bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fractalkine Is a Novel Human Adipochemokine Associated With Type 2 Diabetes
Authors: Shah Rachana , Hinkle Christine C. , Ferguson Jane F. , Mehta Nehal N. , Li Mingyao , Qu Liming , Lu Yun , Putt Mary E. , Ahima Rexford S. , Reilly Muredach P. 
Published: April 2011

OBJECTIVE
Leukocyte infiltration of adipose is a critical determinant of obesity-related metabolic diseases. Fractalkine (CX3CL1) and its receptor (CX3CR1) comprise a chemokine system involved in leukocyte recruitment and adhesion in atherosclerosis, but its role in adipose inflammation and type 2 diabetes is unknown.

RESEARCH DESIGN AND METHODS
CX3CL1 mRNA and protein were quantified in subcutaneous adipose and blood during experimental human endotoxemia and in lean and obese human adipose. CX3CL1 cellular source was probed in human adipocytes, monocytes, and macrophages, and CX3CL1-blocking antibodies were used to assess its role in monocyte-adipocyte adhesion. The association of genetic variation in CX3CR1 with metabolic traits was determined in a community-based sample. Finally, plasma CX3CL1 levels were measured in a case-control study of type 2 diabetes.

RESULTS
Endotoxemia induced adipose CX3CL1 mRNA (32.7-fold, P &lt; 1 × 10−5) and protein (43-fold, P = 0.006). Obese subjects had higher CX3CL1 levels in subcutaneous adipose compared with lean (0.420 ± 0.387 vs. 0.228 ± 0.187 ng/mL, P = 0.04). CX3CL1 was expressed and secreted by human adipocytes and stromal vascular cells. Inflammatory cytokine induction of CX3CL1 in human adipocytes (27.5-fold mRNA and threefold protein) was completely attenuated by pretreatment with a peroxisome proliferator–activated receptor-γ agonist. A putative functional nonsynonymous single nucleotide polymorphism (rs3732378) in CX3CR1 was associated with adipose and metabolic traits, and plasma CX3CL1 levels were increased in patients with type 2 diabetes vs. nondiabetics (0.506 ± 0.262 vs. 0.422 ± 0.210 ng/mL, P &lt; 0.0001).

CONCLUSIONS
CX3CL1-CX3CR1 is a novel inflammatory adipose chemokine system that modulates monocyte adhesion to adipocytes and is associated with obesity, insulin resistance, and type 2 diabetes. These data provide support for CX3CL1 as a diagnostic and therapeutic target in cardiometabolic disease.
Dedifferentiation of Immortalized Human Podocytes in Response to Transforming Growth Factor-β
Authors: Herman-Edelstein Michal , Thomas Merlin C. , Thallas-Bonke Vicki , Saleem Moin , Cooper Mark E. , Kantharidis Phillip 
Published: April 2011

OBJECTIVE
Diabetic nephropathy is associated with dedifferentiation of podocytes, losing the specialized features required for efficient glomerular function and acquiring a number of profibrotic, proinflammatory, and proliferative features. These result from tight junction and cytoskeletal rearrangement, augmented proliferation, and apoptosis.

RESEARCH DESIGN AND METHODS
Experiments were performed in conditionally immortalized human podocytes developed by transfection with the temperature-sensitive SV40-T gene. Cells were then cultured in the presence of transforming growth factor (TGF)-β1 or angiotensin II in the presence or absence of a selective inhibitor of the TGF-β type I receptor kinase, SB-431542. Gene and protein expression were then examined by real-time RT-PCR and immunofluorescence, and correlated with changes observed in vivo in experimental diabetes.

RESULTS
Treatment of cells with TGF-β1 resulted in dynamic changes in their morphology, starting with retraction and shortening of foot processes and finishing with the formation of broad and complex tight junctions between adjacent podocytes. This dedifferentiation was also associated with dose- and time-dependent reduction in the expression of glomerular epithelial markers (nephrin, p-cadherin, zonnula occludens-1) and increased expression of mesenchymal markers (α−smooth muscle actin, vimentin, nestin), matrix components (fibronectin, collagen I, and collagen IV α3), cellular proliferation, and apoptosis. The induction of diabetes in mice was also associated with similar changes in morphology, protein expression, and proliferation in glomerular podocytes.

