Red lines versus negotiables: how exposure to wartime violence influences support for peace settlements in Ukraine

The article is devoted to the study of administrative and legal mechanisms for countering threats from enemy unmanned aerial vehicles (UAVs) in the rear regions of Ukraine under martial law. The author draws attention to the transformation of security priorities in connection with the active use of drones by the enemy for attacks on the civilian population and critical civilian infrastructure, which requires a rethinking of the role of administrative law in responding to new technological challenges. The article outlines a range of administrative and legal problems associated with the unpreparedness of individual executive bodies to effectively respond to threats from the air, as well as the fragmentation of the current regulatory and legal framework in this area. It is determined that the main functions of responding to such threats are mainly entrusted to military formations, while the administrative and legal potential of state authorities in the rear remains insufficiently involved. Particular attention is paid to the issue of the institutional capacity of local authorities and the State Emergency Service, the National Police, etc. to create and implement administrative and legal instruments to respond to challenges related to hostile UAVs in the rear. The author concludes that it is necessary to form a stable regulatory and legal framework for responding to threats from drones in the rear, as well as to intensify administrative and legal activities on the ground. As a result, directions for improving administrative legislation are proposed, taking into account the experience of a full-scale war and drone attacks on peaceful settlements in Ukraine, in particular regarding the implementation of a joint civil-military air traffic control system, increasing the readiness of state authorities and creating conditions for a rapid response to threats from UAVs. The author proposes his own scheme of interaction between the military and civil authorities of Ukraine to counter threats from hostile UAVs in rear settlements. The scheme is built taking into account current regulatory and legal acts. A number of technical and organizational solutions to counter threats from UAVs have also been proposed.

This opinion piece of different Arab views and perspectives on the ‘Arab Spring’ and its significance and repercussions in the Arab Gulf region comprises three papers: ‘Repercussions of the Arab movements for democracy on the Saudi street’, by Mohammed Iben Sunitan; ‘Arab Spring … fleeting or perpetual?’, by Jasem Khaled Al-Sadoun; and ‘Repercussions of the Arab movements for democracy in Bahrain’, by Ali Mohammed Fakhro. Iben Sunitan posits a framework for a reading of the repercussions of the current movements on the Arab street in Saudi Arabia in a brief but highly informative account of the various Saudi opposition groups since the inception of the state under King ‘Abd al-’Aziz bin Sa9ud. The author details the various strategies that have been employed by Saudi monarchs for dealing with or assimilating various opposition groups that have appeared and he examines the new dynamics of a situation in which the youth figure prominently and the house of Al Sa9ud is at a crossroads where it must successfully adapt to the new objective conditions and atmosphere engendered by the climactic and momentous events of 2011. Al-Sadoun deals with numerous issues that pertain to the Gulf region in general such as age demographics, unemployment, economic issues, and the question of what he terms the dichotomy of ‘projects of rule’ as opposed to modern ‘projects of state’, where the former have tended to characterize the Arab world at the expense of both efforts to modernize and democratize. In the global context al-Sadoun sees hope for democratic transition provided that various Gulf rulerships and governments arrive at the conclusion that voluntary democratic reform is considerably less costly than suppression of the popular will. With regard to Tunisia and Egypt – despite serious socio-economic challenges in the latter – he sees promise in the models of Malaysia and Turkey. Fakhro deals with the particular situation in Bahrain characterized by ‘missed opportunities’ as well as regional military intervention, where peaceful demonstrations with initial moderate, legitimate demands pertaining to parliamentary representation and housing concerns that started in public areas such as the Pearl Roundabout were handled ineptly by the government, which chose to deal with them by force from the outset. Both sides crossed ‘red lines’ as demands escalated and demonstrators were gunned down not far from the royal palace. The King has called for an unconditional national dialogue; and while the situation has apparently calmed down for the moment, there remains grave concern over the future course of events. All three articles provide useful information and insight into the socio-political and economic dynamics of opposition movements in the Arab Gulf and the nature of their interaction with different types of political authority where it remains to be seen whether or not the prevailing climate of the ‘Arab Spring’ will persist in bringing about structural and genuine democratic reforms or whether protests will ultimately dissipate or assimilated through traditional means.

