bluuebunny/crossref_metadata_2025 huggingface dataset:
The late-antique eruption of Vesuvius in A.D. 472 and its impact from the Bay of Naples to Aeclanum
Authors: De Simone Girolamo Ferdinando , Russell Ben
Published: October 2019

The eruption of A.D. 79 has long dominated archaeological discourse on Vesuvius. Other eruptions, both earlier and later, have received less attention but are no less valuable from an archaeological point of view.1 Those eruptions deposited distinctive volcanic materials often easily identifiable in the stratigraphic record, thereby providing dated termini ante quos, which can in turn offer a snapshot of life around the volcano in different periods. The eruption of A.D. 79 provides just such an horizon for 1st-c. A.D. Campania; the earlier ‘Avellino pumices eruption’ does the same for the Bronze Age.2 By tracking the volcanic deposits that can be tied to such events, the situation on the ground prior to the eruptions can be examined, as can the ways in which communities and landscapes reacted to, and recovered from, them.
The Bouleuterion and its environs in Early Imperial Aphrodisias
Authors: Quatember Ursula
Published: October 2019

Research on the remains of the monumental city center of Aphrodisias has been ongoing for over a century. After an Italian mission began here in 1937,1 work was intensified from 1961 under the direction of K. T. Erim of New York University and has continued since 1990 under R. R. R. Smith.2 While many of the projects have yielded results for the High Imperial, late-antique and Byzantine periods, our knowledge of the Late Hellenistic and Early Imperial monuments outside the temple area remains scant. The layout of urban spaces such as the Agora or the “South Pool Complex” is owed to the Early Imperial period and mostly saw only minor changes.3 But while the general urban plan persisted, the Late Hellenistic and Early Imperial buildings were often replaced or remodelled as the urban space was transformed. This is particularly true for the area north of the Agora and south of the Temple of Aphrodite (fig. 1). This paper intends to re-assess our evidence for the function of this space in the Early Imperial period.
Permanent pacing post-Fontan is not associated with reduced long-term survival
Authors: Hall Sally J. , Cullington Damien , Thomson John D. R. , Bentham James R.
Published: October 2019

Background:

The Fontan procedure is the final stage of surgical palliation for a single-ventricle circulation. Significant complications are common including rhythm disturbance necessitating implantation of a permanent pacemaker. This has been widely considered a negative prognostic indicator.

Methods:

This single-centre, retrospective case control study involved all patients who underwent the Fontan procedure at the Leeds Congenital Heart Unit between 1990 and 2015 and have had regular follow-up in Yorkshire and Humber, United Kingdom. 167 Fontan patients were identified of which 2 were excluded for having a pre-procedure pacemaker. Of the remainder, 23 patients required a pacemaker. Outcomes were survival, early and late complications, need for further intervention and oxygen saturation in long-term follow-up.

Results:

There was no difference in survival (30-day survival pacemaker 92.6%, sinus rhythm 90.5%, p = 0.66, 1-year pacemaker 11.1%, sinus rhythm 10.1%, p = 1). The pacemaker group was more likely to have cerebral or renal complications in the first-year post-procedure (acute kidney injury: sinus rhythm 0.8%, pacemaker 19.1%, p = 0.002). No difference was observed in longer term complications including protein losing enteropathy (sinus rhythm 3.5%, pacemaker 0% p = 1). There was no difference in saturations between the two groups at follow-up. Paced patients were more likely to have required further intervention, with a higher incidence of cardiopulmonary bypass procedures (sinus rhythm 6.3%, pacemaker 35%, p < 0.001).

Conclusions:

Despite an increase in early complications and the need for further interventions, pacemaker requirement does not appear to affect long-term survival following the Fontan procedure.
Desirable difficulties while learning collocations in a second language: Conditions that induce L1 interference improve learning
Authors: Pulido Manuel F. , Dussias Paola E.
Published: October 2019

Learning conventional verb-noun combinations in a second language is known to be highly problematic when word choices differ from those in the native language. Grounded on recent proposals of desirable difficulties in vocabulary learning (Bjork & Kroll, 2015), we tested Spanish learners of English on a new paradigm that aimed to induce interference from the native language during lexical selection in a second language, as a way to train regulation of the dominant language. Results showed that recall rates were significantly higher in the group of learners that practiced in conditions of L1-interference. Faster RTs showed more efficient lexical selection in those same learners. Additionally, RTs revealed that the more successful learners in both groups incurred a cost in accessing verb choices congruent with the native language, a finding that is consistent with an inhibitory account.
Studying Identities with Experiments: Weighing the Risk of Posttreatment Bias Against Priming Effects
Authors: Klar Samara , Leeper Thomas , Robison Joshua
Published: October 2019

Scholars from across the social sciences argue that identities – such as race, ethnicity, and gender – are highly influential over individuals’ attitudes, actions, and evaluations. Experiments are becoming particularly integral for allowing identity scholars to explain how these social attachments shape our political behavior. In this letter, we draw attention to how identity scholars should approach the common practice of assessing moderators, measuring control variables, and detecting effect heterogeneity using covariates. Special care must be taken when deciding where to place measures of demographic covariates in identity-related experiments, as these cases pose unique challenges from how scholars traditionally approach experimental design. We argue in this letter that identity scholars, particularly those whose subjects identify as women or minorities, are often right to measure covariates of interest posttreatment.
Strong Neotectonic Block Rotations, Related to the Africa‐Eurasia Convergence in Northern Algeria: Paleomagnetic Evidence From the Mitidja Basin
Authors: Derder M.E.M. , Djellit H. , Henry B. , Maouche S. , Amenna M. , Bestandji R. , Ymel H. , Gharbi S. , Abtout A. , Dorbath C.
Published: October 2019

