פרסומים

A significant fraction of disease-causing mutations affects pre-mRNA splicing. These mutations can generate both aberrant and correct transcripts, the level of which varies among different patients. An inverse correlation was found between this level and disease severity, suggesting a role for splicing regulation as a genetic modifier. Overexpression of splicing factors increased the level of correctly spliced RNA, transcribed from minigenes carrying disease-causing splicing mutations. However, whether this increase could restore the protein function was unknown. Here, we demonstrate that overexpression of Htra2-beta1 and SC35 increases the level of normal cystic fibrosis transmembrane conductance regulator (CFTR) transcripts in cystic-fibrosis-derived epithelial cells carrying the 3849+10 kb C --> T splicing mutation. This led to activation of the CFTR channel and restoration of its function. Restoration was also obtained by sodium butyrate, a histone deacetylase inhibitor, known to upregulate the expression of splicing factors. These results highlight the therapeutic potential of splicing modulation for genetic diseases caused by splicing mutations.

We offer a case-study in irrationality, showing that even in a high stakes, deliberate context, highly intelligent professionals may adopt dominated practices. Multiple-choice tests (MCTs) enjoy many advantages that made them popular tools in educational and psychological measurement. But they suffer from the so-called guessing problem: test-makers cannot distinguish lucky guesses from answers based on knowledge. One way professional test-makers have dealt with this problem is by attempting to lower the incentive to guess, through penalizing errors (called formula scoring). Another is to rid tests of various cues (e.g., a preponderance of correct answers in middle positions) that might help testwise test-takers guess at better than chance odds. Key balancing is the strategy test-takers adopted for ridding tests of positional biases. We show that formula scoring and key balancing, though widespread and intuitively appealing, are in fact "irrational" practices. They do not dispose of the guessing problem and are fraught with problems of their own. Yet they persist, even in the presence of more rational alternatives: Number right scoring is superior to formula scoring, and key randomization is superior to key balancing.

 Institutional frameworks powerfully determine the goals, violence, and trajectories of identitarian movements-including secessionist movements. However, both small-N and large-N researchers disagree on the question of whether ‘‘power-sharing’’ arrangements, instead of repression, are more or less likely to mitigate threats of secessionist mobilizations by disaffected, regionally concentrated minority groups. The PS-I modeling platform was used to create a virtual country ‘‘Beita,’’ containing within it a disaffected, partially controlled, regionally concentrated minority. Drawing on constructivist identity theory to determine behaviors by individual agents in Beita, the most popular theoretical positions on this issue were tested. Data were drawn from batches of hundreds of Beita histories produced under rigorous experimental conditions. The results lend support to sophisticated interpretations of the effects of repression vs. responsive or representative types of power-sharing. Although in the short run repression works to suppress ethnopolitical mobilization, it does not effectively reduce the threat of secession. Power-sharing can be more effective, but it also tends to encourage larger minority identitarian movements.

Olfactoric imagery is abundantly employed in the Bramhall-Hobbes controversy. I survey some examples and then turn to the possible significance of this. I argue that by forcing Hobbes into the figurative exchange Bramhall scores points in terms of moving the controversy into ground that is not covered by the limited view of rationality that Hobbes is committed to according to his rhetoric (at least as Bramhall perceives it). Bramhall clearly wants to move from cool argument to a more affluent rhetorical appeal. I argue that choosing such a richer epistemology coheres with Bramhall’s deeper anxieties regarding the moral method used in the Leviathan. This essay thus deviates from other form-content analysis of Hobbes, in attempting to examine his rhetoric in practice, under the pressure of controversy. My more general concern is in relating seemingly formal polemical choices to moral concerns.

The text we are dealing with here 1 consists of ritual instructions found in an all-year-round siddur in Aragonese Romance. The instructions, which are inserted in the ritual of the Passover holiday service are in accordance with tradition; they appear in the local language spoken by the Jews.
There are many Passover HaggmJoth originating in the Iberian Peninsula, including some with ritual instructions in Castilian and Portuguese romances but none has been preserved in Leonese Romance; they are also less numerous in Catalan Romance. The same is true of the books containing only the daily and Sabbath rituals (siddurim) and the prayer services for the different holidays of the Jewish year (mahzorim). The instructions concerning the Passover ritual in Judeo-Aragonese Romance I am dealing wi th here are part of a siddur that contains the liturgy for the whole circle of the year, weekdays, Sabbaths and festivals. It is found in the Bodleiana Library in Oxford.

Se discuten varios aspectos sobre la transmisión y recepción del Me'am Lo'ez de Bereshit (1730) de Yacob Julí (1685-1732), así como las principales fórmulas introductorias empleadas por su autor, las cuales aportan una valiosa información sobre la situación comunicativa en la que tenía lugar su transmisión. En qué situaciones se leía esta obra o a quién iba dirigida son algunas de las cuestiones a las que se da respuesta.

An extension of Condorcet's paradox by McGarvey (1953) asserts that for every asymmetric relation R on a finite set of candidates there is a strict-preferences voter profile that has the relation R as its strict simple majority relation. We prove that McGarvey's theorem can be extended to arbitrary neutral monotone social welfare functions which can be described by a strong simple game G if the voting power of each individual, measured by the it Shapley-Shubik power index, is sufficiently small. Our proof is based on an extension to another classic result concerning the majority rule. Condorcet studied an election between two candidates in which the voters' choices are random and independent and the probability of a voter choosing the first candidate is p > 1/2. Condorcet's Jury Theorem asserts that if the number of voters tends to infinity then the probability that the first candidate will be elected tends to one. We prove that this assertion extends to a sequence of arbitrary monotone strong simple games if and only if the maximum voting power for all individuals tends to zero.