bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small but versatile: the extraordinary functional and structural diversity of the β-grasp fold
Authors: Burroughs A Maxwell , Balaji S , Iyer Lakshminarayan M , Aravind L 
Published: July 2007

AbstractBackgroundThe β-grasp fold (β-GF), prototyped by ubiquitin (UB), has been recruited for a strikingly diverse range of biochemical functions. These functions include providing a scaffold for different enzymatic active sites (e.g. NUDIX phosphohydrolases) and iron-sulfur clusters, RNA-soluble-ligand and co-factor-binding, sulfur transfer, adaptor functions in signaling, assembly of macromolecular complexes and post-translational protein modification. To understand the basis for the functional versatility of this small fold we undertook a comprehensive sequence-structure analysis of the fold and developed a natural classification for its members.ResultsAs a result we were able to define the core distinguishing features of the fold and numerous elaborations, including several previously unrecognized variants. Systematic analysis of all known interactions of the fold showed that its manifold functional abilities arise primarily from the prominent β-sheet, which provides an exposed surface for diverse interactions or additionally, by forming open barrel-like structures. We show that in the β-GF both enzymatic activities and the binding of diverse co-factors (e.g. molybdopterin) have independently evolved on at least three occasions each, and iron-sulfur-cluster-binding on at least two independent occasions. Our analysis identified multiple previously unknown large monophyletic assemblages within the β-GF, including one which unifies versions found in the fasciclin-1 superfamily, the ribosomal protein L25, the phosphoribosyl AMP cyclohydrolase (HisI) and glutamine synthetase. We also uncovered several new groups of β-GF domains including a domain found in bacterial flagellar and fimbrial assembly components, and 5 new UB-like domains in the eukaryotes.ConclusionEvolutionary reconstruction indicates that the β-GF had differentiated into at least 7 distinct lineages by the time of the last universal common ancestor of all extant organisms, encompassing much of the structural diversity observed in extant versions of the fold. The earliest β-GF members were probably involved in RNA metabolism and subsequently radiated into various functional niches. Most of the structural diversification occurred in the prokaryotes, whereas the eukaryotic phase was mainly marked by a specific expansion of the ubiquitin-like β-GF members. The eukaryotic UB superfamily diversified into at least 67 distinct families, of which at least 19–20 families were already present in the eukaryotic common ancestor, including several protein and one lipid conjugated forms. Another key aspect of the eukaryotic phase of evolution of the β-GF was the dramatic increase in domain architectural complexity of proteins related to the expansion of UB-like domains in numerous adaptor roles.ReviewersThis article was reviewed by Igor Zhulin, Arcady Mushegian and Frank Eisenhaber.
Endothelial Microparticle Levels Are Similar in Acute Ischemic Stroke and Stroke Mimics Due to Activation and Not Apoptosis/Necrosis
Authors: Williams Justin B. , Jauch Edward C. , Lindsell Christopher J. , Campos Begoña 
Published: July 2007

BackgroundEndothelial microparticles (EMPs) are <2‐μm membranous blebs from endothelial cell membranes that have been demonstrated to be elevated in vasculopathic conditions. One study has demonstrated elevated EMPs in acute ischemic stroke (AIS) versus age‐ and comorbidity‐matched controls. ObjectivesTo determine the level of EMPs in stroke mimics and AIS and determine if EMPs are released as a result of activation or apoptosis/necrosis in AIS. MethodsEMP levels in plasma of patients with AIS and stroke mimic patients were quantified by flow cytometry. Stroke status was verified in all patients by magnetic resonance imaging. Patients were matched for age and comorbidities. Markers for apoptosis/necrosis (platelet/endothelial cell adhesion molecule‐1 [PECAM‐1]/CD31 antigen) and activation (E‐selectin/CD62e antigen) were compared. A PECAM‐1/E‐selectin ratio of >4.0 was used to determine whether EMPs were generated via activation or apoptosis/necrosis. Data were compared between groups using the Mann‐Whitney U test. ResultsEMP levels were similar in stroke mimic patients when compared with AIS; there was no difference between groups (PECAM‐1, p = 0.393; E‐selectin, p = 0.579). The PECAM‐1/E‐selectin ratio was also similar for AIS and stroke mimics, and all were >4.0. ConclusionsEMP levels were similar in patients with AIS and stroke mimic patients. The PECAM‐1/E‐selectin ratio demonstrated that EMPs were generated via activation and not apoptosis/necrosis. This suggests that EMPs may not be a good marker for AIS, given the inability to discriminate between stroke mimics and AIS.
Phase II Clinical Trial of the Epothilone B Analog, Ixabepilone, in Patients With Non–Small-Cell Lung Cancer Whose Tumors Have Failed First-Line Platinum-Based Chemotherapy
Authors: Vansteenkiste Johan , Lara Primo N. , Le Chevalier Thierry , Breton Jean-Luc , Bonomi Philip , Sandler Alan B. , Socinski Mark A. , Delbaldo Catherine , McHenry Brent , Lebwohl David , Peck Ronald , Edelman Mark 
Published: July 2007

