bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation
Authors: Maurissen Lisbeth F. A. , Thomassen M. Christella L. G. D. , Nicolaes Gerry A. F. , Dahlbäck Björn , Tans Guido , Rosing Jan , Hackeng Tilman M.
Published: December 2007

Protein S expresses cofactor activity for activated protein C (APC) by enhancing the APC-catalyzed proteolysis at R306 in factor Va. It is generally accepted that only free protein S is active and that complex formation with C4b-binding protein (C4BP) inhibits the APC-cofactor activity of protein S. However, the present study shows that protein S-C4BP expresses APC-cofactor activity and stimulates APC-catalyzed proteolysis at R306 more than 10-fold, but instead inhibits proteolysis at R506 by APC 3- to 4-fold. Free protein S stimulates APC-catalyzed cleavage at R306 approximately 20-fold and has no effect on cleavage at R506. The resulting net effect of protein S-C4BP complex formation on APC-catalyzed factor Va inactivation is a 6- to 8-fold reduction in factor Va inactivation when compared with free protein S, which is not explained by inhibition of APC-cofactor activity of protein S at R306, but by generation of a specific inhibitor for APCcatalyzed proteolysis at R506 of factor Va. These results are of interest for carriers of the factor VLeiden mutation (R506Q), as protein S-C4BP effectively enhances APC-catalyzed factor Va (R306) inactivation in plasma containing factor VLeiden.
Aurora kinase inhibitory VX-680 increases Bax/Bcl-2 ratio and induces apoptosis in Aurora-A-high acute myeloid leukemia
Authors: Huang Xue-Fei , Luo Shao-Kai , Xu Jie , Li Juan , Xu Duo-Rong , Wang Li-Hui , Yan Min , Wang Xian-Ren , Wan Xiang-Bo , Zheng Fei-Meng , Zeng Yi-Xin , Liu Quentin
Published: December 2007

Previously, we and others showed that mitotic Aurora-A kinase (Aur-A) was required for accurate mitotic entry and proper spindle assembly. In this study, we found that expression of Aur-A was markedly elevated in bone marrow mononuclear cells (BMMCs) obtained from a significant portion of de novo acute myeloid leukemia (AML) patients. Targeting human primary AML cells with Aur-A kinase inhibitory VX-680 led to apoptotic cell death in a dose-dependent manner. Importantly, VX-680–induced cell death was preferentially higher in Aur-A-high primary leukemic blasts compared with Aur-A-low AML (P < .001) or normal BMMCs (P < .001), suggesting the possible pharmacologic window in targeting Aurora kinase among Aur-A-high VX-680–sensitive leukemia patients. VX-680–induced cell death in AML cell lines was accompanied by formation of monopolar mitotic spindles, G2/M phase arrest, decreased phosphorylated(p)-Akt-1, and increased proteolytic cleavage of procaspase-3 and poly(ADP)ribose polymerase. Notably, VX-680 increased Bax/Bcl-2 expression ratio, a favorable proapoptotic predictor for drug response and survival in AML. Lastly, VX-680 enhanced the cytotoxic effect of the chemotherapeutic agent etoposide (VP16) on AML cells. Together, we concluded that Aurora kinases were potentially therapeutic targets for AML and that Aur-A-high expression may serve as a differential marker for selective treatment.
Bortezomib blocks Bax degradation in malignant B cells during treatment with TRAIL
Authors: Liu Feng-Ting , Agrawal Samir G. , Gribben John G. , Ye Hongtao , Du Ming-Qing , Newland Adrian C. , Jia Li
Published: December 2007

Proapoptotic Bcl-2 family member Bax is a crucial protein in the induction of apoptosis, and its activation is required for this process. Here we report that Bax is a short-lived protein in malignant B cells and Bax protein levels decreased rapidly when protein synthesis was blocked. Malignant B cells were relatively resistant to tumor necrosis factor–related apoptosis inducing ligand (TRAIL)–induced apoptosis, and this correlated with low basal Bax protein levels. Furthermore, during treatment with TRAIL, the resistant cell lines showed prominent Bax degradation activity. This degradation activity was localized to mitochondrial Bax and could be prevented by truncated Bid, a BH3-only protein; in contrast, cytosolic Bax was relatively stable. The proteasome inhibitor bortezomib is a potent drug in inducing apoptosis in vitro in malignant B-cell lines and primary chronic lymphocytic leukemic (CLL) cells. In CLL cells, bortezomib induced Bax accumulation, translocation to mitochondria, conformational change, and oligomerization. Accumulation and stabilization of Bax protein by bortezomib-sensitized malignant B cells to TRAIL-induced apoptosis. This study reveals that Bax instability confers resistance to TRAIL, which can be reversed by Bax stabilization with a proteasome inhibitor.
A large-scale proteomic analysis of human embryonic stem cells
Authors: Schulz Thomas C , Swistowska Anna Maria , Liu Ying , Swistowski Andrzej , Palmarini Gail , Brimble Sandii N , Sherrer Eric , Robins Allan J , Rao Mahendra S , Zeng Xianmin
Published: December 2007

Background

Much of our current knowledge of the molecular expression profile of human embryonic stem cells (hESCs) is based on transcriptional approaches. These analyses are only partly predictive of protein expression however, and do not shed light on post-translational regulation, leaving a large gap in our knowledge of the biology of pluripotent stem cells.

