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For every non-integral $\alpha>1$, the sequence of the integer parts of $n^{\alpha}$ $(n=1,2,\ldots)$ is called the Piatetski-Shapiro sequence with exponent $\alpha$, and let $\mathrm{PS}(\alpha)$ denote the set of all those terms. For all $X\subseteq \mathbb{N}$, we say that an equation $y=ax+b$ is solvable in $X$ if the equation has infinitely many solutions of distinct pairs $(x,y)\in X^2$. Let $a,b\in \mathbb{R}$ with $a\neq 1$ and $0\leq b, Comment: 12 pages

The achievement of molecular orientation control by rubbing and pressing poly(3-alkylthiophene)s is a powerful technique to improve the performance of organic electronic devices. We report here that the rubbing and pressing of blackish-brown 3-methoxythiophene oligomer powders yield layer and tablet samples with gold tones, respectively. Specular reflectivity, colorimetric, and X-ray diffraction measurements reveal that this gold tone is caused by an increase in the ratio of edge-on lamellar crystallites to face-on ones, which is promoted by rubbing/pressing. In contrast to the 3-alkylthiophene polymer, which develops a dominant face-on lamellar structure, rubbing of the 3-methoxythiophene oligomer increases the relative amount of edge-on lamellar crystallites to face-on lamellar ones. Furthermore, gold tone development in the tablet samples is limited to the near-surface area, despite the fact that pressure is also applied to the tablet bulk. These specific chemical events are explained by considering the repulsive interactions between the 3-methoxythiophene backbone and the functional groups on the surface of the substrate employed during the rubbing/pressing processes. Despite the lower applied pressure, gold tone development by rubbing is accompanied by a higher reflective property than by pressing because of the formation of larger relative amounts and sizes of edge-on lamellar crystallites, which are responsible for the gold tone.

Graphical Abstract Abstract Objective Nonalcoholic steatohepatitis is a chronic liver disease caused by the progression of hepatocellular death and inflammation from simple steatosis. However, the pathogenesis of this disease remains unclear. Lipid peroxidation is one of the most critical factors in the development of nonalcoholic steatohepatitis; however, oxidised lipids – the products of lipid peroxidation – are insufficiently analysed. Here, we comprehensively analysed oxidised lipids in the liver during nonalcoholic steatohepatitis development in a choline-deficient, l-amino acid-defined, high-fat diet-fed mouse model. Methods Liver from C57BL/6J mice, fed a standard diet or a choline-deficient l-amino acid-defined high-fat diet for 1, 3, or 6 weeks, were collected to evaluate fibrosis, steatosis, inflammation, liver injury, and oxidised lipid production and to observe the suppression of these parameters upon vitamin E administration. In addition, organellar localisation of lipid peroxidation was assessed using fluorescence imaging. Finally, a mitochondria-targeted antioxidant was administered to model mice to investigate the mechanism underlying lipid peroxidation. Results We found an accumulation of oxidised triglycerides in the early stages of nonalcoholic steatohepatitis. Furthermore, our data indicate that oxidised triglycerides are generated by lipid peroxidation in lipid droplets due to mitochondria-derived reactive oxygen species. Conclusion These results suggest the importance of lipid droplet peroxidation in the progression of nonalcoholic steatohepatitis and may contribute to the development of therapeutic methods for nonalcoholic steatohepatitis in the future. Significance statement We demonstrate the specific and early occurrence of lipid peroxidation in nonalcoholic steatohepatitis pathogenesis and propose a previously unknown mechanism of disease progression.

The Multiple Choice Polytope (MCP) is the prediction range of a random utility model due to Block and Marschak (1960). Fishburn (1998) offers a nice survey of the findings on random utility models at the time. A complete characterization of the MCP is a remarkable achievement of Falmagne (1978). Apart for a recognition of the facets by Suck (2002), the geometric structure of the MCP was apparently not much investigated. Recently, Chang, Narita and Saito (2022) refer to the adjacency of vertices while Turansick (2022) uses a condition which we show to be equivalent to the non-adjacency of two vertices. We characterize the adjacency of vertices and the adjacency of facets. To derive a more enlightening proof of Falmagne Theorem and of Suck result, Fiorini (2004) assimilates the MCP with the flow polytope of some acyclic network. Our results on adjacencies also hold for the flow polytope of any acyclic network. In particular, they apply not only to the MCP, but also to three polytopes which Davis-Stober, Doignon, Fiorini, Glineur and Regenwetter (2018) introduced as extended formulations of the weak order polytope, interval order polytope and semiorder polytope (the prediction ranges of other models, see for instance Fishburn and Falmagne, 1989, and Marley and Regenwetter, 2017).

