Historians should not only Bend over Old Books: an Interview with Professor Georg G. Iggers / Los historiadores no deberían inclinarse sólo sobre viejos libros. Entrevista con el profesor Georg G. Iggers

 En esta entrevista, el profesor Georg G. Iggers, uno de los principales expertos internacionales de la especialidad de la historia de la historiografía, hace un repaso por su carrera e ideas. Habla de su juventud, cuando tuvo que huir de la Alemania nazi con sus padres, de su identidad judía, de los primeros pasos de su educación y de sus estudios universitarios en los Estados Unidos, su interés por los saint-simonianos y sus primeros contactos con la historia intelectual europea, su compromiso con el movimiento contra la guerra de Vietnam, su formación e intereses filosóficos, sus diálogos con los autores postmodernistas, y su interés hacia la historia “global” de la historiografía.Palabras claveJudaísmo, historia de las ideas, derechos civiles, historia global de la historiografía. AbstractIn this interview, Professor Georg G. Iggers, one of the foremost international experts in the specialty of the history of historiography, provides an overview of his career and ideas. He talks about his youth when he had to flee Nazi Germany with his parents; his Jewish identity; the early years of his education and university studies in the US; his interest in the Saint-Simonians and his initial contacts with European intellectual history; his involvement in the movement against the Vietnam War; his philosophical training and interests; his conversations with post-modern authors; and his interest in a “global” history of historiography.Key WordsJudaism, history of ideas, civil rights, global history of historiography

