On the expressive power of read-once determinants

We introduce and study the notion of read-$k$ projections of the determinant: a polynomial $f \in \mathbb{F}[x_1, \ldots, x_n]$ is called a {\it read-$k$ projection of determinant} if $f=det(M)$, where entries of matrix $M$ are either field elements or variables such that each variable appears at most $k$ times in $M$. A monomial set $S$ is said to be expressible as read-$k$ projection of determinant if there is a read-$k$ projection of determinant $f$ such that the monomial set of $f$ is equal to $S$. We obtain basic results relating read-$k$ determinantal projections to the well-studied notion of determinantal complexity. We show that for sufficiently large $n$, the $n \times n$ permanent polynomial $Perm_n$ and the elementary symmetric polynomials of degree $d$ on $n$ variables $S_n^d$ for $2 \leq d \leq n-2$ are not expressible as read-once projection of determinant, whereas $mon(Perm_n)$ and $mon(S_n^d)$ are expressible as read-once projections of determinant. We also give examples of monomial sets which are not expressible as read-once projections of determinant

Binding of Superantigen Toxins into the CD28 Homodimer Interface Is Essential for Induction of Cytokine Genes That Mediate Lethal Shock

Bacterial superantigen toxins bind directly to the dimer interface of CD28, the principal co-stimulatory receptor, to induce a lethal cytokine storm, and peptides that prevent this binding can suppress superantigen lethality

Caspase involvement in autophagy

Caspases are a family of cysteine proteases widely known as the principal mediators of the apoptotic cell death response, but considerably less so as the contributors to the regulation of pathways outside cellular demise. In regards to autophagy, the modulatory roles of caspases have only recently begun to be adequately described. In contrast to apoptosis, autophagy promotes cell survival by providing energy and nutrients through the lysosomal degradation of cytoplasmic constituents. Under basal conditions autophagy and apoptosis cross-regulate each other through an elaborate network of interconnections which also includes the interplay between autophagyrelated proteins (ATGs) and caspases. In this review we focus on the effects of this crosstalk at the cellular level, as we aim to concentrate the main observations from research conducted so far on the fine-tuning of autophagy by caspases. Several members of this protease-family have been found to directly interact with key ATGs involved in different tiers across the autophagic cascade. Therefore, we firstly outline the core mechanism of macroautophagy in brief. In an effort to emphasize the importance of the intricate cross-regulation of ATGs and caspases, we also present examples drawn from Drosophila and plant models regarding the contribution of autophagy to apoptotic cell death during normal development

A mouse model of creatine transporter deficiency reveals impaired motor function and muscle energy metabolism

Creatine serves as fast energy buffer in organs of high-energy demand such as brain and skeletal muscle. L-Arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase are responsible for endogenous creatine synthesis. Subsequent uptake into target organs like skeletal muscle, heart and brain is mediated by the creatine transporter (CT1, SLC6A8). Creatine deficiency syndromes are caused by defects of endogenous creatine synthesis or transport and are mainly characterized by intellectual disability, behavioral abnormalities, poorly developed muscle mass, and in some cases also muscle weakness. CT1-deficiency is estimated to be among the most common causes of X-linked intellectual disability and therefore the brain phenotype was the main focus of recent research. Unfortunately, very limited data concerning muscle creatine levels and functions are available from patients with CT1 deficiency. Furthermore, different CT1-deficient mouse models yielded conflicting results and detailed analyses of their muscular phenotype are lacking. Here, we report the generation of a novel CT1-deficient mouse model and characterized the effects of creatine depletion in skeletal muscle. HPLC-analysis showed strongly reduced total creatine levels in skeletal muscle and heart. MR-spectroscopy revealed an almost complete absence of phosphocreatine in skeletal muscle. Increased AGAT expression in skeletal muscle was not sufficient to compensate for insufficient creatine transport. CT1-deficient mice displayed profound impairment of skeletal muscle function and morphology (i.e., reduced strength, reduced endurance, and muscle atrophy). Furthermore, severely altered energy homeostasis was evident on magnetic resonance spectroscopy. Strongly reduced phosphocreatine resulted in decreased ATP/Pi levels despite an increased inorganic phosphate to ATP flux. Concerning glucose metabolism, we show increased glucose transporter type 4 expression in muscle and improved glucose clearance in CT1-deficient mice. These metabolic changes were associated with activation of AMP-activated protein kinase - a central regulator of energy homeostasis. In summary, creatine transporter deficiency resulted in a severe muscle weakness and atrophy despite different compensatory mechanisms

Zero Knowledge Protocols from Succinct Constraint Detection

We study the problem of constructing proof systems that achieve both soundness and zero knowledge unconditionally (without relying on intractability assumptions). Known techniques for this goal are primarily *combinatorial*, despite the fact that constructions of interactive proofs (IPs) and probabilistically checkable proofs (PCPs) heavily rely on *algebraic* techniques to achieve their properties. We present simple and natural modifications of well-known algebraic IP and PCP protocols that achieve unconditional (perfect) zero knowledge in recently introduced models, overcoming limitations of known techniques. 1. We modify the PCP of Ben-Sasson and Sudan [BS08] to obtain zero knowledge for NEXP in the model of Interactive Oracle Proofs [BCS16,RRR16], where the verifier, in each round, receives a PCP from the prover. 2. We modify the IP of Lund, Fortnow, Karloff, and Nisan [LFKN92] to obtain zero knowledge for #P in the model of Interactive PCPs [KR08], where the verifier first receives a PCP from the prover and then interacts with him. The simulators in our zero knowledge protocols rely on solving a problem that lies at the intersection of coding theory, linear algebra, and computational complexity, which we call the *succinct constraint detection* problem, and consists of detecting dual constraints with polynomial support size for codes of exponential block length. Our two results rely on solutions to this problem for fundamental classes of linear codes: * An algorithm to detect constraints for Reed--Muller codes of exponential length. This algorithm exploits the Raz--Shpilka [RS05] deterministic polynomial identity testing algorithm, and shows, to our knowledge, a first connection of algebraic complexity theory with zero knowledge. * An algorithm to detect constraints for PCPs of Proximity of Reed--Solomon codes [BS08] of exponential degree. This algorithm exploits the recursive structure of the PCPs of Proximity to show that small-support constraints are locally spanned by a small number of small-support constraints