Background Remimazolam has less cardiovascular depressant effects than propofol in non-cardiac surgical patients. However, the efficacy and safety of remimazolam in cardiac surgery with cardiopulmonary bypass (CPB) have not been reported. We present a case of successful anesthetic management using remimazolam in cardiac surgery with CPB. Case presentation A 76-year-old female was scheduled for mitral valve repair, tricuspid annuloplasty, maze procedure, and left atrial appendage closure. We used remimazolam in induction (6.0 mg/kg/h) and maintenance (0.6–1.0 mg/kg/h) of general anesthesia, and the bispectral index value was maintained in the range of 36 to 48 including the period of CPB. Hemodynamics, mixed venous oxygen saturation, and bilateral regional cerebral oxygen saturation were maintained within acceptable ranges. There was no intraoperative awareness/recall or serious complications associated with remimazolam throughout the perioperative period. Conclusions Remimazolam can be used the same as other existing anesthetics in cardiac surgery with CPB.

We present revealed-preference characterizations of the most common models of intertemporal choice: the model of exponentially discounted concave utility, and some of its generalizations. Our characterizations take consumption data as primitives, and provide nonparametric revealed-preference tests. We apply our tests to data from two recent experiments and find that our axiomatization delivers new insights and perspectives on datasets that had been analyzed by traditional parametric methods. (JEL C91, D11, D15)

In this paper, we construct a subset of $\mathbb{R}^d$ which asymptotically and omnidirectionally contains arithmetic progressions but has Assouad dimension 1. More precisely, we say that $F$ asymptotically and omnidirectionally contains arithmetic progressions if we can find an arithmetic progression of length $k$ and gap length $\Delta>0$ with direction $e\in S^{d-1}$ inside the $\epsilon \Delta$ neighbourhood of $F$ for all $\epsilon>0$, $k\geq 3$ and $e\in S^{d-1}$. Moreover, the dimension of our constructed example is the lowest-possible because we prove that a subset of $\mathbb{R}^d$ which asymptotically and omnidirectionally contains arithmetic progressions must have Assouad dimension greater than or equal to 1. We also get the same results for arithmetic patches, which are the higher dimensional extension of arithmetic progressions., Comment: 7 pages

We compared sequence types (STs) of Mycoplasma pneumoniae isolates from Japan during 2002-2019. ST3 and ST14 dominated during 2002-2016, and ST7 and ST33 dominated during 2018-2019. These STs were associated with a decrease in macrolide-resistant strains after an epidemic of infection with M. pneumoniae during 2011-2012.

The paper establishes a tight relation between nonstandard behaviors in the domains of risk and time, by considering a decision-maker with non-expected utility preferences who believes that only present consumption is certain while any future consumption is uncertain. We provide the first complete characterizations of the two-way relations between the certainty effect and present bias, and between the common ratio effect and temporal reversals. (JEL D11, D15, D81, D91)

This study investigates the existence of tuples $(k, \ell, m)$ of integers such that all of $k$, $\ell$, $m$, $k+\ell$, $\ell+m$, $m+k$, $k+\ell+m$ belong to $S(\alpha)$, where $S(\alpha)$ is the set of all integers of the form $\lfloor \alpha n^2 \rfloor$ for $n\geq \alpha^{-1/2}$ and $\lfloor x\rfloor$ denotes the integer part of $x$. We show that $T(\alpha)$, the set of all such tuples, is infinite for all $\alpha\in (0,1)\cap \mathbb{Q}$ and for almost all $\alpha\in (0,1)$ in the sense of the Lebesgue measure. Furthermore, we show that if there exists $\alpha>0$ such that $T(\alpha)$ is finite, then there is no perfect Euler brick. We also examine the set of all integers of the form $\lceil \alpha n^2 \rceil$ for $n\in \mathbb{N}$., Comment: 23 pages, 2 figures

Insulin is an essential peptide hormone that maintains blood glucose levels. Although the mechanisms underlying insulin exocytosis have been investigated, the mechanism of proinsulin export from the endoplasmic reticulum (ER) remains unclear. Here, we demonstrated that Surf4, a cargo receptor homolog, regulates the ER export of proinsulin via its recruitment to ER exit sites (ERES). Under high-glucose conditions, Surf4 expression was upregulated, and Surf4 proteins mainly localized to the ER at a steady state and accumulated in the ERES, along with proinsulin in rat insulinoma INS-1 cells. Surf4-knockdown resulted in proinsulin retention in the ER and decreased the levels of mature insulin in secretory granules, thereby significantly reducing insulin secretion. Surf4 forms an oligomer and can physically interact with proinsulin and Sec12, essential for COPII vesicle formation. Our findings suggest that Surf4 interacts with proinsulin and delivers it into COPII vesicles for ER export in co-operation with Sec12 and COPII.