Ice flow modelling of ice shelves and ice caps

Ice shelves and ice caps constitute a great proportion of the glacial ice mass that covers 10% of the global land surface and is vulnerable to climate change. Large scale ice flow models are widely used to investigate the mechanisms behind the observed physical processes and predict their future stability and variability under climate change. This thesis aims at providing general remarks on the application of ice flow models in studying glaciological problems through investigating the evolution of an Antarctic ice shelf under climate change and the mechanisms of fast ice flowing events (surges) in an Arctic ice cap. In addition discussions of the equivalence of two significantly different expressions for the rate factor in Glen’s flow are also provided. Off-line coupling between the Lambert Glacier-Amery Ice Shelf (LG-AIS) drainage system, East Antarctica, and the climate system by employing a hierarchy of models from general circulation models, through high resolution regional atmospheric and oceanic models, to a vertically integrated ice flow model has been carried out. The adaptive mesh refinement technique is specifically implemented for resolving the problem concerning grounding line migration. Sensitivity tests investigating the importance of various parameters and boundary conditions are carried out in ice flow models with different approximations for Austfonna Ice-cap, Svalbard to investigate the surge event in one of its basins, Basin 3. Inverse modelling of basal friction coefficient is specifically implemented. A continuum to discrete multi-model approach is implemented for simulations of Basin 3. LG-AIS drainage system will be rather stable in the face of future warming over 21st and 22nd centuries. Although the ice shelf thins in most of the simulations there is little grounding line retreat. The change of ice thickness and velocity in the ice shelf is mainly influenced by the basal melt distribution. And the Lambert, Fisher and Mellor glaciers are most sensitive to thinning of the ice shelf south of Clemence Massif. The sea level rise contribution of LG-AIS is modest as the increased accumulation computed by the atmosphere models outweighs ice stream acceleration. Using a temporally fixed basal friction field obtained through inverse modelling is insufficient to simulate the future changes of the fast flowing surging glacier in Basin 3. And the evolution of basal friction patterns, and in turn basal processes are among the most important factors during the surge in Basin 3. A system of processes and feedback involving till deformation and basal hydrology is more likely to explain both the seasonal accelerations and the ongoing inter-annual speed-up more than a hard-bed mechanism. The continuum to discrete multi-model approach provides the possible locations of the crevasses that can potentially cut through the full length of the ice and deliver surface melt water down to the bed. The calculated basal water flow paths according to hydraulic potential indicate that the summer speed up events and the initiation of the acceleration in the southern part of the basin can be explained by either a direct enhancement to the ice flow through basal lubrication or a lagged-in-time mechanism through the outflow of accumulated water in the over-deepening area. Keywords: ice flow modelling, climate change, sea level rise, future projection, basal sliding, basal hydrology, surface melt, surging glacier, Lambert Glacier-Amery Ice Shelf, Austfonna Ice-cap, Antarctic, SvalbardKymmentä prosenttia maapallon maapinta-alasta peittää tiivistyneen jään kerroksia, jotka eivät sula pois kesän aikana ja jotka virtaavat oman painonsa alla. Jäähyllyt ja lakijäätiköt muodostavat suuren osan näistä jäätiköiksi kutsutuista jäämassiiveista. Näiden tutkimus hyödyntää tietokoneohjelmia, jotka matemaattisten yhtälöiden mukaan kuvaavat jään fysikaalisia prosesseja. Tällaisten numeeristen mallien avulla voimme ymmärtää, kuinka jäätiköt käyttäytyvät sekä nykyisessä ympäristössään että tulevaisuudessa ilmaston muuttuessa. Tässä väitöskirjassa käytän numeerisia malleja tutkiakseni, kuinka Etelämantereen jääpeite muuttuu seuraavien 100–200 vuoden aikana ilmastonmuutoksen vaikutuksesta sekä sitä, mikä laukaisee arktisen lakijäätikön muutoksen pitkästä rauhallisen virtauksen kaudesta verrattain lyhytaikaiseen, nopeaan virtaustapahtumaan. Lisäksi tarkastelen kysymystä miksi kahta laajalti käytössä olevaa eriävää muotoilua voidaan käyttää Glenin virtauslain kertoimesta (laki kuvaa jännityksen ja venymän suhdetta). Näiden tutkimusten avulla aikomuksenani on parantaa numeeristen mallien käyttöä jäätikkötutkimuksessa. Lambertin jäätikkö – Ameryn jäähylly (Lambert Glacier – Amery Ice Shelf, LG-AIS) valumajärjestelmä on yksi Itä-Antarktikan suurimmista. Ameryn jäähylly käy tällä hetkellä läpi vakaata ja luonnollista virtauskautta poikien jäävuoria mereen. Ilmastonmuutoksen myötä tämän valumajärjestelmän kohtalo seuraavan 100–200 vuoden aikana on kuitenkin avoin. Numeerista jään virtauksen mallia käytetään tässä työssä valumajärjestelmän muutosten tutkimiseen. Malli ottaa huomioon lumen kertymisen ja jäätikön pohjan sulamisen ilmastomalleista saatujen pakotteiden puitteissa. Tulokset osoittavat, että vaikka Ameryn jäähylly saattaa sulaa merkittävästi, LG-AIS virtausjärjestelmä pysyy vakaana myös 2100- ja 2200-luvuilla. Myös jäämassan nettotuotto valtamereen tulee olemaan melko vähäistä, joten sen vaikutus merenpinnan korkeuteen on pieni. Austfonnan Basin 3 lakijäätikön Huippuvuorilla uskotaan olevan ajoittaisen nopean virtauksen tyypin jäätikkö. Siinä vallitsee pitkäaikainen, hidas virtaus, jonka lyhyet, hyvin nopean virtauksen kaudet väliin katkaisevat. Kahta eri jäävirtausmallia käyttäen olen yrittänyt selittää niitä mekanismeja, jotka vaikuttivat vuonna 2011 alkaneeseen liikkeen nopeutumiseen. Tulokset osoittavat, että jäätikön pohjan liike vaikuttaa voimakkaasti kiihtyvään virtaukseen ja hyvin todennäköisesti myös jäätikön alla sijaitsevan sedimentin muovautuminen ja jäätikön alaiseen hydrologiaan. Sitten vuoden 2008 tämän jäätikön virtaus on kiihtynyt portaittaisesti jokaisen kesän sulamiskauden päätyttyä. Diskreetti partikkelimalli, joka jakaa jäätikön pieniin partikkeleihin ja kykenee tuottamaan syviä halkeamia jäätikköön, käytetään portaittaisen kiihtymisen selittämiseen. Tämä malli tuottaa sellaisten halkeamien sijainnit, jotka voisivat toimia virtauskanavina sulamisvedelle ja viedä tätä jäätikön pohjan hydrologiseen järjestelmään. Mahdollisiksi selityksiksi portaittaiselle kiihtymiselle voidaan antaa joko sulamisveden liukastava vaikutus jäätikön pohjassa tai sitten jäätikön pohjaan kertyneen veden kelluttava vaikutus