Purpose Ixabepilone is the first in a new class of antineoplastic agents, the epothilones and their analogs. This international, randomized, phase II trial assessed two administration schedules of ixabepilone as second-line therapy in patients with non–small-cell lung cancer (NSCLC). Patients and Methods Patients had experienced disease progression after one prior cisplatin- or carboplatin-based chemotherapy regimen. Ixabepilone was administered as a single 32 mg/m2 3-hour infusion (77 patients; arm A) or a 6 mg/m2 1-hour infusion daily for 5 consecutive days (69 patients; arm B) in a 3-week cycle. Results The intent-to-treat objective response rate was 14.3% in arm A and 11.6% in arm B. Median duration of response was 8.7 months (95% CI, 5.3 to 9.5 months) in arm A and 9.6 months (95% CI, 6.1 to 19.7 months) in arm B. Median time to progression was 2.1 months (95% CI, 1.4 to 2.8 months) for arm A and 1.5 months (95% CI, 1.4 to 2.8 months) for arm B. Median survival was 8.3 months (95% CI, 5.8 to 11.5 months) for arm A, and 7.3 months (95% CI, 5.7 to 11.7 months) for arm B; the 1-year survival rate (both cohorts) was 38%. Responses occurred in patients with taxane-pretreated and platinum-refractory tumors. Both regimens had an acceptable toxicity profile. Myelosuppression was manageable, manifesting primarily as neutropenia and leukopenia. Neuropathy was primarily sensory, generally mild to moderate in severity, and mostly reversible (both regimens). Conclusion Single-agent ixabepilone had clinically relevant activity and an acceptable safety profile in patients with advanced NSCLC whose tumors had failed one prior platinum-based chemotherapy regimen.
Phase II Trial of Ixabepilone, an Epothilone B Analog, in Patients With Metastatic Breast Cancer Previously Untreated With Taxanes
Authors: Denduluri Neelima , Low Jennifer A. , Lee James J. , Berman Arlene W. , Walshe Janice M. , Vatas Ujala , Chow Catherine K. , Steinberg Seth M. , Yang Sherry X. , Swain Sandra M. 
Published: July 2007

Purpose Ixabepilone is an epothilone B analog that binds to microtubules and results in microtubule stabilization and mitotic arrest. Ixabepilone was evaluated for efficacy and safety in a phase II clinical trial for women with metastatic breast cancer. Patients and Methods Patients were eligible if they had not previously received treatment with a taxane and had measurable metastatic breast cancer. Ixabepilone was administered at 6 mg/m2/d intravenously days 1 through 5 every 3 weeks until unacceptable toxicity or disease progression. Patients underwent pretreatment and post-treatment tumor biopsies, and tissues were analyzed for acetylated α-tubulin, tau-1, and p53 expression when possible. Results Twenty-three patients received 210 cycles with a median of eight cycles (range, two to 22 cycles) per patient. Thirteen patients (57%; exact 95% CI, 34.5% to 76.8%) had partial responses, six patients (26%) had stable disease, and four patients (17%) had progressive disease. Median time to progression and duration of response were 5.5 and 5.6 months, respectively. Four patients required dose reductions for neutropenia, neuropathy, or fatigue. Grade 3 or 4 toxicities included neutropenia (22%), fatigue (13%), anorexia (9%), and motor neuropathy (4%). Thirty-nine percent of patients experienced grade 1, 13% experienced grade 2, and none experienced grade 3/4 sensory neuropathy. The six patients with paired biopsies all had increases in tumor α-tubulin acetylation after treatment. Baseline or cycle 2 acetylated α-tubulin, tau-1, or p53 expression did not correlate with clinical response. Conclusion Women with metastatic breast cancer previously untreated with taxanes have a meaningful durable response to single-agent ixabepilone therapy. Minimal hematologic toxicity and no grade 3 sensory neuropathy were noted.
Calculation of the elastic deformation of textile beams during yarn winding
Authors: Vicentini V 
Published: July 2007