Solution-cast coating films of perchlorate-doped oligo(3-methoxythiophene) exhibited a gold-like luster similar to that of metallic gold despite the involvement of no metals. However, the development mechanism of the luster remains ambiguous. To understand the mechanism, we performed scanning electron microscopic analysis, variable-angle spectral reflectance measurements, and ellipsometry measurements on ClO4−-doped oligo(3-methoxythiophene) cast film with a gold-like luster. The results revealed that the lustrous color of the film was not induced by the submicron-sized regular structures (structural color), nor by the high-density free electrons (reflective response based on Drude model), but by the large optical constants (refractive index and extinction coefficient) of the film, as speculated previously.

Proteins synthesized within the endoplasmic reticulum (ER) are exported from ER exit sites via coat protein complex II (COPII)-coated vesicles. Although the mechanisms of COPII-vesicle formation at the ER exit sites are highly conserved among species, vertebrate cells secrete a wide range of materials, including collagens and chylomicrons, which form bulky structures within the ER that are too large to fit into conventional carriers. Transport ANd Golgi Organization 1 (TANGO1) was initially identified as a cargo receptor for collagens but has been recently rediscovered as an organizer of ER exit sites. We would like to review recent advances in the mechanism of large cargo secretion and organization of ER exit sites through the function of TANGO1.

In 2010, Matom��ki investigated the set of $A>1$ such that the integer part of $ A^{c^k} $ is a prime number for every $k\in \mathbb{N}$, where $c\geq 2$ is any fixed real number. She proved that the set is uncountable, nowhere dense, and has Lebesgue measure $0$. In this article, we show that the set has Hausdorff dimension $1$., 15 pages

We demonstrate a method of micromotion minimization of a trapped ion in a linear Paul trap based on the precision measurement of the ion trapping position displacement due to a stray electric field in the radial plane by ion fluorescence imaging. The amount of displacement in the radial plane is proportional to the strength of a stray electric field. Therefore, we evaluated the micromotion compensation condition by measuring the ion displacements from the ion equilibrium position using two different radial trap frequencies with various combinations of the compensation voltage. The residual electric field uncertainty of this technique reached a few volts per meter. This compensation technique does not depend on the orientation of the incident cooling laser or the detuning and imaging direction. Therefore, this method is suitable for a planar ion trap, a stylus ion trap, which limits the propagation angle of lasers, or miniaturized ion trap systems for sensing and metrological applications., 7 pages, 5 figures

Let $(c_k)_{k\in \mathbb{N}}$ be a sequence of positive integers. We investigate the set of $A>1$ such that the integer part of $A^{c_1\cdots c_k}$ is always a prime number for every positive integer $k$. Let $\mathcal{W}(c_k)$ be this set. The first goal of this article is to determine the topological structure of $\mathcal{W}(c_k)$. Under some conditions on $(c_k)_{k\in \mathbb{N}}$, we reveal that $\mathcal{W}(c_k)\cap [0,a]$ is homeomorphic to the Cantor middle third set for some $a$. The second goal is to propose an algebraically independent subset of $\mathcal{W}(c_k)$ if $c_k$ is rapidly increasing. As a corollary, we disclose that the minimum of $\mathcal{W}(k)$ is transcendental. In addition, we apply the main result to the set of $A>1$ such that the integer part of $A^{3^{k!}}$ is always a prime number. As a consequence, we give a certain infinite subset of this set which is algebraically independent. Furthermore, we also get results on the rational approximation, $\mathbb{Q}$-linear independence, and numerical calculations of elements in $\mathcal{W}(c_k)$., 27 pages

We propose a new measure of deviations from the expected utility theory. For any positive number e, we give a characterization of the datasets with a rationalization that is within e (in beliefs, utility, or perceived prices) of expected utility theory, under the assumption of risk aversion. The number e can then be used as a measure of how far the data is to the expected utility theory. We apply our methodology to data from three large-scale experiments. Many subjects in these experiments are consistent with utility maximization, but not with expected utility maximization. Our measure of distance to expected utility is correlated with the subjects’ demographic characteristics.

