bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth Hormone Deficiency by Growth Hormone Releasing Hormone-Arginine Testing Criteria Predicts Increased Cardiovascular Risk Markers in Normal Young Overweight and Obese Women
Authors: Utz Andrea L. , Yamamoto Ami , Hemphill Linda , Miller Karen K.
Published: April 2008

Context: Little is known about the relationship between GH and cardiovascular risk markers in women without organic hypothalamic/pituitary disease.

Objective: The objective of the study was to determine whether healthy young overweight and obese women, who would be classified as having GH deficiency (GHD) based on standard criteria used in hypopituitarism (peak GH after stimulation with GHRH and arginine < 5 ng/ml), have increased cardiovascular risk markers.

Design: This was a cross-sectional study.

Setting: The study was conducted at the General Clinical Research Center.

Study Participants: Forty-five women of reproductive age, mean age 33.1 ± 1.2 yr and mean body mass index (BMI) 30.9 ± 1.0 kg/m2.

Intervention: There was no intervention.

Main Outcome Measures: Measures included carotid intima-medial thickness, high-sensitivity C-reactive protein (hsCRP), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein, triglycerides, E-selectin, soluble intercellular adhesion molecule-1, TNF-α receptor I, TNF-α receptor II, fasting insulin levels, and oral glucose tolerance testing.

Results: Twenty-six percent of overweight or obese subjects and none with BMI less than 25 kg/m2 met criteria for GHD. Subjects who met GHD criteria had a mean BMI of 37.0 ± 1.7 kg/m2 (range 28.6–43.6 kg/m2), and their mean waist circumference (110.1 ± 3.5 cm) was higher than in overweight/obese women with GH sufficiency (P = 0.007). Mean carotid intima-media thickness, hsCRP, soluble intercellular adhesion molecule-1, TNF-α receptor I, and TNF-α receptor II levels were higher, and HDL lower, in women meeting GHD criteria than in GH sufficiency. Differences in HDL, hsCRP, and TNF-α receptor II remained after controlling for age plus BMI, waist circumference, or trunk fat. There were no differences in measures of insulin resistance.

Conclusions: There may be a relative GHD syndrome in overweight and obese women without organic pituitary or hypothalamic disease that confers increased cardiovascular risk, independent of weight.
Interaction between theDrosophilaheterochromatin proteins SUUR and HP1
Authors: Pindyurin Alexey V. , Boldyreva Lidiya V. , Shloma Victor V. , Kolesnikova Tatiana D. , Pokholkova Galina V. , Andreyeva Evgeniya N. , Kozhevnikova Elena N. , Ivanoschuk Igor G. , Zarutskaya Ekaterina A. , Demakov Sergey A. , Gorchakov Andrey A. , Belyaeva Elena S. , Zhimulev Igor F.
Published: April 2008

SUUR (Suppressor of Under-Replication) protein is responsible for late replication and, as a consequence, for DNA underreplication of intercalary and pericentric heterochromatin in Drosophila melanogaster polytene chromosomes. However, the mechanism by which SUUR slows down the replication process is not clear. To identify possible partners for SUUR we performed a yeast two-hybrid screen using full-length SUUR as bait. This identified HP1, the well-studied heterochromatin protein, as a strong SUUR interactor. Furthermore, we have determined that the central region of SUUR is necessary and sufficient for interaction with the C-terminal part of HP1, which contains the hinge and chromoshadow domains. In addition, recruitment of SUUR to ectopic HP1 sites on chromosomes provides evidence for their association in vivo. Indeed, we found that the distributions of SUUR and HP1 on polytene chromosomes are interdependent: both absence and overexpression of HP1 prevent SUUR from chromosomal binding, whereas SUUR overexpression causes redistribution of HP1 to numerous sites occupied by SUUR. Finally, HP1 binds to intercalary heterochromatin when histone methyltransferase activity of SU(VAR)3-9 is increased. We propose that interaction with HP1 is crucial for the association of SUUR with chromatin.
EML3 is a nuclear microtubule-binding protein required for the correct alignment of chromosomes in metaphase
Authors: Tegha-Dunghu Justus , Neumann Beate , Reber Simone , Krause Roland , Erfle Holger , Walter Thomas , Held Michael , Rogers Phill , Hupfeld Kerstin , Ruppert Thomas , Ellenberg Jan , Gruss Oliver J.
Published: April 2008

Assembly of the mitotic spindle requires a global change in the activity and constitution of the microtubule-binding-protein array at mitotic onset. An important subset of mitotic microtubule-binding proteins localises to the nucleus in interphase and essentially contributes to spindle formation and function after nuclear envelope breakdown. Here, we used a proteomic approach to selectively identify proteins of this category and revealed 50 poorly characterised human gene products, among them the echinoderm microtubule-associated-protein-like gene product, EML3. Indirect immunofluorescence showed that EML3 colocalises with spindle microtubules throughout all mitotic stages. In interphase, EML3 colocalised with cytoplasmic microtubules and accumulated in interphase nuclei. Using YFP-fusion constructs of EML3, we located a nuclear localisation signal and confirmed the microtubule-binding domain of EML3. Functional analysis of EML3 using time-lapse fluorescence microscopy and detailed end-point analysis of phenotypes after siRNA knockdown demonstrates an important role for EML3 in correct metaphase chromosome alignment. Our proteomic identification screen combined with sensitive phenotypic analysis therefore provides a reliable platform for the identification and characterisation of proteins important for correct cell division.
Fos cooperation with PTEN loss elicits keratoacanthoma not carcinoma, owing to p53/p21WAF-induced differentiation triggered by GSK3β inactivation and reduced AKT activity
Authors: Yao Denggao , Alexander Claire L. , Quinn Jean A. , Chan Weng-Chyn , Wu Hong , Greenhalgh David A.
Published: April 2008

