Neuraminidases (NA) are sialic acid-cleaving enzymes that are used by both bacteria and viruses. These enzymes have sialoside structure-related binding and cleaving preferences. Differentiating between these enzymes requires using a large array of hard-to-access sialosides. In this work, we used electrochemical impedimetric biosensing to differentiate among several pathogene-related NAs. We used a limited set of sialosides and tailored the surface properties. Various sialosides were grafted on two different surfaces with unique properties. Electrografting on glassy carbon electrodes provided low-density sialoside-functionalized surfaces with a hydrophobic submonolayer. A two-step assembly on gold electrodes provided a denser sialoside layer on a negatively charged submonolayer. The synthesis of each sialoside required dozens of laborious steps. Utilizing the unique protein–electrode interaction modes resulted in richer biodata without increasing the synthetic load. These principles allowed for profiling NAs and determining the efficacy of various antiviral inhibitors.
The fact that philosophy is systematic—that philosophical issues are thoroughly interconnected—was a commonplace among nineteenth century idealists, then neglected by analytic philosophers throughout much of the twentieth century, and has now finally started to get some renewed attention. But other than calling attention to the fact, few philosophers have tried to say what it consists in, or what its implications are. I argue that the systematicity of philosophy has disastrous epistemological implications. In particular, it implies philosophical skepticism: philosophers are rationally prohibited from believing any philosophical thesis. The argument goes by way of a new principle that connects inquiry with what is rational to believe. I conclude with a discussion of the relationship between my argument and other, more well-trodden arguments for philosophical skepticism.
A close connection between public opinion and policy is considered a vital element of democracy. However, legislators cannot be responsive to all voters at all times with regard to the policies the latter favor. We argue that legislators use their speaking time in parliament to offer compensatory speech to their constituents who might oppose how they voted on a policy, in order to reestablish themselves as responsive to the public’s wishes. Leveraging the case of Brexit, we show that legislators pay more attention to constituents who might be dissatisfied with how they voted. Furthermore, their use of rhetorical responsiveness is contingent on the magnitude of the representational deficit they face vis-à-vis their constituency. Our findings attest to the central role of parliamentary speech in maintaining responsiveness. They also demonstrate that communicative responsiveness can substitute for policy responsiveness
Demyelination and axonal injury in chronic-progressive Multiple Sclerosis (MS) are presumed to be driven by a neurotoxic bystander effect of meningeal-based myeloid infiltrates. There is an unmet clinical need to attenuate disease progression in such forms of CNS-compartmentalized MS. The failure of systemic immune suppressive treatments has highlighted the need for neuroprotective and repair-inducing strategies. Here, we examined whether direct targeting of CNS myeloid cells and modulating their toxicity may prevent irreversible tissue injury in chronic immune-mediated demyelinating disease. To that end, we utilized the experimental autoimmune encephalomyelitis (EAE) model in Biozzi mice, a clinically relevant MS model. We continuously delivered intracerebroventricularly (ICV) a retinoic acid receptor alpha agonist (RARα), as a potent regulator of myeloid cells, in the chronic phase of EAE. We assessed disease severity and performed pathological evaluations, functional analyses of immune cells, and single-cell RNA sequencing on isolated spinal CD11b+ cells. Although initiating treatment in the chronic phase of the disease, the RARα agonist successfully improved clinical outcomes and prevented axonal loss. ICV RARα agonist treatment inhibited pro-inflammatory pathways and shifted CNS myeloid cells toward neuroprotective phenotypes without affecting peripheral infiltrating myeloid cell phenotypes, or peripheral immunity. The treatment regulated cell-death pathways across multiple myeloid cell populations and suppressed apoptosis, resulting in paradoxically marked increased neuroinflammatory infiltrates, consisting mainly of microglia and CNS / border-associated macrophages. This work establishes the notion of bystander neurotoxicity by CNS immune infiltrates in chronic demyelinating disease. Furthermore, it shows that targeting compartmentalized neuroinflammation by selective regulation of CNS myeloid cell toxicity and survival reduces irreversible tissue injury, and may serve as a novel disease-modifying approach.
Ovarian cancer is the most fatal cancer of female reproductive organs. Ovarian cancer is typically diagnosed at a late stage, after metastasis occurred, leading to a 5-years relative survival rate of only ∼5%. Here, we demonstrate the anti-ovarian cancer properties of a peptide derived from the human protein CISD2/NAF-1 (3D-NAF-144-67-6K). This peptide selectively permeates the plasma membrane of ovarian cancer SKOV-3 cells without affecting healthy cells. 3D-NAF-144-67-6K targets and destroys the cancer cells’ mitochondria which leads to cancer cell death. In vivo studies of mice carrying xenograft tumours of SKOV-3 showed that the peptide significantly decreased the overall size and growth rate of both primary and metastatic ovarian cancer tumours. We further show that 3D-NAF-144-67-6K has a broad-spectrum anticancer activity targeting leukaemia, brain, and pancreas cancer cells. Our study suggests that 3D-NAF-144-67-6K could be used, alone or in drug combinations, to treat ovarian cancer and improve patient survival.