A Piatetski-Shapiro sequence with exponent $\alpha$ is a sequence of integer parts of $n^\alpha$ $(n = 1,2,\ldots)$ with a non-integral $\alpha > 0$. We let $\mathrm{PS}(\alpha)$ denote the set of those terms. In this article, we study the set of $\alpha$ so that the equation $ax + by = cz$ has infinitely many pairwise distinct solutions $(x,y,z) \in \mathrm{PS}(\alpha)^3$, and give a lower bound for its Hausdorff dimension. As a corollary, we find uncountably many $\alpha > 2$ such that $\mathrm{PS}(\alpha)$ contains infinitely many arithmetic progressions of length $3$., Comment: 21 pages

By using the work of Frantzikinakis and Wierdl, we can see that for all $d\in\mathbb{N}$, $\alpha\in(d,d+1)$, and integers $k\ge d+2$ and $r\ge1$, there exist infinitely many $n\in\mathbb{N}$ such that the sequence $(\lfloor{(n+rj)^\alpha}\rfloor)_{j=0}^{k-1}$ is represented as $\lfloor{(n+rj)^\alpha}\rfloor=p(j)$, $j=0,1,\ldots,k-1$, by using some polynomial $p(x)\in\mathbb{Q}[x]$ of degree at most $d$. In particular, the above sequence is an arithmetic progression when $d=1$. In this paper, we show the asymptotic density of such numbers $n$ as above. When $d=1$, the asymptotic density is equal to $1/(k-1)$. Although the common difference $r$ is arbitrarily fixed in the above result, we also examine the case when $r$ is not fixed. Most results in this paper are generalized by using functions belonging to Hardy fields., Comment: 43 pages, 1 figure

We extend the Luce model of discrete choice theory to satisfactorily handle zero-probability choices. The Luce mode struggles to explain choices that are not made. The model requires that if an alternative y is never chosen when x is available, then there is no set of alternatives from which y is chosen with positive probability. In our model, if an alternative y is never chosen when x is available, then we infer that y is dominated by x. While dominated by x, y may still be chosen with positive probability, when grouped with a comparable set of alternatives.

We develop an axiomatic model that builds on Luce's (1959) model to incorporate a role for perception. We identify agents' "perception priorities" from their violations of Luce's axiom of independence from irrelevant alternatives. Using such perception priorities, we adjust choice probabilities to account for the effects of perception. Our axiomatization requires that the agents' adjusted random choice conforms to Luce's model. Our model can explain the attraction, compromise, and similarity effects, which are very well-documented behavioral phenomena in individual choice.

Response time is the time an agent needs to make a decision. One fundamental finding in psychology and neuroscience is that, in a binary choice, there is a monotonic relationship between the response time and the difference between the utilities of the two options. We consider situations in which utilities are not observed, but rather inferred from revealed preferences: meaning they are inferred from subjects’ choices. Given data on subjects’ choices, and the time to make those choices, we give conditions on the data that characterize the property that response time is a monotonic function of utility differences.

Mammalian ER exit sites (ERES) export a variety of cargo molecules, including oversized cargoes such as collagens. Maeda et al. report a direct interaction between TANGO1 and Sec16 at ERES, which is not only important for their correct localization but also critical for the organization of ERES., Mammalian endoplasmic reticulum (ER) exit sites export a variety of cargo molecules including oversized cargoes such as collagens. However, the mechanisms of their assembly and organization are not fully understood. TANGO1L is characterized as a collagen receptor, but the function of TANGO1S remains to be investigated. Here, we show that direct interaction between both isoforms of TANGO1 and Sec16 is not only important for their correct localization but also critical for the organization of ER exit sites. The depletion of TANGO1 disassembles COPII components as well as membrane-bound ER-resident complexes, resulting in fewer functional ER exit sites and delayed secretion. The ectopically expressed TANGO1 C-terminal domain responsible for Sec16 binding in mitochondria is capable of recruiting Sec16 and other COPII components. Moreover, TANGO1 recruits membrane-bound macromolecular complexes consisting of cTAGE5 and Sec12 to the ER exit sites. These data suggest that mammalian ER exit sites are organized by TANGO1 acting as a scaffold, in cooperation with Sec16 for efficient secretion.

