Charge of a quasiparticle in a superconductor

Nonlinear charge transport in superconductor–insulator–superconductor (SIS) Josephson junctions has a unique signature in the shuttled charge quantum between the two superconductors. In the zero-bias limit Cooper pairs, each with twice the electron charge, carry the Josephson current. An applied bias V_SD leads to multiple Andreev reflections (MAR), which in the limit of weak tunneling probability should lead to integer multiples of the electron charge ne traversing the junction, with n integer larger than 2Δ/eV_SD and Δ the superconducting order parameter. Exceptionally, just above the gap eV_SD ≥ 2Δ, with Andreev reflections suppressed, one would expect the current to be carried by partitioned quasiparticles, each with energy-dependent charge, being a superposition of an electron and a hole. Using shot-noise measurements in an SIS junction induced in an InAs nanowire (with noise proportional to the partitioned charge), we first observed quantization of the partitioned charge q = e*/e = n, with n = 1–4, thus reaffirming the validity of our charge interpretation. Concentrating next on the bias region eV_SD ～ 2Δ, we found a reproducible and clear dip in the extracted charge to q? ～ 0.6, which, after excluding other possibilities, we attribute to the partitioned quasiparticle charge. Such dip is supported by numerical simulations of our SIS structure.Excitations in superconductors (Bogoliubov quasiparticles) can be described according to the Bardeen–Cooper–Schrieffer (BCS) theory (1) as an energy-dependent superposition of an electron with amplitude u(ε), and a hole with amplitude v(ε), where the energy ε is measured relative to the Fermi energy (2). Evidently, the expectation value of the charge operator (applied to the quasiparticle wave function), which we address as the quasiparticle charge e* = q(ε)e, is smaller than the charge of an electron, q(ε) = |u(ε)|² ? |ν(ε)|² (3). Solving the Bogoliubov–de Gennes equations, one finds that |u(ε)|2=1/2[1+(ε2−Δ2/ε)] and |v(ε)|2=1/2[1−(ε2−Δ2/ε)], with the expected charge evolving with energy according to q(ε)=ε2−Δ2/ε––vanishing altogether at the superconductor gap edges (3). Note, however, that the quasiparticle wave function is not an eigenfunction of the charge operator (3, 4). Properties of quasiparticles, such as the excitation spectra (5), lifetime (6–10), trapping (11), and capturing by Andreev bound states (12, 13), had already been studied extensively; however, studies of their charge are lagging. In the following we present sensitive shot-noise measurements in a Josephson junction, resulting in a clear observation of the quasiparticle charge being smaller than e, q(eV_SD∼2Δ) < 1, and evolving with energy, as expected from the BCS theory.To observe the BCS quasiparticles in transport we study a superconductor–insulator–superconductor (SIS) Josephson junction in the nonlinear regime. The overlap between the wave functions of the quasiparticles in the source and in the drain is expected to result in a tunneling current of their effective charge. This is in contrast with systems which are incoherent (14, 15) or with an isolated superconducting island, where charge conservation leads to traversal of multiples of e – Coulomb charge (16). As current transport in the nonlinear regime results from “multiple Andreev reflections” (MAR), it is prudent to make our measurements credible by first measuring the charge in this familiar regime.In short, the MAR process, described schematically in Fig. 1, carries a signature of the shuttled charge between the two superconductors (SCs), being a consequence of n traversals through the junction (as electron-like and hole-like quasiparticles), with n an integer larger than 2Δ/eV_SD. A low transmission probability t (via tunneling through a barrier) in the bias range 2Δ/n < eV_SD < 2Δ/(n ? 1) assures dominance of the lowest order MAR process (higher orders are suppressed as tⁿ), with the charge evolving in nearly integer multiples of the electron charge. Although there is already a substantial body of theoretical (3, 17–23) and experimental (24–29) studies of the MAR process, charge determination without adjustable parameters is still missing. An important work by Cron et al. (27) indeed showed a staircase-like behavior of the charge using “metallic break junctions;” however, limited sensitivity and the presence of numerous conductance channels some of which with relatively high transmission probabilities did not allow exact charge quantization. Our shot-noise measurements, performed on a quasi-1D Josephson junction (single-mode nanowire) allowed clear observation of charge quantization without adjustable parameters. To count a few advantages: (i) the transmission of the SIS junction could be accurately controlled using a back-gate; (ii) this, along with our high sensitivity in noise measurements, enabled us to pinch the junction strongly (thus suppressing higher MAR orders); and (iii) with the Fermi level located near the 1D channel van Hove singularity, a rather monoenergetic distribution could be injected (SI Appendix, section S7).Open in a separate windowFig. 1.MAR. Illustrations of the leading processes contributing to the current as function of bias. In general, for 2Δ/(n ? 1) > eV_SD > 2Δ/n the leading charge contribution to the current is ne. An electron-like quasiparticle is denoted by a full circle, whereas a hole-like quasiparticle is denoted by an empty circle. (A) When the bias is larger than the energy gap, eV_SD > 2Δ, the leading process is a single-path tunneling of single quasiparticles from the full states (Left) to the empty states (Right). This current is proportional to the transmission coefficient t. Higher-order MAR process (dashed box), being responsible for tunneling of Cooper pairs, is suppressed as t². (B) For 2Δ > eV_SD > Δ, the main charge contributing to the current is 2e with probability t². (C) For Δ > eV_SD > 2Δ/3, the main charge contributing to the current is 3e with probability t³.     

