Preface

The legal process is often invoked to resolve scientific or economic problems such as may arise when a bridge collapses, or an aeroplane crashes, or a ship sinks; or when a mishap occurs on the operating table; or when patent protection is sought for an invention claimed to be novel; or when it is necessary to assess the effect of a commercial practice on competition in a market; or when a baby dies, for no apparent reason, in its cot; or when it is sought to identify a fingerprint on a murder weapon.     

Regulation of intracellular pH

The approach that most animal cells employ to regulate intracellular pH (pH(i)) is not too different conceptually from the way a sophisticated system might regulate the temperature of a house. Just as the heat capacity (C) of a house minimizes sudden temperature (T) shifts caused by acute cold and heat loads, the buffering power (beta) of a cell minimizes sudden pH(i) shifts caused by acute acid and alkali loads. However, increasing C (or beta) only minimizes T (or pH(i)) changes; it does not eliminate the changes, return T (or pH(i)) to normal, or shift steady-state T (or pH(i)). Whereas a house may have a furnace to raise T, a cell generally has more than one acid-extruding transporter (which exports acid and/or imports alkali) to raise pH(i). Whereas an air conditioner lowers T, a cell generally has more than one acid-loading transporter to lower pH(i). Just as a house might respond to graded decreases (or increases) in T by producing graded increases in heat (or cold) output, cells respond to graded decreases (or increases) in pH(i) with graded increases (or decreases) in acid-extrusion (or acid-loading) rate. Steady-state T (or pH(i)) can change only in response to a change in chronic cold (or acid) loading or chronic heat (or alkali) loading as produced, for example, by a change in environmental T (or pH) or a change in the kinetics of the furnace (or acid extrudes) or air conditioner (or acid loaders). Finally, just as a temperature-control system might benefit from environmental sensors that provide clues about cold and heat loading, at least some cells seem to have extracellular CO(2) or extracellular HCO(3)(-) sensors that modulate acid-base transport.     

Risk Assessment Applications Beyond Baseline Risks and Clean-Up Goals

Historically, the phrase “Risk Assessment” brought to mind a thick Superfund-type baseline risk assessment or clean-up goal derivation document filled with pages of tables with endless seemingly unrelated algorithms and numbers. Over the last decade, the principles of risk and exposure assessment have gained wide-reaching acceptance and are increasingly utilized to help solve other environmental impact, occupational health, or risk mitigation design problems. The typical objective of the classic risk assessment is the evaluation of current or future risks from exposure to contaminated media within the framework of a regulatory waste management or remediation program. Risk-based techniques are increasingly being used on a voluntary basis (i.e., outside of the standard regulatory arena) to demonstrate the presence, absence, or extent of environmental or health-related concerns in specific exposure circumstances. Likewise, a risk or exposure evaluation may be useful in determining the need for, or the legitimacy of, a public health advisory, alone or in conjunction with remedial or mitigative actions. Finally, risk-based techniques often find their way into the courtroom. Three case studies are presented in which riskbased solutions were employed to assist in resolving environmental or health-related issues: (1) a reversal of a fish consumption advisory; (2) an evaluation of arsenic in soil on and adjacent to a school facility; and (3) a challenge to a case of alleged methyl bromide exposure in a litigation context. In each case, the use of risk assessment principles was employed beyond the classic baseline risk assessment to address an applied problem of toxicological significance.     

Symposium on diarrhea. 2. Clinical diagnosis of the causes of diarrhea.

Elucidation of the cause of diarrhea is facilitated by considering which of three principal determinants are of relevance in a particular case. These determinants relate to the onset (whether diarrhea is acute or chronic), to infection or an absence ofinfection and to the presence in the stool of blood or mucus, or both. Diagnosis is also facilitated by taking an accurate and full history, conducting a physical examination, performing sigmoidoscopy and, with proper care, attempting a therapeutic diagnosis. Findings from investigations should then enable one to arrive at a diagnosis. The diagnosis can be reached in an orderly fashion by classifying the types of diarrhea into eight categories: with respect to the acute or chronic onset a case of diarrhea may be noninfectious, without blood or mucus in the stool; noninfectious, with blood or mucus, or both; infectious, without blood or mucus; and infectious, with blood or mucus in the stool.     