To investigate gene synergism in multistage skin carcinogenesis, the RU486-inducible cre/lox system was employed to ablate Pten function (K14.cre/Δ5Ptenflx) in mouse epidermis expressing activated Fos (HK1.Fos). RU486-treated HK1.Fos/Δ5Ptenflx mice exhibited hyperplasia, hyperkeratosis and tumours that progressed to highly differentiated keratoacanthomas, rather than to carcinomas, owing to re-expression of high p53 and p21WAF levels. Despite elevated MAP kinase activity, cyclin D1 and cyclin E2 overexpression, and increased AKT activity that produced areas of highly proliferative papillomatous keratinocytes, increasing levels of GSK3β inactivation induced a novel p53/p21WAF expression profile, which subsequently halted proliferation and accelerated differentiation to give the hallmark keratosis of keratoacanthomas. A pivotal facet to this GSK3β-triggered mechanism centred on increasing p53 expression in basal layer keratinocytes. This increase in expression reduced activated AKT expression and released inhibition of p21WAF, which accelerated keratinocyte differentiation, as indicated by unique basal layer expression of differentiation-specific keratin K1 alongside premature filaggrin and loricrin expression. Thus, Fos synergism with Pten loss elicited a benign tumour context where GSK3β-induced p53/p21WAF expression continually switched AKT-associated proliferation into differentiation, preventing further progression. This putative compensatory mechanism required the critical availability of normal p53 and/or p21WAF, otherwise deregulated Fos, Akt and Gsk3β associate with malignant progression.
Do young patients with malunited fractures of the distal radius inevitably develop symptomatic post-traumatic osteoarthritis?
Authors: Forward D. P. , Davis T. R. C. , Sithole J. S.
Published: April 2008

Fractures of the distal radius occurring in young adults are treated increasingly by open surgical techniques, partly because of concern that failure to restore the alignment of the fracture accurately may cause symptomatic post-traumatic osteoarthritis in future years. We reviewed 106 adults who had sustained a fracture of the distal radius between 1960 and 1968 and who were below the age of 40 years at the time of injury. We carried out a clinical and radiological assessment at a mean follow-up of 38 years (33 to 42).

No patient had required a salvage procedure. While there was radiological evidence of post-traumatic osteoarthritis after an intra-articular fracture in 68% of patients (27 of 40), the disabilities of the arm, shoulder and hand (DASH) scores were not different from population norms, and function, as assessed by the Patient Evaluation Measure, was impaired by less than 10%. Ordinal logistic regression analysis showed a significant relationship between narrowing of the joint space and extra-articular malunion (dorsal angulation and radial shortening) as well as intra-articular injury. Multivariate analysis revealed that grip strength had fallen to 89% of that of the uninjured side in the presence of dorsal malunion, but no measure of extra-articular malunion was significantly related to either the Patient Evaluation Measure or DASH scores.

While anatomical reduction is the principal aim of treatment, imperfect reduction of these fractures may not result in symptomatic arthritis in the long term, and this should be considered when counselling patients on the risks and benefits of the many treatment options available.
Multimodal thromboprophylaxis following primary hip arthroplasty
Authors: Daniel J. , Pradhan A. , Pradhan C. , Ziaee H. , Moss M. , Freeman J. , McMinn D. J. W.
Published: April 2008

We report a retrospective review of the incidence of venous thromboembolism in 463 consecutive patients who underwent primary total hip arthroplasty (487 procedures). Treatment included both total hip replacement and hip resurfacing, and the patients were managed without anticoagulants. The thromboprophylaxis regimen included an antiplatelet agent, generally aspirin, hypotensive epidural anaesthesia, elastic compression stockings and early mobilisation. In 258 of these procedures (244 patients) performed in 2005 (cohort A) mechanical compression devices were not used, whereas in 229 (219 patients) performed during 2006 (cohort B) bilateral intermittent pneumatic calf compression was used.

All operations were performed through a posterior mini-incision approach. Patients who required anticoagulation for pre-existing medical problems and those undergoing revision arthroplasty were excluded. Doppler ultrasonographic screening for deep-vein thrombosis was performed in all patients between the fourth and sixth post-operative days. All patients were reviewed at a follow-up clinic six to ten weeks after the operation. In addition, reponse to a questionnaire was obtained at the end of 12 weeks post-operatively.