Fate of a mutation in a fluctuating environment

Natural environments are never truly constant, but the evolutionary implications of temporally varying selection pressures remain poorly understood. Here we investigate how the fate of a new mutation in a fluctuating environment depends on the dynamics of environmental variation and on the selective pressures in each condition. We find that even when a mutation experiences many environmental epochs before fixing or going extinct, its fate is not necessarily determined by its time-averaged selective effect. Instead, environmental variability reduces the efficiency of selection across a broad parameter regime, rendering selection unable to distinguish between mutations that are substantially beneficial and substantially deleterious on average. Temporal fluctuations can also dramatically increase fixation probabilities, often making the details of these fluctuations more important than the average selection pressures acting on each new mutation. For example, mutations that result in a trade-off between conditions but are strongly deleterious on average can nevertheless be more likely to fix than mutations that are always neutral or beneficial. These effects can have important implications for patterns of molecular evolution in variable environments, and they suggest that it may often be difficult for populations to maintain specialist traits, even when their loss leads to a decline in time-averaged fitness.Evolutionary trade-offs are widespread: Adaptation to one environment often leads to costs in other conditions. For example, drug resistance mutations often carry a cost when the dosage of the drug decays (1), and seasonal variations in climate can differentially select for certain alleles in the summer or winter (2). Similarly, laboratory adaptation to specific temperatures (3, 4) or particular nutrient sources (5, 6) often leads to declines in fitness in other conditions. Related trade-offs apply to any specialist phenotype or regulatory system that incurs a general cost to confer benefits in specific environmental conditions (7). Despite the ubiquity of these trade-offs, it is not always easy to predict when a specialist phenotype can evolve and persist. How useful must a trait be on average to be maintained? How regularly does it need to be useful? How much easier is it to maintain in a larger population compared with a smaller one?The answers to these questions depend on two major factors. First, how often do new mutations create or destroy a specialist phenotype, and what are their typical costs and benefits across environmental conditions? This is fundamentally an empirical question, which depends on the costs and benefits of the trait in question, as well as its genetic architecture (e.g., the target size for loss-of-function mutations that disable a regulatory system). In this paper, we focus instead on the second major factor: given that a particular mutation occurs, how does its long-term fate depend on its fitness in each condition and on the details of the environmental fluctuations?To address this question, we must analyze the fixation probability of a new mutation that experiences a time-varying selection pressure. This is a classic problem in population genetics, and has been studied by a number of previous authors. The effects of temporal fluctuations are simplest to understand when the timescales of environmental and evolutionary change are very different. For example, when the environment changes more slowly than the fixation time of a typical mutation, its fate will be entirely determined by the environment in which it arose (8). On the other hand, if environmental changes are sufficiently rapid, then the fixation probability of a mutation will be determined by its time-averaged fitness effect (9, 10). In these extreme limits, the environment can have a profound impact on the fixation probability of a new mutation, but the fluctuations themselves play a relatively minor role. In both cases, the effects of temporal variation can be captured by defining a constant effective selection pressure, which averages over the environmental conditions that the mutation experiences during its lifetime. This result is the major reason why temporally varying selection pressures are neglected throughout much of population genetics, despite the fact that truly constant environments are rare.However, this