For Iran, the Nagorno-Karabakh conflict and its peaceful settlement were and remain closely related to national security interests. The basis of Iran's national security is anchored in the protection of all the layers of Iranian identity. Taking into consideration that this identity consists of Iranian, Islamic, Shiite and Revolutionary elements, we can argue that the attempt to impose a military solution to the Nagorno-Karabakh conflict and, particularly, the direct involvement of Turkey and foreign mercenaries in the conflict, has been and still remains a threat to all components of Iran’s security. The status quo of the Nagorno-Karabakh conflict has effectively hindered the implementation of the Azerbaijan-Northern Iran-Turkey pan-Turkic program. Moreover, the neutralization of this obstacle has been one of the important components of the security of Iran's identity. Azerbaijan, with the support of Turkey, is consistently trying to advance the idea of “one nation, two states”, presenting the northern provinces of Iran as “Southern Azerbaijan” and talking about the need to unite them with the Republic of Azerbaijan. In the context of this ideology and the struggle of the Pan-Iranian ideology against it, preventing the expansion of Azerbaijani forces toward the east and southeast was within Iran’s immediate interests. It is not surprising that in the aftermath of the 44-Day War in Karabakh, Iran has implemented several military drills across the Iran-Azerbaijan borders. The latest one is the largest and it has been accompanied by several anti-Azerbaijani statements from Iranian officials. In addition, Iranian officials have repeatedly stated that the territorial integrity of the Republic of Armenia is a red line for Iran and the North-South Corridor is of vital importance for Tehran. From the perspective of Iran’s Islamic identity, the current Azerbaijani state, with its secular approaches and pro-American, pro-Israeli policies, is considered a threat in the context of regional countries which are founded on Islamic values. Many Iranian experts and state officials believe that the Israeli technologies and human resources which have been used by Azerbaijan can also be used against Iran. From the perspective of Shiite identity, although Azerbaijan is a country with a Shiite majority population, the facts surrounding repressions in cities with a significant religious population make Azerbaijan an enemy of Shiite identity. The policy adopted by Azerbaijan around religious organizations inspires Iran to raise legitimate questions about the sincerity of Azerbaijan’s Shiite identity. During and after last year’s war, the transfer of Sunni mercenaries to Azerbaijan has also had a major impact on the security of Northern Iran. It is crucial to remember that Iran has made it a national security priority to fight against Sunni extremist groups in Syria, Iraq, Libya and other parts of the region, asserting that if they are not eliminated outside of Iran’s borders, they will end up in the country proper. During the war, Iran’s officials repeatedly stressed the importance of the withdrawal of those mercenaries from the region. The presence of the mercenaries in the region was condemned not only by the representatives of the Ministry of Foreign Affairs of Iran and by the Majles but also in a statement made by Iran’s leader, Ayatollah Ali Khamenei, on 3 November 2020. From the perspective of Iran’s revolutionary identity, the existence of Azerbaijan’s clan-based state authorities and the reliance of Azerbaijani politics on foreign economic and political actors in a polarized society make Azerbaijan an obstacle for the dissemination of Iran’s revolutionary values. Thus, we can state that while Iran’s response to the escalation of the conflict in Nagorno-Karabakh was neutral and balanced, as it has been traditionally, Iran still has strong concerns about Azerbaijan’s behavior and desire for a military solution, Turkey’s involvement and the arrival of mercenaries in the region. Furthermore, Tehran’s statements about the sovereign territories of Armenia being its red line, especially when it comes to the southern Syunik region after the trilateral agreement of 9 November, make Iran’s security in the northern regions very vulnerable. This is the reason why Iran has been proactive with regards to its statements about regional stability and peace while also initiating a series of visits to both Azerbaijan and Armenia to boost all the possible regional projects, especially concerning the North-South Corridor.

While the present dispensation in Kabul can be regarded as relatively more stable than the regimes in recent pre-2001 period, a number of challenges — security, political and socio-economic — continue to persist. The Afghan National Army and other law enforcing agencies find it hard to fend off the continuously increasing and assertive strength of resistance forces. Talks between the representatives of Kabul government and the resistance forces have been reinitiated in Qatar but the outcome and future course remains too little to talk about. Their contacts can only be regarded as ‘talks about talks’ for complete withdrawal of foreign troops and the positions on Constitution among the major issues on the road to a possible yet hard-to-achieve negotiated settlement. Economy and quality of life are far from satisfactory and are actually in danger of further deterioration. If a negotiated and peaceful settlement is desired, then both the sides will have to soften their stances to an extent. The role of regional countries as well as the UN — not really in the lead so far — will assume a critical significance. This is a revised and updated version of the paper presented in international symposium on “The Situation in Afghanistan after NATO's Withdrawal”, held in Istanbul under the auspices of South Asia Strategic Research Center on May 5–7, 2015.