No symptomatic calf or above-knee deep-vein thrombosis or pulmonary embolism occurred. In 25 patients in cohort A (10.2%) and in ten patients in cohort B (4.6%) asymptomatic calf deep-vein thromboses were detected ultrasonographically. This difference was statistically significant (p = 0.03). The regimen followed by cohort B offers the prospect of a low incidence of venous thromboembolism without subjecting patients to the higher risk of bleeding associated with anticoagulant use.
The assessment of the ulnar nerve at the elbow by ultrasonography in children
Authors: Shen P.-C. , Chern T.-C. , Wu K.-C. , Tai T.-W. , Jou I.-M.
Published: April 2008

We evaluated the morphological changes to the ulnar nerve of both elbows in the cubital tunnel by sonography in a total of 237 children, of whom 117 were aged between six and seven years, 66 between eight and nine years, and 54 between ten and 11 years. We first scanned longitudinally in the extended elbow and then transversely at the medial epicondyle with the elbow extended to 0°. We repeated the scans with the elbow flexed at 45°, 90°, and 120°. There were no significant differences in the area of the ulnar nerve, but the diameter increased as the elbow moved from extension to flexion in all groups. More importantly, the ulnar nerve was subluxated anteriorly on to the medial epicondyle by 1.5% to 1.9% in extended elbows, by 5.9% to 7.9% in those flexed to 45°, by 40.0% to 44% in those flexed to 90°, and by 57.4% to 58.1% in those flexed to 120°, depending on the age group. Sonography clearly and accurately showed the ulnar nerve and was useful for localising the nerve before placing a medial pin. Because the ulnar nerve may translate anteriorly onto the medial epicondyle when the elbow is flexed to 90° or more, it should never be overlooked during percutaneous medial pinning.
Identifying the cellular basis for reimplantation failure in repair of the rotator cuff
Authors: Simon D. W. N. , Clarkin C. E. , Das-Gupta V. , Rawlinson S. C. F. , Emery R. J. , Pitsillides A. A.
Published: April 2008

We examined cultured osteoblasts derived from paired samples from the greater tuberosity and acromion from eight patients with large chronic tears of the rotator cuff.

We found that osteoblasts from the tuberosity had no apparent response to mechanical stimulation, whereas those derived from the acromion showed an increase in alkaline phosphatase activity and nitric oxide release which is normally a response of bone cells to mechanical strain. By contrast, we found that cells from both regions were able to respond to dexamethasone, a well-established promoter of osteoblastic differentiation, with the expected increase in alkaline phosphatase activity.

Our findings indicate that the failure of repair of the rotator cuff may be due, at least in part, to a compromised capacity for mechanoadaptation within the greater tuberosity. It remains to be seen whether this apparent decrease in the sensitivity of bone cells to mechanical stimulation is the specific consequence of the reduced load-bearing history of the greater tuberosity in these patients.
A ten-year follow-up of the Reflection cementless acetabular component
Authors: Civinini R. , D’Arienzo M. , Innocenti M.
Published: April 2008

We reviewed the long-term results at ten to 12 years of 118 total hip replacements in 109 patients using a second-generation hemispherical cementless acetabular component (Reflection) designed to address the problem of backside wear. Five patients (five hips) died and six patients (seven hips) were lost to follow-up. The remaining 98 patients (106 hips) had a mean age of 62.9 years (34.0 to 86.2) A rate of revision for aseptic loosening of 0.9%, and predictable results were found with respect to radiological evidence of fixation, lack of pain, walking ability, range of movement and function. One component was revised for aseptic loosening, and of the 101 hips (95.2%) that did not have a revision, minor osteolytic lesions of the pelvis were seen in six (5.9%). Kaplan-Meier survival analysis for the total cohort of 118 hips revealed a 96.4% survival at both ten (95% confidence interval 90 to 98) and 12 years (95% confidence interval 86 to 98).
The treatment of benign lesions of the proximal femur with non-vascularised autologous fibular strut grafts
Authors: George B. , Abudu A. , Grimer R. J. , Carter S. R. , Tillman R. M.
Published: April 2008

We report our experience of treating 17 patients with benign lesions of the proximal femur with non-vascularised, autologous fibular strut grafts, without osteosynthesis. The mean age of the patients at presentation was 16.5 years (5 to 33) and they were followed up for a mean of 2.9 years (0.4 to 19.5). Histological diagnoses included simple bone cyst, fibrous dysplasia, aneurysmal bone cysts and giant cell tumour. Local recurrence occurred in two patients (11.7%) and superficial wound infection, chronic hip pain and deep venous thrombosis occurred in three. Pathological fracture did not occur in any patient following the procedure.

We conclude that non-vascularised fibular strut grafts are a safe and satisfactory method of treating benign lesions of the proximal femur.
The creep and wear of highly cross-linked polyethylene
Authors: Glyn-Jones S. , McLardy-Smith P. , Gill H. S. , Murray D. W.
Published: April 2008

The creep and wear behaviour of highly cross-linked polyethylene and standard polyethylene liners were examined in a prospective, double-blind randomised, controlled trial using radiostereometric analysis.

We randomised 54 patients to receive hip replacements with either highly cross-linked polyethylene or standard liners and determined the three-dimensional penetration of the liners over three years.

After three years the mean total penetration was 0.35 mm (SD 0.14) for the highly cross-linked polyethylene group and 0.45 mm (SD 0.19) for the standard group. The difference was statistically significant (p = 0.0184). From the pattern of penetration it was possible to discriminate creep from wear. Most (95%) of the creep occurred within six months of implantation and nearly all within the first year. There was no difference in the mean degree of creep between the two types of polyethylene (highly cross-linked polyethylene 0.26 mm, SD 0.17; standard 0.27 mm, SD 0.2; p = 0.83). There was, however, a significant difference (p = 0.012) in the mean wear rate (highly cross-linked polyethylene 0.03 mm/yr, SD 0.06; standard 0.07 mm/yr, SD 0.05). Creep and wear occurred in significantly different directions (p = 0.01); creep was predominantly proximal whereas wear was anterior, proximal and medial.