simple result is crucially dependent on the assumption that environmental changes are much slower or much faster than all evolutionary processes. When these timescales start to overlap, environmental fluctuations can have important qualitative implications that cannot be summarized by any effective selection pressure, even when a mutation experiences many environmental epochs over its lifetime. As we will show below, this situation is not an unusual special case, but a broad regime that becomes increasingly relevant in large populations. In this regime, the fate of each mutation depends critically on its fitness in each environment, the dynamics of environmental changes, and the population size.Certain aspects of this process have been analyzed in earlier studies. Much of this earlier work focuses on the dynamics of a mutation in an infinite population (11–24). However, these infinite-population approaches are fundamentally unsuitable for analyzing the fixation probabilities of mutations that are neutral or deleterious on average (and even for mutations that are beneficial on average, population sizes must often be unrealistically large for this infinite population size approximation to hold). Another class of work has focused explicitly on finite populations, but only in the case where the environment varies stochastically from one generation to the next (25–31). Later work has extended this analysis to fluctuations on somewhat longer timescales, but this work is still restricted to the special case where selection cannot change allele frequencies significantly during an individual environmental epoch (9, 32, 33).These studies have provided important qualitative insights into various aspects of environmental fluctuations. However, we still lack both a quantitative and conceptual understanding of more significant fluctuations, where selection in each environment can lead to measurable changes in allele frequency. This gap is particularly relevant because significant changes in allele frequency are the most clearly observable signal of variable selection in natural populations.In this work, we analyze the fate of a new mutation that arises in an environment that fluctuates between two conditions either deterministically or stochastically on any timescale. We provide a full analysis of the fixation probability of a mutation when evolutionary and environmental timescales are comparable and allele frequencies can change significantly in each epoch. We find that even in enormous populations, natural selection is often very inefficient at distinguishing between mutations that are beneficial and deleterious on average. In addition, substitution rates of all mutations are dramatically increased by variable selection pressures. This can lead to counterintuitive results. For instance, mutations that result in a trade-off but are predominantly deleterious during their lifetime can be much more likely to fix than mutations that are always neutral or even beneficial. Thus, it may often be difficult for populations to maintain specialist traits, even when loss-of-function mutations are selected against on average. This can lead to important signatures on the genetic level, e.g., in elevated rates of nonsynonymous to synonymous substitutions (dN/dS) (34).     

Manifestation of malakoplakia in a urethral diverticulum in a female patient

We report about a rare case of malakoplakia in a female urethral diverticulum. A 25-year-old patient with a long history of recurrent urinary tract infections and a plum-sized, painful swelling on the vaginal roof presented for operative treatment. In the anamnesis the patient reported about two spontaneous perforations, emptying several millilitres of pus each time. After total operative excision using a vaginal approach the histology showed malakoplakia in a urethral diverticulum. We found the typical intracytoplasmatic "Michaelis-Gutmann bodies" as well as "von Hansemann cells". Postoperatively we excluded an underlying tumour disease or a chronic infection. The further urological diagnostics (cystoscopy and MRI) were without any pathological findings. In patients with atypical cystic tumours of the urogenital tract, especially with an immune deficiency, malakoplakia should be taken in consideration. The preferred therapy is surgical management followed by long-term antibiosis as well as a close follow-up as recurrences are frequent.     