This study contributes to growing scholarly interest in teacher-led, school-based learning communities and the characteristics of teacher dialogue and social interaction that support professional learning in these settings. Based on existing conceptual distinctions proposed in the literature, we term this type of teacher dialogue "collaborative inquiry into practice" (CLIP) and propose a systematic and reliable tool to measure it. We then employ a quantitative, comparative research design to study how different teacher team activities (i.e., video-analysis, peer consultations, and pedagogical planning) shape the extent to which teachers engage in CLIP. Fifty-four transcribed teacher meeting excerpts were analyzed with the CLIP coding scheme, assessing different aspects of inquiry-based reasoning, participation, and content. Quantitative comparisons and illustrative examples show that CLIP was lowest during peer consultations, in part because teachers were often not positioned as agents of change in such conversations. Pedagogical planning activities featured more instances of inquiry into each other’s ideas. Contrary to common assumptions, collaborative video analysis activities were not characterized by increased attention to student thinking or inquiry orientation. Our findings provide new insights into teacher-led, collaborative learning in on-the-job settings, as well as practical implications for the design of school-based professional learning communities.
Traditionally, rock engravings were studied through their visual characteristics. They have been analyzed with comparative and interpretative methodologies of iconography and iconology. However, there has been a recent shift towards identifying production processes, allowing reconstruction of operational characteristics through various methods. Nevertheless, the studies of the technological aspects typically focus on the operational and the mechanical, often omitting the visuality of the outcome. In the current paper, we are using ArchCUT3-D software for computational analysis of 3-D data acquired from various rock engravings located in Timna Park, southern Israel. We show how micro-morphological evidence, extracted from the engraved lines, can decode technical trends and variabilities in a technique’s particular implementation. Then, we conduct a focused examination of one group of engraved figures in order to establish a link between execution techniques and visual considerations. Based on our results and the following discussion, we suggest the term Techné to indicate the choice of technique that goes beyond the instrumental or purely operative perspectives. We highlight the intentional choice, which designs the visual rhetoric of the engraved marks and suggests cultural concepts that contrived the procedural processes.
A recurrent theme of narratives by concentration-camp survivors is reciting poetry. For intellectuals in the camps, reciting verses was an aid to survival, aloophole of mental freedom, available only when the prisoners were not being driven to depletion at “general works.” Poetry also facilitated genuine human contact, helped the prisoners inscribe themselves into specific historical and cultural traditions, and re-mediated the verses that belonged to those traditions. The latter function of poetry recital was operative not only during the imprisonments but also during the composition of the narratives after the liberation: the memoirists not only found meanings in the cultural traditions on which their sense of identity depended but also helped to maintain these traditions for their own sake.
The increased prevalence of AI technology developed or adapted for military use raises difficult questions relating to the compatibility of this new technology with international law in general, and international human rights law (IHRL) in particular. This is because the move away from human discretion and agency to decision making by machines in contexts involving the use of lethal force implicates some of the most basic human rights, including the right to life. Indeed, the Human Rights Committee, the expert body entrusted with monitoring the application of the International Covenant on Civil and Political Rights, has expressed in 2018 its view on the relationship between the emergence of new military AI and respect for the right to life.
The present article will review the terms of the IHRL debate surrounding the introduction of AI technology into military contexts and its relationship to the right to life. In Part One, I will review briefly some actual and potential applications of AI in military contexts. Part Two deals with three principal objections against introducing military AI to battlefield environments: the capacity of autonomous or semi-autonomous AI systems to properly apply international humanitarian law (IHL), concerns about de facto lowering of standards of humanitarian protection and other ethical and legal implications of transferring certain life and death decision from humans to machines. Part Three reviews, in light of the three principled objections, specific proposals by the ICRC to limit the use of AI in military contexts (limiting the scope and manner of use of autonomous weapon systems, and excluding unpredictable and lethal systems). And Part Four reviews the main issues discussed in this article from the vantage point of the right to life under IHRL, as elaborated in General Comment No. 36.
Gil Bergman, Bruchiel-Spanier, Netta , Bluman, Omer , Levi, Noam , Harpaz, Sara , Malchick, Fyodor , Wu, Langyuan , Sonoo, Masato , Chae, Munseok S, Wang, Guoxiu , Mandler, Daniel , Aurbach, Doron , Zhang, Yong , Shpigel, Netanel , ו Sharon, Daniel . 2024. “To What Extent Do Anions Affect The Electrodeposition Of Zn?”. Journal Of Materials Chemistry A, 12, Pp. 14456-14466. doi:10.1039/d4ta01466a.
Gil Bergman, Spanier, Netta , Blumen, Omer , Levy, Noam , Harpaz, Sara , Malchik, Fyodor , Wu, Langyuan , Sonoo, Masato , Chae, Munseok S, Wang, Guoxiu , Mandler, Daniel , Aurbach, Doron , Zhang, Yong , Shpigel, Netanel , ו Sharon, Daniel . 2024. “To What Extent Do Anions Affect The Electrodeposition Of Zn?”. Journal Of Materials Chemistry A. . Publisher's Versionתקציר
Zinc metal, with its high theoretical capacity and low cost, stands out as a promising anode material for affordable high energy-density storage technologies in rechargeable batteries. However, obtaining a high...
