Structural Similarity Index

Ceftriaxone sodium is a third generation cephalosporin. This antibiotic cannot be absorbed orally owing to its very less permeation through GI epithelia. Other problem associated with the drug is its acid labile nature. The present study attempts to increase the intestinal permeability of BCS Class III drug ceftriaxone sodium by using certain intestinal absorption enhancers. The blend of permeation enhancer, drug, and other excipients were incorporated into Beads to formulate the final dosage form. To enhance the permeation, intestinal permeation enhancers were used in various molar ratios with the drug. The effect of absorption enhancers on the lipophilicity of ceftriaxone sodium was determined by means of the n-octanol/water system. The changes in partition coefficient by the octanol/water system were confirmed using an in vitro transport model with excised animal intestinal membrane. The results indicated that there is significant improvement in the permeability of the drug and the extent of enhancement was highly dependent on the type of used absorption enhancer. Permeation enhancer and drug were formulated into beads further evaluated for permeability by using biological membrane. The release profile of ceftriaxone from beads was observed in both gastric and intestinal pH (7.4 buffer). Release of drug from the beads in both the media was found to occur predominantly by diffusion following non Fickian transport mechanism and was higher and more rapid in intestinal pH than in gastric pH. The results obtained from this study indicate that ceftriaxone sodium could be successfully delivered orally when formulated with permeation enhancers.

Non-invasive strategies for the analysis of endogenous DNA damage are of interest for the purpose of monitoring genomic exposure to biologically produced chemicals. We have focused our research on the biological processing of DNA adducts and how this may impact the observed products in biological matrixes. Preliminary research has revealed that pyrimidopurinone DNA adducts are subject to enzymatic oxidation in vitro and in vivo and that base adducts are better substrates for oxidation than the corresponding 2′-deoxynucleosides. We tested the possibility that structurally similar exocyclic base adducts may be good candidates for enzymatic oxidation in vitro. We investigated the in vitro oxidation of several endogenously occurring etheno adducts [1,N 2 -ε-guanine (1,N 2 -ε-Gua), N 2 ,3-ε-Gua, heptanone-1,N 2 -ε-Gua, 1,N 6 -ε-adenine (1,N 6 -ε-Ade), and 3,N 4 -ε-cytosine (3,N 4 -ε-Cyt)] and their corresponding 2′-deoxynucleosides. Both 1,N 2 -ε-Gua and heptanone-1,N 2 -ε-Gua were substrates for enzymatic oxidation in rat liver cytosol; heteronuclear NMR experiments revealed that oxidation occurred on the imidazole ring of each substrate. In contrast, the partially or fully saturated pyrimidopurinone analogues [i.e., 5,6-dihydro-M 1 G and 1,N 2propanoguanine (PGua)] and their 2′-deoxynucleoside derivatives were not oxidized. The 2′-deoxynucleoside adducts, 1,N 2 -ε-dG and 1,N 6 -ε-dA, underwent glycolytic cleavage in rat liver cytosol. Together, these data suggest that multiple exocyclic adducts undergo oxidation and glycolytic cleavage in vitro in rat liver cytosol, in some instances in succession. These multiple pathways of biotransformation produce an array of products. Thus, the biotransformation of exocyclic adducts may lead to an additional class of biomarkers suitable for use in animal and human studies.

Gross Brukkaros is a volcano-shaped inselberg rising 600 m above the Nama plain in southern Namibia. It evolved in several steps starting with the intrusion of a laccolithic body which caused uplift and radial fissuring of the overlying rocks, Cambrian, Permocarbon iferous and Upper Cretaceous Kalahari sediments as well as Jurassic dolerite sills. On the radial fissures more than 100 carbonatite dykes and 74 carbonatite diatremes were emplaced. The eruption from these dykes and diatremes caused a mass deficiency in the laccolith and subsidence of its roof, i.e. a downsag caldera formed collecting thick reworked sedimentary and pyroclastic debris. The carbonatite diatremes point to phreatomagmatic explosive activity because of occurrence of only non-vesicular carbonatite ash grains and lapilli and because the hydrogeology was conducive to such explosive activity: a near surface groundwater table is indicated by unconsolidated Kalahari sediments and the free groundwater table of the c...

Prof Laurie Dickie's review and feedback helped the author in finalizing the manuscript. Dr Janine Rutledge, CBS Communication skills Centre, provided fruitful suggestions on the grammar and semantics of the text in the thesis. The author wishes to acknowledge the feedback and critical comments made by the juries, Professor Tommi Karhela and Associate Professor Mustafa Jarrar that greatly helped to improvise the structure and contents of the thesis. The author has utilized this opportunity to update the contents in the thesis based on latest work done in the areas of "ontology modelling", "big-data systems" and "business data analytics". The support and the immense patience from all the family members are well respected.

