bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Static Pressure and Temperature in Building Acoustics
Authors: Wittstock Volker , Bethke Christian
Published: September 2003

The influence of static pressure and temperature on sound reduction indices, impact sound pressure levels, improvements of impact sound pressure levels and sound reduction indices, and relative installation noise levels is investigated. Theory revealed a systematic influence on sound reduction index and normalized impact sound pressure level. Firstly, the sound power radiated by a vibrating structure is directly proportional to the sound impedance in air and therefore to static pressure and temperature to the power of −0.5. Secondly, the sound pressure produced in a room by a sound source also depends on sound impedance, i.e. on static pressure and temperature. Since the excitation of a test specimen is not influenced by static pressure or temperature, the two effects are not compensated by any other mechanism, thus temperature and static pressure also influence sound reduction index and normalized impact sound pressure level. Experimental verification involved measurement of sound reduction index in a small test suite at static pressures between 307 and 970 hPa. Measurement results for single-shell structures showed the expected behaviour, whereas results for double-shell structures revealed a considerable scatter with a tendency towards even larger temperature and static pressure influences. For comparison of the acoustic properties of building elements, it is therefore advisable to introduce a normalized sound reduction index and a normalized impact sound pressure level, with both referred to reference conditions of static pressure and temperature. Improvements in impact sound pressure levels and sound reduction index, and relative installation noise levels are determined from changes in sound level differences. Since each difference is influenced in the same manner by meteorological conditions, the resulting improvement is independent of static pressure and temperature, as long as the differences were determined under the same meteorological conditions.
Venlafaxine Hydrochloride for the Treatment of Hot Flashes
Authors: Schober Christina E , Ansani Nicole T
Published: September 2003

OBJECTIVE:

To review the literature evaluating venlafaxine for the treatment of hot flashes.

DATA SOURCES:

Clinical literature accessed through MEDLINE (1966–August 2002), PubMed, Harrison's Online, and references of reviewed articles. Key terms used were venlafaxine, Effexor, hot flashes, and vasomotor symptoms.

DATA SYNTHESIS:

Not all patients experiencing hot flashes are candidates for traditional hormonal therapy. Nonhormonal alternatives have long been explored, but conflicting evidence of efficacy exists.

CONCLUSIONS:

Venlafaxine is an effective nonhormonal alternative for relief from uncontrolled hot flashes.
Safety and Efficacy of Influenza Vaccine in Children
Authors: Goldstein Leslie GB
Published: September 2003

OBJECTIVE:

To describe the safety and efficacy of influenza vaccines in asthmatic children.

DATA SOURCES:

Literature was identified by a MEDLINE search (2002–March 2003). Key search terms included asthma, exacerbation, children, vaccine, and influenza.

DATA SYNTHESIS:

Concerns that the influenza vaccine may exacerbate asthma attacks have kept many asthmatic children from receiving this immunization. Researchers have conducted studies to determine the burden of influenza on asthmatic children, the safety of influenza vaccines, and their benefit in the presence of glucocorticoid burst therapy in the same population.

CONCLUSIONS:

Influenza vaccines tested are safe and efficacious in asthmatic children.
C-Reactive Protein, Antiinflammatory Drugs, and Quality of Life in Diabetes
Authors: Cummings Doyle M , King Dana E , Mainous Arch G
Published: September 2003

BACKGROUND:

C-reactive protein (CRP) is an important biological marker of inflammation that has been linked to cardiovascular disease. The extent to which the inflammatory processes associated with elevated CRP concentrations impair physical functioning and quality of life, and whether this is modulated by hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) and aspirin, which have been shown to lower CRP concentrations, is unclear.

OBJECTIVE:

To determine whether an association exists between CRP concentrations and health-related quality of life among patients with diabetes, and to determine whether the association is affected by use of statins and nonsteroidal antiinflammatory drugs (NSAIDs).

METHODS:

A trained interviewer collected self-reported information regarding demographics, health-related quality of life (SF-12), and medication use, and a nurse collected a blood sample from 86 adult subjects with type 2 diabetes mellitus who were part of a larger population-based survey. The serum was analyzed for CRP using a highly sensitive assay.

RESULTS:

In simple bivariate analysis, there was a significant inverse relationship between CRP and the physical health component score of health-related quality of life (Spearman correlation coefficient [r] = −0.26; p = 0.025). For subjects on statins (r = −0.44; p = 0.02; n = 27), this relationship persisted, while for patients on NSAIDs or aspirin (r = −0.21; p = 0.17; n = 44), no relationship was observed. Similar findings were observed with self-rated health alone as an outcome variable. However, stepwise linear regression revealed no consistent relationship between CRP and health-related quality of life (i.e., standardized SF-12 physical component score) when demographic variables, disease duration, glucose control, serum creatinine, smoking, and medication use were controlled for.

CONCLUSIONS:

In multivariate regression modeling, the initial inverse relationship between CRP and health-related quality of life was lost, suggesting that other covariates are responsible for this association. While statins and NSAIDs may impact CRP or health-related quality of life independently, they do not appear to modulate a relationship between these factors.
Prolonged Thrombocytopenia Associated with Isotretinoin
Authors: Moeller Karen E , Touma Susan C
Published: September 2003

OBJECTIVE:

To report a case of severe prolonged thrombocytopenia possibly associated with isotretinoin.