Exponentiated Exponential Family: An Alternative to Gamma and Weibull Distributions

In this article we study some properties of a new family of distributions, namely Exponentiated Exponential distribution, discussed in Gupta , Gupta , and Gupta (1998). The Exponentiated Exponential family has two parameters (scale and shape) similar to a Weibull or a gamma family. It is observed that many properties of this new family are quite similar to those of a Weibull or a gamma family, therefore this distribution can be used as a possible alternative to a Weibull or a gamma distribution. We present two real life data sets, where it is observed that in one data set exponentiated exponential distribution has a better fit compared to Weibull or gamma distribution and in the other data set Weibull has a better fit than exponentiated exponential or gamma distribution. Some numerical experiments are performed to see how the maximum likelihood estimators and their asymptotic results work for finite sample sizes.     

A Modified In vitro Invasion Assay to Determine the Potential Role of Hormones,Cytokines and/or Growth Factors in Mediating Cancer Cell Invasion

Blood serum serves as a chemoattractant towards which cancer cells migrate and invade, facilitating their intravasation into microvessels. However, the actual molecules towards which the cells migrate remain elusive. This modified invasion assay has been developed to identify targets which drive cell migration and invasion. This technique compares the invasion index under three conditions to determine whether a specific hormone, growth factor, or cytokine plays a role in mediating the invasive potential of a cancer cell. These conditions include i) normal fetal bovine serum (FBS), ii) charcoal-stripped FBS (CS-FBS), which removes hormones, growth factors, and cytokines and iii) CS-FBS + molecule (denoted “X”). A significant change in cell invasion with CS-FBS as compared to FBS, indicates the involvement of hormones, cytokines or growth factors in mediating the change. Individual molecules can then be added back to CS-FBS to assay their ability to reverse or rescue the invasion phenotype. Furthermore, two or more factors can be combined to evaluate the additive or synergistic effects of multiple molecules in driving or inhibiting invasion. Overall, this method enables the investigator to determine whether hormones, cytokines, and/or growth factors play a role in cell invasion by serving as chemoattractants or inhibitors of invasion for a particular type of cancer cell or a specific mutant. By identifying specific chemoattractants and inhibitors, this modified invasion assay may help to elucidate signaling pathways that direct cancer cell invasion.     

Starvation period and age affect the response of female Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) to odor and visual cues

The effects of starvation or age on the walking or flying response of female Frankliniella occidentalis to visual and/or odor cues in two types of olfactometer were examined in the laboratory. The response of walking thrips starved for 0, 1, 4, or 24h to an odor cue (1microl of 10% p-anisaldehyde) was examined in a Y-tube olfactometer. The take-off and landing response of thrips (unknown age) starved for 0, 1, 4, 24, 48 or 72h, or of thrips of different ages (2-3 days or 10-13 days post-adult emergence) starved for 24h, to a visual cue (98 cm(2) yellow sticky trap) and/or an odor cue (0.5 or 1.0 ml p-anisaldehyde) was examined in a wind tunnel. More thrips walked up the odor-laden arm in the Y-tube when starved for at least 4h (76%) than satiated thrips (58.7%) or those starved for 1h (62.7%, P<0.05). In the wind tunnel experiments the percentage of thrips to fly or land on the sticky trap increased between satiated thrips (7.3% to fly, 3.3% on trap) and those starved for 4h (81.2% to fly, 29% on trap) and decreased between thrips starved for 48 (74.5% to fly, 23% on trap) and 72 h (56.5% to fly, 15.5% on trap, P<0.05). Fewer younger thrips (38.8%) landed on a sticky trap containing a yellow visual cue of, those that flew, than older thrips (70.4%, P<0.05), although a similar percentage of thrips flew regardless of age or type of cue present in the wind tunnel (average 44%, P>0.05).     

