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• Reveals distinct roles of the preparatory and payoff phases of glycolysis in hematopoietic stem cells (HSCs). • Glycolysis-defective quiescent HSCs keep adenosine-triphosphate levels by mitochondrial compensation. • The nonoxidative pentose phosphate pathway (PPP) compensates for Gpi1 deficiency. • Gapdh deficiency impairs proliferative HSCs by lacking compensatory PPP. In physiological conditions, most adult hematopoietic stem cells (HSCs) maintain a quiescent state. Glycolysis is a metabolic process that can be divided into preparatory and payoff phases. Although the payoff phase maintains HSC function and properties, the role of the preparatory phase remains unknown. In this study, we aimed to investigate whether the preparatory or payoff phases of glycolysis were required for maintenance of quiescent and proliferative HSCs. We used glucose-6-phosphate isomerase (Gpi1) as a representative gene for the preparatory phase and glyceraldehyde-3-phosphate dehydrogenase (Gapdh) as a representative gene for the payoff phase of glycolysis. First, we identified that stem cell function and survival were impaired in Gapdh-edited proliferative HSCs. Contrastingly, cell survival was maintained in quiescent Gapdh- and Gpi1-edited HSCs. Gapdh- and Gpi1-defective quiescent HSCs maintained adenosine-triphosphate (ATP) levels by increasing mitochondrial oxidative phosphorylation (OXPHOS), whereas ATP levels were decreased in Gapdh-edited proliferative HSCs. Interestingly, Gpi1-edited proliferative HSCs maintained ATP levels independent of increased OXPHOS. Oxythiamine, a transketolase inhibitor, impaired proliferation of Gpi1-edited HSCs, suggesting that the nonoxidative pentose phosphate pathway (PPP) is an alternative means to maintain glycolytic flux in Gpi1-defective HSCs. Our findings suggest that OXPHOS compensated for glycolytic deficiencies in quiescent HSCs, and that in proliferative HSCs, nonoxidative PPP compensated for defects in the preparatory phase of glycolysis but not for defects in the payoff phase. These findings provide new insights into regulation of HSC metabolism, which could have implications for development of novel therapies for hematologic disorders. [ABSTRACT FROM AUTHOR]

Dedifferentiated liposarcoma occurs predominantly in the retroperitoneum. Given the paucity of cases, information on the clinical characteristics of this entity in the extremities and trunk wall is quite limited. In particular, the significance of preoperative evaluation and principles of intraoperative management of the different components, i.e., well-differentiated and dedifferentiated areas, are still to be defined. Clinical characteristics, treatment outcomes, and risk factors for poor oncological outcomes in cases of dedifferentiated liposarcoma in the extremity or trunk wall were analyzed by a retrospective, multicentric study. A total of 132 patients were included. The mean duration from the initial presentation to dedifferentiation was 101 months in dedifferentiation-type cases. The 5-year local recurrence-free survival, metastasis-free survival, and disease-specific survival rates were 71.6%, 75.7%, and 84.7%, respectively. Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis. A percentage of dedifferentiated area over 87.5%, marginal/intralesional margin, and R1/2 resection in the dedifferentiated area were independent risk factors for local recurrence. Dedifferentiated areas over 36 cm2, French Federation of Cancer Centers Sarcoma Group grade III, and intralesional or marginal resection were independent risk factors for metastasis. A dedifferentiated area over 77 cm2 and lung metastasis were independent risk factors for disease-specific mortality. The typical clinical characteristics of dedifferentiated liposarcoma in the extremity and trunk wall were reconfirmed in the largest cohort ever. The evaluation of the dedifferentiated area in terms of grade, extension, and pathological margin, together with securing adequate surgical margins, was critical in the management of this entity. ● The mean time to dedifferentiation was 101 months in dedifferentiation type. ● The 5-year local recurrence and metastasis-free survival were 71.6% and 75.7%. ● The 5-year disease-specific survival rate was 84.7%. ● Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis. ● Grade, extension, and margin in the dedifferentiated area are critical to outcomes. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.icarus.2010.04.021 Byline: Hiroshi Kobayashi (a), Hidekazu Tanaka (b), Alexander V. Krivov (a), Satoshi Inaba (c) Keywords: Planetary formation; Planetesimals; Collisional physics; Origin, Solar System; Jovian planets Abstract: As planetary embryos grow, gravitational stirring of planetesimals by embryos strongly enhances random velocities of planetesimals and makes collisions between planetesimals destructive. The resulting fragments are ground down by successive collisions. Eventually the smallest fragments are removed by the inward drift due to gas drag. Therefore, the collisional disruption depletes the planetesimal disk and inhibits embryo growth. We provide analytical formulae for the final masses of planetary embryos, taking into account planetesimal depletion due to collisional disruption. Furthermore, we perform the statistical simulations for embryo growth (which excellently reproduce results of direct N-body simulations if disruption is neglected). These analytical formulae are consistent with the outcome of our statistical simulations. Our results indicate that the final embryo mass at several AU in the minimum-mass solar nebula can reach about [approximately equal to]0.1 Earth mass within 10.sup.7 years. This brings another difficulty in formation of gas giant planets, which requires cores with [approximately equal to]10 Earth masses for gas accretion. However, if the nebular disk is 10 times more massive than the minimum-mass solar nebula and the initial planetesimal size is larger than 100km, as suggested by some models of planetesimal formation, the final embryo mass reaches about 10 Earth masses at 3-4AU. The enhancement of embryos' collisional cross sections by their atmosphere could further increase their final mass to form gas giant planets at 5-10AU in the Solar System. Author Affiliation: (a) Astrophysical Institute and University Observatory, Friedrich Schiller University, Schillergaesschen 2-3, 07745 Jena, Germany (b) Institute of Low Temperature Science, Hokkaido University, Kita-Ku Kita 19, Nishi 8, Sapporo 060-0819, Japan (c) School of International Liberal Studies, Waseda University, 1-6-1 Nishi-Waseda, Shinjuku-ku, Tokyo 169-8050, Japan Article History: Received 25 February 2010; Revised 23 April 2010; Accepted 23 April 2010

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.icarus.2009.10.004 Byline: Hiroshi Kobayashi (a)(b), Hidekazu Tanaka (b) Keywords: Collisional physics; Asteroids, Dynamics; Planetary dynamics; Planetary formation Abstract: Mass depletion of bodies through successive collisional disruptions (i.e., collision cascade) is one of the most important processes in the studies of the asteroids belt, the Edgeworth-Kuiper belt, debris disks, and planetary formation. The collisional disruption is divided into two types, i.e., catastrophic disruption and cratering. Although some studies of the collision cascades neglected the effect of cratering, it is unclear which type of disruption makes a dominant contribution to the collision cascades. In the present study, we construct a simple outcome model describing both catastrophic disruption and cratering, which has some parameters characterizing the total ejecta mass, the mass of the largest fragment, and the power-law exponent of the size distribution of fragments. Using this simple outcome model with parameters, we examine the model dependence of the mass depletion time in collision cascades for neglect of coalescence of colliding bodies due to high collisional velocities. We find the cratering collisions are much more effective in collision cascades than collisions with catastrophic disruption in a wide region of the model parameters. It is also found that the mass depletion time in collision cascades is mainly governed by the total ejecta mass and almost insensitive to the mass of the largest fragment and the power-law exponent of fragments for a realistic parameter region. The total ejecta mass is usually determined by the ratio of the impact energy divided by the target mass (i.e. Q-value) to its threshold value Q.sub.D.sup.a for catastrophic disruption, as well as in our simple model. We derive a mass depletion time in collision cascades, which is determined by Q.sub.D.sup.a of the high-mass end of collision cascades. The mass depletion time derived with our model would be applicable to debris disks and planetary formation. Author Affiliation: (a) Astrophysical Institute and University Observatory, Friedrich Schiller University, Schillergaesschen 2-3, 07745 Jena, Germany (b) Institute of Low Temperature Science, Hokkaido University, Kita-Ku Kita 19 Nishi 8, Sapporo 060-0819, Japan Article History: Received 12 June 2009; Revised 24 September 2009; Accepted 1 October 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.icarus.2009.01.002 Byline: Hiroshi Kobayashi (a)(b), Sei-ichiro Watanabe (b), Hiroshi Kimura (c)(a), Tetsuo Yamamoto (a) Keywords: Celestial mechanics; Interplanetary dust; Debris disk Abstract: Dust particles exposed to the stellar radiation and wind drift radially inward by the Poynting-Robertson (P-R) drag and pile up at the zone where they begin to sublime substantially. The reason they pile up or form a ring is that their inward drifts due to the P-R drag are suppressed by stellar radiation pressure when the ratio of radiation pressure to stellar gravity on them increases during their sublimation phases. We present analytic solutions to the orbital and mass evolution of such subliming dust particles, and find their drift velocities at the pileup zone are almost independent of their initial semimajor axes and masses. We derive analytically an enhancement factor of the number density of the