Simulating the roles of crevasse routing of surface water and basal friction on the surge evolution of Basin 3, Austfonna ice cap

The marine-terminating outlet in Basin 3, Austfonna ice cap, has been accelerating since the mid-1990s. Stepwise multi-annual acceleration associated with seasonal summer speed-up events was observed before the outlet entered the basin-wide surge in autumn 2012. We used multiple numerical models to explore hydrologic activation mechanisms for the surge behaviour. A continuum ice dynamic model was used to invert basal friction coefficient distributions using the control method and observed surface velocity data between April 2012 and July 2014. This has provided input to a discrete element model capable of simulating individual crevasses, with the aim of finding locations where meltwater entered the glacier during the summer and reached the bed. The possible flow paths of surface meltwater reaching the glacier bed as well as those of meltwater produced at the bed were calculated according to the gradient of the hydraulic potential. The inverted friction coefficients show the "unplugging" of the stagnant ice front and expansion of low-friction regions before the surge reached its peak velocity in January 2013. Crevasse distribution reflects the basal friction pattern to a high degree. The meltwater reaches the bed through the crevasses located above the margins of the subglacial valley and the basal melt that is generated mainly by frictional heating flows either to the fast-flowing units or potentially accumulates in an overdeepened region. Based on these results, the mechanisms facilitated by basal meltwater production, crevasse opening and the routing of meltwater to the bed are discussed for the surge in Basin 3.Peer reviewe

Planning analysis for locally advanced lung cancer: dosimetric and efficiency comparisons between intensity-modulated radiotherapy (IMRT), single-arc/partial-arc volumetric modulated arc therapy (SA/PA-VMAT)

<p>Abstract</p> <p>Purpose</p> <p>To analyze the differences between the intensity-modulated radiotherapy (IMRT), single/partial-arc volumetric modulated arc therapy (SA/PA-VMAT) techniques in treatment planning for locally advanced lung cancer.</p> <p>Materials and methods</p> <p>12 patients were retrospectively studied. In each patient's case, several parameters were analyzed based on the dose-volume histograms (DVH) of the IMRT, SA/PA-VMAT plans respectively. Also, each plan was delivered to a phantom for time comparison.</p> <p>Results</p> <p>The SA-VMAT plans showed the superior target dose coverage, although the minimum/mean/maximum doses to the target were similar. For the total and contralateral lungs, the higher V_5/10, lower V_20/30and mean lung dose (MLD) were observed in the SA/PA-VMAT plans (<it>p </it>< 0.05, respectively). The PA-VMAT technique improves the dose sparing (V₂₀, V₃₀and MLD) of the controlateral lung more notably, comparing to those parameters of the IMRT and SA-VMAT plans respectively. The delivered monitor units (MUs) and treatment times were reduced significantly with VMAT plans, especially PA-VMAT plans (for MUs: mean 458.3 <it>vs</it>. 439.2 <it>vs</it>. 435.7 MUs, <it>p </it>< 0.05 and for treatment time: mean 13.7 <it>vs</it>. 10.6 <it>vs</it>. 6.4 minutes, <it>p </it>< 0.01).</p> <p>Conclusions</p> <p>The SA-VMAT technique achieves highly conformal dose distribution to the target. Comparing to the IMRT plans, the higher V_5/10, lower V_20/30and MLD were observed in the total and contralateral lungs in the VMAT plans, especially in the PA-VMAT plans. The SA/PA-VMAT plans also reduced treatment time with more efficient dose delivering. But the clinical benefit of the VMAT technique for locally advanced lung cancer needs further investigations.</p