Results

Here we describe the use of two large-scale western blot assays to identify over 600 proteins expressed in undifferentiated hESCs, and highlight over 40 examples of multiple gel mobility variants, which are suspected protein isoforms and/or post-translational modifications. Twenty-two phosphorylation events in cell signaling molecules, as well as potential new markers of undifferentiated hESCs were also identified. We confirmed the expression of a subset of the identified proteins by immunofluorescence and correlated the expression of transcript and protein for key molecules in active signaling pathways in hESCs. These analyses also indicated that hESCs exhibit several features of polarized epithelia, including expression of tight junction proteins.

Conclusion

Our approach complements proteomic and transcriptional analysis to provide unique information on human pluripotent stem cells, and is a framework for the continued analyses of self-renewal.
Pancreatectomy for non-pancreatic malignancies results in improved survival after R0 resection
Authors: Varker Kimberly A , Muscarella Peter , Wall Kristian , Ellison Christopher , Bloomston Mark
Published: December 2007

Background

Pancreatectomy has a high morbidity but remains the only chance of cure for pancreatic cancer. Its efficacy for non-pancreatic malignancies is less clear. We reviewed our experience with pancreatectomy for non-pancreatic malignancies to determine outcomes and identify predictors of survival.

Patients and methods

The records of patients who underwent pancreatectomy for non-pancreatic malignancies between 1990 and 2005 were reviewed. Survival curves were constructed using the Kaplan-Meier method and compared using log-rank analysis. Cox proportional hazards was used to identify predictors of survival.

Results

29 patients (18 M/11 F) with a mean age of 59.9 years (range 29–86) underwent pancreatectomy for non-pancreatic malignancies. 19 (66%) primary malignancies were GI in origin. Most operations were undertaken with curative intent (76%), whereas the remainder was for symptom palliation. Pancreatectomy was completed for metastatic disease in 7 patients (24%) or en bloc to achieve negative margins in 22 patients (76%). Complete (i.e., R0) resection was achieved in 17 (59%). Perioperative mortality was 3%. Median follow-up was 15 months (range 7–172). Median overall survival was 12 months with 1-year survival of 48%. Significant predictors of improved survival by univariate analysis were R0 resection, non-GI primary, and pancreatic metastasectomy (vs. en bloc resection). Only R0 resection was predictive of long-term survival by multivariate analysis (median 21 months vs. 6).

Conclusion

Pancreatic resection for non-pancreatic malignancies can be completed with minimal mortality. However, incomplete resection results in poor overall survival. Pancreatectomy for non-pancreatic malignancies should only be undertaken if complete resection is possible.
The role of epithelial Toll-like receptor signaling in the pathogenesis of intestinal inflammation
Authors: Gribar Steven C , Anand Rahul J , Sodhi Chhinder P , Hackam David J
Published: December 2007

Emerging evidence suggests that the innate immune system, comprised of Toll-like receptors (TLRs) and their associated molecules, plays a pivotal role in the regulation of intestinal inflammation and in the response to invading pathogens. Although TLRs are thought to have predominantly beneficial effects in pathogen recognition and bacterial clearance by leukocytes, their dysregulation and unique signaling effects within intestinal epithelia in the setting of inflammation may have devastating consequences. For instance, activation of TLR4 in enterocytes leads to an inhibition of enterocyte migration and proliferation as well as the induction of enterocyte apoptosis—factors that would be expected to promote intestinal injury while inhibiting intestinal repair. TLR signaling has been shown to be abnormal in several intestinal inflammatory diseases, including Crohn’s disease, ulcerative colitis, and necrotizing enterocolitis. This review serves to examine the evidence regarding the patterns of expression and signaling of TLRs in the intestinal mucosa at basal levels and during physiologic stressors to gain insights into the pathogenesis of intestinal inflammation. We conclude that the data reviewed suggest that epithelial TLR signaling—acting in concert with TLR signaling by leukocytes—participates in the development of intestinal inflammation. We further conclude that the evidence reviewed provides a rationale for the development of novel, epithelial-specific, TLR-based agents in the management of diseases of intestinal inflammation.
The re-emerging role of the intestinal microflora in critical illness and inflammation: why the gut hypothesis of sepsis syndrome will not go away
Authors: Alverdy John C , Chang Eugene B
Published: December 2007

Recent advances in the ability to genetically interrogate microbial communities within the intestinal tract of humans have revealed many striking findings. That there may be as many as 300 unculturable and unclassified microbes within the human intestinal tract opens the possibility that yet-unidentified microbes may play a role in various human diseases [1]. Technologically, the regional and spatial aspects of intestinal microbial communities can now be better appreciated by emerging genetic and in vivo imaging systems using a bioinformatics approach [2]. Finally, in situ PCR of tissues and blood now allows the detection of microbes at concentrations that would otherwise remain undetected by culture alone [3]. In the aggregate, these studies have empowered clinicians to readdress the issue of how our microbial partners are affected by extreme states of physiologic stress and antibiotic use through the course of critical illness. The role of microbes in systemic inflammatory states, such as systemic inflammatory response syndrome, as well as in primary intestinal mucosal diseases, such as necrotizing enterocolitis, inflammatory bowel disease, and ischemia-reperfusion injury, can now be more completely defined, and the microbial genes that mediate the immune activation during these disorders can be identified. The 2008 roadmap initiative at the National Institutes of Health to fully define the human microbiome is further testament to the power of this technology and the importance of understanding how intestinal microbes, their genes, and their gene products affect the course of human disease and inflammation.
Effects of Previous Antiresorptive Therapy on the Bone Mineral Density Response to Two Years of Teriparatide Treatment in Postmenopausal Women with Osteoporosis
Authors: Boonen Steven , Marin Fernando , Obermayer-Pietsch Barbara , Simões Maria E. , Barker Clare , Glass Emmett V. , Hadji Peyman , Lyritis George , Oertel Heide , Nickelsen Thomas , McCloskey Eugene V.
Published: December 2007