particles at the outer edge of the sublimation zone from the solutions. We show that the formula of the enhancement factor reproduces well numerical simulations in the previous studies. The enhancement factor for spherical dust particles of silicate and carbon extends from 3 to more than 20 at stellar luminosities L.sub.a=0.8-500L.sub.a, where L.sub.a is solar luminosity. Although the enhancement factor for fluffy dust particles is smaller than that for spherical particles, sublimating particles inevitably form a dust ring as long as their masses decrease faster than their surface areas during sublimation. The formulation is applicable to dust ring formation for arbitrary shape and material of dust in dust-debris disks as well as in the Solar System. Author Affiliation: (a) Institute of Low Temperature Science, Hokkaido University, Kita-Ku Kita 19 Nishi 8, Sapporo 060-0819, Japan (b) Department of Earth and Planetary Sciences, Graduate School of Environmental Studies, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan (c) Center for Planetary Science, Graduate School of Science, Kobe University, Nada-ku Rokkodai-cho 1-1, Kobe 657-8501, Japan Article History: Received 7 March 2008; Revised 16 October 2008; Accepted 8 January 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.icarus.2008.02.005 Byline: Hiroshi Kobayashi (a)(b), Sei-ichiro Watanabe (b), Hiroshi Kimura (a), Tetsuo Yamamoto (a) Keywords: Debris disks; Ices; Celestial mechanics Abstract: In a disk with a low optical depth, dust particles drift radially inward by the Poynting-Robertson (P-R) drag rather than are blown out by stellar radiation pressure following destructive collisions. We investigate the radial distribution of icy dust composed of pure ice and refractory materials in dust-debris disks taking into account the P-R drag and ice sublimation. We find that icy dust particles form a dust ring by their pile-ups at the edge of their sublimation zone, where they sublime substantially at the temperature 100-110 K. The distance of the dust ring is 20-35 AU from the central star with its luminosity L.sub.a[less than or approximately equal to]30L.sub.a and 65(L.sub.a/100L.sub.a).sup.1/2 AU for L.sub.aa[sup.3]30L.sub.a, where L.sub.a is the solar luminosity. The effective optical depth is enhanced by a factor of 2 for L.sub.a[less than or approximately equal to]100L.sub.a and more than 10 for L.sub.aa[sup.3]100L.sub.a. The optical depth of the outer icy dust disk exceeds that of the inner disk filled with refractory particles, namely, the residue of ice sublimation, which are further subjected to the P-R effect. As a result, an inner hole is formed inside the sublimation zone together with a dust ring along the outer edge of the hole. Author Affiliation: (a) Institute of Low Temperature Science, Hokkaido University, Kita-ku Kita 19 Nishi 8, Sapporo 060-0819, Japan (b) Department of Earth and Planetary Sciences, Graduate School of Environmental Studies, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan Article History: Received 17 October 2007; Revised 24 January 2008

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.icarus.2005.02.017 Byline: Hiroshi Kobayashi (a), Shigeru Ida (b), Hidekazu Tanaka (b) Keywords: Kuiper belt objects; Orbits; Origin; Solar System Abstract: We investigate the influence of a stellar fly-by encounter on the Edgeworth-Kuiper belt objects through numerical orbital calculations, in order to explain both mass depletion and high orbital inclinations of the classical Edgeworth-Kuiper belt (CEKB) objects, which have semimajor axis of 42-48 AU and perihelia beyond 35 AU. The observationally inferred total mass of the CEKB is [approximately equal to]1/10 Earth masses, which is only [approximately equal to]0.02 of that extrapolated from the minimum-mass solar nebula model. The CEKB consists of bimodal population: 'hot population' with inclinations ia0.2-0.6 radians and 'cold population' with ia0.1. The observationally suggested difference in size and color of objects between the two populations may imply different origins of the two populations. We find that both the depletion of solid materials in the CEKB and the formation of the hot population are accounted for by a single close stellar encounter with pericenter distance of 80-100 AU and inclination relative to the initial protoplanetary disk a50[degrees]-70[degrees]. Such a stellar encounter highly pumps up eccentricities of most objects in the CEKB and then their perihelia migrate within 35 AU. These objects would be removed by Neptune's perturbations after Neptune is formed at or migrates to the current position (30 AU). Less than 10% of the original objects remain in stable orbits with small eccentricities and perihelion distances larger than 35 AU, in the CEKB, which is consistent with the observation. We find that i of the remaining objects are as large as that of the observed hot population. The only problem is how to stop Neptune's migration at [approximately equal to]30 AU, which is addressed in a separate paper. The depletion by the stellar encounter extends deeply