Surprising Observations Research Articles

Polaronic model of two-level systems in amorphous solids

While two levels systems (TLSs) are ubiqitous in solid state systems, microscopic understanding of their nature remains an outstanding problem. Conflicting phenomenological models are used to describe TLSs in seemingly similar materials when probed with different experimental techniques. Specifically, bulk measurements in amorphous solids have been interpreted using the model of a tunneling atom or group of atoms, whereas TLSs observed in the insulating barriers of Josephson junction qubits have been understood in terms of tunneling of individual electrons. Motivated by recent experiments studying TLSs in Josephson junctions, especially the effects of elastic strain on TLS properties, we analyze interaction of the electronic TLS with phonons. We demonstrate that strong polaronic effects lead to dramatic changes in TLS properties. Our model gives a quantitative understanding of the TLS relaxation and dephasing as probed in Josephson junction qubits, while providing an alternative interpretation of bulk experiments. We demonstrate that a model of polaron dressed electronic TLS leads to estimates for the density and distribution of parameters of TLSs consistent with bulk experiments in amorphous solids. This model explains such surprising observations of recent experiments as the existence of minima in the energy of some TLSs as a function of strain and makes concrete predictions for the character of TLS dephasing near such minima. We argue that better understanding of the microscopic nature of TLSs can be used to improve properties of quantum devices, from an enhancement of relaxation time of TLSs, to creating new types of strongly interacting optomechanical systems.

State Specific Stabilization of H+ + H2(j) Collision Complexes

Stabilization of H3(+) collision complexes has been studied at nominal temperatures between 11 and 33 K using a 22-pole radio frequency (rf) ion trap. Apparent binary rate coefficients, k(*) = kr + k3[H2], have been measured for para- and normal-hydrogen at number densities between some 10(11) and 10(14) cm(-3). The state specific rate coefficients extracted for radiative stabilization, kr(T;j), are all below 2 × 10(-16) cm(3) s(-1). There is a slight tendency to decrease with increasing temperature. In contrast to simple expectations, kr(11 K;j) is for j = 0 a factor of 2 smaller than for j = 1. The ternary rate coefficients for p-H2 show a rather steep T-dependence; however, they are increasing with temperature. The state specific ternary rate coefficients, k3(T;j), measured for j = 0 and derived for j = 1 from measurements with n-H2, differ by an order of magnitude. Most of these surprising observations are in disagreement with predictions from standard association models, which are based on statistical assumptions and the separation of complex formation and competition between stabilization and decay. Most probably, the unexpected collision dynamics are due to the fact that, at the low translational energies of the present experiment, only a small number of partial waves participate. This should make exact quantum mechanical calculations of kr feasible. More complex is three-body stabilization, because it occurs on the H5(+) potential energy surface.

MDA5

Myocarditis is an inflammation of the heart muscle, which frequently follows microbial infections. Picornaviruses and adenoviruses are the most commonly identified viral etiologic agents.1 Cardiac injury results from both virus infection/replication and host inflammatory responses, but in either case, elimination of the virus from the heart can have a beneficial effect on disease outcome as is evident from clinical trials treating biopsy-proven, virus-positive patients with interferon β (IFNβ).2 The success of type I IFN therapy in myocarditis may partly depend on the initiating etiologic agent, as virus clearance and cardiac improvement was greater in patients with enteroviruses than with parvovirus B19 or human herpesvirus 6.2 This finding is not surprising as it is well known that virus families vary dramatically in their sensitivity to type I IFN, in part because many viruses have developed immune evasion mechanisms targeting this innate host defense mechanism.3 Enteroviruses of the Picornavirus family are small, nonenveloped, positive-sensed, single-stranded RNA viruses, which are classically among the most sensitive to type I IFN, with encephalomyocarditis virus (EMCV) being one of the most IFN sensitive of the enteroviruses.4 Article see p 326 Type I IFN are induced through virus-sensing pattern recognition receptors (PRR) of the innate immunity system, which recognize shared pathogen-associated molecular patterns between many infectious agents.5 PRRs include Toll-like, retinoic acid-inducible gene I (RIG-I)-like, nucleotide-binding oligomerization domain receptors (NOD)-like, C-type lectin and possibly absent in melanoma 2 (AIM2)-like receptors; a diverse subcellular compartmentalization of the pattern recognition receptors allows optimal recognition of their relevant pathogen-associated molecular patterns. Toll-like receptors (TLR) are primarily implicated in reacting to extracellular bacterial pathogen-derived molecules (TLR5 [flagellin], TLR4 [lipopolysaccharide], TLR2/1, or TLR2/6 [lipoprotein]) and are located in the plasma membrane; in contrast, RIG-I-like (single-stranded/double-stranded RNA) and NOD-like (muramyl tripeptide/muramyl dipeptide) receptors are located in the …