Golgi fragmentation and ER exit site dissociation are considered as the leading causes of mitotic block of secretion from the ER. Although the mechanisms of Golgi fragmentation have been extensively characterized, ER exit block early in mitosis is not well-understood. We previously found that TANGO1 organizes ER exit sites by directly interacting with Sec16. Here, we showed that TANGO1 is phosphorylated by casein kinase 1 (CK1) during mitosis. Interestingly, the interaction with Sec16 was abrogated by phosphorylation of TANGO1, leading to dissociation of the ER exit sites. Moreover, a TANGO1 mutant deficient in phosphorylation inhibited the mitotic dissociation of ER exit sites. In contrast, a TANGO1 mutant mimicking CK1-mediated phosphorylation dissociated ER exit sites in interphase cells. Although CK1 activity remains constant throughout the cell cycle, PP1, a phosphatase for which activity decreases during mitosis, participates in the regulation of TANGO1 phosphorylation. This is the first report demonstrating the mechanisms of ER exit site dissociation during mitosis.

The endoplasmic reticulum (ER) is a major regulator of cellular proteostasis. However, only little is known about signaling molecules resident to this organelle. Centonze et al. identify LTK as the first ER-resident receptor tyrosine kinase and show that it stimulates secretory trafficking out of the ER., The endoplasmic reticulum (ER) is a key regulator of cellular proteostasis because it controls folding, sorting, and degradation of secretory proteins. Much has been learned about how environmentally triggered signaling pathways regulate ER function, but only little is known about local signaling at the ER. The identification of ER-resident signaling molecules will help gain a deeper understanding of the regulation of ER function and thus of proteostasis. Here, we show that leukocyte tyrosine kinase (LTK) is an ER-resident receptor tyrosine kinase. Depletion of LTK as well as its pharmacologic inhibition reduces the number of ER exit sites and slows ER-to-Golgi transport. Furthermore, we show that LTK interacts with and phosphorylates Sec12. Expression of a phosphoablating mutant of Sec12 reduces the efficiency of ER export. Thus, LTK-to-Sec12 signaling represents the first example of an ER-resident signaling module with the potential to regulate proteostasis.

Secretory proteins are exported from special domains of the endoplasmic reticulum (ER) termed ER exit sites, via COPII-coated carriers. We recently showed that TANGO1 and Sec16 cooperatively organize mammalian ER exit sites for efficient secretion. However, the detailed spatial organization of mammalian ER exit sites is yet to be revealed. Here, we used super-resolution confocal live imaging microscopy (SCLIM) to investigate the localization of endogenous proteins, and we identified domains abundant in transmembrane complexes (TANGO1/cTAGE5/Sec12) juxtaposed to Sec16. Interestingly, this domain can be distinguished from the inner and the outer coats of COPII proteins within each mammalian ER exit site. Cargoes are partially concentrated in the domain for secretion. Our results suggest that mammalian ER exit sites compartmentalize proteins according to their function in COPII vesicle formation.

Golgi fragmentation and ER exit site disassembly are considered to be the leading causes of the mitotic block of secretion from the ER. Although the mechanisms of Golgi fragmentation have been extensively characterized, ER exit block early in mitosis is not well understood. We previously demonstrated that TANGO1 organizes ER exit sites by directly interacting with Sec16. In this study, we identified TANGO1 as a regulator of ER exit site disassembly during mitosis. TANGO1 phosphorylation was observed to be coordinately regulated by a kinase (CK1) and a phosphatase (PP1). CK1-mediated TANGO1 phosphorylation reduces binding to Sec16, leading to the disassembly of ER exit sites. CK1 constantly phosphorylates TANGO1, whereas PP1-mediated dephosphorylation of TANGO1 decreases during mitosis. Thus, the phosphorylation status of TANGO1, which is controlled by balanced activities of the kinase CK1 and the phosphatase PP1, regulates the organization of ER exit sites during the cell cycle.

