Earlier Presumption Research Articles

Structure and Interaction Prediction in Prokaryotic RNA Biology.

Many years of research in RNA biology have soundly established the importance of RNA-based regulation far beyond most early traditional presumptions. Importantly, the advances in "wet" laboratory techniques have produced unprecedented amounts of data that require efficient and precise computational analysis schemes and algorithms. Hence, many in silico methods that attempt topological and functional classification of novel putative RNA-based regulators are available. In this review, we technically outline thermodynamics-based standard RNA secondary structure and RNA-RNA interaction prediction approaches that have proven valuable to the RNA research community in the past and present. For these, we highlight their usability with a special focus on prokaryotic organisms and also briefly mention recent advances in whole-genome interactomics and how this may influence the field of predictive RNA research.

Clinical Genetic Aspects of ASD Spectrum Disorders.

Early presumptions opined that autism spectrum disorder (ASD) was related to the rearing of these children by emotionally-distant mothers. Advances in the 1960s and 1970s clearly demonstrated the biologic basis of autism with a high heritability. Recent advances have demonstrated that specific etiologic factors in autism spectrum disorders can be identified in 30%–40% of cases. Based on early reports newer, emerging genomic technologies are likely to increase this diagnostic yield to over 50%. To date these investigations have focused on etiologic factors that are largely mono-factorial. The currently undiagnosed causes of ASDs will likely be found to have causes that are more complex. Epigenetic, multiple interacting loci, and four dimensional causes (with timing as a variable) are likely to be associated with the currently unidentifiable cases. Today, the “Why” is more important than ever. Understanding the causes of ASDs help inform families of important issues such as recurrence risk, prognosis, natural history, and predicting associated co-morbid medical conditions. In the current era of emerging efforts in “personalized medicine”, identifying an etiology will be critical in identifying endo-phenotypic groups and individual variations that will allow for tailored treatment for persons with ASD.

Early Presumption on the 28d Strength of Cement-Clay Composite Powder Mixed Mortar

Based on the mixing ratio design of the cement-clay composite powder mixed mortar ,in this article,the 28d strength was early presumed by the 7d strength;by the method of mathematical statistics, different regression equations were established and the results were compared,which indicated that exponential equation had a better stability;the early presumption of 28 day strength of cement-clay composite powder Mixed Mortar provided a scientific basis for engineering construction.

Prediction of response to anti-EGFR antibodies in metastatic colorectal cancer: looking beyond EGFR inhibition

GENERAL COMMENTARY article Front. Immunol., 07 January 2013Sec. Vaccines and Molecular Therapeutics Volume 3 - 2012 | https://doi.org/10.3389/fimmu.2012.00409

The evolving role of monoclonal antibodies in colorectal cancer: early presumptions and impact on clinical trial development.

Targeted biologic agents have an established role in treating metastatic colorectal cancer (mCRC). Bevacizumab, a recombinant monoclonal antibody against the vascular endothelial growth factor ligand is approved by the U.S. Food and Drug Administration (FDA) for bevacizumab-naïve patients. Cetuximab, a chimeric monoclonal antibody (mAb) against the epidermal growth factor receptor (EGFR) is FDA approved as a single agent, or in combination with irinotecan, in both irinotecan-naïve and refractory patients, and has additional efficacy in combination with oxaliplatin. Panitumumab, a fully human EGFR mAb, is FDA approved as a single agent in refractory patients but has additional efficacy in combination with chemotherapy. After reaching a temporary therapeutic plateau of FDA-approved agents for the treatment of mCRC, pivotal results have developed that critically affect the care for these patients. Correlative data from randomized trials of EGFR inhibitors across disease settings have demonstrated higher response rates, specifically for patients with wild-type K-RAS tumors. The interpretation of the B-RAF mutation and other molecular markers may further define the appropriateness of anti-EGFR therapy. Recent literature revealed that the first-line use of combined anti-EGFR therapy plus bevacizumab resulted in inferior outcomes and additional toxicities. Furthermore, the role of biologic agents for locally advanced colon cancer cannot be advocated at this time. With impending changes in the health care system, the economic impact of mAbs will continue to be scrutinized. Hence, as the significance of molecular markers continues to develop, their role as it pertains to the appropriate use of biologic agents in the treatment of mCRC will continue to evolve.