Separate Modulations of Human V1 Associated with Spatial Attention and Task Structure

HORTICULTURAL PLANT BREEDING: PAST ACCOMPLISHMENTS, FUTURE DIRECTIONS

Full text Figures and data Side by side Abstract eLife digest Introduction Results Discussion Materials and methods References Decision letter Author response Article and author information Metrics Abstract Influenza virus penetrates cells by fusion of viral and endosomal membranes catalyzed by the viral hemagglutinin (HA). Structures of the initial and final states of the HA trimer define the fusion endpoints, but do not specify intermediates. We have characterized these transitions by analyzing low-pH-induced fusion kinetics of individual virions and validated the analysis by computer simulation. We detect initial engagement with the target membrane of fusion peptides from independently triggered HAs within the larger virus-target contact patch; fusion then requires engagement of three or four neighboring HA trimers. Effects of mutations in HA indicate that withdrawal of the fusion peptide from a pocket in the pre-fusion trimer is rate-limiting for both events, but the requirement for cooperative action of several HAs to bring the fusing membranes together leads to a long-lived intermediate state for single, extended HA trimers. This intermediate is thus a fundamental aspect of the fusion mechanism. https://doi.org/10.7554/eLife.00333.001 eLife digest Influenza is caused by viruses that infect birds and mammals. These viruses enter cells when two lipid bilayers—one surrounding the virus, the other enclosing the cellular compartment into which the virus has been engulfed—merge to form a single unified membrane. This process, known as membrane fusion, allows the RNA of the virus to gain access to the host cell's molecular machinery, which it commandeers to produce multiple copies of itself and to direct the assembly of new virus particles. The process of membrane fusion generally includes an intermediate hemifused state in which only the adjacent monolayers from each bilayer have merged. In addition to its role in virology, membrane fusion is critical for many other biological processes, including exocytosis, protein trafficking and the fertilization of eggs by sperm. Efficient membrane fusion requires a catalyst, and a glycoprotein known as the influenza hemagglutinin performs this role for the influenza virus. The hemagglutinin is found on the surface of the virus, and a typical influenza virus particle can have a few hundred such molecules on its surface. When an influenza virus particle binds to the surface of a cell (as a result of these hemagglutinin molecules interacting with cellular receptor molecules), the cell engulfs the virus into an internal compartment called an endosome. Acidification of the endosome, part of the cell's normal activity, triggers a sequence of conformational changes in the hemagglutinin molecules on the surface of the virus. One part of the hemagglutinin inserts itself into the endosomal membrane, and further conformational changes draw the endosomal and viral membranes together into an intermediate, hemifused state; the process then continues until fusion of the two membranes is complete. Previous work has suggested that an average of three hemagglutinin molecules are required to fuse the endosomal and viral membranes. Ivanovic et al. have now investigated the molecular details of this process and described the time course of conformational changes undergone by the hemagglutinin molecules from the moment the pH is lowered within the endosome until the time when hemifusion of the endosomal and viral membranes is complete. They find, among other things, that hemifusion proceeds rapidly only when three or four immediately adjacent hemagglutinin molecules have inserted into the endosomal membrane. Since membrane fusion is a very general cellular process, the findings of Ivanovic et al. are relevant to many areas of cell biology, in addition to having potential applications in virology. https://doi.org/10.7554/eLife.00333.002 Introduction Fusion of two lipid-bilayer membranes is a thermodynamically favorable process, but it crosses a high kinetic barrier as the two bilayers approach each other. Efficient fusion therefore requires a catalyst, a role served in living cells by a fusion protein or protein complex. The influenza virus hemagglutinin (HA) has become an important paradigm of a fusion catalyst, in part because of early crystallographic and mechanistic studies and in part because of continued concern about a virus that caused tens of millions of deaths during the 20th century. HA facilitates fusion by undergoing a large-scale conformational change, coupled to the two fusing membranes (virus and target). Our current picture of HA-mediated membrane fusion, illustrated in Figure 1A (Harrison, 2008), comes from HA structures in both pre- and post-fusion conformations and from inferences about transient intermediate states. HA is a homotrimer, synthesized as an inactive precursor, [HA0]3, and activated for fusion by proteolytic cleavage of each chain into HA1 and HA2, yielding [HA1-HA2]3. At the N-terminus of HA2 is a hydrophobic ‘fusion peptide', which following cleavage inserts firmly into a pocket