Pharmacological manipulation of sincalide (CCK-8)-induced suppression of feeding

The current study involves an investigation of the possible neurotransmitter systems involved in the ability of exogenously administered sincalide (cholecystokinin octapeptide, CCK-8) to suppress feeding. Male rats previously trained to obtain food either during a daily 3-hr session, or conditioned to obtain food pellets on a fixed-ratio or fixed-interval schedule of reinforcement, were treated IP with CCK-8, following pretreatment with representative drugs of several pharmacological classes. Pretreatment with phenoxybenzamine, tolazoline, yohimbine, morphine, haloperidol or picrotoxin reduced the efficacy of CCK-8. However, pretreatment with naloxone or clonidine potentiated the suppressant action of CCK-8 on feeding. Propranolol, diphenhydramine, cimetidine, atropine, d-amphetamine, fenfluramine or diazepam pretreatment either had no effect or no consistent action in altering the activity of CCK-8. The ability of CCK-8 to suppress feeding was not altered by subacute treatment with the anorectics, d-amphetamine or fenfluramine, using a regimen known to induce tolerance. These data indicate that CCK-8 exerts a different mechanism of action than that of fenfluramine or d-amphetamine, and furthermore, that noradrenergic, dopaminergic, GABAergic or endogenous opioid systems either mediate or can modify the effect of CCK-8 on feeding.     

拟寄生蜂搜索产卵过程中对寄主的竞争

综述拟寄生蜂搜索产卵过程中对寄主竞争的最新研究进展.这类竞争具有四种方式,即标记寄主、杀卵和杀幼、守护寄主和捕食寄主.（1）标记寄主常涉及寄主标记信息素,这是由雌蜂在产卵前、产卵时或产卵后分泌的化学物质.寄主标记信息素常介导拟寄生蜂对已寄生和健康寄主的辨别、减少过寄生和多寄生、减轻种内和种间竞争压力.（2）雌蜂遇到已寄生寄主时,很多种类杀死前一雌蜂遗留的卵和幼虫,再产下自己的卵.雌蜂使用三种方法杀卵和杀幼,即产卵器穿刺、取食和使用有毒物质.通过杀卵和杀幼,产卵雌蜂清除了前一雌蜂遗留的后代,主动改善了寄主品质,从而有利于自身后代的生存.（3）守护寄主在肿腿蜂科、缘腹细蜂科、金小蜂科、缨小蜂科和茧蜂科中均有报道,守护者驱逐入侵者以保护后代及健康寄主.（4）捕食寄主不仅减少了健康寄主数量,且直接导致已寄生寄主中拟寄生蜂卵和幼虫的死亡.雌蜂一般在体内成熟卵量较少时捕食寄主.讨论了研究拟寄生蜂搜索产卵过程中竞争寄主的理论意义和实际应用价值.     

Royal College of Physicians and Surgeons of Canada: annual meeting draws over 2000 physicians

In a review of 19 years'' experience with inhalation of foreign bodies by children the 33 patients (mean age 28 months) were found to have presented most frequently with wheezing or coughing, or both, of recent onset, and to have decreased air entry, rhonchi or respiratory stridor, or a combination of these signs. Eighteen children had inhaled a nut, a pea or a bean. The other 15 had inhaled various organic and inorganic objects. All the children underwent bronchoscopy, and the foreign body was completely removed in 19 during the first procedure; the remainder required repeated bronchoscopy or direct surgical removal of the foreign body, or both. Permanent disability or death was not encountered. The findingsof the study indicate that early bronchoscopic removal is the preferred treatment when a child inhales a foreign body.     