Significant tectonic clockwise rotations were evidenced in the Tell Atlas (Neogene Algerian Cheliff basin) by previous paleomagnetic studies. For northwestern Africa and in the context of the Africa‐Eurasia convergence, they provided a new argument validating a kinematic model, based on transpression with shortening accommodated by clockwise block rotations. To corroborate this deformation pattern at a larger scale, new paleomagnetic studies were performed on 349 cores in the Mitidja basin, of Mio‐Plio‐Quaternary age, in the Algerian Tell Atlas. This intramontaneous basin is structured by two regional major E‐W to WNW‐ESE dextral shear zones. Primary magnetization data were obtained in 43 out of the 49 sampled sites. This magnetization is carried by Ti‐poor titanomagnetite. Its direction shows that significant tectonic block rotations affected this basin since 16 Ma. Zones located between the E‐W and WNW‐ESE major structures are affected by coherent clockwise rotations (average magnitude of 48°) of large blocks, compartmented by presently associated sinistral NE‐SW faults. Along the shearing structures, smaller blocks, resulting from the fragmentation of the large blocks, show various rotations, many of which are of large magnitude. These rotations, similar to those highlighted previously in the Cheliff basin, are interpreted as resulting from bookshelf, consequence of the Africa‐Eurasia plates convergence in the Tell Atlas.
Deforestation Could Exacerbate Drought in the Amazon
Authors: Wheeling Kate
Published: October 2019

Researchers use high-resolution satellite images to parse the effects of land use changes on the energy balance between the rain forest and the atmosphere.
Evaluating a Regional Climate Model Simulation of Greenland Ice Sheet Snow and Firn Density for Improved Surface Mass Balance Estimates
Authors: Alexander P. M. , Tedesco M. , Koenig L. , Fettweis X.
Published: October 2019

Modeling vertical profiles of snow and firn density near the surface of the Greenland ice sheet (GrIS) is key to estimating GrIS mass balance, and by extension, global sea level change. To understand sources of error in simulated GrIS density, we compare GrIS density profiles from a leading regional climate model with coincident in situ measurements. We identify key contributors to model density and mass balance biases, including underestimated simulated fresh snow density (which leads to underestimation of density in the top 1 m of snow by ~10%). In areas undergoing frequent melting, positive density biases (of 7% in the top 1 m, and 10% between 1 and 10 m) are likely associated with errors in representing meltwater production, retention, and refreezing. The results highlight the importance of accurately capturing fresh snow density and meltwater processes in models used to estimate GrIS mass balance change.
East‐West Difference in the Ionospheric Response of the March 1989 Great Magnetic Storm Throughout East Asian Region
Authors: Zhao Biqiang , Yang Changjun , Cai Yihui , Jin Yuyan , Liang Yu , Ding Feng , Yue Xinan , Wan Weixing
Published: October 2019

The effects of the 13–14 March 1989 great magnetic storm on the East Asian ionosphere have been re‐investigated using ground‐based and satellite measurements as well as theoretical simulation. Within introduction of new data like the Chinese ionosondes and DMSP F8 and F9 and low‐equatorial magnetometer data, we are able to track the ionospheric response at both the bottomside and topside ionosphere from middle to low latitude to obtain an overall understanding of storm‐time ionospheric change. Through the comparative study of different longitude bands, we found that the East‐Asian ionosphere was characterized by a strong westward electron density gradient persisting over a day at both the bottomside and topside ionosphere at mid‐low latitudes during the main and recovery phases of the storm. This feature was not studied in the previous literature for this event at this area. We then examine the effect through a numerical simulation work from the Thermosphere Ionosphere Electrodynamics General Circulation Model under Apex and Dipole geomagnetic fields. It is seen that the model well reproduces the zonal gradients during this event under realistic geomagnetic field model. The conditions favor for this structure requires a hemispheric asymmetry response of storm thermosphere as well as background condition and also the storm development which requires further investigation. This study shows that even very close stations would manifest totally different storm behaviors during the superstorm event suggesting a great challenge in the space weather prediction.
On the Thermodynamic Preconditioning of Arctic Air Masses and the Role of Tropopause Polar Vortices for Cold Air Outbreaks From Fram Strait
Authors: Papritz Lukas , Rouges Emmanuel , Aemisegger Franziska , Wernli Heini
Published: October 2019