near the axis of the trimer (Chen et al., 1998). Exposure to low pH, which during infection occurs in an endosome, causes the HA1 ‘head' to separate from the HA2 ‘stem' and enables a set of HA2 conformational transformations: (1) release of the fusion peptide from its pre-fusion pocket; (2) HA2 extension; (3) insertion of the fusion peptide into the target membrane; (4) fold-back of the extended HA2 intermediate (Figure 1A) (Skehel and Wiley, 2000). This last step brings together the fusion peptide and the C-terminal, transmembrane segment of each HA2, anchored respectively in the viral and target membranes, which thus approach each other, either as apposed protrusions or as a single, target-membrane protrusion (Kuzmin et al., 2001; Lee, 2010). Fusion then ensues, initially as hemifusion (merger of only the proximal membrane leaflets) and then as formation of a continuous aqueous channel. Figure 1 with 1 supplement see all Download asset Open asset Single-virion analysis of fusion-promoting conformational change in influenza virus HA. (A) Hydrophobic fusion peptide (red asterisk) is initially inserted into a pocket near the trimer threefold axis. HA assumes an ‘open' conformation upon proton binding allowing fusion-peptide release and membrane insertion. The fold-back of the extended intermediate causes hemifusion. The known pre-fusion and post-fusion HA structures are colored, and the inferred structural transitions are showed in gray. (B) Left: Tile view from pH drop (t0) of a virion initially displaying directed motion (white arrow) followed by arrest (ta) then hemifusion (th). Red circle marks the final virion location. Arrowheads mark two virions that were arrested at pH drop and hemifused at or just before t40 s and t68 s respectively. Right: Fluorescence trace of the virion circled in (A) (red line), line fitting the timing of virion arrest at its target location (black line) and parameters t0 (green vertical line), ta (blue horizontal line) and th (orange horizontal line) and arrest to hemifusion, ta–h (dark orange horizontal line). (C) tlag(pHdrop–arrest) for all virions for which arrest values could be derived (left) and tlag(arrest–hemifusion) for all virions for which both arrest and hemifusion values could be derived (right) with gamma-distribution fit (black line). Data are pooled from three independent experiments. (D) Mean tlag(pHdrop–arrest) and tlag(arrest–hemifusion). Error bars represent the standard error of the mean. (E) and (F) N derived from fitting tlag(pHdrop-arrest) (E) and tlag(arrest–hemifusion) (F) with gamma probability density. (G) Rate constants derived from fitting tlag(arrest–hemifusion) and tlag(pHdrop–arrest) with gamma probability density and keeping N fixed (N = 3) for both processes. (B–G) X31-HA virions have X31 HA in otherwise Udorn genetic background. Data shown are from representative experiments performed on the same day (n = 50 to 150) unless indicated that multiple experiments were pooled. Error bars represent 95% confidence interval for gamma fit-derived values unless otherwise indicated. Please refer to Figure 1—figure supplement 1 for all histogram and gamma-distribution fit data plotted in (D–G). https://doi.org/10.7554/eLife.00333.003 We report here a series of experiments that probe the relationship between HA structural properties and kinetic intermediates in the fusion pathway. Floyd et al. (2008) devised a method to monitor in real time the fusion of individual influenza virus particles with planar bilayers. Their results led to the conclusion that fusion requires on average three HA trimers, each of which independently undergoes the same, rate-limiting rearrangement, but they left undetermined the relationship between this conclusion and the inferred intermediates in Figure 1A. In the experiments reported here, we correlate HA structure with observed variations in fusion kinetics by comparing rates for appropriate HA mutants. We conclude that irreversible engagement of fusion peptides from 3–4 neighboring [HA1-HA2]3 trimers, within a much larger virus-target-membrane interface, leads to subsequent rearrangements that rapidly and cooperatively induce membrane merger. Release of the fusion peptide from its pocket is rate-limiting for membrane engagement. A long-lived membrane-inserted extended intermediate is a fundamental aspect of the fusion mechanism. Results Hemifusion times and particle arrest We recorded in real time a large number of individual influenza virions (approximately 1000 virions per field of view), labeled with a lipophilic fluorophore (R18), as they fused with a supported planar bilayer (see ‘Materials and methods'). We followed hemifusion as a spike in individual virion fluorescence resulting from R18 fluorescence dequenching upon dilution into the target membrane (Figure 1B). We also observed a previously undetected fusion intermediate. Upon initiating the flow of buffer for pH exchange, most virions started to move under the hydrodynamic force while retaining contacts with the target bilayer. The particles arrested at various times after the pH drop, but invariably preceding hemifusion (Figure 1B; Video 1). The arrest was irreversible (Videos 2 and 3). A subset (approximately 20% at pH 5.5 and 5.65) of virions