The annotated Frankenstein

An annotated and illustrated edition of Mary Shelley's classic work, celebrating its 200th anniversary in 2018. First published in 1818, has spellbound, disturbed, and fascinated readers for generations. One of the most haunting and enduring works ever written in English, it has inspired numerous retellings and sequels in virtually every medium, making the myth familiar even to those who have never read a word of Mary Shelley's remarkable novel. Now, this freshly annotated, illustrated edition illuminates the novel and its electrifying afterlife with unmatched detail and vitality. From the first decade after publication, Frankenstein became a byword for any new, disturbing developments in science, technology, and human imagination. The editors' Introduction explores the fable's continuing presence in popular culture and intellectual life as well as the novel's genesis and composition. Mary Shelley's awareness of European politics and history, her interest in the poets and philosophical debates of the day, and especially her genius in distilling her personal traumas come alive in this engaging essay. The editors' commentary, placed conveniently alongside the text, provides stimulating company. Their often surprising observations are drawn from a lifetime of reading and teaching the novel. A wealth of illustrations, many in color, immerses the reader in Shelley's literary and social world, in the range of artwork inspired by her novel, as well as in Frankenstein's provocative cinematic career. The fresh light that The Annotated casts on a story everyone thinks is familiar will delight readers while deepening their understanding of Mary Shelley's novel and the Romantic era in which it was created.

Immuno- and Constitutive Proteasomes Do Not Differ in Their Abilities to Degrade Ubiquitinated Proteins

SummaryImmunoproteasomes are alternative forms of proteasomes that have an enhanced ability to generate antigenic peptides. Recently, Seifert and colleagues reported surprising observations concerning the functions of immunoproteasomes and cellular responses to interferon-γ: (1) that immunoproteasomes degrade ubiquitinated proteins faster than the constitutive proteasomes, (2) that polyubiquitin conjugates accumulate after interferon-γ treatment but then are preferentially degraded by immunoproteasomes, and (3) that immunoproteasome deficiency causes the formation of inclusions and more severe experimental autoimmune encephalomyelitis (EAE). In contrast, we find that polyubiquitin conjugates do not transiently accumulate following IFNγ-treatment and that immunoproteasomes do not prevent the formation of intracellular inclusions or protect against EAE. Furthermore, purified 26S constitutive and immunoproteasomes bind ubiquitin conjugates similarly and degrade them at similar rates. We conclude that, although immunoproteasomes can increase the generation of peptides appropriate for MHC class I presentation, they do not degrade ubiquitinated proteins more efficiently than constitutive particles.

Speed-Selectivity Paradox in the Protein Search for Targets on DNA: Is It Real or Not?

Protein search for targets on DNA starts all major biological processes. Although significant experimental and theoretical efforts have been devoted to investigation of these phenomena, mechanisms of protein-DNA interactions during the search remain not fully understood. One of the most surprising observations is known as a speed-selectivity paradox. It suggests that experimentally observed fast findings of targets require smooth protein-DNA binding potentials, while the stability of the specific protein-DNA complex imposes a large energy gap which should significantly slow down the protein molecule. We developed a discrete-state stochastic approach that allowed us to investigate explicitly target search phenomena and to analyze the speed-selectivity paradox. A general dynamic phase diagram for different search regimes is constructed. The effect of the target position on search dynamics is investigated. Using experimentally observed parameters, it is found that slow protein diffusion on DNA does not lead to an increase in the search times. Thus, our theory resolves the speed-selectivity paradox by arguing that it does not exist. It is just an artifact of using approximate continuum theoretical models for analyzing protein search in the region of the parameter space beyond the range of validity of these models. In addition, the presented method, for the first time, provides an explanation for fast target search at the level of single protein molecules. Our theoretical predictions agree with all available experimental observations, and extensive Monte Carlo computer simulations are performed to support analytical calculations.

Telecommunications in South Africa: Governance of who is actually regulating?

Although the Republic of South Africa telecommunications market is a maturing one with a large customer base to serve, it has been repeatedly been observed over the past few years that many good intentions were formulated in the regulatory sphere with sometimes poor outcomes and unclear governance. A number of surprising observations have been made on the outcomes, the delays or other process related events linked to regulatory measures. The paper thus researches first, from a governance point of view, who is actually regulating the telecommunications industry; it identifies next opportunities and bottlenecks whereby a change might happen to reach the expected outcomes. A political economy methodology is taken, backed up by extensive field work over 2010 and 2011, leading to a web of conjectures providing answers to the first question, based on an extensive analysis of key stakeholders goals, positions and interactions. Finally, a number of measures are proposed to improve the governance, regulatory impact and efficiency, and evolve the South African telecommunications eco-system.