CASE SUMMARY:

A 27-year-old white woman developed severe thrombocytopenia and elevated transaminases after 3½ months of treatment with isotretinoin. Prior to the onset of thrombocytopenia, the patient had also received a 10-day course of cephalexin. Rectal bleeding was reported by the patient, who was otherwise asymptomatic. Liver enzyme values returned to normal approximately 1 week after discontinuation of isotretinoin; however, platelet counts required approximately 2 months to normalize. Based on the Naranjo probability scale, possible causality exists between isotretinoin and thrombocytopenia.

DISCUSSION:

The exact mechanism by which isotretinoin caused thrombocytopenia in this patient is not clearly understood. To our knowledge, only 3 previous cases of isotretinoin-associated thrombocytopenia have been reported. The long recovery process that occurred in our patient is possibly a direct result of the long elimination half-life of both the parent compound and active metabolites of isotretinoin.

CONCLUSIONS:

Clinicians prescribing isotretinoin should be aware of the potential life-threatening consequence of thrombocytopenia, and a complete blood cell count with platelets should be part of the routine monthly monitoring in all patients receiving isotretinoin therapy.
Multivitamin Supplements May Affect Warfarin Anticoagulation in Susceptible Patients
Authors: Kurnik Daniel , Lubetsky Aharon , Loebstein Ronen , Almog Shlomo , Halkin Hillel
Published: September 2003

OBJECTIVE:

To report an interaction of a multivitamin preparation containing small amounts of vitamin K1 (25 μg) with warfarin in a case series and to assess the prevalence of vitamin K1 deficiency in ambulatory anticoagulated patients.

CASE SUMMARIES:

We describe 3 patients whose anticoagulation was stabilized with warfarin in whom initiation or cessation of a self-prescribed multivitamin supplement delivering 25 μg of vitamin K1 daily was associated with an otherwise unexplained significant fall or rise in international normalized ratio (INR), respectively, with major thrombosis or hemorrhage in 2. This interaction was rated probable on the Naranjo probability scale. Suspecting vitamin K1 deficiency as an explanation for this oversensitivity, we assessed the prevalence of vitamin K1 deficiency in our clinic by determining plasma vitamin K1 levels in 179 stable consecutive patients, finding very low levels (<0.1 ng/mL) in 22 of 179 (12%).

DISCUSSION:

Vitamin K1 supplements of 25 μg daily are far below the dose thought to affect anticoagulant control. We hypothesize that, in our patients, unsuspected vitamin K1 deficiency caused an oversensitivity to small vitamin K1 supplements. In patients with low vitamin K1 status, even such low doses represent a significant increment in daily intake, thus lowering the sensitivity to warfarin. Our analysis suggests that low vitamin K1 status exists in a small, but important, minority of ambulatory patients undergoing anticoagulation.

CONCLUSIONS:

Clinicians should instruct anticoagulated patients to report the use of multivitamin supplements and inquire about it in cases of unexplained INR changes.
Adult education and humanity's relationship with nature reflected in language, metaphor, and spirituality: A call to action
Authors: Hill Lilian H. , Johnston Julie D.
Published: September 2003

Language, metaphor, and spirituality express people's beliefs about their relationships with the natural
world. For the earth and its beings to survive, extensive changes in our relationships and cultural assumptions in
the natural world are called for, and these will necessarily change the literature and practice of adult
education.
Environmental justice: Environmental adult education at the confluence of oppressions
Authors: Hill Robert J.
Published: September 2003

Environmental adult education contributes to environmental justice learning by mobilizing citizen
participation, popular activism, and direct action which are essential for democracy and for healthy people and
ecosystems.
Environmental popular education and indigenous social movements in India
Authors: Kapoor Dip
Published: September 2003

Practical and theoretical considerations of activist‐educators using environmental popular education in
indigenous social movements in India are explored. The responses of these social movements to destructive
development are linked with the theoretical dialogue on environmental adult education and social transformation.
A pragmatic approach towards assessment of control loop performance
Authors: Huang B.
Published: September 2003

In this paper, a pragmatic approach to process modelling and control loop performance assessment is proposed. We consider the following practical scenarios: the control loop of concern is operated by a simple controller such as PI/PID controller; a simple open‐loop/closed‐loop step response data is available or an open‐loop/closed‐loop step test can be readily performed; the control loop may be subject to significant disturbances and/or measurement noises. Our objectives are: (1) to estimate a continuous‐time process model from the step response data; (2) to assess control loop performance with a pragmatic benchmark in terms of both output performance and input variation, and identify practically attainable control loop performance. We will summarize the theory and algorithms developed for such a relatively comprehensive analysis. A number of simulation studies are presented to demonstrate the feasibility of the proposed methodology. Copyright © 2003 John Wiley & Sons, Ltd.
Mutations in CYP11B1 gene: Phenotype–genotype correlations
Authors: Zhu Yuan‐Shan , Cordero Juan J. , Can Selcuk , Cai Li‐Qun , You Xueke , Herrera Cecilia , DeFillo‐Ricart Mariano , Shackleton Cedric , Imperato‐McGinley Julianne
Published: September 2003