Bioreactors for 3-dimensional high-density culture of human cells

A bioreactor was developed as an instrument to culture human or animal cells that require attachment in a large quantity or at a high density. The purpose for developing such a bioreactor is two-fold: to produce a large quantity of animal or human cells that have been modified by gene recombination technology to accommodate manufacture of physiologically-active substances or human proteins on an industrial scale; and for research to culture animal cells to form a high-density 3-dimensional structure as a morphological or functional tissue or organ entity. In the current report, the circulatory flow bioreactor and radial flow bioreactor (RFB) are introduced, in which the former can be scaled up. As a small bioreactor produced for the latter purpose, a rotary cell culture system and novel multicoaxial hollow-fiber bioreactor are introduced. Finally, a small RFB culture system that was scaled down by the present author and his collaborators for the study of a 3-dimensional high density culture system is described. The RFB can be readily scaled up for manufacturing or scaled down for research purposes. This is a cell culturing system that can induce the functions of human tissues by preparing a high density 3-dimensional organization of cells of human origin.     

Protein tagging and detection with engineered self-assembling fragments of green fluorescent protein

Existing protein tagging and detection methods are powerful but have drawbacks. Split protein tags can perturb protein solubility or may not work in living cells. Green fluorescent protein (GFP) fusions can misfold or exhibit altered processing. Fluorogenic biarsenical FLaSH or ReASH substrates overcome many of these limitations but require a polycysteine tag motif, a reducing environment and cell transfection or permeabilization. An ideal protein tag would be genetically encoded, would work both in vivo and in vitro, would provide a sensitive analytical signal and would not require external chemical reagents or substrates. One way to accomplish this might be with a split GFP, but the GFP fragments reported thus far are large and fold poorly, require chemical ligation or fused interacting partners to force their association, or require coexpression or co-refolding to produce detectable folded and fluorescent GFP. We have engineered soluble, self-associating fragments of GFP that can be used to tag and detect either soluble or insoluble proteins in living cells or cell lysates. The split GFP system is simple and does not change fusion protein solubility.     

A clinical approach to common electrolyte problems: 2. Potassium imbalances.

A clinical approach to potassium imbalances is presented. Hypokalemia is rarely due solely to a reduced intake of potassium; instead, it usually results from a potassium flux into the cells or increased loss of the element, at times combined with a decreased intake. The clinician must seek the cause of the intracellular flux or the source of the gastrointestinal or renal loss. The causes of gastrointestinal losses are generally self evident. Renal potassium wasting, though, generally results from increased mineralocorticoid activity, an increased rate of urinary flow or of sodium delivery to the distal nephron, or both, hypomagnesemia or a combination of these factors. Hyperkalemia may be factitious, but usually it is caused by a flux of potassium from the cells or a decrease in the renal loss of potassium, the latter being mediated by a reduction in renal function, mineralocorticoid activity, or the rate of urinary flow or sodium delivery, or both. In both hypokalemia and hyperkalemia, treatment must be guided by the specific clinical circumstances.     

General properties and phylogenetic utilities of nuclear ribosomal DNA and mitochondrial DNA commonly used in molecular systematics

To choose one or more appropriate molecular markers or gene regions for resolving a particular systematic question among the organisms at a certain categorical level is still a very difficult process. The primary goal of this review, therefore, is to provide a theoretical information in choosing one or more molecular markers or gene regions by illustrating general properties and phylogenetic utilities of nuclear ribosomal DNA (rDNA) and mitochondrial DNA (mtDNA) that have been most commonly used for phylogenetic researches. The highly conserved molecular markers and/or gene regions are useful for investigating phylogenetic relationships at higher categorical levels (deep branches of evolutionary history). On the other hand, the hypervariable molecular markers and/or gene regions are useful for elucidating phylogenetic relationships at lower categorical levels (recently diverged branches). In summary, different selective forces have led to the evolution of various molecular markers or gene regions with varying degrees of sequence conservation. Thus, appropriate molecular markers or gene regions should be chosen with even greater caution to deduce true phylogenetic relationships over a broad taxonomic spectrum.     