We conclude that penetration in the first six months is creep-dominated, but after one year virtually all penetration is due to wear. Highly cross-linked polyethylene has a 60% lower rate of wear than standard polyethylene and therefore will probably perform better in the long term.
Is return to professional rugby union likely after anterior cervical spinal surgery?
Authors: Andrews J. , Jones A. , Davies P. R. , Howes J. , Ahuja S.
Published: April 2008

We have examined the outcome in 19 professional rugby union players who underwent anterior cervical discectomy and fusion between 1998 and 2003. Through a retrospective review of the medical records and telephone interviews of all 19 players, we have attempted to determine the likelihood of improvement, return to professional sport and the long-term consequences. We have also attempted to relate the probability of symptoms in the neck and radicular pain in the arm to the position of play. Neck and radicular pain were improved in 17 patients, with 13 returning to rugby, the majority by six months after operation. Of these, 13 returned to their pre-operative standard of play, one to a lower level and five have not played rugby again. Two of those who returned to the game have subsequently suffered further symptoms in the neck, one of whom was obliged to retire. The majority of the players with problems in the neck were front row forwards.

A return to playing rugby union after surgery and fusion of the anterior cervical spine is both likely and safe and need not end a career in the game.
Etravirine Has No Effect on QT and Corrected QT Interval in HIV-Negative Volunteers
Authors: Peeters Monika , Janssen Katrien , Kakuda Thomas N , Schöller-Gyüre Monika , Lachaert Ruth , Hoetelmans Richard MW , Woodfall Brian , Smedt Goedele De
Published: April 2008

Background:

Etravirine (TMC125), a next-generation nonnucleoside reverse transcriptase inhibitor, has shown antiviral efficacy in 2 large Phase 3 trials. In vitro and in vivo studies have shown that etravirine is not associated with proarrhythmic potential. Electrocardiograms (ECGs) from healthy and HIV 1–infected volunteers showed no clinically relevant changes.

Objective:

To evaluate the effect of 2 etravirine dosing regimens on QT/corrected QT interval (QTc) in HIV-negative volunteers and assess pharmacokinetic and additional safety parameters.

Methods:

A double-blind, double-dummy, randomized, placebo- and active-controlled, 4-period crossover trial was conducted in 41 HIV-negative volunteers. Participants received 4 regimens: etravirine 200 mg twice daily, etravirine 400 mg once daily, moxifloxacin 400 mg once daily (positive control), and placebo in separate 8-day sessions, with each followed by a washout period of 14 or more days. On days -1, 1, and 8 of each session, ECGs were recorded at 11 time points over 12 hours. Pharmacokinetic profiles of etravirine regimens were evaluated and safety was assessed.

Results:

Thirty-seven subjects completed the study. For etravirine, the upper limit of the 90% CIs of mean time-matched differences in QTc determined using Fridericia's formula (QTcF) was below 10 msec at all time points, the threshold for prolonged QT as defined by regulatory guidelines. The maximum mean (90% CI) difference of time-matched changes in QTcF versus placebo on day 1 was +0.1 msec (–2.6 to 2.9), -0.2 msec (-2.6 to 2.1), and +10.1 msec (7.3 to 12.8) for etravirine 200 mg twice daily, etravirine 400 mg once daily, and moxifloxacin, respectively. On day 8, these values were +0.6 msec (-2.1 to 3.3), -1.0 msec (-4.4 to 2.5), and +10.3 msec (6.8 to 13.9), respectively. Etravirine produced no clinically significant changes in other ECG parameters. No significant differences between males and females were observed. Both etravirine regimens had similar pharmacokinetic exposure and safety profiles.

Conclusions:

Etravirine does not prolong the QTc interval. No clinically relevant ECG changes were observed in HIV-negative volunteers. Short-term dosing of etravirine in HIV-negative volunteers was generally safe and well tolerated.
Perceptuo-Motor Interactions during Prehension Movements
Authors: Verhagen Lennart , Dijkerman H. Chris , Grol Meike J. , Toni Ivan
Published: April 2008

Adaptive behavior relies on the integration of perceptual and motor processes. In this study, we aimed at characterizing the cerebral processes underlying perceptuo-motor interactions evoked during prehension movements in healthy humans, as measured by means of functional magnetic resonance imaging. We manipulated the viewing conditions (binocular or monocular) during planning of a prehension movement, while parametrically varying the slant of the grasped object. This design manipulates the relative relevance and availability of different depth cues necessary for accurate planning of the prehension movement, biasing visual information processing toward either the dorsal visual stream (binocular vision) or the ventral visual stream (monocular vision). Two critical nodes of the dorsomedial visuomotor stream [V6A (anterior visual area 6) and PMd (dorsal premotor cortex)] increased their activity with increasing object slant, regardless of viewing conditions. In contrast, areas in both the dorsolateral visuomotor stream [anterior intraparietal area (AIP) and ventral premotor cortex (PMv)] and in the ventral visual stream [lateral-occipital tactile-visual area (LOtv)] showed differential slant-related responses, with activity increasing when monocular viewing conditions and increasing slant required the processing of pictorial depth cues. These conditions also increased the functional coupling of AIP with both LOtv and PMv. These findings support the view that the dorsomedial stream is automatically involved in processing visuospatial parameters for grasping, regardless of viewing conditions or object characteristics. In contrast, the dorsolateral stream appears to adapt motor behavior to the current conditions by integrating perceptual information processed in the ventral stream into the prehension plan.
Structural Insights into Aberrant Topological Patterns of Large-Scale Cortical Networks in Alzheimer's Disease
Authors: He Yong , Chen Zhang , Evans Alan
Published: April 2008