The problem of winding yarn on beams is examined. A theoretical calculation of the pressures on and the deformation of the beams is developed. In a first approximation the beam is assumed to be completely rigid and in a second approximation the elasticity of the barrel and flanges is taken into account. The results, developed on several types of yarn and on beams of various shapes and forms, are compared with experimental data obtained during a series of tests by the I.D.I. of Turin, Italy, on beams during use.
Large deformation of time-dependent materials in uniaxial tension
Authors: Soden P D W , Sowerby R 
Published: July 2007

Unaxial tensile tests have been conducted on commercially pure lead and cellulose nitrate, both time-dependent materials. It is shown that it is possible to predict all the important features of a tensile stress-strain curve from creep-test data, including the dependence of the curve upon extension rate. The behaviour of cellulose nitrate at the yield point is shown to be similar in nature to that of lead at the ultimate point. The stresses at these particular points were predicted with remarkable accuracy from the creep data over a range of extension rates from 1 per cent per minute up to 100 per cent per minute.
A photoelastic examination of the stresses in rolls during rolling
Authors: Khayyat F A , Lancaster P R 
Published: July 2007

The paper describes some experiments to determine the stress distribution in rolls during the rolling of pure lead. The rolls were made from a hard transparent resin and the isochromatics and isoclinics were recorded whilst rolling was in progress. From these recordings the stress distributions were obtained. Particular reference was made to conditions of normal and shear stress at the contacting surfaces. The paper gives results for three roll diameters and for each of these four roll loads were applied. The experiments were carried out for both dry and lubricated conditions. The results of this work show a variation of the shear stress at the surface of contact accompanied by a change of sign at the neutral point. The normal roll-pressure curves are in general agreement with those found by workers using other techniques. The results also indicate a significant variation in the ratio (shear stress/normal pressure) over the contact surface, although this was decreased by lubrication. For a given roll load and diameter lubricated rolling, as opposed to dry rolling, increases the reduction but appears to have no effect on lateral spread. For a given roll load a decrease in roll diameter results in an increase in reduction, lateral spread, mean roll pressure, and friction.
Stresses at keyway ends near shoulders
Authors: Fessler H , Rogers C C , Stanley P 
Published: July 2007

The photoelastic stress analysis of a series of shouldered shafts with keyways in the shanks is described. Direct loading and torsion have been studied. The shoulder-fillet ratio (shoulder-fillet radius/shank diameter) and the distance between keyway end and shoulder have been varied but both the ratio of the shoulder diameter to the shank diameter and the ratio of the keyway-fillet radius to the shank diameter were held constant through the model series. It is shown for both forms of loading that variations in the shoulder-fillet ratio have no significant effect on the greater principal stresses in the keyway fillet when the keyway end touches the shoulder-fillet toe; appreciable changes are caused in the stresses at the top of the keyway wall for torsional loading. Shoulder-fillet stresses are also presented. The dependence of the keyway stresses on the distance between shoulder fillet and keyway end has been studied; important stress reductions occur when the keyway end is continued through the shoulder fillet and into the shoulder proper. Maximum-stress indices for combined direct and torsional loads are derived for a particular geometry.
Continuous subcutaneous hydrocortisone infusion in Addison’s disease
Authors: Løvås Kristian , Husebye Eystein S 
Published: July 2007

Objective: The conventional replacement therapy in Addison’s disease (AD) does not restore the normal diurnal cortisol rhythm. We explored the feasibility and safety of continuous s.c. hydrocortisone infusion (CSHI) as a novel mode of glucocorticoid replacement therapy.
Design and methods: Seven patients with AD were treated with CSHI in an open-labelled clinical study for up to three months. Adequacy of glucocorticoid replacement was assessed by 24 h blood and saliva sampling in one patient and by salivary cortisol day curves in six outpatients. Subjective health status was monitored by the Short Form-36 questionnaire.
Results: CSHI re-established the circadian variation and normal levels of cortisol in the patients, with minor day-to-day variation. Most of the patients could reduce their glucocorticoid dose considerably without adverse reactions. The treatment was well tolerated and positively evaluated by the patients.
Conclusions: CSHI is technically feasible and safe in patients with AD. A daily dose of ~10 mg/m2 body surface area/day restores the circadian variation and normal levels of salivary cortisol in most patients, which is close to the estimated daily requirement. We hypothesise that selected patients will benefit from restoration of the circadian cortisol rhythm.
Locoregional recurrence and death from medullary thyroid carcinoma in a contemporaneous series: 5-year results
Authors: Machens Andreas , Hofmann Christine , Hauptmann Steffen , Dralle Henning 
Published: July 2007

