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Smaller Volume (smaller + volume)
Selected AbstractsCommercial manufacturing scale formulation and analytical characterization of therapeutic recombinant antibodiesDRUG DEVELOPMENT RESEARCH, Issue 3 2004Reed J. Harris Abstract Stable therapeutic antibody dosage forms present production technology challenges, particularly when high-concentration formulations are needed to meet the elevated dose requirements that are generally required for successful antibody therapy. Solid dosage forms, such as lyophilized powders, are generally more stable than liquid formulations. High-concentration drug products can be achieved by reconstitution of the lyophilisate in a smaller volume than its initial (pre-lyophilization) volume, but requires a significant vial overfill. High-concentration liquid formulations are becoming feasible as new techniques and technologies become available. Analytical methods to detect subtle molecular variations have been developed to demonstrate manufacturing consistency. Some molecular heterogeneity is contributed by conserved sites, such as Asn297 glycosylation and the loss of heavy chain C-terminal Lys residues. Characteristics that affect potency, stability, or immunogenicity must be elucidated for each therapeutic antibody. Drug Dev. Res. 61:137,154, 2004. © 2004 Wiley-Liss, Inc. [source] A geochronological approach to understanding the role of solar activity on Holocene glacier length variability in the Swiss AlpsGEOGRAFISKA ANNALER SERIES A: PHYSICAL GEOGRAPHY, Issue 4 2006Anne Hormes ABSTRACT. We present a radiocarbon data set of 71 samples of wood and peat material that melted out or sheared out from underneath eight presentday mid-latitude glaciers in the Central Swiss Alps. Results indicated that in the past several glaciers have been repeatedly less extensive than they were in the 1990s. The periods when glaciers had a smaller volume and shorter length persisted between 320 and 2500 years. This data set provides greater insight into glacier variability than previously possible, especially for the early and middle Holocene. The radiocarbon-dated periods defined with less extensive glaciers coincide with periods of reduced radio-production, pointing to a connection between solar activity and glacier melting processes. Measured long-term series of glacier length variations show significant correlation with the total solar irradiance. Incoming solar irradiance and changing albedo can account for a direct forcing of the glacier mass balances. Long-term investigations of atmospheric processes that are in interaction with changing solar activity are needed in order to understand the feedback mechanisms with glacier mass balances. [source] Enhancement of heat transfer in hydrogen storage tank with hydrogen absorbing alloy (optimum fin layout)HEAT TRANSFER - ASIAN RESEARCH (FORMERLY HEAT TRANSFER-JAPANESE RESEARCH), Issue 3 2008Yuichi Mitsutake Abstract Optimization of the fin layout in a metal hydride (MH) bed has been sought to enhance poor heat transmission in a hydrogen storage tank, and to obtain a maximum hydrogen absorption rate with a smaller volume of fins. Two different fin configurations, radial and circular fins, in a vertical cylindrical reactor vessel were tested with a La-Ni-based AB5 type hydrogen storage alloy. A two-dimensional transient heat conduction analysis, coupled with predicted temperature and concentration of absorbed hydrogen in the bed for the exothermic hydride reaction, was used to evaluate enhancement of the hydrogen absorption time. The estimated temperature and concentration agreed within 6 K and 8.5%, respectively, with our experimental results. The effect of thickness and the spacing and shape of fins on the hydrogen absorption time were analytically evaluated, so that the optimum range of the each fin layout was obtained by the trade off between absorption time and reduction in the MH volume due to the volume occupied by fins. The hydrogen absorption time for the recommended layout of circular fins was reduced to approximately one-third of that without fins. © 2008 Wiley Periodicals, Inc. Heat Trans Asian Res, 37(3): 165,183, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20195 [source] In vitro and in vivo tumor growth inhibition by a p16-mimicking peptide in p16INK4A -defective, pRb-positive human melanoma cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2005Douglas M. Noonan The cell cycle regulatory pathway responsible for the control of the late-G1 checkpoint is found recurrently altered in human malignant melanoma, often due to lack of functional p16 or pRb (pRb-1) proteins. Here we examined the ability of p16-derived