Fram Strait is a hot spot of Arctic cold air outbreaks (CAOs), which typically occur within the northerly flow associated with a strong low tropospheric east‐west pressure gradient between Svalbard and Greenland. This study investigates the processes in the inner Arctic that thermodynamically precondition air masses associated with CAOs south of Fram Strait where they lead to negative potential temperature anomalies often in excess of 15 K. Kinematic backward trajectories from Fram Strait are used to quantify the Arctic residence time and to analyze the thermodynamic evolution of these air masses. Additionally, the study explores the importance of cyclonic tropopause polar vortices (TPVs) for CAO formation south of Fram Strait. Results from a detailed case study and the climatological analysis of the 100 most intense CAOs from Fram Strait in the ERA‐Interim period reveal that (i) air masses that cause CAOs (CAO air masses) reside longer in the inner Arctic compared to those that do not (NO‐CAO air masses), and they originate from climatologically colder regions; (ii) the 10‐day accumulated cooling is very similar for CAO and NO‐CAO air masses indicating that the transport history and northerly origin of the air masses is more decisive for the formation of an intense negative temperature anomaly south of Fram Strait than an enhanced inner Arctic diabatic cooling; (iii) 40% (29%) of the top 40 (100) CAOs are related to a TPV in the vicinity of Fram Strait; (iv) TPVs confine anomalously cold air masses within their associated low tropospheric cold dome leading to enhanced accumulated radiative cooling.
Fill and Spill Hillslope Runoff Representation With a Richards Equation‐Based Model
Authors: Camporese M. , Paniconi C. , Putti M. , McDonnell J. J.
Published: October 2019

Integrated surface‐subsurface hydrological models (ISSHMs) are well established numerical tools to investigate water flow and contaminant transport processes over a wide range of spatial and temporal scales. However, their ability to correctly reproduce the response of hydrological systems to natural and anthropogenic forcing depends largely on the accuracy of model parameterization, including the level of detail in the representation of the bedrock. This latter is typically incorporated in some way via the bottom boundary of the model domain. Issues of bedrock topography, variable soil depth, and the resulting hillslope storage distribution representation in ISSHMs are vitally important but to date have received little attention. A standard treatment of the bottom boundary, especially in large catchment and continental scale applications, is to model it as a flat or inclined (e.g., parallel to the surface) impermeable base (sometimes with some simple leakage term). This approach does not allow the model to correctly reproduce bedrock‐controlled threshold responses such as the fill and spill process, as observed across many hillslope and catchment scale field studies. It is still unclear whether Richards equation‐based numerical models are actually able to generate such responses. Here we use a Richards equation‐based model (CATHY) to simulate internal transient subsurface stormflow dynamics observed at the well‐characterized Panola experimental hillslope in Georgia (USA). Soil and bedrock properties were calibrated starting from values reported in previous studies at the site. Our simulation results show that the model was able to reproduce threshold mechanisms, which in turn affected both the integrated and distributed hydrologic responses of the Panola hillslope. We then developed a set of virtual experiments with modified boundary conditions and base topography at the soil‐bedrock interface to explore the bedrock boundary control on transient groundwater flow patterns. Our results show that accurate representation of the lower boundary is crucial for ISSHM simulations of hillslope‐scale storm runoff and for connectivity of transient groundwater. We summarize our findings with the development of a new bedrock topographic wetness index that takes into account the unsaturated infiltration dynamics. The index is able to help represent the spatial variability of water table response over the bedrock surface compared to standard surface topography‐based indices. This new index may be useful in larger‐scale ISSHM applications where an exact bedrock topography representation is not feasible or possible.
Programmable broadband optical field spectral shaping with megahertz resolution using a simple frequency shifting loop
Authors: Schnébelin Côme , Azaña José , Guillet de Chatellus Hugues
Published: October 2019

Controlling the temporal and spectral properties of light is crucial for many applications. Current state-of-the-art techniques for shaping the time- and/or frequency-domain field of an optical waveform are based on amplitude and phase linear spectral filtering of a broadband laser pulse, e.g., using a programmable pulse shaper. A well-known fundamental constraint of these techniques is that they can be hardly scaled to offer a frequency resolution better than a few GHz. Here, we report an approach for user-defined optical field spectral shaping using a simple scheme based on a frequency shifting optical loop. The proposed scheme uses a single monochromatic (CW) laser, standard fiber-optics components and low-frequency electronics. This technique enables efficient synthesis of hundreds of optical spectral components, controlled both in phase and in amplitude, with a reconfigurable spectral resolution from a few MHz to several tens of MHz. The technique is applied to direct generation of arbitrary radio-frequency waveforms with time durations exceeding 100 ns and a detection-limited frequency bandwidth above 25 GHz.
Plasmodium Infection Induces Dyslipidemia and a Hepatic Lipogenic State in the Host through the Inhibition of the AMPK-ACC Pathway
Authors: Kluck George Eduardo Gabriel , Wendt Camila Hübner Costabile , Imperio Guinever Eustaquio do , Araujo Maria Fernanda Carvalho , Atella Tainá Correa , da Rocha Isabella , Miranda Kildare Rocha , Atella Georgia Correa
Published: October 2019

