of cancer. Connexins expressed in stromal cells were correlated with metastasis and were implicated in regulating metastatic behaviors of cancer cells. Recent studies have revealed that connexins can contribute to cellular phenotypes via multiple ways, namely 1) GJIC, 2) C-terminal tail-mediated signaling, and 3) cell-cell adhesion during gap junction formation. Both expression levels and the subcellular localization could participate determining the functional roles of connexins in cancer. Compounds targeting connexins were thus tested as potential therapeutics intervening metastasis or chemoresistance. This review focuses on the recent findings in the correlation between the expression of connexins and patients’ prognosis, their roles in metastasis and chemoresistance, as well as the implications and concerns of using connexin-targeting drugs as anti-metastatic therapeutics. Overall, connexins may serve as biomarkers for cancer prognosis and as therapeutic targets for intervening metastasis and chemoresistance.

Most lung cancer patients are diagnosed late with metastasis, which is the major cause of cancer-related death and recurrent tumors that often exhibit chemoresistance. In the present study, we initially identified gap junction beta-4 protein (Gjb4) to be overexpressed in highly metastatic cancer cells selected by their enhanced binding to serum components. Overexpression or knockdown of Gjb4 increased or decreased lung metastasis of syngeneic mice, respectively. We found that Gjb4 expression was higher in lung tumors than normal tissues (p = 0.0026), and Gjb4 levels in blood buffy coat samples showed significant performance in diagnosing stage I–III (p = 0.002814) and stage IV (p

Background and aims Although it is important to analyze the hemodynamic factors related to the right ventricle (RV) after left ventricular assist device (LVAD) implantation, previous studies have focused only on the alteration of the ventricular shape and lack quantitative analysis of the various hemodynamic parameters. Therefore, we quantitatively analyzed various hemodynamic parameters related to the RV under normal, heart failure (HF), and HF incorporated with continuous flow LVAD therapy by using a computational model. Methods In this study, we combined a three-dimensional finite element electromechanical model of ventricles, which is based on human ventricular morphology captured by magnetic resonance imaging (MRI) with a lumped model of the circulatory system and continuous flow LVAD function in order to construct an integrated model of an LVAD implanted-cardiovascular system. To induce systolic dysfunction, the magnitude of the calcium transient function under HF condition was reduced to 70% of the normal value, and the time constant was reduced by 30% of the normal value. Results Under the HF condition, the left ventricular end systolic pressure decreased, the left ventricular end diastolic pressure increased, and the pressure in the right atrium (RA), RV, and pulmonary artery (PA) increased compared with the normal condition. The LVAD therapy decreased the end-systolic pressure of the LV by 41%, RA by 29%, RV by 53%, and PA by 71%, but increased the right ventricular ejection fraction by 52% and cardiac output by 40%, while the stroke work was reduced by 67% compared with the HF condition without LVAD. The end-systolic ventricular tension and strain decreased with the LVAD treatment. Conclusion LVAD enhances CO and mechanical unloading of the LV as well as those of the RV and prevents pulmonary hypertension which can be induced by HF.

Biological responses on biomaterials occur either on their surface or at the interface. Therefore, surface characterization is an essential step in the fabrication of ideal biomaterials for achieving effective control of the interaction between the material surface and the biological environment. Herein, we applied femtosecond laser ablation on electrospun fibrous scaffolds to fabricate various hierarchical patterns with a focus on the alignment of cells. We investigated the simultaneously stimulated response of cardiomyoblasts based on multiple topographical cues, including scales, oriented directions, and spatial arrangements, in the fibrous scaffolds. Our results demonstrated a synergistic effect on cell behaviors of one or more structural arrangements in a homogeneous orientation, whereas antagonistic effects were observed for cells arranged on a surface with heterogeneous directions. Taken together, these results indicate that our hierarchically patterned fibrous scaffolds may be useful tools for understanding the cellular behavior on fibrous scaffolds used to mimic an extracellular matrix-like environment. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1732-1742, 2018.

Diagenetic silica enrichment in fracture‐associated halos that crosscut lacustrine and unconformably overlying aeolian sedimentary bedrock is observed on the lower north slope of Aeolis Mons in Gale crater, Mars. The diagenetic silica enrichment is colocated with detrital silica enrichment observed in the lacustrine bedrock yet extends into a considerably younger, unconformably draping aeolian sandstone, implying that diagenetic silica enrichment postdates the detrital silica enrichment. A causal connection between the detrital and diagenetic silica enrichment implies that water was present in the subsurface of Gale crater long after deposition of the lacustrine sediments and that it mobilized detrital amorphous silica and precipitated it along fractures in the overlying bedrock. Although absolute timing is uncertain, the observed diagenesis likely represents some of the most recent groundwater activity in Gale crater and suggests that the timescale of potential habitability extended considerably beyond the time that the lacustrine sediments of Aeolis Mons were deposited.