Susceptibility of food-borne bacteria to binary combinations of antimicrobials at selected a(w) and pH

AIM: To evaluate the antibacterial susceptibilities of food-borne bacteria to individual and binary mixtures of a synthetic antimicrobial agent with a natural phenolic compound. METHODS AND RESULTS: Antibacterial susceptibilities of Escherichia coli, Listeria innocua, Salmonella Typhimurium and Staphylococcus aureus to individual and binary mixtures of potassium sorbate with a phenolic compound (thymol, carvacrol, or eugenol) were evaluated, at selected water activity (a(w); 0.99 or 0.97) and pH (5.5 or 4.5). The bacteria studied were susceptible to the action of the antimicrobials individually with minimal inhibitory concentrations that varied from 800-ppm potassium sorbate for Staph. aureus at a(w) 0.99, and pH 5.5 to 100-ppm thymol or carvacrol for the four studied bacteria at a(w) 0.97 and pH 4.5. Several binary mixtures of potassium sorbate with thymol, carvacrol or eugenol inhibited bacterial growth. Antimicrobial agent inhibitory concentrations in the mixture varied among bacteria, additionally depending on the a(w) and the pH tested. CONCLUSIONS: Synergistic binary mixtures with fractional inhibitory concentration index <0.6 include 100- or 200-ppm potassium sorbate with 50- or 100-ppm thymol, carvacrol or eugenol. SIGNIFICANCE AND IMPACT OF THE STUDY: The synergistic combinations could be useful in reducing the amounts of antimicrobials needed to inhibit growth, thus diminishing consumer concerns regarding chemical preservatives.     

Experimental study of changes in osteoblastic shape induced by calcitonin and parathyroid extract in an organ culture system

Summary Neonate rat endocranial osteoblasts were cultured on their bone surfaces in control medium (CC) or medium to which either parathyroid extract (PTE) or calcitonin (CT) had been added for 2, 4, 8 or 24 h. Some were cultured for 24 h in CC, then for 2, 4, 8 or 24 h in either CT or PTE medium; or for 24 h in PTE, then for 2, 4, 8 or 24 h in either CC or CT; or 24 h in CT and 2, 4, 8 or 24 h in CC. The dorsal ruffling of the cells in CC was found to be suppressed by later culturing with PTE and the disoriented cells reorganized to form arrays of parallel cells. The effects of PTE were also reversed by CC or CT: the osteoblasts in the second culture (CC) lost elongation and order, and proceeded through a proliferative phase before exhibiting the ruffling form similar to a single CC 24 h culture. PTE-cultured osteoblasts showed an increase in cell overlap and contact so that a more competent barrier was formed separating the bone from the medium. In control or CT medium, however, intercellular gaps were greater than in vivo.We are grateful for the expert technical assistance of Elaine Bailey, for laboratory facilities kindly provided by Dr. Martin Evans, and for financial support from the Medical Research Council     

C-ME: a 3D community-based, real-time collaboration tool for scientific research and training

The need for effective collaboration tools is growing as multidisciplinary proteome-wide projects and distributed research teams become more common. The resulting data is often quite disparate, stored in separate locations, and not contextually related. Collaborative Molecular Modeling Environment (C-ME) is an interactive community-based collaboration system that allows researchers to organize information, visualize data on a two-dimensional (2-D) or three-dimensional (3-D) basis, and share and manage that information with collaborators in real time. C-ME stores the information in industry-standard databases that are immediately accessible by appropriate permission within the computer network directory service or anonymously across the internet through the C-ME application or through a web browser. The system addresses two important aspects of collaboration: context and information management. C-ME allows a researcher to use a 3-D atomic structure model or a 2-D image as a contextual basis on which to attach and share annotations to specific atoms or molecules or to specific regions of a 2-D image. These annotations provide additional information about the atomic structure or image data that can then be evaluated, amended or added to by other project members.     

