When resources collide: Towards a theory of coincidence in information spaces

This paper is an attempt to lay out foundations for a general theory of coincidence in information spaces such as the World Wide Web, expanding on existing work on bursty structures in document streams and information cascades. We elaborate on the hypothesis that every resource that is published in an information space, enters a temporary interaction with another resource once a unique explicit or implicit reference between the two is found. This thought is motivated by Erwin Shroedingers notion of entanglement between quantum systems. We present a generic information cascade model that exploits only the temporal order of information sharing activities, combined with inherent properties of the shared information resources. The approach was applied to data from the world's largest online citizen science platform Zooniverse and we report about findings of this case study

Synthesizing a σ^z\hat{\sigma}_z spin-dependent force for optical, metastable, and ground state trapped-ion qubits

A single bichromatic field near-resonant to a qubit transition is typically used for $\hat{\sigma}_x$ or $\hat{\sigma}_y$ M{\o}lmer-S{\o}rensen type interactions in trapped ion systems. Using this field configuration, we present a novel scheme to synthesize a $\hat{\sigma}_z$ spin-dependent force instead; this basis change merely requires adjusting the beat-note frequency of the bichromatic field. We implement this scheme with a laser near-resonant to a quadrupole transition in $^{88}$Sr$^+$. We characterise its robustness to optical phase and qubit frequency offsets and demonstrate its versatility by entangling optical, metastable, and ground state qubits.Comment: O. B\u{a}z\u{a}van and S. Saner contributed equally to this wor

Breaking the entangling gate speed limit for trapped-ion qubits using a phase-stable standing wave

All laser-driven entangling operations for trapped-ion qubits have hitherto been performed without control of the optical phase of the light field, which precludes independent tuning of the carrier and motional coupling. By placing $^{88}$Sr$^+$ ions in a $\lambda=674$ nm standing wave, whose relative position is controlled to $\approx\lambda/100$, we suppress the carrier coupling by a factor of $18$, while coherently enhancing the spin-motion coupling. We experimentally demonstrate that the off-resonant carrier coupling imposes a speed limit for conventional traveling-wave M{\o}lmer-S{\o}rensen gates; we use the standing wave to surpass this limit and achieve a gate duration of $15\ \mu$s, restricted by the available laser power.Comment: S. Saner and O. B\u{a}z\u{a}van contributed equally to this wor

An overview of the cutaneous porphyrias

This is an overview of the cutaneous porphyrias. It is a narrative review based on the published literature and my personal experience; it is not based on a formal systematic search of the literature. The cutaneous porphyrias are a diverse group of conditions due to inherited or acquired enzyme defects in the porphyrin–haem biosynthetic pathway. All the cutaneous porphyrias can have (either as a consequence of the porphyria or as part of the cause of the porphyria) involvement of other organs as well as the skin. The single commonest cutaneous porphyria in most parts of the world is acquired porphyria cutanea tarda, which is usually due to chronic liver disease and liver iron overload. The next most common cutaneous porphyria, erythropoietic protoporphyria, is an inherited disorder in which the accumulation of bile-excreted protoporphyrin can cause gallstones and, rarely, liver disease. Some of the porphyrias that cause blistering (usually bullae) and fragility (clinically and histologically identical to porphyria cutanea tarda) can also be associated with acute neurovisceral porphyria attacks, particularly variegate porphyria and hereditary coproporphyria. Management of porphyria cutanea tarda mainly consists of visible-light photoprotection measures while awaiting the effects of treating the underlying liver disease (if possible) and treatments to reduce serum iron and porphyrin levels. In erythropoietic protoporphyria, the underlying cause can be resolved only with a bone marrow transplant (which is rarely justifiable in this condition), so management consists particularly of visible-light photoprotection and, in some countries, narrowband ultraviolet B phototherapy. Afamelanotide is a promising and newly available treatment for erythropoietic protoporphyria and has been approved in Europe since 2014

Hexokinase 3 enhances myeloid cell survival via non-glycolytic functions.