Introduction: EUROFORS was a 2-yr prospective, randomized trial of postmenopausal women with established osteoporosis, designed to investigate various sequential treatments after teriparatide 20 μg/d for 1 yr. The present secondary analysis examined the effects of 2 yr of open-label teriparatide in women previously treated with antiresorptive drugs for at least 1 yr.

Methods: A subgroup of 245 women with osteoporosis who had 2 yr of teriparatide treatment were stratified by previous predominant antiresorptive treatment into four groups: alendronate (n = 107), risedronate (n = 59), etidronate (n = 30), and non-bisphosphonate (n = 49). Bone mineral density (BMD) at the lumbar spine and hip was determined after 6, 12, 18, and 24 months, and bone formation markers were measured after 1 and 6 months.

Results: Significant increases in bone formation markers occurred in all groups after 1 month of teriparatide treatment. Lumbar spine BMD increased at all visits, whereas a transient decrease in hip BMD, which was subsequently reversed, was observed in all groups. BMD responses were similar in all previous antiresorptive groups. Previous etidronate users showed a higher increase at the spine but not at the hip BMD. Duration of previous antiresorptive therapy and lag time between stopping previous therapy and starting teriparatide did not affect the BMD response at any skeletal site. Treatment-emergent adverse events were similar to those reported in treatment-naive postmenopausal women with osteoporosis treated with teriparatide.

Conclusions: Teriparatide induces positive effects on BMD and markers of bone formation in postmenopausal women with established osteoporosis, regardless of previous long-term exposure to antiresorptive therapies.
Kallmann’s Syndrome: A Comparison of the Reproductive Phenotypes in Men Carrying KAL1 and FGFR1/KAL2 Mutations
Authors: Salenave Sylvie , Chanson Philippe , Bry Hélène , Pugeat Michel , Cabrol Sylvie , Carel Jean Claude , Murat Arnaud , Lecomte Pierre , Brailly Sylvie , Hardelin Jean-Pierre , Dodé Catherine , Young Jacques
Published: December 2007

Context: Kallmann’s syndrome (KS) is a genetically heterogeneous disorder consisting of congenital hypogonadotropic hypogonadism (CHH) with anosmia or hyposmia.

Objective: Our objective was to compare the reproductive phenotypes of men harboring KAL1 and FGFR1/KAL2 mutations.

Design and Patients: We studied the endocrine features reflecting gonadotropic-testicular axis function in 39 men; 21 had mutations in KAL1 and 18 in FGFR1/KAL2, but none had additional mutations in PROK-2 or PROKR-2 genes.

Results: Puberty failed to occur in the patients with KAL1 mutations, all of whom had complete CHH. Three patients with FGFR1/KAL2 mutations had normal puberty, were eugonadal, and had normal testosterone and gonadotropin levels. Cryptorchidism was more frequent (14 of 21 vs. 3 of 15; P < 00.1) and testicular volume (2.4 ± 1.1 vs. 5.4 ± 2.4 ml; P < 0.001) was smaller in CHH subjects with KAL1 mutations than in subjects with FGFR1/KAL2 mutations. The mean basal plasma FSH level (0.72 ± 0.47 vs. 1.48 ± 0.62 IU/liter; P < 0.05), serum inhibin B level (19.3 ± 10.6 vs. 39.5 ± 19.3 pg/ml; P < 0.005), basal LH plasma level (0.57 ± 0.54 vs. 1.0 ± 0.6 IU/liter; P < 0.01), and GnRH-stimulated LH plasma level (1.2 ± 1.0 vs. 4.1 ± 3.5 IU/liter; P < 0.01) were significantly lower in the subjects with KAL1 mutations. LH pulsatility was studied in 13 CHH subjects with KAL1 mutations and seven subjects with FGFR1/KAL2 mutations; LH secretion was nonpulsatile in all the subjects, but mean LH levels were lower in those with KAL1 mutations.

Conclusion: KAL1 mutations result in a more severe reproductive phenotype than FGFR1/KAL2 mutations. The latter are associated with a broader spectrum of pubertal development and with less severe impairment of gonadotropin secretion.
Effects of Graded Doses of Testosterone on Erythropoiesis in Healthy Young and Older Men
Authors: Coviello Andrea D. , Kaplan Beth , Lakshman Kishore M. , Chen Tai , Singh Atam B. , Bhasin Shalender
Published: December 2007

Context: Erythrocytosis is a dose-limiting adverse effect of testosterone therapy, especially in older men.

Objective: Our objective was to compare the dose-related changes in hemoglobin and hematocrit in young and older men and determine whether age-related differences in erythropoietic response to testosterone can be explained by changes in erythropoietin and soluble transferrin receptor (sTfR) levels.

Design: We conducted a secondary analysis of data from a testosterone dose-response study in young and older men who received long-acting GnRH agonist monthly plus one of five weekly doses of testosterone enanthate (25, 50, 125, 300, or 600 mg im) for 20 wk.