Recent research on Alzheimer's disease (AD) has shown that cognitive and memory decline in this disease is accompanied by disrupted changes in the coordination of large-scale brain functional networks. However, alterations in coordinated patterns of structural brain networks in AD are still poorly understood. Here, we used cortical thickness measurement from magnetic resonance imaging to investigate large-scale structural brain networks in 92 AD patients and 97 normal controls. Brain networks were constructed by thresholding cortical thickness correlation matrices of 54 regions and analyzed using graph theoretical approaches. Compared with controls, AD patients showed decreased cortical thickness intercorrelations between the bilateral parietal regions and increased intercorrelations in several selective regions involving the lateral temporal and parietal cortex as well as the cingulate and medial frontal cortex regions. Specially, AD patients showed abnormal small-world architecture in the structural cortical networks (increased clustering and shortest paths linking individual regions), implying a less optimal topological organization in AD. Moreover, AD patients were associated with reduced nodal centrality predominantly in the temporal and parietal heteromodal association cortex regions and increased nodal centrality in the occipital cortex regions. Finally, the brain networks of AD were about equally as robust to random failures as those of controls, but more vulnerable against targeted attacks, presumably because of the effects of pathological topological organization. Our findings suggest that the coordinated patterns of cortical morphology are widely altered in AD patients, thus providing structural evidence for disrupted integrity in large-scale brain networks that underlie cognition. This work has implications for our understanding of how functional deficits in patients are associated with their underlying structural (morphological) basis.
Anticipatory Activity in Anterior Cingulate Cortex Can Be Independent of Conflict and Error Likelihood
Authors: Aarts Esther , Roelofs Ardi , van Turennout Miranda
Published: April 2008

Previous studies have found no agreement on whether anticipatory activity in the anterior cingulate cortex (ACC) reflects upcoming conflict, error likelihood, or actual control adjustments. Using event-related functional magnetic resonance imaging, we investigated the nature of preparatory activity in the ACC. Informative cues told the participants whether an upcoming target would or would not involve conflict in a Stroop-like task. Uninformative cues provided no such information. Behavioral responses were faster after informative than after uninformative cues, indicating cue-based adjustments in control. ACC activity was larger after informative than uninformative cues, as would be expected if the ACC is involved in anticipatory control. Importantly, this activation in the ACC was observed for informative cues even when the information conveyed by the cue was that the upcoming target evokes no response conflict and has low error likelihood. This finding demonstrates that the ACC is involved in anticipatory control processes independent of upcoming response conflict or error likelihood. Moreover, the response of the ACC to the target stimuli was critically dependent on whether the cue was informative or not. ACC activity differed among target conditions after uninformative cues only, indicating ACC involvement in actual control adjustments. Together, these findings argue strongly for a role of the ACC in anticipatory control independent of anticipated conflict and error likelihood, and also show that such control can eliminate conflict-related ACC activity during target processing. Models of frontal cortex conflict-detection and conflict-resolution mechanisms require modification to include consideration of these anticipatory control properties of the ACC.
Vision Triggers an Experience-Dependent Sensitive Period at the Retinogeniculate Synapse
Authors: Hooks Bryan M. , Chen Chinfei
Published: April 2008

In the mammalian visual system, sensory experience is widely thought to sculpt cortical circuits during a precise critical period. In contrast, subcortical regions, such as the thalamus, were thought to develop at earlier ages in a vision-independent manner. Recent studies at the retinogeniculate synapse, however, have demonstrated an influence of vision on the formation of synaptic circuits in the thalamus. In mice, dark rearing from birth does not alter normal developmental maturation of the connection between retina and thalamus. However, deprivation 20 d after birth [postnatal day 20 (p20)] resulted in dramatic weakening of synaptic strength and an increase in the number of retinal inputs that innervate a thalamic relay neuron. Here, by quantifying changes in synaptic strength and connectivity in response to different time windows of deprivation, we find that several days of vision after eye opening is necessary for triggering experience-dependent plasticity. Shorter periods of visual experience do not permit similar experience-dependent synaptic reorganization. Furthermore, changes in connectivity are rapidly reversible simply by restoring normal vision. However, similar plasticity did not occur when shifting the onset of deprivation to p25. Although synapses still weakened, recruitment of additional retinal inputs no longer occurred. Therefore, synaptic circuits in the visual thalamus are unexpectedly malleable during a late developmental period, after the time when normal synapse elimination and pruning has occurred. This thalamic sensitive period overlaps temporally with experience-dependent changes in the cortex, suggesting that subcortical plasticity may influence cortical responses to sensory experience.
Embryonically Expressed GABA and Glutamate Drive Electrical Activity Regulating Neurotransmitter Specification
Authors: Root Cory M. , Velázquez-Ulloa Norma A. , Monsalve Gabriela C. , Minakova Elena , Spitzer Nicholas C.
Published: April 2008