had already arrested at the onset of imaging or had done so before the pH drop. For lower final pH, a larger fraction had arrested by the time the pH drop was complete (Table 1). We determined lag times between pH drop and individual virion arrest (tlag(pHdrop–arrest)) and between arrest and hemifusion (tlag(arrest–hemifusion)) whenever both values could be extracted from the data (Figure 1B,C), for a range of proton concentrations between 2 and 100 µM (pH 5.65–4) (Figure 1D). Mean values for tlag(pHdrop–arrest) and tlag(arrest–hemifusion) show the same pH dependence, with mean tlag(pHdrop–arrest) being about an order of magnitude shorter throughout the tested pH range. Video 1 Download asset This video cannot be played in place because your browser does support HTML5 video. You may still download the video for offline viewing. Download as MPEG-4 Download as WebM Download as Ogg X31-HA WT virion hemifusion at pH 5.5 from t0 to t230 s at 20× the actual rate. https://doi.org/10.7554/eLife.00333.005 Video 2 Download asset This video cannot be played in place because your browser does support HTML5 video. You may still download the video for offline viewing. Download as MPEG-4 Download as WebM Download as Ogg Virion arrest is an irreversible intermediate of fusion. X31-HA WT virions were imaged. pH was dropped from 7.4 to 5.65 then brought back up to 7.4. Buffer flow was kept constant except when it was stopped to allow for the source buffer exchange back to neutral (between approximately t45 s and t95 s). https://doi.org/10.7554/eLife.00333.006 Video 3 Download asset This video cannot be played in place because your browser does support HTML5 video. You may still download the video for offline viewing. Download as MPEG-4 Download as WebM Download as Ogg Virion arrest is an irreversible intermediate of fusion. A different field of view of the same experimental lane used in Video 2 after the events imaged in Video 2. pH was dropped to pH 5.65. There is a marked reduction in the mobile fraction in Video 3 relative to early times shown in Video 2. Furthermore, prearrested virions proceeded to hemifusion despite the intermediate reneutralization step. The videos are shown at 20× the actual rate. https://doi.org/10.7554/eLife.00333.007 Table 1 Arrest and hemifusion statistics for X31-HA WT and arrest statistics for S4GHA2Udorn virions https://doi.org/10.7554/eLife.00333.008 Virion arrest to hemifusion*pH drop to virion arrest†pH 5.5X31-HA WT‡X31-HA WT‡S4GHA2Udorn§Number of virions3801215401Mean lag time (s)#105.1 ± 2.710.3 ± 0.29 ± 0.4N¶3.7 ± 0.63.4 ± 0.23.4 ± 0.3Rate constant (s−1) ¶0.032 ± 0.0060.33 ± 0.020.37 ± 0.03Mobile at pH drop**81%76%Mobile that hemifused**75%65%Static that hemifused**82%81%pH 4.5Number of virions155392385Mean lag time (s) #13.3 ± 0.61.4 ± 0.0041.4 ± 0.004Mobile at pH drop**46%38% * tlag(arrest–hemifusion) for all virions for which both arrest and hemifusion values could be derived. † tlag(pHdrop–arrest) for all mobile virions for which arrest values could be derived. ‡ X31-HA WT data are pooled from three independent experiments. § S4GHA2Udorn data are pooled from two independent experiments. # Errors represent the standard error of the mean. ¶ Errors represent the 95% confidence interval for the values derived from gamma-probability fits shown in Figure 1C (X31-HA virions) or Figure 4C (S4GHA2Udorn virions). ** Percentages are derived from entire data sets. We can fit the distributions for both tlag(pHdrop–arrest) and tlag(arrest–hemifusion) with one describing a requirement for N independent events (either parallel or sequential; Feller, 1968), each with rate constant, k (Figure 1C and Table 1). For any given particle, the two lag times are uncorrelated, ruling out any mutual dependence on overall particle properties such as length (Figure 2). We have further controlled for virion length by using only shorter-virion fractions in our experiments (see ‘Materials and methods'). From the distributions, we derive N = 3–4 both for the number of events required to arrest virions following pH drop (Figure 1E and Table 1) and for the number of events required for hemifusion of the arrested particle (Figure 1F and Table 1) (see ‘Materials and methods'); the latter is similar to the value obtained previously from tlag(pHdrop–hemifusion) distributions (Floyd et al., 2008). Figure 2 Download asset Open asset Virion arrest and hemifusion lag times are uncorrelated. tlag(arrest–hemifusion) vs tlag(pHdrop–arrest) for X31-HA virions at pH 5.5 (n = 380). Data are pooled from three independent experiments also shown in Figure 1C, Table 1 and Figure 4A,B (X31–HA). https://doi.org/10.7554/eLife.00333.009 A simple interpretation of virion arrest is that insertion of fusion peptides from a number of independent HA trimers (3 or 4) into the target membrane anchors the particle. Bulk experiments have shown that short incubations of virions with target membranes at pH 5 and 0°C lead to insertion of a small subset of fusion peptides and stable virus anchoring not associated with membrane fusion (Tsurudome et al., 1992). We attribute the majority of pre-arrested events during high pH experiments (pH 5.5 and above) to imperfections in the bilayer or defective virions; the observed increase