The short isoform of TANGO1, termed TANGO1S, is necessary for collagen secretion from the ER independently of TANGO1L. TANGO1L and TANGO1S form individual complexes at ER exit sites and cooperatively participate in collagen export from the ER., Collagens synthesized within the endoplasmic reticulum (ER) are too large to fit in conventional COPII-coated transport vesicles; thus their export from the ER requires specialized factors. TANGO1 (L) is an integral membrane protein that binds to collagen and the coatomer of vesicles and is necessary for collagen secretion from the ER. Here we characterized the short isoform of TANGO1 (TANGO1S), lacking the collagen-binding domain, and found that it was independently required for collagen export from the ER. Moreover, we found that each of the TANGO1 isoforms forms a stable protein complex with factors involved in collagen secretion: TANGO1L/cTAGE5/Sec12 (900 kDa) and TANGO1S/cTAGE5/Sec12 (700 kDa). Of interest, TANGO1S and TANGO1L seemed to be interchangeable in exporting collagen from the ER. Our results suggest that mammalian ER exit sites possess two different-sized membrane-bound macromolecular complexes that specifically function in large-cargo export from the ER.

How ER exit sites disassemble during mitosis is not well understood. Transport ANd Golgi Organization 1 (TANGO1, also known as MIA3), a cargo receptor originally identified for collagens, acts as a hub for ER exit site disassembly under the control of Casein Kinase 1 (CK1)-mediated phosphorylation and Protein Phosphatase 1 (PP1)-mediated dephosphorylation. Impaired dephosphorylation during mitosis induces ER exit site disassembly.

Secretory proteins synthesized within the endoplasmic reticulum (ER) are exported via coat protein complex II (COPII)-coated vesicles. The formation of the COPII-coated vesicles is initiated by activation of the small GTPase, Sar1. cTAGE5 directly interacts with a guanine-nucleotide exchange factor (GEF), Sec12, and a GTPase-activating protein (GAP) of Sar1, Sec23. We have previously shown that cTAGE5 recruits Sec12 to the ER exit sites for efficient production of activated Sar1 for collagen secretion. However, the functional significance of the interaction between cTAGE5 and Sec23 has not been fully elucidated. In this study, we showed that cTAGE5 enhances the GAP activity of Sec23 toward Sar1. In addition, the interaction of cTAGE5 with Sec23 is necessary for collagen exit from the ER. Our data suggests that cTAGE5 acts as a Sar1 GTPase regulator for collagen secretion.

We provide a theory of random intertemporal choice. Agents exhibit stochastic choice over consumption due to preference shocks to discounting attitudes. We first demonstrate how the distribution of these preference shocks can be uniquely identified from random choice data. We then provide axiomatic characterizations of some common random discounting models, including exponential and quasi-hyperbolic discounting. In particular, we show how testing for exponential discounting under stochastic choice involves checking for both a stochastic version of stationarity and a novel axiom characterizing decreasing impatience.

This short paper gives another proof of the infinitude of primes by using upper box dimension, which is one of fractal dimensions., Comment: 4 pages

Altruism refers to a willingness to benefit others, even at one's own expense. In contrast, selfishness refers to prioritizing one's own interests with no consideration for others. However, even if an agent is selfish, he might nevertheless act as if he were altruistic out of selfish concerns triggered when his action is observed; that is, he might seek to feel pride in acting altruistically and to avoid the shame of acting selfishly. We call such behavior impurely altruistic. Alternatively, even if an agent is altruistic, he might nevertheless give in to the temptation to act selfishly. We call such behavior impurely selfish. This paper axiomatizes a model that distinguishes altruism from impure altruism and selfishness from impure selfishness. In the model, unique real numbers separately capture altruism and the other forces of pride, shame, and the temptation to act selfishly. We show that the model can describe recent experiments on dictator games with an exit option. In addition, we describe an empirical puzzle that government spending only partially crowds out consumers' donations, contrary to the prediction based on standard consumer theory.

Cargo proteins exported from the endoplasmic reticulum to the Golgi apparatus are typically transported in coat protein complex II (COPII)-coated vesicles of 60–90 nm diameter. Several cargo molecules including collagens and chylomicrons form structures that are too large to be accommodated by these vesicles, but their secretion still requires COPII proteins. Here, we first review recent progress on large cargo secretions derived especially from animal models and human diseases, which indicate the importance of COPII proteins. We then discuss the recent isolation of specialized factors that modulate the process of COPII-dependent cargo formation to facilitate the exit of large-sized cargoes from the endoplasmic reticulum. Based on these findings, we propose a model that describes the importance of the GTPase cycle for secretion of oversized cargoes. Next, we summarize reports that describe the structures of COPII proteins and how these results provide insight into the mechanism of assembly of the large cargo carriers. Finally, we discuss what issues remain to be solved in the future.