Setting: The study took place at a General Clinical Research Center.

Participants: Participants included 60 older men aged 60–75 yr and 61 young men aged 19–35 yr.

Outcome Measures: Outcome measures included hematocrit and hemoglobin and serum erythropoietin and sTfR levels.

Results: Hemoglobin and hematocrit increased significantly in a linear, dose-dependent fashion in both young and older men in response to graded doses of testosterone (P < 0.0001). The increases in hemoglobin and hematocrit were significantly greater in older than young men. There was no significant difference in percent change from baseline in erythropoietin or sTfR levels across groups in either young or older men. Changes in erythropoietin or sTfR levels were not significantly correlated with changes in total or free testosterone levels.

Conclusions: Testosterone has a dose-dependent stimulatory effect on erythropoiesis in men that is more pronounced in older men. The testosterone-induced rise in hemoglobin and hematocrit and age-related differences in response to testosterone therapy may be mediated by factors other than erythropoietin and sTfR.
Bone Mineral Density Changes during the Menopause Transition in a Multiethnic Cohort of Women
Authors: Finkelstein Joel S. , Brockwell Sarah E. , Mehta Vinay , Greendale Gail A. , Sowers MaryFran R. , Ettinger Bruce , Lo Joan C. , Johnston Janet M. , Cauley Jane A. , Danielson Michelle E. , Neer Robert M.
Published: December 2007

Context: Rates of bone loss across the menopause transition and factors associated with variation in menopausal bone loss are poorly understood.

Objective: Our objective was to assess rates of bone loss at each stage of the transition and examine major factors that modify those rates.

Design, Setting, and Participants: We conducted a longitudinal cohort study of 1902 African-American, Caucasian, Chinese, or Japanese women participating in The Study of Women’s Health Across the Nation. Women were pre- or early perimenopausal at baseline.

Outcome Measure: We assessed bone mineral density (BMD) of the lumbar spine and total hip across a maximum of six annual visits.

Results: There was little change in BMD during the pre- or early perimenopause. BMD declined substantially in the late perimenopause, with an average loss of 0.018 and 0.010 g/cm2·yr from the spine and hip, respectively (P < 0.001 for both). In the postmenopause, rates of loss from the spine and hip were 0.022 and 0.013 g/cm2·yr, respectively (P < 0.001 for both). During the late peri- and postmenopause, bone loss was approximately 35–55% slower in women in the top vs. the bottom tertile of body weight. Apparent ethnic differences in rates of spine bone loss were largely explained by differences in body weight.

Conclusions: Bone loss accelerates substantially in the late perimenopause and continues at a similar pace in the first postmenopausal years. Body weight is a major determinant of the rate of menopausal BMD loss, whereas ethnicity, per se, is not. Healthcare providers should consider this information when deciding when to screen women for osteoporosis.
GULLAH NEGATION: A VARIABLE ANALYSIS
Authors: Weldon Tracey L.
Published: December 2007

This article provides a variable analysis of negation in Gullah and considers the implications of the observed patterns of variability for the debate over the history and development of African American English (AAE). For many years now, linguists have debated over the possibility of an AAE-creole connection and have hypothesized in particular about the putative role of Gullah (or a Gullah-like creole) on the origins and development of AAE. In recent years, negation has become a central topic in this debate, with examinations of variable negation in both early and contemporary varieties of AAE. However, practically no analysis has been done on the system of variable negation in Gullah. This study aims to fill this gap in the literature by providing a quantitative analysis of variable negation in both copula and noncopula constructions in Gullah. While no definitive claims are made about the AAE-Gullah connection based on this analysis, certain patterns in the data, such as the alternation between ain't and didn't in past contexts, allow for the possibility of a historical connection between the two varieties.
LIKEAND LANGUAGE IDEOLOGY: DISENTANGLING FACT FROM FICTION
Authors: D'Arcy Alexandra
Published: December 2007

The selective attention paid to the language of adolescents has led to the enduring belief that young people are ruining the language and that, as a consequence, the language is degenerating. One feature of contemporary vernaculars that is often held up as exemplification of these ideological principles is like, the “much-deplored interjection... that peppers the talk of so many of the unpliant young these days” (Wilson 1987, 92). There is, in fact, an intricate lore surrounding like. It includes the idea that like is meaningless, that women say it more than men do, and that it is an Americanism, introduced by the Valley Girls. This article systematically addresses ideologically driven myths about the uses and users of like. Drawing on empirical data, it seeks to disentangle the facts from the fiction that has been cultivated in the general social consciousness. It is argued that most beliefs about like are either false (e.g., meaninglessness, Valley Girl creationism) or too broad to reflect any coherent reality (e.g., the role of women). However, in examining individual beliefs about like, it becomes clear that each contributes to the perpetuation of others in important and nontrivial ways.
Evaluation of Thermal Requirements for the Propagation and Recovery of June Suckers
Authors: Kindschi Greg A , Toner Matt , Fraser William C , Routledge M Doug , Wilson Maureen , Converse Yvette
Published: December 2007

