bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlling the Superior Reliability of Lead Free Assemblies With Short Standoff Height Through Design and Materials Selection
Authors: Arfaei B. , Wentlent L. , Joshi S. , Anselm M. , Borgesen P. 
Published: October 2013

We have recently demonstrated a significantly longer life in accelerated thermal cycling for Land Grid Arrays (LGAs) assembled only with SAC305 solder paste than for the corresponding SAC305 based BGA assemblies. This superior performance was shown to be a direct effect of the solder microstructure. The final Sn solidification temperature strongly affects the initial microstructure of a SnAgCu solder joint, including the Sn grain morphology, and thus the thermomechanical behavior of the joint. Right after reflow, larger BGA joints of SnAgCu alloys, which solidify at higher temperature, reveal either a single β-Sn grain or three large grains with clearly defined boundaries formed by cyclic twinning. The orientations of the highly anisotropic Sn grains are not yet controllable in manufacturing, leading to substantial statistical scatter in the performance of the solder joints. Typical LGA solder joint dimensions, however, tend to facilitate greater undercooling and the formation of an alternative interlaced twinning microstructure.
A systematic study was undertaken to identify the parameters that control the interlaced twinning microstructure. Sn grain structures were characterized by crossed polarizer microscopy and electron backscatter diffraction (EBSD). Precipitate sizes and distributions were measured using backscattered scanning electron microscopy and quantified using image analysis software. Systematic effects of solder alloy, dimensions and pad finishes were identified. Recommendations are made as to design and materials selection. The practicality of controlling the desired microstructure, as well as potential disadvantages for certain applications is discussed.
Plasmodium falciparum Polymorphisms Associated with
Ex Vivo
Drug Susceptibility and Clinical Effectiveness of Artemisinin-Based Combination Therapies in Benin
Authors: Dahlström Sabina , Aubouy Agnès , Maïga-Ascofaré Oumou , Faucher Jean-François , Wakpo Abel , Ezinmègnon Sèm , Massougbodji Achille , Houzé Pascal , Kendjo Eric , Deloron Philippe , Le Bras Jacques , Houzé Sandrine 
Published: October 2013

ABSTRACT

Artemisinin-based combination therapies (ACTs) are the main option to treat malaria, and their efficacy and susceptibility must be closely monitored to avoid resistance. We assessed the association of
Plasmodium falciparum
polymorphisms and
ex vivo
drug susceptibility with clinical effectiveness. Patients enrolled in an effectiveness trial comparing artemether-lumefantrine (
n
= 96), fixed-dose artesunate-amodiaquine (
n
= 96), and sulfadoxine-pyrimethamine (
n
= 48) for the treatment of uncomplicated malaria 2007 in Benin were assessed.
pfcrt
,
pfmdr1
,
pfmrp1
,
pfdhfr
, and
pfdhps
polymorphisms were analyzed pretreatment and in recurrent infections. Drug susceptibility was determined in fresh baseline isolates by
Plasmodium
lactate dehydrogenase enzyme-linked immunosorbent assay (ELISA). A majority had 50% inhibitory concentration (IC
50
) estimates (the concentration required for 50% growth inhibition) lower than those of the 3D7 reference clone for desethylamodiaquine, lumefantrine, mefloquine, and quinine and was considered to be susceptible, while dihydroartemisinin and pyrimethamine IC
50
s were higher. No association was found between susceptibility to the ACT compounds and treatment outcome. Selection was observed for the
pfmdr1
N86 allele in artemether-lumefantrine recrudescences (recurring infections) (4/7 [57.1%] versus 36/195 [18.5%]), and of the opposite allele, 86Y, in artesunate-amodiaquine reinfections (new infections) (20/22 [90.9%] versus 137/195 [70.3%]) compared to baseline infections. The importance of
pfmdr1
N86 in lumefantrine tolerance was emphasized by its association with elevated lumefantrine IC
50
s. Genetic linkage between N86 and Y184 was observed, which together with the low frequency of 1246Y may explain regional differences in selection of
pfmdr1
loci. Selection of opposite alleles in artemether-lumefantrine and artesunate-amodiaquine recurrent infections supports the strategy of multiple first-line treatment. Surveillance based on clinical,
ex vivo
, molecular, and pharmacological data is warranted.
Correlates of Immune Protection following Cutaneous Immunization with an Attenuated Burkholderia pseudomallei Vaccine
Authors: Silva Ediane B. , Goodyear Andrew , Sutherland Marjorie D. , Podnecky Nicole L. , Gonzalez-Juarrero Mercedes , Schweizer Herbert P. , Dow Steven W. 
Published: October 2013