Objective: Studies of outcome in patients with medullary thyroid carcinoma require long follow-ups to accrue enough cancer-specific events. Owing to time-dependent changes in diagnosis and therapy, long observation periods render studies susceptible to ‘time bias’ which can yield spurious results. This study was designed to investigate cancer-specific event rates after initial neck resection in contemporaneous patients recruited within less than a decade.
Design: Institutional cohort study of 128 consecutive patients who underwent compartment-oriented neck surgery between 1994 and 2002 at a tertiary surgical center for hitherto untreated medullary thyroid carcinoma.
Methods: The Kaplan–Meier method was used in conjunction with the log-rank test for analysis of time-dependent outcomes.
Results: Follow-up was available for 120 patients (94%) including 63 rearranged during transfection (RET) carriers. There were six locoregional recurrences in the 110 patients with clear surgical margins at initial neck resection, and 12 cancer-specific deaths in the 120 patients with available follow-up. On Kaplan–Meier analysis, most clinicopathological variables were significantly associated with recurrence-free survival and cancer-specific survival. Within the median observation period of 64.5 months, patients with node-negative tumors did not develop locoregional recurrence or die from their malignancies. The low event rates precluded multivariate analyses with all clinicopathological variables. With our extensive surgical approach, median recurrence-free survival and cancer-specific survival at 5 years were 95.2 and 89.3% respectively.
Discussion: Compared with literature data, our 5-year locoregional recurrence rate of 4.8% appeared very favorable, and our 5-year cancer-specific mortality rate of 10.7% was among the lowest ever reported. The growing proportion of localized medullary thyroid carcinomas among contemporaneous patients can be expected to ultimately lower the event rates, complicating future studies of outcome.
Association between glycosylated hemoglobin, left ventricular mass and aortic function in nondiabetic individuals with insulin resistance
Authors: Stakos Dimitrios A , Schuster Dara P , Sparks Elizabeth A , Meis Sophia Boudoulas , Wooley Charles F , Osei Kwame , Boudoulas Harisios 
Published: July 2007

Objective: An association between glycosylated hemoglobin (GHb) and cardiovascular mortality in nondiabetic individuals has recently been reported. Prompt detection of nondiabetic individuals with high-normal GHb and early cardiovascular involvement may be of value for preventive strategies. In this investigation, a possible relationship between GHb, aortic function and left ventricular (LV) mass in nondiabetic individuals has been studied.
Methods: A total of 263 nondiabetic African–Americans, aged 22–63 (mean 42 ± 8) years were studied. All individuals were first degree relatives of diabetic patients, had normal oral glucose tolerance test (2-h OGTT) and decreased peripheral action of insulin. LV diameters and mass (echocardiography); ascending and abdominal aortic distensibility (echocardiography, arterial pressure); pulse wave velocity (PWV; electrocardiography, Doppler); fasting glucose; GHb; insulin sensitivity index (SI) and 2-h OGTT were measured. Multiple linear and logistic regression analyses were used to identify significant independent associations of fasting glucose; GHb; SI and 2-h OGTT with aortic function and LV mass.
Results: In fully adjusted multivariate logistic regression analysis, GHb predicted lower values of aortic distensibility (odds ratio (OR) 1.67 95% CI (1.04–2.75), P=0.04); higher PWV (OR 1.79 95% CI (1.09–2.93), P=0.022); and higher values of LV mass (OR 1.56 95% CI (1.08–2.88), P=0.029). Fasting glucose, SI, and 2 h OGTT were not associated with aortic function and LV mass.
Conclusion: Higher GHb concentrations, even within ‘normal’ range, are independently associated with stiffer aorta and increased LV mass and thus may detect nondiabetic individuals at increased cardiovascular risk.
Metformin administration improves leukocyte count in women with polycystic ovary syndrome: a 6-month prospective study
Authors: Orio Francesco , Manguso Francesco , Di Biase Sebastiano , Falbo Angela , Giallauria Francesco , Labella Donato , Tolino Achille , Lombardi Gaetano , Colao Annamaria , Palomba Stefano 
Published: July 2007