11β‐hydroxylase deficiency, an autosomal recessive disorder, is the second most common cause of congenital adrenal hyperplasia. We studied four subjects with classic 11β‐hydroxylase deficiency and severe hypertension: a 46,XX affected subject from a Turkish family with severe ambiguity of the external genitalia and hypertension, and three affected 46,XY subjects from a Dominican kindred with isosexual precocious puberty and severe hypertension. The affected subjects had significantly elevated plasma 11‐desoxycortisol, 11‐desoxycorticosterone, Δ4‐androstenedione, and testosterone. To determine the molecular genetic defects, genomic DNA was isolated from the leukocytes of affected subjects and their family members. The encoding region of the 11β‐hydroxylase gene (CYP11B1) was amplified by PCR with specific primers. Using single‐stranded DNA conformational polymorphism (SSCP) and DNA sequencing, a nonsense mutation in exon 6 of CYP11B1 in the affected 46,XX subject from the Turkish family was identified, where a cytosine was substituted by a thymidine, resulting in the replacement of glutamine (CAG) by a stop codon (TAG) at amino acid position 338 (Q338X). In the three 46,XY Dominican boys, the mutation was also a nonsense mutation in exon 6 of CYP11B1, where a cytosine was substituted by a thymidine, resulting in the replacement of glutamine (CAG) by a stop codon (TAG) at amino acid position 356 (Q356X). Both mutations result in the biosynthesis of a truncated 11β‐hydroxylase protein with loss of enzymatic activity. Heterozygosity was determined in family members of both probands including parents and siblings. These results indicate that mutations of CYP11B1 in these subjects are responsible for their clinical syndromes. © 2003 Wiley‐Liss, Inc.
Pulmonary atresia/ventricular septal defect associated with facial port‐wine stain and retinal vascular abnormality: A new constellation?
Authors: Tan Hüseyin , Cevi̇z Naci , Baykal Orhan , Büyükavcı Mustafa , Bilici Necmettin
Published: September 2003

A case with pulmonary atresia/ventricular septal defect associated with port‐wine stain and retinal vascular abnormality is reported. Clinical findings were similar to both PHACE syndrome and Sturge–Weber syndrome (SWS). But, the most frequent and well‐known features of both syndromes were absent. So, it could not be concluded whether this is a new constellation or an incomplete form of one of the two syndromes. In both situations, presence of a complex congenital heart disease that has not been reported previously makes this case original. © 2003 Wiley‐Liss, Inc.
Personality and stereotype in osteogenesis imperfecta: Behavioral phenotype or response to life's hard challenges?
Authors: Ablon Joan
Published: September 2003

Fifty‐five adults with osteogenesis imperfecta [OI] types III and IV were interviewed to chronicle their medical, personal, and social experiences in living with OI. Subjects were recruited through the Osteogenesis Imperfecta Foundation, through physician referrals, and through other persons with OI. One purpose of the research was to examine the stereotypes of high intelligence and euphoric personality often attributed to persons with OI, and to explore whether these characteristics might constitute a behavioral phenotype. Participants were observed by the researcher to be characteristically bright, talkative, articulate, “up” emotionally, and accomplished. In fact, most of the persons illustrated well the characteristics of the stereotype. Participants suggested and described life experiences and difficult medical and social challenges which they felt could contribute to the development of the attributed characteristics. The history of the “euphoric” attribution is traced. Many participants expressed derision concerning this attribution. The commonly understood meaning of this term trivializes the years of painful medical procedures, suffering, and related hardships experienced by subjects in their lives. I suggest that the concept of “resilience” offers a more appropriate context for related future research with this population. The consideration of the exceptional challenges faced by persons with OI and others with such demanding medical conditions throughout their life cycles would add a significant environmental dimension to the study of behavioral phenotypes. © 2003 Wiley‐Liss, Inc.
Spondyloepimetaphyseal dysplasia with multiple dislocations, leptodactylic type: Report of a new patient and review of the literature
Authors: Mégarbané A. , Ghanem I. , Le Merrer M.
Published: September 2003

A 6‐year‐old boy with congenital hip dislocation, developmental delay, short stature, macrocephaly, low set ears, short neck, and hyperlaxity of the wrists and fingers is described. Radiographs disclosed mainly the presence of thoracic scoliosis, narrow interpedicular distances, metaphyseal vertical striations, very small irregular epiphyses, right hip dislocation, luxation of both elbows, and severe delay of ossification of the epiphyses and the carpal bones. These features are very close to the newly described entity: spondyloepimetaphyseal dysplasia and multiple dislocations. This patient brings to light the differential diagnosis and confirms the specificity of the radiological findings of this new entity. © 2003 Wiley‐Liss, Inc.
Juberg–Hayward syndrome: Report of a new patient with severe phenotype and novel clinical features
Authors: Hedera Peter , Innis Jeffrey W.
Published: September 2003

We report a patient with severe mental retardation (MR), microcephaly, Dandy–Walker malformation, bilateral lip/palate clefts, hypertrophied sublingual frenulum, lobular tongue, absent thumbs, and other skeletal abnormalities, including Y‐shaped metacarpals and urogenital abnormalities. High‐resolution karyotype and subtelomeric fluorescence in situ hybridization were normal. We propose that his clinical picture is most consistent with Juberg–Hayward or orocraniodigital syndrome. Several clinical features present in our patient (unilateral distal displacement of elbow position, second‐site radioulnar synostosis, bilateral Y‐shaped metacarpal, lobular tongue, hypertrophic frenuli, Dandy–Walker malformation) have not previously been reported in this condition, thus expanding the phenotypic spectrum of this rare condition. The presence of these novel findings suggests possible overlap with other syndromes, such as orofaciodigital and Malpuech syndromes. © 2003 Wiley‐Liss, Inc.
Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene: Double‐layer patella as a reliable sign
Authors: Mäkitie Outi , Savarirayan Ravi , Bonafé Luisa , Robertson Stephen , Susic Miki , Superti‐Furga Andrea , Cole William G.
Published: September 2003

Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene result in a family of skeletal dysplasias, which comprise lethal (achondrogenesis type 1B and atelosteogenesis type 2) and non‐lethal conditions (diastrophic dysplasia and recessive multiple epiphyseal dysplasia (rMED)). The most frequent mutation is R279W, which in a homozygous state results in rMED with bilateral clubfoot, MED, and “double layered” patella. We describe three patients with rMED caused by a previously unreported homozygous mutation in the DTDST gene. The three patients (from two families) were born to healthy, non‐consanguineous parents. All developed signs of hip dysplasia in early childhood and two had episodes of recurrent patella dislocation. Two underwent bilateral total hip replacements at ages 13 and 14 years. The feet, external ears, and palate were normal. Stature was normal in all cases. Radiographs showed dysplastic femoral heads, mild generalized epiphyseal dysplasia, abnormal patella ossification, and normal hands and feet. Direct sequence analysis of genomic DNA demonstrated a homozygous 1984T > A (C653S) change in the DTDST gene in all patients. The clinically normal parents were heterozygous for the change. This is the first description of a homozygous C653S mutation of the DTDST gene. Hip dysplasia and patella hypermobility dominates the otherwise mild phenotype. These patients further expand the range of causative mutations in the DTD skeletal dysplasia family. © 2003 Wiley‐Liss, Inc.
Rett syndrome in a 47,XXX patient with a de novo MECP2 mutation
Authors: Hammer Sara , Dorrani Naghmeh , Hartiala Jaana , Stein Stuart , Schanen N. Carolyn
Published: September 2003

Rett syndrome is caused by mutation in MECP2, a gene located on Xq28 and subject to X‐inactivation. MECP2 encodes methyl CpG‐binding protein 2, a widely expressed transcriptional repressor of methylated DNA. Mutations in MECP2 are primarily de novo events in the male germ line and thus lead to an excess of affected females. Here we report the identification of a unique 47,XXX girl with relatively mild atypical Rett syndrome leading initially to a diagnosis of infantile autism with regression. Mutation analysis of the MECP2 gene identified a de novo MECP2 mutation, L100V. Examination of a panel of X‐linked microsatellite markers indicated that her supernumerary X chromosome is maternally derived. X‐inactivation patterns were determined by analysis of methylation of the androgen receptor locus, and indicated preferential inactivation of her paternal allele. The parental origin of her MECP2 mutation could not be determined because she was uninformative for intronic polymorphisms flanking her mutation. This is the first reported case of sex chromosome trisomy and MECP2 mutation in a female, and it illustrates the importance of allele dosage on the severity of Rett syndrome phenotype. © 2003 Wiley‐Liss, Inc.
Rett syndrome in adolescent and adult females: Clinical and molecular genetic findings
Authors: Smeets E. , Schollen E. , Moog U. , Matthijs G. , Herbergs J. , Smeets H. , Curfs L. , Schrander‐Stumpel C. , Fryns J.P.
Published: September 2003

Rett syndrome (RTT) is a neurodevelopmental disorder which is diagnosed clinically. We report on 30 adolescent and adult females with classical or atypical RTT of whom 24 have a MECP2 mutation. In these 24 females, the clinical manifestations, degree of severity, and disorder profiles are discussed as well as the genotype phenotype correlation. After X‐chromosome inactivation (XCI) study in these cases, we found no correlation between skewing and milder phenotype. Three large deletions were found after additional Southern blot analysis in three classical RTT cases. We confirm that early truncating mutations in MECP2 are responsible for a more severe course of the disorder. Three disorder profiles related to the missense mutations R133C and R306C, and to deletions in the C terminal segment are described and are of interest for further clinical study on larger numbers of cases. The R133C genotype has a predominantly autistic presentation while the R306C genotype is associated with a slower disease progression. The phenotype of the “hotspot” deletions in the C terminal segment is predominantly characterized by rapid progressive neurogenic scoliosis. Older women with RTT are underdiagnosed: seven adults were first diagnosed as having RTT between 29 and 60 years of age, and confirmed on finding a MECP2 mutation. Knowledge of the clinical phenotype of RTT at an adult age is important for all involved in the care of these individuals. The involvement of the parent support group is very important in this matter. © 2003 Wiley‐Liss, Inc.
Association of the serotonin transporter gene with sudden infant death syndrome: A haplotype analysis
Authors: Weese‐Mayer Debra E. , Zhou Lili , Berry‐Kravis Elizabeth M. , Maher Brion S. , Silvestri Jean M. , Marazita Mary L.
Published: September 2003