in the immobile fraction at lower pH might result from genuine triggering and membrane insertion of HA fusion peptides upon proton binding during the pH transition (see ‘Materials and methods'). Site-directed HA mutations and the rate-limiting step for HA rearrangement To probe the molecular mechanism of arrest and its relationship to the mechanism of hemifusion (for which membrane insertion of the fusion peptide is clearly critical), we generated recombinant virus particles with site-directed mutations in HA. We used a set of plasmids derived from the A/Udorn/72 H3 influenza strain. The HA of Udorn is 97% identical in amino-acid sequence to that of X-31, the virus used in previous experiments (Floyd et al., 2008) and also the source of HA in otherwise Udorn genetic background in the experiments in Figure 1. Nonetheless, recombinant virions with Udorn HA had shorter hemifusion lag times in the physiologically relevant pH regime (pH > 4.5) than did those with X-31 HA (Figure 3A, Videos 1 and 4). Moreover, the Udorn-HA particles did not show directed motion under flow at any observable time point—that is, they had arrested by the time the low-pH transition was complete (see ‘Materials and methods'). The Udorn hemifusion lag time (tlag(pHdrop–hemifusion)) distribution between pH 5.65 and 4 gave a pH-independent value of N close to 3 (Figure 3B), showing that differences between Udorn and X31 HAs do not affect the number of rate-limiting steps between virion arrest and hemifusion, but only their individual rate constants (Figure 3C). Figure 3 with 1 supplement see all Download asset Open asset Udorn virions have accelerated hemifusion kinetics. (A) Mean tlag(pHdrop–hemifusion) for Udorn and mean tlag(arrest–hemifusion) for X31-HA virions. Error bars represent the standard error of the mean. (B) N derived from fitting tlag(pHdrop–hemifusion) with gamma probability density. (C) Rate constants derived from fitting tlag(pHdrop-arrest) for Udorn and tlag(arrest–hemifusion) for X31-HA virions with gamma probability density and keeping each N fixed (N = 3). (B–C) Error bars represent 95% confidence interval for gamma fit-derived values. (A–C) Data shown are from representative experiments performed on the same day (n = 50 to 350). Please refer to Figure 3—figure supplement 1 for all histogram and gamma-distribution fit data plotted in (A–C). (D) Top left: Ribbon representation of X31-HA trimer (Weis et al., 1990) showing positions of all residues that differ in Udorn-HA (arrowhead) including Gly4HA2 (asterisk). Top right: Cartoon of an HA monomer emphasizing Asp112HA2-fusion peptide hydrogen bond network and showing positions of residues along the HA2 chain. Bottom: Close-up of the Asp112HA2-fusion peptide network (region marked with an orange square on top left). https://doi.org/10.7554/eLife.00333.010 Comparison of the Udorn and X-31 HA amino-acid sequences suggests that one particular difference might account for the accelerated fusion kinetics of the former—a substitution of serine for glycine at position four in HA2. Udorn is the only strain in the database with this substitution, glycine being otherwise universally conserved (Nobusawa et al., 1991; Cross et al., 2009). In the pre-fusion conformation of HA, Gly4HA2 participates in a network of polar hydrogen-bond interactions with the carboxylate of Asp112 HA2, which is also strictly conserved (Figure 3D) (Wilson et al., 1981; Weis et al., 1990; Russell et al., 2004). A serine substitution would weaken or interrupt this interaction, because the glycine has a backbone conformation not allowed for other residues. Previous studies have reported an elevated pH threshold of fusion for cell-surface expressed HA at or Asp112 et al., et al., Gly4HA2 might also a conformation of the membrane-inserted fusion-peptide et al., but its does not critical for fusion-peptide insertion into membranes et al., We generated a series of HA in the of recombinant to the for fusion kinetics of the and of the fusion-peptide in activated HA. These and as as in both Figure 4A,B and Videos 1 and our analysis of hemifusion rates for these at pH The hemifusion, and the S4GHA2Udorn it (Figure Moreover, WT Udorn virions do not show motion at pH drop, while S4GHA2Udorn virions do (Videos 5 and Table 1). parameters for derived from the tlag(pHdrop–arrest) distribution for the S4GHA2Udorn particles are from those for X31-HA WT (Figure 4C and Table 1). These show that a single and thus the same molecular process, both the rate of arrest and the rate of hemifusion. Figure 4 with 1 supplement see all Download asset Open asset release from its pre-fusion pocket is a rate-limiting molecular rearrangement in the physiologically relevant pH (A) pH mean tlag(arrest–hemifusion) for X31-HA S4GHA2Udorn and mean tlag(pHdrop–hemifusion) for Udorn and (B) N derived from fits of the data also in (C) of tlag(arrest–hemifusion) distribution for S4GHA2Udorn virions at pH 5.5 with the fit (black line). (D) pH mean tlag(pHdrop–hemifusion) for indicated virions. (E) N derived from fits of the data also in Data shown are from pooled independent experiments for Udorn and X31-HA WT and for Udorn and X31-HA virions; = to Error bars represent the standard error of the mean and or the 95% confidence