Spatial SINR Games of Base Station Placement and Mobile Association

We study the question of determining locations of base stations (BSs) that may belong to the same or to competing service providers. We take into account the impact of these decisions on the behavior of intelligent mobile terminals that can connect to the base station that offers the best utility. The signal-to-interference-plus-noise ratio (SINR) is used as the quantity that determines the association. We first study the SINR association-game: We determine the cells corresponding to each base stations, i.e., the locations at which mobile terminals prefer to connect to a given base station than to others. We make some surprising observations: 1) displacing a base station a little in one direction may result in a displacement of the boundary of the corresponding cell to the opposite direction; 2) a cell corresponding to a BS may be the union of disconnected subcells. We then study the hierarchical equilibrium in the combined BS location and mobile association problem: We determine where to locate the BSs so as to maximize the revenues obtained at the induced SINR mobile association game. We consider the cases of single frequency band and two frequency bands of operation. Finally, we also consider hierarchical equilibria in two frequency systems with successive interference cancellation.

That's disgusting: unraveling the mysteries of repulsion

Why do we watch horror movies? What is the best way to persuade someone to quit smoking? Why are we more likely to buy a given item if an attractive person has just touched it? And what on earth is the appeal of competitive eating? In this lively, colorful new book, Rachel Herz answers these questions and more, shedding light on an incredible range of human traits-from food preferences and sexual attraction to moral codes and political ideology-by examining them through the lens of a fascinating subject: disgust. One of the most complex human emotions, disgust is the product of both culture and instinct and so it allows us a unique perspective on the relationship between nature and nurture. A component of fear and prejudice, it also gives us powerful-sometimes disturbing-insights into the fabric of society. Herz draws on the latest psychological studies and neurological research to offer surprising observations about human behavior and biology. For example, we learn that a man's scent matters more than his looks or his income in determining whether or not a given woman will find him attractive, that lust and disgust activate the same area of the brain, and that watching a gory movie triggers your immune system as if you were facing an actual threat. We even learn that washing your hands after thinking about a past misdeed-a la Lady Macbeth-can help you feel less guilty. What makes That's Disgusting so remarkable is Herz's ability to weave these curious findings and compelling facts into a narrative that tackles important questions. What matters more: our brain wiring or our upbringing? Is there such a thing as normal? And how might politicians and marketers use disgust to manipulate us? Combining lucid scientific explanations and fascinating research with a healthy dose of humor, That's Disgusting illuminates issues that are central to our lives: love, hate, fear, empathy, prejudice, humor, and happiness.

The acceptance and adoption of continuous auditing by internal auditors: A micro analysis

The umbrella of “advanced technology” covers a range of techniques widely used in the U.S. to provide strategic advantage in a very competitive business environment. There is an enormous amount of information contained within current-generation information systems, some of which is processed on a real-time basis. More importantly, the same holds true for actual business transactions. Having accurate and reliable information is vital and advantageous to businesses, especially in the wake of the recent recession. Therefore, the need for ongoing, timely assurance of information utilizing continuous auditing (CA) and continuous control monitoring (CM) methodologies is becoming more apparent. To that end, we have conducted interviews with 22 internal audit managers and 16 internal audit staff members at 9 leading internal audit organizations to examine the status of technology adoption, to evaluate the development of continuous auditing, and to assess the use of continuous control monitoring. We found that several companies in our study were already involved in some form of continuous auditing or control monitoring while others are attempting to adopt more advanced audit technologies. We also made a large number of surprising observations on managerial, technology training and absorption, and other issues. According to our audit maturity model, all of the companies were classified between the “traditional audit” stage and the “emerging stage,” not having yet reached the “continuous audit” stage. This paper,11This paper is one output of a research program undertaken between the Continuous Auditing and Research Laboratory (CARLAB) at Rutgers Business School and KPMG, whose aim was to obtain a 360-degree view of the state of the art of CA, encompassing its use by both external and internal auditors. The authors are appreciative for the comments received in many presentations and in particular to Prof. Alexander Kogan's suggestions. to our knowledge, is the first to study CA technology adoption in a micro level by an interview approach.

