bluuebunny/crossref_metadata_2025_split huggingface dataset:
A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1‐year prospective randomized intervention study
Authors: Elhayany A. , Lustman A. , Abel R. , Attal‐Singer J. , Vinker S. 
Published: September 2009

Background: The appropriate dietary intervention for overweight persons with type 2 diabetes mellitus (DM2) is unclear. Trials comparing the effectiveness of diets are frequently limited by short follow‐up times and high dropout rates. Aim: The effects of a low carbohydrate Mediterranean (LCM), a traditional Mediterranean (TM), and the 2003 American Diabetic Association (ADA) diet were compared, on health parameters during a 12‐month period. Methods: In this 12‐month trial, 259 overweight diabetic patients (mean age 55 years, mean body mass index 31.4 kg/m2) were randomly assigned to one of the three diets. The primary end‐points were reduction of fasting plasma glucose, HbA1c and triglyceride (TG) levels. Results: 194 patients out of 259 (74.9%) completed follow‐up. After 12 months, the mean weight loss for all patients was 8.3 kg: 7.7 kg for ADA, 7.4 kg for TM and 10.1 kg for LCM diets. The reduction in HbA1c was significantly greater in the LCM diet than in the ADA diet (−2.0 and −1.6%, respectively, p < 0.022). HDL cholesterol increased (0.1 mmol/l ± 0.02) only on the LCM (p < 0.002). The reduction in serum TG was greater in the LCM (−1.3 mmol/l) and TM (−1.5 mmol/l) than in the ADA (−0.7 mmol/l), p = 0.001. Conclusions: An intensive 12‐month dietary intervention in a community‐based setting was effective in improving most modifiable cardiovascular risk factors in all the dietary groups. Only the LCM improved HDL levels and was superior to both the ADA and TM in improving glycaemic control.
Exenatide compared with long‐acting insulin to achieve glycaemic control with minimal weight gain in patients with type 2 diabetes: results of the Helping Evaluate Exenatide in patients with diabetes compared with Long‐Acting insulin (HEELA) study
Authors: Davies M. J. , Donnelly R. , Barnett A. H. , Jones S. , Nicolay C. , Kilcoyne A. 
Published: September 2009

Aim: The Helping Evaluate Exenatide in overweight patients with diabetes compared with Long‐Acting insulin (HEELA) study was designed to examine whether the glucagon‐like peptide‐1 (GLP‐1) receptor agonist, exenatide, could improve HbA1c (≤7.4%) with minimal weight gain (≤1 kg) compared with insulin glargine. Methods: Patients [body mass index (BMI) >27 kg/m2] with elevated cardiovascular risk and type 2 diabetes inadequately controlled on two or three oral antidiabetes drugs (OADs) were randomized to add‐on exenatide 5–10 μg b.i.d. (n = 118) or insulin glargine o.d. (titrated to target fasting plasma glucose ≤5.6 mmol/l; n = 117) for 26 weeks. Results: The study population had baseline mean (s.d.) age of 56.5 (9.1) years and BMI of 34.1 (5.3) kg/m2, and 58.5% of patients were taking two OADs. Mean baseline HbA1c was 8.65 (0.68)% in the exenatide group and 8.48 (0.66)% in the insulin glargine group. The proportions of patients achieving the composite endpoint of HbA1c ≤7.4% with weight gain ≤1 kg were 53.4% for the exenatide group and 19.8% for the insulin glargine group (p < 0.001 for exenatide vs. insulin glargine). Exenatide and insulin glargine did not demonstrate a significant difference in HbA1c improvements [least square (LS) mean [s.e.m.]: −1.25 [0.09]% and −1.26 [0.09]% respectively; p = 0.924], but had divergent effects on body weight (−2.73 [0.31] vs. +2.98 [0.31] kg respectively, p < 0.001) after 26 weeks. There were more treatment‐related adverse events with exenatide but a lower incidence of nocturnal hypoglycaemia, with no differences in overall or severe hypoglycaemia. Conclusions: Additional treatment with exenatide resulted in significantly more overweight and obese patients with an elevated cardiovascular risk and type 2 diabetes achieving better glycaemic control with minimal weight gain compared with insulin glargine.
Firm Experience and Market Entry by Venture Capital Firms (1962–2004)
Authors: Dimov Dimo , Martin de Holan Pablo 
Published: September 2009