Malaria is a major parasitic disease of humans and is a health public problem that affects more than 100 countries. In 2017, it caused nearly half a million deaths out of 219 million infections. Malaria is caused by the protozoan parasites of the genus Plasmodium and is transmitted by female mosquitoes of the genus Anopheles. Once in the bloodstream, Plasmodium merozoites invade erythrocytes and proliferate until the cells lyses and release new parasites that invade other erythrocytes. Remarkably, they can manipulate the vertebrate host’s lipid metabolism pathways, since they cannot synthesize lipid classes that are essential for their development and replication. In this study, we show that mice infected with Plasmodium chabaudi present a completely different plasma profile from control mice, with marked hyperproteinemia, hypertriglyceridemia, hypoglycemia, and hypocholesterolemia. In addition, white adipose and hepatic tissue and analyses from infected animals revealed the accumulation of triacylglycerol in both tissues and free fatty acids and free cholesterol in the liver. Hepatic mRNA and protein expression of key enzymes and transcription factors involved in lipid metabolism were also altered by P. chabaudi infection, leading to a lipogenic state. The enzyme 5′ AMP-activated protein kinase (AMPK), a master regulator of cell energetic metabolism, was also modulated by the parasite, which reduced AMPK phosphorylation levels upon infection. Pretreatment with metformin for 21 days followed by infection with P. chabaudi was effective in preventing infection of mice and also lowered the hepatic accumulation of lipids while activating AMPK. Together, these results provide new and important information on the specific molecular mechanisms induced by the malaria parasite to regulate hepatic lipid metabolism in order to facilitate its development, proliferation, and lifespan in its vertebrate host.
Getting zeolite catalysts to play your tune: methyl carboxylate esters as switchable promoters for methanol dehydration to DME
Authors: Dennis-Smither Benjamin J. , Yang Zhiqiang , Buda Corneliu , Liu Xuebin , Sainty Neil , Tan Xingzhi , Sunley Glenn J.
Published: October 2019

Methyl carboxylate esters are found to reversibly fine tune the productivity of zeolite catalysts for making dimethyl ether from methanol.
A facile method to fabricate a porous Si/C composite with excellent cycling stability for use as the anode in a lithium ion battery
Authors: Zhang Xiaosong , Zhou Le , Zhang Yi , Yan Shunrong , Huang Junjie , Fang Zebo
Published: October 2019

Porous Si/C with excellent cycling stability has been fabricated by dehydrating Si/sucrose mixed powder with concentrated H2SO4.
Photo-controlled chirality transfer and FRET effects based on pseudo[3]rotaxane
Authors: Fu Hong-Guang , Zhang Heng-Yi , Zhang Hao-Yang , Liu Yu
Published: October 2019

A photochromic pseudo[3]rotaxane exhibited chirality transfer and FRET abilities was constructed. The transferred chiral signals could be controlled by UV light and heating, which will provide deep insight into developing chiral advanced materials.
A Pd-catalyzed asymmetric allylic substitution cascade via an asymmetric desymmetrization for the synthesis of bicyclic dihydrofurans
Authors: Xu Kai , Liu Hao , Hou Yilin , Shen Jiefeng , Liu Delong , Zhang Wanbin
Published: October 2019

Chiral bicyclic dihydrofurans bearing two vicinal carbon stereocenters have been synthesized in high yields and with up to 97% ee via a Pd-catalyzed asymmetric allylic substitution cascade and an asymmetric desymmetrization process.
EDA complex directed N-centred radical generation from nitrosoarenes: a divergent synthetic approach
Authors: Ghosh Soumen , Kumar Gautam , Naveen Naveen , Pradhan Suman , Chatterjee Indranil
Published: October 2019

N-Centred radicals generated via the formation of EDA complexes are added to electron-deficient allylsulfones to produce isoxazolidines, aziridines or β-amino acid derivatives.
Cooperative proton transportation based on the reversible single crystal–single crystal transformation in a highly water-stable Cu-MOF with its facile and scalable preparation
Authors: Zhang Jun , Ma Xiaofan , Kong Weili , Lu Guodong , Xuan Xiaopeng
Published: October 2019

A Cu-MOF with excellent acid–base stability in boiling water was constructed under mild conditions. This MOF was very suitable for scaled-up preparation, and exhibits distinct proton conductivity at temperatures above and below 75 °C.
Hierarchical MoS2/MoO3 nanotubes with excellent electrochemical performance: MoS2 bubbles on MoO3 nanotubes
Authors: Ma Ying , Jia Yulong , Lin Yinhe , Shi Wenbing
Published: October 2019

Hierarchical MoS2/MoO3 nanotubes consisting of bubble-like hollow MoS2 nanospheres and MoO3 nanotubes were fabricated with excellent electrochemical performance. The growth mechanism of hierarchical MoS2/MoO3 nanotubes was proposed.
Stacking interactions of borazine: important stacking at large horizontal displacements and dihydrogen bonding governed by electrostatic potentials of borazine
Authors: Malenov Dušan P. , Aladić Andrea J. , Zarić Snežana D.
Published: October 2019

A detailed scan of potential energy surfaces for borazine stacking revealed important interactions encountered in borazine crystal structures.
A theoretical insight into furfural conversion catalyzed on the Ni(111) surface
Authors: Ren Guoqing , Wang Guiru , Mei Hua , Xu Yan , Huang Ling
Published: October 2019

Furfural conversion catalyzed on the Ni(111) surface leads to diverse products, resulting from the strong interaction between the furanic ring and the surface.
Water-assisted stability of carbene: cyclic voltammetric investigation of 1-ethyl-3-methylimidazolium ethylsulfate ionic liquid
Authors: Jain Preeti , Chaudhari Vijay R. , Kumar Anil
Published: October 2019

In this work, we report electrochemical studies on imidazolium-based ionic liquids with an objective to explore the possibility of carbene formation in their dilute aqueous solutions.
Altered short chain fatty acid profiles induced by dietary fiber intervention regulate AMPK levels and intestinal homeostasis
Authors: Li Qian , Chen Haixia , Zhang Min , Wu Tao , Liu Rui
Published: October 2019