Chromium exhibits adverse effects at environmental relevant concentrations in chronic toxicity assay system of nematode Caenorhabditis elegans

Here we investigated whether the assay system (10-d) in Caenorhabditis elegans can be used to evaluate chronic toxicity of chromium (Cr(VI)) at environmental relevant concentrations ranging from 5.2μgL−1 to 260μgL−1. The results indicated that lethality, locomotion behavior as revealed by head thrash, body bend, and forward turn, metabolism as revealed by pumping rate and mean defecation cycle length, intestinal autofluorescence, and ROS production were severely altered in Cr chronically exposed nematodes at environmental relevant concentrations. The most surprising observations were that head thrash, body bend, intestinal autofluorescence, and ROS production in 13μgL−1 Cr exposed nematodes were significantly influenced. The observed adverse effects of Cr on survival, locomotion behavior, and metabolism were largely due to forming severe intestinal autofluorescence and ROS production. Therefore, our findings demonstrate the usefulness of chronic toxicity assay system in C. elegans in evaluating the chronic toxicity of toxicants at environmental relevant concentrations.

Lifestyle behaviors in women undergoing in vitro fertilization: a prospective study

To determine the lifestyle behaviors of women before and during an IVF cycle. Prospective survey. Private academically affiliated infertility center. One hundred eighteen women, ages 18-44, scheduled to undergo an assisted reproductive technology (ART) cycle using their own eggs. None. Lifestyle history and daily habit survey. In the month before their IVF cycle, 92% exercised, 3% smoked, 73% drank alcohol, 76% drank caffeinated beverages, 14% took herbs, and 30% underwent acupuncture. During their ART cycle, 100% exercised, 2% smoked, 49% drank alcohol, 77% drank caffeine, 12% took herbs, and 47% underwent acupuncture. This is the first prospective assessment of numerous lifestyle habits during an ART cycle. A number of surprising observations were made. Despite physician recommendation against it, some ART patients took herbs while cycling. Patients continue to exercise regularly and drink caffeine daily, and almost half continued to drink alcohol. Lifestyle behavior counseling should be considered for patients pursuing ART. NCT01119391.

Enantiomeric pairs reveal that key medicinal chemistry parameters vary more than simple physical property based models can explain

An on-going trend in the medicinal chemistry literature is to link physical properties of a molecule that are achiral (such as lipophilicity) to biological or pharmaceutical properties (such as pharmacokinetics and toxicity) which depend upon interactions with chiral entities. In contrast, we have explored the variation in key pharmaceutical properties between enantiomeric pairs where only the three-dimensional arrangement of atoms changes. The analysis reveals that many properties are sensitive to changes in stereochemistry and quantifies this dependence. Any variation between enantiomers cannot be explained by achiral descriptors. The analysis highlights those properties where chiral lability or measurements on racemates might be misleading and permits deductions to be made from paired experiments in which two enantiomers are studied. The analysis suggests an inherent advantage to lead optimization in a chiral series where improvement into an attractive part of chemical space might be complemented by a selection between two enantiomers with different pharmacokinetic or safety profiles. Hence, in the early stages of a drug discovery program extra preference should be given to chiral series. Surprising observations are that permeability and efflux in cell based assays are not chirally dependent whereas in vivo volume of distribution does change between enantiomers.

Bone-seeking TRAP conjugates: surprising observations and their implications on the development of gallium-68-labeled bisphosphonates

BackgroundBisphosphonates possess strong affinity to bone. 99mTc bisphosphonate complexes are widely used for bone scintigraphy. For positron emission tomography (PET) bone imaging, Ga-68-based PET tracers based on bisphosphonates are highly desirable.FindingsTwo trimeric bisphosphonate conjugates of the triazacyclononane-phosphinate (TRAP) chelator were synthesized, labeled with Ga-68, and used for microPET imaging of bone in male Lewis rats. Both Ga-68 tracers show bone uptake and, thus, are suitable for PET bone imaging. Surprisingly, Ga-71 nuclear magnetic resonance data prove that Ga(III) is not located in the chelating cavity of TRAP and must therefore be bound by the conjugated bisphosphonate units.ConclusionThe intrinsic Ga-68 chelating properties of TRAP are not needed for Ga-68 PET bone imaging with TRAP-bisphosphonate conjugates. Here, TRAP serves only as a trimeric scaffold. For preparation of Ga-68-based bone seekers for PET, it appears sufficient to equip branched scaffolds with multiple bisphosphonate units, which serve both Ga-68-binding and bone-targeting purposes.

Isotonic estimation of survival under a misattribution of cause of death.

