Insights on life cycle and cell identity regulatory circuits for unlocking genetic improvement in Zygosaccharomyces and Kluyveromyces yeasts.

Evolution has provided a vast diversity of yeasts that play fundamental roles in nature and society. This diversity is not limited to genotypically homogeneous species with natural interspecies hybrids and allodiploids that blur species boundaries frequently isolated. Thus, life cycle and the nature of breeding systems have profound effects on genome variation, shaping heterozygosity, genotype diversity and ploidy level.

The restriction modification system of Bacillus licheniformis MS1 and generation of a readily transformable deletion mutant.

Restriction modification systems (R-M systems), consisting of a restriction endonuclease and a cognate methyltransferase, constitute an effective means of a cell to protect itself from foreign DNA. Identification, characterization, and deletion of the restriction modification system BliMSI, a putative isoschizomer of ClaI from Caryophanon latum, were performed in the wild isolate Bacillus licheniformis MS1. BliMSI was produced as recombinant protein in Escherichia coli, purified, and in vitro analysis demonstrated identical restriction endonuclease activity as for ClaI.

Double-blind study of the actively transported levodopa prodrug XP21279 in Parkinson's disease.

The objective of this study was to assess the efficacy, safety, and pharmacokinetics of XP21279-carbidopa in patients with Parkinson's disease who experience motor fluctuations compared with immediate-release carbidopa-levodopa tablets. XP21279 is a levodopa prodrug that is actively absorbed by high-capacity nutrient transporters expressed throughout the gastrointestinal tract and then rapidly converted to levodopa by carboxylesterases. XP21279-carbidopa sustained-release bilayer tablets were developed to overcome pharmacokinetic limitations of levodopa by providing more continuous exposure.

Randomised clinical trial: arbaclofen placarbil in gastro-oesophageal reflux disease--insights into study design for transient lower sphincter relaxation inhibitors.

Background: Arbaclofen placarbil is a pro-drug of the gamma-aminobutyric acid-B agonist R-baclofen that has been shown to reduce reflux episodes in patients with gastro-oesophageal reflux disease (GERD).

Aim: To evaluate the efficacy and safety of arbaclofen placarbil vs. placebo as adjunctive therapy in subjects with troublesome GERD symptoms despite therapy with once-daily doses of a proton pump inhibitor (PPI) and to identify the characteristics of patients who were responders.

Actively transported levodopa prodrug XP21279: a study in patients with Parkinson disease who experience motor fluctuations.

Objective: The objectives of this study were to assess the pharmacokinetic profile, efficacy, and safety of XP21279 administered with carbidopa (CD) in subjects with Parkinson disease (PD) experiencing motor fluctuations and explore dose correspondence between CD-levodopa (LD) and XP21279 administered with CD.

Methods: Subjects received CD-LD 3 or 4 times daily for 2 weeks, followed by XP21279 plus CD 3 times daily for 2 weeks at fixed dosing times, allowing dose adjustment to optimize clinical response, in this multiple-dose, multicenter, open-label, 2-period, sequential-treatment study. Pharmacokinetic parameters, including LD exposure, were assessed over 16 hours on the last day of each treatment period.

Efficacy and safety study of arbaclofen placarbil in patients with spasticity due to spinal cord injury.

Study Design: Randomized, double-blind, placebo-controlled, two-period crossover.

Objectives: To evaluate the efficacy and safety of arbaclofen placarbil (AP) in patients with spasticity secondary to spinal cord injury (SCI).

Setting: United States and Canada.

Arbaclofen placarbil in GERD: a randomized, double-blind, placebo-controlled study.

Objectives: It has been shown that arbaclofen placarbil (AP) inhibits reflux in gastroesophageal reflux disease (GERD) following single oral dosing. This study evaluated the efficacy and safety of AP over 4 weeks in subjects with symptomatic GERD.

Methods: One hundred fifty-six subjects with heartburn and/or regurgitation ≥3 days/week and either no history of taking proton pump inhibitors (PPIs naive, n=58) or at least partial symptom response to PPI therapy (PPI responsive, n=98) were enrolled in this randomized, double-blind, placebo-controlled trial.