Butanoate-mediated maintenance of intestinal integrity and homeostasis and the AMPK-dependent co-regulated pathway.
pH-Controlled photocatalytic abatement of RhB by an FeWO4/BiPO4 p–n heterojunction under visible light irradiation
Authors: Mahendran Nithya , Udayakumar Sathya , Praveen Keerthi
Published: October 2019

The novel FeWO4/BiPO4 heterojunction generates an inner electric field to promote electron–hole separation efficiency and is a proficient photocatalyst.
Organocatalytic enantioselective conjugate addition of pyrazolin-5-ones to arylomethylidene malonates
Authors: Sharma Arun , Sharma Vivek , Chimni Swapandeep Singh
Published: October 2019

An efficient asymmetric organocatalytic conjugate addition reaction of pyrazolin-5-ones with arylomethylidene malonates has been successfully developed by employing bifunctional Cinchona derived thiourea organocatalyst.
Synthesis of dibenzo[a,d]cycloheptanoids via aryne insertion into 2-arylidene-1,3-indandiones
Authors: Payili Nagaraju , Rekula Santhosh Reddy , Aitha Anjaiah , Mutha V. V. S. R. N. Anji Karun , Gangu Naidu Challa , Yennam Satyanarayana
Published: October 2019

A cascade synthetic strategy for the direct synthesis of dibenzo[a,d]cycloheptanoids and dibenz[a,c]anthracene-9,14-dione derivatives from aryne precursors has been developed.
Aryldithiocarbamates as thiol alternatives in Cu-catalyzed C(aryl)–S coupling reactions using aryldiazonium tetrafluoroborate salts
Authors: Dutta Soumya , Saha Amit
Published: October 2019

Aryldithiocarbamates have been used as thiol substitutes in C(aryl)–S cross coupling reactions with aryldiazonium salts to produce unsymmetrical diaryl sulfides.
Encapsulation of the cytoskeleton: towards mimicking the mechanics of a cell
Authors: Bashirzadeh Yashar , Liu Allen P.
Published: October 2019

The cytoskeleton of a cell controls all the aspects of cell shape changes. Such conserved and effective control over the mechanics of the cell makes the cytoskeletal components great candidates for bottom-up synthetic biology studies.
Correction: One-step synthesis of a dual-emitting carbon dot-based ratiometric fluorescent probe for the visual assay of Pb2+ and PPi and development of a paper sensor
Authors: Gao Yifang , Jiao Yuan , Zhang Huilin , Lu Wenjing , Liu Yang , Han Hui , Gong Xiaojuan , Li Lei , Shuang Shaomin , Dong Chuan
Published: October 2019

Correction for ‘One-step synthesis of a dual-emitting carbon dot-based ratiometric fluorescent probe for the visual assay of Pb2+ and PPi and development of a paper sensor’ by Yifang Gao et al., J. Mater. Chem. B, 2019, 7, 5502–5509.
The growth of amyloid fibrils: rates and mechanisms
Authors: Buell Alexander K.
Published: October 2019

Amyloid fibrils are β-sheet-rich linear protein polymers that can be formed by a large variety of different proteins. These assemblies have received much interest in recent decades, due to their role in a range of human disorders. However, amyloid fibrils are also found in a functional context, whereby their structural, mechanical and thermodynamic properties are exploited by biological systems. Amyloid fibrils form through a nucleated polymerisation mechanism with secondary processes acting in many cases to amplify the number of fibrils. The filamentous nature of amyloid fibrils implies that the fibril growth rate is, by several orders of magnitude, the fastest step of the overall aggregation reaction. This article focusses specifically on in vitro experimental studies of the process of amyloid fibril growth, or elongation, and summarises the state of knowledge of its kinetics and mechanisms. This work attempts to provide the most comprehensive summary, to date, of the available experimental data on amyloid fibril elongation rate constants and the temperature and concentration dependence of amyloid fibril elongation rates. These data are compared with those from other types of protein polymers. This comparison with data from other polymerising proteins is interesting and relevant because many of the basic ideas and concepts discussed here were first introduced for non-amyloid protein polymers, most notably by the Japanese school of Oosawa and co-workers for cytoskeletal filaments.
The third coming: Thalidomide and a final goodbye
Authors: Raza Azra
Published: October 2019

The cyclical rise, fall and resurrection of thalidomide has become one of the most instructive stories in medicine, told most poignantly by Stephens and Brynner1 in their recent book. In the early 1950s, when pathogens were considered to be the primary causative agents of most human diseases, two chemists working for the pharmaceutical company Chemie Grunenthal heated the peptide pthalimidoglutaramide in an attempt to synthesize novel antibiotics. They obtained a compound with a three-ring structure, which they named thalidomide.
Cytoskeleton signalling: 7 November 2001
Authors: Machesky Laura , Burd Gary
Published: October 2019

Laura Machesky was invited by the University of Leicester to present a seminar at a meeting sponsored by the Biochemical Society in November. “Laura was involved in discovering actin-related proteins (Arps)”, says host Jim Norman introducing her achievements. “She also elucidated the key mechanism by which actin polymerization is controlled.”
Biomolecules in fossil remains: Multidisciplinary approach to endurance
Authors: Nielsen-Marsh Christina
Published: October 2019