A novel nanoparticle drug delivery system based on PEGylated hemoglobin for cancer therapy

Proteins such as albumin, gelatin, casein, transferrin, and collagen are widely used as drug delivery systems. However, only albumin-based paclitaxel (PTX) formulation AbraxaneVR (PTX-albumin NPs prepared by nab-technology) has been successfully developed for treating metastatic breast cancer clinically due to abundant materials, simple industrial scale-up process, and well tumor-targeting ability. Hemoglobin (Hb) is another protein used for drug delivery with similar advantages. In this study, we successfully synthesized PEG-Hb nanoparticles loading with PTX based on previously well-established acid-denatured method. PEG-Hb-PTX NPs showed enhanced cellular uptake and great cellular inhibition ability in vitro. Moreover, our animal study showed that PEGylated NPs greatly accumulated in tumor tissues and exhibited excellent anticancer activity in vivo. We found that PEG-Hb-PTX NPs possess a better in vivo antitumor effect than the commercially available TaxolVR formulation. We believe that PEG-Hb has great potential as an efficient drug delivery system for further clinic study

Importance of basal boundary conditions in transient simulations : case study of a surging marine-terminating glacier on Austfonna, Svalbard

We assess the importance of basal boundary conditions for transient simulations of Basin 3, Austfonna ice cap between January 1995 and December 2011 and for the surge starting in 2012 by carrying out simulations with the full-Stokes model Elmer/Ice and the vertically-integrated model BISICLES. Time-varying surface mass-balance data from the regional climate model HIRHAM5 are downscaled according to elevation. Basal friction coefficient is varied through time by interpolating between two data-constrained inversions of surface velocity fields, from 1995 and 2011. Evolution of the basal boundary condition appears to be much more important for mass discharge and the dynamic response of the fast flowing unit in Basin 3 than either model choice or the downscaling method for the surface mass balance. In addition, temporally linear extrapolation of the evolution of basal friction coefficient beyond the 2011 distribution could not reproduce the expansion of the acceleration observed in southern Basin 3 between January 2012 and June 2013. This implies that changes in basal friction patterns, and in turn basal processes that are not currently represented in either model, are among the most important factors for the 2012 acceleration.Peer reviewe

Involved-field irradiation or elective-nodal irradiation in neoadjuvant chemo-radiotherapy for locally-advanced esophageal cancer: comprehensive analysis for dosimetry, treatment-related complications, impact on lymphocyte, patterns of failure and survival

PurposeTo compare the differences between involved-field irradiation (IFI) and elective nodal irradiation (ENI) in selecting the optimal target area for neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC).Materials and methodsWe retrospectively analyzed 267 patients with LA-ESCC, of whom 165 underwent ENI and 102 underwent IFI. Dosimetry, treatment-related complications, pathological responses, recurrence/metastasis patterns, and survival were compared between the two groups.ResultsThe median follow-up duration was 27.9 months. The R0 resection rates in the IFI and ENI groups were 95.1% and 92.7%, respectively (p=0.441), while the pathological complete response (pCR) rates were 42.2% and 34.5%, respectively (p=0.12). The ENI group received higher radiation doses to the heart (HV30:23.9% vs. 18%, p=0.033) and lungs (LV30:7.7% vs. 4.9%, p&lt;0.001) than the IFI group. Consequently, the ENI group showed a higher incidence of grade 2 or higher radiation pneumonitis (30.3% vs. 17.6%, p=0.004) and pericardial effusion (26.7% vs. 11.8%, p=0.021) than the IFI group. Post-operation fistulas were observed in 3 (2.9%) and 17 cases (10.3%) in the IFI and ENI groups, respectively (p=0.026). In the multivariate analysis, smoking, positive lymph node involvement (pN+), and anastomotic fistula were independent predictors of overall survival (OS). The pN+ patients exhibited a greater propensity for recurrence compared to pN- patients, especially in the first year of follow-up (6.67% vs. 0.56%, p=0.003).ConclusionThe ENI group had a higher incidence of radiation-induced adverse events compared to the IFI group, likely due to the higher radiation doses to normal tissues. Considering the similar disease-free survival (DFS) and OS rates in the two groups, IFI may be suitable for nCRT in patients with LA-ESCC, although further prospective studies are warranted

