Incremental Composition in Distributional Semantics

Journal of Logic, Language and Information - Despite the incremental nature of Dynamic Syntax (DS), the semantic grounding of it remains that of predicate logic, itself grounded in set theory, so...     

Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders

Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel K_v1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of-function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype–phenotype correlation, variability, and predicted functional impact of KCNA2 variants.     

Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments

Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world’s population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.     

The Causes and Potential Injurious Effects of Elevated Serum Leptin Levels in Chronic Kidney Disease Patients

Leptin is an adipokine that regulates appetite and body mass and has many other pleiotropic functions, including regulating kidney function. Increased evidence shows that chronic kidney disease (CKD) is associated with hyperleptinemia, but the reasons for this phenomenon are not fully understood. In this review, we focused on potential causes of hyperleptinemia in patients with CKD and the effects of elevated serum leptin levels on patient kidney function and cardiovascular risk. The available data indicate that the increased concentration of leptin in the blood of CKD patients may result from both decreased leptin elimination from the circulation by the kidneys (due to renal dysfunction) and increased leptin production by the adipose tissue. The overproduction of leptin by the adipose tissue could result from: (a) hyperinsulinemia; (b) chronic inflammation; and (c) significant lipid disturbances in CKD patients. Elevated leptin in CKD patients may further deteriorate kidney function and lead to increased cardiovascular risk.     

Identification of the Catalytic Residues in the Cyclase Domain of the Class IV Lanthipeptide Synthetase SgbL

Lanthipeptides belong to the family of ribosomally synthesized and post-translationally modified peptides (RiPPs) and are subdivided into different classes based on their processing enzymes. The three-domain class IV lanthipeptide synthetases (LanL enzymes) consist of N-terminal lyase, central kinase, and C-terminal cyclase domains. While the catalytic residues of the kinase domains (mediating ATP-dependent Ser/Thr phosphorylations) and the lyase domains (carrying out subsequent phosphoserine/phosphothreonine (pSer/pThr) eliminations to yield dehydroalanine/dehydrobutyrine (Dha/Dhb) residues) have been characterized previously, such studies are missing for LanL cyclase domains. To close this gap of knowledge, this study reports on the identification and validation of the catalytic residues in the cyclase domain of the class IV lanthipeptide synthetase SgbL, which facilitate the nucleophilic attacks by Cys thiols on Dha/Dhb residues for the formation of β-thioether crosslinks.     

Auger Analysis of Hot-Pressed and Sintered Silicon Carbide

Intergranular and transgranular chemistries of hot-pressed and sintered silicon carbides were investigated by Auger electron spectroscopy. Results indicated major differences in grain-boundary compositions between the two. Hot-pressed silicon carbide displayed a complex intergranular chemistry. Sintered silicon carbide displayed grain facets that were free of impurities and additives. The observed intergranular chemistries for both silicon carbides are discussed in terms of their relation to the processing methods.     

Nelder-Mead Simplex Optimization Routine for Large-Scale Problems: A Distributed Memory Implementation

The Nelder-Mead simplex method is an optimization routine that works well with irregular objective functions. For a function of $n$ parameters, it compares the objective function at the $n+1$ vertices of a simplex and updates the worst vertex through simplex search steps. However, a standard serial implementation can be prohibitively expensive for optimizations over a large number of parameters. We describe an implementation of the Nelder-Mead method in parallel using a distributed memory. For $p$ processors, each processor is assigned $(n+1)/p$ vertices at each iteration. Each processor then updates its worst local vertices, communicates the results, and a new simplex is formed with the vertices from all processors. We also describe how the algorithm can be implemented with only two MPI commands. In simulations, our implementation exhibits large speedups and is scalable to large problem sizes.     

Direct Ink-Jet Printing of Vertical Walls

Direct jet printing can assemble ceramic powder into a three dimensional shape by firing droplets of ink through a nozzle to build a multiple layered structure. As with stereolithography and selective laser sintering, the surface texture is expected to witness the layered assembly. The ability to create vertical walls by direct ink-jet printing was explored using a test piece based on a maze. The structure and topography are discussed in terms of droplet spreading and drying.     

Oligomer and Polymer Formation in Hexamethylcyclotrisiloxane (D<Subscript>3</Subscript>) – Hydrosilane Systems Under Catalysis by tris(pentafluorophenyl)borane

Summary Reactions of hexamethylcyclotrisiloxane, D₃, with 1,1,3,3-tetramethyldisiloxane, ^HMM^H, 1,1,1,3,3-pentamethyldisiloxane, ^HMM, phenyldimethylsilane and phenylmethylsilane catalyzed by tris(pentafluorophenyl)borane were studied. These reactions lead to ring opening of D₃ by the SiH reactant producing open chain oligomers with hydrosilane functionality at one or both chain ends. The reactivity of the hydrosilanes toward D₃ decreases in the series: PhMeSiH₂ > ^HMM^H > PhMe₂SiH > ^HMM. Competitive self-oligomerization of ^HMM^H and ^HMM also occurs. Primary products of these processes are able to enter into reactions with the SiH and D₃ reactants; some also undergo cyclization. Thus, consecutive and competitive processes lead to a series of various oligohomologues. Gas chromatography in conjunction with chemical ionization mass spectroscopy permitted identification of structure and determination of the basic directions of these oligomerization processes. Polysiloxanes of higher molecular weight may be also formed in some of these systems. The reactions, which occur in the systems studied, are rationalized on the basis of the mechanism involving the hydride transfer from silicon to trivalent boron. This includes the transient formation of tertiary trisilyloxonium borate which decomposes by the hydride transfer to one of the silicon atoms of the trisilyloxonium center. Footnote: This paper is dedicated to Professor Ian Manners in recognition of his significant contributions to the field of organometallic polymers.