Introduction: Polycystic ovary syndrome (PCOS) is a common disorder associated with a wide range of endocrine and metabolic abnormalities. Low-grade chronic inflammation is a related complication recently observed in PCOS. Increased white blood cell (WBC) count was previously reported in PCOS women.
Objective: To evaluate the effects of six months metformin administration on WBC count in PCOS women.
Patients and methods: Fifty normal-weight PCOS women without additional metabolic or cardiovascular diseases were enrolled and treated with metformin (850 mg twice daily) for 6 months in a prospective baseline-controlled clinical study. At baseline and after treatment, WBC count and C-reactive protein (CRP) were evaluated in each patient. The whole hormonal profile, serum insulin and glucose levels (at fasting and during a 75 g 2-h oral glucose tolerance test), serum lipid profile were also assessed.
Results: A significant difference was observed in WBC count (7050 ± 552 vs 6080 ± 577 cell/mm3 ± s.d., P<0.001) and CRP levels (1.8 ± 0.9 vs 1.1 ± 0.6 mg/l ± s.d., P<0.001) after metformin treatment in comparison with baseline values. SHBG levels and the free androgen index also changed significantly (P<0.001). Finally, high-density lipoproteins and the area under curve for glucose/area under curve for insulin ratio also significantly increased (P<0.001), whereas low-density lipoproteins and area under curve for insulin were significantly reduced (P<0.001). No other change was found in any of the biochemical parameters evaluated.
Conclusion: A six-month course of metformin reduces WBC count in PCOS women.
Surgical Outcomes for Velopharyngeal Insufficiency in Velocardiofacial Syndrome and Nonsyndromic Patients
Authors: Milczuk Henry A. , Smith Dana S. , Brockman Janet H. 
Published: July 2007

Objective: To compare speech outcomes after operative intervention for velopharyngeal insufficiency between velocardiofacial syndrome patients and nonsyndromic patients. Design: Retrospective cohort study. Setting: Tertiary academic center. Patients: Cohorts of 14 velocardiofacial syndrome and 15 nonsyndromic patients without overt cleft palate who underwent operative procedures to correct velopharyngeal insufficiency. All velocardiofacial syndrome patients were positive for 22q11.2 microdeletion by fluorescent in situ hybridization and possessed phenotypic features of velocardiofacial syndrome. Interventions: Operative procedures, including sphincter pharyngoplasty, Furlow palatoplasty, or both, were selected based on preoperative endoscopic assessments of velopharyngeal motion and residual gap size and shape, as well as velocardiofacial syndrome status. Five single and 9 combined procedures were performed in the velocardiofacial syndrome group, whereas 13 single and 2 combined procedures were performed in the nonsyndromic group. Outcome Measures: Pre- and post-op evaluation was conducted by a speech pathologist. Assessment parameters scored on a numerical scale included speech intelligibility, resonance, nasal air emissions, and overall severity of velopharyngeal insufficiency. Postoperative complications were recorded. Results: Most velocardiofacial syndrome patients and nonsyndromic patients demonstrated significant improvements in all parameters. Comparison of the two groups demonstrated similar improvements in both. Changes in speech resonance were significantly different between the two groups, whereas other speech parameters did not reach significance. There was no difference in airway complications between groups. Conclusions: Velocardiofacial syndrome patients may have comparable outcomes to nonsyndromic patients in selective surgical management of velopharyngeal insufficiency. In addition, the data demonstrate the efficacy of a single-stage combined procedure without increased morbidity.
Birth Prevalence of Oral Clefting in Northern Iran
Authors: Golalipour Mohammad Jafar , Mirfazeli Arezo , Behnampour Naser 
Published: July 2007

Objective: To explore the prevalence of oral clefting in northern Iran. Setting: In the Dezyani hospital 37,951 live births from 1998 through 2003 were screened for oral clefts. Clinical and demographic factors of diagnosed cases, including birth date, ethnicity, type of oral cleft, parental consanguinity, and coexisting anomalies, were recorded for analysis. Results: The overall prevalence of oral clefting was 0.97 per 1000 live births. The prevalence of cleft lip with or without cleft palate and isolated cleft palate was 0.60 and 0.37 per 1000, respectively. The prevalence of oral clefting was 1.08 per 1000 male births and 0.86 per 1000 female births. With respect to parental ethnicity, the prevalence of oral clefting was 0.86, 0.88, and 1.47 per 1000 in Fars, Turkman, and Sistani, respectively. Conclusions: The prevalence of oral cleft among live births in the Dezyani hospital is similar to that reported in the previous studies for Iran and whites.