ABSTRACT

Infections with the Gram-negative bacterium
Burkholderia pseudomallei
(melioidosis) are associated with high mortality, and there is currently no approved vaccine to prevent the development of melioidosis in humans. Infected patients also do not develop protective immunity to reinfection, and some individuals will develop chronic, subclinical infections with
B. pseudomallei
. At present, our understanding of what constitutes effective protective immunity against
B. pseudomallei
infection remains incomplete. Therefore, we conducted a study to elucidate immune correlates of vaccine-induced protective immunity against acute
B. pseudomallei
infection. BALB/c and C57BL/6 mice were immunized subcutaneously with a highly attenuated, Select Agent-excluded
purM
deletion mutant of
B. pseudomallei
(strain Bp82) and then subjected to intranasal challenge with virulent
B. pseudomallei
strain 1026b. Immunization with Bp82 generated significant protection from challenge with
B. pseudomallei
, and protection was associated with a significant reduction in bacterial burden in lungs, liver, and spleen of immunized mice. Humoral immunity was critically important for vaccine-induced protection, as mice lacking B cells were not protected by immunization and serum from Bp82-vaccinated mice could transfer partial protection to nonvaccinated animals. In contrast, vaccine-induced protective immunity was found to be independent of both CD4 and CD8 T cells. Tracking studies demonstrated uptake of the Bp82 vaccine strain predominately by neutrophils in vaccine-draining lymph nodes and by smaller numbers of dendritic cells (DC) and monocytes. We concluded that protection following cutaneous immunization with a live attenuated
Burkholderia
vaccine strain was dependent primarily on generation of effective humoral immune responses.
Does the width of the surgical margin of safety or premalignant dermatoses at the negative surgical margin affect outcome in surgically treated penile cancer?
Authors: Gunia Sven , Koch Stefan , Jain Anjun , May Matthias 
Published: October 2013

AimsTo evaluate the prognostic impact of the width of negative surgical margins (NSM) and associated and preinvasive lesions at the NSM in patients with penile squamous cell cancer (PSC).MethodsEnrolling 87 patients with NSM who underwent surgery for PSC, the archived margin slides and entirely wax-embedded surgical margins were retrieved from the pathology files. After step sections were cut, margins were stained with antibodies against CK5/6, p16, p53 and Ki-67 and subjected to in situ hybridisation for high-risk human papillomavirus (HPV). All NSM were histologically examined for squamous hyperplasia (SH), lichen sclerosus (LS) and subtypes of penile intraepithelial neoplasia (PeIN). Then, histological findings were correlated with cancer-specific mortality (CSM, median follow-up 34 months; IQR 6–70).ResultsAll NSM were negative for high-risk HPV and exhibited SH (p16 and p53 negative, Ki-67 variably positive), LS (p16 negative, variable p53 and Ki-67 positivity) and differentiated PeIN (dPeIN; p16 negative, Ki-67 positive, variable p53 positivity) in 28 (32%), 30 (34%) and 22 (25%) cases, respectively, whereas PeIN subtypes other then dPeIN did not occur. Pathological tumour stage was the only independent predictive parameter with respect to CSM in the multivariable analysis (p=0.001).ConclusionsSH, LS and dPeIN are frequent histological findings at the NSM of surgically treated PSC. However, neither the width of the NSM nor dPeIN, LS or SH at the NSM influences prognostic outcome.
Old age mortality and macroeconomic cycles
Authors: Rolden Herbert J A , van Bodegom David , van den Hout Wilbert B , Westendorp Rudi G J 
Published: October 2013