Purpose: The proinflammatory cytokine interleukin-32 (IL-32) is a novel tumor marker highly expressed in various human carcinomas, including gastric cancer. However, its effects on prognosis of patients with gastric cancer and cancer metastasis are virtually unknown at present. The main aim of this study was to explore the clinical significance of IL-32 in gastric cancer and further elucidate the molecular mechanisms underlying IL-32–mediated migration and invasion. Experimental Design: Gastric cancer cells with ectopic expression or silencing of IL-32 were examined to identify downstream molecules and establish their effects on cell motility, invasion, and lung metastasis in vivo. Results: IL-32 was significantly upregulated in gastric cancer and positively correlated with aggressiveness of cancer and poor prognosis. Ectopic expression of IL-32 induced elongated morphology and increased cell migration and invasion via induction of IL-8, VEGF, matrix metalloproteinase 2 (MMP2), and MMP9 expression via phosphor-AKT/phospho-glycogen synthase kinase 3β/active β-catenin as well as hypoxia-inducible factor 1α (HIF-1α) signaling pathways. Conversely, depletion of IL-32 in gastric cancer cells reversed these effects and decreased lung colonization in vivo. Examination of gene expression datasets in oncomine and staining of gastric cancer specimens demonstrated the clinical significance of IL-32 and its downstream molecules by providing information on their coexpression patterns. Conclusions: IL-32 contributes to gastric cancer progression by increasing the metastatic potential resulting from AKT, β-catenin, and HIF-1α activation. Our results clearly suggest that IL-32 is an important mediator for gastric cancer metastasis and independent prognostic predictor of gastric cancer. Clin Cancer Res; 20(9); 2276–88. ©2014 AACR.

How high can public debt rise without compromising fiscal solvency? We answer this question using a stochastic model of sovereign default in which risk-neutral investors lend to a government that displays ‘fiscal fatigue’, whereby its ability to increase primary balances cannot keep pace with rising debt. As a result, the government faces an endogenous debt limit beyond which debt cannot be rolled over. Using data for 23 advanced economies over the period 1970–2007, we find evidence of a fiscal reaction function with these features, and use it to compute ‘fiscal space’, defined as the difference between current debt ratios and the estimated debt limits.

Data gathered with the Dynamic Albedo of Neutron (DAN) instrument onboard rover Curiosity were analyzed for variations in subsurface neutron flux and tested for possible correlation with local geological context. A special DAN observation campaign was executed, in which 18 adjacent DAN active measurements were acquired every 0.75-1.0 m to search for the variations of subsurface hydrogen content along a 15 m traverse across geologic contacts between the Sheepbed and Gillespie Lake members of the Yellowknife Bay formation. It was found that several subunits in Sheepbed and Gillespie Lake could be characterized with different depth distributions of water-equivalent hydrogen (WEH) and different chlorine-equivalent abundance responsible for the distribution of neutron absorption elements. The variations of the average WEH at the top 60 cm of the subsurface are estimated at up to 2-3%. Chlorine-equivalent neutron absorption abundances ranged within 0.8-1.5%. The largest difference in WEH and chlorine-equivalent neutron absorption distribution is found between Sheepbed and Gillespie Lake. Key Points DAN special campaign in Yellowknife Bay DAN local measurements of water and chlorine abundance Correlation of DAN measurements and geological context ©2014. American Geophysical Union. All Rights Reserved.

Mars' Atmosphere from Curiosity The Sample Analysis at Mars (SAM) instrument on the Curiosity rover that landed on Mars in August last year is designed to study the chemical and isotopic composition of the martian atmosphere. Mahaffy et al. (p. 263 ) present volume-mixing ratios of Mars' five major atmospheric constituents (CO 2 , Ar, N 2 , O 2 , and CO) and isotope measurements of 40 Ar/ 36 Ar and C and O in CO 2 , based on data from one of SAM's instruments, obtained between 31 August and 21 November 2012. Webster et al. (p. 260 ) used data from another of SAM's instruments obtained around the same period to determine isotope ratios of H, C, and O in atmospheric CO 2 and H 2 O. Agreement between the isotopic ratios measured by SAM with those of martian meteorites, measured in laboratories on Earth, confirms the origin of these meteorites and implies that the current atmospheric reservoirs of CO 2 and H 2 O were largely established after the period of early atmospheric loss some 4 billion years ago.