Paranthropus aethiopicus); KNM-ER 801 (molar attributed to P. boisei 27 ); KNM-ER 1805E (premolar attributed to H. habilis 27 ); KNM-ER 1482B (molar attributed to H. rudolfensis 27 ); KNM-ER 809B (molar attributed to H. ergaster 27 ); KNM-ER 3733 (lower right P4 attributed to H. ergaster 27 ); Sangiran S7-37 (upper right M1 and P4 attributed to H. erectus); and Tabun C1 (fragment of lower left ®rst molar metaconid; attributed to Neanderthal).

English abstract We propose a Web-based application for revising an OWL ontology. The main functionality of this application consists in changing as less as possible an initial ontology when adding a new piece of knowledge such as an axiom, an assertion. To be able to ensure such a minimal change in preserving consistency of the resulting ontology, we use a set of models generated by a tableau algorithm to characterize the semantics of an ontology, and define a semantic distance between ontologies. Our Web-based application provides also other services such as visualizing an OWL ontology in a succinct syntax, inputting an OWL axiom/assertion.

Plant B-type cyclin genes are expressed specifically in late G2-and M-phases during the cell cycle. Their promoters contain a common cis -acting element, called the MSA (M-specific activator) element, that is necessary and sufficient for periodic promoter activation. This motif also is present in the tobacco kinesin-like protein gene NACK1 , which is expressed with timing similar to that of B-type cyclin genes. In this study, we show that G2/M-phase-specific activation of the NACK1 promoter also is regulated by the MSA element, suggesting that a defined set of G2/M-phase-specific genes are coregulated by an MSA-mediated mechanism. In a search for MSA binding factors by yeast one-hybrid screening, we identified three different Myb-like proteins that interact specifically with the MSA sequence. Unlike the majority of plant Myb-like proteins, these Myb proteins, NtmybA1, NtmybA2, and NtmybB, have three imperfect repeats in the DNA binding domain, as in animal c-Myb proteins. During the cell cycle, the level of NtmybB mRNA did not change significantly, whereas the levels of NtmybA1 and A2 mRNAs fluctuated and peaked at M-phase, when B-type cyclin genes were maximally induced. In transient expression assays, NtmybA1 and A2 activated the MSA-containing promoters, whereas NtmybB repressed them. Furthermore, expression of NtmybB repressed the transcriptional activation mediated by NtmybA2. Our data show that a group of plant Myb proteins that are structurally similar to animal c-Myb proteins have unexpected roles in G2/M-phase by modulating the expression of B-type cyclin genes and may regulate a suite of coexpressed genes.

The assessment of biomaterial compatibility relies heavily on the analysis of macroscopic cellular responses to material interaction. However, new technologies have become available that permit a more profound understanding of the molecular basis of cell–biomaterial interaction. Here, both conventional phenotypic and contemporary transcriptomic (DNA microarray-based) analysis techniques were combined to examine the interaction of cells with a homologous series of copolymer films that subtly vary in terms of surface hydrophobicity. More specifically, we used differing combinations of N- isopropylacrylamide, which is presently used as an adaptive cell culture substrate, and the more hydrophobic, yet structurally similar, monomer N-tert- butylacrylamide. We show here that even discrete modifications with respect to the physiochemistry of soft amorphous materials can lead to significant impacts on the phenotype of interacting cells. Furthermore, we have elucidated putative links between...

Adrenomedullin is a peptide hormone extracted from pheochromocytoma in humans has 52 amino acid held together by a single disulphide bond. The name adrenomedullin was given as it is abundantly found in adrenal medulla, comes under calcitonin gene-related peptide family. Production of adrenomedullin is up-regulated by several factors such as oxidative stress, pro-inflammatory cytokines, angiotensin II, hypoxia, hyperglycemia, natriuretic peptide and aldosterone. It is synthesized as part of a larger precursor molecule, termed preproadrenomedullin. Adrenomedullin receptor consists of seven transmembrane domains and belongs to G-protein dependent receptor family. This peptide has not only a potent hypotensive and vasorelaxing effect but it performs various biological functions. It has potent effects on cell migration, growth, and apoptosis. So with this overview adrenomedullin is a novel peptide hormone that plays significant physiological functions in different systems of the body.

Candida infection is found among a wide population including immuno-compromised individuals like HIV/AIDS patients with worldwide distribution. Candidiasis is the commonest opportunistic infection in the immunocompromised group. It shows considerable variations among age group, sex, socio-economic status, immune status, species differentiation and some other aspects. HIV/AIDS patients attending Out Patients’ Department (OPD) of School of Tropical Medicine, Kolkata, were included in this study with the aim to assess the prevalence of Oropharyngeal Candidiasis (OPC) among them. Information were collected from 160 patients clinically suspected for Oropharyngeal Candidiasis and with low CD4 count (< 50 cells/c.mm). A pre-tested questionnaire along with the informed consent from the patient was used for collection of information on socio-economic details from these cases. Study subjects were further investigated by collection of specimens from the site of lesions and characterization ...