BackgroundAs mortality is more and more concentrated at old age, it becomes critical to identify the determinants of old age mortality. It has counter-intuitively been found that mortality rates at all ages are higher during short-term increases in economic growth. Work-stress is found to be a contributing factor to this association, but cannot explain the association for the older, retired population.MethodsHistorical figures of gross domestic product (Angus Maddison) were compared with mortality rates (Human Mortality Database) of middle aged (40–44 years) and older people (70–74 years) in 19 developed countries for the period 1950–2008. Regressions were performed on the de-trended data, accounting for autocorrelation and aggregated using random effects models.ResultsMost countries show pro-cyclical associations between the economy and mortality, especially with regard to male mortality rates. On average, for every 1% increase in gross domestic product, mortality increases with 0.36% for 70-year-old to 74-year-old men (p<0.001) and 0.38% for 40-year-old to 44-year-old men (p<0.001). The effect for women is 0.18% for 70-year-olds to 74-year-olds (p=0.012) and 0.15% for 40-year-olds to 44-year-olds (p=0.118).ConclusionsIn developed countries, mortality rates increase during upward cycles in the economy, and decrease during downward cycles. This effect is similar for the older and middle-aged population. Traditional explanations as work-stress and traffic accidents cannot explain our findings. Lower levels of social support and informal care by the working population during good economic times can play an important role, but this remains to be formally investigated.
The role of metamorphic fluids in the formation of ore deposits
Authors: Yardley Bruce W. D. , Cleverley James S. 
Published: October 2013

Abstract

Many ore deposits are hosted by metamorphic rocks, and metamorphic fluids have been invoked as a source for various deposits, especially gold deposits. Metamorphic fluid compositions reflect original sedimentary environment: continental shelf sequences yield saline metamorphic fluids with little dissolved gas while metasediments from accretionary and oceanic settings host less saline fluids with significant CO
2
contents.

The principal difficulty in reconciling ore deposits with a metamorphic origin is that many form quickly (
c.
1 Ma), whereas metamorphic heating is slow (
c.
10–20 °/Ma). Gravitational instability means that fluid cannot be retained. Metamorphic ores may nevertheless form by: (a) segregation leading to enrichment of pre-existing concentrations; (b) infiltration of water-rich fluids from schists into marbles at high temperature overstepping decarbonation reactions and allowing fast reaction that locally draws down temperature; and (c) rapid uplift driving dehydration reactions owing to pressure drop.

Some orogenic lode gold deposits fit well with a purely metamorphic origin during rapid uplift, but others are problematic. At Sunrise Dam, Western Australia, anomalies in Sr-isotope ratios and in apatite compositions indicate a partial mantle/magmatic source. Low salinity, H
2
O–CO
2
fluids commonly associated with hydrothermal gold reflect the effect of salt on gas solubility, not the origin of the fluid.
Generation of Prostate Tumor–Initiating Cells Is Associated with Elevation of Reactive Oxygen Species and IL-6/STAT3 Signaling
Authors: Qu Yi , Oyan Anne Margrete , Liu Runhui , Hua Yaping , Zhang Jigang , Hovland Randi , Popa Mihaela , Liu Xiaojun , Brokstad Karl A. , Simon Ronald , Molven Anders , Lin Biaoyang , Zhang Wei-dong , McCormack Emmet , Kalland Karl-Henning , Ke Xi-Song 
Published: October 2013

AbstractHow prostate cancer is initiated remains a topic of debate. In an effort to establish a human model of prostate carcinogenesis, we adapted premalignant human prostate EPT2-D5 cells to protein-free medium to generate numerous tight prostate spheres (D5HS) in monolayer culture. In contrast to EPT2-D5 cells, the newly generated D5HS efficiently formed large subcutaneous tumors and subsequent metastases in vivo, showing the tumorigenicity of D5HS spheres. A striking production of interleukin (IL)-6 mRNA and protein was found in D5HS cells. The essential roles of IL-6 and the downstream STAT3 signaling in D5HS tumor sphere formation were confirmed by neutralizing antibody, chemical inhibitors, and fluorescent pathway reporter. In addition, elevated reactive oxygen species (ROS) produced upon protein depletion was required for the activation of IL-6/STAT3 in D5HS. Importantly, a positive feedback loop was found between ROS and IL-6 during tumor sphere formation. The association of ROS/IL-6/STAT3 to the carcinogenesis of human prostate cells was further examined in xenograft tumors and verified by limiting dilution implantations. Collectively, we have for the first time established human prostate tumor–initiating cells based on physiologic adaption. The intrinsic association of ROS and IL-6/STAT3 signaling in human prostate carcinogenesis shed new light on this relationship and define therapeutic targets in this setting. Cancer Res; 73(23); 7090–100. ©2013 AACR.
APG350 Induces Superior Clustering of TRAIL Receptors and Shows Therapeutic Antitumor Efficacy Independent of Cross-Linking via Fcγ Receptors
Authors: Gieffers Christian , Kluge Michael , Merz Christian , Sykora Jaromir , Thiemann Meinolf , Schaal René , Fischer Carmen , Branschädel Marcus , Abhari Behnaz Ahangarian , Hohenberger Peter , Fulda Simone , Fricke Harald , Hill Oliver 
Published: October 2013