Neurotransmitter signaling in the mature nervous system is well understood, but the functions of transmitters in the immature nervous system are less clear. Although transmitters released during embryogenesis regulate neuronal proliferation and migration, little is known about their role in regulating early neuronal differentiation. Here, we show that GABA and glutamate drive calcium-dependent embryonic electrical activity that regulates transmitter specification. The number of neurons expressing different transmitters changes when GABA or glutamate signaling is blocked chronically, either using morpholinos to knock down transmitter-synthetic enzymes or applying pharmacological receptor antagonists during a sensitive period of development. We find that calcium spikes are triggered by metabotropic GABA and glutamate receptors, which engage protein kinases A and C. The results reveal a novel role for embryonically expressed neurotransmitters.
Connexin 43 Hemichannels Are Permeable to ATP
Authors: Kang Jian , Kang Ning , Lovatt Ditte , Torres Arnulfo , Zhao Zhuo , Lin Jane , Nedergaard Maiken
Published: April 2008

Astrocytes are electrically nonexcitable cells that communicate by means of Ca2+signaling. Long-distance intercellular Ca2+waves are initiated by release of ATP and activation of purinergic receptors on nearby cells. Previous studies have implicated connexin 43 (Cx43) in ATP release, but definitive proof that ATP exits through Cx43 hemichannels does not exist. Here, through several alternative approaches, we show that ATP anions can permeate through Cx43 hemichannels. First, openings of Cx43 hemichannels were detected in both cell-attached and inside-out patch recordings in C6 cells expressing Cx43, but not in C6 cells expressing Cx43-eGFP (enhanced green fluorescent protein) or a C-terminus truncation mutant of Cx43. Second, Cx43 hemichannel openings were inhibited by three structurally different gap-junction channel blockers, but not by the P2X7blocker Brilliant blue G. Third, bioluminescence imaging of ATP combined with single-channel recording in the inside-out patch configuration showed that ATP efflux coincided with channel openings and was absent when the Cx43 hemichannel was closed. Fourth, ion replacement experiments confirmed that Cx43 hemichannels are permeable to ATP. In summary, these observations provide the first direct evidence for efflux of ATP through Cx43 hemichannels. Furthermore, a putative Cx43 hemichannel with characteristics identical to the Cx43 hemichannel in C6 cells was identified in the membrane of hippocampal astrocytes in acutely prepared slices.
Activation of the Amyloid Cascade in Apolipoprotein E4 Transgenic Mice Induces Lysosomal Activation and Neurodegeneration Resulting in Marked Cognitive Deficits
Authors: Belinson Haim , Lev Dimitri , Masliah Eliezer , Michaelson Daniel M.
Published: April 2008

The allele E4 of apolipoprotein E (apoE4), the most prevalent genetic risk factor for Alzheimer's disease, is associated histopathologically with elevated levels of brain amyloid. This led to the suggestion that the pathological effects of apoE4 are mediated by cross-talk interactions with amyloid β peptide (Aβ), which accentuate the pathological effects of the amyloid cascade. The mechanisms underlying the Aβ-mediated pathological effects of apoE4 are unknown. We have shown recently that inhibition of the Aβ-degrading enzyme neprilysin in brains of wild-type apoE3 and apoE4 mice results in rapid and similar elevations in their total brain Aβ levels. However, the nucleation and aggregation of Aβ in these mice were markedly affected by the apoE genotype and were specifically enhanced in the apoE4 mice. We presently used the neprilysin inhibition paradigm to analyze the neuropathological and cognitive effects that are induced by apoE4 after activation of the amyloid cascade. This revealed that apoE4 stimulates isoform specifically the degeneration of hippocampal CA1 neurons and of entorhinal and septal neurons, which is accompanied by the accumulation of intracellular Aβ and apoE and with lysosomal activation. Furthermore, these neuropathological effects are associated isoform specifically with the occurrence of pronounced cognitive deficits in the ApoE4 mice. These findings provide the firstin vivoevidence regarding the cellular mechanisms underlying the pathological cross talk between apoE4 and Aβ, as well as a novel model system of neurodegenerationin vivothat is uniquely suitable for studying the early stages of the amyloid cascade and the effects thereon of apoE4.
Comments on “Electrical conductivity of open-cell metal foams” by K.P. Dharmasena and H.N.G. Wadley [J. Mater. Res. 17, 625 (2002)]
Authors: Pervukhina Marina , Lebedev Maxim
Published: April 2008

Electrical conductivity of open-cell metallic foam calculated by Dharmasena and Wadley using the tetrakaidecahedral cell-based model with ligaments of constant or varying triangular cross sections along the cell edges was mistakenly concluded to strongly overestimate measured electrical conductivities of the open-cell aluminum foams (ERG Duocel). Accurate analysis shows that the model with triangular ligaments on the contrary underestimates the experimental results. A tetrakaidecahedral cell-based model that takes into account the particular ligament geometry, which is determined by constant mean curvature of ligament surfaces, is shown to explain the experimental data of electrical conductivity of the Duocel foams ranging in relative density from 4% to 12%.
Modeling of grain refinement: Part III. Al–7Si–0.3Mg aluminum alloy
Authors: Yao X. , McDonald S.D. , Dahle A.K. , Davidson C.J. , StJohn D.H.
Published: April 2008