Serotonergic receptor binding in the arcuate nucleus, n. raphé obscurus, and other medullary regions is decreased in sudden infant death syndrome (SIDS) cases. Further, an insertion/deletion polymorphism in the promoter region of the serotonin transporter protein (5‐HTT) gene has recently been associated with risk of SIDS. This polymorphism differentially regulates 5‐HTT expression, with the long allele (L), the SIDS‐associated allele, being a more effective promoter than the short allele (S). To further elucidate the role of the 5‐HTT gene in SIDS, we investigated the 5‐HTT intron 2 polymorphism, which also differentially regulates 5‐HTT expression with the 12 repeat allele being the more effective promoter. In a cohort of 90 SIDS cases (44 African‐American and 46 Caucasian) and gender/ethnicity‐matched controls, significant positive associations were found between SIDS and the intron 2 genotype distribution (P‐value = 0.041) among African‐American SIDS vs. African‐American controls, specifically with the 12/12 genotype (P‐value = 0.03), and with the 12 repeat allele (P‐value=0.018). The frequency of the 12/12 genotype and 12‐repeat allele was significantly different (P < 0.001) between the African‐American and Caucasian SIDS cases. Furthermore, the promoter and intron 2 loci were in significant linkage disequilibrium, and the L‐12 haplotype was significantly associated with SIDS in the African‐American (P = 0.002) but not Caucasian (P = 0.117) subgroups. These results indicate a relationship between SIDS and the 12‐repeat allele of the intron 2 variable number tandem repeat of the 5‐HTT gene in African‐Americans, and a significant role of the haplotype containing the 12‐repeat allele and the promoter L‐allele in defining SIDS risk in African‐Americans. These data, if confirmed in larger studies, may begin to explain the differences in SIDS incidence by ethnicity, suggest a role for levels of 5‐HTT expression in generation of SIDS susceptibility, and provide an important tool for identifying at‐risk individuals and estimating the risk of recurrence. © 2003 Wiley‐Liss, Inc.
Collection and analysis of hematopoietic progenitor cells from cynomolgus macaques (Macaca fascicularis): Assessment of cross‐reacting monoclonal antibodies
Authors: Shibata Hiroaki , Hanazono Yutaka , Ageyama Naohide , Nagashima Takeyuki , Ueda Yasuji , Hasegawa Mamoru , Ozawa Keiya , Yoshikawa Yasuhiro , Terao Keiji
Published: September 2003

Previous studies have shown that hematopoietic progenitor cells can be isolated from human or nonhuman primate bone marrow (BM) cells. In the present study, we studied the cross‐reactivity of 13 anti‐human CD34, two anti‐human c‐Kit, and one anti‐human CD133 monoclonal antibodies (mAbs) with cynomolgus macaque (Macaca fascicularis) BM cells, using flow cytometric analysis, cell enrichment, and clonogenic assay. Among the 13 anti‐human CD34 mAbs assessed, six cross‐reacted as previously reported by other groups. However, only three of these six mAbs (clones 561, 563, and 12.8) recognized cynomolgus CD34+ cells that formed progenitor colonies when grown in methylcellulose culture. Similarly, of the two anti‐human c‐Kit mAbs (clones NU‐c‐kit and 95C3) that were previously reported to cross‐react with cynomolgus BM cells, only one (clone NU‐c‐kit) resulted in a similar outcome. The anti‐human CD133 mAb (clone AC133) also cross‐reacted with cynomolgus BM cells, although these cells did not give rise to colonies when grown in culture. These results suggest that antibodies that cross‐react with nonhuman primate cells may not identify the hematopoietic cells of interest. In addition, while the CD34 mAb (clone 561) results in the selection of hematopoietic progenitor cells of all lineages when assessed in methylcellulose culture, the c‐Kithigh fraction (NU‐c‐kit) exclusively identifies erythroid‐specific progenitor cells after growth in culture. It is important to consider these findings when selecting cross‐reacting mAbs to identify cells of hematopoietic lineages in macaque species. Am. J. Primatol. 61:3–12, 2003. © 2003 Wiley‐Liss, Inc.
Hematology of a natural population of toque macaques (Macaca sinica) at polonnaruwa, Sri Lanka
Authors: Ekanayake Dilrukshi K. , Horadagoda Neil U. , Sanjeevani G.K. Madura , Arulkanthan Appudurai , Gunatilake K.A. Sunil , Dittus Wolfgang P.J.
Published: September 2003

Hematological studies were conducted in three wild groups of toque macaques (Macaca sinica) inhabiting the Polonnaruwa Sanctuary in northeastern Sri Lanka. The macaques were temporarily trapped and anesthetized, and femoral blood was drawn from 35 males and 37 females (age range: 0.33–24.5 yr). Statistically significant (P<0.05) differences were observed by sex for total plasma proteins (PP), and by age for red blood cell (RBC) counts, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular Hb (MCH), mean corpuscular Hb concentration (MCHC), PP, erythrocyte sedimentation rate (ESR), differential and absolute neutrophil counts, differential lymphocyte counts, and absolute eosinophil counts. In general, the results were similar to those reported for other species of colony‐bred and free‐ranging macaques. However, there also were differences. First, in contrast to earlier studies of nonhuman primates, we examined the hematology of infants. Compared to other age classes, infants (<1 yr old) had lower RBC, Hb, MCHC, and ESR values, and a higher MCV. These findings were similar to those obtained in human infants. Second, we observed variations in hematology among social groups in relation to their ecology. Two groups (IH3 and M3) had ready access to water throughout the dry season (the period of sampling), whereas the third group (J) did not. The Hb, RBC, and PP values obtained in groups IH3 and M3 were similar to those reported in other macaque species. However, these parameters in group J were significantly (P<0.01) higher, which suggests that this group (representing about 26% of the sample) had been dehydrated during the dry season. Finally, two indices indicative of injury and infection–the ESR and leukocyte counts–were higher in the wild toque macaques than has been reported for other species of macaques held in captivity, and about 15% of the toque macaques sampled had extreme outlier values for these parameters; however, none were visibly ill or died. These results suggest that wild toque macaques are subject to a wide array of physical and biological insults that are unique to natural populations. Am. J. Primatol. 61:13–28, 2003. © 2003 Wiley‐Liss, Inc.
Crocodylian forelimb musculature and its relevance to Archosauria
Authors: Meers Mason B.
Published: September 2003