Svante Pääbo, a leading pioneer in the study of ancient DNA, eloquently described the recovery of genetic information from the fossil record as a 21st Century form of genetic time travel1. The advent of PCR made possible the amplification of small amounts of DNA from fossil samples and allowed the direct study of phylogenetics from extinct organisms. Prior to this development, phylogenetic relationships determined by genetic variation relied mostly upon sequences from living organisms. The concept of time travel, via the analysis of ancient biomolecules, can be broadened to encompass numerous types of biomolecular information recovered from ancient bones. For example, palaeodiets and palaeoclimates can be reconstructed from stable isotopes of bone collagen, and estimations of age are obtained from amino acid racemization rates.
Teaching the scientists of tomorrow
Authors: Dallimore Liz
Published: October 2019

As part of its inquiry into Science Education for 14 –19-year-olds, the Commons Science and Technology Committee heard evidence jointly from the Institute of Biology, the Institute of Mathematics and its Applications, the Institute of Physics, the Royal Society and the Royal Society of Chemistry. All five also submitted written evidence, in which the general overview was that the science curriculum is too inflexible and the content is too overloaded. This leaves little room for creativity and diversity that is essential for the teaching of science.
Short-term academic contracts -- is anything being done?: Supporting Excellence in the Science Base
Authors: Withnall Mike
Published: October 2019

The Roberts Review of the Supply of Scientists and Engineers identified the lack of a clear career structure for university contract research staff, uncertain prospects and increasingly uncompetitive salaries among reasons why postgraduates are reluctant to start academic research careers. On the basis of this, the Commons Science and Technology Committee launched an inquiry in July into the implications of short-term contracts and whether initiatives like the Concordat and the Research Careers Initiative have improved the lives of contract research staff.
Teaching the scientists of tomorrow
Authors: Fink John B.
Published: October 2019

It is fitting that on the very day of the ‘Biochemists in pursuit of numeracy’ colloquium at Biochemical Society's Cardiff Meeting, a letter on the subject should appear in that morning's edition of The Times1. It described the following exchange:Writer: “Give me a kilogram of your best cheddar.” Clerk: “We are only allowed to sell in grams, sir.” Writer: “Just give me one thousand grams then!”
Metabolomics: Pandora's Box or Aladdin's Cave?
Authors: Brindle Kevin M.
Published: October 2019

Functional genomics, the elucidation of gene function from studies of the effects of gene modification on cellular phenotype, has prompted the development of massively parallel and increasingly comprehensive screening tools for assessing the expression of mRNAs (transcriptomics) and proteins (proteomics). For a more complete description of the effects of changes in genotype or physiological conditions on cellular phenotype, we also need to define the status of a third class of biomolecules in the cell, the small-molecule metabolites. Study of the latter has been termed metabolomics and the metabolite complement the metabolome.
Still some cause for concern: Biochemistry Graduate Employment Survey 2001
Authors: Withnall Mike
Published: October 2019

The proportion of graduates with First Class Honours going on to research degrees increased (from 52.3% to 55.8%), as did the proportion of PhD graduates starting postdoc positions increased (from 35.7% to 42.7%). Nevertheless, the proportions of First Class Honours graduates and of first degree graduates overall continuing biochemical training were still lower than their values in the 1990s. The high proportion (10.9%) with Class 2.2 Honours in the research pool suggests a lack of competition for PhD places. The proportions of first-degree and Master's graduates remaining in science for their first post (53.2% and 72.2%, respectively) were similar to the previous year, whereas that of PhD graduates increased (from 55.8% to 62.7%). Unemployment was low.
Traffic watch: Live-cell imaging
Authors: Stephens David J.
Published: October 2019

Microscopy has been at the core of cell biology research ever since the coining of the term ‘cell’ by Robert Hooke in the 17th Century1. For many years, it has been possible to gain insight into ‘steady-state’ cellular function from the analysis of fixed samples, but it is only relatively recently that imaging of living cells has become a widely used tool to support biochemical and electron microscopy studies. Membrane traffic research, which by its very nature is a highly dynamics process, has benefited hugely from the ability to image specific processes in living cells and tissues.
Haem-thiolate redox enzymes: cytochrome P450 BM3 versus nitric oxide synthase: Power versus control
Authors: Chapman Stephen K. , Daff Simon , Ost Tobias W.B.
Published: October 2019

More than one-third of all enzymes catalyse the oxidation or reduction of a substrate and are therefore classed as oxidoreductases or redox enzymes. The, often complex, redox chemistry involved here is made possible by surprisingly few redox-active cofactors. Of these, flavin nucleotides (FAD and FMN) and haem groups are arguably the most significant. The P450 cytochromes (P450s) and nitric oxide synthases (NOSs) represent a very large and immensely important group of enzymes, which utilize both of these cofactors.
Tissue engineering: Designing for health
Authors: Hardingham Tim
Published: October 2019

The tissue engineering that is now emerging in biomedical research groups is concerned with living tissues and how we can harness biological processes to achieve healing and repair, where it is otherwise failing. It aims to develop our scientific understanding of how living cells function, so that we can gain control and direct their activity to the promote the repair of damaged and diseased tissue1.
Unravelling Nature's Networks: From Microarray and Proteomic Analysis to Systems Biology: University of Sheffield, 21–22 July 2003
Authors: Monk Nick , Lawrence Neil
Published: October 2019