The family of hexokinases (HKs) catalyzes the first step of glycolysis, the ATP-dependent phosphorylation of glucose to glucose-6-phosphate. While HK1 and HK2 are ubiquitously expressed, the less well-studied HK3 is primarily expressed in hematopoietic cells and tissues and is highly upregulated during terminal differentiation of some acute myeloid leukemia (AML) cell line models. Here we show that expression of HK3 is predominantly originating from myeloid cells and that the upregulation of this glycolytic enzyme is not restricted to differentiation of leukemic cells but also occurs during ex vivo myeloid differentiation of healthy CD34+ hematopoietic stem and progenitor cells. Within the hematopoietic system, we show that HK3 is predominantly expressed in cells of myeloid origin. CRISPR/Cas9 mediated gene disruption revealed that loss of HK3 has no effect on glycolytic activity in AML cell lines while knocking out HK2 significantly reduced basal glycolysis and glycolytic capacity. Instead, loss of HK3 but not HK2 led to increased sensitivity to ATRA-induced cell death in AML cell lines. We found that HK3 knockout (HK3-null) AML cells showed an accumulation of reactive oxygen species (ROS) as well as DNA damage during ATRA-induced differentiation. RNA sequencing analysis confirmed pathway enrichment for programmed cell death, oxidative stress, and DNA damage response in HK3-null AML cells. These signatures were confirmed in ATAC sequencing, showing that loss of HK3 leads to changes in chromatin configuration and increases the accessibility of genes involved in apoptosis and stress response. Through isoform-specific pulldowns, we furthermore identified a direct interaction between HK3 and the proapoptotic BCL-2 family member BIM, which has previously been shown to shorten myeloid life span. Our findings provide evidence that HK3 is dispensable for glycolytic activity in AML cells while promoting cell survival, possibly through direct interaction with the BH3-only protein BIM during ATRA-induced neutrophil differentiation

Language attitudes, linguistic authority and independence in 21st century Catalonia

peer-reviewedIn a context of increasing linguistic and cultural diversity and political uncertainty in Catalonia, this article reports on a research project which set out to explore the attitudes of members of independence organisations operating in the city of Girona toward the Catalan and Spanish languages. This study approaches language attitudes through the theoretical lens of linguistic authority, in particular, the concepts of anonymity and authenticity. The data, gathered from six focus groups, provide an insight on the nature of linguistic authority in contemporary Catalonia. Two themes emerge in the informants’ discussion of Catalan and Spanish: ‘twenty-first Century Catalanisme’ and ‘Embracing Linguistic Diversity’. The comments of the respondents indicate that, against the backdrop of the independence process in the region, bilingualism and multilingualism have become highly valued in the territory. In addition, this study suggests that a fuller understanding of the situation in Catalonia may be facilitated by qualitative approaches, which explore attitudes in-depth

EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks

BACKGROUND AND AIMS: Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. APPROACH AND RESULTS: EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization. CONCLUSIONS: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies. (Hepatology 2020;71:1546-1558)

Reducing the Key Size of McEliece Cryptosystem from Automorphism-induced Goppa Codes via Permutations

In this paper, we propose a new general construction to reduce the public key size of McEliece cryptosystems constructed from automorphism-induced Goppa codes. In particular, we generalize the ideas of automorphism-induced Goppa codes by considering nontrivial subsets of automorphism groups to construct Goppa codes with a nice block structure. By considering additive and multiplicative automorphism subgroups, we provide explicit constructions to demonstrate our technique. We show that our technique can be applied to automorphism-induced Goppa codes based cryptosystems to further reduce their key sizes

EXPLORE: A prospective, multinational natural history study of patients with acute hepatic porphyria with recurrent attacks

BACKGROUND AND AIMS: Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. APPROACH AND RESULTS: EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization. CONCLUSIONS: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies. (Hepatology 2020;71:1546-1558)