Determining the optimal rearing temperature for the June sucker Chasmistes liorus has been identified as a key component necessary for the design of a new June sucker hatchery and for achieving the June Sucker Recovery Implementation Program supplementation goal of 350,000 fish of 20-cm length annually. A laboratory study was conducted to monitor the performance of June suckers reared at average temperatures of 8.3, 10.1, 12.3, 14.0, 16.1, 18.5, 20.5, 21.8, 23.9, 25.9, 27.9, and 29.7°C for 16 weeks. In this study, quadratic regression analysis was used to determine maximum condition factor and weight gain, respectively, and 22.5°C and 21.9°C were identified as the maximum water temperatures. According to this same regression analysis, the maximum feed efficiency and total length increase occurred at 21.6°C and 23.7°C, respectively, during the 16-week study. The modified acclimated chronic exposure water temperature (50% survival for 60 d) was greater than 27.9°C. Spinal and fin deformities increased during this study in all treatments, and these malformations appear to be diet related. There was no temperature effect on deformities, but temperature did affect overall survival.
Groundwater flow beneath Late Weichselian glacier ice in Nordfjord, Norway
Authors: Moeller Carolyn A. , Mickelson D.M. , Anderson M.P. , Winguth C.
Published: December 2007

Basal water pressure and water flow patterns are significant factors in controlling the behavior of an ice sheet, because they influence ice-sheet thickness, stability and extent. Water produced by basal melting may infiltrate the subsurface, or occur as sheet or channelized flow at the ice/bed interface. We examine subglacial groundwater conditions along a flowline of the Scandinavian ice sheet through Nordfjord, in the western fjords region of southern Norway, using a steady-state, twodimensional groundwater-flow model. Meltwater input to the groundwater model is calculated by a two-dimensional, time-dependent, thermomechanically coupled ice-flow model oriented along the same flowline. Model results show that the subglacial sediments could not have transmitted all the meltwater out of the fjord during times of ice advance and when the ice sheet was at its maximum position at the edge of the continental shelf. In order for pore-water pressures to remain below the overburden pressure of the overlying ice, other paths of subglacial drainage are necessary to remove excess water. During times of retreat, the subglacial aquifer is incapable of transmitting all the meltwater that was probably generated. Pulses of meltwater reaching the bed could explain nonclimatically driven margin readvances during the overall retreat phase.
Investigating surface movements of debris-covered Miage glacier, Western Italian Alps, using dendroglaciological analysis
Authors: Pelfini Manuela , Santilli Maurizio , Leonelli Giovanni , Bozzoni Mauro
Published: December 2007

Dendroglaciological analysis of supraglacial trees represents an example of applied dendro- geomorphological methods in reconstructing glacier variations. Supraglacial trees react to glacier ice and debris movement, assuming typical shapes with modified radial growth. In this paper, based on treering analysis of Larix decidua Mill., we investigate the relationship between the distribution and growth of trees located on the most famous and representative debris-covered glacier in the Italian Alps (Miage glacier, Valle d’Aosta) and the superficial movements of ice and debris in the lower part of the tongue. Different growth anomalies (e.g. pointer years, compression wood, abrupt growth changes) were identified and dated. Three reference tree-ring chronologies based on undisturbed larches growing outside the glacier were constructed for comparison with tree-ring data from supraglacial trees. The oldest sampled trees colonized the glacier surface just before 1960. The simultaneous presence of different disturbance indicators occurred mainly between 1984 and 1990 on the southern lobe and during the period 1989–93 on the northern glacier lobe. These results fit with glaciological data documenting volume and surface-level variations in the same period.
Glacier meltwater and runoff modelling, Keqicar Baqi glacier,southwestern Tien Shan, China
Authors: Zhang Yong , Liu Shiyin , Ding Yongjian
Published: December 2007

Meltwater and runoff from Keqicar Baqi glacier, a large glacier in the southwestern Tien Shan, northwestern China, are simulated using a modified degree-day model including potential clear- sky direct solar radiation, coupled with a linear reservoir model for the period 1 July to 12 September 2003. There is good agreement between modelled and measured meltwater at ablation stakes and between simulated and observed runoff at the glacier terminus. A reconstruction of glacier meltwater and runoff from an assumed debris-free surface during the study period shows that the effect of the debris layer on glacier meltwater generation crucially affects glacier runoff. The model is also used to calculate glacier runoff given the climate scenario resulting from a doubling of CO2 as projected by the ReCM2 regional climate model. The projected changes in temperature and precipitation vary from 0 to 2.7°C and from 0 to 25%, respectively. Results indicate that glacier runoff increases linearly with temperature over these ranges whether or not the debris layer is taken into consideration. The effect of change in temperature is much more noticeable than that for change in precipitation. Due to the debris layer predominantly covering (and insulating) the ablation area, the response of glacier runoff is less sensitive to temperature increase with a debris-covered surface than with a debris-free surface. Glacier runoff is also markedly reduced when a reduced glacier area is prescribed in the +2.7°C scenario.
Expanding the snow-climate classification with avalanche-relevant information: initial description of avalanche winter regimes for southwestern Canada
Authors: Haegeli Pascal , McClung David M.
Published: December 2007

