bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep transcriptomic profiling reveals the similarity between endothelial cells cultured under static and oscillatory shear stress conditions
Authors: Qiao Congzhen , Meng Fan , Jang Inhwan , Jo Hanjoong , Chen Y. Eugene , Zhang Jifeng
Published: July 2016

Atherosclerosis is a multifactorial disease that preferentially develops in specific regions in the arterial tree. This characteristic is mainly attributed to the unique pattern of hemodynamic shear stress in vivo. High laminar shear stress (LS) found in straight lumen exerts athero-protective effects. Low or oscillatory shear stress (OS) present in regions of lesser curvature and arterial bifurcations predisposes arterial intima to atherosclerosis. Shear stress-regulated endothelial function plays an important role in the process of atherosclerosis. Most in vitro research studies focusing on the molecular mechanisms of endothelial function are performed in endothelial cells (ECs) under cultured static (ST) condition. Some findings, however, are not recapitulated in subsequent translational studies, mostly likely due to the missing biomechanical milieu. Here, we profiled the whole transcriptome of primary human coronary arterial endothelial cells (HCAECs) under different shear stress conditions with RNA sequencing. Among 16,313 well-expressed genes, we detected 8,177 that were differentially expressed in OS vs. LS conditions and 9,369 in ST vs. LS conditions. Notably, only 1,618 were differentially expressed in OS vs. ST conditions. Hierarchical clustering of ECs demonstrated a strong similarity between ECs under OS and ST conditions at the transcriptome level. Subsequent pairwise heat mapping and principal component analysis gave further weight to the similarity. At the individual gene level, expressional analysis of representative well-known genes as well as novel genes showed a comparable amount at mRNA and protein levels in ECs under ST and OS conditions. In conclusion, the present work compared the whole transcriptome of HCAECs under different shear stress conditions at the transcriptome level as well as at the individual gene level. We found that cultured ECs are significantly different from those under LS conditions. Thus using cells under ST conditions is unlikely to elucidate endothelial physiology. Given the revealed high similarities of the endothelial transcriptome under OS and ST conditions, it may be helpful to understand the underlying mechanisms of OS-induced endothelial dysfunction from static cultured endothelial studies.
Aromatic Hydrocarbon Receptor Suppresses Prostate Cancer Bone Metastasis Cells-Induced Vasculogenesis of Endothelial Progenitor Cells under Hypoxia
Authors: Huang Shuai , Guo Yuanqing , Jacobi Angela , Li Ziqing , Huang Sheng , He Jianan , Liu Xingmo , Tang Yubo
Published: July 2016

Background/Aims: Hypoxia leads to the development of neovascularization in solid tumor by regulating VEGF expression. Aromatic hydrocarbon receptor (AHR), a receptor for dioxin-like compounds, functions as a transcription factor through dimerization with hypoxia-inducible factors 1β (HIF-1β) and inhibits the secretion of vascular endothelial growth factor (VEGF). The purpose of this study was to explore whether AHR can suppress hypoxia-induced VEGF production in prostate bone metastasis cells and repress neovascularization in endothelial progenitor cells (EPCs), and, if so, through what mechanisms. Methods: PC-3 or LNCaP cells induced angiogenesis was detected by Matrigel-based tube formation assay, mRNA expression levels was measured by qRT-PCR, VEGF secretion level was determined by ELISA assay, respectively. Results: AHR activation inhibits hypoxia-induced adhesiveness and vasculogenesis of EPCs induced by PC-3 or LNCaP cells under hypoxia. Moreover, AHR activation suppressed hypoxia-induced VEGF production in PC-3 and LNCaP cells (48 ± 14% in PC-3, p = 0.000; 41 ± 14% in LNCaP, p = 0.000) by attenuating HIF-1α and HIF-1β level that in turn diminished the angiogenic ability of EPCs in vitro. Furthermore, we found the mRNA level of hypoxia-inducible factors 1α (HIF-1α) (1.54 ± 0.13 fold in PC-3, p = 0.002, 1.62 ± 0.12 fold in LNCaP, p = 0.001) and HIF-1β (1.67 ± 0.23 fold in PC-3, p = 0.007; 1.75 ± 0.26 fold in LNCaP, p=0.008) were upregulated in prostate cancer bone metastasis PC-3 and LNCaP cell lines in response to hypoxia, and revealed that the regulation of VEGF by HIF-1α and HIF-1β was possibly mediated by the activation of phosphatidylinositol 3-kinase pathway. Conclusion: By providing a mechanistic insight into the modulation of neovascularization by AHR ligand, we suggest that AHR ligand has a strong potential of being a new therapeutic agent with applications in the field of bone metastatic prostate cancer.
Combination of Sitagliptin and Insulin against Type 2 Diabetes Mellitus with Neuropathy in Rats: Neuroprotection and Role of Oxidative and Inflammation Stress
Authors: Kelany Mohamed Elsayed , Hakami Tahir M. , Omar Adel H. , Abdallah Mohamed A.
Published: July 2016