CONCLUSIONS
In response to TGF-β and other TGF-dependent stimuli, mature podocytes undergo dedifferentiation that leads to effacement of foot processes, morphologic flattening, and increased formation of intercellular tight junctions. This simplification of their phenotype to a more embryonic form is also associated with reentry of mature podocytes into the cell cycle, which results in enhanced proliferation and apoptosis. These “pathoadaptive” changes are seen early in the diabetic glomerulus and ultimately contribute to albuminuria, glomerulosclerosis, and podocytopenia.
HLA-A2–Matched Peripheral Blood Mononuclear Cells From Type 1 Diabetic Patients, but Not Nondiabetic Donors, Transfer Insulitis to NOD-scid/γcnull/HLA-A2 Transgenic Mice Concurrent With the Expansion of Islet-Specific CD8+ T cells
Authors: Whitfield-Larry Fatima , Young Ellen F. , Talmage Garrick , Fudge Elizabeth , Azam Anita , Patel Shipra , Largay Joseph , Byrd Warren , Buse John , Calikoglu Ali S. , Shultz Leonard D. , Frelinger Jeffrey A. 
Published: April 2011

OBJECTIVE
Type 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing β-cells. NOD mice provide a useful tool for understanding disease pathogenesis and progression. Although much has been learned from studies with NOD mice, increased understanding of human type 1 diabetes can be gained by evaluating the pathogenic potential of human diabetogenic effector cells in vivo. Therefore, our objective in this study was to develop a small-animal model using human effector cells to study type 1 diabetes.

RESEARCH DESIGN AND METHODS
We adoptively transferred HLA-A2–matched peripheral blood mononuclear cells (PBMCs) from type 1 diabetic patients and nondiabetic control subjects into transgenic NOD-scid/γcnull/HLA-A*0201 (NOD-scid/γcnull/A2) mice. At various times after adoptive transfer, we determined the ability of these mice to support the survival and proliferation of the human lymphoid cells. Human lymphocytes were isolated and assessed from the blood, spleen, pancreatic lymph node and islets of NOD-scid/γcnull/A2 mice after transfer.

RESULTS
Human T and B cells proliferate and survive for at least 6 weeks and were recovered from the blood, spleen, draining pancreatic lymph node, and most importantly, islets of NOD-scid/γcnull/A2 mice. Lymphocytes from type 1 diabetic patients preferentially infiltrate the islets of NOD-scid/γcnull/A2 mice. In contrast, PBMCs from nondiabetic HLA-A2–matched donors showed significantly less islet infiltration. Moreover, in mice that received PBMCs from type 1 diabetic patients, we identified epitope-specific CD8+ T cells among the islet infiltrates.

CONCLUSIONS
We show that insulitis is transferred to NOD-scid/γcnull/A2 mice that received HLA-A2–matched PBMCs from type 1 diabetic patients. In addition, many of the infiltrating CD8+ T cells are epitope-specific and produce interferon-γ after in vitro peptide stimulation. This indicates that NOD-scid/γcnull/A2 mice transferred with HLA-A2–matched PBMCs from type 1 diabetic patients may serve as a useful tool for studying epitope-specific T-cell–mediated responses in patients with type 1 diabetes.
Medical Expenditures Associated With Diabetes Among Privately Insured U.S. Youth in 2007
Authors: Shrestha Sundar S. , Zhang Ping , Albright Ann , Imperatore Giuseppina 
Published: April 2011

OBJECTIVE
To estimate, among privately insured youth in the U.S., medical expenditures associated with diabetes and the difference in medical expenditures between individuals with insulin-treated diabetes mellitus (ITDM) and with non-ITDM (NITDM).

RESEARCH DESIGN AND METHODS
Using the 2007 MarketScan commercial claims and encounter database, we analyzed data for 49,356 youth (aged ≤19 years) who were continuously enrolled in fee-for-service health plans. Youth with diabetes (cases) were identified from inpatient, outpatient, and pharmaceutical drug claims. Each case was matched with five controls (without diabetes) by age (±2 years), sex, census region, and urban versus rural residence. We used regression models to estimate medical expenditures in total and by component (inpatient, outpatient, and medication).

RESULTS
The predicted mean annual total per-person medical expenditures were $9,061 for youth with diabetes and $1,468 for those without, an excess of $7,593 for those with diabetes; of which, 43% was for prescription drugs. The predicted mean annual total expenditures were $9,333 for ITDM youth and $5,683 for NITDM youth, respectively, an excess of $3,650 for those with ITDM diabetes, of which 59% was for prescription drugs.