Existing snow-climate classifications are primarily based on meteorological parameters that describe the average weather during the main winter months. However, field experience and measurements show that the characteristics of weak snowpack layers, including type, structure and details of formation, are primary indicators of avalanches that form. Despite its importance in the characteristics of local avalanche activity, weak-layer information is currently not a formal part of any snow-climate classification scheme. The focus of this study is the analysis of persistent snowpack weak layers in southwestern Canada. Observations from the industrial information exchange (InfoEx) of the Canadian Avalanche Association are used to examine the frequency, sequence and distribution of the most common types of snowpack weakness and their related avalanche activity. The results show significant temporal and spatial variations in areas with the same snow-climate characteristics. The weak-layer patterns observed in transitional snow-climate areas are clearly more complex than a simple combination of maritime and continental influences. ‘Avalanche winter regime’ is suggested as a new classification term that describes the snowpack structures relevant for local avalanche activity and complements the existing snow-climate classification system. Three preliminary avalanche winter regimes are identified for southwestern Canada.
Tributary glacier surges: an exceptional concentration at Panmah Glacier, Karakoram Himalaya
Authors: Hewitt Kenneth
Published: December 2007

Four tributaries of Panmah Glacier have surged in less than a decade, three in quick succession between 2001 and 2005. Since 1985, 13 surges have been recorded in the Karakoram Himalaya, more than in any comparable period since the 1850s. Ten were tributary surges. In these ten a full run-out of surge ice is prevented, but extended post-surge episodes affect the tributary and main glacier. The sudden concentration of events at Panmah Glacier is without precedent and at odds with known surge intervals for the glaciers. Interpretations must consider the response of thermally complex glaciers, at exceptionally high altitudes and of high relief, to changes in a distinctive regional climate. It is suggested that high-altitude warming affecting snow and glacier thermal regimes, or bringing intense, short-term melting episodes, may be more significant than mass-balance change.
Do loading path and specimen thickness affect the brittle compressive failure of ice?
Authors: Fortt A.L. , Schulson E.M.
Published: December 2007

Compressive experiments were performed on square (160 mm × 160 mm) prismatic specimens of columnar-grained, S2 freshwater ice, biaxially loaded across the columns at −10°C. The work focused on brittle behavior, achieved by deforming the specimens at an applied strain rate of 4.5 ± 1.2 × 10 3s 1 in the direction of shortening. The results show that the specimen thickness (25–150 mm) has no detectable effect on the terminal failure strength of the ice. Likewise, the strength of the ice when loaded under proportional loading, where the minor stress varies during the test, was similar to that when loaded under a constant minor stress, implying that terminal failure depends only on the stress state and not on the path taken.
Forty-seven new subglacial lakes in the 0–110° E sector of East Antarctica
Authors: Popov Sergey V. , Masolov Valery N.
Published: December 2007

During the summer field seasons of 1987–91, studies of central East Antarctica by airborne radio-echo sounding commenced. This scientific work continued in the 1990s in the Vostok Subglacial Lake area and along the traverse route from Mirny, and led to the discovery of 16 new subglacial water cavities in the areas of Domes Fuji and Argus and the Prince Charles Mountains. Twenty-nine subglacial water cavities were revealed in the area near Vostok, along with a feature we believe to be a subglacial river. Two subglacial lakes were discovered along the Mirny–Vostok traverse route. These are located 50 km north of Komsomolskaya station and under Pionerskaya station. We find high geothermal heat flux in the vicinity of the largest of the subglacial lakes, and suggest this may be due to their location over deep faults where additional mantle heat is available.
Light reflection and transmission by a temperate snow cover
Authors: Perovich Donald K.
Published: December 2007

An understanding of the reflection and transmission of light by snow is important for snow thermodynamics, hydrology, ecology and remote sensing. Snow has an intricate microstructure replete with ice/air interfaces that scatter light. Spectral observations of light reflection and transmission, from 400 to 1000 nm, were made in temperate snowpacks, under cold and under melting conditions. The optical observations were made using a dual-detector spectroradiometer. One detector was placed above the snow surface to monitor the incident and reflected solar irradiance, and the second detector was placed at the base of snow cover to measure downwelling irradiance. The optical measurements were supplemented by a physical characterization of the snow, including depth, density and an estimate of grain size. In general, transmitted light levels were low and showed a strong spectral dependence, with maximum values between 450 and 550 nm. For example, a 10 cm thick snow layer reduced visible transmission (500 nm) to about 5% of the incident irradiance, and infrared transmission (800 nm) to less than 1%. Extinction coefficients were in the range 3–30 m−1, and tended to decrease slightly as the snow aged and increase as snow density increased.
Maleic Anhydride, Maleic Acid, and Fumaric Acid
Authors: Hood David K.
Published: April 2024

This Chapter review will provide an update for the physical properties, chemical properties (eg transformations), applications, and manufacture of maleic anhydride, maleic acid and fumaric acid. This Chapter review will primarily focus on recent technical developments that are aligned to current world events and important societal macrotrends, particularly sustainable and nature derived materials and processes.
Oncolytic adenoviruses and immunopeptidomics: a convenient marriage
Authors: Garcia‐Moure Marc , Gillard Andrew G. , Alonso Marta M. , Fueyo Juan , Gomez‐Manzano Candelaria
Published: April 2024

Oncolytic viruses (OVs) are biological therapeutic agents that selectively destroy cancer cells while sparing normal healthy cells. Besides direct oncolysis, OV infection induces a proinflammatory shift in the tumor microenvironment and the release of tumor‐associated antigens (TAAs) that might induce an anti‐tumor immunity. Due to their immunostimulatory effect, OVs have been explored for cancer vaccination against specific TAAs. However, this approach usually requires genetic modification of the virus and the production of a new viral vector for each target, which is difficult to implement for low prevalent antigens. In a recent study, Chiaro et al. presented an elegant proof of concept on how to implement the PeptiCRAd vaccination platform to overcome this limitation for the treatment of mesothelioma. Authors showed the feasibility of identifying immunogenic TAAs in human mesothelioma and using them to coat oncolytic adenovirus particles. The result was a customized virus‐based cancer vaccine that circumvents time and resource‐consuming steps incurred from genetically engineering viruses. Although some questions remain to be addressed, this interesting approach suggests novel strategies for personalized cancer medicine using oncolytic virotherapy.
Health Consequences of Climate Change
Authors: Hughes Fintan , Romanello Maria , Walawender Maria , Montgomery Hugh
Published: April 2024