The biochemical characterization of protein structures has led to a better understanding of allergens, their structure/function relationship, and can be very powerful in identifying protein sequences with significant structural similarity to known allergens. However, for scientists, regulators and food manufacturers there exists a need for acquiring additional data on potential allergenicity of proteins, particularly, biotechnology derived molecules in food products for which minimal or no prior human exposure information is available. Since human exposure testing, while direct, is unacceptable, understanding allergy in animals has been used to investigate the allergic response on a molecular level as well as test the potential in vivo allergenicity of food proteins. Rodents seem to be the most likely candidate for assessing allergenicity. For development of an animal test system for allergenicity characterization and testing, a number of criteria are required for qualification for ...

Here, we introduce TOPStrings (TOPS+), a highly abstract string-based model of protein topology which permits efficient computation of structure comparison, and can optionally represent ligand information. In this model we consider loops as secondary structure elements (SSEs) as well as helices and strands; in addition we represent ligands as first class objects. Interactions between SSEs, and between SSEs and ligands are described by incoming and outgoing arcs, and SSEs are annotated with arc interaction direction and type. We are able to abstract away from the ligands themselves, to give a model characterized by a regular grammar rather than the context sensitive grammar of the original TOPS model (Gilbert, et al., 2000; Gilbert, et al., 2001; Viksna and Gilbert, 2001). Our TOPStrings model is sufficiently descriptive to obtain biologically meaningful results and has the advantage of permitting fast string-based structure matching and comparison as well as avoiding issues of NP-co...

This study analyses the influence of word problem's context and structure, and capturing the structure and using analogies on problem-solving. A 2x3x2 factorial design was used with two between-subjects variables -capturing the structure and the use of analogies- and one withinsubjects variable -structural complexity of word problem-. Two types of booklets containing two word problems that differ from each other in structure (and each type of booklet having problems of different context) and questions about capturing the structure and using analogies in problem solving, were administered to 66 third-year pre-service primary teachers from the same university (University of Valencia,Spain). The results of the ANOVAs showed that: a) Problems increase in difficulty when they have complex structure and low familiarity context, and b) Capturing the structure and the use of analogies are needed to solve structurally complex problems.

Se desarrollan dos estudios exploratorios para analizar el éxito en la transferencia en resolución de problemas a partir de análogos. Las diferentes analogías entre problemas ‘ejemplo’ y ‘propuestos’ se suponen construidas a partir de dos variables: la Superficie y la Estructura. Los resultados muestran que cuando los contextos de los problemas son familiares para los estudiantes, las analogías superficiales pueden ocultar las diferencias estructurales. Sin embargo, cuando los contextos de los problemas son no-familiares para los estudiantes, el único efecto significativo procede de la igualdad/diferencia estructural. El efecto global de la familiaridad de los problemas es una reducción sistemática del éxito en la transferencia en problemas no familiares, sea cual sea la relación entre problema ‘ejemplo’ y problema ‘propuesto'.

En este trabajo se analiza la influencia del nivel académico, de los estudios cursados, de la estructura y contexto del problema, de la captación de la estructura y del uso de analogías, en la resolución de problemas. Se ha utilizado un diseño factorial con un factor intra-sujetos y varios factores entre-sujetos, que se han seleccionado en función de la hipótesis a contrastar. Se ha administrado a 181 estudiantes de secundaria dos tipos de cuadernillos que contienen dos problemas y preguntas sobre la captación de la estructura y uso de analogías. Los resultados de pruebas estadísticas no paramétricas muestran que: a) El nivel académico y el tipo de estudios cursados son variables cruciales en la resolución de problemas; b) La captación de la estructura influye decisivamente para resolver los problemas, pero no el uso de analogías; y c) Los estudiantes resuelven significativamente mejor los problemas de estructura sencilla y contexto familiar.

Resumen: En este trabajo se introduce el concepto de transferencia en el aprendizaje, se clasifican en sus diferentes tipos y se discute su importancia en la resolución de problemas de ciencias y matemáticas. Además se discute el papel de los procesos de transferencia y cómo se pueden mejorar en la enseñanza de las ciencias. A partir de todo ello, se recomiendan algunas medidas instruccionales que pueden ser aplicadas en el aula de ciencias. Palabras clave: transferencia, resolución de problemas, enseñanza y aprendizaje de las ciencias.

The vibrational properties of yttrium orthovanadate (YVO 4 ) single crystals, with tetragonal zircon structure, have been investigated by means of polarized micro-Raman spectroscopy and ab initio calculations. Raman spectra were taken at different polarizations and orientations carefully set by the use of a micromanipulator, so that all of the twelve Raman-active modes, expected on the basis of the group theory, were selected in turn and definitively assigned in wave number and symmetry. In particular the E g (4) mode, assigned incorrectly in previous literature, has been observed at 387 cm -1 . Moreover, the very weak E g (1) mode, peaked at about 137 cm -1 , was clearly observed only under some excitation wavelengths, and its peculiar Raman excitation profile was measured within a wide region of the visible. Finally, ab initio calculations based on density-functional theory have been performed in order to determine both Raman and infrared vibrational modes and to corroborate the experimental results. The rather good agreement between computational and experimental frequencies is slightly better than in previous computational works and supports our experimental symmetry assignments.

La communication de la science a une importance cruciale : diffusion des connaissances, régulation de la concurrence, etc. Elle est, de nos jours, influencée par diverses exigences institutionnelles et sociales dont l’évaluation de la recherche qui détermine de nombreux avantages : accès aux financements, reconnaissance positive, etc. Face à la double injonction – de prescriptions externes et d’une autorégulation au sein du champ scientifique - le chercheur adopte des stratégies variées allant de la conformité à la déviance, pour atteindre leurs objectifs personnels et professionnels. Ces dynamiques soulèvent des questions sur leur comportement et les facteurs guidant leurs choix que nous essayons de comprendre à travers cette étude, en examinant le rôle de la compétence perçue. La théorie du comportement planifié (TCP) est utilisée pour étudier la prévisibilité et la compréhension du comportement humain, en se concentrant sur l’intention, l’attitude, les normes sociales et la perception du contrôle. L’impact de cette dernière a été évalué dans une enquête auprès de 100 chercheurs. Les résultats montrent que la maîtrise de la publication scientifique varie, avec une confiance élevée dans les collaborations nationales et la publication dans des revues évaluées par les pairs, mais une maîtrise moindre dans la publication en anglais et l’utilisation des médias numériques. L’analyse par régression révèle une corrélation modérée mais significative entre le contrôle perçu et le comportement, suggérant que le renforcement de la perception de contrôle peut améliorer les comportements de communication scientifique. La formation et le développement des compétences en communication sont essentiels pour accroître la productivité scientifique.

El objetivo de este trabajo fue determinar el efecto que las similitudes de objeto tienen sobre las evaluaciones de calidad de una analogía. Los participantes divididos en dos grupos puntuaron en qué medida consideraban que ciertos pares de hechos eran análogos. Mientras que al primer grupo se les resaltó la relación implicada en las situaciones a comparar, al segundo se les enmarcó dicha comparación en una categoría relacional de esquema. Las evaluaciones de calidad del primer grupo fueron mayores cuando las situaciones comparadas involucraban objetos taxonómicamente similares, efecto que no fue hallado en el segundo grupo. En este grupo, lo que afectó la evaluación de las analogías fueron las similitudes de objeto relacionadas con una dimensión de la categoría esquemática que enmarcaba la comparación. Los resultados se interpretan desde un enfoque alternativo sobre el razonamiento analógico el enfoque de la asignación categorial. Se discuten implicaciones para este campo disciplin...

Experimental studies on analogical re- trieval have shown that interdomain retrieval is less frequent than intradomain retrieval. Using a production paradigm, Blanchette and Dunbar (2000) obtained opposite results. Dunbar (2001) hypothesized that when analogs are encoded in natural settings, retrieval is not constrained by superficial similarity. The study reported here complemented the production paradigm with two additional controls: 1) a survey of natu- rally encoded sources available in long-term memory, and 2) a measure of analogical re- trieval that was less vulnerable to report bias. Comparison between available and retrieved sources demonstrated that retrieval under a production paradigm—just as retrieval under a reception paradigm—is strongly constrained by superficial similarity.

The fast developing field of molecule-based magnets involving organic and coordination chemistry provides the physicist with a multitude of novel compounds of unprecedented structure. The magnetic structure of Cu 4 ͑tetren͓͒W͑CN͒ 8 ͔ 4 ͑1͒ was shown to consist of weakly coupled double layers. By contrast, in the structurally similar compound Cu 2+x Cu 4 ͓W͑CN͒ 8 ͔ 4 ͑2͒ the free spaces between the double layers are filled with paramagnetic copper͑II͒ ions leading to a unique magnetic network. Both compounds exhibit the transition to a magnetically ordered phase at T c Ϸ 33 K and T c Ϸ 40 K, respectively. The critical behavior of 1 and 2 is investigated using complementary methods: ac magnetometry, relaxation calorimetry, and muon spin-rotation spectroscopy. Apart from ␣, ␤, and ␥, critical exponents and Ј describing the combined scaling of excess entropy and order parameter are determined for both compounds. This type of scaling is verified for 1, the system revealing the signatures of the Berezinskii-Kosterlitz-Thouless transition. For 2 their values imply that the system is close to the universality class of the three-dimensional Heisenberg model. The relatively small value of exponent ␥ = 1.05 for 2 indicates the presence of noncollinearity in the spin arrangement. Exponents and Ј for 2 are also found consistent with noncollinear models. The shift of the heat-capacity anomaly toward higher temperatures with increasing applied field indicates the presence of ferromagnetic interactions in 2.

was rapidly removed by rotary evaporator from a solution of about 1 mg of 33 in ether, and the appropriate solvent was immediately added. The solution was then p l a d in an NMFt tube and sealed. The NMR tube was placed in a constant temperature bath at 25.0 "C. At periodic time intervals, the tube was analyzed by 'gF N M R (probe maintained at 25 OC). Depending on the solvent, the signal due to the CFBCOPH product appears 1.e1.5 ppm upfield from that of the covalent trifluoroacetate. Rates of solvolyses of trifluoroacetate 43 in HOAc and (C-F3)&HOH were determined by UV spectroscopy at 290 nm.

Bioinformatics is an interdisciplinary field of information technology for understanding biological data from genome to protein. It includes a combination of fields of science, computer science, statistics, mathematics, and engineering to analyze, interpret and derive biological data. This chapter describes how to use Bioinformatics to identify pathogen virulence factor peptide sequence similarities in human nerve tissue proteins and for evaluation as antibody engineering target peptides.

Organic fluoronium ions can be described as positively charged molecules in which the most electronegative and least polarizable element fluorine engages in two partially covalent bonding interactions to two carbon centers. While recent solvolysis experiments and NMR spectroscopic studies on a metastable [C–F–C]+fluoronium ion strongly support the divalent fluoronium structure over the alternative rapidly equilibrating classical carbocation, the model system has, to date, eluded crystallographic analysis to confirm this phenomenon in the solid state. Herein, we report the single crystal structure of a symmetrical [C–F–C]+fluoronium cation. Besides its synthesis and crystallographic characterization as the [Sb2F11]−salt, vibrational spectra are discussed and a detailed analysis concerning the nature of the bonding situation in this fluoronium ion and its heavier halonium homologues is performed, which provides detailed insights on this molecular structure.

The growing demand for accurate geospatial analysis in sectors such as climate monitoring, precision agriculture, urban
infrastructure planning, and disaster response has intensified the need for high-resolution satellite imagery. However, practical
limitations such as sensor hardware constraints, atmospheric interference, and limited bandwidth during data transmission often
result in low-resolution or visually degraded images. These artifacts can hinder decision-making processes and reduce the
effectiveness of downstream tasks like object detection, segmentation, and classification.
In response to these challenges, this study proposes a deep learning-based image enhancement framework using a Convolutional
Neural Network (CNN)-driven Generative Adversarial Network (GAN). The system is composed of a generator that learns to
transform blurry, low-resolution satellite images into sharper, more detailed representations, and a discriminator that encourages
the generator to produce outputs indistinguishable from real high-resolution imagery. Unlike conventional super-resolution
techniques based on interpolation or overly complex modelslike ESRGAN, the proposed architecture leverages a streamlined CNN
design optimized for computational efficiency and practical usability.
The training process utilizes paired datasets of low- and high-resolution satellite images, with preprocessing steps that normalize
image input and unify spatial dimensions. The model was trained using binary crossentropy loss and evaluated based on
perceptual quality and visual accuracy. A dedicated inference pipeline allows real-time enhancement of user-provided images via
command-line input, saving the improved result to an output directory for easy access. Experimental results confirm the model’s
capacity to recover fine details, sharpen structures, and improve image interpretability, even in noisy or blurred input conditions.
This research highlights the potential of lightweight CNN-GAN systems as accessible, deployable solutions for enhancing
satellite imagery in low-resource environments, field operations, or educational platforms. The approach bridges the gap between
academic advancement and practical applicability in Earth observation domains.

Capistruin, a ribosomally synthesized post-translationally modified peptide produced by Burkholderia thailandensis E264, efficiently inhibits growth of Burkholderia and closely related Pseudomonas strains. The functional target of capistruin is unknown. Capistruin is a threadedlasso peptide (lariat peptide), comprising an N-terminal 9-amino-acid ring followed by a 10amino-acid C-terminal tail that is threaded through the ring. The structure of capistruin is similar to that of microcin J25 (MccJ25), a threaded-lasso antibacterial peptide that is produced by some strains of Escherichia coli and targets DNA-dependent RNA polymerase (RNAP). Here, we show that capustruin, like MccJ25, inhibits wild-type E. coli RNAP but not mutant, MccJ25-resistant, E. coli RNAP. We show further that an E. coli strain resistant to MccJ25 due to a mutation in an RNAP subunit gene exhibits resistance to capistruin. The results indicate that the structural similarity of capistruin and MccJ25 reflects functional similarity and suggest that the functional target of capistruin, and possibly other threaded-lasso peptides, is bacterial RNAP.

The always increasing complexity of digital system is overcome in design flows based on Transaction Level Modeling (TLM) by designing and verifying the system at different abstraction levels. The design implementation starts from a TLM high-level description and, following a topdown approach, it is refined towards a corresponding RTL model. However, the bottom-up approach is also adopted in the design flow when already existing RTL IPs are abstracted to be reused into the TLM system. In this context, proving the equivalence between a model and its refined or abstracted version is still an open problem. In fact, traditional equivalence definitions and formal equivalence checking methodologies presented in the literature cannot be applied due to the very different internal characteristics of the models, including structure organization and timing. Targeting this topic, the paper presents a formal definition of equivalence based on events, and then, it shows how such a definition can be used for proving the equivalence in the RTL vs. TLM context, without requiring timing or structural similarities between the modules to be compared. Finally, the paper presents a practical use of the proposed theory, by proving the correctness of a methodology that automatically abstracts RTL IPs towards TLM implementations.

The Neogene environment and paleovegetation of today's semi-arid and arid Central Asia remain elusive. Little is known about the effect of paleoclimatic change on the distribution and ecological response mechanisms of aquatic plants, especially on the Tibetan Plateau. Here, we report a new species of Nelumbo Adanson, including leaves, receptacles, and fruits, namely Nelumbo delinghaensis sp. nov., from the Upper Youshashan Formation of the upper Middle Miocene in the northern Qaidam Basin on the Tibetan Plateau. The new species comprises centrally peltate leaves with 12-15 actinodromous primary veins and a receptacle embedded with ca. 15-30 fruits, with an unlobed central disc. Megafossils of lotus from northwest China broaden the geographical and stratigraphic ranges of Nelumbo. Our findings suggest that a large freshwater lake body surrounded by temperate forests and grassland developed in the Qaidam Basin during the late Middle Miocene, in sharp contrast to the present desert vegetation. The climate used to be sufficiently warm and moist enough to support a forest-steppe ecosystem with abundant freshwater bodies.

The clam Scapharca inaequivalvis possesses two cooperative oxygen binding hemoglobins in its red cells: a homodimeric HbI and a heterotetrameric A2B2 HbII. Each AB dimeric half of HbII is assembled very similarly to that of the well studied HbI. This study presents crystal structures of HbII along with oxygen binding data both in the crystalline state and in wet nanoporous silica gels. Despite very similar ligand-linked structural transitions observed in HbI and HbII crystals, HbII in the crystal or encapsulated in silica gels apparently exhibits minimal cooperativity in oxygen binding, in contrast with the full cooperativity exhibited by HbI crystals. However, oxygen binding curves in the crystal indicate the presence of a significant functional inequivalence of A and B chains. When this inequivalence is taken into account, both crystal and R state gel functional data are consistent with the conservation of a tertiary contribution to cooperative oxygen binding, quantitatively similar to that measured for HbI, and are in keeping with the structural information. Furthermore, our results indicate that to fully express the cooperative ligand binding, HbII requires quaternary transitions hampered by crystal lattice and gel encapsulation, revealing greater complexity in cooperative function than the direct communication across a dimeric interface observed in HbI.

Hydroacylation is a relatively new and little explored process which is highly atom economic and potentially an attractive process. Intramolecular systems have become valuable tools for the formation of 5-membered rings with enantioselective versions now known. The range of substrates for other ring sizes and in particular intermolecular systems is still very limited and often high temperatures and pressures are needed for effective reactions. Recently a large amount of work has been carried out to extend the range of substrates and improve the conditions needed for reaction. Many methods of reducing the problem of competitive decarbonylation have been explored and new systems using both additives and chelation strategies have led to the formation of acyclic ketone products. The range of substrates able to react with aldehydes has been extended to include alkynes leading to useful enone products. Despite these advances there is still no general method for the hydroacylation of aliphatic aldehydes. In this thesis some background into hydroacylation and the recent developments will be outlined. It will then discuss the development of a range of aldehydes with p-sulfur atoms, acting as chelating substrates, which can efficiently react with a range of alkenes, alkynes and allenes. An improvement to the catalyst system will be reported along with some evidence as to why this new system is beneficial. Lastly the first enantioselective intermolecular hydroacylation reaction will be explored using allenes as substrates. Firstly a big thank you to Mike Willis for his unending enthusiasm for the project and all his ideas and help. To Gordon Currie an equal thank you for making me so welcome on placement and putting up with all the smelly chemicals I brought with me. Also thank you to 'Team Rhodium' especially Rob Woodward and James Osborne who were always ready with ideas when mine were running out. I am also grateful to Andy Weller and Gemma Moxham for their work on the inorganic side of the catalyst project. Also thank you to the EPSRC Mass Spectrometry service for all their work, and the technical staff at the University of Bath. A huge thank you to all the members of the Willis group past and present for making it a fun three years especially those in Lab 0.26 for putting up with my endless singing