abstractIn this paper, we examine a firm's decision to enter new markets as related to the depth and breadth of its experience and the relative distance of those markets. We situate our discussion and analysis in the context of the venture capital (VC) industry, and examine whether and when US VC firms enter five high‐technology investment markets through first‐ or later‐round investments. This setting allows us to observe both the firms that chose to enter a new market and those that did not, and analyse the antecedents of these decisions. We find that VC firms overall are less likely to enter distant markets; those with broader experience are more likely to make first‐round entries. In addition, VC firms with deeper investment experience are more likely to make first‐round entries in proximate markets and less likely to enter distant markets and make later‐round entries. These results offer interesting implications for the literature on organizational learning and entrepreneurship.
Magnetic Resonance Imaging in Dogs with Neurologic Impairment Due to Acute Thoracic and Lumbar Intervertebral Disk Herniation
Authors: Levine J.M. , Fosgate G.T. , Chen A.V. , Rushing R. , Nghiem P.P. , Platt S.R. , Bagley R.S. , Kent M. , Hicks D.G. , Young B.D. , Schatzberg S.J. 
Published: September 2009

Background: Magnetic resonance imaging (MRI) is a correlate to physical examination in various myelopathies and a predictor of functional outcome.Objectives: To describe associations among MRI features, neurological dysfunction before MRI, and functional outcome in dogs with disk herniation.Animals: One hundred and fifty‐nine dogs with acute thoracolumbar disk herniation.Methods: Retrospective case series. Signalment, initial neurological function as assessed by a modified Frankel score (MFS), and ambulatory outcome at hospital discharge and >3 months (long‐term) follow‐up were recorded from medical records and telephone interview of owners. Associations were estimated between these parameters and MRI signal and morphometric data.Results: Dogs with intramedullary T2W hyperintensity had more severe pre‐MRI MFS (median 2, range 0–4) and lower ambulatory proportion at long‐term follow‐up (0.76) than those dogs lacking hyperintensity (median MFS 3, range 0–5; ambulatory proportion, 0.93) (P=.001 and .013, respectively). Each unit of T2W length ratio was associated with a 1.9 times lower odds of long‐term ambulation when adjusted for pre‐MRI MFS (95% confidence interval 1.0–3.52, P=.05). Dogs with a compressive length ratio >1.31 (which was the median ratio within this population) had more severe pre‐MRI MFS (median 3, range 0–5) compared with those with ratios ≤1.31 (median MFS 3, range 0–4; P=.006).Conclusions and Clinical Importance: MRI features were associated with initial injury severity in dogs with thoracolumbar disk herniation. Based on results of this study, the T2W length ratio and presence of T2W intramedullary hyperintensity appear to be predictive of long‐term ambulatory status.
Characterization of a New Metallo-β-Lactamase Gene,
bla
NDM-1
, and a Novel Erythromycin Esterase Gene Carried on a Unique Genetic Structure in
Klebsiella pneumoniae
Sequence Type 14 from India
Authors: Yong Dongeun , Toleman Mark A. , Giske Christian G. , Cho Hyun S. , Sundman Kristina , Lee Kyungwon , Walsh Timothy R. 
Published: September 2009