CONCLUSIONS
The excess medical expenditures associated with diabetes, ITDM in particular, among youth are substantial. Our estimates of excess expenditures can be used to assess the economic burden of diabetes overall and by diabetes treatment mode. Our estimated excess expenditure for NITDM may be used for evaluating the economic efficiency of interventions aimed at preventing type 2 diabetes in U.S. youth.
Matrix metalloproteinases at key junctions in the pathomechanism of stroke
Authors: Rottenberger Zsolt , Kolev Krasimir 
Published: April 2011

Abstract
Matrix metalloproteinases play a crucial role in the remodelling of the extracellular matrix through direct degradation of its structural proteins and control of extracellular signalling. The most common cause of ischemic brain damage is an atherothrombotic lesion in the supplying arteries. The progress of the atherosclerotic plaque development and the related thrombotic complications are mediated in part by matrix metalloproteinases. In addition to their role in the underlying disease, various members of this protease family are upregulated in the acute phase of ischemic brain damage as well as in the post-ischemic brain recovery following stroke. This review summarizes the current understanding of the matrix metalloproteinase-related molecular events at three stages of the ischemic cerebrovascular disease (in the atherosclerotic plaque, in the neurovascular unit of the brain and in the regenerating brain tissue).
Simultaneous Blood Temperature Control and Blood Volume Control Reduces Intradialytic Symptoms
Authors: Veljančicć Ljubiša , Popović Jovan , Radović Milan , Ahrenholz Peter , Ries Wolfgang , Frenken Leon , Wojke Ralf 
Published: April 2011

Purpose Intra-dialytic morbid events (IME; e.g. hypotension, cramps, headaches) are frequent complications during hemodialysis (HD), known to be associated with ultrafiltration-induced hypovolemia and body temperature changes. Feedback control of blood volume adjusts the ultrafiltration rate in order to keep the blood volume above the patient's individual limit; feedback control of blood temperature maintains the mean arterial blood temperature at the individual pre-dialytic level. Each of these methods reduces the frequency of IME. Methods In a randomized clinical trial the simultaneous application of both feedback controls was investigated for the first time. In 15 weeks, each patient went through 3 study phases: an observational screening phase, a standard phase (STD), and a blood temperature- and blood volume-control phase (CTL). Patients with at least 5 sessions with IME out of 15 sessions in the screening phase were eligible for the study and randomized either into sequence STD-CTL or CTL-STD. Results 26 patients completed the study according to protocol, and 778 HD treatments were analyzed. The general treatment parameters were similar in both study phases: treatment duration (STD: 244 min, CTL: 243 min, NS), pre-dialytic weight (STD: 72.3 kg, CTL: 72.2 kg, NS), and weight loss due to ultrafiltration (STD: 3.26 kg, CTL: 3.15 kg, NS). The proportion of HD treatments with IME was 32.8% during STD and 18.0% during CTL (p=0.024). Conclusions The frequency of HD sessions with IME was significantly reduced by 45% compared to standard HD in this randomized clinical trial by use of individualized HD treatments with simultaneous feedback control of blood volume and blood temperature.
Anatomy as the backbone of an integrated first year medical curriculum: Design and implementation
Authors: Klement Brenda J. , Paulsen Douglas F. , Wineski Lawrence E. 
Published: April 2011

AbstractMorehouse School of Medicine chose to restructure its first year medical curriculum in 2005. The anatomy faculty had prior experience in integrating courses, stemming from the successful integration of individual anatomical sciences courses into a single course called Human Morphology. The integration process was expanded to include the other first year basic science courses (Biochemistry, Physiology, and Neurobiology) as we progressed toward an integrated curriculum. A team, consisting of the course directors, a curriculum coordinator, and the Associate Dean for Educational and Faculty Affairs, was assembled to build the new curriculum. For the initial phase, the original course titles were retained but the lecture order was reorganized around the Human Morphology topic sequence. The material from all four courses was organized into four sequential units. Other curricular changes included placing laboratories and lectures more consistently in the daily routine, reducing lecture time from 120 to 90 minute blocks, eliminating unnecessary duplication of content, and increasing the amount of independent study time. Examinations were constructed to include questions from all courses on a single test, reducing the number of examination days in each block from three to one. The entire restructuring process took two years to complete, and the revised curriculum was implemented for the students entering in 2007. The outcomes of the restructured curriculum include a reduction in the number of contact hours by 28%, higher or equivalent subject examination average scores, enhanced student satisfaction, and a first year curriculum team better prepared to move forward with future integration. Anat Sci Educ 4:157–169, 2011. © 2011 American Association of Anatomists.
β NO Turns and Helices Induced by β2‐Aminoxy Peptides: Synthesis and Conformational Studies
Authors: Jiao Zhi‐Gang , Chang Xiao‐Wei , Ding Wei , Liu Guo‐Jun , Song Ke‐Sheng , Zhu Nian‐Yong , Zhang Dan‐Wei , Yang Dan 
Published: April 2011