The robust and adaptable behaviours of cells and tissues depend on the operation of complex regulatory biochemical networks. The elucidation of the structure and functioning of such networks poses many daunting challenges. Recently developed experimental techniques, such as large-scale profiling of gene expression and protein interactions, provide unprecedented amounts of information on the molecular composition of cells. The size (and often variable quality) of the resulting data sets necessitates the use of sophisticated computational schemes for the analysis, mining and integration of the data. In all but the simplest cases, the complexity of the networks is such that it is impossible to provide an intuitive picture of the principles governing their dynamic behaviour without synthesizing the experimental data into a coherent mathematical model of the underlying system.
The Lambert Report: like the curate's egg: Supporting Excellence in the Science Base
Authors: Withnall Mike
Published: October 2019

The Lambert Report of the interaction between business and universities confirms what the Biochemical Society has been stating for several years in policy submissions to the government — that the major problem is a lack of business pull for knowledge transfer rather than of university push. The Report largely excludes the pharmaceutical and biotech industries from this criticism. It notes, however, that Britain is strong in basic research, but is less good at bringing ideas to market, and quotes the statistic that UK academic papers are cited by other researchers 53% more often than studies from Germany, but the latter makes 230% more patent applications. Sections of the Report dealing with how the situation might be improved illustrate some contradictions in existing policies.
Ricin: A potential agent for bioterrorism
Authors: Lord Mike , Phillips Gary , Griffiths Gareth
Published: October 2019

Ricin is a plant protein found in the seeds of Ricinus communis and is potently toxic to mammalian cells. The active component of ricin is an enzyme, and cytotoxicity results from the catalytic modification of ribosomes, rendering them unable to synthesize protein. Because of the ready availability of R. communis seeds, and the abundance and ease of production of ricin, this toxin is a potential agent for bioterrorism.
Protection against covert releases: Preparing for the worst
Authors: Shone Cliff
Published: October 2019

Providing an effective defence against biological attack is complicated by the large number of potential agents, which range from viruses that cause haemorrhagic fever to bacterial toxins, some of which are only rarely encountered in nature. Defence strategies must be equally diverse, and include such measures as enhanced epidemiological surveillance, vaccination, treatment with antimicrobial agents and passive administration of antibodies. Implementation of such strategies is by no means straightforward and a significant amount of research and development is still needed.
Education report: September 2003–August 2004
Authors: Mills Sheila
Published: October 2019

The last 12 months have been a period of change, exciting new ventures and consolidation of activities on the education front. The new Education Committee has demonstrated the value of its breadth of membership and support in the programme of work undertaken. The Society works closely with sister societies within the BioSciences Federation to promote the life sciences generally, and in addition organizes a full programme to cover biochemical education, from schools through to postdoctoral research and teaching, and engaging with the public.
Promiscuity in the Archaea: The enzymology of their metabolic pathways
Authors: Danson Michael J. , Hough David W.
Published: October 2019

The pathways of central metabolism provide the metabolic connections between the catabolic (degradative) and anabolic (biosynthetic) routes in all living organisms. In hyperthermophilic Archaea, we have discovered a promiscuous central metabolic pathway that catabolizes a variety of sugars using a single set of enzymes. This article explores the structural basis of this promiscuity in enzymes that have to maintain their integrity at temperatures approaching 100°C.
Copper and the prion protein: Function and dysfunction
Authors: Viles John H.
Published: October 2019

The prion protein (PrP) has the ability to infect a host, and that infectivity is conferred by its conformation. The concept of an infectious protein presents a fascinating subject for those interested in protein structure. Cu2+ binds to a region of PrP vital for prion propagation, suggesting that the misfolding and fibrillization of PrP may be profoundly influenced by the presence of Cu2+ ions. The normal function of the prion protein has yet to be established, but its affinity for Cu2+ also suggests a role in copper homoeostasis.
Closing the gap between lifestyle commentary and chemical realities
Authors: Brown Tracey
Published: October 2019

“Apparently all this detox stuff is a load of rubbish!”, remarked another parent as we huddled together in early January waiting for our children to finish school, picking apart our New Year's resolutions. “I heard a DJ talking about it this morning; your liver can get rid of a near-lethal dose of alcohol in a couple of days!”.
Intron splicing: A general two-metal mechanism for RNA and protein catalysts
Authors: Strobel Scott A.
Published: October 2019

I first met my Yale colleagues Joan Steitz and Tom Steitz while I was postdoctoral fellow at the University of Colorado working on the group I intron splicing mechanism with Thomas Cech. Cech's discovery of the RNA self-splicing group I intron in 1981 provided the first demonstration that not all enzymes are proteins. The Steitz's, famous for their work in pre-mRNA splicing and X-ray structure determination, respectively, spent a sabbatical leave in Colorado from 1992 to 1993, where they enjoyed the high quality of the RNAfocused science that was present there. It was a scientific bonus for me to have both of them attend the weekly Cech laboratory group meetings and to regularly bump into them in the lunchroom.
Glycobiology and medicine: High-throughput glycan analysis and disease markers
Authors: Dwek Pauline M. Rudd and Raymond A.
Published: October 2019