The musculoskeletal anatomy of the crocodylian forelimb is documented to facilitate functional morphological studies of extant and extinct archosaurs. Comparative descriptions of muscles of the forelimb of several crocodylian species are presented, including attachment sites, innervation, and anatomical functions. The muscular anatomy of the crocodylian forelimb is highly conservative among the different species; however, interspecific differences do occur. Interspecific anatomical variation is interpreted functionally, and discussed in the context of the terrestrial locomotion of crocodylians as it applies to the forelimb. In addition, muscular apomorphies are identified among a phylogenetically diverse sample of extant crocodylians, providing insight into the evolution of forelimb anatomy in a clade of archosaurs possessing highly variable terrestrial locomotor behaviors. Anat Rec Part A 274A:891–916, 2003. © 2003 Wiley‐Liss, Inc.
Presystemic metabolism and intestinal absorption of antipsoriatic fumaric acid esters
Authors: Werdenberg D. , Joshi R. , Wolffram S. , Merkle H.P. , Langguth P.
Published: September 2003

Psoriasis is a chronic inflammatory skin disease. Its treatment is based on the inhibition of proliferation of epidermal cells and interference in the inflammatory process. A new systemic antipsoriasis drug, which consists of dimethylfumarate and ethylhydrogenfumarate in the form of their calcium, magnesium and zinc salts has been introduced in Europe with successful results. In the present study, a homologous series of mono‐ and diesters of fumaric acid has been studied with respect to the sites and kinetics of presystemic ester degradation using pancreas extract, intestinal perfusate, intestinal homogenate and liver S9 fraction. In addition, intestinal permeability has been determined using isolated intestinal mucosa as well as Caco‐2 cell monolayers, in order to obtain estimates of the fraction of the dose absorbed for these compounds. Relationships between the physicochemical properties of the fumaric acid esters and their biological responses were investigated. The uncharged diester dimethylfumarate displayed a high presystemic metabolic lability in all metabolism models. It also showed the highest permeability in the Caco‐2 cell model. However, in permeation experiments with intestinal mucosa in Ussing‐type chambers, no undegraded DMF was found on the receiver side, indicating complete metabolism in the intestinal tissue. The intestinal permeability of the monoesters methyl hydrogen fumarate, ethyl hydrogen fumarate, n‐propylhydrogen fumarate and n‐pentyl hydrogen fumarate increased with an increase in their lipophilicity, however, their presystemic metabolism rates likewise increased with increasing ester chain length. It is concluded that for fumarates, an increase in intestinal permeability of the more lipophilic derivatives is counterbalanced by an increase in first‐pass extraction. Copyright © 2003 John Wiley & Sons, Ltd.
Effect of wood ash treatment on improving the fermentability of wood hydrolysate
Authors: Miyafuji Hisashi , Danner Herbert , Neureiter Markus , Thomasser Christiane , Braun Rudolf
Published: September 2003

Softwood hydrolysates were overlimed with wood ash to improve the fermentability of hydrolysates. It could be demonstrated in fermentation tests that wood ash treatment increases fermentability compared to the hydrolysates untreated and treated with alkaline compounds such as Ca(OH)2, NaOH, and KOH, which are commonly used for overliming. The enhanced fermentability of the hydrolysate treated with wood ash is due to the reduction of the inhibitors of the fermentation such as furan and phenolic compounds and to nutrient effects of some inorganic components from the wood ash on the fermentation. © 2003 Wiley Periodicals. Biotechnol Bioeng 84: 390–393, 2003.
An integrated approach to optimization of Escherichia coli fermentations using historical data
Authors: Coleman Matthew C. , Buck Kristan K. S. , Block David E.
Published: September 2003

Using a fermentation database for Escherichia coli producing green fluorescent protein (GFP), we have implemented a novel three‐step optimization method to identify the process input variables most important in modeling the fermentation, as well as the values of those critical input variables that result in an increase in the desired output. In the first step of this algorithm, we use either decision‐tree analysis (DTA) or information theoretic subset selection (ITSS) as a database mining technique to identify which process input variables best classify each of the process outputs (maximum cell concentration, maximum product concentration, and productivity) monitored in the experimental fermentations. The second step of the optimization method is to train an artificial neural network (ANN) model of the process input–output data, using the critical inputs identified in the first step. Finally, a hybrid genetic algorithm (hybrid GA), which includes both gradient and stochastic search methods, is used to identify the maximum output modeled by the ANN and the values of the input conditions that result in that maximum. The results of the database mining techniques are compared, both in terms of the inputs selected and the subsequent ANN performance. For the E. coli process used in this study, we identified 6 inputs from the original 13 that resulted in an ANN that best modeled the GFP fluorescence outputs of an independent test set. Values of the six inputs that resulted in a modeled maximum fluorescence were identified by applying a hybrid GA to the ANN model developed. When these conditions were tested in laboratory fermentors, an actual maximum fluorescence of 2.16E6 AU was obtained. The previous high value of fluorescence that was observed was 1.51E6 AU. Thus, this input condition set that was suggested by implementing the proposed optimization scheme on the available historical database increased the maximum fluorescence by 55%. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 274–285, 2003.
A study of oxygen transfer in shake flasks using a non‐invasive oxygen sensor
Authors: Gupta Atul , Rao Govind
Published: September 2003