Low-income countries routinely experience exogenous disturbances-sharp swings in the terms of trade, export demand, natural disasters, and volatile financial flows-that contribute to higher volatility in aggregate output and consumption compared with other countries. Assessing Reserve Adequacy in Low-Income Countries presents the findings of an analysis of a range of external shocks faced by these countries, beginning with a discussion of the impact of external shocks on macroeconomic growth, volatility, and welfare. Although sound macroeconomic and prudential policy frameworks are the first line of defense for limiting vulnerability, international reserves constitute the main form of self-insurance against such shocks. The evidence suggests that low-income countries with reserve coverage above three months of imports were better able to smooth consumption and absorption in the face of external shocks compared with those with lower reserve holdings. The analysis also points to the importance of country characteristics and vulnerabilities in assessing reserve adequacy

We undertook a prospective study comparing the unreamed interlocking nail to Hoffmann external skeletal fixation (ESF) in the treatment of 36 consecutive patients with open type IIIA and IIIB tibia fractures. The choice of interlocking nail or Hoffmann ESF was randomized, ultimately producing four different patient groups: group 1, type IIIA fractures treated by interlocking nail; group 2, type IIIA fractures treated by ESF; group 3, type IIIB fractures with interlocking nail; and group 4, type IIIB fractures with ESF. The average length of follow-up was 20.5 months. The infection rate was highest in group 3 (3 of 8). The malrotation, malunion, and nonunion rates were highest in group 4 and lowest in group 1. These results suggest the unreamed interlocking nail is a good choice for the treatment of open type IIIA tibia fractures, but not recommended for the treatment of open type IIIB tibia fractures because of the high infection rate.

This paper examines why surges in capital flows to emerging market economies (EMEs) occur, and what determines the allocation of capital across countries during such surge episodes. We use two different methodologies to identify surges in EMEs over 1980-2009, differentiating between those mainly caused by changes in the country's external liabilities (reflecting the investment decisions of foreigners), and those caused by changes in its assets (reflecting the decisions of residents). Global factors-including US interest rates and risk aversion¡-are key to determining whether a surge will occur, but domestic factors such as the country's external financing needs (as implied by an intertemporal optimizing model of the current account) and structural characteristics also matter, which explains why not all EMEs experience surges. Conditional on a surge occurring, moreover, the magnitude of the capital inflow depends largely on domestic factors including the country's external financing needs, and the exchange rate regime. Finally, while similar factors explain asset- and liability-driven surges, the latter are more sensitive to global factors and contagion.

In this note, the authors reexamine the issue of debt sustainability in a large group of advanced economies. Their hypothesis is that, when debt is in a moderate range, its dynamics are sustainable in the sense that increases in debt elicit sufficient increases in primary fiscal balances to stabilize the debt-to-GDP ratio. At high debt levels, however, the dynamics may turn unstable, and the debt ratio may not converge to a finite level. Such a framework allows the authors to define a “debt limit” that is consistent with a country’s historical track record of adjustment in the sense that, without an extraordinary fiscal effort, any debt increment beyond this limit would cause debt to increase without bound. This debt limit is not an absolute and immutable barrier, however, but rather defines a critical point above which a country’s normal fiscal response to rising debt becomes insufficient to maintain debt sustainability. Nor should this debt limit be interpreted as being in any sense the optimal level of public debt. Indeed, since this limit delineates the point at which fiscal solvency is called into question—and the analysis abstracts entirely from liquidity/rollover risk—prudence dictates that countries will typically want to be well below their debt limit. Given a country’s normal pattern of adjustment, “fiscal space” is then simply the difference between its debt limit and its current level of debt.

This paper examines the various roles of IMF financing in crisis prevention. Emerging market economies that experienced financial crises in the past have been subject to enormous economic and social costs, highlighting the importance of crisis prevention. While the main defense against a crisis lies in a country’s own policies and institutional framework, the IMF can contribute to these efforts through its surveillance activities, provision of technical assistance, and promotion of standards and codes. But the IMF may be able to contribute to crisis prevention more directly by providing contingent financial support. This paper explores the theoretical basis of, and empirical evidence for, possible “crisis prevention programs.”

Quantum dots (QD) are fluorescent semiconductor nanocrystals that are emerging as superior alternatives to the conventional organic dyes used in biological applications. Although QDs offer several advantages over conventional fluorescent dyes, including greater photostability and a wider range of excitation and (or) emission wavelengths, their toxicity has been an issue in its wider use as an analytic, diagnostic and therapeutic tool. We prepared a conjugate QD with an internalizing antibody and demonstrated that the QD–antibody conjugate is efficiently internalized into cells and is visible even after multiple divisions. We demonstrate that the internalized QD is nontoxic to cells and provides a sensitive tool for long-term molecular imaging.