Chaos in a simple model of a delta network

The flux partitioning in delta networks controls how deltas build land and generate stratigraphy. Here, we study flux-partitioning dynamics in a delta network using a simple numerical model consisting of two orders of bifurcations. Previous work on single bifurcations has shown periodic behavior arising due to the interplay between channel deepening and downstream deposition. We find that coupling between upstream and downstream bifurcations can lead to chaos; despite its simplicity, our model generates surprisingly complex aperiodic yet bounded dynamics. Our model exhibits sensitive dependence on initial conditions, the hallmark signature of chaos, implying long-term unpredictability of delta networks. However, estimates of the predictability horizon suggest substantial room for improvement in delta-network modeling before fundamental limits on predictability are encountered. We also observe periodic windows, implying that a change in forcing (e.g., due to climate change) could cause a delta to switch from predictable to unpredictable or vice versa. We test our model by using it to generate stratigraphy; converting the temporal Lyapunov exponent to vertical distance using the mean sedimentation rate, we observe qualitatively realistic patterns such as upwards fining and scale-dependent compensation statistics, consistent with ancient and experimental systems. We suggest that chaotic behavior may be common in geomorphic systems and that it implies fundamental bounds on their predictability. We conclude that while delta “weather” (precise configuration) is unpredictable in the long-term, delta “climate” (statistical behavior) is predictable.

Deltas are landforms arising from the deposition of sediment by a river entering a standing body of water. Deltas worldwide are highly populated and widely relied upon for agriculture and navigation but are under threat of collapse due to relative sea-level rise and sediment-supply reduction (1–3). Additionally, delta deposits are important reservoirs for groundwater and hydrocarbons, and better understanding their stratigraphic architecture would improve prediction of subsurface fluid flow (4).Delta networks deliver sediment to different parts of the delta, controlling where land is built. Deltas have been proposed to self-organize their flux partitioning for a given network topology (5). The flux partitioning in the network can change over time through the process of avulsion, which may result in the abandonment of old channels and creation of new ones or merely a shift in the flux partitioning without modification of the number of channels (termed “soft avulsion”) (6). A wide body of research has aimed to better understand avulsions in order to better predict their timing and location and to explore how deltas record themselves in stratigraphy (7–14).Our ability to accurately predict the future evolution of river deltas is hampered by our incomplete representation of the physical processes in our models, as well as uncertainty in boundary conditions. A similar problem arises in the prediction of subsurface stratigraphy based on incomplete data. Is there a fundamental limit to our ability to accurately predict delta evolution, which would apply even if we could perfectly simulate the relevant physical processes and boundary conditions?Complex and irregular behavior, typically assumed to be stochastic, can be found everywhere in geomorphology. Examples include the motions of bedload particles (15), the evolution of dune fields (16), the organization of drainage networks (17, 18), the dynamics of braided (19) and meandering (20) rivers, and the kinematics of delta surfaces (21). Reproducing in detail the irregular dynamics of geomorphic systems is beyond the reach of existing models, but it is unknown to what extent detailed prediction of these systems is impossible rather than “merely” difficult.In chaotic systems, long-term prediction is fundamentally impossible. Strogatz (22) proposed the following definition of chaos: “Chaos is aperiodic long-term behavior in a deterministic system that exhibits sensitive dependence on initial conditions.” Sensitive dependence on initial conditions refers to the idea that two systems started with nearly identical initial conditions diverge exponentially. This means that any error in our measurement of a system’s initial condition will grow exponentially through time. Because we can never measure a system with infinite precision, this implies a fundamental limit to long-term prediction. In contrast to stochastic systems, unpredictability arises in chaotic systems despite their lack of randomness; chaotic systems are by definition deterministic.While many geomorphic systems display highly complex dynamics, demonstrating chaotic behavior is difficult. Major challenges include the lack of very long time series, which are typically required to detect chaos (23–25), and the fact that some methods to detect chaos can be fooled by certain types of noise (26). In the study of geomorphic systems, some have attempted to use spatial information to supplement the lack of temporal information needed to detect chaos (27), for example, from a time series of ripple migration (28).Despite the complex behavior of natural geomorphic systems, a growing body of research on so-called “reduced-complexity models” has shown that complex dynamics that are at least qualitatively similar to those of natural systems can be generated even by models obeying relatively simple rules (16, 19, 29–34). Demonstration of chaotic dynamics in an idealized and simplified model of a natural system can be a strong suggestion that the system is chaotic; for example, the Lorenz equations are an extreme simplification of atmospheric convection but are believed to indicate that the atmosphere is itself chaotic (35). Chaotic behavior has been uncovered in models of geological phenomena such as earthquakes (36) and the geodynamo (37). Dynamic stratigraphic models are typically nonlinear dissipative systems and, therefore, are potentially susceptible to exhibiting chaos (38). More generally, the same could be said of many geomorphological models. However, to date, demonstrations of chaos in geomorphological models are rare: one example is from Pelletier (39), who identified deterministic chaos in a model of landform evolution, albeit with a definition of chaos that differs from the one we use in this paper. Another example is Phillips (40), who found chaos in a difference equation modeling regolith cover on a hillslope. Chaos has also been proposed for numerical models of river meandering (41, 42).In this paper, we consider a numerical model of a simple delta network. The network consists of three coupled bifurcations: a channel splits into two branches at a bifurcation, each of which split into two additional branches. Our model is a further extension of the quasi-one dimensional (1D) bifurcation model developed by Bolla Pittaluga et al. (43) (hereafter, BRT) and extended by Salter et al. (44, 45) (hereafter, SPV) to include the effect of deposition in the downstream branches. We find that the coupling between the upstream and downstream bifurcations leads to chaotic dynamics in the flux partitioning of the network. This suggests that delta networks that have coupled bifurcations behave chaotically and that it is possible to quantitatively estimate the time scale over which long-term detailed prediction of their avulsion dynamics becomes impossible.     