We describe a study of oxygen transfer in shake flasks using a non‐invasive optical sensor. This study investigates the effect of different plugs, presence of baffles, and the type of media on the dissolved oxygen profiles during Escherichia coli fermentation. We measured the volumetric mass transfer coefficient (kLa) under various conditions and also the resistances of the various plugs. Finally, we compared shake flask kLa with that from a stirred tank fermentor. By matching kLa's we were able to obtain similar growth and recombinant protein product formation kinetics in both a fermentor and a shake flask. These results provide a quantitative comparison of fermentations in a shake flask vs. a bench‐scale fermentor and should be valuable in guiding scale‐up efforts. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 351–358, 2003.
Titrostat: A reliable technique for continuous cultivation of microorganisms utilizing liquid or gaseous water insoluble substrates
Authors: Mutafov S. , Angelova B. , Schmauder H.‐P. , Avramova T. , Boyadjieva L.
Published: September 2003

We describe a method for continuous cultivation of microorganisms utilizing liquid or gaseous water insoluble substrates as a single source of carbon and energy. The water insoluble substrate, which is also the growth‐limiting factor, enters the cultivation space as a manually adjustable single‐compound material flow. All nonlimiting nutrients (with the exception of oxygen) enter the cultivation space as ingredients of titrant solution which feed rate is reliably coupled to the rate of substrate addition by means of the system titrator.

The method provides mild starting conditions appropriate for primary isolation of microorganisms utilizing substrates with growth‐inhibiting properties such as BTEX (benzene, toluene, ethylbenzene, and xylene). The sound control over the microbial specific growth rate makes it suitable for precise kinetic studies as well.

We provide a detailed description of both the principles of the method and the equipment used. The dependence of the systems operative range on the concentration of titrant solution is illustrated in the case of continuous cultivation of a mixed bacterial culture on toluene. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 160–169, 2003.
Fabrication of nickel and chromium nanoparticles using the protein cage of apoferritin
Authors: Okuda Mitsuhiro , Iwahori Kenji , Yamashita Ichiro , Yoshimura Hideyuki
Published: September 2003

The iron storage protein, apoferritin, has a cavity in which iron is oxidized and stored as a hydrated oxide core. The size of the core is about 7 nm in diameter and is regulated by the cavity size. The cavity can be utilized as a nanoreactor to grow inorganic crystals. We incubated apoferritin in nickel or chromium salt solutions to fabricate hydroxide nanoparticles in the cavity. By using a solution containing dissolved carbon dioxide and by precisely controlling the pH, we succeeded in fabricating nickel and chromium cores. During the hydroxylation process of nickel ions a large portion of the apoferritin precipitated through bulk precipitation of nickel hydroxide. Bulk precipitation was suppressed by adding ammonium ions. However, even in the presence of ammonium ions the core did not form using a degassed solution. We concluded that carbonate ions were indispensable for core formation and that the ammonium ions prevented precipitation in the bulk solution. The optimized condition for nickel core formation was 0.3 mg/mL horse spleen apoferritin and 5 mM ammonium nickel sulfate in water containing dissolved carbon dioxide. The pH was maintained at 8.65 using two buffer solutions: 150 mM HEPES (pH 7.5) and 195 mM CAPSO (pH 9.5) with 20 mM ammonium at 23°C. The pH had not changed after 48 h. After 24 h of incubation, all apoferritins remained in the supernatant and all of them had cores. Recombinant L‐ferritin showed less precipitation even above a pH of 8.65. A chromium core was formed under the following conditions: 0.1 mg/mL apoferritin, 1 mM ammonium chromium sulfate, 100 mM HEPES (pH 7.5) with a solution containing dissolved carbon dioxide. About 80% of the supernatant apoferritin (0.07 mg/mL) formed a core. In nickel and chromium core formation, carbonate ions would play an important role in accelerating the hydroxylation in the apoferritin cavity compared to the bulk solution outside. © 2003 Wiley Periodicals. Biotechnol Bioeng 84: 187–194, 2003.
Physicochemical and blood compatibility characterization of polypyrrole surface functionalized with heparin
Authors: Li Yali , Neoh Koon Gee , Cen Lian , Kang En‐Tong
Published: September 2003