The effect of food with varying fat content on the clinical pharmacokinetics of gabapentin after oral administration of gabapentin enacarbil.

Unlabelled: Gabapentin enacarbil, an actively transported prodrug of gabapentin, provides sustained and dose-proportional exposure to gabapentin.

Objective: To evaluate the effect of food of varying fat content on the pharmacokinetics and tolerability of gabapentin enacarbil. METHODS, MATERIALS AND SUBJECTS: A randomized, open-label, crossover study of 1,200 mg gabapentin enacarbil was conducted in 12 healthy adults, under four conditions: fasted, or following low-fat (200 - 300 kcal total, approximately 6% from fat), moderate-fat (500 - 600 kcal total, approximately 30% from fat) or high-fat meals (1,000 kcal total, approximately 50% from fat), separated by a washout period of >or= 5 days.

Arbaclofen placarbil decreases postprandial reflux in patients with gastroesophageal reflux disease.

Objectives: Arbaclofen placarbil (AP), previously designated as XP19986, is an investigational prodrug of the active R-isomer of baclofen, a gamma-aminobutyric acid agonist reflux inhibitor. The aim of this study was to assess the efficacy and safety of AP for decreasing meal-induced reflux episodes in patients with gastroesophageal reflux disease (GERD).

Methods: We conducted a multicenter, randomized, double-blind, crossover study comparing single doses of AP with placebo.

Exogenous expression of caspase-14 induces tumor suppression in human salivary cancer cells by inhibiting tumor vascularization.

Background: Current therapeutic approaches to salivary gland cancer are often associated with severe disfigurement and loss of glandular function, which are traumatic to the patients. Exploration of novel treatment approaches, such as gene therapy, is needed.

Materials And Methods: The human salivary gland cancer cell line HSG was transiently transfected with full length human caspase-14 cDNA.

Advantages of an electrical control and energy management system.

This paper discusses an electrical control and energy management system (ECEMS) that was installed at Indian Petrochemicals Corporation Limited (IPCL) Nagathone Gas Cracker complex located in Maharashtra, India. This distributed control system (DCS) provided computer assisted control in the areas of: Demand control; Automatic generation control, including MW and MVAR management; Power factor control; Automatic tap changer control; Load shedding; Automatic synchronization of generator and ties; Remote control of breakers. Previously, IPCL, like most other petrochemical companies in India, relied on operator control for power house functions.

Prospective study of risk factors for Alzheimer's disease: results at 7.5 years.

Objective: The primary goal of this study was to evaluate increased platelet membrane fluidity as a putative risk factor for Alzheimer's disease and its relationship to the APOE epsilon4 genotype.

Method: This report describes the results of a prospective, longitudinal study of 330 initially asymptomatic, first-degree relatives of probands with Alzheimer's disease.

Results: Nine incident cases of Alzheimer's disease were detected during the first 2,220 subject-years of the follow-up period.

Educating for collaborative practice.

Objective: To describe a baccalaureate-level course which is designed to help allied health professions students develop an understanding of collaborative practice among interdisciplinary components of a health care system and to report on a survey which assessed the effectiveness of the course for clinical laboratory science graduates.

Setting: University of Kentucky, a large (24,000 students) state-assisted institution

Practice Description: Baccalaureate clinical laboratory science program

Practice Innovation: A college-wide course helps students develop an understanding of the linkages of the major components of a health care system and introduces the techniques necessary to function in an interdisciplinary team.

Main Outcomes Measure: Perception of benefit from the course by clinical laboratory science graduates.

Prospective study of increased platelet membrane fluidity as a risk factor for Alzheimer's disease: results at 5 years.

Objective: The primary goal of this study was to evaluate increased platelet membrane fluidity as a putative risk factor for Alzheimer's disease.

Method: This report describes the initial results of a prospective, longitudinal study of 330 initially asymptomatic, first-degree relatives of probands with Alzheimer's disease.

Results: Five incident cases of Alzheimer's disease were detected during the first 1,582 subject-years of the follow-up period.