Aims: The present study evaluated the effects of sitagliptin-insulin against type 2 diabetes mellitus with neuropathy in rats and possible neuroprotective mechanisms. Methods: Diabetes was induced in 32 adult male albino rats by 6-week high-fat high-sugar diet followed by streptozotocin 30 mg/kg intraperitoneal injection. For 4 weeks thereafter, diabetic rats were divided into 4 groups, each group receiving one of the following daily: vehicle (untreated diabetic), insulin 10 IU/kg SC, sitagliptin 30 mg/kg PO or sitagliptin-insulin. We assessed systolic blood pressure (SBP), blood glucose, serum insulin and advanced glycation end-products (AGEs), thermal hyperalgesia and sciatic nerve tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) and sciatic histopathology. Results: Compared to untreated and insulin-treated groups, sitagliptin decreased SBP, serum AGEs and sciatic MDA and TNF-α, and increased serum insulin and sciatic SOD, but insulin decreased blood glucose more. Sitagliptin-insulin (greater than sitagliptin or insulin alone) superiorly decreased and increased the above respective parameters, and ameliorated hyperalgesia and sciatic histopathological changes, but was similar to insulin in decreasing blood glucose, and similar to sitagliptin in rising serum insulin. Conclusions: Sitagliptin-insulin combination produced hypoglycemic and neuroprotective effect and ameliorated hyperalgesia, oxidative stress and inflammation more than either drug alone. This combination might have clinical efficacy in uncontrolled type 2 diabetes with neuropathy.
Constitutive GITR Activation Reduces Atherosclerosis by Promoting Regulatory CD4
+
T-Cell Responses—Brief Report
Authors: Meiler Svenja , Smeets Esther , Winkels Holger , Shami Annelie , Pascutti Maria Fernanda , Nolte Martijn A. , Beckers Linda , Weber Christian , Gerdes Norbert , Lutgens Esther
Published: July 2016

Objective—

Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is expressed on CD4
+
effector memory T cells and regulatory T cells; however, its role on these functionally opposing cell types in atherosclerosis is not fully understood.

Approach and Results—

Low-density lipoprotein receptor–deficient mice (
Ldlr
−/−
) were lethally irradiated and reconstituted with either bone marrow from B-cell–restricted
Gitrl
transgenic mice or from wild-type controls and fed a high-cholesterol diet for 11 weeks. Chimeric
Ldlr
−/−
Gitrl
tg
mice showed a profound increase in both CD4
+
effector memory T cells and regulatory T cells in secondary lymphoid organs. Additionally, the number of regulatory T cells was significantly enhanced in the thymus and aorta of these mice along with increased
Gitrl
and
Il-2
transcript levels. Atherosclerotic lesions of
Ldlr
−/−
Gitrl
tg
chimeras contained more total CD3
+
T cells as well as Foxp3
+
regulatory T cells overall, leading to significantly less severe atherosclerosis.

Conclusions—

These data indicate that continuous GITR stimulation through B cell
Gitrl
acts protective in a mouse model of atherosclerosis by regulating the balance between regulatory and effector memory CD4
+
T cells.
Hypoxia-Inducible Factor-1α Expression in Macrophages Promotes Development of Atherosclerosis
Authors: Aarup Annemarie , Pedersen Tanja X. , Junker Nanna , Christoffersen Christina , Bartels Emil D. , Madsen Marie , Nielsen Carsten H. , Nielsen Lars B.
Published: July 2016

Objective—

Atherosclerotic lesions contain hypoxic areas, but the pathophysiological importance of hypoxia is unknown. Hypoxia-inducible factor-1α (HIF-1α) is a key transcription factor in cellular responses to hypoxia. We investigated the hypothesis that HIF-1α has effects on macrophage biology that promotes atherogenesis in mice.

Approach and Results—

Studies with molecular probes, immunostaining, and laser microdissection of aortas revealed abundant hypoxic, HIF-1α–expressing macrophages in murine atherosclerotic lesions. To investigate the significance of macrophage HIF-1α,
Ldlr
−/−
mice were transplanted with bone marrow from mice with HIF-1α deficiency in the myeloid cells or control bone marrow. The HIF-1α deficiency in myeloid cells reduced atherosclerosis in aorta of the
Ldlr
−/−
recipient mice by ≈72% (
P
=0.006).

In vitro, HIF-1α–deficient macrophages displayed decreased differentiation to proinflammatory M1 macrophages and reduced expression of inflammatory genes. HIF-1α deficiency also affected glucose uptake, apoptosis, and migratory abilities of the macrophages.

Conclusions—

HIF-1α expression in macrophages affects their intrinsic inflammatory profile and promotes development of atherosclerosis.
Osteopontin, a Key Mediator Expressed by Senescent Pulmonary Vascular Cells in Pulmonary Hypertension
Authors: Saker Mirna , Lipskaia Larissa , Marcos Elisabeth , Abid Shariq , Parpaleix Aurelien , Houssaini Amal , Validire Pierre , Girard Philippe , Noureddine Hiba , Boyer Laurent , Vienney Nora , Amsellem Valerie , Marguerit Laurent , Maitre Bernard , Derumeaux Geneviève , Dubois-Rande Jean-Luc , Jourdan-Lesaux Claude , Delcroix Marion , Quarck Rozenn , Adnot Serge
Published: July 2016

Objective—

Senescent pulmonary artery smooth muscle cells (PA-SMCs) may contribute to the pathogenesis of pulmonary hypertension by producing secreted factors. The aim of this study was to explore the role in pulmonary hypertension of extracellular matrix proteins released by senescent PA-SMCs.

Approach and Results—

Polymerase chain reaction array analysis of human PA-SMCs undergoing replicative senescence revealed osteopontin upregulation, which mediated the stimulatory effect of senescent PA-SMC media and matrix on PA-SMC growth and migration. Osteopontin was upregulated in lungs from patients with chronic obstructive pulmonary disease or idiopathic pulmonary arterial hypertension. Prominent osteopontin immunostaining was noted in PA-SMCs that also stained for p16 at sites of vascular hypertrophy, and lung osteopontin levels correlated closely with age. Compared with younger mice, 1-year-old mice displayed higher lung osteopontin levels, right ventricular systolic pressure, pulmonary vessel muscularization, and numbers of PA-SMCs stained for p16 or p21 and also for osteopontin. No such changes with age were observed in osteopontin
−/−
mice, which developed attenuated pulmonary hypertension during hypoxia. Compared with cultured PA-SMCs from young mice, PA-SMCs from 1-year-old mice grew faster; a similar fast growth rate was seen with PA-SMCs from young mice stimulated by matrix or media from old mice. Differences between old/young mouse PA-SMC growth rates were suppressed by antiosteopontin antibodies. PA-SMCs from osteopontin
−/−
mice grew more slowly than did wild-type PA-SMCs; they were stimulated by wild-type PA-SMCs media and matrix, and this effect was stronger with PA-SMCs from older versus younger mice.

Conclusions—

Osteopontin is a key mediator released by senescent PA-SMCs and contributing to pulmonary hypertension progression.
Role of Microvascular Tone and Extracellular Matrix Contraction in the Regulation of Interstitial Fluid
Authors: Mallat Ziad , Tedgui Alain , Henrion Daniel
Published: July 2016

The pathophysiology of aortic dissection is poorly understood, and its risk is resistant to medical treatment. Most studies have focused on a proposed pathogenic role of transforming growth factor-β in Marfan disease and related thoracic aortic aneurysms and aortic dissections. However, clinical testing of this concept using angiotensin II type 1 receptor antagonists to block transforming growth factor-β signaling fell short of promise. Genetic mutations that predispose to thoracic aortic aneurysms and aortic dissections affect components of the extracellular matrix and proteins involved in cellular force generation. Thus, a role for dysfunctional mechanosensing in abnormal aortic wall remodeling is emerging. However, how abnormal mechanosensing leads to aortic dissection remains a mystery. Here, we review current knowledge about the regulation of interstitial fluid dynamics and myogenic tone and propose that alteration in contractile force reduces vascular tone in the microcirculation (here, aortic vasa vasorum) and leads to elevations of blood flow, transmural pressure, and fluid flux into the surrounding aortic media. Furthermore, reduced contractile force in medial smooth muscle cells coupled with alteration of structural components of the extracellular matrix limits extracellular matrix contraction, further promoting the formation of intramural edema, a critical step in the initiation of aortic dissection. The concept is supported by several pathophysiological and clinical observations. A direct implication of this concept is that drugs that lower blood pressure and limit interstitial fluid accumulation while preserving or increasing microvascular tone would limit the risk of dissection. In contrast, drugs that substantially lower microvascular tone would be ineffective or may accelerate the disease and precipitate aortic dissection.
Significant Differences in Antigen-Induced Transendothelial Migration of Human CD8 and CD4 T Effector Memory Cells
Authors: Manes Thomas D. , Pober Jordan S.
Published: July 2016

Objective—

Circulating human T effector memory cell (T
EM
) recognition of nonself MHC (major histocompatibility complex) molecules on allograft endothelial cells can initiate graft rejection despite elimination of professional antigen-presenting cells necessary for naive T-cell activation. Our previous studies of CD4 T
EM
have established that engagement of the T-cell receptor not only activates T cells but also triggers transendothelial migration (TEM) by a process that is distinct from that induced by activating chemokine receptors on T cells, being slower, requiring microtubule-organizing center–directed cytolytic granule polarization to and release from the leading edge of the T cell, and requiring engagement of proteins of the endothelial cell lateral border recycling compartment. Although CD4 T
EM
may contribute to acute allograft rejection, the primary effectors are alloreactive CD8 T
EM
. Whether and how T-cell receptor engagement affects TEM of human CD8 T
EM
is unknown.

Approach and Results—

We modeled TEM of CD8 T
EM
across cultured human microvascular endothelial cells engineered to present superantigen under conditions of venular shear stress in vitro in a flow chamber. Here, we report that T-cell receptor engagement can also induce TEM of this population that similarly differs from chemokine receptor–driven TEM with regard to kinetics, morphological manifestations, and microtubule-organizing center dynamics as with CD4 T
EM
. However, CD8 T
EM
do not require either cytolytic granule release or interactions with proteins of the lateral border recycling compartment.

Conclusions—

These results imply that therapeutic strategies designed to inhibit T-cell receptor–driven recruitment based on targeting granule release or components of the lateral border recycling compartment will not affect CD8 T
EM
and are unlikely to block acute rejection in the clinic.
Proliferation and Recruitment Contribute to Myocardial Macrophage Expansion in Chronic Heart Failure
Authors: Sager Hendrik B. , Hulsmans Maarten , Lavine Kory J. , Moreira Marina B. , Heidt Timo , Courties Gabriel , Sun Yuan , Iwamoto Yoshiko , Tricot Benoit , Khan Omar F. , Dahlman James E. , Borodovsky Anna , Fitzgerald Kevin , Anderson Daniel G. , Weissleder Ralph , Libby Peter , Swirski Filip K. , Nahrendorf Matthias
Published: July 2016

Rationale:

Macrophages reside in the healthy myocardium, participate in ischemic heart disease, and modulate myocardial infarction (MI) healing. Their origin and roles in post-MI remodeling of nonischemic remote myocardium, however, remain unclear.

Objective:

This study investigated the number, origin, phenotype, and function of remote cardiac macrophages residing in the nonischemic myocardium in mice with chronic heart failure after coronary ligation.

Methods and Results:

Eight weeks post MI, fate mapping and flow cytometry revealed that a 2.9-fold increase in remote macrophages results from both increased local macrophage proliferation and monocyte recruitment. Heart failure produced by extensive MI, through activation of the sympathetic nervous system, expanded medullary and extramedullary hematopoiesis. Circulating Ly6C
high
monocytes rose from 64±5 to 108±9 per microliter of blood (
P
<0.05). Cardiac monocyte recruitment declined in

Ccr2
−/−

mice, reducing macrophage numbers in the failing myocardium. Mechanical strain of primary murine and human macrophage cultures promoted cell cycle entry, suggesting that the increased wall tension in post-MI heart failure stimulates local macrophage proliferation. Strained cells activated the mitogen-activated protein kinase pathway, whereas specific inhibitors of this pathway reduced macrophage proliferation in strained cell cultures and in the failing myocardium (
P
<0.05). Steady-state cardiac macrophages, monocyte-derived macrophages, and locally sourced macrophages isolated from failing myocardium expressed different genes in a pattern distinct from the M1/M2 macrophage polarization paradigm. In vivo silencing of endothelial cell adhesion molecules curbed post-MI monocyte recruitment to the remote myocardium and preserved ejection fraction (27.4±2.4 versus 19.1±2%;
P
<0.05).

Conclusions:

Myocardial failure is influenced by an altered myeloid cell repertoire.
Impact of Hypothermia Initiation and Duration on Perihemorrhagic Edema Evolution After Intracerebral Hemorrhage
Authors: Volbers Bastian , Herrmann Sabrina , Willfarth Wolfgang , Lücking Hannes , Kloska Stephan P. , Doerfler Arnd , Huttner Hagen B. , Kuramatsu Joji B. , Schwab Stefan , Staykov Dimitre
Published: July 2016

Background and Purpose—

Intracerebral hemorrhage (ICH) causes high morbidity and mortality. Recently, perihemorrhagic edema (PHE) has been suggested as an important prognostic factor. Therapeutic hypothermia may be a promising therapeutic option to treat PHE. However, no data exist about the optimal timing and duration of therapeutic hypothermia in ICH. We examined the impact of therapeutic hypothermia timing and duration on PHE evolution.

Methods—

In this retrospective, single-center, case–control study, we identified patients with ICH treated with mild endovascular hypothermia (target temperature 35°C) from our institutional database. Patients were grouped according to hypothermia initiation (early: days 1–2 and late: days 4–5 after admission) and hypothermia duration (short: 4–8 days and long: 9–15 days). Patients with ICH matched for ICH volume, age, ICH localization, and intraventricular hemorrhage were identified as controls. Relative PHE, temperature, and intracranial pressure course were analyzed. Clinical outcome on day 90 was assessed using the modified Rankin scale (0–3=favorable and 4–6=poor).

Results—

Thirty-three patients with ICH treated with hypothermia and 37 control patients were included. Early hypothermia initiation led to relative PHE decrease between admission and day 3, whereas median relative PHE increased in control patients (−0.05 [interquartile range, −0.4 to 0.07] and 0.07 [interquartile range, −0.07 to 0.26], respectively;
P
=0.007) and patients with late hypothermia initiation (0.22 [interquartile range 0.12–0.27];
P
=0.037). After day 3, relative PHE increased in all groups without difference. Outcome was not different between patients treated with hypothermia and controls.

Conclusions—

Early hypothermia initiation after ICH onset seems to have an important impact on PHE evolution, whereas our data suggest only limited impact later than day 3 after onset.
A Split Analysis of Plurality: Number in Amharic
Authors: Kramer Ruth
Published: July 2016

Plural morphemes are conventionally analyzed as realizations of Num-(ber). However, much recent research has investigated idiosyncratic/‘‘lexical’’ plural systems where some or all of the plural morphemes are realizations of some other syntactic head. The focus of this article is the intricate plural system of Amharic (Ethiosemitic), where there is considerable evidence that plural morphology is split between two heads: Num and the nominalizing head n. The article thus provides further empirical evidence that the morphosyntax of plurality does not involve Num alone; it also develops a novel analysis of a plural system that relies on two different morphosyntactic heads.
“Early birds” take it easy: diurnal timing is correlated with overall level in activity of zebrafish larvae
Authors: Amin Bawan , Slabbekoorn Hans , Schaaf Marcel , Tudorache Christian
Published: July 2016

Individual animals show consistent differences in behavioural responses when coping with environmental challenges. Consistency over time and across context in a behavioural trait is an indication for animal personality. Chronotypes refer to consistent inter-individual differences in diurnal rhythmicity driven by underlying variation in circadian clock processes. Personality traits and chronotype may relate to a single behavioural syndrome, but few studies have investigated such a link explicitly. Here, we explored zebrafish larvae for the presence of consistency in activity levels and timing, and their correlation with and without external cues (Zeitgeber: light–dark cycle versus constant light). We found individual consistency in activity level and timing, and their correlation independent of the presence of Zeitgeber: early-active individuals were less active overall than late-active individuals. Our study suggests a link between personality and chronotype and provides new insights into the early development of individual variation in behavioural tendencies of zebrafish.
Typification of thirty six names of thirty five recognized taxa in Impatiens (Balsaminaceae), endemic to Western Ghats
Authors: SINGH RAJEEV KUMAR
Published: July 2016

The genus Impatiens Linnaeus (1753: 937) consists of about 1000 species, distributed in the tropical and subtropical regions of the Old World as well as in the northern temperate regions (Mabberley 2008). In India there are about 215 species of Impatiens recorded so far, of which 142 species are endemic, and the diversity occurs in two regions, viz. the Eastern Himalayas and the Western Ghats. During systematic study of this genus in the Western Ghats region of India, I realized that it was necessary to typify 36 binomials of 35 recognized endemic species from the Western Ghats, because no specific herbarium sheet was cited as holotype in protologue of these names and also yet not typified (Vivekananthan et al. 1997, Rathakrishnan 2005, Bhaskar 2012). Here lectotypes are chosen for 35 names and a neotype for one name. The images of the lectotypes, isolectotypes, residual syntypes and neotype specimens at BR, E, G, K, M, MPU, NY and P are available online (http://www.br.fgov.be/research/collections/herbarium, http://elmer.rbge.org.uk/bgbase/vherb/bgbasevherb.php, http://www.ville-ge.ch/musinfo/bd/cjb/chg, http://apps.kew.org/herbcat/navigator.do, https://plants.jstor.org, http://www.collections.univ-montp2.fr/herbier-mpu-presentation/base-de-donnees-botanique-herbier-mpu, http://sweetgum.nybg.org/science/vh & https://science.mnhn.fr/institution/mnhn/search/form), while those at BSI, CAL and MH are not available online. Therefore, the images of selected lectotypes from MH are provided here.
Taxonomic status of Clematis acerifolia var. elobata, based on molecular evidence
Authors: YAN SHUANG-XI , LIU HUI-JIE , LIN LE-LE , LIAO SHUAI , LI JIN-YU , PEI LIN-YING , XIE LEI
Published: July 2016

The morphologically based taxonomic status of Clematis acerifolia var. elobata has been controversial. This study used two nuclear (ITS and ETS) and six plastid (rps16, rpl16, accD, trnS-trnG, atpB-rbcL, and trnV-atpE) molecular markers, and a DNA barcoding analysis to address the taxonomic status of C. acerifolia var. elobata and the relationship among other Clematis species. Our results showed that the discrimination power of ITS, ETS, and atpB-rbcL was better than that of the other tested DNA regions. When all tested sequences combined, most of the sampled taxa were resolved. Though the two taxa are closely related, they have differentiated clearly and formed two clades respectively. The mean divergence of the two taxa was 0.78%, which was higher than closely related Clematis species such as C. heracleifolia and C. pinnata (0.50 %). Considering molecular divergence, morphological differences, and distribution area, we raised C. acerifolia var. elobata to species level.
The genus Dromanthomorphus Pic, 1921 (Coleoptera, Cleroidea: Malachiidae) in South-East Asia
Authors: TSHERNYSHEV SERGEI E.
Published: July 2016

South-East Asian species of the genus Dromanthomorphus Pic, 1921 and several species provisionally attributed to Hadrocnemus Kraatz, 1895 are studied, and their taxonomic position is specified. Three new species are described from the Philippines: D. subflabellatus Tshernyshev, sp. n., D. restrictus Tshernyshev, sp. n. and D. subtilis Tshernyshev, sp. n. Seven species are transferred from Hadrocnemus to Dromanthomorphus, D. apoensis (Wittmer, 1999) comb. n., D. blaisei (Pic, 1926) comb. n., D. chiangensis (Wittmer, 1999) comb. n., D. depressicornis (Pic, 1919) comb. n., D. gravieri (Pic, 1923) comb. n., D. javanus (Wittmer, 1989) comb. n. and D. tonkineus (Pic, 1919) comb. n. Three species are transferred from Dromanthomorphus to Oculapalochrus Tshernyshev, 2015, O. ranuensis Wittmer 1990 comb. n., O. saigonensis (Pic, 1951) comb. n. and O. suttoni Wittmer, 1995 comb. n., and two species from Dromanthomorphus to Mimapalochrus Tshernyshev, 2015, M. cingalensis (Champion, 1921) comb. n. and M. dolokensis Wittmer, 1999 comb. n. Illustrations of male external appearance, metathoracic appendage, urites and genitalia, and distribution maps are provided. A determination key to all species of Dromanthomorphus from South-East Asia is also proposed.
Global Soil Moisture Estimation by Assimilating AMSR-E Brightness Temperatures in a Coupled CLM4–RTM–DART System
Authors: Zhao Long , Yang Zong-Liang , Hoar Timothy J.
Published: July 2016

Very few frameworks exist that estimate global-scale soil moisture through microwave land data assimilation (DA). Toward this goal, such a framework has been developed by linking the Community Land Model, version 4 (CLM4), and a microwave radiative transfer model (RTM) with the Data Assimilation Research Testbed (DART). The deterministic ensemble adjustment Kalman filter (EAKF) within DART is utilized to estimate global multilayer soil moisture by assimilating brightness temperature observations from the Advanced Microwave Scanning Radiometer for Earth Observing System (AMSR-E). A 40-member ensemble of Community Atmosphere Model, version 4.0 (CAM4.0), reanalysis is adopted to drive CLM4 simulations. Space-specific, time-invariant microwave parameters are precalibrated to minimize uncertainties in RTM. Besides, various methods are designed to upscale AMSR-E observations for computational efficiency and time shift CAM4.0 forcing to facilitate global daily assimilations. A series of experiments are conducted to quantify the DA sensitivity to microwave parameters, choice of assimilated observations, and different CLM4 updating schemes. Evaluation results indicate that the newly established CLM4–RTM–DART framework improves the open-loop CLM4-simulated soil moisture. Precalibrated microwave parameters, rather than their default values, can ensure a more robust global-scale performance. In addition, updating near-surface soil moisture is capable of improving soil moisture in deeper layers (0–30 cm), while simultaneously updating multilayer soil moisture fails to obtain intended improvements. Future work is needed to address the systematic bias in CLM4 that cannot be fully covered through the ensemble spread in CAM4.0 reanalysis.
A Finescale Radar Examination of the Tornadic Debris Signature and Weak-Echo Reflectivity Band Associated with a Large, Violent Tornado
Authors: Houser Jana Lesak , Bluestein Howard B. , Snyder Jeffrey C.
Published: July 2016

High-resolution data of the tornadic debris signature (TDS) and weak-echo reflectivity band (WRB) associated with a large, violent tornado on 24 May 2011 in central Oklahoma are examined using a rapid-scan, X-band, polarimetric, mobile Doppler radar. Various characteristics of these features and their evolution are examined over time intervals of 20 s or less. The formation of the TDS, debris fallout, and inhomogeneities in the TDS structure, are analyzed from volumetric and single-elevation observations. Constant-radius vertical cross sections of Doppler velocity, reflectivity, and copolar cross-correlation coefficient are compared at various times during the tornado’s life cycle; from them it is found that the weak echo column (WEC) is considerably narrower than the TDS and the WEC is confined to the strong gradient of Doppler velocities in the tornado’s core. The TDS of the mature tornado extends radially outward, bound approximately by the 40 m s−1 radial isodop.

Rapid-scan, near-surface data were collected for a period of 6 min, during which 2-s single-elevation PPI updates at 1° were available at heights below 100 m above radar level. During this period, a WRB associated with a visually observed horizontal vortex developed east of the tornado, along the leading edge of the secondary rear-flank gust front, as the tornado was rapidly intensifying. A relationship was noted between reduced radar-observed reflectivity and increased radar-observed radial convergence/divergence in the vicinity of the horizontal vortex as it strengthened. This feature is qualitatively analyzed and hypotheses explaining its generation and structure are discussed.
The Role of Consumer Narrative Enjoyment and Persuasion Awareness in Product Placement Advertising
Authors: Gillespie Brian , Joireman Jeff
Published: July 2016

Researchers have repeatedly demonstrated that consumers respond to commercial messages based on the advertising techniques through which they are delivered. One growing technique is product placement advertising, generally defined as the inclusion of products and brands in media designed with a similar form and appearance to nonadvertising content. Importantly, consumer opinions of product placement as an advertising technique have gone relatively unexamined. A model is therefore proposed to outline factors that influence consumers’ attitudes toward product placement advertising. Results across two studies indicate (a) product placements play a role in consumers’ narrative enjoyment, which positively influences attitudes toward product placement advertising, (b) consumers’ awareness of the persuasive intent of product placement negatively influences attitudes toward product placements, and (c) perceptions of product placements along these narrative enjoyment and persuasion awareness dimensions affect brand evaluations of placed products. Managerial implications, theoretical contributions, and directions for future research are discussed.
An Analysis of Productivity Spillovers from Foreign Direct Investment in India’s Services Sector
Authors: Thakur Pooja , Burange L.G.
Published: July 2016

The paper tries to study productivity spillovers from foreign direct investment in the services sector of India. Using firm-level data for the period 2000–2010, horizontal and vertical spillovers are tested with the help of panel data fixed effects ‘within’ model. Spillovers across different industries of the services sector are also examined. It is inferred that horizontal spillovers positively affect total factor productivity of domestic firms in the services sector. Spillovers through backward vertical channels and forward vertical channels are, however, encountered to be negative. At an industry level, it is deduced that productivity spillovers vary across different industries with horizontal spillovers being more dominant than vertical spillovers.
Who Are to Be the Successors of European Jewry? The Restitution of German Jewish Communal and Cultural Property
Authors: Lustig Jason
Published: July 2016

Who are to be the successors of European Jewry? This question faced Jewish leaders after the Holocaust, in terms both legal – inheriting heirless property – as well as spiritual – carrying forward Jewish culture. Looted Jewish property was never merely a matter of inheritance. Instead, disputes revolved around the future of Jewish life. While Jewish restitution organizations sought control of former communal property to use around the world, some German-Jewish émigrés and survivors in Germany sought to establish themselves as direct successors to former Jewish communities and institutions. Such debates set the stage and the stakes for mass archival transfer to Israel/Palestine in the 1950s. The fate of the German Jewish communal archives highlights the nature of postwar restitution debates as proxy for the issue of the continuation of Jewish culture and history, calling into question the nature of restitution itself. As opposed to policies of proportional allocation to meet the needs of radically diminished Jewish communities, wholesale transfer of archives reflected a belief in a radical rupture in German Jewish existence as well as Israel’s position as successor to European Jewry. The fate of the archives, which broke with archival practices of provenance, concretized and validated the historical rupture represented by the Holocaust.
Counterfeits or Shanzhai? The Role of Face and Brand Consciousness in Luxury Copycat Consumption
Authors: Jiang Ling , Shan Juan
Published: July 2016

This study responds to the emergence of the Shanzhai phenomenon in the international marketplace and introduces the Shanzhai phenomenon into the consumer behavior literature by defining it and comparing it with well-known concepts like luxury counterfeits. More specifically, it examines how consumers’ face and brand consciousness influence their willingness to buy luxury counterfeits rather than Shanzhai products. The results show that consumers who are more face conscious are more likely to choose luxury counterfeits than Shanzhai products. In addition, consumers’ face consciousness elicits a high concern for well-known brands, which also in turn leads to a more favorable attitude toward luxury counterfeits than Shanzhai products. These findings enable researchers to better understand consumers’ responses toward both Shanzhai and counterfeit products and help companies that are protecting their original brands to tailor their consumer-directed measures more effectively.
Can the International Criminal Court contribute to the Responsibility to Protect?
Authors: Schiff Benjamin N
Published: July 2016

The Responsibility to Protect (R2P) norm asserts that states have duties beyond their borders to help avoid, respond to, and prevent recurrence of circumstances that produce massive human rights violations. Actions undertaken to implement those duties can include aid, reform, or more muscular involvements. The need for such engagement implies that the target state’s government is losing or has lost its legitimacy. Labeling by the International Criminal Court (ICC) of a conflict as a ‘situation’ under its purview asserts that large-scale crimes are likely taking place for which individuals should be held accountable. This should trigger R2P considerations. However, the fit between R2P and the ICC is uncomfortable. Although the ICC may appear a useful tool for R2P, forays into the politics of R2P by the ICC are undertaken at its peril. Moreover, so far, the ICC has not clearly had positive effects upon conflict. While the ICC can be idealized as a contributor to R2P, coordination is formally non-existent and the Court’s protection effects are ambiguous.
The Perils of Panic
Authors: Sinha Michael S. , Parmet Wendy E.
Published: July 2016

This Article explores the connections between emerging infectious diseases, domestic disease panics, global health, and the law by comparing the American response to Ebola to the initial American response to the AIDS epidemic. We demonstrate that in both cases the arrival of a new deadly disease was initially met with fear, stigma and the use of law to “other” those associated with the disease. We begin by reviewing the initial responses to the AIDS epidemic. We then offer a brief history of emerging infectious disease scares over the past few decades, highlighting the problematic rhetoric that paved the way for the Ebola panic. We then review the 2014 Ebola outbreak, noting its similarities and distinctions from the early AIDS epidemic. Finally, we examine United States policies regarding HIV and Ebola in Africa. We conclude with some tentative observations about the relationship between germ panics, law, and public health.
Firm-Led Malaria Prevention in the United States, 1910-1920
Authors: Carson Byron
Published: July 2016

In the absence of capable government services, a railroad company in Texas and multiple cotton mills in North Carolina successfully prevented malaria in the early twentieth century. This Article looks through the lens of economics to understand how and why people had the incentive to privately coordinate malaria prevention during this time, but not after. These firms, motivated by increases in productivity and profit, implemented extensive anti-malaria programs and used their hierarchical organizational structures to monitor performance. The factors underlying the decline of private prevention include a fall in the overall rate of malaria, the increasing presence of the federal government, and technological innovations that lowered exposure to mosquitoes. Understanding how, why, and when firms can prevent diseases has important implications for current disease policy, especially where governments, international organizations, and technologies are not enough.
Leveraging Novel and Existing Pathways to Approve New Therapeutics to Treat Serious Drug-Resistant Infections
Authors: Hwang Thomas J. , Kesselheim Aaron S.
Published: July 2016

Accelerating the development and approval of novel therapeutics has emerged as a key public health priority given the mortality, morbidity, and economic costs associated with infections caused by drug-resistant bacteria. However, there is limited empirical evidence to guide policymaking, such as the factors that may disadvantage antibiotics compared to other classes of drugs. In this Article, we empirically examine characteristics of the key clinical trials underpinning FDA's approval of antibiotics and other drugs over the past decade. Despite perceptions that antibiotic trials are larger and more difficult to conduct, we find that antibiotic trials are no larger than those conducted for drugs approved in other disease areas with high unmet medical needs, suggesting that policymakers may need to target other levers to meaningfully stimulate innovation. We discuss the risks and benefits of harnessing new and existing regulatory pathways to speed the approval of new drugs, particularly those intended to treat patients with serious and life-threatening infections, and we evaluate ways that proposals for new regulatory pathways could be improved to better prioritize and expedite the approval of therapies with the greatest potential for patient health benefits.
Exploring the Obstacles to Implementing Economic Mechanisms to Stimulate Antibiotic Research and Development
Authors: Baraldi Enrico , Ciabuschi Francesco , Leach Ross , Morel Chantal M. , Waluszewski Alexandra
Published: July 2016

This Article examines the potential stakeholder-related obstacles hindering the implementation of mechanisms to re-ignite the development of novel antibiotics. Proposed economic models and incentives to drive such development include: Public Funding of Research and Development (“R&D”), Tax Incentives, Milestone Prizes, End Payments, Intellectual Property (“IP”) and Exclusivity Extensions, Pricing and Reimbursement Incentives, Product Development Partnerships (“PDPs”), and the Options Market for Antibiotics model. Drawing on personal experience and understanding of the antibiotic field, as well as stakeholder consultation and numerous expert meetings within the DRIVE-AB project and Uppsala Health Summit 2015, the Authors identify obstacles attributable to the following actors: Universities and Research Institutes, Small and Medium-sized Enterprises (“SMEs”), Large Pharmaceutical Companies, Marketing Approval Regulators, Payors, Healthcare Providers, National Healthcare Authorities, Patients, and Supranational Institutions.

The analysis also proposes a characterization and ranking of the difficulty associated with implementing the reviewed mechanisms. Public Funding of R&D, Pricing and Reimbursement Incentives, and PDPs are mechanisms expected to meet highly systemic barriers (i.e., obstacles across the entire antibiotic value chain), imposing greater implementation challenges in that they require convincing and involving several motivationally diverse actors in order to have much effect.
The Economic Theory of Patent Protection and Pandemic Influenza Vaccines
Authors: Eccleston-Turner Mark
Published: July 2016

The creation of new vaccines is one of the key challenges in the battle against global infectious diseases. Therefore, creating the optimal conditions for innovation in vaccines is one of the most important roles law may undertake in this battle. In relation to pharmaceuticals, the economic theory of patent protection is commonly cited by industry and in the academic literature to justify the patenting of life-saving medicines and vaccines. The economic theory of patent protection holds that innovation occurs due to patents protecting the research and development investment made by the innovator. Proponents of this theory claim that without patents such innovation in medicines and vaccines would occur at a significantly reduced rate. This Article considers the applicability of the economic theory of patent protection to pandemic influenza vaccines. This Article examines a number of factors relevant to patent law, theory, and innovation including: the patent landscape for pandemic influenza vaccines; the market dominance enjoyed by manufacturers; the actual risk posed by imitators making generic vaccines if patent protection were not in place; and, the licensing and regulatory provisions for creating generic vaccines.

According to the economic theory of patent protection, a patent incentivizes innovation by providing an innovator with a temporary monopoly regarding their innovation, and by protecting them from the threat posed by imitators who wish to make a cheap replica of the product. However, even without a patent, pandemic influenza vaccine manufacturers are in this position. Due to economies of scale and the complicated regulatory and licensing frameworks relevant to bringing a pandemic influenza vaccine to market, manufacturers are at little to no risk from generic imitators. Moreover, there is a very strong incentive to innovate because pandemic influenza vaccine manufacturers are selling a product for which demand exceeds supply to a captive market of nations and organizations, each of which is hoping to secure as much vaccine as possible. The unique conditions associated with pandemic influenza vaccines appear to provide more of an incentive to innovate and research in this field than the fact that the innovations can be patented.
Intracerebral GM-CSF contributes to transendothelial monocyte migration in APP/PS1 Alzheimer’s disease mice
Authors: Shang De S , Yang Yi M , Zhang Hu , Tian Li , Jiang Jiu S , Dong Yan B , Zhang Ke , Li Bo , Zhao Wei D , Fang Wen G , Chen Yu H
Published: July 2016

Although tight junctions between human brain microvascular endothelial cells in the blood–brain barrier prevent molecules or cells in the bloodstream from entering the brain, in Alzheimer’s disease, peripheral blood monocytes can “open” these tight junctions and trigger subsequent transendothelial migration. However, the mechanism underlying this migration is unclear. Here, we found that the CSF2RB, but not CSF2RA, subunit of the granulocyte-macrophage colony-stimulating factor receptor was overexpressed on monocytes from Alzheimer’s disease patients. CSF2RB contributes to granulocyte-macrophage colony-stimulating factor-induced transendothelial monocyte migration. Granulocyte-macrophage colony-stimulating factor triggers human brain microvascular endothelial cells monolayer tight junction disassembly by downregulating ZO-1 expression via transcription modulation and claudin-5 expression via the ubiquitination pathway. Interestingly, intracerebral granulocyte-macrophage colony-stimulating factor blockade abolished the increased monocyte infiltration in the brains of APP/PS1 Alzheimer’s disease model mice. Our results suggest that in Alzheimer’s disease patients, high granulocyte-macrophage colony-stimulating factor levels in the brain parenchyma and cerebrospinal fluid induced blood–brain barrier opening, facilitating the infiltration of CSF2RB-expressing peripheral monocytes across blood–brain barrier and into the brain. CSF2RB might be useful as an Alzheimer’s disease biomarker. Thus, our findings will help to understand the mechanism of monocyte infiltration in Alzheimer’s disease pathogenesis.
Between rights and denials: Bedouin indigeneity in the Negev/Naqab
Authors: Yiftachel Oren , Roded Batya , Kedar Alexandre (Sandy)
Published: July 2016

The paper examines the nature of indigenous identity among Bedouin Arabs in Negev/Naqab, Israel, against a background of conceptual, legal and political controversy. It traces theoretically and comparatively the rise of indigeneity as a relational concept, deriving from colonial and postcolonial settings. The concept is shown to be part of the globalization of human rights struggle, with a potential of the indigeneity discourse to empower colonized and exploited minorities, as well as provide a platform for transitional justice. The heart of the paper provides a rebuttal of several arguments made by a group of scholars associated with the Israeli state, named here “the deniers”, who have worked to reject Bedouin (and general Palestinian) claims for indigenous status, thereby denying their entitlement to a range of human and communal rights. The paper offers a systematic examination of historical and geographic evidence and reveals that “the deniers” have raised several relevant questions and dilemmas. However, these do not undermine the typical indigenous characteristics of the Naqab Bedouin Arabs. Research shows clearly that Bedouins belong within the group of indigenous societies according to accepted international definitions and norms. This understanding obliges the Israeli state to protect Bedouin Arabs from further removals, dispossession and marginalization, as well as correct, where possible, the profound damage caused by their past dispossession, eviction and marginalization.