A surface modification technique was developed for the covalent immobilization of heparin onto electrically conductive polypyrrole (PPY) film. The PPY film was first graft copolymerized with poly(ethylene glycol) methacrylate (PEGMA) and then activated with cyanuric chloride (CC). Heparin was then immobilized onto the film through the reaction between the chloride groups of CC and the amine and/or hydroxyl groups of heparin. X‐ray photoelectron spectroscopy (XPS) was used to characterize the surface‐modified film after each stage. The biocompatibility of the surface‐modified PPY was evaluated using plasma recalcification time (PRT) and platelet adhesion. After surface modification, the film had improved wettability while retaining significant electrical conductivity. With immobilized heparin, platelet adhesion and platelet activation on PPY film was significantly suppressed, and the PRT was significantly prolonged. Electrical stimulation also plays a positive role in decreasing platelet adhesion and increasing PRT on pristine and surface‐modified PPY films. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 305–313, 2003.
Complex catalytic colloids on the basis of firefly luciferase as optical nanosensor platform
Authors: Pastorino Laura , Disawal Sandeep , Nicolini Claudio , Lvov Yuri M. , Erokhin Victor V.
Published: September 2003

In the present work the layer‐by‐layer nano‐assembly technique was used for the development of complex catalytic microparticles on the basis of firefly luciferase (FL). FL films containing 1, 2, or 3 monolayers were assembled on silver electrode QCM‐resonators and on 520‐nm diameter sulfonated polystyrene latex by alternate adsorption of FL and polycations using electrostatic interactions for the interlayer interaction. The assembly process was studied with quartz crystal microbalance, UV‐vis spectroscopy, and microelectrophoresis (surface potential). Structural studies of the resulting multilayers confirmed stepwise deposition of FL and cationic poly(dimethyldiallyl ammonium chloride) with a bilayer thickness of 14 nm; a systematic shift of the surface potential from +28 mV for poly(dimethyldiallyl ammonium chloride) to –14 mV for luciferase outermost layer was established. The functionality and stability of the biocolloids were demonstrated by monitoring the intensity of the light emission. Factors influencing the light emitted upon catalytic activity of FL such as the number of luciferase layers in the film and polyion layer at the outermost layer were studied. © 2003 Wiley Periodicals. Biotechnol Bioeng 84: 286–291, 2003.
High cell density induces spontaneous bifurcations of dissolved oxygen controllers during CHO cell fermentations
Authors: Chung John D. , Chang Conway C. , Groves James Ashley
Published: September 2003

High cell density cultures of CHO cells growing in a bioreactor under dissolved oxygen control were found to undergo spontaneous bifurcations and a subsequent loss of stability some time into the fermentation. This loss of stability was manifested by sustained and amplified oscillations in the bioreactor dissolved oxygen concentration and in the oxygen gas flow rate to the reactor. To identify potential biological and operational causes for the phenomenon, linear stability analysis was applied in a neighborhood of the experimentally observed bifurcation point. The analysis revealed that two steady state process gains, KP1 and KP2, regulated kla and gas phase oxygen concentration inputs, respectively, and the magnitude of KP1 was found to determine system stability about the bifurcation point. The magnitude of KP1, and hence the corresponding open‐loop steady state gain KOL1, scaled linearly with the bioreactor cell density, increasing with increasing cell density. These results allowed the generation of a fermentation stability diagram, which partitioned KC‐N operating space into stable and unstable regions separated by the loci of predicted critically stable controller constants, KC,critical, as a function of bioreactor cell density. This consistency of this operating diagram with experimentally observed changes in system stability was demonstrated. We conclude that time‐dependent increases in cell density are the cause of the observed instabilities and that cell density is the critical bifurcation parameter. The results of this study should be readily applicable to the design of a more robust controller. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 224–232, 2003.
Metabolic model for acetate uptake by a mixed culture of phosphate‐ and glycogen‐accumulating organisms under anaerobic conditions
Authors: Yagci Nevin , Artan Nazik , Çokgör Emine Ubay , Randall Clifford W. , Orhon Derin
Published: September 2003

This paper proposes a new metabolic model for acetate uptake by a mixed culture of phosphate‐ and glycogen‐accumulating organisms (PAOs and GAOs) under anaerobic conditions. The model uses variable overall stoichiometry based on the assumption that PAOs may have the ability of using the glyoxylate pathway to produce the required reducing power for polyhydroxyalkonate (PHA) synthesis. The proposed model was tested and verified by experimental results. A sequencing batch reactor system was operated for enhanced biological phosphorus removal (EBPR) with acetate as the sole carbon source at different influent acetate/phosphate ratios. The resulting experimental data supported the validity of the proposed model, indicating the presence of GAOs for all tested HAc/P ratios, especially under P‐limiting conditions. Strong agreement is observed between experimental values and model predictions for all model components, namely, PHB production, PHA composition, glycogen utilization, and P release. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 359–373, 2003.
Image analysis of light distribution in a photobioreactor
Authors: Jung Sang‐Kyu , Lee Sun Bok
Published: September 2003

Light intensity is a crucial factor that determines the growth of photosynthetic cells. This study analyzed the light distribution in a photobioreactor by processing images, captured with a digital camera, of a rectangular photobioreactor containing Synechococcus sp. PCC6801 as a model microorganism. The gray‐scale images obtained clearly demonstrate the variation of the light‐distribution profiles upon changing cell concentrations and external light intensity. Image‐processing techniques were also used to predict the cell density in the photobioreactor. By analyzing the digitized image data with a neural network model, we were able to predict the cell concentrations in the photobioreactor with a <5% error. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 394–397, 2003.