Exploiting the Autozygome to Support Previously Published Mendelian Gene-Disease Associations: An Update

There is a growing interest in standardizing gene-disease associations for the purpose of facilitating the proper classification of variants in the context of Mendelian diseases. One key line of evidence is the independent observation of pathogenic variants in unrelated individuals with similar phenotypes. Here, we expand on our previous effort to exploit the power of autozygosity to produce homozygous pathogenic variants that are otherwise very difficult to encounter in the homozygous state due to their rarity. The identification of such variants in genes with only tentative associations to Mendelian diseases can add to the existing evidence when observed in the context of compatible phenotypes. In this study, we report 20 homozygous variants in 18 genes (ADAMTS18, ARNT2, ASTN1, C3, DMBX1, DUT, GABRB3, GM2A, KIF12, LOXL3, NUP160, PTRHD1, RAP1GDS1, RHOBTB2, SIGMAR1, SPAST, TENM3, and WASHC5) that satisfy the ACMG classification for pathogenic/likely pathogenic if the involved genes had confirmed rather than tentative links to diseases. These variants were selected because they were truncating, founder with compelling segregation or supported by robust functional assays as with the DUT variant that we present its validation using yeast model. Our findings support the previously reported disease associations for these genes and represent a step toward their confirmation.

An Antonym Substitution-based Model on Linguistic Steganography Method

<p class="IJASEITAbtract"><span lang="EN-GB">This paper implement the antonym procedure in substitution-based approach for linguistic steganography that is expected to be an alternative to the existing substitution approach that using synonym. This method is hidden the message as existing approach, however that is changing the semantic of the stego text from cover text as the medium. This paper proposed the development method is named Antonym Substitution-based that applied based on implementation linguistic steganography in covering the secret message. This approach refines the word choices makes antonym substitution-based approach linguistically is comparable with the previous effort of synonym substitution. Furthermore, this paper also used the verification and validation approaches as the procedure to evaluate performance of this method. The evaluation through verification approach used in order to determine the effectiveness and quality performance. This proposed method is expected has become the new technique implementation of linguistic steganography in process securing secret message that hide in the text medium.</span></p>

The First Attempts for the Syntax of the Regional Variety of Chameria

This paper is part of the chainwork that deals the syntax study of the dialect of the province of Chameria, a prominent and conservative language of the south of Albania. This study is the second in this regard. Initially, we were dealing with the intonation of Chams and mainly with its syntactic value (Troplini 2016). For the syntax of the of the regional variety of Chameria, there is no previous effort. In this paper, as a basic literature, we have only used our previous works for the Cham in the sociolinguistic framework, where we were dealing with phonetic, morphological, lexical, historical linguistics etc. Our first effort also underlines the first difficulties of this syntactic treatment, as well as the objectives that need to be fulfilled in the perspective, through a deep scientific monograph that will conclude a long-term gap in the study of the cham variety in terms of syntax. The method we used is the inductive one. The work has been based on a qualitative research basis. We are based on a series of direct interviews with elderly speakers of this province who were born mainly in Chameria and subjected to ethnic cleansing. This generation well preserves the most southern and extreme Albanian talk. In this study, we intend to highlight some of the most important phenomena of the Cham variety which will then serve for a deep work in terms of syntax.

Thoughts on Constitutions: Occasioned by a Congress on Iceland’s Democracy

On June 3, 2017, a “Congress on Iceland’s Democracy” met in Berkeley—an outgrowth of a previous effort in Iceland to “crowd source” a new constitution. The citizens of Iceland had led their parliament to create a new and extraordinarily representative convention consisting of citizens more-or-less chosen randomly from all walks of life. The convention functioned completely in the open and excluded all politicians. The result, approved overwhelmingly in a 2012 national referendum, would truly have been a “constitution of the people.” Despite the approval by huge majorities, in 2013, it failed in parliament as a result of fierce lobbying by vested interests against the provision that Iceland’s natural resources would be constitutionally mandated to benefit the public, rather than continuing to be held by private owners. Regardless of its prospects for success, Icelandic efforts should be of great interest to all constitutional scholars, and to those scholars and practitioners who seek a more open and inclusive way to formulate policy, including constitutions—the fundamental law of a state. Intended to stimulate further debate, this essay pursues some initial reflections on the U.S. Constitution specifically, and of constitutions in general. It also examines the role of elites, especially in constitutional formulation, and here pays special attention to the United States.

Shadow and Spillover Effects of Competition in NBA Playoffs

The National Basketball Association (NBA) playoffs are structured as an elimination tournament where reseeding does not occur after each round. This structure leads to situations where future competitors (the shadow effect) and previous effort (the spillover effect) affect current performance. Using data from the 2009-2014 NBA playoffs, results here find that, when a future opponent is known, a series favorite is significantly more likely to win a game when the future opponent is weaker than expected. Estimates also provide evidence that greater previous effort by teams increases the probability the series favorite wins a game.

The Saturated Impulse for Fully Clamped Square Plates Subjected to Linear-Decay Pressure Pulse

Saturated impulse refers to the critical value beyond which the deflection of the beam or plate under pulse loading will no longer increase with further applied load. Previous effort has been made to study the saturate impulse for structures under rectangular pressure pulse loading. Through theoretical analysis, the present paper investigates the saturated impulse for fully clamped square plates subjected to linear-decay pressure pulse, which is closer to explosive loading pulse. The results indicate that the saturated impulse does exist if the decay duration is greater than a certain value (i.e. the minimum decay duration). The saturated impulse, saturated deflection and saturated duration all have nonlinearly relations with the dimensionless applied pressure, and grow with the increase of the decay duration.

The UN Norms for Transnational Corporations

The proposed draft Norms on the Responsibilities of Transnational Corporations and Other Business Enterprises with Regard to Human Rights addressed to transnational corporations are making their way through the human rights channels in the United Nations. A previous effort in the United Nations failed twenty years ago. The Norms would urge those firms to adhere to a long list of treaties on the environment, labour standards, human rights, and the like. They would enter into a field already occupied by numerous principles and guidelines generated by many different institutions with varying degrees of authority. The addition of these norms to that corpus seems of marginal utility.

An Anatomy of the Historical Revolution in Renaissance France*

In his Dessein de l'histoire nouvelle des françois, Lancelot Voisin de La Popelinière offered a blueprint for a French history of broader range and deeper reach than any previous effort. He divided his proposed work into three parts: pre-Roman Gaul, Roman Gaul, and the kingdom of France from the Merovingians to the present. Part one would concern “the form of government, public and private, of the Gauls living in liberty before the Romans had envied, undermined, and eventually seized their dominion.” It would detail their religion (its priests and rituals), their nobility (its composition, privileges, and lifestyle), the lesser social orders (merchants, artisans, and commoners), and their public institutions (laws, magistrates, and other officials) — “in brief, everything notable about so little-known a state.” Part two would follow the same pattern but in even greater detail, examining the changes introduced by the Romans in “religion, administration, justice, military discipline, finances, and business, ” as well as social changes.

L. Boom as Dreamer in Finnegans Wake

It has taken a relatively short time for critics to become convinced of the basic continuity of James Joyce's entire body of work, despite Joyce's own protestations while in the process of creation that he had forgotten each previous effort in favor of the one in progress. While concerned with Leopold Bloom, Joyce impatiently asserted that “Stephen no longer interests me. He has a shape that can't be changed,” and when writing Finnegans Wake, he contemptuously shrugged off Ulysses: “Ulysses! Who wrote it? I've forgotten it.” It was imperative for him as an artist to concentrate on his new effort, and since he acted as his own publicity agent, it was necessary for him to call attention to it; but a retrospective appraisal should take note of the manner in which each work overlaps with one another: the child in the first three stories of Dubliners is very much the child Stephen in the first chapter of A Portrait of the Artist, Richard Rowan in Exiles is a projected image of the mature Stephen, and Shem the Penman is a caricature of both. Finnegans Wake in fact is a summation of all that Joyce had previously written: it recapitulates themes and motifs, reworks many of the same characters, and puns every previous Joyce title into its fabric. The Dreamer in the Wake is more than just a single individual, even if one assumes that on the literal level we are viewing the dream of publican H. C. Earwicker.