AbstractHerein, we report an efficient route for the asymmetric synthesis of β2‐aminoxy acids as well as experimental and theoretical studies of conformations of peptides composed of β2‐aminoxy acids. The nine‐membered‐ring intramolecular hydrogen bonds, namely, β NO turns, are generated between adjacent residues in those peptides, in accordance with our computational results. The presence of two consecutive homochiral β NO turns leads to the formation of β NO helical structures in solution, although both helical (composed of two β NO turns of the same handedness) and reverse‐turn (composed of two β NO turns with opposite handedness) structures are of similar stability, as suggested by theoretical studies. Nevertheless, two slightly different conformations, with the same handedness, of β2‐aminoxy monomers have been observed in the solid state and in solution according to our X‐ray and 2D NOESY studies.
Origins and distribution of nerves to the female urinary bladder: New anatomical findings in the sex differences
Authors: Yamaguchi Kumiko , Kobayashi Mayumi , Kato Tomoyasu , Akita Keiichi 
Published: April 2011

AbstractThe development of nerve‐sparing procedures is important in preventing bladder dysfunction following radical hysterectomy. In this study, we dissected 14 halves of 7 female pelvises (age range: 46–86 years; mean age: 74 years) to examine the origins, courses, and distributions of nerve branches to the bladder in females in detail, and 6 halves of 3 male pelvises (age range: 71–85 years, mean age: 78 years) to compare with the female specimens. Nerve branches to the bladder originated mainly from the inferior hypogastric plexus, but independent direct branches running along the ureter from the hypogastric nerve were also distributed particularly to the trigone in all female specimens. We classified these independent branches into four types according to their relationship to the ureter. In males the numbers of the independent branches were small and they were difficult to find. The present observations indicate that nerve distribution patterns to the bladder differ between females and males. In nerve sparing procedures for radical hysterectomy, the area between the ureter and the hypogastric nerve is important. Clin. Anat. 24:880–885, 2011. © 2011 Wiley‐Liss, Inc.
Going Full Circle: Phase‐Transition Thermodynamics of Ionic Liquids
Authors: Preiss Ulrich , Verevkin Sergey P. , Koslowski Thorsten , Krossing Ingo 
Published: April 2011

AbstractWe present the full enthalpic phase transition cycle for ionic liquids (ILs) as examples of non‐classical salts. The cycle was closed for the lattice, solvation, dissociation, and vaporization enthalpies of 30 different ILs, relying on as much experimental data as was available. High‐quality dissociation enthalpies were calculated at the G3 MP2 level. From the cycle, we could establish, for the first time, the lattice and solvation enthalpies of ILs with imidazolium ions. For vaporization, lattice, and dissociation enthalpies, we also developed new prediction methods in the course of our investigations. Here, as only single‐ion values need to be calculated and the tedious optimization of an ion pair can be circumvented, the computational time is short. For the vaporization enthalpy, a very simple approach was found, using a surface term and the calculated enthalpic correction to the total gas‐phase energy. For the lattice enthalpy, the most important constituent proved to be the calculated conductor‐like screening model (COSMO) solvation enthalpy in the ideal electric conductor. A similar model was developed for the dissociation enthalpy. According to our assessment, the typical error of the lattice enthalpy would be 9.4 kJ mol−1, which is less than half the deviation we get when using the (optimized) Kapustinskii equation or the recent volume‐based thermodynamics (VBT) theory. In contrast, the non‐optimized VBT formula gives lattice enthalpies 20 to 140 kJ mol−1 lower than the ones we assessed in the cycle, because of the insufficient description of dispersive interactions. Our findings show that quantum‐chemical calculations can greatly improve the VBT approaches, which were parameterized for simple, inorganic salts with ideally point‐shaped charges. In conclusion, we suggest the term “augmented VBT”, or “aVBT”, to describe this kind of theoretical approach.
Towards a Fully Synthetic MUC1‐Based Anticancer Vaccine: Efficient Conjugation of Glycopeptides with Mono‐, Di‐, and Tetravalent Lipopeptides Using Click Chemistry
Authors: Cai Hui , Huang Zhi‐Hua , Shi Lei , Zhao Yu‐Fen , Kunz Horst , Li Yan‐Mei 
Published: April 2011