Abstract
Cancer cells can be specifically driven into apoptosis by activating Death-receptor-4 (DR4; TRAIL-R1) and/or Death-receptor-5 (DR5; TRAIL-R2). Albeit showing promising preclinical efficacy, first-generation protein therapeutics addressing this pathway, especially agonistic anti-DR4/DR5-monoclonal antibodies, have not been clinically successful to date. Due to their bivalent binding mode, effective apoptosis induction by agonistic TRAIL-R antibodies is achieved only upon additional events leading to antibody-multimer formation. The binding of these multimers to their target subsequently leads to effective receptor-clustering on cancer cells. The research results presented here report on a new class of TRAIL-receptor agonists overcoming this intrinsic limitation observed for antibodies in general. The main feature of these agonists is a TRAIL-mimic consisting of three TRAIL-protomer subsequences combined in one polypeptide chain, termed the single-chain TRAIL-receptor–binding domain (scTRAIL-RBD). In the active compounds, two scTRAIL-RBDs with three receptor binding sites each are brought molecularly in close proximity resulting in a fusion protein with a hexavalent binding mode. In the case of APG350—the prototype of this engineering concept—this is achieved by fusing the Fc-part of a human immunoglobulin G1 (IgG1)-mutein C-terminally to the scTRAIL–RBD polypeptide, thereby creating six receptor binding sites per drug molecule. In vitro, APG350 is a potent inducer of apoptosis on human tumor cell lines and primary tumor cells. In vivo, treatment of mice bearing Colo205-xenograft tumors with APG350 showed a dose-dependent antitumor efficacy. By dedicated muteins, we confirmed that the observed in vivo efficacy of the hexavalent scTRAIL–RBD fusion proteins is—in contrast to agonistic antibodies—independent of FcγR-based cross-linking events. Mol Cancer Ther; 12(12); 2735–47. ©2013 AACR.
Severe Cutaneous and Neurologic Toxicity in Melanoma Patients during Vemurafenib Administration Following Anti-PD-1 Therapy
Authors: Johnson Douglas B. , Wallender Erika K. , Cohen Daniel N. , Likhari Sunaina S. , Zwerner Jeffrey P. , Powers Jennifer G. , Shinn Lisa , Kelley Mark C. , Joseph Richard W. , Sosman Jeffrey A. 
Published: October 2013

Abstract
Immune checkpoint inhibitors such as ipilimumab and targeted BRAF inhibitors have dramatically altered the landscape of melanoma therapeutics over the past few years. Agents targeting the programmed cell death-1/ligand (PD-1/PD-L1) axis are now being developed and seem to be highly active clinically with favorable toxicity profiles. We report on two patients with BRAF V600E–mutant melanoma who were treated with anti-PD-1 agents as first-line therapy without significant toxicity, followed by vemurafenib at disease progression. Both patients developed severe hypersensitivity drug eruptions with multiorgan injury early in their BRAF inhibitor treatment course. One patient subsequently developed acute inflammatory demyelinating polyneuropathy, and the other developed anaphylaxis upon low-dose vemurafenib rechallenge. Further investigation of the immune response during combination or sequences of melanoma therapeutics is warranted. Furthermore, clinicians should maintain a high index of suspicion for these toxicities when vemurafenib is administered following an anti-PD-1 agent. Cancer Immunol Res; 1(6); 373–7. ©2013 AACR.
A Stochastic Skeleton Model for the MJO
Authors: Thual Sulian , Majda Andrew J. , Stechmann Samuel N. 
Published: October 2013

Abstract
The Madden–Julian oscillation (MJO) is the dominant mode of variability in the tropical atmosphere on intraseasonal time scales and planetary spatial scales. Despite the primary importance of the MJO and the decades of research progress since its original discovery, a generally accepted theory for its essential mechanisms has remained elusive. In recent work by two of the authors, a minimal dynamical model has been proposed that recovers robustly the most fundamental MJO features of (i) a slow eastward speed of roughly 5 m s−1, (ii) a peculiar dispersion relation with dω/dk ≈ 0, and (iii) a horizontal quadrupole vortex structure. This model, the skeleton model, depicts the MJO as a neutrally stable atmospheric wave that involves a simple multiscale interaction between planetary dry dynamics, planetary lower-tropospheric moisture, and the planetary envelope of synoptic-scale activity. In this article, it is shown that the skeleton model can further account for (iv) the intermittent generation of MJO events and (v) the organization of MJO events into wave trains with growth and demise, as seen in nature. The goal is achieved by developing a simple stochastic parameterization for the unresolved details of synoptic-scale activity, which is coupled to otherwise deterministic processes in the skeleton model. In particular, the intermittent initiation, propagation, and shut down of MJO wave trains in the skeleton model occur through these stochastic effects. This includes examples with a background warm pool where some initial MJO-like disturbances propagate through the western region but stall at the peak of background convection/heating corresponding to the Maritime Continent in nature.
Diagnosing the Strength of Land–Atmosphere Coupling at Subseasonal to Seasonal Time Scales in Asia
Authors: Liu Di , Wang Guiling , Mei Rui , Yu Zhongbo , Gu Huanghe 
Published: October 2013

Abstract
This paper focuses on diagnosing the strength of soil moisture–atmosphere coupling at subseasonal to seasonal time scales over Asia using two different approaches: the conditional correlation approach [applied to the Global Land Data Assimilation System (GLDAS) data, the Climate Forecast System Reanalysis (CFSR) data, and output from the regional climate model, version 4 (RegCM4)] and the Global Land–Atmosphere Coupling Experiment (GLACE) approach applied to the RegCM4. The conditional correlation indicators derived from the model output and the two observational/reanalysis datasets agree fairly well with each other in the spatial pattern of the land–atmosphere coupling signal, although the signal in CFSR data is stronger and spatially more extensive than the GLDAS data and the RegCM4 output. Based on the impact of soil moisture on 2-m air temperature, the land–atmosphere coupling hotspots common to all three data sources include the Indochina region in spring and summer, the India region in summer and fall, and north-northeastern China and southwestern Siberia in summer. For precipitation, all data sources produce a weak and spatially scattered signal, indicating the lack of any strong coupling between soil moisture and precipitation, for both precipitation amount and frequency. Both the GLACE approach and the conditional correlation approach (applied to all three data sources) identify evaporation and evaporative fraction as important links for the coupling between soil moisture and precipitation/temperature. Results on soil moisture–temperature coupling strength from the GLACE-type experiment using RegCM4 are in good agreement with those from the conditional correlation analysis applied to output from the same model, despite substantial differences between the two approaches in the terrestrial segment of the land–atmosphere coupling.
Prevalence of menstrual migraine: A population-based study
Authors: Vetvik Kjersti G , MacGregor E Anne , Lundqvist Christofer , Russell Michael B 
Published: October 2013

Aim To present data from a population-based epidemiological study on menstrual migraine. Material and methods Altogether, 5000 women aged 30–34 years were screened for menstrual migraine. Women with self-reported menstrual migraine in at least half of their menstrual cycles were invited to an interview and examination. We expanded the International Classification of Headache Disorders III beta appendix criteria on menstrual migraine to include both migraine without aura and migraine with aura, as well as probable menstrual migraine with aura and migraine without aura. Results A total of 237 women were included in the study. The prevalence among all women was as follows: any type of menstrual migraine 7.6%; menstrual migraine without aura 6.1%; menstrual migraine with aura 0.6%; probable menstrual migraine without aura 0.6%; probable menstrual migraine with aura 0.3%. The corresponding figures among female migraineurs were: any type of menstrual migraine 22.0%, menstrual migraine without aura 17.6%, menstrual migraine with aura 1.7%, probable menstrual migraine without aura 1.6% and probable menstrual migraine with aura 1.0%. Conclusion More than one of every five female migraineurs aged 30–34 years have migraine in ≥50% of menstruations. The majority has menstrual migraine without aura and one of eight women had migraine with aura in relation to their menstruation. Our results indicate that the ICHD III beta appendix criteria of menstrual migraine are not exhaustive.