One of the fundamental insights of quantum mechanics is that complete knowledge of the state of a quantum system is not possible. Such incomplete knowledge of a physical system is the norm rather than the exception. This is becoming increasingly apparent as we apply scientific methods to increasingly complex situations. Empirically intensive disciplines in the biological, human, and geosciences all operate in situations where valid conclusions must be drawn, but deductive completeness is impossible. This paper argues that such situations are emerging examples of Open World Science. In this paradigm, scientific models are known to be acting with incomplete information. Open World models acknowledge their incompleteness, and respond positively when new information becomes available. Many methods for creating Open World models have been explored analytically in quantitative disciplines such as statistics, and the increasingly mature area of machine learning. This paper examines the role of quantum theory and quantum logic in the underpinnings of Open World models, examining the importance of structural features of such as noncommutativity, degrees of similarity, induction, and the impact of observation. Quantum mechanics is not a problem around the edges of classical theory, but is rather a secure bridgehead in the world of science to come.

Evolution is a slow but sure process of perfecting design to give a life-form a natural advantage in a competitive environment. The resulting complexity and performance are so sophisticated that, by and large, they are yet to be matched by man-made devices. They offer a vast array of design inspirations. The lessons from swimming and flying animals that are useful to fluids engineering devices are considered. The science and engineering of this subject—termed “biorobotics” here—are reviewed. The subject, being of dynamic objects, spans fluid dynamics, materials, and control, as well as their integration. The emphasis is on understanding the underlying science and design principles and applying them to transition to human usefulness rather than to conduct any biomimicry. First, the gaps between nature and man-made devices in terms of fluids engineering characteristics are quantitatively defined. To bridge these gaps, we then identify the underlying science principles in the productio...

A menopause-induced estrogen deficiency might increase body-fat accumulation, insulin resistance, and abnormal blood sugar and lipids. Thus, postmenopausal women have a high risk of cardiovascular diseases. Some studies indicated that soy can improve the syndrome of menopause, and whole-grain foods can reduce blood cholesterol concentrations. In the present study, under a 1200-kcal diet, overweight postmenopausal women ingested soybean/brown rice (SBR) as their grains for lunch for 12 weeks, and the effects on the anthropometric profile, body composition, blood profile, and plasma isoflavone levels were assessed. After 12 week of SBR intake, dietary fiber intake (21.5 ± 6.7 g) was higher than that of the control group. Body weight (BW), waist circumference (WC), hip circumference (HC), and the waist-hip ratio (WHR) had decreased in both groups. The body-fat percentage and android-fat percentage had also decreased in both groups. Blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) did not change during the intervention period. In the SBR and control groups, serum triglycerides (TGs) decreased, and high-density lipoprotein cholesterol (HDL-C) rose. In contrast, serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) had decreased in the SBR group at 12 weeks compared with week 0. Diastolic blood pressure (DBP) significantly decreased in the SBR group. Changes in dietary fiber and soy protein intake were significantly negatively correlated with the body-fat percentage and gynoid-fat percentage changes. In conclusion, under energy restriction, SBR intake can reduce serum TC, LDL-C, and DBP in overweight postmenopausal women.

Background Thyroid storm is an endocrine emergency and life-threatening condition discovered in 1926. There is no specific laboratory parameter that can differentiate or distinguish between thyroid storm and primary hyperthyroidism. Diagnosis is made on a clinical scoring system, including the Burch–Wartofsky point scale and Japanese Thyroid Association scoring system. The management is early diagnosis, immediate initiation of anti-thyroid medications, intensive care monitoring, and prevention of multiorgan failure. Case presentation A 30-year-old Pakistani female presented with complaint of headache, vomiting, and generalized weakness for 3 weeks. She had an episode of seizure-like activity at home, and so was rushed to the emergency department. A detailed thyroid examination revealed a soft, nontender gland with no enlargement or bruit and no exophthalmos. Her thyroid-stimulating hormone was extremely low, with high free triiodothyronine and thyroxine. Thyroglobulin was 425 ng/ml ...