peptides to mimic p16 function in two exemplary human melanoma cell lines: the p16-defective, pRb-positive A375M cells and p16-positive, pRb-defective A2058 cells. The synthetic p16-mimicking peptides strongly induced apoptosis in p16,, pRb+ A375M cells in vitro, while they had significantly less activity on p16+, pRb, A2058 cells. The most active p16-mimicking peptide, p16-AP9, also potently inhibited in vivo growth of the A375M melanoma. Treated tumors showed a threefold smaller volume (P,<,0.025) and a significant reduction of the mitotic index and of PCNA expression. Growth of A2058 cells in vivo was not affected by treatment with the p16-mimicking peptide. Our results demonstrate that p16-mimicking peptides can induce apoptosis in vitro and that can inhibit tumor growth in vivo in p16-defective, pRb-expressing human melanoma cells, suggesting that p16-mimicking peptides can represent a promising tool for targeted therapy in selected cancer phenotypes. © 2004 Wiley-Liss, Inc. [source] Relationship between excision volume, margin status, and tumor size with the development of local recurrence in patients with ductal carcinoma-in-situ treated with breast-conserving therapyJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2001Frank A. Vicini MD Abstract Background and Objectives We reviewed our institution's experience treating patients with ductal carcinoma-in-situ (DCIS) with breast-conserving therapy (BCT) to help define the interrelationship between excision volume, margin status, and tumor size with local recurrence. Methods From January 1980 to December 1993, 146 patients received BCT for DCIS. All patients underwent excisional biopsy and 95 cases (64%) underwent re-excision. Each patient received whole breast radiation to a median dose of 45 Gy. An additional 139 cases (94%) received a supplemental boost to the tumor bed (median total dose 60.4 Gy). The median follow-up is 7.2 years. Results Seventeen patients developed an ipsilateral breast failure for a 5- and 10-year actuarial rate of 10.2 and 12.4%, respectively. On multivariate analysis, patient age, margin status, the number of slides containing DCIS, the number of DCIS/cancerization of lobules (COL) foci near (< 5,mm) the margin, and a smaller volume of excision (< 60,cm3) were all independently associated with outcome. Although the local recurrence rate generally decreased as margin distance increased, these differences did not achieve statistical significance unless the volume of excision was taken into consideration. Conclusions These findings suggest that the success of BCT is directly related to the degree of surgical removal of DCIS and that margin status alone may be suboptimal in defining excision adequacy. J. Surg. Oncol. 2001;76:245,254. © 2001 Wiley-Liss, Inc. [source] Bladder diary patterns in detrusor overactivity and urodynamic stress incontinence,NEUROUROLOGY AND URODYNAMICS, Issue 6 2007Matthew Parsons Abstract Aims Our aims were: (1) to describe and compare frequency-volume and incontinence episode patterns in patients with urodynamic stress incontinence (USI) and detrusor overactivity (DO) as measured by a hand-written and computer-analyzed bladder diary and (2) to compare degree of separation between these clinical groups produced by raw diary measurements and after age- and total-volume-adjustment against a reference population. Materials and Methods We studied 58 patients with USI, 29 with DO, and 22 with both USI and DO. From 3-day hand-written and computer-analyzed bladder diaries, we calculated average and maximum volume voided (Vol/Void), voiding frequency and volume voided over 24 hr, and number, size and type (whether accompanied by activity or urge) of incontinence episodes. Results Compared to the USI patients, the DO patients tended to have (1) higher voiding frequency, (2) lower Vol/Void, (3) more urge-related, than activity-related leaks, (4) smaller volume, and equally frequent leaks and (5) more severe incontinence symptoms. The age- and volume-adjusted percentiles better separated the USI and DO groups' frequency and volume measurements than did the raw measurements. Unexpectedly high percentages of our USI patients had low Vol/Void measurements, high voiding frequency, and predominantly urge-related leaks. A subgroup of 29 USI patients with "low" (average volume <30th reference population percentile) Vol/Void measurements had high incidences of urgency and urge-related leaks. Conclusions Reference population percentiles better separate the frequency/volume patterns of USI and DO than do the raw measurements. We found a subgroup of USI patients that had an OAB-like clinical picture. Neurourol. Urodynam. 