ABSTRACT

A Swedish patient of Indian origin traveled to New Delhi, India, and acquired a urinary tract infection caused by a carbapenem-resistant
Klebsiella pneumoniae
strain that typed to the sequence type 14 complex. The isolate,
Klebsiella pneumoniae
05-506, was shown to possess a metallo-β-lactamase (MBL) but was negative for previously known MBL genes. Gene libraries and amplification of class 1 integrons revealed three resistance-conferring regions; the first contained
bla
CMY-4
flanked by IS
EcP1
and
blc
. The second region of 4.8 kb contained a complex class 1 integron with the gene cassettes
arr
-
2
, a new erythromycin esterase gene;
ereC
;
aadA1
; and
cmlA7
. An intact IS
CR1
element was shown to be downstream from the
qac
/
sul
genes. The third region consisted of a new MBL gene, designated
bla
NDM-1
, flanked on one side by
K. pneumoniae
DNA and a truncated IS
26
element on its other side. The last two regions lie adjacent to one another, and all three regions are found on a 180-kb region that is easily transferable to recipient strains and that confers resistance to all antibiotics except fluoroquinolones and colistin. NDM-1 shares very little identity with other MBLs, with the most similar MBLs being VIM-1/VIM-2, with which it has only 32.4% identity. As well as possessing unique residues near the active site, NDM-1 also has an additional insert between positions 162 and 166 not present in other MBLs. NDM-1 has a molecular mass of 28 kDa, is monomeric, and can hydrolyze all β-lactams except aztreonam. Compared to VIM-2, NDM-1 displays tighter binding to most cephalosporins, in particular, cefuroxime, cefotaxime, and cephalothin (cefalotin), and also to the penicillins. NDM-1 does not bind to the carbapenems as tightly as IMP-1 or VIM-2 and turns over the carbapenems at a rate similar to that of VIM-2. In addition to
K. pneumoniae
05-506,
bla
NDM-1
was found on a 140-kb plasmid in an
Escherichia coli
strain isolated from the patient's feces, inferring the possibility of in vivo conjugation. The broad resistance carried on these plasmids is a further worrying development for India, which already has high levels of antibiotic resistance.
Superior Protective Immunity against Murine Listeriosis by Combined Vaccination with CpG DNA and RecombinantSalmonella entericaSerovar Typhimurium
Authors: Berchtold Christina , Panthel Klaus , Jellbauer Stefan , Köhn Brigitte , Roider Elisabeth , Partilla Miriam , Heesemann Jürgen , Endres Stefan , Bourquin Carole , Rüssmann Holger 
Published: September 2009

ABSTRACTPreexisting antivector immunity can severely compromise the ability ofSalmonella entericaserovar Typhimurium live vaccines to induce protective CD8 T-cell frequencies after type III secretion system-mediated heterologous protein translocation in orally immunized mice. To circumvent this problem, we injected CpG DNA admixed to the immunodominant p60217-225peptide fromListeria monocytogenessubcutaneously into BALB/c mice and coadministered a p60-translocatingSalmonellastrain by the orogastric route. The distribution of tetramer-positive p60217-225-specific effector and memory CD8 T cells was analyzed by costaining of lymphocytes with CD62L and CD127. In contrast to the single oral application of recombinantSalmonellaor single immunization with CpG and p60, in the spleens from mice immunized with a combination of both vaccine types a significantly higher level of p60-specific CD8 T cells with a predominance of the effector memory T-cell subset was detected. In vivo protection studies revealed that this CD8 T-cell population conferred sterile protective immunity against a lethal infection withL. monocytogenes. However, p60-specific central memory CD8 T cells induced by single vaccination with CpG and p60 were not able confer effective protection against rapidly replicating intracellularListeria. In conclusion, we provide compelling evidence that the combination ofSalmonellatype III-mediated antigen delivery and CpG immunization is an attractive novel vaccination strategy to modulate CD8 differentiation patterns toward distinct antigen-specific T-cell subsets with favorable protective capacities.
Effect of the O-Antigen Length of Lipopolysaccharide on the Functions of Type III Secretion Systems in
Salmonella enterica
Authors: Hölzer Stefanie U. , Schlumberger Markus C. , Jäckel Daniela , Hensel Michael 
Published: September 2009

ABSTRACT

The virulence of
Salmonella enterica
critically depends on the functions of two type III secretion systems (T3SS), with the
Salmonella
pathogenicity island 1 (SPI1)-encoded T3SS required for host cell invasion and the SPI2-T3SS enabling
Salmonella
to proliferate within host cells. A further T3SS is required for the assembly of the flagella. Most serovars of
Salmonella
also possess a lipopolysaccharide with a complex O-antigen (OAg) structure. The number of OAg units attached to the core polysaccharide varies between 16 and more than 100 repeats, with a trimodal distribution. This work investigated the correlation of the OAg length with the functions of the SPI1-T3SS and the SPI2-T3SS. We observed that the number of repeats of OAg units had no effect on bacterial motility. The interaction of
Salmonella
with epithelial cells was altered if the OAg structure was changed by mutations in regulators of OAg. Strains defective in synthesis of very long or long and very long OAg species showed increased translocation of a SPI1-T3SS effector protein and increased invasion. Invasion of a strain entirely lacking OAg was increased, but this mutant strain also showed increased adhesion. In contrast, translocation of a SPI2-T3SS effector protein and intracellular replication were not affected by modification of the OAg length. Mutant strains lacking the entire OAg or long and very long OAg were highly susceptible to complement killing. These observations indicate that the architecture of the outer membrane of
Salmonella
is balanced to permit sufficient T3SS function but also to confer optimal protection against antimicrobial defense mechanisms.
Live migration of direct-access devices
Authors: Kadav Asim , Swift Michael M. 
Published: September 2009