interval for gamma fit-derived values and Please refer to Figure supplement 1 for all histogram and gamma-distribution fit data plotted in and Video 4 Download asset This video cannot be played in place because your browser does support HTML5 video. You may still download the video for offline viewing. Download as MPEG-4 Download as WebM Download as Ogg Udorn WT virion hemifusion at pH 5.5 from t0 to s at 20× the actual rate. Video 5 Download asset This video cannot be played in place because your browser does support HTML5 video. You may still download the video for offline viewing. Download as MPEG-4 Download as WebM Download as Ogg virion hemifusion at pH 5.5 from t0 to s at 20× the actual rate. Video Download asset This video cannot be played in place because your browser does support HTML5 video. You may still download the video for offline viewing. Download as MPEG-4 Download as WebM Download as Ogg S4GHA2Udorn virion hemifusion at pH 5.5 from t0 to s at 20× the actual rate. Video Download asset This video cannot be played in place because your browser does support HTML5 video. You may still download the video for offline viewing. Download as MPEG-4 Download as WebM Download as Ogg virion hemifusion at pH 5.5 from t0 to t40 s at 20× the actual rate. Video Download asset This video cannot be played in place because your browser does support HTML5 video. You may still download the video for offline viewing. Download as MPEG-4 Download as WebM Download as Ogg virion hemifusion at pH 5.5 from t0 to s at 20× the actual rate. Data from that the has an important on hemifusion rate at pH mutations hemifusion of both Udorn and X31-HA but the on the latter is (Figure We from these that the contacts between the fusion-peptide residues and and that the change then this source of of the mutations change the values of N derived from the pH 5.5 tlag(arrest–hemifusion) distributions for tlag(pHdrop–hemifusion) (Figure showing that these changes do not affect the number of We conclude that for these release of the fusion peptide from its pre-fusion pocket is a rate-limiting step in the transition from arrest to hemifusion. The changes in fusion kinetics by the including the fit obtained from a probability distribution that assumes changes in the rates of all N events (see ‘Materials and further support our that N is to the number of HA trimers that independently their fusion peptides before a transition can The rate of arrest for either of the was for to detect motion (Videos and We therefore could not N from arrest distributions for those but we could that fusion-peptide release from its pocket is rate-limiting for virion arrest as as for hemifusion. At pH and the described have mean values for tlag(pHdrop–hemifusion) (Figure Moreover, the lag times have become pH because most of the relevant have become A subset than at pH of X31-HA WT and S4GHA2Udorn virions directed motion under the force of buffer flow at the pH drop, both with mean times of just under s (Table 1). the tlag(pHdrop–hemifusion) distributions with a gamma probability density values of N (between 3 and for all the that changes with pH is not the number of rate-limiting rearrangements to hemifusion but only their rate (Figure of Asp112 mutations that affect of the fusion peptide in its pre-fusion pocket and the fusion rate at pH 5.5 have or on the fusion rate at pH and The value of N and the that a fraction of the X31-HA WT and S4GHA2Udorn particles show directed motion after the pH drop that at pH rate-limiting rearrangement membrane insertion of the fusion The of mutations at positions 4 and in HA2 on hemifusion at the physiologically relevant pH of 5.5 that the steps the rate of arrest the time of pH and the rate of transition from arrest to hemifusion are the same, that is, both are by the rate of fusion-peptide also result from the action of several HA trimers each undergoing this rate-limiting rearrangement as indicated by the of their individual lag time distributions value of under different proton concentrations (Figure 1). The rate constants derived from gamma distribution fitting of the tlag(pHdrop–arrest) data about to than those for (Figure that the in each arrest and hemifusion, is by different A simple interpretation of these is that virion arrest results from fusion-peptide release and irreversible target-membrane insertion from several HA trimers in the of virus-target membrane contact and that hemifusion is by the same HA fusion-peptide release and membrane but requires a for the that is, their to each other, and is thus to a different of molecular events in the contact between virion and target membrane To the of our and to probe the relationship between the value of N derived from gamma-distribution fitting of hemifusion lag times and the actual number of HA trimers in the hemifusion we the following computer (Figure We a contact of various between 50 and HAs as a of trimers. Our of a contact that can up to about 50 HA trimers, shown in Figure is on of a virion with in et al., 2010). used in our current experiments are on average approximately and et al., see ‘Materials and and thus the actual contact can on average up to about HA trimers. For each virion we obtained lag times for individual HA triggering and