Fossil fuel use is harming human health and the resulting climate change presents a risk that has arrived substantially sooner than anticipated. Frequent and intense heat waves, storms, droughts and wildfires are causing widespread cardiovascular disease, respiratory disease, malnutrition and childhood illness. Extreme weather events and associated economic losses are driving a wave of climate migration; billions more people will be displaced over the coming century.

These effects being seen now are the result of only 1.14°C of warming. Greenhouse gas emissions continue to rise because of increasing fossil fuel use and we are currently on track for 2.8–3.5°C of warming by the end of the century. The planet is crossing dangerous tipping points, triggering positive feedback loops in planetary heating. There is a narrow window of time during which climate action can prevent the collapse of the human ecosystem.

Key Concepts

Fossil fuel use is driving accelerating climate change that is bringing about the collapse of the human ecosystem.

Extreme weather events, flooding, forest fires and drought are bringing about vast human suffering through cardiac disease, respiratory disease, maternal & childhood illness, malnutrition, and forced migration.

Catastrophic human impacts are already being seen at only 1.14°C of warming, and greenhouse gas emissions continue to rise.
Repurposing DailyQA3 for an efficient and spot position sensitive daily quality assurance tool for proton therapy
Authors: Tan Hong Qi , Koh Calvin Wei Yang , Lew Kah Seng , Yeap Ping Lin , Chua Clifford Ghee Ann , Lee James Kuan Huei , Wong Yun Ming , Wibawa Andrew , Master Zubin , Lee James Cheow Lei , Park Sung Yong
Published: April 2024

Introduction

Daily quality assurance is an integral part of a radiotherapy workflow to ensure the dose is delivered safely and accurately to the patient. It is performed before the first treatment of the day and needs to be time and cost efficient for a multiple gantries proton center. In this study, we introduced an efficient method to perform QA for output constancy, range verification, spot positioning accuracy and imaging and proton beam isocenter coincidence with DailyQA3.

Methods

A stepped acrylic block of specific dimensions is fabricated and placed on top of the DailyQA3 device. Treatment plans comprising of two different spread‐out Bragg peaks and five individual spots of 1.0 MU each are designed to be delivered to the device. A mathematical framework to measure the 2D distance between the detectors and individual spot is introduced and play an important role in realizing the spot positioning and centering QA. Lastly, a 5 months trends of the QA for two gantries are presented.

Results

The outputs are monitored by two ion chambers in the DailyQA3 and a tolerance of are used. The range of the SOBPs are monitored by the ratio of ion chamber signals and a tolerance of is used. Four diodes at from the central ion chambers are used for spot positioning QA, while the central ion chamber is used for imaging and proton beam isocenter coincidence QA. Using the framework, we determined the absolute signal threshold corresponding to the offset tolerance between the individual proton spot and the detector. A tolerances are used for both the positioning and centering QA. No violation of the tolerances is observed in the 5 months trends for both gantries.

Conclusion

With the proposed approach, we can perform four QA items in the TG224 within 10 min.
Children's long‐term memory for a staged repeated event: A preliminary investigation
Authors: Earhart Becky , Deck Sarah L. , Brubacher Sonja P. , Powell Martine B.
Published: April 2024

In this study, we examined children's memory for a staged repeated event after a two‐year delay to gain insights about how they represented the events in long‐term memory. Children aged 4–8 experienced six events and were interviewed about the last occurrence shortly after the event and 2 years later (N = 29). Various characteristics of their memory reports at the delayed interview were analyzed (e.g., accuracy, specificity). Though the event was brief and embedded within their school day, the patterns in recall suggest that children represented the events as distinct from what usually happens at school. For example, all children were able to recall accurate information, and incorrect details were most often details they experienced during another occurrence of the events. The results of this preliminary investigation are considered in relation to prominent theories of event memory, and generate interesting directions for future repeated‐event research.
Prevalence and Associations Between Metabolic Syndrome Components and Hyperuricemia by Race: Findings From US Population, 2011–2020
Authors: Kim Yun Jin , Kim Sunghwan , Seo Ji Hwan , Cho Sung Kweon
Published: April 2024

Objective

We explored the trend in prevalence of hyperuricemia and metabolic syndrome in US populations and investigated associations between components of metabolic syndrome and hyperuricemia by race.

Methods

We analyzed data from the four most recent National Health and Nutrition Examination Survey (NHANES) cycles (2011 to March 2020), comprising 10,175 participants. Hyperuricemia is defined as serum urate >7.0 mg/dL (men) or >5.7 mg/dL (women), following the NHANES‐III guideline. The definition of metabolic syndrome follows the National Cholesterol Education Program's Adult Treatment Panel III guideline. We estimated the prevalence of metabolic syndrome and hyperuricemia in each cycle and performed subgroup analyses with logistic regression to investigate the patterns of associated components of metabolic syndrome with hyperuricemia.