Virtual machine migration greatly aids management by allowing flexible provisioning of resources and decommissioning of hardware for maintenance. However, efforts to improve network performance by granting virtual machines direct access to hardware currently prevent migration. This occurs because (1) theVMMcannot migrate the state of the device, and (2) the source and destination machines may have different network devices, requiring different drivers to run in the migrated virtual machine.
In this paper, we describe a lightweight software mechanism for migrating virtual machines with direct hardware access. We base our solution on shadow drivers, an agent in the guest OS kernel that efficiently captures and restores the state of a device driver. On the source machine, the shadow driver monitors the state of the driver and device. After migration, the shadow driver uses this information to configure a driver for the corresponding device on the destination machine. We implement shadow driver migration for Linux network drivers running on the Xen hypervisor. Shadow driver migration requires a migration downtime similar to the driver initialization time, short enough to avoid disrupting active TCP connections. We find that the performance overhead, compared to direct hardware access, is negligible and is much lower than using a virtual NIC.
Recombinant canine B-domain–deleted FVIII exhibits high specific activity and is safe in the canine hemophilia A model
Authors: Sabatino Denise E. , Freguia Christian Furlan , Toso Raffaella , Santos Andrey , Merricks Elizabeth P. , Kazazian Haig H. , Nichols Timothy C. , Camire Rodney M. , Arruda Valder R. 
Published: September 2009

AbstractProduction of recombinant B-domain–deleted canine factor VIII (cFVIII-BDD) unexpectedly revealed superior protein yields with 3-fold increased specific activity relative to human FVIII-BDD (hFVIII-BDD). We also determined that activated cFVIII-BDD is more stable than activated hFVIII-BDD. Furthermore, cFVIII-BDD is efficient at inducing hemostasis in human plasma containing FVIII inhibitors. Infusion of cFVIII-BDD in hemophilia A dogs resulted in correction of the disease phenotype with a pharmacokinetic profile similar to clinical experience with hFVIII-BDD. Notably, immune tolerance challenges with cFVIII-BDD in young and adult hemophilia A dogs did not induce the formation of neutralizing or nonneutralizing antibodies to cFVIII. These data establish the framework to quantitatively investigate the efficacy and safety in preclinical studies of novel therapies for hemophilia A.
Development of a high-throughput method for the systematic identification of human proteins nuclear translocation potential
Authors: Hoat Trinh Xuan , Bertin Nicolas , Ninomiya Noriko , Fukuda Shiro , Usui Kengo , Kawai Jun , Hayashizaki Yoshihide , Suzuki Harukazu 
Published: September 2009

Abstract

Background
Important clues to the function of novel and uncharacterized proteins can be obtained by identifying their ability to translocate in the nucleus. In addition, a comprehensive definition of the nuclear proteome undoubtedly represents a key step toward a better understanding of the biology of this organelle. Although several high-throughput experimental methods have been developed to explore the sub-cellular localization of proteins, these methods tend to focus on the predominant localizations of gene products and may fail to provide a complete catalog of proteins that are able to transiently locate into the nucleus.