Several authors have indicated that incorrectly classified cause of death for prostate cancer survivors may have played a role in the observed recent peak and decline of prostate cancer mortality. Motivated by the suggestion we studied a competing risks model where other cause of death may be misattributed as a death of interest. We first consider a naïve approach using unconstrained nonparametric maximum likelihood estimation (NPMLE), and then present the constrained NPMLE where the survival function is forced to be monotonic. Surprising observations were made as we studied their small-sample and asymptotic properties in continuous and discrete situations. Contrary to the common belief that the non-monotonicity of a survival function NPMLE is a small-sample problem, the constrained NPMLE is asymptotically biased in the continuous setting. Other isotonic approaches, the supremum (SUP) method and the Pooled-Adjacent-Violators (PAV) algorithm, and the EM algorithm are also considered. We found that the EM algorithm is equivalent to the constrained NPMLE. Both SUP method and PAV algorithm deliver consistent and asymptotically unbiased estimator. All methods behave well asymptotically in the discrete time setting. Data from the Surveillance, Epidemiology and End Results (SEER) database are used to illustrate the proposed estimators.

Neonatal diethylstilbestrol exposure disrupts female reproductive tract structure/function via both direct and indirect mechanisms in the hamster

We assessed neonatal diethylstilbestrol (DES)-induced disruption at various endocrine levels in the hamster. In particular, we used organ transplantation into the hamster cheek pouch to determine whether abnormalities observed in the post-pubertal ovary are due to: (a) a direct (early) mechanism or (b) an indirect (late) mechanism that involves altered development and function of the hypothalamus and/or pituitary. Of the various disruption endpoints and attributes assessed: (1) some were consistent with the direct mechanism (altered uterine and cervical dimensions/organization, ovarian polyovular follicles, vaginal hypospadius, endometrial hyperplasia/dysplasia); (2) some were consistent with the indirect mechanism (ovarian/oviductal salpingitis, cystic ovarian follicles); (3) some were consistent with a combination of the direct and indirect mechanisms (altered endocrine status); and (4) the mechanism(s) for one (lack of corpora lutea) was uncertain. This study also generated some surprising observations regarding vaginal estrous assessments as a means to monitor periodicity of ovarian function in the hamster.

Workshop on Extreme Physics

SummaryNever before has there been such a wealth of versatile ground- and space-based facilities with which to detect variable emission across the electromagnetic spectrum and beyond, to non-EM signals such as neutrinos and gravitational waves, to probe the most extreme phenomena in the Universe. The variable sky is already providing a wealth of new and surprising observations of phenomena such as GRBs, SNe and AGN that are pushing current theories beyond the state of the art. Multi-messenger follow-up will soon become de rigeur, and upcoming radio and optical all-sky transient surveys will revolutionise the study of the transient Universe. In addition to the technical and data challenges presented by such surveys, a major new challenge will be the interpretation of the wealth of available data and the identification of the underlying physics of new classes of variable (and potentially exotic) objects. Theoretical predictions will be vital for interpreting these future transient discoveries.The goal of this workshop was to bring together theorists and observers in order to identify unexplored synergies across three main research areas of extreme physics: gamma-ray bursts, supernovæ and, more generically, relativistic jets. It aimed to discuss key outstanding questions in these rapidly moving fields, such as the composition and acceleration of GRB and AGN jets, GRB progenitors and central engines, the origin of the wide range of observed variability time-scales in GRB prompt and after-glow light curves and related cosmological applications, the physics of the newly-discovered ultra-luminous SN-like optical transients—as well as to speculate on what we might hope to discover with future technology.The workshop absorbed two 90-minute sessions, selecting 3 main science topics (Relativistic Jets, GRBs and SNe) which it organised as structured discussions driven by a series of short but provocative questions. The final session featured a panel-led debate but with full audience participation.

Lifestyle behaviors in women undergoing IVF

Lifestyle behaviors in women undergoing IVF

Telecommunications in South Africa: Who is Actually Regulating?

Although the Republic of South Africa telecommunications market is a maturing one with a large customer base to serve, it has been repeatedly been observed over the past few years that many good intentions were formulated in the regulatory sphere with sometimes poor outcomes. A number of surprising observations have been made on the outcomes, the delays or other process related events linked to regulatory measures. The paper thus researches first who is actually regulating the telecommunications industry, and identifies next opportunities and bottlenecks whereby a change might happen to reach the expected outcomes. A political economy methodology is taken, backed up by extensive field work over 2010 and 2011, leading to a web of conjectures providing answers to the first question, based on an extensive analysis of key stakeholders goals, positions and interactions. Finally, a number of measures are proposed to improve the regulatory impact and efficiency, and evolve the South African telecommunications eco-system.

What Do We Really Know about How CD4 T Cells Control Mycobacterium tuberculosis?

What Do We Really Know about How CD4 T Cells Control Mycobacterium tuberculosis?