The UL14 protein of herpes simplex virus type 1 (HSV-1) is highly conserved in herpesvirus family. However, its exact function during the HSV-1 replication cycle is little known. In the present study, a high throughput yeast twohybrid system was employed to screen the cellular factors interacting with UL14, and Wve target candidates were yielded: (1) TSC22 domain family protein 3 (TSC22D3); (2) Mediator of RNA polymerase II transcription subunit 8 isoform 1(MED8); (3) Runt-related transcription factor 3 (RUNX3); (4) Arrestin beta-2 (ARRB2); (5) Cereblon (CRBN). Indirect immunoXuorescent assay showed that both TSC22D3 and MED8 co-localized with UL14. Co-immunoprecipitation assay demonstrated that UL14 could be immunoprecipitated by TSC22D3, suggesting that UL14 interacted with TSC22D3 under physiological condition. In summary, this study opened up new avenues toward delineating the function and physiological signiWcance of UL14 during the HSV-1 replication cycle.

Parotid Secretory Protein (PSP) (C20orf70) is a salivary protein of unknown function. The protein belongs to the palate, lung and nasal epithelium clone (PLUNC) family of mucosal secretory proteins that are predicted to be structurally similar to lipid-binding and host defense proteins including bactericidal/permeability-increasing protein and lipopolysaccharide-binding protein. However, the PLUNC proteins exhibit significant sequence variation and different biological functions have been proposed for different family members. This study tested the functional implications of the proposed similarity of PSP to the acute phase protein Lipopolysaccharide-Binding Protein (LBP). PSP was identified in human saliva and was soluble in 75% ethanol, as shown for other PLUNC proteins. PSP binds lipopolysaccharide and can be eluted by non-ionic detergent, but not by urea or high salt. A synthetic PSP peptide, GL13NH2, which corresponds to a lipopolysaccharide-inhibiting peptide from LBP, inhibited the binding of lipopolysaccharide to both PSP and lipopolysaccharide-binding protein. Peptides from other regions of PSP and the control peptide polymyxin B showed no effect on the binding of PSP to lipopolysaccharide. GL13NH2 also inhibited lipopolysaccharide-stimulated secretion of tumor necrosis factor from macrophages. The other PSP peptides had no effect in this assay. PSP peptides had no or only minor effect on macrophage cell viability. These results indicate that PSP is a lipopolysaccharidebinding protein that is functionally related to LBP, as suggested by their predicted structural similarities.

This paper reports an ew approach to modifying the sound produced by aw ind instrument. The approach is based on modal active control, which enables adjustment of the damping and the frequencies of the different resonances of as ystem. As elf-sustained oscillating wind instrument can be modeled as an excitation source coupled to aresonator via anon-linear coupling. The aim of this study is to present simulations of modal active control applied to amodeled self-sustained oscillating wind instrument in order to modify its playing properties. The modeled instrument comprises acylindrical tube coupled to areed and incorporates acollocated loudspeaker and microphone; it can thus be considered to approximate as implified clarinet. Modifications of the pitch, the strength of the harmonics of the sound produced by the instrument, and of the oscillation threshold are obtained while controlling the first tworesonances of the modeled instrument.

Summary: A structured folding pathway, which is a time ordered sequence of folding events, plays an important role in the protein folding process and hence, in the conformational search. Pathway prediction, thus gives more insight into the folding process and is a valuable guiding tool to search the conformation space. In this paper, we propose a novel ‘unfolding’ approach to predict the folding pathway. We apply graph-based methods on a weighted secondary structure graph of a protein to predict the sequence of unfolding events. When viewed in reverse this yields the folding pathway. We demonstrate the success of our approach on several proteins whose pathway is partially known.

The mammalian Na + -H + exchanger isoform 1 (NHE1) is a plasma membrane protein that regulates intracellular pH in the myocardium by removing one intracellular hydrogen ion in exchange for one extracellular sodium ion. While NHE1 regulates intracellular pH, it is also involved in the damage that occurs to the myocardium with ischemia and reperfusion. Additionally, NHE1 levels are elevated in cardiac diseases such as hypertrophy, and NHE1 inhibition can reduce ischemia-reperfusion damage and prevent heart hypertrophy in animal models. Recently, it has been demonstrated that elevation of NHE1 levels occurs in several kinds of hearts disease. Surprisingly, the effect of elevation of these levels is varied, sometimes having beneficial and sometimes detrimental effects.

The sodium/proton exchanger isoform 1 (NHE1) is an ubiquitous plasma membrane protein that regulates intracellular pH by removing excess intracellular acid. NHE1 is important in heart disease and cancer, making it an attractive therapeutic target. Although much is known about the function of NHE1, current structural knowledge of NHE1 is limited to two conflicting topology models: a low-resolution molecular envelope from electron microscopy, and comparison with a crystal structure of a bacterial homologue, NhaA. Our laboratory has used high-resolution nuclear magnetic resonance (NMR) spectroscopy to investigate the structures of individual transmembrane helices of NHE1 — a divide and conquer approach to the study of this membrane protein. In this review, we discuss the structural and functional insights obtained from this approach in combination with functional data obtained from mutagenesis experiments on the protein. We also compare the known structure of NHE1 transmembrane segment...