into [approximately equal to]30-35AU, which provides the basis of the formation model for the cold population through Neptune's outward migration by Levison and Morbidelli (2003, Nature, 426, 419-421). The combination of our model with Levison and Morbidelli's model could consistently explain the mass depletion, truncation at 50 AU, bimodal distribution in i, and differences in size and color between the hot and the cold populations in the CEKB. Author Affiliation: (a) Graduate School of Environmental Studies, Nagoya University, E-125 Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan (b) Department of Earth and Planetary Sciences, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8551, Japan Article History: Received 26 March 2004; Revised 24 February 2005

Background: Eribulin is a tubulin and microtubule-targeting drug that has clinical benefit in overall survival (OS) for patients with advanced soft tissue sarcoma. Eribulin's efficacy has been confirmed in several clinical trials, although no clinically useful biomarkers have been identified. We therefore sought to clarify the predictive factor of eribulin treatment, while focusing on systemic inflammation and immune response values.Methods: This study included 33 advanced STS patients treated with eribulin between March 2016 and September 2019. We evaluated the associations of clinical factors influencing the efficacy of eribulin treatment and systemic inflammatory and immune response, including the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the systemic inflammation response index (SIRI), and the prognostic nutrition index (PNI), with progression-free survival (PFS) and OS using the Kaplan-Meier method and log-rank test.Results: NLR, LMR, PLR, SIRI, and PNI were unassociated with PFS. Compared with patients with SIRI <1.5, those with an SIRI ≥1.5 had a significantly shorter OS [median OS 15 months (95% confidence interval [CI] 8-not reached) vs. 7 months (95% CI 3-14), P = 0.04]. Moreover, the PFS tended to be shorter for patients with SIRI ≥1.5 who received chemotherapy after eribulin treatment than in those with SIRI >1.5 [median PFS 92.5 days (95% CI 27-204) vs. 133 days (95% CI 36-507), P = 0.08].Conclusions: High SIRI values may predict poorer overall survival and the efficacy of subsequent drugs after eribulin treatment among patients with advanced soft tissue sarcoma. [ABSTRACT FROM AUTHOR]

We investigate the effects of a passing stellar encounter on a planetesimal disk through analytical calculations and numerical simulations, and derive the boundary radius ([a.sub.planet]) outside which planet formation is inhibited by disruptive collisions with high relative velocities. S. Ida, J. Larwood, and A. Burkert (2000, Astrophys. J. 528, 1013-1025) suggested that a stellar encounter caused inhibition of planet formation in the outer part of a protoplanetary disk. We study orbital eccentricity (e) and inclination (i) of planetesimals pumped up by perturbations of a passing single star. We also study the degree of alignment of longitude of pericenter and ascending node to estimate relative velocities between the planetesimals. We model a protoplanetary system as a disk of massless particles circularly orbiting a host star, following S. Ida, J. Laywood, and A. Burkert (2000, Astrophys. J. 528,1013-1025). The massless particles represent planetesimals. A single star as massive as the host star encounters the protoplanetary system. Numerical orbital simulations show that in the inner region at semimajor axis a [??] 0.2 D where D is the pericenter distance of the encounter, e and i have power-law dependence on (a/D) as e [varies] [(a/D).sup.5/2] and i [varies] [(a/D).sup.3/2], and the longitudes are aligned, independent of the encounter parameters. In the outer region a [??] 0.2 D, and the radial gradient is steeper and is not expressed by a single power law. The longitudes are not aligned. Since planet accretion is inhibited by e as small as 0.01, we focus on the weakly perturbed inner region. We analytically reproduce the power-law dependence and explicitly give numerical factors of the power-law dependence as functions of encounter parameters. We derive the boundary radius ([a.sub.planet]) of the planet-forming region as a function of dynamical parameters of a stellar cluster, assuming the protoplanetary system belongs to the stellar cluster. The radial gradient of e is so steep that the boundary is sharply determined. Planetesimal orbits are significantly modified beyond the boundary, while they are almost intact inside the boundary. This tendency is strengthened by reduction of relative velocity due to the longitude alignment in the inner region. We find a planet [a.sub.planet] ~ 40-60 AU in the case of D ~ 150-200 AU. D ~ 200 AU may be likely to occur in a relatively dens cluster. We point out that the size of planetary systems ([a.sub.planet]) born in a dense cluster may be necessarily restricted to that comparable to the size of a planet region (~30-40 AU) of our Solar System. Key Words: celestial mechanics; orbits; planetesimal; accretion.