Electrophotocatalytic Si–H Activation Governed by Polarity-Matching Effects

Liberal democracies are expected to provide residents with both negative rights, such as limitations against the abuse of police powers, and some range of positive (social) rights, such as access to social benefits. These rights are commonly deemed to apply equally, without respect to individuals’ ascriptive backgrounds. Existing research, often in the US context and focused on social programs, shows both support for abstract rights and group-specific prejudices. We interrogate whether similar patterns exist in Canada and innovate by directly examining negative and positive rights in the same study. Using a series of novel survey experiments, we demonstrate the degree to which categorical inequalities based on race and legal status affect public support for rights provision in Canada. Both rights are more recognized for citizens relative to out-of-status migrants, and legal status at times interacts with racialized minority status. Rights appear far from universal in the minds of Canadians.

This paper presents results from a series of survey experiments testing the effects of various arguments on relative evaluations of ranked-choice (RCV) and choose-one ballots. We examine data from the 2020 Collaborative Multiracial Post-Election Survey (CMPS), allowing for comparisons across racial groups. Reformers have emphasized the voter’s ability to have their vote transferred to a lower-ranked candidate as a positive aspect of the system. However, we find that an explanation of RCV’s vote-transfer properties does not increase public support. Furthermore, when given a choice between the single and ranked voting methods, a majority within each racial group prefers the single vote. However, Latino, Asian American, and MENA respondents express a stronger preference for RCV than white respondents. Democrats also evaluate RCV more favorably than Republicans. Furthermore, communicating that RCV helps elect more women and people of color increases support among Democrats but not Republicans across most racial groups. This is consistent with other findings around growing partisan differences in views toward diversity and descriptive representation. Finally, a message emphasizing voter confusion has little impact on public support for RCV. Arguments about the impact of electoral systems are found to influence public preferences more than descriptions of those systems’ key properties.

Past studies suggest that domestic public support for compliance with international human rights law can constrain governments to comply with human rights law. But the question remains: Why does the public care about compliance? Using a series of survey experiments in South Korea and the United States, this study finds that constituents are concerned about compliance in one issue area—such as human rights—because they believe it will affect the country's reputation in other domains of international law. Cross-national survey experiments demonstrate that past noncompliance negatively affects the South Korean public's second-order beliefs about the likelihood of future compliance across different issue areas. However, past noncompliance has a limited impact on the US public's first-order beliefs across different domains.

This chapter reviews individual-voter-level hypotheses with experimental evidence from an original survey of fifteen hundred victims and nonvictims in Colombia. It evaluates whether war winners as candidates are able to shift voters' reference points in order to launder violent pasts and cultivate a reputation for security. With a series of survey experiments, the chapter also examines the party strategy of Restrained Leviathan, which comprises of military and civilian candidates and a platform convergent on the interests of the moderate voter. The chapter discusses whether the political strategy called the Tactical Immoderate, comprising civilian candidates, proves more successful for the militarily disadvantaged belligerent. It looks at alternative mechanisms of voter coercion and voter ignorance.

ABSTRACTWhile previous research has investigated how coproduction can improve the quality and efficiency of public services, less is known about its effects on how citizens view government. Thus, we investigate how coproduction may influence trust in government using a series of survey experiments. Although our main results are generally in the expected direction, they are not significant statistically and thus suggest little or no causal effect of coproduction on trust. Limitations of our approach, as well as directions for future experimental research along these lines, are discussed.

As early as the late 1950s with the work of Herbert Simon, psychologists began questioning the value of unbounded rationality in economic modeling, noting that the human brain faced its own evolved limited and imperfect internal resources. Daniel Kahneman and Amos Tversky in the 1970s began calling into serious question the neoclassical methodological approach by running a series of laboratory and survey experiments that found substantial gaps between the predictions of economic models grounded in perfect rationality and the way real people behave or say they would behave. In the late 1980s and continuing into this century, Richard Thaler uncovered a small library of “anomalies” in people’s behaviors, as judged by predictions from neoclassical economics, grounded in contemporary times (but not in earlier eras) in perfect rationality. A growing cadre of behavioral economists have gone further, concluding that people are so frequently “irrational” that they are “predictably irrational,” suggesting that neoclassical economists should fold their analytical efforts.

UPDATE: Please see updated paper for a description of a differential attrition problem that will require changes to the analysis and further experimentation. Although partisan orientations are sometimes characterized as the unmoved movers of political evaluations and vote choice, both panel surveys and aggregate time-series indicate that partisan change does occur. To date, however, researchers have seldom attempted to induce a change in partisanship experimentally. Guided by longstanding explanations of how people come to acquire and update their partisan attachments, we worked with media consultants to develop persuasive political advertising designed to win partisan converts. These video ads were deployed in a series of multi-wave survey experiments that tracked panel respondents over time in an effort to gauge the messages' immediate and persistent effects on party identification, as well as their downstream effects on political evaluations and voting preferences. We find that party-focused messaging operates as theoretically expected, especially at high dosages, producing small but demonstrable effects on partisanship with downstream consequences for political preferences. The fact that these effects dissipate over time helps illuminate individual- and aggregate-level patterns of partisan change.