Results

In the most recent cycle (2017 to March 2020), the prevalence of metabolic syndrome was 45.9% and that of hyperuricemia was 20.7%. Over the 2011 to 2020 period, a significant rise in metabolic syndrome prevalence was observed among Hispanic and Asian populations, and the prevalence of hyperuricemia has increased significantly only in the Hispanic population. After adjustment for confounding factors, patients with metabolic syndrome exhibited a higher hyperuricemia in women than in men. Elevated blood pressure was the strongest factor with hyperuricemia. The association was the weakest in the Asian population. Waist circumference was the only significant factor associated with hyperuricemia in the Asian population.

Conclusion

The prevalence of metabolic syndrome has an increasing pattern, but there was no specific decadal trend in prevalence of hyperuricemia. There is an ethnicity‐specific association of metabolic syndrome and hyperuricemia, especially among Asians.

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Racial Differences in Plasma Microbial Translocation and Plasma Microbiome, Implications in Systemic Lupus Erythematosus Disease Pathogenesis
Authors: Wen Xiaoting , Ogunrinde Elizabeth , Wan Zhuang , Cunningham Melissa , Gilkeson Gary , Jiang Wei
Published: April 2024

Objective

Black groups have increased prevalence and accelerated pathogenicity of systemic lupus erythematosus (SLE) compared to other ethnic/racial groups. The microbiome and systemic microbial translocation are considered contributing factors to SLE disease pathogenesis. However, racial differences in the plasma microbiome and microbial translocation in lupus remain unknown.

Methods

In the current study, we investigated plasma levels of microbial translocation (lipopolysaccharide [LPS] and zonulin) and the plasma microbiome using microbial 16S RNA sequencing of Black and White patients with SLE and Black and White healthy controls.

Results

Plasma microbial translocation was increased in Black patients versus in White patients and in patients with SLE versus healthy controls regardless of race. Compared to sex, age, and disease status, race had the strongest association with plasma microbiome differences. Black groups (Black controls and Black patients) had lower α‐diversity than White groups (White controls and White patients) and more distinct β‐diversity. Black and White patients demonstrated differences in plasma bacterial presence, including Staphylococcus and Burkholderia. Compared to White patients, Black patients had higher SLE Disease Activity Index (SLEDAI) scores and urinary protein levels as well as a trend for increased anti–double‐stranded DNA (dsDNA) antibody levels consistent with the known increased severity of lupus in Black patients overall. Certain plasma bacteria at the genus level were identified that were associated with the SLEDAI score, urinary protein, and anti‐dsDNA antibody levels.

Conclusion

This study reveals racial differences in both quality and quantity of plasma microbial translocation and identified specific plasma microbiome differences associated with SLE disease pathogenesis. Thus, this study may provide new insights into future potential microbiome therapies on SLE pathogenesis.
Hyper‐Elastic Deformation via Martensitic Phase Transformation in Cadmium Telluride
Authors: Luo Kun , Han Xiao , Cappola Jonathan , Li Dian , Zheng Yufeng , Li Lin , Yan Feng , An Qi
Published: April 2024

Cadmium telluride (CdTe) is a highly promising material for photovoltaics (PV) and photodetectors due to its light‐absorbing properties. However, efficient design and use of flexible devices require a deep understanding of its atomic‐level deformation mechanism. Herein, uniaxial compression deformation of CdTe monocrystalline with varying crystal orientations is investigated using molecular dynamics (MD) with a newly developed machine‐learning force field (ML‐FF), alongside in‐situ micropillar compression experiments. The findings reveal that CdTe bulk deformation is dominated by reversible martensitic phase transformation, whereas CdTe pillar deformation is primarily driven by dislocation nucleation and movement. CdTe monocrystals possess exceptional super‐recoverable deformation along the <100> orientation due to hyper‐elastic processes induced by martensitic transformation. This discovery not only sheds light on the peculiarities observed in micropillar experimental measurements, but also provides pivotal insights into the fundamental deformation behaviors of CdTe and similar II–VI compounds under various stress conditions. These insights are crucial for the innovative design and enhanced functionality of future flexible electronic devices.
Sound Characteristics and Mechanical Properties of Metal Powder Chamber Structures Composite Materials Formed by Laser Powder Bed Fusion
Authors: Li Jianliang , Guo Chunhuan , Jiang Fengchun , Shao Shuaiqi , Sun Qianfei
Published: April 2024

Granular damping technology is a widely used method in aerospace and other industries to reduce vibration and noise. However, the technique still faces challenges such as secondary processing, additional structure, single structure, and residual stress. This article introduces a new composite material, the metal powder chamber structure (MPCS), formed through the laser powder bed fusion technology. The article explores the effects of factors like arrangement mode, volume fraction, and powder chamber diameter on the sound and mechanical properties of MPCS. The study shows that MPCS improves the sound insulation effect of the material and defies the mass law of sound insulation. The sample 4B40 using a body‐centered cubic arrangement has a sound insulation coefficient of 52 dB. The sound absorption efficiency curve presents a double peak, and the sample 6F60 exhibits the highest sound absorption efficiency of 0.76. MPCS changes the deformation stage of the material stress–strain curve, and different MPCS also alters the compression deformation mode of the composite material. By studying the effects of MPCS on sound and mechanical properties, it is hoped to provide a better and more sustainable solution for vibration and noise reduction.