26:800,806, 2007. © 2007 Wiley-Liss, Inc. [source] Smaller amygdala is associated with anxiety in patients with panic disorderPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2009Fumi Hayano phd Aims:, Anxiety a core feature of panic disorder, is linked to function of the amygdala. Volume alterations in the brain of patients with panic disorder have previously been reported, but there has been no report of amygdala volume association with anxiety. Methods:, Volumes of hippocampus and amygdala were manually measured using magnetic resonance imaging obtained from 27 patients with panic disorder and 30 healthy comparison subjects. In addition the amygdala was focused on, applying small volume correction to optimized voxel-based morphometry (VBM). State,Trait Anxiety Inventory and the NEO Personality Inventory Revised were also used to evaluate anxiety. Results:, Amygdala volumes in both hemispheres were significantly smaller in patients with panic disorder compared with control subjects (left: t = ,2.248, d.f. = 55, P = 0.029; right: t = ,2.892, d.f. = 55, P = 0.005). VBM showed that structural alteration in the panic disorder group occurred on the corticomedial nuclear group within the right amygdala (coordinates [x,y,z (mm)]: [26,,6,,16], Z score = 3.92, family-wise error-corrected P = 0.002). The state anxiety was negatively correlated with the left amygdala volume in patients with panic disorder (r = ,0.545, P = 0.016). Conclusions:, These findings suggested that the smaller volume of the amygdala may be associated with anxiety in panic disorder. Of note, the smaller subregion in the amygdala estimated on VBM could correspond to the corticomedial nuclear group including the central nucleus, which may play a crucial role in panic attack. [source] IMAGING STUDY: Prefrontal cortex morphometry in abstinent adolescent marijuana users: subtle gender effectsADDICTION BIOLOGY, Issue 4 2009Krista Lisdahl Medina ABSTRACT Adult human studies suggest frontal dysfunction associated with chronic marijuana (MJ) use, but due to continued neuromaturation, adult studies may not generalize to adolescents. This study characterized prefrontal cortex (PFC) morphometry in chronic MJ-using adolescents following 1 month of monitored abstinence. Data were collected from MJ users (n = 16) and controls (n = 16) aged 16,18. Extensive exclusionary criteria included co-morbid psychiatric and neurologic disorders. Substance use and anatomical measures were collected after 28 days of monitored abstinence. PFC volumes were ascertained from manual tracing by reliable raters on high-resolution magnetic resonance images. After controlling for lifetime alcohol use, gender and intracranial volume, MJ users did not differ from controls in PFC volume. However, marginal group-by-gender interactions were observed (P < 0.09): female MJ users demonstrated comparatively larger PFC volumes while male MJ users had smaller volumes compared with same-gender controls. Further, group status and total PFC volume interacted in predicting executive functioning (P < 0.05). Among MJ users, smaller PFC total volume was associated with better executive functioning while the opposite pattern was seen among the controls. These preliminary results indicate that gender may moderate the relationship between MJ use and PFC morphometry. Given the relationship between larger PFC total volumes and poorer executive functioning among MJ users, female MJ users may be at increased risk for neurocognitive consequences. Future research will measure PFC gray and white matter separately and follow boys and girls over adolescence to examine the influence of MJ use on neurodevelopment. [source] Altered volume and hemispheric asymmetry of the superficial cortical layers in the schizophrenia planum temporaleEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2009John F. Smiley Abstract In vivo structural MRI studies in schizophrenia auditory cerebral cortex have reported smaller volumes and, less consistently, have reported altered hemispheric asymmetry of volumes. We used autopsy brains from 19 schizophrenia and 18 nonpsychiatric male subjects to measure the volume asymmetry of the planum temporal (PT). We then used the most recently autopsied 11 schizophrenia and 10 nonpsychiatric brains to measure the widths and fractional volumes of the upper (I,III) and lower (IV,VI) layers. Measurements of whole PT gray matter volumes did not show significant changes in schizophrenia. Nevertheless, laminar volume measurements revealed that the upper layers of the PT comprise a smaller fraction of the total cortex in schizophrenia than in nonpsychiatric brains. Subdivision of the PT showed that this change was especially prominent caudally, beyond