Oligosaccharides provide specific recognition epitopes that can initiate biological function, particularly when the sugars are attached to secreted or cell-surface glycoproteins. It is therefore essential that, in any given physiological state, glycan processing and the relative proportions of different glycoform populations are reproducible so that the sugars can perform their functions effectively and without error. In contrast with the direct template control exerted on protein expression by DNA, appropriate glycosylation processing depends on the integrated, optimal functioning of many cellular pathways.
Change all around: The political view
Authors: Starkey Phyllis
Published: October 2019

As a scientist, albeit one who has been out of active science for a decade, I am of course well aware of the dangers of arguing from the particular to the general, and anecdotal evidence based on a sample of one is clearly not statistically significant. But looking back on my own scientific career does highlight a number of factors that are often cited in studies of women and science.
Protein post-translational modifications: Introduction
Authors: Bannister Andrew J. , Crane-Robinson Colyn
Published: October 2019

Organisms exist in a continually changing environment: they are constantly bombarded and challenged with stimuli to which they must respond in order to survive. Such responses require three essential steps: detection/initiation, transmission and read-out. In practice, a cell detects a particular signal, such as the presence of a hormone or the appearance of a potentially damaging free radical, and activates a series of enzymes in a signalling cascade that ultimately determines the appropriate biological outcome. These responses are largely achieved via PTMs (post-translational modifications) of pre-existing proteins by specific enzymes. In this series of articles, experts in the relevant subject areas review our current understanding of the major PTMs and how they affect their target proteins.
Biochemistry – explaining life: A workshop for (AS Level) L6th Students
Authors: Timson David J.
Published: October 2019

We wished to run a workshop for L6th students (and others at an equivalent stage) in order to introduce them to biochemistry as a subject area. There were two main reasons for doing this: (i) although biochemistry forms part of the AS Biology and Chemistry syllabuses, it does not have an identity in its own right, and (ii) we have observed a misconception among some students in that age group that, in order to pursue a career in medical research, it is necessary to have a degree in medicine or pharmacy.
From the beginnings: How biochemistry has evolved as a discipline
Authors: Morange Michel
Published: October 2019

Biochemists see in the cell-free fermentation experiments of Eduard Buchner in 18971, the birth date of their discipline (also named biological chemistry), before the introduction of the word in the titles of journals and the names of learned societies2. These experiments tolled the death knell of the vitalistic claims that chemistry in organisms was different from organic chemistry in the laboratory. They opened the way to the elucidation of the central metabolic pathways.
Braving the dragons: How to nurture biochemist entrepreneurs
Authors: Crocker Glenn , Mugge Martijn
Published: October 2019

Series five of BBC TV's Dragons' Den has just finished, and anyone with a modicum of entrepreneurial spirit will have chanced a glance at the small screen to admire or admonish those who seek investment from the Dragons. TV entertainment it may be, but most weeks there are lessons to be learned from the experienced investors as they interrogate the hopeful and often hapless contestants. Never before has the making or breaking of business deals been made so accessible to the prime time viewer and raised so many questions about the nature of what constitutes a great investment.
The race to control aging and diseases: Sir2/SirT1 against Ras, TOR and Akt/S6K
Authors: Longo Valter D.
Published: October 2019

In Saccharomyces cerevisiae, the glucose/nutrient signalling Ras2 and Tor/Sch9 signal transduction pathways promote growth, reduce stress resistance and block entry into a survival mode that can cause an up to 10-fold lifespan extension. The down-regulation of similar pathways activated by the insulin/IGF (insulin-like growth factor)-1-like growth factors extends the lifespan of nematode worms up to 10-fold and, when combined with calorie restriction, doubles that of mice. This lifespan extension is mediated by the activation of transcription factors that regulate metabolic pathways as well as stress-resistance proteins such as antioxidant enzymes. Another family of enzymes whose activation is widely implicated in the regulation of aging is the Sir2/ SirT1 (sirtuin) deacetylase family. Although their overexpression/activation has modest lifespan extension effects in lower eukaryotes and does not appear to extend the lifespan of mice, their central role in the regulation of glucose and fat metabolism and of many other systems makes sirtuin-activating drugs candidates for the treatment and prevention of several diseases. Here I briefly review and compare the effect of sirtuins and glucose/growth factor signalling pathways in the regulation of stress resistance and aging.
The answer is elemental
Authors: Hare Dominic , Bishop David , Austin Christine , Doble Philip
Published: October 2019

Trace elements play a key role in a wide range of biological processes. A full understanding of those processes requires a knowledge not only of the genomics and proteomics of the organism, but also the distribution and concentration of trace elements. A new application of inductively coupled plasma mass spectrometry (ICP-MS) provides the capability to directly visualize trace elements in soft tissue, offering the promise of improved diagnosis and monitoring of disease.
Can parasites be good for you?: The cost and potential benefit of hookworm infection
Authors: Pritchard David
Published: October 2019

Is the human-infecting parasitic hookworm Necator americanus the ‘American murderer’ or a therapeutic agent? The following article describes current thinking around this interesting infection. At high infection intensities, the worm is undoubtedly pathogenic, and must be treated by de-worming or, in the future, by vaccination. Conversely, low doses of this immune-suppressive infection could be beneficial to the treatment of immunological diseases such as allergy and auto-immunity. The challenge currently facing scientists is to find a safe dose of sufficient intensity to provide benefit without causing distress to the patient. This will be an interesting immunological journey, and early indications suggest that therapeutic dosing regimes can be developed.