Spin–Spin Interactions Across the “Cove” in the (Z) and (E) Isomers of 1,1′‐Difluoro‐9,9′‐bifluorenylidene

AbstractIn the (Z) isomer, but not in the (E) isomer of title compound 1, moderate 19F,19F spin–spin coupling across the “cove” is observed [J(F,F) = 11.0 Hz], which is deemed to obey a through‐space mechanism. The coupling between the isochronous fluorine nuclei of 1Z causes second‐order effects in the 1H, 13C and 19F NMR spectra of this compound and allows its easy distinction from the (E) isomer. A B3LYP/6‐31+G(d) calculation of 1Z as an isolated molecule was carried out which gave a non‐bonded F,F distance d(F,F) of 2.711 Å and an angle between the two C–F bond vectors of 34.1°. The computed F···F compliance constant of 6.96 Å/mdyn points to a very weak interaction. According to our previous correlation between d(F,F) and through‐space J(F,F), the F,F distance in 1Z would be expected to go along with a coupling constant of ca. 46 Hz. This discrepancy between prediction and experiment gives support to our earlier presumption that a simple d(F,F)/J(F,F) correlation may not sufficiently describe through‐space couplings and that an angular factor should also be taken into account. An X‐ray diffraction study of 1Z resulted in an F,F distance of 2.638 Å and an angle between the C–F bonds of 36.4°, in fair agreement with the MO calculation. The rigidity of the (Z) isomer was studied using theoretical compliance constants. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

The use of circular wire external fixation in the treatment of salvage ankle arthrodesis

The authors retrospectively reviewed their experience with circular wire external fixation in the treatment of salvage ankle arthrodesis during the past 9 years. The results of 43 cases in a difficult patient population are presented with an average follow-up of 27.0 months. Thirty-three patients (80.5%) went on to achieve a solid fusion or stable pseudarthrosis. A minimum of a 4-ring frame construct was applied for an average of 96.1 days. The major complication rate was 51.2%, including 3 below-knee amputations (7.3%), 7 unstable nonunions (17.1%), 7 cases of osteomyelitis and/or deep-space infection (16.3%), 3 malunions (7.3%), and 2 tibial stress fractures (4.7%). The incidence of complications occurred similarly in patients with Charcot arthropathy, failed total ankle arthroplasty, septic fusion, posttraumatic deformity, or avascular necrosis of the talus, whereas it was relatively higher in patients who were diabetics, smokers, or had an increased body mass index. In addition, the incidence of a nonunion tended to increase with longer follow-up, suggesting that early presumption of a solid union may be erroneous. Based on our defined criteria of a stable, well-aligned fusion without severe pain or activity restrictions, 28 patients (68.3%) had a good result. Circular wire external fixation can be a viable treatment for complex ankle salvage pathology; however, it is difficult to predict the prospects of success or failure.

Sympathy and its discontents: ‘Greatest happiness’ versus the ‘general good’

The paper explicates the utilitarian principle of sympathy in terms of the shape of what has been called the ‘sympathetic gradient’, which determines the allocation of goods to those close by and afar. It examines challenges to the utilitarian impartial weighting scheme that emerged in the literary community, and from evolutionary biology. As sympathy came to be seen as an impediment to evolutionary perfection, voices urged that sympathy be suppressed. Darwin's Descent of Man explicitly countenanced the suppression of sympathy in a trade-off of happiness for the perfection of the race. A post-Darwinian argument concerning a different capacity for pleasure accompanied the demise of sympathy in utilitarian economic analysis. Utilitarians then moved from the early presumption of ‘everyone to count for one’ to counting ‘every equal increment of pleasure’ equally.

Evolving toward Project-Specific Reliability: Are We Sure It's a Good Idea?

The writers of current standards and specifications for load and resistance factor design (LRFD) envisioned that those documents would be used by designers in a manner similar to that used in prior (allowable stress design) formats. They presumed that designs would be accomplished by satisfying a series of checking equations in which the structural resistance exceeds the demand on the structure. While these early developers used reliability analysis tools to derive the load and resistance factors, they did not envision that reliability analysis would evolve into a tool to be directly used by designers. In spite of those early presumptions, the evolving reality is that reliability analysis procedures are now available to an increasing number of individual designers. Sooner or later, these designers will attempt to use reliability analysis to assist them in their project-specific or, more likely, product-specific designs. This paper discusses limitations and potential pitfalls of reliability analysis when used in routine structural design. Specific examples focus on wood design. The conclusion reiterates the premise that LRFD, not theoretical reliability analysis, is the proper tool for use in daily design.

High-performance Co/Pt multilayer magneto-optical disk using ultrathin seed layers

We have prepared high-performance disks based on Co/Pt multilayers using ultrathin seed layers. Both crystalline (such as ZnO) and amorphous [such as indium-tin-oxide (ITO) and Si] materials were used as seed layers. We found that very thin layers of these materials enhance coercivity, squareness of the Kerr loop, and perpendicular anisotropy of the Co/Pt superlattices. These beneficial effects are obtained with a seed layer as thin as 0.2 nm. This is incontrast with the earlier presumptions that indicated much thicker layers, about 80 nm of crystalline material, were required to improve the texture of the Co/Pt multilayer for sufficient enhancement in the coercivity. Further, the data indicated that disks with amorphous seed layers generally have higher perpendicular anisotropy and lower recording noise as compared to those with crystalline ZnO. We have prepared disks using a thin amorphous ITO seed layer and a simple disk structure: grooved PC/ITO/12[Co/Pt]/lacquer overcoat. The performance of these disks is similar to that a commercial TbFeCo media. This media has potential for low cost manufacturing.

Aeroacoustics

SummaryThe high noise levels of early turbojet aircraft forced attention to be given to the mechanics of the noise generation process and ways were urgently sought for silencing their high speed propulsive flows. The subject of aeroacoustics was born with this problem, the subject being the variety of ways in which sound and flow interact, with the early emphasis being on sound generated aerodynamically. Sound was thought to be a by-product of the flow arid believed to have a negligible back-reaction on it.The search for noise suppression has been extremely successful, so much so, that engine noise is no longer a problem likely to constrain future aircraft operations. Silencing technology has made enormous strides by avoiding as much as possible the very high speed jet flows that were a feature of early engines. But that avenue is not available to supersonic aircraft, which still wait for ways of making their operation acceptably quiet to be identified.Aeroacoustics has brought into being a much deeper insight into the interactions of sound and flow, and some of the early presumptions about the mechanisms of noise creation have had to be rethought. Some of the advances have come from entirely new directions, for example, from anti-sound, a silencing idea based on the destructive cancellation of interfering waves, which has advanced to a state that provides a useful new technology. Some new understanding follows the discovery that flow-acoustic interactions are not always the one-way process previously assumed. Sound can affect flow, especially so when the flow is unstable. It is of course the very unstable flows that make most noise so, taken together, these developments indicate that control might one day be exercised by actively managing the unsteady flows, making them more useful and desirable than before. Indeed examples are now known where control has made possible the avoidance of a powerful performance-limiting instability that previously made that flow regime a prohibited operational zone, a development of aeroacoustics that is probably far more significant than its noise suppression role. That line of thought is expanded in this paper, which concludes with the speculation that active control might now be offering an avenue for approaching die high speed jet noise problem from a completely new direction. Of course it is far too early to know whether that approach can provide a way for removing the take-off noise constraint currently threatening the viability of supersonic transports, but it might; that makes it very important indeed, for it is hard to see any alternative.

Tricritical points in H2O–oil–amphiphile mixtures

Quaternary mixtures of water (A), an oil (B), a nonionic amphiphile (C), and an appropriately chosen fourth component offer an opportunity for searching for tricritical points (tcp) at atmospheric pressure. It is shown that for reaching a tcp, one has to couple an A–B–C mixture that shows the phase sequence 2_→3→2̄ with rising temperature, with a second ternary mixture that shows a 2_→2̄ transition, the bar denoting in which of the two phases the amphiphile is mainly dissolved. With weakly structured solutions, that is, with short-chain amphiphiles as (C) this can be done by either adding an oil with a lower carbon number, or by adding a nonaqueous polar protic solvent such as formamide. With strongly structured solutions, that is, with long-chain amphiphiles, one has to add a short-chain amphiphile for destroying the structure as a prerequisite for reaching a tcp. Insofar, our earlier presumption that with long-chain amphiphiles, a tcp may also be reached, either by increasing their amphiphilicity or by lowering the carbon number of the oil, does not seem to apply. Experience shows that in A–B–C′ mixtures with sufficiently short-chain amphiphiles as C′ that separate into three phases: the amphiphile-rich middle phase always wets the A/B interface. If a short-chain amphiphile is added to an A–B–C mixture with a nonwetting middle phase one will, therefore, inevitably find a nonwetting→wetting transition as one approaches a tcp.

Primate hemoglobins: Polymorphisms and evolutionary patterns

Abstract In this rrport we illustrate the apparently great incidence in the number of different kinds of electrophoretically undetectable intraspecies variants found in the course of characterizing primate hemoglobin α, β and δ sequences. Our primary interest is to assess the significance of such findings in a setting provided by fixed amino acid differences that have accumulated between species during primate evolution. Observed non-randomness in fixed mutations, with respect to both linear distribution and certain kinds of change, is interpreted as due to the restrictive effects of natural selection rather than to either differential mutability at particular positions or disturbed permutations of the genetic code in general. Thus, in the micropatterns of accumulated mutation, we adduce strong evidence for Darwinism. However, we also find that the δ chain of minor hemoglobin A2 (α2δ2)—while apparently visible to selection—seems less restricted than the β chain of the major component, hemoglobin A (α2β2). Such findings are used to support our earlier presumption that comparative changes in β and δ can serve as a model for evaluating mechanisms of amino acid replacement during evolution. We believe that equivalence between β and δ in the numbers of recognizable fixed mutations is more easily explained by non-adaptive mechanisms than by adaptive ones. The frequencies of seven different kinds of electrically neutral variants found within-species during detailed analysis of ∼70 allele products are reported here. Most, if not all, are common. We propose that the overall incidence of different kinds of electrically neutral polymorphisms is probably at least fivefold greater than the kinds of electrophoretically detectable polymorphism. In their electrical neutrality and location the electrophoretically silent polymorphisms strongly resemble the fixed mutations accumulated during evolution of primate hemoglobin chains and are thus candidates for the transient phase of non-adaptive evolution.

On the mechanism of ribonuclease secretion in the murine exocrine pancreas

In the rat pancreas, normal diurnal and pilocarpine-induced variations in the protein, ribonuclease (RNase), and water content were studied. The results show a considerable variation in the dirunal content of RNase, whereas the protein and water concentrations remained constant. Furthermore, the experiments provide evidence that RNase is secreted by means of a mechanism partly independent of other proteins and that every zymogen granule does not contain the same amount of the enzyme. The earlier presumption that there are at least two intracellular storage forms of the enzyme is confirmed and the intracellular variability in the capacity to attract anti-RNase antibodies is explained.