We develop a behavioral axiomatic characterization of subjective expected utility (SEU) under risk aversion. Given is an individual agent's behavior in the market: assume a finite collection of asset purchases with corresponding prices. We show that such behavior satisfies a “revealed preference axiom” if and only if there exists a SEU model (a subjective probability over states and a concave utility function over money) that accounts for the given asset purchases.

Hepatic fibrosis is caused by exaggerated wound healing response to chronic injury, which eventually leads to hepatic cirrhosis. Differentiation of hepatic stellate cells (HSCs) to myofibroblast-like cells by inflammatory cytokines is the critical step in fibrosis. This step is accompanied by enlargement of the endoplasmic reticulum (ER) and Golgi apparatus, suggesting that protein synthesis and secretion are augmented in the activated HSCs. However, the process of rearrangement of secretory organelles and their functions remain to be fully elucidated. Here, we revealed that differentiation alters early secretory gene expression. We observed significant isoform-specific upregulation of the inner coat protein complex II (COPII) components, Sec23A and Sec24D, via the transmembrane bZIP transcription factor, CREB3L2/BBF2H7, during HSC activation. Moreover, knockdown of these components abrogated the activation, suggesting that Sec23A/Sec24D-mediated ER to Golgi trafficking is required for HSC activation.

Proteins synthesized within the endoplasmic reticulum (ER) are transported to the Golgi via coat protein complex II (COPII)-coated vesicles. The formation of COPII-coated vesicles is regulated by the GTPase cycle of Sar1. Activated Sar1 is recruited to ER membranes and forms a pre-budding complex with cargoes and the inner-coat complex. The outer-coat complex then stimulates Sar1 inactivation and completes vesicle formation. The mechanisms of forming transport carriers are well-conserved among species; however, in mammalian cells, several cargo molecules such as collagen, and chylomicrons are too large to be accommodated in conventional COPII-coated vesicles. Thus, special cargo-receptor complexes are required for their export from the ER. cTAGE5/TANGO1 complexes and their isoforms have been identified as cargo receptors for these macromolecules. Recent reports suggest that the cTAGE5/TANGO1 complex interacts with the GEF and the GAP of Sar1 and tightly regulates its GTPase cycle to accomplish large cargo secretion.

Autophagosomes are double-membrane vesicles generated during autophagy. Biogenesis of the autophagosome requires membrane acquisition from intracellular compartments, the mechanisms of which are unclear. We previously found that a relocation of COPII machinery to the ER-Golgi intermediate compartment (ERGIC) generates ERGIC-derived COPII vesicles which serve as a membrane precursor for the lipidation of LC3, a key membrane component of the autophagosome. Here we employed super-resolution microscopy to show that starvation induces the enlargement of ER-exit sites (ERES) positive for the COPII activator, SEC12, and the remodeled ERES patches along the ERGIC. A SEC12 binding protein, CTAGE5, is required for the enlargement of ERES, SEC12 relocation to the ERGIC, and modulates autophagosome biogenesis. Moreover, FIP200, a subunit of the ULK protein kinase complex, facilitates the starvation-induced enlargement of ERES independent of the other subunits of this complex and associates via its C-terminal domain with SEC12. Our data indicate a pathway wherein FIP200 and CTAGE5 facilitate starvation-induced remodeling of the ERES, a prerequisite for the production of COPII vesicles budded from the ERGIC that contribute to autophagosome formation.

We provide estimates for the dimensions of sets in $\mathbb{R}$ which uniformly avoid finite arithmetic progressions. More precisely, we say $F$ uniformly avoids arithmetic progressions of length $k \geq 3$ if there is an $\epsilon>0$ such that one cannot find an arithmetic progression of length $k$ and gap length $\Delta>0$ inside the $\epsilon \Delta$ neighbourhood of $F$. Our main result is an explicit upper bound for the Assouad (and thus Hausdorff) dimension of such sets in terms of $k$ and $\epsilon$. In the other direction, we provide examples of sets which uniformly avoid arithmetic progressions of a given length but still have relatively large Hausdorff dimension. We also consider higher dimensional analogues of these problems, where arithmetic progressions are replaced with arithmetic patches lying in a hyperplane. As a consequence we obtain a discretised version of a `reverse Kakeya problem': we show that if the dimension of a set in $\mathbb{R}^d$ is sufficiently large, then it closely approximates arithmetic progressions in every direction., Comment: 8 pages