Preliminary evaluation of besipirdine for the treatment of Alzheimer's disease. Besipirdine Study Group.

Besipirdine hydrochloride (HP 749) is an indole-substituted analog of 4-aminopyridine. Besipirdine enhances both cholinergic and adrenergic neurotransmission in the central nervous system, and may have greater efficacy than purely cholinergic agents in treating dementia due to Alzheimer's disease. The present study examined the efficacy and tolerability of two doses of besipirdine (5 and 20 mg BID) in 275 patients with Alzheimer's disease during 3 months of treatment and during 3 months after withdrawal of treatment.

A treatment and withdrawal trial of besipirdine in Alzheimer disease.

Besipirdine hydrochloride (HP 749) is an indole-substituted analog of 4-aminopyridine. Besipirdine enhances both cholinergic and adrenergic neurotransmission in the central nervous system. The present study examined the efficacy and tolerability of two doses of besipirdine (5 and 20 mg b.

Potential patterns--conceptual and practical issues in interdisciplinary education.

Interdisciplinary education is, again, a timely topic. It has been seen as an important strategy in recent reports and commissions dealing with the future of the health care system and its personnel needs. The present article reviews conceptual and practical issues in the design, development, and implementation of interdisciplinary education in allied health.

A "bridging" (safety/tolerance) study of besipirdine hydrochloride in patients with Alzheimer's disease.

Besipirdine hydrochloride is a novel compound with cholinergic and adrenergic activity being investigated as a treatment for Alzheimer's disease (AD). The pharmacodynamics of some anti-dementia drugs are known to differ in patients with AD as compared with elderly normals. The present study was designed to determine the maximum tolerated dose (MTD) of multiple oral doses of besipirdine in AD patients.

Sensitivity and specificity for dementia of population-based criteria for cognitive impairment: the MoVIES project.

Background: Few norms exist for the elderly on the cognitive tests commonly used to screen for dementia; conventional cutpoints used in clinical settings may be of limited value in population screening. A particular problem is posed by elderly populations with low educational levels, as performance on most cognitive tests is affected by education. Thus, a healthy but poorly educated population may obtain test scores in the range considered impaired in the clinical setting.

Serum autoantibodies in patients with Alzheimer's disease and vascular dementia and in nondemented control subjects.

Background And Purpose: In this study we sought to evaluate the clinical significance of serum autoantibodies to dementing processes.

Methods: We assessed 40 age-matched subjects: 10 patients with probable Alzheimer's disease, 10 with possible Alzheimer's disease with cerebrovascular disease, 10 with vascular dementia, and 10 nondemented control subjects. Serum from each subject was tested for the presence of antithyroglobulin antibody, thyroid antimicrosomal antibody, gastric anti-parietal cell antibody, anti-smooth muscle antibody, antinuclear antibody, rheumatoid factor, antineuronal antibody, and anticardiolipin antibody.

Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study.

Objective: To examine the effects of cobalamin repletion on cognition in elderly subjects with low serum cobalamin and evidence of cognitive dysfunction.

Design: Time series data collected in an open trial of parenteral cobalamin therapy.

Settings: Outpatient geriatric assessment centers, inpatient geropsychiatry unit, and tertiary care university hospital.

Serum auto-antibodies in Alzheimer's disease.

The prevalence and clinical significance of non-CNS auto-antibodies in the serum of patients with probable and possible Alzheimer's disease (AD) was determined. Serum was obtained from 88 patients and 55 normal controls. Serum from each subject was tested for the presence of seven different auto-antibodies.

Effects of age, gender, and education on cognitive tests in a rural elderly community sample: norms from the Monongahela Valley Independent Elders Survey.

A random sample of 1,350 persons aged 65 years and older in a rural community underwent cognitive screening as part of a survey to establish a population-based registry of dementing disorders. The screening battery included the neuropsychological tests of the assessment protocol used in the National Institute on Aging multicenter Consortium to Establish a Registry for Alzheimer's Disease (CERAD). This paper reports a large body of normative neuropsychological data from this sample with members of relatively low socioeconomic status.