Following Part I [X. Yao, et al., J. Mater. Res.23(5), 1282 (2008)] and Part II [X. Yao, et al., J. Mater. Res.23(5), 1292 (2008)] the cellular automation–finite control volume method (CAFVM) model was used to study the grain formation and microstructure morphology resulting from solidification of a commercial Al–Si–Mg alloy with Al–Ti–B grain refiner additions. The model incorporates the effect of the introduced solute Ti and the alloying elements of Si and Mg on the growth restriction factor, constitutional undercooling, and nucleation parameters. With respect to grain refinement, it is found that the alloying elements, Si and Mg, play a role that is similar to Ti qualitatively while different quantitatively. Accordingly, a concept of “equivalent solute” determined by phase diagram parameters such as the solute partitioning coefficient and the liquidus slope is proposed to clarify the effect of each solute in the alloy on grain formation during solidification. Based on the calculations and on comparison to the experimental data, a possible mechanism of grain refinement in this alloy system is proposed.
Poroelastic nanoindentation responses of hydrated bone
Authors: Oyen Michelle L.
Published: April 2008

Indentation techniques are used for the measurement of mechanical properties of a wide range of materials. Typical elastic analysis for spherical indentation is applicable in the absence of time-dependent deformation, but is inappropriate for materials with time-dependent creep responses active in the experimental time frame. In the current work, a poroelastic analysis—a mechanical theory incorporating fluid motion through a porous elastic network—is used to examine spherical indentation creep responses of hydrated biological materials. Existing analytical and finite element solutions for the poroelastic Hertzian indentation problem are reviewed, and a poroelastic parameter identification scheme is developed. Experimental data from nanoindentation of hydrated bone immersed in water and polar solvents (ethanol, methanol, acetone) are examined within the poroelastic framework. Immersion of bone in polar solvents with decreasing polarity results in increased stiffness, decreased Poisson’s ratio, and decreased hydraulic permeability. Nanoindentation poroelastic analysis results are compared with existing literature for bone poroelasticity at larger length scales, and the effective pore size probed in indentation creep experiments was estimated to be 1.6 nm, consistent with the scale of fundamental collagen–apatite interactions. Results for water permeability in bone were compared with studies of water diffusion through fully dense bone.
Oxidation of copper alloys studied by analytical transmission electron microscopy cross-sectional specimens
Authors: Honkanen Mari , Vippola Minnamari , Lepistö Toivo
Published: April 2008

In this work, the oxide structures of three polycrystalline copper grades, unalloyed oxygen-free (OF) copper and alloyed CuAg and deoxidized high-phosphor (DHP) copper, were studied using cross-sectional analytical transmission electron microscopy (AEM) samples. The oxidation treatments were carried out in air at 200 and 350 °C for different exposure times. The detailed oxide layer structures were characterized by AEM. At 200 °C, a nano-sized Cu2O layer formed on the all copper grades. At 350 °C, a nano-sized Cu2O layer formed first on the all copper grades. After longer exposure time at 350 °C, a crystalline CuO layer grew on the Cu2O layer of the unalloyed OF-copper. In the case of the alloyed CuAg- and DHP-copper, a crystalline and columnar shaped layer, consisting of Cu2O and CuO grains, formed on the nanocrystalline Cu2O layer. At 350 °C, the unalloyed copper oxidized notably slower than the alloyed coppers, and its oxide structures were different than those of the alloyed coppers.
Oxidation of Al–Au intermetallics and its consequences studied by x-ray photoelectron spectroscopy
Authors: Sritharan T. , Li Y.B. , Xu C. , Zhang S.
Published: April 2008

Three common Al–Au intermetallics, Al2Au, AlAu2, and AlAu4, were oxidized in the air and characterized using x-ray photoelectron spectroscopy in terms of the elemental chemical state. It was found that there is an increasing trend of oxidation in these intermetallics as the Au content increases. AlAu4 shows the greatest tendency to oxidize with two extra peaks appearing on the Au 4f spectra after long exposure time in air. The surface of AlAu2, although fully oxidized, reveals only one Au 4f peak shift as depth increases. Al2Au was the least oxidizing compound, and the oxide is thin. The binding energies of Al 2p and Au 4f peaks were measured and reported. The Au atoms trapped in the oxide layers exhibit higher binding energy emissions compared to those of elemental Au.
Formation of dense silicon carbide by liquid silicon infiltration of carbon with engineered structure
Authors: Margiotta Jesse C. , Zhang Dajie , Nagle Dennis C. , Feeser Caitlin E.
Published: April 2008

Fully dense and net-shaped silicon carbide monoliths were produced by liquid silicon infiltration of carbon preforms with engineered bulk density, median pore diameter, and chemical reactivity derived from carbonization of crystalline cellulose and phenolic resin blends. The ideal carbon bulk density and minimum median pore diameter for successful formation of fully dense silicon carbide by liquid silicon infiltration are 0.964 g cm−3and approximately 1 μm. By blending crystalline cellulose and phenolic resin in various mass ratios as carbon precursors, we were able to adjust the bulk density, median pore diameter, and overall chemical reactivity of the carbon preforms produced. The liquid silicon infiltration reactions were performed in a graphite element furnace at temperatures between 1414 and 1900 °C and under argon pressures of 1550, 760, and 0.5 Torr for periods of 10, 15, 30, 60, 120, and 300 min. Examination of the results indicated that the ideal carbon preform was produced from the crystalline cellulose and phenolic resin blend of 6:4 mass ratio. This carbon preform has a bulk density of 0.7910 g cm−3, an actual density of 2.1911 g cm−3, median pore diameter of 1.45 μm, and specific surface area of 644.75 m2g−1. The ideal liquid silicon infiltration reaction conditions were identified as 1800 °C, 0.5 Torr, and 120 min. The optimum reaction product has a bulk density of 2.9566 g cm−3, greater than 91% of that of pure β–SiC, with a β–SiC volume fraction of approximately 82.5%.
Structure and properties of reactive direct current magnetron sputtered niobium aluminum nitride coatings
Authors: Barshilia Harish C. , Deepthi B. , Rajam K.S. , Bhatti Kanwal Preet , Chaudhary Sujeet
Published: April 2008