Evaluation of a new fluorescence quantitative PCR test for diagnosing Helicobacter pylori infection in children

Abstract Background Numerous diagnostic tests are available to detect Helicobactor pylori (H. pylori). There has been no single test available to detect H. pylori infection reliably. We evaluated the accuracy of a new fluorescence quantitative PCR (fqPCR) for H. pylori detection in children. Methods Gastric biopsy specimens from 138 children with gastritis were sent for routine histology exam, rapid urease test (RUT) and fqPCR. 13C-urea breath test (13C-UBT) was carried out prior to endoscopic procedure. Gastric fluids and dental plaques were also collected for fqPCR analysis. Results 38 children (27.5%) were considered positive for H. pylori infection by gold standard (concordant positive results on 2 or more tests). The remaining 100 children (72.5%) were considered negative for H. pylori. Gastric mucosa fqPCR not only detected all 38 H. pylori positive patients but also detected 8 (8%) of the 100 gold standard-negative children or 11 (10.7%) of the 103 routine histology-negative samples. Therefore, gastric mucosa fqPCR identified 46 children (33.3%) with H. pylori infection, significantly higher than gold standard or routine histology (P&lt;0.01). Both gastric fluid and dental plaque fqPCR only detected 32 (23.2%) and 30 (21.7%) children with H. pylori infection respectively and was significantly less sensitive than mucosa fqPCR (P&lt;0.05) but was as sensitive as non-invasive UBT. Conclusions Gastric mucosa fqPCR was more sensitive than routine histology, RUT, 13C-UBT alone or in combination to detect H. pylori infection in children with chronic gastritis. Either gastric fluid or dental plaque PCR is as reliable as 13C-UBT for H. pylori detection.Peer Reviewe

piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity

Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has recently been recognized, studies on the role and functional mechanism of piRNAs in lung adenocarcinoma (LUAD) development and progression are limited. In this study, we identified 10 differently expressed piRNAs in LUAD tissues compared to normal tissues, among which, piR-hsa-211106 expression levels were downregulated in LUAD tissues and cell lines. Furthermore, the effects of piR-hsa-211106 on the malignant phenotypes and chemosensitivity of LUAD cells were detected by gain- and loss-of-function analyses in vitro and in vivo, which showed that piR-hsa-211106 inhibited LUAD cell proliferation, tumor growth, and migration, but promoted apoptosis. Moreover, our finding indicated that piR-hsa-211106 is a potential therapeutic target that synergistically imparts anticancer effects with a chemotherapeutic agent for LUAD-cisplatin. Further mechanistic investigation indicated that piR-hsa-211106 could bind to pyruvate carboxylase (PC) by RNA pull down and RNA immunoprecipitation assays and inhibited PC mRNA and protein expression. Our study demonstrates that piR-hsa-211106 inhibits LUAD progression by hindering the expression and function of PC and enhances chemotherapy sensitivity, suggesting that piR-hsa-211106 is a novel diagnostic and therapeutic target for LUAD

Assessing Reproducibility of Inherited Variants Detected With Short-Read Whole Genome Sequencing

Background: Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results: To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when \u3e 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×. Conclusions: Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS