question:You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.Title:A role for a single-stranded junction in RNA binding and specificity by the Tetrahymena group I ribozymePaper sections:<p>While much focus is placed on highly conserved regions of proteins and functional RNAs, these molecules also contain regions that have limited or no apparent conservation. There are regions of RNAs, such as telomeric RNA, SRP RNA, spliceosomal RNAs, and self-splicing introns, that are conserved only in subgroups,1,2 and there are sequences of no obvious conservation that nevertheless occur in regions that might be expected to have functional consequences.3 Here we report a multifaceted investigation of one such region, the J1/2 junction in the Tetrahymena group I intron (Figure 1).</p><p>J1/2 is not globally conserved in either length or sequence among different group I intron sub-groups or within the IC1 subgroup that includes the Tetrahymena intron.2,4, Nonetheless, J1/2 connects the substrate-containing P1 duplex to the rest of the intron (Figure 1A), and docking of the P1 duplex into tertiary interactions with the intron's catalytic core is a necessary step that precedes the chemical reaction6,7 (Figure 1A). It was previously shown that shortening or lengthening J1/2 decreases the fidelity of splice site selection in the Tetrahymena ribozyme reaction; the length changes weakened docking of the P1 duplex into tertiary interactions in the correct register and thereby favored docking into and cleavage from alternative registers.4,7 These mutational effects were not as expected for a simple tether, but the prior experiments could not distinguish whether tether flexibility, functional interactions with J1/2, non-native interactions with mutant J1/2 sequences, or steric constraints from the remainder of the ribozyme were responsible.</p><p>To understand the role of J1/2, we first used fluorescence polarization anisotropy (FPA) to assess the dynamics of the P1 duplex attached to ribozymes with J1/2 sequence that were systematically mutated. We related the effects of these J1/2 mutations on P1 dynamics to their functional consequences as assessed by single molecule FRET assays of P1 docking and assays of catalytic activity. The results revealed a role for the central A of the AAA J1/2 sequence (A29; Figure 1B & C), and further mutational tests and sequence analyses provided support for a tertiary interaction involving this residue.</p><p>To modulate the flexibility of J1/2, we systemically replaced the A residues with U's, as U residues stack less well than A residues.9,10 Eight ribozymes were investigated, with J1/2 sequences of AAA, AAU, AUA, UAA, AUU, UAU, UUA and UUU. 6-Methyl isoxanthopterin (6-MI) was incorporated into the P1 duplex of each ribozyme (Figure S1A). This fluorescent base analog has the unusual property of maintaining a high quantum yield within helices and thus can be used to follow dynamic properties of individual helices within complex RNAs.11,12 In its open state (Figure 1A, left), the P1 helix is connected to the remainder of the ribozyme by J1/2 but appears to make no specific tertiary interactions.12,13 As expected for the behavior of a tether, the anisotropy decreases, and thus dynamics increase, as the number of U residues in J1/2 increases (Figure S1B). In other words, there is greater randomization of the position of P1 during the fluorescent lifetime of 6-MI as more U residues are introduced.</p><p>A simple prediction from a tether model would be that the effect of J1/2 mutations on increasing mobility in the open complex would inversely correlate with the stability of the docked complex, as increased conformational freedom would disfavor the more positioned docked complex. The docking equilibrium constants of the eight mutants were obtained by monitoring the open and closed states using a single molecule FRET (smFRET) assay14-16 (see Supporting Information for details). We observed a striking discordance of the anisotropy and docking behaviors (Figure 2A). Whereas introduction of U residues at any position increased mobility, the docking equilibrium constant was only substantially affected by substitution of the central A, A29. Mutation of either or both of the flanking A residues had effects of less than threefold on docking (Figure 2A, blue), whereas mutation of the central A decreased docking by ~30 fold (Figure 2A, red), regardless of the identity of the flanking residues. This same trend was observed for ribozyme activity in assays that monitored both docking and the chemical step (Figure 2B), but with about three-fold larger effects of A29, either because there is a small additional effect on the chemical step or because the magnitude of the docking effect differs slightly under the different assay conditions.</p>Conditions<p>50 mM Na•MOPS, pH 7.0, 10 mM MgCl2 and 25 °C (see Supporting Information for details).</p><p>The simplest model to account for all of the data is that the J1/2 flexibility difference between 3A and 3U contributes little to P1 docking and that J1/2 stabilizes P1 docking through tertiary interactions involving A29. To further test this model, we carried out additional mutagenesis studies.</p><p>We first tested the base specificity of the putative A29 interaction by determining the catalytic activity of two additional J1/2 mutants with sequences of AGA and ACA. The values of kobs for these mutants were within three fold of that for AUA mutant, with both reacting >80 fold slower than the wild type AAA (Table S1). Thus, the residue 29 effect is specific to A.</p><p>We next wanted to identify potential interaction partners for A29. We first crudely assessed the geometrical accessibility of A29 to other residues. Using the structural model for the Tetrahymena group I intron,8 we considered residues within a sphere with its origin at A31 and a radius of 11 Å, roughly the length of an extended 2 nt linker.18 Among the accessible residues, we found that two base pairs in the P2 stem, A31•U56 and G32•C55 (Figure 1B), exhibited some degree of sequence co-conservation with A29 (i.e., the second residue of J1/2 that is 5′ of P2; see below). Double mutant cycles were used to test for interactions19 between A29 and these P2 base pairs. Briefly, the effect from mutation of each of the putative interaction partners (A29 and each of the P2 base pairs) were determined alone and together (Table S1). If there were an interaction, then a lessened effect would be expected with the other mutation present. Such a dependence was observed with A29 and the A31•U56 base pair (Figure 3A). Mutation of either A29 or A31•U56 alone gave 40-80 fold effects, whereas each mutation in a background in which the other mutation is already made gave an effect of <5 fold. In contrast, mutation of G32•C55 had no significant effect, and there was a similar large effect from mutation of A29 whether the G32•C55 base pair was wild type or mutant (Figure 3B). While the simplest model for the functional interaction between A29 and the A31•U56 base pair would be a base triple, additional mutagenesis tests provided no evidence for an isosteric base triple (Table S4). Specifically, double mutant cycles revealed that whereas there was energetic coupling of A29 with the A31•U56 mutant to C•G (Figure 3A), as noted above, no energetic coupling was observed with G•C and U•A base pairs (Tables S4). Thus, more complex models, involving additional interactions and/or conformation rearrangements must be invoked.</p><p>We mutated additional residues potentially in the vicinity of A29. Modest coupling was observed for residue A95 (3 fold), A304 (2 fold) and A270 (≥10 fold enhancement of the A29 effect) (Table S4 and S5 and unpublished results). Conversely, A269 and the first two base pairs of P2.1 have no energetic interaction with A29 (Table S5 and unpublished results). These results support a model in which A29 is situated near to and possibly interacts with A31•U56, and also provide evidence for an extended network of indirect interactions that extends to the the catalytic core (A270 and A304, Figure S3). The absence of a larger anisotropy effect for the A29 mutants than for the other J1/2 mutants (Figure S1B; Table S1) suggests that this interaction network does not include A29 in the undocked state (Figure S1B). Thus, the A29 interaction very likely forms along with docking of P1.</p><p>The functional interaction between the A29 of J1/2 and the A31•U56 base pair led us to look more closely at potential phylogenetic relationships using the extensive sequence database for group I introns.20 We found, within the IC1 subgroup of introns, that the mutual information (MI)21 is significantly higher between residue 29, the second residue upstream of P2, and residues 31 and 56 (MI = 0.29 and 0.19, respectively), which compose the first base pair in P2, than the MI between residue 29 and random residues in the rest of the intron sequence (MI = 0.06 ± 0.06; See Table S2 for more information). The high MI comes from a strong co-conservation between A29 and the A31•U56 base pair and is further illustrated in Figure 4 using sequence logos.23 The observed sequence co-conservation between A29 and the A31•U56 base pair is consistent with a functional interaction, as supported by the double-mutant cycles described above. Despite the strong co-conservation, there is no covariation and no observed isosteric three-base combinations of residue 29, 31 and 56, also matching the experimental functional tests described above (Table S4).</p><p>A conserved number of residues of twelve from a GNRA tetraloop at the end of the P2 helix to the conserved G•U wobble cleavage site in P1 was previously observed in several group I intron subgroups (IC3, IB2, IB4, IA1, IA2 and IA3),2,22,23 but not in the IC1 subgroup that lacks this tetraloop.2 We asked whether there might be an analogous relationship for the IC1 subgroup that includes the Tetrahymena intron (Table 1). Many introns within the IC1 subgroup have a combined length of J1/2 and P1 (up to the conserved G•U pair, Figure 1) of nine (327 of 810, red diagonal in Table 1), and nearly all of these introns have an A residue two residues upstream of P2 and an A•U base pair as the first base pair of P2 (314 of 327; Table 1, red). Thus, a measuring mechanism is suggested, consistent with prior observations of reduced 5′-splice site fidelity upon lengthening or shortening J1/2 of the Tetrahymena intron.4,7</p><p>Interestingly, a significant number of IC1 introns do not follow this "rule of nine", with some of these other introns having and some not having the above-noted A•U base pair (e.g., Table 1, blue & green). It appears that there have been multiple solutions within this subgroup for ensuring accurate 5′-splice site selection, and there is more to be learned about the evolutionary journey of these fascinating catalytic RNAs.</p><p>Counterintuitively, junction sequences without apparent conservation may be used liberally to optimize RNA function. We have shown that J1/2 plays sophisticated roles in RNA function. J1/2 is important for substrate binding and ribozyme activity through interactions involving the center A of J1/2, A29, of the Tetrahymena intron. A29 interacts with an extended network of residues connecting J1/2 with the RNA core. Further, A29 and the constant J1/2 and P1 length allow distal tuning of the ribozyme activity and specificity via a molecular ruler. These results suggest that regions referred to as 'linkers' can be important to function. Junctions that are not constrained to form secondary or tertiary structures may be able to extensively explore sequence and conformational space and thus rapidly evolve new functional interactions. The ability of J1/2, a seemingly nonconserved linker, to be co-opted for function provides an important precedent and model for dissection the function of other structured RNAs.</p>

question:Can you write a code snippet which change the color of this SVG to another one?<svg width="32" height="32" viewBox="0 0 32 32" fill="none" xmlns="http://www.w3.org/2000/svg"><path d="M2.2896 2H10.7104C11.4193 2 12 2.52754 12 3.17145C12 3.81536 11.4193 4.3429 10.7104 4.3429H7.8323V10.8208C7.8323 11.4647 7.26009 12 6.55124 12C5.84239 12 5.26165 11.4725 5.26165 10.8285V4.3429H2.2896C1.58075 4.3429 1 3.81536 1 3.17145C1 2.52754 1.58075 2 2.2896 2Z" fill="#212121"/><path d="M23.6366 2.01116C23.6581 2.00922 23.6796 2.00728 23.7011 2.00728C24.4151 2.00728 25 2.53444 25 3.17788V10.8216C25 11.4651 24.4409 12 23.7269 12C23.0129 12 22.428 11.4728 22.428 10.8294V5.75164L19.8645 8.06183C19.5892 8.30215 19.228 8.41068 18.8753 8.39518C18.514 8.41844 18.1527 8.30215 17.886 8.06183L15.5978 5.99972V10.8216C15.5978 11.4651 15.0129 11.9922 14.2989 11.9922C13.5849 11.9922 13 11.4651 13 10.8216V3.18563C13 2.87554 13.1204 2.5732 13.3785 2.34063C13.757 1.99178 14.3247 1.91425 14.7978 2.09256C14.9527 2.14682 15.0903 2.2321 15.2108 2.34063L18.8581 5.62761L22.5054 2.34063C22.7978 2.08481 23.1935 1.97627 23.572 2.01503C23.5935 2.01503 23.6151 2.0131 23.6366 2.01116Z" fill="#212121"/></svg>

question:[https://mba.tuck.dartmouth.edu/pages/faculty/ken.french/data_library.html](https://mba.tuck.dartmouth.edu/pages/faculty/ken.french/data_library.html)We can see that the Winner and Loser portfolios are determined by the cumulative return from t-12 to t-2.To construct the WML factor here, size(market cap) must also be considered.What date's market capitalization should be considered?Since the WML factor is rebalanced every month, should I determine the 'Small' and 'Big' portfolios monthly based on marketcaps of companies at t-1?Or should I sort it out once a year, just considering June's size, like when I make SMB factor?

question:A question that occasionally arises is what is the best way to determine the changelist that you last synced to in Perforce. This is often needed for things like injecting the changelist number into the revision info by the automatic build system.

question:i need this code to work in go:from typing import Tupledef complex_string_mixer(s1: str, s2: str) -> str: """ Intertwine two strings, perform a leftward cyclic rotation followed by reversing the merged result. """ # Check if lengths of both strings match if len(s1) != len(s2): raise ValueError("Both strings should be of equal length.") # Check if both strings are not empty if len(s1) == 0 or len(s2) == 0: raise ValueError("Both strings should not be empty.") # Intertwining the strings intertwined = ''.join(i+j for i, j in zip(s1, s2)) # Execute a leftward cyclic shift cyclic_shifted = intertwined[1:] + intertwined[0] # Reverse the combined string reversed_string = cyclic_shifted[::-1] return reversed_stringi'd love some insight into how the translated code works.

question:I have two different ways of displaying items in a WPF application. The first uses a WrapPanel and the second a vertical StackPanel. I can switch between the two ways of displaying my items by switching the host panel between the two types. This does work but you get an instance change in layout. Instead I want the child items to animate between the two layouts to give a nice smooth effect to the user. Any ideas how I could go about achieving that? Do I need to a Canvas instead and work out the positioning of children manually? That would be a real pain!