By using a simple intertemporal model of the current account, I show that the exchange rate elasticity of the trade balance would ceteris paribus be smaller for countries with higher government spending ratios (relative to GDP) and with more limited scope for private consumption smoothing. This finding may have important implications for the design of adjustment programs and for resolving current global imbalances. It could also help explain and reconcile mixed empirical findings on trade elasticities.

By using a simple intertemporal model of the current account, I show that the exchange rate elasticity of the trade balance would ceteris paribus be smaller for countries with higher government spending ratios (relative to GDP) and with more limited scope for private consumption smoothing. This finding may have important implications for the design of adjustment programs and for resolving current global imbalances. It could also help explain and reconcile mixed empirical findings on trade elasticities.

This paper examines how debt maturity affects the debt limit, defined as the maximum amount of debt a government can afford without defaulting. We develop a model where investors are risk neutral, the primary balance is stochastic but exogenous, and default occurs solely due to the government’s inability to pay. We find that debt limit is higher for long-term debt. Underlying this finding is the intrinsic advantage of long-term debt to price in future upside potential in fiscal outcomes in its current price. Such advantage makes long-term debt effectively cheaper than short-term debt at the margin, and leads to a higher debt limit. Simulation results suggest that the effect of debt maturity on debt limit could be substantial—particularly, if fiscal outcomes are subject to large uncertainty.

This paper presents an analytical framework for considering the role of IMF-supported programs in preventing crises, particularly capital account crises. The model builds upon the global games framework to establish a unique relationship between the crisis probability and the parameters of the program, which is assumed to be negotiated between the IMF and the member country, taking explicit account of each party's interests. In the model, from the perspective of the borrowing country, IMF financing and policy adjustment are (perfect) substitutes inasmuch as they both contribute to the country's liquidity and thus reduce the likelihood of a crisis. In equilibrium, however, IMF financing promotes stronger policies, implying that financing and adjustment are strong complements in crisis prevention. Conditionality plays a crucial role in sustaining the program, providing mutual assurances-to the member country that, if it undertakes the agreed policies, financing will indeed be forthcoming, and to the IMF that the country will implement the agreed policies as the IMF disburses its resources. The model helps explain how liquidity crises may come about, how IMF support can reduce the likelihood of a crisis by providing liquidity and sustaining stronger policies, and why the observed mix between financing and adjustment may vary across programs.

This collection of papers examines IMF-supported programs over the period 1995-2000 in both middle-income and low-income countries. In order to seek insights from a comparison across different types of programs, the sections entitled"Objectives and Outcomes," "Policy Formulation and Analytical Frameworks," and "Macroeconomic and Structural Policies" address a number of questions regarding the economic programs for which national authorities seek the IMF’s financial support: the specific goals of IMF-supported programs, and the challenges they face; how programs are formulated; the components of programs; and how program success should be judged.

In this study, we examined the effect of overexpression of tissue inhibitor of metalloproteinase (TIMP)-3 on the angiogenic phenotype expressed by vascular endothelial cells (ECs). ECs were infected with a recombinant adenovirus carrying the TIMP-3 gene at various multiplicities of infection, and TIMP-3 expression by transfected cells was confirmed by Western blotting and reverse zymography. At transfection doses of 6.25, 12.5, 25, 50 and 100 multiplicity of infection, EC migration was reduced to 66, 45, 25, 17 and 5%, respectively, of that of the control. At the multiplicity of infection of 20, capillary tube length was reduced by 80% compared to that of the control. Thus, expression of TIMP-3 by ECs effectively inhibited EC migration and tube formation. Overexpression of TIMP-3 by ECs may be considered a gene therapy strategy for the treatment of pathological angiogenesis such as cancer and diabetic retinopathy.

The title compound, 2-(2-cyano-2-ethoxycarbonylethyl)-8-quinolinol (I), C15H14N2O3, crystallizes in the triclinic system, space group P1 with cell constants: a = 5.9476(5), b = 9.9004(5), c = 12.3459(4)A, α = 68.468(9), β = 82.168(14), γ = 89.144(15)°, V = 669.44(7)A3, Z = 2. 2-(2,2-Dicyanovinyl)-8-quinolinol (II), C13H7N3O, crystallizes in the triclinic system, space group P1 with a = 7.040(4), b = 8.131(5), c = 10.198(5)A, α = 97.01(2), β = 108.93(3), γ = 102.45(2)°, V = 527.4(5)A3, Z = 2. The structure of II adopts a planar conformation.