A reactive direct current magnetron sputtering system was used to prepare NbAlN coatings at different nitrogen flow rates and substrate bias voltages. Various properties of NbAlN coatings were studied using x-ray diffraction, scanning electron microscopy, atomic force microscopy, x-ray photoelectron spectroscopy, nanoindentation, the four-probe method, a solar spectrum reflectometer and emissometer, spectroscopic ellipsometry, micro-Raman spectroscopy, and potentiodynamic polarization techniques. Single-phase NbAlN with B1 NaCl structure was obtained for the coatings prepared at a nitrogen flow rate in the range of 1.5–3 sccm, a substrate bias voltage of −50 to −210 V, and a substrate temperature of 300 °C. Nanoindentation data showed that the optimized NbAlN coating exhibited a maximum hardness of 2856 kg/mm2. An approximately 100-nm-thick NbAlN–NbAlON tandem on copper substrate exhibited a high absorptance (0.93) and a low emittance (0.06), suitable for solar-selective applications. The spectroscopic ellipsometry and resistivity data established the metallic nature of NbAlN and the semitransparent behavior of NbAlON coatings. The corrosion resistance of NbAlN coatings was superior to that of the mild steel substrate. The addition of aluminum in NbN coatings increased the onset of oxidation in air from 350 to 700 °C. Vacuum-annealed NbAlN coatings were structurally stable up to 700 °C and retained their high hardness up to a temperature of 650 °C.
Phase stability and cohesive properties of Au–Sn intermetallics: A first-principles study
Authors: Ghosh G.
Published: April 2008

The total energies and cohesive properties of 29 Au–Sn intermetallics (stable, metastable, and virtual) are calculated from first-principles density-functional theory (DFT) employing ultrasoft pseudopotentials (USPP) and both local-density approximation (LDA) and generalized gradient approximation (GGA) for the exchange-correlation functional. Among the intermetallics considered, the ground-state structures are found to be AuSn, AuSn2, and AuSn4. Another phase Au5Sn, though present in the equilibrium diagram, lies slightly above the ground state convex hull. The formation energies of stable phases calculated using USPP–LDA and USPP–GGA are nearly the same. Except for AuSn, calorimetric data for enthalpies of formation show a good agreement with the calculated formation energies. Based on our first-principles results, it is argued that the structures of two metastable phases arecP52-type γ brass (isotypic with Al4Cu9) at Au–20.5 at.% Sn andhP1-type γ (isotypic with HgSn6–10) at Sn–8 at.% Au. For the intermetallics considered in this study, we provide optimized values of lattice parameters and Wyckoff positions. The experimental lattice parameters show a better agreement with those calculated using USPP–LDA than with USPP–GGA. The results presented here form the basis for creating a reliable thermodynamic database to facilitate calculations of stable and metastable phase diagrams of binary and multicomponent systems containing Au and Sn, relevant to electronic packaging and many other joining applications.
Effect of film chemistry on refractive index of plasma-enhanced chemical vapor deposited silicon oxynitride films: A correlative study
Authors: Naskar S. , Wolter S.D. , Bower C.A. , Stoner B.R. , Glass J.T.
Published: April 2008

Thick SiOxNy films were deposited by radiofrequency (rf) plasma chemical vapor deposition using silane (SiH4) and nitrous oxide (N2O) source gases. The influence of deposition conditions of gas flow ratio, rf plasma mixed-frequency ratio (100 kHz, 13.56 MHz), and rf power on the refractive index were examined. It was observed that the refractive index of the SiOxNy films increased with N and Si concentration as measured via x-ray photoelectron spectroscopy. Interestingly, a variation of refractive index with N2O:SiH4 flow ratio for the two drive frequencies was observed, suggesting that oxynitride bonding plays an important role in determining the optical properties. The two drive frequencies also led to differences in hydrogen concentration that were found to be correlated with refractive index. Hydrogen concentration has been linked to significant optical absorption losses above index values of ∼1.6, which we identified as a saturation level in our films.
Measurement of impact toughness of eutectic SnPb and SnAgCu solder joints in ball grid array by mini-impact tester
Authors: Xu Yuhuan , Ou Shengquan , Tu K.N. , Zeng Kejun , Dunne Rajiv
Published: April 2008

The most frequent cause of failure for wireless, handheld, and portable consumer electronic products is an accidental drop to the ground. The impact may cause interfacial fracture of ball-grid-array solder joints. Existing metrology, such as ball shear and ball pull tests, cannot characterize the impact-induced high speed fracture failure. In this study, a mini-impact tester was utilized to measure the impact toughness and to characterize the impact reliability of both eutectic SnPb and SnAgCu solder joints. The annealing effect at 150 °C on the impact toughness was investigated, and the fractured surfaces were examined. The impact toughness of SnAgCu solder joints with the plating of electroless Ni/immersion Au (ENIG) became worse after annealing, decreasing from 10 or 11 mJ to 7 mJ. On the other hand, an improvement of the impact toughness of eutectic SnPb solder joints with ENIG was recorded after annealing, increasing from 6 or 10 to 15 mJ. Annealing has softened the bulk SnPb solder so that more plastic deformation can occur to absorb the impact energy.