Heschl's gyrus, whereas similar but less pronounced changes were found in the rostral PT and Heschl's gyrus. Complementary measures of laminar widths showed that the altered fractional volume in the caudal left PT was due mainly to ,8% thinner upper layers. However, the caudal right PT had a different profile, with thicker lower layers and comparatively unchanged upper layers. Thus, in the present study, laminar measurements provided a more sensitive method for detecting changes than measurement of whole PT volumes. Besides findings in schizophrenia, our cortical width measurements revealed normal hemispheric asymmetries consistent with previous reports. In schizophrenia, the thinner upper layers of the caudal PT suggest disrupted corticocortical processing, possibly affecting the multisensory integration and phonetic processing of this region. [source] A voxel-based morphometry study of frontal gray matter correlates of impulsivity,HUMAN BRAIN MAPPING, Issue 4 2009Koji Matsuo Abstract Impulsivity is a personality trait exhibited by healthy individuals, but excessive impulsivity is associated with some mental disorders. Lesion and functional neuroimaging studies indicate that the ventromedial prefrontal region (VMPFC), including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and medial prefrontal cortex, and the amygdala may modulate impulsivity and aggression. However, no morphometric study has examined the association between VMPFC and impulsivity. We hypothesized that healthy subjects with high impulsivity would have smaller volumes in these brain regions compared with those with low impulsivity. Sixty-two healthy subjects were studied (age 35.4 ± 12.1 years) using a 1.5-T MRI system. The Barratt impulsiveness scale (BIS) was used to assess impulsivity. Images were processed using an optimized voxel-based morphometry (VBM) protocol. We calculated the correlations between BIS scale scores and the gray matter (GM) and white matter (WM) volumes of VMPFC and amygdala. GM volumes of the left and right OFC were inversely correlated with the BIS total score (P = 0.04 and 0.02, respectively). Left ACC GM volumes had a tendency to be inversely correlated with the BIS total score (P = 0.05). Right OFC GM volumes were inversely correlated with BIS nonplanning impulsivity, and left OFC GM volumes were inversely correlated with motor impulsivity. There were no significant WM volume correlations with impulsivity. The results of this morphometry study indicate that small OFC volume relate to high impulsivity and extend the prior finding that the VMPFC is involved in the circuit modulating impulsivity. Hum Brain Mapp 2009. © 2008 Wiley-Liss, Inc. [source] The amounts and deposition patterns of fibrin-type fibrinoid at the villous surface are altered in pregnancy at high altitudeJOURNAL OF ANATOMY, Issue 5 2002T. M. Mayhew In pregnancy at high altitude, there is preplacental (hypobaric) hypoxia and intrauterine fetal growth is restricted. Previous studies on placentas from Amerindian and nonindigenous women completing term pregnancies at low (LA; 400 m) and high (HA; 3600 m) altitudes in Bolivia showed that HA placentas had smaller surface areas of villi and smaller volumes of fibrin type fibrinoid (FTF). Recently we devised a stereological method for testing whether perivillous FTF (pFTF) is randomly distributed at the surface of villous trophoblast. Here the method is applied to test 2 experimental hypotheses: [1] deposition of pFTF is nonrandom regardless of altitude and [2] deposition patterns differ between altitudes. Uniform random samples of microscopical fields were drawn from Masson trichrome stained sections and intersection counts used to estimate the surface areas of, and patterns of pFTF on, 4 regions of trophoblast: nonsyncytial knots (nonSK), syncytial knots (SK), syncytial bridges (SB) and denudation sites (DEN). Absolute areas were compared by 2-way analyses of variance. Expected and observed distributions were compared by (2 and contingency table analyses. At LA the mean (SEM) volume of FTF was 8.4 (1.54) cm3 and villous surface area was 7.0 (0.43) m2. At HA FTF volume was reduced by about 50% (P < 0.01) and villous surface by 20% (P < 0.01). The surface composition of trophoblast in LA placentas was nonSK (91%), SK (5%) and SB and DEN (both less than 3%). Relative surfaces were not significantly altered in HA placentas but, due to the impoverished growth of villi at HA, the changes represented a real decline in absolute surface of nonSK. At HA, the total surface of pFTF on trophoblast decreased by about 40%, from 4430 (564) cm2,2570 (406) cm2 (P < 0.01). At both altitudes pFTF deposition was preferentially found at DEN (12-fold