Report of a case of a giant phytobezoar in a patient with a duodenal bulb ulcer.

A case of a large phytobezoar (750 g weight and with the length of 29 cm) due to Khormalou (Persimmon) is being reported in a young patient with chief complaint of abdominal pains and concomitant duodenal ulcer. Review of the literature in this subject shows that bezoars of this size and weight are relatively rare in healthy individuals.     

Tuberculosis screening after detection of a case in a paediatric haemato-oncology unit in a low prevalence country

BackgroundThere are no guidelines to screen haemato-oncologic children when a tuberculosis (TB) outbreak is suspected.MethodsAfter exposition to an adult with active TB, children exposed from a haemato-oncology unit were screened according to immunosuppression status and time of exposure. Until an evaluation after 8–12 weeks from last exposure, isoniazid was indicated to those with negative initial work-up.ResultsAfter 210 interventions, we detected a case of pulmonary TB, and another with latent TB infection. Pulmonary findings and treatment approach were challenging in some patients.ConclusionsThe TB screening of oncologic children required a multidisciplinary approach, and clinicians managed challenging situations.     

某民航机场食品厂面粉库发现热带无爪螨

目的调查某民航机场食品厂面粉库有无热带无爪螨孳生,观察热带无爪螨的形态结构特征。方法采集该机场食品厂面粉库的面粉样本,用直接镜检法分离其中孳生的热带无爪螨,并制作玻片标本,于光学显微镜下观察鉴定。结果于采集的面粉样本中发现了热带无爪螨雌成螨,镜下可见该螨近似球形,无背板,足无爪。表皮内突Ⅰ发达,于中线处相连。生殖孔位于足Ⅲ~Ⅳ水平,被一对斜生的生殖褶覆盖。足Ⅲ、Ⅳ无感棒。交配囊呈长而稍弯并逐渐变细的管状结构,伸出螨体末端。结论某民航食品厂面粉库厂中发现了热带无爪螨,该螨主要鉴别特征为无背板,足无栉齿状亚跗鳞片和爪;足Ⅰ膝节仅有1根感棒,且足Ⅲ、Ⅳ无感棒。     

Assessing the Effect of a Polypharmacy Medication Adherence Simulation Project in a Geriatrics Course in a College of Pharmacy

The Geriatric Pharmacy elective course at the University of Kentucky College of Pharmacy uses a simulated medication adherence project to increase awareness of adherence concerns facing older adults who take multiple medications. This study evaluated the effect of this project. Students enrolled in this 3–credit hour course in 2002 to 2007 participated in the 10-day project followed by a live classroom discussion and a reflective assignment. Evaluations of the project were administered to the students on Blackboard. Two hundred thirty-seven health professional students (99% pharmacy) participated in the course project. Open-ended comments in the evaluations and reflective assignments were retrospectively analyzed using a qualitative research method known as thematic analysis. The majority (83%) of comments were positive. Students indicated the greatest learning experiences in the categories of empathy and adherence. This simulated medication adherence project is one tool that may be used to increase students' awareness of the difficulties with medication adherence that their patients may encounter.     