Does the margin of stability measure predict medio-lateral stability of gait with a constrained-width base of support?

This study aimed to determine the validity of the centre of mass position (COM) position and extrapolated COM (XCOM), relative to the base of support, for predicting medio-lateral stability during a walking task where the base of support width is limited. Nine young healthy participants walked on a narrow beam. Three-dimensional motion capture was used to calculate the COM and XCOM relative to the base of support. Steps were classified as having either the COM or XCOM inside or outside the base of support, and were classified as successful (stable – foot placed on the beam) or failed (unstable – foot stepped off the beam). If the COM or XCOM are valid measures of stability, they should be within the base of support for successful steps and outside the base of support for failed steps. Classifying the COM and XCOM inside or outside the base of support correctly predicted successful or failed steps in 69% and 58% of cases, respectively. When the COM or XCOM were outside the base of support, walking faster seemed to help participants to maintain stability. The further the COM or XCOM were outside the base of support during a successful step, the more likely participants were to fail on a subsequent step. The results of this study suggest that both COM and XCOM are valid measures of stability during a beam walking task, but that classifying COM and XCOM as inside or outside the base of support may be over-simplistic.     

Autism Spectrum Disorder Initiation by Inflammation-Facilitated Neurotoxin Transport

Autism spectrum disorders have been linked to genetics, gut microbiota dysbiosis (gut dysbiosis), neurotoxin exposures, maternal allergies or autoimmune diseases. Two barriers to ingested neurotoxin transport into the central nervous system of a fetus or child are the gastrointestinal wall of the mother or child and the blood–brain barrier of the fetus or child. Inflammation from gut dysbiosis or inflammation from a disease or other agent can increase the gastrointestinal wall and the blood–brain barrier permeabilities to enable neurotoxins to reach the brain of a fetus or child. Postnatal gut dysbiosis is a particular inflammation risk for autism spectrum disorders caused by neurotoxin transport into a child's brain. An extensive gut dysbiosis or another source of inflammation such as a disease or other agent in combination with neurotoxins, including aluminum, mercury, lead, arsenic, cadmium, arsenic, organophosphates, and neurotoxic bacterial toxins and fungal toxins resulting from the gut dysbiosis, can elevate neurotoxin levels in a fetal or child brain to cause neurodevelopmental damage and initiate an autism spectrum disorder. The neurotoxins aluminum and mercury are especially synergistic in causing neurodevelopmental damage. There are three plausible causational pathways for autism spectrum disorders. They include inflammation and neurotoxin loading into the fetal brain during the prenatal neurodevelopment period, inflammation and neurotoxin loading into the brain during the postnatal neurodevelopment period or a two-stage loading of neurotoxins into the brain during both the prenatal and postnatal neurodevelopment periods.

     

Induction of fumarase in resting Euglena

Exposure of dark-grown resting (carbon deficient) Euglena to light, ethanol or malate produced a transient increase in the specific activity of fumarase. Fumarase levels decreased 8–12 h after the start of induction and this decrease could not be prevented by additional inducer. During the period of fumarase accumulation, cycloheximide prevented further fumarase synthesis and enzyme levels decreased at a rate comparable to the rate of decline normally observed 8–12 h after the start of induction. Although the addition of ethanol to ethanol-induced cultures or malate to malate-induced cultures 12 or 24 h after the initial induction failed to maintain or induce additional fumarase synthesis, the addition of organic carbon to photoinduced cells 8 or 24 h after light exposure induced additional enzyme synthesis. Additional enzyme synthesis was not induced when ethanol- or malate-induced cells were exposed to light 12 or 24 h after organic carbon addition. Light exposure or ethanol addition failed to induce fumarase synthesis during balanced growth indicating that fumarse inducibility is a property of resting cells.