greater than expected for a random distribution). Pattern differences were detected between altitudes. In HA placentas the amount of pFTF deposited on nonSK regions was about 45% less (P < 0.05); apparent changes on SK and SB regions were not significant. These histometric findings suggest that the coagulation-fibrinolysis steady state is altered at HA and favours greater fibrinolysis. At least some of the fibrinolytic or anticoagulant activity seems to reside in or on thinner regions of villous trophoblast and the placenta may be a relatively privileged site in terms of fibrinolysis. Also, reduced deposition of pFTF is probably linked to changes in the steady state of trophoblast turnover which seems to be perturbed in HA pregnancies. [source] Parietal Gray Matter Volume Loss Is Related to Spatial Processing Deficits in Long-Term Abstinent Alcoholic MenALCOHOLISM, Issue 10 2009George Fein Background:, We previously demonstrated relatively intact cognitive function (with the exception of suggestive evidence for persistent deficits in spatial information processing) in middle-aged long-term abstinent alcoholics (LTAA, abstinent for 6 months or more) compared to age and gender comparable nonalcoholic controls (NAC) (Fein et al., 2006). Methods:, In the current study, we examine cortical gray matter volumes in the same samples to determine whether gray matter volumes in LTAA are consistent with the cognitive results , i.e., exhibiting gray matter volumes comparable to NAC in most brain regions, except for possible indications of persistent shrinkage in the parietal lobe subserving spatial information processing. Results:, We found gray matter shrinkage in LTAA in the parietal lobe consistent with the spatial processing deficits in this same sample. More compelling, in LTAA, the magnitude of parietal gray matter shrinkage was negatively associated with spatial processing domain performance and positively associated with alcohol dose. Gray matter volume deficits were present in the occipital and other cortical tissue, but poorer visuospatial test performance correlated significantly with smaller volumes in the parietal cortex only. Conclusions:, Taken together, the cognitive and structural imaging data provide compelling evidence that chronic alcohol abuse results in shrinkage of the parietal cortex with associated deficits in spatial information processing. [source] Multicellular-like compartmentalization of cytoplast in fossil larger foraminiferaLETHAIA, Issue 2 2002CARLES FERRÀNDEZ-CAÑADELL Foraminifera are usually between 0.1 and 1 mm in size, thus falling within the range of the largest eukaryotic cells. However, some fossil and extant foraminiferal species reach diameters of more than 100 mm. One hypothesis of how these gigantic sizes could have been attained by these unicellular organisms is the temporary compartmentalization of cytoplasm into smaller volumes of effective metabolism, as reported for several recent species. Evidence of this phenomenon is shown in fossil genera of larger foraminifera belonging to five families of Cretaceous to Oligocene age. Alternative interpretations are discussed. [source] BPH with coexisting overactive bladder dysfunction,an everyday urological dilemmaNEUROUROLOGY AND URODYNAMICS, Issue 3 2001Tomas Knutson Abstract The aim of this study was to use a systematic schedule, including urodynamics, to describe the rate of coexisting overactive bladder (OB) in patients with bladder outlet obstruction (BOO) caused by benign prostatic hyperplasia (BPH). We also identified differences between the patients with pure BOO compared with those with BOO combined with OB (BOO,+,OB). One hundred and sixty-two men referred to our clinic due to LUTS were included. Patients with a history that might affect their bladder function were excluded. After cystometry and pressure,flow studies, the patients were divided into pure BOO and BOO,+,OB. Of the 162 men, 55% had pure BOO. BOO,+,OB was found in 45%. Age, s-PSA, voided volume, and obstruction grade differed significantly between the groups. The patients with BOO,+,OB were older, had a higher s-PSA, voided smaller volumes, and were more obstructed. We found no differences in TRUS-volume, Q-max, IPS score, or PVR. There was a strong association between OB and BOO, the percentage of OB increasing with increased obstruction. TRUS-volume, Q-max, IPS score, and PVR did not predict whether the patients had a combined BOO,+,OB or not. These findings indicate that BOO is a progressive disease, which in time causes pronounced obstruction and perhaps in itself contributes to the development of OB. Neurourol. Urodynam. 20:237,247, 2001. © 2001 Wiley-Liss, Inc. [source] | |||||||||||||