Image of a left atrial mass after a cardiopulmonary bypass in a child

Invagination of an appendage into the left atrium is a rare complication. It occurs spontaneously or after open‐heart surgery. In our case, a postoperative transesophageal echocardiogram, after closure of a ventricular septal defect in a 5‐month‐old infant, revealed a large mass in the left atrium. A diagnosis of a left appendage inversion was confirmed after external examination of the heart. Herein, we provide echocardiographic images before, during, and after manual reversion of the left appendage. Misdiagnosis of this complication could have led to an additional unnecessary surgical procedure that could have impacted on the patient's morbidity.     

Hyperviscosity as a complication in a variety of disorders

For a considerable time, hyperviscosity syndrome has been widely recognized as a serious manifestation of polycythemia and plasma cell dyscrasia. In this article a number of conditions will be considered in which the association with hyperviscosity has been more recently recognized and is less widely known. These conditions are hyperleukocytosis, retinoic acid therapy, and connective tissue disease such as rheumatoid arthritis. The essential problems in the first two are the hugely elevated white cell count (WCC) and the mechanical properties of the leukocytes, in other words, their relatively poor deformability and their adhesiveness for the endothelium. In the last, the essential problem is hugely elevated plasma viscosity due to immunocomplexes. They lead to increased flow resistance, especially in the microvessels, abnormal flow, and significant clinical symptoms. The details of the causes of the hyperviscosity, the symptoms that result, and the forms of treatment are discussed.     

Management of a rifampicin-resistant meningococcal infection in a teenager

We report a secondary case of rifampicin-resistant meningococcal disease and our experience in managing contact cases. Rifampicin resistance resulting from rpoB gene mutations is still uncommon enough that changing the current recommendations for chemoprophylaxis is unwarranted. However, ensuring limited but appropriate chemoprophylaxis may prevent the development of antimicrobial resistance. Thus, the definition of contact cases should be strictly respected. In the case of culture-positive Neisseria meningitidis, in vitro susceptibility testing to rifampicin must be systematically performed in order to detect rifampicin-resistant strains and, thus, institute appropriate prophylaxis in order to prevent secondary transmission.     

Dissection of a viral autoprotease elucidates a function of a cellular chaperone in proteolysis

Replication of positive-strand RNA viruses involves translation of polyproteins which are proteolytically processed into functional peptides. These maturation steps often involve virus-encoded autoproteases specialized in generating their own N or C termini. Nonstructural protein 2 (NS2) of the pestivirus bovine viral diarrhea virus represents such an enzyme. Bovine viral diarrhea virus NS2 creates in cis its own C terminus and thereby releases an essential viral replication factor. As a unique feature, this enzyme requires for proteolytic activity stoichiometric amounts of a cellular chaperone termed Jiv (J-domain protein interacting with viral protein) or its fragment Jiv90. To obtain insight into the structural organization of the NS2 autoprotease, the basis for its restriction to cis cleavage, as well as its activation by Jiv, we dissected NS2 into functional domains. Interestingly, an N-terminal NS2 fragment covering the active center of the protease, cleaved in trans an artificial substrate composed of a C-terminal NS2 fragment and two downstream amino acids. In the authentic NS2, the 4 C-terminal amino acids interfered with binding and cleavage of substrates offered in trans. These findings strongly suggest an intramolecular product inhibition for the NS2 autoprotease. Remarkably, the chaperone fragment Jiv90 independently interacted with protease and substrate domain and turned out to be essential for the formation of a protease/substrate complex that is required for cleavage. Thus, the function of the cell-derived protease cofactor Jiv in proteolysis is regulation of protease/substrate interaction, which ultimately results in positioning of active site and substrate peptide into a cleavage-competent conformation.