Background: Phosphaturic mesenchymal tumors primarily cause tumor-induced osteomalacia, a rare paraneoplastic syndrome, and half occur in soft tissues. There are few reports about the surgical margins of these tumors. This study aimed to clarify the optimal surgical margin for phosphaturic mesenchymal tumors by analyzing radiological and histopathological features.Methods: This study included eight cases, seven primary and one recurrent, of tumor-induced osteomalacia caused by soft-tissue phosphaturic mesenchymal tumors that were surgically treated between January 2000 and January 2019. We evaluated the radiological and histopathological features of all tumors and investigated the correlation of these features, the surgical margin, and recurrence of hypophosphatemia.Results: The tumors were located in superficial (n = 5) and deep (n = 3) tissues. Six of the eight tumors had a clear boundary, but five had an irregular margin. Three tumors had a hypointense rim on T2-weighted images, indicating fibrous tumor encapsulation. Histopathological analysis revealed infiltrative growth in six of the eight tumors, which correlated with an irregular margin seen on imaging. Although there was no recurrence in patients treated with an intended wide margin >1 cm, one of the three patients treated with marginal tumor resection experienced a recurrence of hypophosphatemia, with histopathological analysis showing infiltration of subcutaneous fat. In contrast, two tumors with clear boundaries, regular margins, and fibrous capsule seen on imaging, had no infiltrative growth and were cured by marginal resection. In one recurrent case, tumor infiltration was observed in the previous surgical scar, which was not detected on preoperative imaging.Conclusions: Soft-tissue phosphaturic mesenchymal tumors with an irregular boundary seen on imaging tend to be infiltrative, especially into subcutaneous fat, and should be treated by at least a 1-cm wide margin resection. Tumors with a fibrous capsule with clear and regular margins are cured by marginal margin resection. These findings could inform surgeons' decisions regarding the resection of soft-tissue phosphaturic mesenchymal tumors. [ABSTRACT FROM AUTHOR]

Background: Soft tissue metastasis is rarer than bone metastasis. Patients with soft tissue metastasis generally have a dismal prognosis. The treatment for metastatic lesions is sometimes difficult, because the prognostic factors of patients with soft tissue metastasis remain unelucidated. Therefore, this study aimed to identify these prognostic factors.Methods: Thirty-one patients with soft tissue metastasis were included in the study. We evaluated associations of overall survival with clinical parameters and inflammatory markers using Kaplan-Meier curves and Cox proportional hazards models.Results: Twelve patients received surgery for soft tissue metastasis, while radiation therapy was performed in six cases. The median overall survival after the detection of soft tissue metastasis was 11 months. Univariate analysis revealed that detection of soft tissue metastasis after the multidisciplinary treatment (P = 0.01); solitary metastasis (P = 0.0003); and pretreatment C-reactive protein (CRP) level < 0.4 mg/dL (P < 0.0001), white blood cell count < 8500 × 103/μL (P = 0.0003), and neutrophil-to-lymphocyte ratio < 5 (P = 0.02) were significant good prognostic factors. Multivariate analysis revealed that a CRP value < 0.4 mg/dL (P = 0.07) and solitary metastasis (P = 0.09) were possible significant predictors of survival. Furthermore, in case of CRP levels <0.4 mg/dL and metastatic tumor resection, patients had a good prognosis; however, when the CRP levels increased to 0.4 mg/dL and above, patients had a poor prognosis, irrespective of tumor resection.Conclusions: CRP is potentially useful for determining the indication of radical metastasectomy in soft tissue metastasis. [ABSTRACT FROM AUTHOR]

A solitary fibrous tumor (SFT) is a rare neoplasm with recurrent NAB2-STAT6 gene fusion. An SFT may develop almost anywhere throughout the body, including the head and neck region, and is characterized by a broad spectrum of malignancy. Here we present a case involving a 57-year-old male with a dumbbell-shaped SFT in the cervical spine that mimicked schwannoma. Repeated fine-needle aspiration cytology failed to establish a definitive diagnosis. Given that the tumor size increased significantly over a 10-month period, open biopsy was then performed. Though the biopsy result was inconclusive, a nonepithelial tumor, including sclerosing epithelioid fibrosarcoma or ossifying fibromyxoid tumor, was suspected. The tumor was then completely removed together with adjacent parts of C2 and C3 vertebrae and left vertebral artery via combined anterior and posterior approaches. Histologically, the tumor consisted of round cells with prominent stromal hyalinization and was immunohistochemically positive for STAT6, CD34, and cytokeratin. Finally, Todai OncoPanel, a next-generation sequencing-based molecular profiling system using formalin-fixed paraffin-embedded samples, demonstrated fusion transcript in which NAB2 exon 6 was fused to STAT6 exon 16 supporting the diagnosis of SFT, while whole-exome sequencing analysis detected no somatic mutations which were known to be oncogenic. [ABSTRACT FROM AUTHOR]