AbstractThe membrane‐bound tumor‐associated glycoprotein MUC1 is aberrantly glycosylated in cancer cells compared with normal cells, and is therefore considered an attractive target for cancer immunotherapy. However, tumor‐associated glycopeptides from MUC1 do not elicit a sufficiently robust immune response. Therefore, antitumor vaccines were developed, which consist of MUC1 glycopeptides as the B epitopes and immune‐stimulating toll‐like receptor 2 (TLR 2) lipopeptide ligands. These fully synthetic vaccine candidates were prepared by solid‐phase synthesis of the MUC1 glycopeptides. The Pam3Cys lipopeptide, also synthesized on solid‐phase, was C‐terminally coupled to oligovalent lysine cores, which N‐terminally incorporate O‐propargyl oligoethylene glycol acyl side chains. The MUC1 glycopeptides and lipopeptide lysine constructs were then conjugated by click chemistry to give oligovalent synthetic vaccines. Oligovalent glycopeptide–lipopeptide conjugates are considered more immunogenic than their monovalent analogues.
CAFS: a novel lightweight cache‐based scheme for large‐scale intrusion alert fusion
Authors: Wen Sheng , Zhou Wei , Xiang Yang , Zhou Wanlei 
Published: April 2011

SUMMARYIn this paper, we present some practical experiences on implementing an alert fusion mechanism from our project. After investigation on most of the existing alert fusion systems, we found the current body of work alternatively weighed down in the mire of insecure design or rarely deployed because of their complexity. As confirmed by our experimental analysis, unsuitable mechanisms could easily be submerged by an abundance of useless alerts. Even with the use of methods that achieve a high fusion rate and low false positives, attack is also possible. To find the solution, we carried out analysis on a series of alerts generated by well‐known datasets as well as realistic alerts from the Australian Honey‐Pot. One important finding is that one alert has more than an 85% chance of being fused in the following five alerts. Of particular importance is our design of a novel lightweight Cache‐based Alert Fusion Scheme, called CAFS. CAFS has the capacity to not only reduce the quantity of useless alerts generated by intrusion detection system, but also enhance the accuracy of alerts, therefore greatly reducing the cost of fusion processing. We also present reasonable and practical specifications for the target‐oriented fusion policy that provides a quality guarantee on alert fusion, and as a result seamlessly satisfies the process of successive correlation. Our experiments compared CAFS with traditional centralized fusion. The results showed that the CAFS easily attained the desired level of simple, counter‐escapable alert fusion design. Furthermore, as a lightweight scheme, CAFS can easily be deployed and excel in a large amount of alert fusions, which go towards improving the usability of system resources. To the best of our knowledge, our work is a practical exploration in addressing problems from the academic point of view. Copyright © 2011 John Wiley & Sons, Ltd.
Multi‐Field Effect on the Electronic Properties of Silicon Nanowires
Authors: Zhang Ren Qin , Hou Chao , Gao Nan , Wen Zi , Jiang Qing 
Published: April 2011

AbstractThe quantum confinement and electronic properties of silicon nanowires (SiNWs) under an external strain field ε and an electric field E—as well as both (ε plus E)—are systematically investigated using density functional theory. These two fields exist in working environments of integrated circuits. It is found that both ε and E lead to a drop of the band gap Eg(ε,E) of the SiNWs. If both fields coexist, the interaction between ε and E causes that Eg(ε,E) becomes orientation‐dependent, which results from variations of both the conduction‐band minimum and the valence‐band maximum. The interaction is further illustrated by the density of states near the Fermi level and the eigenvalue of the highest occupied molecular orbital.
The Rate‐Determining Step is Dead. Long Live the Rate‐Determining State!
Authors: Kozuch Sebastian , Martin Jan M. L. 
Published: April 2011

AbstractThe concept of a rate‐determining step (RD‐Step) is central to the kinetics community, and it is basic knowledge even for the undergraduate chemical student. In spite of this, too many different definitions of the RD‐Step appear in the literature, all of them with drawbacks. This dilemma has been thoroughly studied by several authors in the attempt to “patch” the drawbacks and bring the RD‐Step to a correct physical meaning. Herein we review with simple models the most notable definitions and some challengers of the RD‐Step concept, to conclude with the deduction that there are no rate‐determining steps, only rate‐determining states.