Results
We have developed a method for examining the nuclear localization potential of human gene products at the proteome scale by adapting a mammalian two-hybrid system we have previously developed. Our system is composed of three constructs co-transfected into a mammalian cell line. First, it contains a PCR construct encoding a fusion protein composed of a tested protein, the PDZ-protein TIP-1, and the transactivation domain of TNNC2 (referred to as ACT construct). Second, our system contains a PCR construct encoding a fusion protein composed of the DNA binding domain of GAL4 and the PDZ binding domain of rhotekin (referred to as the BIND construct). Third, a GAL4-responsive luciferase reporter is used to detect the reconstitution of a transcriptionally active BIND-ACT complex through the interaction of TIP-1 and rhotekin, which indicates the ability of the tested protein to translocate into the nucleus. We validated our method in a small-scale feasibility study by comparing it to green fluorescent protein (GFP) fusion-based sub-cellular localization assays, sequence-based computational prediction of protein sub-cellular localization, and current sub-cellular localization data available from the literature for 22 gene products.

Conclusion
Our reporter-based system can rapidly screen gene products for their ability to be translocated to the nucleus. Large-scale applications of the system presented herein should provide invaluable information for a more complete biological atlas.
Imaging short- and long-term training success in chronic aphasia
Authors: Menke Ricarda , Meinzer Marcus , Kugel Harald , Deppe Michael , Baumgärtner Annette , Schiffbauer Hagen , Thomas Marion , Kramer Kira , Lohmann Hubertus , Flöel Agnes , Knecht Stefan , Breitenstein Caterina 
Published: September 2009

Abstract

Background
To date, functional imaging studies of treatment-induced recovery from chronic aphasia only assessed short-term treatment effects after intensive language training. In the present study, we show with functional magnetic resonance imaging (fMRI), that different brain regions may be involved in immediate versus long-term success of intensive language training in chronic post-stroke aphasia patients.

Results
Eight patients were trained daily for three hours over a period of two weeks in naming of concrete objects. Prior to, immediately after, and eight months after training, patients overtly named trained and untrained objects during event-related fMRI. On average the patients improved from zero (at baseline) to 64.4% correct naming responses immediately after training, and treatment success remained highly stable at follow-up. Regression analyses showed that the degree of short-term treatment success was predicted by increased activity (compared to the pretraining scan) bilaterally in the hippocampal formation, the right precuneus and cingulate gyrus, and bilaterally in the fusiform gyri. A different picture emerged for long-term training success, which was best predicted by activity increases in the right-sided Wernicke's homologue and to a lesser degree in perilesional temporal areas.

Conclusion
The results show for the first time that treatment-induced language recovery in the chronic stage after stroke is a dynamic process. Initially, brain regions involved in memory encoding, attention, and multimodal integration mediated treatment success. In contrast, long-term treatment success was predicted mainly by activity increases in the so-called 'classical' language regions. The results suggest that besides perilesional and homologue language-associated regions, functional integrity of domain-unspecific memory structures may be a prerequisite for successful (intensive) language interventions.
Two-stage case-control association study of dopamine-related genes and migraine
Authors: Corominas Roser , Ribases Marta , Camiña Montserrat , Cuenca-León Ester , Pardo Julio , Boronat Susana , Sobrido María-Jesús , Cormand Bru , Macaya Alfons 
Published: September 2009

AbstractBackgroundWe previously reported risk haplotypes for two genes related with serotonin and dopamine metabolism:MAOAin migraine without aura andDDCin migraine with aura. Herein we investigate the contribution to migraine susceptibility of eight additional genes involved in dopamine neurotransmission.MethodsWe performed a two-stage case-control association study of 50 tag single nucleotide polymorphisms (SNPs), selected according to genetic coverage parameters. The first analysis consisted of 263 patients and 274 controls and the replication study was composed by 259 cases and 287 controls. All cases were diagnosed according to ICHD-II criteria, were Spanish Caucasian, and were sex-matched with control subjects.ResultsSingle-marker analysis of the first population identified nominal associations of five genes with migraine. After applying a false discovery rate correction of 10%, the differences remained significant only forDRD2(rs2283265) andTH(rs2070762). Multiple-marker analysis identified a five-marker T-C-G-C-G (rs12363125-rs2283265-rs2242592-rs1554929-rs2234689) risk haplotype inDRD2and a two-marker A-C (rs6356-rs2070762) risk haplotype inTHthat remained significant after correction by permutations. These results, however, were not replicated in the second independent cohort.ConclusionThe present study does not support the involvement of theDRD1,DRD2,DRD3,DRD5,DBH,COMT,SLC6A3andTHgenes in the genetic predisposition to migraine in the Spanish population.